BioPAX pathway converted from "Signaling by ROBO receptors" in the Reactome database.Signaling by ROBO receptorsThe Roundabout (ROBO) family encodes transmembrane receptors that regulate axonal guidance and cell migration. The major function of the Robo receptors is to mediate repulsion of the navigating growth cones. There are four human Robo homologues, ROBO1, ROBO2, ROBO3 and ROBO4. Most of the ROBOs have the similar ectodomain architecture as the cell adhesion molecules, with five Ig domains followed by three FN3 repeats, except for ROBO4. ROBO4 has two Ig and two FN3 repeats. The cytoplasmic domains of ROBO receptors are in general poorly conserved. However, there are four short conserved cytoplasmic sequence motifs, named CC0-3, that serve as binding sites for adaptor proteins. The ligands for the human ROBO1 and ROBO2 receptors are the three SLIT proteins SLIT1, SLIT2, and SLIT3; all of the SLIT proteins contain a tandem of four LRR (leucine rich repeat) domains at the N-terminus, termed D1-D4, followed by six EGF (epidermal growth factor)-like domains, a laminin G like domain (ALPS), three EGF-like domains, and a C-terminal cysteine knot domain. Most SLIT proteins are cleaved within the EGF-like region by unknown proteases (reviewed by Hohenster 2008, Ypsilanti and Chedotal 2014, Blockus and Chedotal 2016). NELL2 is a ligand for ROBO3 (Jaworski et al. 2015).<br><br>SLIT protein binding modulates ROBO interactions with the cytosolic adaptors. The cytoplasmic domain of ROBO1 and ROBO2 determines the repulsive responses of these receptors. Based on the studies from both invertebrate and vertebrate organisms it has been inferred that ROBO induces growth cone repulsion by controlling cytoskeletal dynamics via either Abelson kinase (ABL) and Enabled (Ena), or RAC1 activity (reviewed by Hohenster 2008, Ypsilanti and Chedotal 2014, Blockus and Chedotal 2016). While there is some redundancy in the function of ROBO receptors, ROBO1 is implicated as the predominant receptor for axon guidance in ventral tracts, and ROBO2 is the predominant receptor for axon guidance in dorsal tracts. ROBO2 also repels neuron cell bodies from the floor plate (Kim et al. 2011).<p>In addition to regulating axon guidance, ROBO1 and ROBO2 receptors are also implicated in regulation of proliferation and transition of primary to intermediate neuronal progenitors through a poorly characterized cross-talk with NOTCH-mediated activation of HES1 transcription (Borrell et al. 2012).<p>Thalamocortical axon extension is regulated by neuronal activity-dependent transcriptional regulation of ROBO1 transcription. Lower neuronal activity correlates with increased ROBO1 transcription, possibly mediated by the NFKB complex (Mire et al. 2012).<p>It is suggested that the homeodomain transcription factor NKX2.9 stimulates transcription of ROBO2, which is involved in regulation of motor axon exit from the vertebrate spinal code (Bravo-Ambrosio et al. 2012).<p>Of the four ROBO proteins, ROBO4 is not involved in neuronal system development but is, instead, involved in angiogenesis. The interaction of ROBO4 with SLIT3 is involved in proliferation, motility and chemotaxis of endothelial cells, and accelerates formation of blood vessels (Zhang et al. 2009).Authored: Garapati, P V, 2008-09-05 06:02:05Reviewed: Kidd, T, 2009-08-18Reviewed: Jaworski, Alexander, 2017-07-31Edited: Garapati, P V, 2008-09-05 06:02:05Edited: Orlic-Milacic, Marija, 2017-06-23Edited: Orlic-Milacic, Marija, 2017-08-04Regulation of expression of SLITs and ROBOsExpression of SLIT and ROBO proteins is regulated at the level of transcription, translation and protein localization and stability. LIM-homeodomain transcription factors LHX2, LHX3, LHX4, LHX9 and ISL1 have so far been implicated in a cell type-dependent transcriptional regulation of ROBO1, ROBO2, ROBO3 and SLIT2 (Wilson et al. 2008, Marcos-Mondejar et al. 2012, Kim et al. 2016). Homeobox transcription factor HOXA2 is involved in transcriptional regulation of ROBO2 (Geisen et al. 2008). Transcription of SLIT1 during optic tract development in Xenopus is stimulated by FGF signaling and may also involve the transcription factor HOXA2, but the mechanism has not been established (Atkinson-Leadbeater et al. 2010). PAX6 and the homeodomain transcription factor NKX2.2 are also implicated in regulation of SLIT1 transcription (Genethliou et al. 2009). An RNA binding protein, MSI1, binds ROBO3 mRNA and promotes its translation, thus increasing ROBO3 protein levels (Kuwako et al. 2010). A poorly studied E3 ubiquitin ligase ZSWIM8 promotes degradation of ROBO3 (Wang et al. 2013). ROBO1 is protein half-life is increased via deubiquitination of ROBO1 by a ubiquitin protease USP33 (Yuasa-Kawada et al. 2009, Huang et al. 2015). Interaction of SLIT2 with DAG1 (dystroglycan) is important for proper localization of SLIT2 at the floor plate (Wright et al. 2012). Interaction of SLIT1 with a type IV collagen COL4A5 is important for localization of SLIT1 to the basement membrane of the optical tectum (Xiao et al. 2011).Authored: Orlic-Milacic, Marija, 2017-06-27Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04LEFT-TO-RIGHTISL1 binds the SLIT2 gene enhancerBased on studies in mice, the transcription factor ISL1, in complex with either LHX3 or LHX4, binds to an evolutionarily conserved LIM-HD binding site in the enhancer of the SLIT2 gene, located in the sixth intron of the SLIT2 gene. The complex of ISL1 and LHX4 regulates SLIT2 expression in branchiomotor neurons, while the complex of ISL1 and LHX3 regulates SLIT2 expression in somatic motor neurons (Kim et al. 2016). From the previous structural studies of the ISL1 complex with LHX3, conducted using mouse and rat proteins, it is known that LDB1 is also part of this complex (Thaler et al. 2002).Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04Converted from EntitySet in ReactomeISL1:LHX3/4:LDB1Reactome DB_ID: 9010608ISL1:LHX3:LDB1Reactome DB_ID: 9010596nucleoplasmGENE ONTOLOGYGO:0005654LHX3LIM/homeobox protein Lhx3LHX3_HUMANReactome DB_ID: 9010582UniProt:Q9UBR4 LHX3LHX3FUNCTION Acts as a transcriptional activator. Binds to and activates the promoter of the alpha-glycoprotein gene, and synergistically enhances transcription from the prolactin promoter in cooperation with POU1F1/Pit-1 (By similarity). Required for the establishment of the specialized cells of the pituitary gland and the nervous system. Involved in the development of interneurons and motor neurons in cooperation with LDB1 and ISL1.SUBUNIT Interacts with POU1F1 (PubMed:26612202). At neuronal promoters, interacts with LDB1, in motor neurons LDB1 is displaced by ISL1 and a ternary complex is formed in which ISL1 contacts both LHX3 and LDB1 (By similarity).DOMAIN The LIM domain specifically interacts with the Pit-1 POU domain and is required for synergistic interactions with Pit-1, but not for basal transcriptional activation events.Homo sapiensNCBI Taxonomy9606UniProtQ9UBR41EQUAL397EQUALReactome Database ID Release 759010582Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010582ReactomeR-HSA-90105821Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010582.1Reactomehttp://www.reactome.org2LDB1 homodimerReactome DB_ID: 9010567LDB1LIM domain-binding protein 1LDB1_HUMANCLIM2Carboxyl-terminal LIM domain-binding protein 2Reactome DB_ID: 8956515UniProt:Q86U70 LDB1LDB1CLIM2FUNCTION Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors. May regulate the transcriptional activity of LIM-containing proteins by determining specific partner interactions. Plays a role in the development of interneurons and motor neurons in cooperation with LHX3 and ISL1. Acts synergistically with LHX1/LIM1 in axis formation and activation of gene expression. Acts with LMO2 in the regulation of red blood cell development, maintaining erythroid precursors in an immature state (By similarity).SUBUNIT Forms homodimers and heterodimers. Interacts with and activates LHX1/LIM1. Interacts with the LIM domains of ISL1 and LMO2. Can assemble in a complex with LMO2 and TAL1/SCL but does not interact with TAL1/SCL directly. Strongly interacts with the LIM2 domain of LMX1A and more weakly with the LIM1 domain. Homodimerization is not required for, and does not effect, LMX1A-binding. Component of a nuclear TAL-1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3. Interacts with LHX6 and LHX9. At neuronal promoters, forms a complex with LHX3 involved in the specification of interneurons, in motor neurons, it is displaced by ISL1 to form a ternary complex in which ISL1 contacts both LHX3 and LDB1 (By similarity). Interacts with ESR1. Interacts with SLK; leading to negatively regulate SLK kinase activity (By similarity). Interacts with YWHAZ (PubMed:16959763). Interacts with PRDM1/BLIMP1 (PubMed:32417234).TISSUE SPECIFICITY Expressed in a wide range of adult tissues including brain, heart, skeletal muscle, colon, thymus, spleen, kidney, liver, small intestine, lung and peripheral blood leukocytes.DOMAIN The dimerization domain is located in the N-terminus.PTM Ubiquitinated by RLIM/RNF12, leading to its degradation by the proteasome.MISCELLANEOUS Acts as a negative coregulator of ESR1-mediated transcription in breast cancer cells.SIMILARITY Belongs to the LDB family.UniProtQ86U702EQUAL411EQUALReactome Database ID Release 758956515Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8956515ReactomeR-HSA-89565151Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8956515.12Reactome Database ID Release 759010567Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010567ReactomeR-HSA-90105671Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010567.11ISL1Insulin gene enhancer protein ISL-1ISL1_HUMANIslet-1Reactome DB_ID: 400478UniProt:P61371 ISL1ISL1FUNCTION DNA-binding transcriptional activator. Recognizes and binds to the consensus octamer binding site 5'-ATAATTAA-3' in promoter of target genes. Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation. Cooperates with the transcription factor POU4F2 to achieve maximal levels of expression of RGC target genes and RGC fate specification in the developing retina. Involved in the specification of motor neurons in cooperation with LHX3 and LDB1. Binds to insulin gene enhancer sequences. Essential for heart development. Marker of one progenitor cell population that give rise to the outflow tract, right ventricle, a subset of left ventricular cells, and a large number of atrial cells as well, its function is required for these progenitors to contribute to the heart. Controls the expression of FGF and BMP growth factors in this cell population and is required for proliferation and survival of cells within pharyngeal foregut endoderm and adjacent splanchnic mesoderm as well as for migration of cardiac progenitors into the heart (By similarity).SUBUNIT At neuronal promoters, displaces LDB1 from LHX3 LIM domain to form a ternary complex in which ISL1 contacts both LHX3 and LDB1. Interacts (via C-terminus) with POU4F2 (via C-terminus). Interacts with POU3F2. Interacts with POU4F3. Interacts (via N-terminal domain) with MLIP; the interaction represses ISL1 transactivator activity (By similarity).TISSUE SPECIFICITY Expressed in subsets of neurons of the adrenal medulla and dorsal root ganglion, inner nuclear and ganglion cell layers in the retina, the pineal and some regions of the brain.PTM Phosphorylated.UniProtP613711EQUAL349EQUALReactome Database ID Release 75400478Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=400478ReactomeR-HSA-4004781Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-400478.12Reactome Database ID Release 759010596Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010596ReactomeR-HSA-90105961Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010596.1ISL1:LHX4:LDB1Reactome DB_ID: 9010601LHX4LIM/homeobox protein Lhx4LHX4_HUMANReactome DB_ID: 9010585UniProt:Q969G2 LHX4LHX4FUNCTION May play a critical role in the development of respiratory control mechanisms and in the normal growth and maturation of the lung. Binds preferentially to methylated DNA (PubMed:28473536).DISEASE A chromosomal aberration involving LHX4 may be a cause of acute lymphoblastic leukemia. Translocation t(1;14)(q25;q32) with IGHG1.UniProtQ969G21EQUAL390EQUALReactome Database ID Release 759010585Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010585ReactomeR-HSA-90105851Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010585.1212Reactome Database ID Release 759010601Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010601ReactomeR-HSA-90106011Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010601.1Reactome Database ID Release 759010608Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010608ReactomeR-HSA-90106081Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010608.1SLIT2 geneReactome DB_ID: 9010561ENSEMBL:ENSG00000145147 SLIT2SLIT2SLIL3ENSEMBLENSG00000145147Reactome Database ID Release 759010561Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010561ReactomeR-HSA-90105611Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010561.1ISL1:LHX3/4:LDB1:SLIT2 geneReactome DB_ID: 901060611Reactome Database ID Release 759010606Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010606ReactomeR-HSA-90106061Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010606.1Reactome Database ID Release 759010541Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010541ReactomeR-HSA-90105411Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010541.112150931Pubmed2002LIM factor Lhx3 contributes to the specification of motor neuron and interneuron identity through cell-type-specific protein-protein interactionsThaler, Joshua PLee, Soo-KyungJurata, Linda WGill, GNPfaff, Samuel LCell 110:237-4927819291Pubmed2016ISL1-based LIM complexes control Slit2 transcription in developing cranial motor neuronsKim, Kyung-TaiKim, NamheeKim, Hwan-KiLee, HojaeGruner, Hannah NGergics, PeterPark, ChungooMastick, Grant SPark, Hae-ChulSong, Mi-RyoungSci Rep 6:36491LEFT-TO-RIGHTSLIT2 gene expression is stimulated by ISL1Based on studies in mice, the transcription factor ISL1, in complex with either LHX3 or LHX4, directly stimulates transcription of the SLIT2 gene. ISL1-mediated regulation of SLIT2 gene transcription in branchiomotor (BM) neurons and somatic motor (SM) neurons involves LHX4 and LHX3, respectively (Kim et al. 2016). Slit2 expression is diminished in Isl1 mutant mice (Lee et al. 2015).<p>SLIT2 is one of gene suggested to be repressed by the transcription factor ARX, involved in neuronal proliferation, migration, maturation and differentiation, as well as axon guidance (reviewed by Friocourt and Parnavelas, 2011).Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04SLIT2SLIT2(31-1529)Slit homolog 2 proteinSLIT2_HUMANReactome DB_ID: 375997extracellular regionGENE ONTOLOGYGO:0005576UniProt:O94813 SLIT2SLIT2SLIL3FUNCTION Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navigation at the ventral midline of the neural tube and projection of axons to different regions. SLIT1 and SLIT2 seem to be essential for midline guidance in the forebrain by acting as repulsive signal preventing inappropriate midline crossing by axons projecting from the olfactory bulb. In spinal chord development may play a role in guiding commissural axons once they reached the floor plate by modulating the response to netrin. In vitro, silences the attractive effect of NTN1 but not its growth-stimulatory effect and silencing requires the formation of a ROBO1-DCC complex. May be implicated in spinal chord midline post-crossing axon repulsion. In vitro, only commissural axons that crossed the midline responded to SLIT2. In the developing visual system appears to function as repellent for retinal ganglion axons by providing a repulsion that directs these axons along their appropriate paths prior to, and after passage through, the optic chiasm. In vitro, collapses and repels retinal ganglion cell growth cones. Seems to play a role in branching and arborization of CNS sensory axons, and in neuronal cell migration. In vitro, Slit homolog 2 protein N-product, but not Slit homolog 2 protein C-product, repels olfactory bulb (OB) but not dorsal root ganglia (DRG) axons, induces OB growth cones collapse and induces branching of DRG axons. Seems to be involved in regulating leukocyte migration.SUBUNIT Interacts with GREM1 (By similarity). Homodimer. Binds ROBO1 and ROBO2 with high affinity.TISSUE SPECIFICITY Fetal lung and kidney, and adult spinal cord. Weak expression in adult adrenal gland, thyroid, trachea and other tissues examined.DOMAIN The leucine-rich repeat domain is sufficient for guiding both axon projection and neuronal migration, in vitro.UniProtO9481331EQUAL1529EQUALReactome Database ID Release 75375997Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=375997ReactomeR-HSA-3759973Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-375997.3Reactome Database ID Release 759010539Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010539ReactomeR-HSA-90105393Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010539.322355284Pubmed2011Identification of Arx targets unveils new candidates for controlling cortical interneuron migration and differentiationFriocourt, GaĆ«lleParnavelas, John GFront Cell Neurosci 5:2825843547Pubmed2015Slit and Semaphorin signaling governed by Islet transcription factors positions motor neuron somata within the neural tubeLee, HojaeKim, MinkyungKim, NamheeMacfarlan, ToddPfaff, Samuel LMastick, Grant SSong, Mi-RyoungExp. Neurol. 269:17-27ACTIVATIONactiveUnit: #Complex1Reactome Database ID Release 759010614Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010614ReactomeR-HSA-90106141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010614.1LEFT-TO-RIGHTSLIT2 binds DystroglycanSLIT2 binds to dystroglycan (DAG1). The interaction involves the C-terminal region of human SLIT2. The species origin of the DAG1 construct was not specified and is assumed to be human. Dystroglycan is required for proper SLIT2 localization within the basement membrane and the floor plate. Dystroglycan glycosylation, mediated at least in part by B4GAT1 (B3GNT1) and ISPD, is likely required for its interaction with SLIT2, but it has not been annotated. Mice mutant for B4gat1, Ispd or Dag1 have axon guidance defects similar to those observed in Slit or Robo mutant mice (Wright et al. 2012).Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04DystroglycanReactome DB_ID: 2328140plasma membraneGENE ONTOLOGYGO:0005886DAG1DAG1(30-653)Alpha-dystroglycanDystroglycan alphaDAG1_HUMANReactome DB_ID: 2328152UniProt:Q14118 DAG1DAG1FUNCTION The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cell migration, and epithelial polarization.SUBUNIT Monomer. Heterodimer of alpha- and beta-dystroglycan subunits which are the central components of the dystrophin-glycoprotein complex. This complex then can form a dystrophin-associated glycoprotein complex (DGC) which is composed of three subcomplexes: a cytoplasmic complex comprised of DMD (or UTRN), DTNA and a number of syntrophins, such as SNTB1, SNTB2, SNTG1 and SNTG2, the transmembrane dystroglycan complex, and the sarcoglycan-sarcospan complex. Interacts (via the N-terminal of alphaDAG1) with LARGE1; the interaction enhances laminin binding (By similarity). Interacts with SGCD. Interacts with AGR2 and AGR3. Interacts (betaDAG1) with DMD; the interaction is inhibited by phosphorylation on the PPXY motif. Interacts (betaDAG1, via its PPXY motif) with UTRN (via its WWW and ZZ domains); the interaction is inhibited by phosphorylation on the PPXY motif. Interacts (betaDAG1, via its phosphorylated PPXY motif) with the SH2 domain-containing proteins, FYN, CSK, NCK and SHC. Interacts (betaDAG1) with CAV3 (via a central WW-like domain); the interaction disrupts the binding of DMD. BetaDAG1 directly interacts with ANK3, but not with ANK2; this interaction does not interfere with DMD-binding and is required for retention at costameres (By similarity). Identified in a dystroglycan complex that contains at least PRX, DRP2, UTRN, DMD and DAG1 (By similarity). Interacts with POMGNT1 (PubMed:27493216).SUBUNIT (Microbial infection) Interacts with lassa virus and lymphocytic choriomeningitis virus glycoprotein (PubMed:16254364, PubMed:19324387).SUBUNIT (Microbial infection) Interacts with surface molecules of mycobacterium leprae.TISSUE SPECIFICITY Expressed in a variety of fetal and adult tissues. In epidermal tissue, located to the basement membrane. Also expressed in keratinocytes and fibroblasts.PTM Autolytic cleavage produces the alpha and beta subunits. In cutaneous cells, as well as in certain pathological conditions, shedding of beta-dystroglycan can occur releasing a peptide of about 30 kDa.PTM SRC-mediated phosphorylation of the PPXY motif of the beta subunit recruits SH2 domain-containing proteins, but inhibits binding to WWW domain-containing proteins, DMD and UTRN. This phosphorylation also inhibits nuclear entry.UniProtQ1411830EQUAL653EQUALReactome Database ID Release 752328152Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2328152ReactomeR-HSA-23281521Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2328152.11DAG1DAG1(654-895)Beta-dystroglycanDAG1_HUMANReactome DB_ID: 2328154654EQUAL895EQUALReactome Database ID Release 752328154Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2328154ReactomeR-HSA-23281541Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2328154.11Reactome Database ID Release 752328140Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2328140ReactomeR-HSA-23281401Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2328140.1SLIT2:DystroglycanReactome DB_ID: 901086911Reactome Database ID Release 759010869Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010869ReactomeR-HSA-90108691Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010869.1Reactome Database ID Release 759010872Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010872ReactomeR-HSA-90108722Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010872.223217742Pubmed2012Dystroglycan organizes axon guidance cue localization and axonal pathfindingWright, Kevin MLyon, Krissy ALeung, HaiwenLeahy, Daniel JMa, LeGinty, David DNeuron 76:931-44LEFT-TO-RIGHTSLIT1 binds COL4A5Based on studies in zebrafish, SLIT1 binds to a type IV collagen COL4A5, which forms the basement membrane on the surface of the optical tectum. COL4A5 and HSPGs may act synergistically to anchor SLIT1 in the basement membrane. ROBO2 receptor is required for lamina-specific axon pathfinding of retinal ganglion cells in the optical tectum (Xiao et al. 2011).Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04SLIT1Slit homolog 1 proteinSLT1_HUMANReactome DB_ID: 204359UniProt:O75093 SLIT1SLIT1KIAA0813MEGF4SLIL1FUNCTION Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navigation at the ventral midline of the neural tube and projection of axons to different regions (By similarity). SLIT1 and SLIT2 together seem to be essential for midline guidance in the forebrain by acting as repulsive signal preventing inappropriate midline crossing by axons projecting from the olfactory bulb.SUBUNIT Interacts with ROBO1 and GREM1.TISSUE SPECIFICITY Predominantly expressed in adult forebrain. Expressed in fetal brain, lung and kidney.UniProtO7509334EQUAL1534EQUALReactome Database ID Release 75204359Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=204359ReactomeR-HSA-2043592Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-204359.2Converted from EntitySet in ReactomeCollagen alpha-5(IV) chainsReactome DB_ID: 21273903x4Hyp-3Hyp-GalHyl-COL4A53,4-Hyp 5-Gal-Hyl collagen alpha-5(IV) chainReactome DB_ID: 2127335UniProt:P29400 COL4A5COL4A5FUNCTION Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.SUBUNIT There are six type IV collagen isoforms, alpha 1(IV)-alpha 6(IV), each of which can form a triple helix structure with 2 other chains to generate type IV collagen network.TISSUE SPECIFICITY Isoform 2 is found in kidney.DOMAIN Alpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain.PTM Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.PTM Type IV collagens contain numerous cysteine residues which are involved in inter- and intramolecular disulfide bonding. 12 of these, located in the NC1 domain, are conserved in all known type IV collagens.PTM The trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys and Met residues.DISEASE Deletions covering the N-terminal regions of COL4A5 and COL4A6, which are localized in a head-to-head manner, are found in the chromosome Xq22.3 centromeric deletion syndrome. This results in a phenotype with features of diffuse leiomyomatosis and Alport syndrome (DL-ATS).SIMILARITY Belongs to the type IV collagen family.UniProtP29400(2S,4R)-4-hydroxyprolineMODMOD:00039(2S,3S)-3-hydroxyprolineMODMOD:00038O5-galactosyl-L-hydroxylysineMODMOD:0191427EQUAL1685EQUALReactome Database ID Release 752127335Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2127335ReactomeR-HSA-21273351Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2127335.13x4Hyp-3Hyp-5Hyl-COL4A53,4-Hyp 5-Hyl collagen alpha-5(IV) chainReactome DB_ID: 2127411(2S,5R)-5-hydroxylysineMODMOD:0003727EQUAL1685EQUALReactome Database ID Release 752127411Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2127411ReactomeR-HSA-21274111Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2127411.13x4Hyp-3Hyp-GlcGalHyl-COL4A53,4-Hyp Glu-Gal-Hyl collagen alpha-5(IV) chainReactome DB_ID: 2127322O5-glucosylgalactosyl-L-hydroxylysineMODMOD:0016227EQUAL1685EQUALReactome Database ID Release 752127322Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2127322ReactomeR-HSA-21273221Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2127322.13x4Hyp-3Hyp-COL4A53,4-hydroxyprolyl collagen alpha-5(IV) chainReactome DB_ID: 212729727EQUAL1685EQUALReactome Database ID Release 752127297Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2127297ReactomeR-HSA-21272971Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2127297.13x4Hyp-GalHyl-COL4A54-Hyp 5-Gal-Hyl collagen alpha-5(IV) chainReactome DB_ID: 212734427EQUAL1685EQUALReactome Database ID Release 752127344Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2127344ReactomeR-HSA-21273441Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2127344.13x4Hyp-5Hyl-COL4A54-Hyp 5-Hyl collagen alpha-5(IV) chainReactome DB_ID: 212733227EQUAL1685EQUALReactome Database ID Release 752127332Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2127332ReactomeR-HSA-21273321Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2127332.13x4Hyp-GlcGalHyl-COL4A54-Hyp Glu-Gal-Hyl collagen alpha-5(IV) chainReactome DB_ID: 212742627EQUAL1685EQUALReactome Database ID Release 752127426Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2127426ReactomeR-HSA-21274261Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2127426.13x4Hyp-COL4A54-hydroxyprolyl collagen alpha-5(IV) chainReactome DB_ID: 212734927EQUAL1685EQUALReactome Database ID Release 752127349Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2127349ReactomeR-HSA-21273491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2127349.1GalHyl-COL4A55-Gal-Hyl collagen alpha-5(IV) chainReactome DB_ID: 212740427EQUAL1685EQUALReactome Database ID Release 752127404Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2127404ReactomeR-HSA-21274041Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2127404.15Hyl-COL4A55-hydroxylysyl collagen alpha-5(IV) chainReactome DB_ID: 212739527EQUAL1685EQUALReactome Database ID Release 752127395Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2127395ReactomeR-HSA-21273951Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2127395.1COL4A5Collagen alpha-5(IV) chainReactome DB_ID: 212730727EQUAL1685EQUALReactome Database ID Release 752127307Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2127307ReactomeR-HSA-21273071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2127307.1GlcGalHyl-COL4A5Glu-Gal-Hyl collagen alpha-5(IV) chainReactome DB_ID: 212744627EQUAL1685EQUALReactome Database ID Release 752127446Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2127446ReactomeR-HSA-21274461Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2127446.1Reactome Database ID Release 752127390Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2127390ReactomeR-HSA-21273901Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2127390.1SLIT1:COL4A5Reactome DB_ID: 901040011Reactome Database ID Release 759010400Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010400ReactomeR-HSA-90104001Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010400.1Reactome Database ID Release 759010396Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010396ReactomeR-HSA-90103961Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010396.121729787Pubmed2011Assembly of lamina-specific neuronal connections by slit bound to type IV collagenXiao, TongStaub, WendyRobles, EstuardoGosse, Nathan JCole, Gregory JBaier, HerwigCell 146:164-76LEFT-TO-RIGHTLHX2 binds to ROBO1 gene locusBased on studies in mice, a LIM-homeodomain transcription factor LHX2 binds to evolutionarily conserved LHX2 binding elements about 30 kb downstream from the ROBO1 gene transcription start site (Marcos-Mondejar et al. 2012).Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04ROBO1 geneReactome DB_ID: 9011093ENSEMBL:ENSG00000169855 ROBO1ROBO1DUTT1ENSEMBLENSG00000169855Reactome Database ID Release 759011093Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011093ReactomeR-HSA-90110931Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011093.1LHX2LIM/homeobox protein Lhx2LHX2_HUMANReactome DB_ID: 9011100UniProt:P50458 LHX2LHX2LH2FUNCTION Acts as a transcriptional activator. Stimulates the promoter of the alpha-glycoprotein gene. Transcriptional regulatory protein involved in the control of cell differentiation in developing lymphoid and neural cell types (By similarity).SUBUNIT Interacts (via LIM domains) with CITED2. Interacts with POU4F2.DOMAIN LIM domains are necessary for transcription activation.UniProtP504581EQUAL406EQUALReactome Database ID Release 759011100Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011100ReactomeR-HSA-90111001Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011100.1LHX2:ROBO1 geneReactome DB_ID: 901111411Reactome Database ID Release 759011114Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011114ReactomeR-HSA-90111141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011114.1Reactome Database ID Release 759011074Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011074ReactomeR-HSA-90110741Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011074.122457488Pubmed2012The lhx2 transcription factor controls thalamocortical axonal guidance by specific regulation of robo1 and robo2 receptorsMarcos-MondĆ©jar, PaulaPeregrĆn, SandraLi, James YCarlsson, LeifTole, ShubhaLópez-Bendito, GuillerminaJ. Neurosci. 32:4372-85LEFT-TO-RIGHTROBO1 gene expression is inhibited by LHX2Based on studies in mice, LHX2, a LIM-homeodomain transcription factor, directly represses transcription of the ROBO1 gene by binding to evolutionarily conserved LHX2 binding sites upstream of the ROBO1 gene promoter region. LHX2 is involved in thalamocortical axon guidance (Marcos-Mondejar et al. 2012). In commissural relay neurons of the dorsal spinal cord, however, ROBO1 expression is not affected by LHX2 (Wilson et al. 2008).<p>Transcription factors GBX2 and LMO3 may be indirectly involved in ROBO1 gene expression regulation by LHX2 (Chatterjee et al. 2012).Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04ROBO1Roundabout homolog 1ROB1_HUMANReactome DB_ID: 204361UniProt:Q9Y6N7 ROBO1ROBO1DUTT1FUNCTION Receptor for SLIT1 and SLIT2 that mediates cellular responses to molecular guidance cues in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development (PubMed:10102268, PubMed:24560577). Interaction with the intracellular domain of FLRT3 mediates axon attraction towards cells expressing NTN1 (PubMed:24560577). In axon growth cones, the silencing of the attractive effect of NTN1 by SLIT2 may require the formation of a ROBO1-DCC complex (By similarity). Plays a role in the regulation of cell migration via its interaction with MYO9B; inhibits MYO9B-mediated stimulation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA (PubMed:26529257). May be required for lung development (By similarity).SUBUNIT Homodimer. Dimerization is mediated by the extracellular domain and is independent of SLIT liganding (PubMed:24673457). Interacts with SLIT1 (By similarity). Interacts with SLIT2 (PubMed:10102268, PubMed:11404413, PubMed:17848514). Interacts with FLRT3 (PubMed:24560577). Interacts with MYO9B (via Rho-GAP domain) (PubMed:26529257).TISSUE SPECIFICITY Widely expressed, with exception of kidney.PTM Ubiquitinated. May be deubiquitinated by USP33.MISCELLANEOUS Maps within a region of overlapping homozygous deletions characterized in both small cell lung cancer cell lines (SCLC) and in a breast cancer cell line. The promoter region of ROBO1 shows complete hypermethylation of CpG sites in the BT-20 breast tumor cell lines, some primary invasive breast carcinomasa and some primary clear cell renal cell carcinomas (CC-RCC).SIMILARITY Belongs to the immunoglobulin superfamily. ROBO family.UniProtQ9Y6N726EQUAL1651EQUALReactome Database ID Release 75204361Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=204361ReactomeR-HSA-2043611Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-204361.1Reactome Database ID Release 759011083Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011083ReactomeR-HSA-90110832Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011083.218701067Pubmed2008A molecular program for contralateral trajectory: Rig-1 control by LIM homeodomain transcription factorsWilson, Sara IShafer, BethLee, Kevin JDodd, JaneNeuron 59:413-2423136391Pubmed2012Gbx2 regulates thalamocortical axon guidance by modifying the LIM and Robo codesChatterjee, MallikaLi, KairongChen, LiMaisano, XuGuo, QiuxiaGan, LinLi, James Y HDevelopment 139:4633-43INHIBITIONactiveUnit: #Protein22Reactome Database ID Release 759011118Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011118ReactomeR-HSA-90111181Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011118.1LEFT-TO-RIGHTUSP33 deubiquitinates ROBO1The ubiquitin protease USP33 deubiquitinates ROBO1, thus stabilizing it and increasing the concentration of ROBO1 at the plasma membrane (Yuasa-Kawada et al. 2009, Huang et al. 2015). USP33 is frequently downregulated in colorectal cancer, which is associated with lymph node metastasis and poor survival (Huang et al. 2015). USP33 is required for SLIT-ROBO1-mediated inhibition of breast cancer cell migration (Yuasa-Kawada et al. 2009). Ubiquitin ligases that ubiquitinate ROBO1 are not known.Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04H2OwaterReactome DB_ID: 29356cytosolGENE ONTOLOGYGO:0005829water [ChEBI:15377]waterChEBICHEBI:15377Reactome Database ID Release 7529356Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29356ReactomeR-ALL-293565Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29356.5COMPOUNDC00001additional informationMIMI:0361PolyUb-ROBO1Reactome DB_ID: 8986095ubiquitinylated lysineMODMOD:0114826EQUAL1651EQUALReactome Database ID Release 758986095Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8986095ReactomeR-HSA-89860951Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8986095.1Converted from EntitySet in ReactomeUbubiquitinReactome DB_ID: 113595RPS27ARPS27A(1-76)ubiquitin (RPS27A)Reactome DB_ID: 939205UniProt:P62979 RPS27ARPS27AUBA80UBCEP1SUBUNIT Ribosomal protein S27a is part of the 40S ribosomal subunit.MISCELLANEOUS Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.MISCELLANEOUS For a better understanding, features related to ubiquitin are only indicated for the first chain.SIMILARITY In the N-terminal section; belongs to the ubiquitin family.SIMILARITY In the C-terminal section; belongs to the eukaryotic ribosomal protein eS31 family.UniProtP629791EQUAL76EQUALReactome Database ID Release 75939205Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939205ReactomeR-HSA-9392051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939205.1UBA52UBA52(1-76)ubiquitin (UBA52)Reactome DB_ID: 939203UniProt:P62987 UBA52UBA52UBCEP2SUBUNIT Ribosomal protein L40 is part of the 60S ribosomal subunit. Interacts with UBQLN1 (via UBA domain).MISCELLANEOUS Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.MISCELLANEOUS For a better understanding, features related to ubiquitin are only indicated for the first chain.SIMILARITY In the N-terminal section; belongs to the ubiquitin family.SIMILARITY In the C-terminal section; belongs to the eukaryotic ribosomal protein eL40 family.UniProtP629871EQUAL76EQUALReactome Database ID Release 75939203Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939203ReactomeR-HSA-9392031Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939203.1UBBUBB(1-76)ubiquitin (UBB 1)Reactome DB_ID: 939214UniProt:P0CG47 UBBUBBSUBUNIT Interacts with SKP1-KMD2A and SKP1-KMD2B complexes.MISCELLANEOUS Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.MISCELLANEOUS The mRNA encoding variant UBB(+1) is produced by an unknown mechanism involving the deletion of a GT dinucleotide in the close proximity of a GAGAG motif (PubMed:9422699). This variant mRNA is found in normal brain, but the encoded protein accumulates only in brain neurofibrillary tangles and neuritic plaques in Alzheimer disease and other tauopathies, as well as polyglutaminopathies (PubMed:14597671). UBB(+1) variant cannot be used for polyubiquitination, is not effectively degraded by the proteasome when ubiquitinated and ubiquitinated UBB(+1) is refractory to disassembly by deubiquitinating enzymes (DUBs). In healthy brain, UBB(+1) C-terminus can be cleaved by UCHL3 (PubMed:21762696).MISCELLANEOUS For a better understanding, features related to ubiquitin are only indicated for the first chain.SIMILARITY Belongs to the ubiquitin family.UniProtP0CG471EQUAL76EQUALReactome Database ID Release 75939214Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939214ReactomeR-HSA-9392141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939214.1UBB(77-152)ubiquitin (UBB 2)Reactome DB_ID: 93921377EQUAL152EQUALReactome Database ID Release 75939213Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939213ReactomeR-HSA-9392131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939213.1UBB(153-228)ubiquitin (UBB 3)Reactome DB_ID: 939230153EQUAL228EQUALReactome Database ID Release 75939230Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939230ReactomeR-HSA-9392301Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939230.1UBCUBC(1-76)ubiquitin (UBC 1)Reactome DB_ID: 939188UniProt:P0CG48 UBCUBCMISCELLANEOUS Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.MISCELLANEOUS For the sake of clarity sequence features are annotated only for the first chain, and are not repeated for each of the following chains.SIMILARITY Belongs to the ubiquitin family.UniProtP0CG481EQUAL76EQUALReactome Database ID Release 75939188Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939188ReactomeR-HSA-9391881Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939188.1UBC(77-152)ubiquitin (UBC 2)Reactome DB_ID: 93916477EQUAL152EQUALReactome Database ID Release 75939164Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939164ReactomeR-HSA-9391641Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939164.1UBC(153-228)ubiquitin (UBC 3)Reactome DB_ID: 939258153EQUAL228EQUALReactome Database ID Release 75939258Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939258ReactomeR-HSA-9392581Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939258.1UBC(229-304)ubiquitin (UBC 4)Reactome DB_ID: 939192229EQUAL304EQUALReactome Database ID Release 75939192Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939192ReactomeR-HSA-9391921Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939192.1UBC(305-380)ubiquitin (UBC 5)Reactome DB_ID: 939232305EQUAL380EQUALReactome Database ID Release 75939232Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939232ReactomeR-HSA-9392321Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939232.1UBC(381-456)ubiquitin (UBC 6)Reactome DB_ID: 939191381EQUAL456EQUALReactome Database ID Release 75939191Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939191ReactomeR-HSA-9391911Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939191.1UBC(457-532)ubiquitin (UBC 7)Reactome DB_ID: 939184457EQUAL532EQUALReactome Database ID Release 75939184Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939184ReactomeR-HSA-9391841Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939184.1UBC(533-608)ubiquitin (UBC 8)Reactome DB_ID: 939239533EQUAL608EQUALReactome Database ID Release 75939239Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939239ReactomeR-HSA-9392391Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939239.1UBC(609-684)ubiquitin (UBC 9)Reactome DB_ID: 939165609EQUAL684EQUALReactome Database ID Release 75939165Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939165ReactomeR-HSA-9391651Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939165.1Reactome Database ID Release 75113595Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113595ReactomeR-HSA-1135951Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-113595.13ACTIVATIONUSP33Ubiquitin carboxyl-terminal hydrolase 33 ecNumber3.4.19.12/ecNumberUBP33_HUMANReactome DB_ID: 5696962UniProt:Q8TEY7 USP33USP33KIAA1097VDU1FUNCTION Deubiquitinating enzyme involved in various processes such as centrosome duplication, cellular migration and beta-2 adrenergic receptor/ADRB2 recycling. Involved in regulation of centrosome duplication by mediating deubiquitination of CCP110 in S and G2/M phase, leading to stabilize CCP110 during the period which centrioles duplicate and elongate. Involved in cell migration via its interaction with intracellular domain of ROBO1, leading to regulate the Slit signaling. Plays a role in commissural axon guidance cross the ventral midline of the neural tube in a Slit-dependent manner, possibly by mediating the deubiquitination of ROBO1. Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination of beta-arrestins (ARRB1 and ARRB2) and beta-2 adrenergic receptor (ADRB2). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta-arrestins, leading to beta-arrestins deubiquitination and disengagement from ADRB2. This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.SUBUNIT Interacts with VHL, leading to its ubiquitination and subsequent degradation. Interacts with ARRB1, ARRB2, ADRB2, DIO2 and ROBO1. Interacts with SELENBP1; in a selenium-dependent manner. Interacts with CCP110.TISSUE SPECIFICITY Widely expressed.DEVELOPMENTAL STAGE Increased expression in S and early G2 phases and lower levels in late G2 and M phases.DOMAIN The UBP-type zinc finger binds 3 zinc ions. However, it does not bind ubiquitin, probably because the conserved Arg in position 86 is replaced by a Glu residue.PTM Ubiquitinated via a VHL-dependent pathway for proteasomal degradation.SIMILARITY Belongs to the peptidase C19 family. USP20/USP33 subfamily.UniProtQ8TEY71EQUAL942EQUALReactome Database ID Release 755696962Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5696962ReactomeR-HSA-56969622Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5696962.2GENE ONTOLOGYGO:0004843gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 758986097Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8986097Reactome Database ID Release 758986083Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8986083ReactomeR-HSA-89860831Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8986083.119706539Pubmed2009Deubiquitinating enzyme USP33/VDU1 is required for Slit signaling in inhibiting breast cancer cell migrationYuasa-Kawada, JunichiKinoshita-Kawada, MarikoRao, YiWu, Jane YProc. Natl. Acad. Sci. U.S.A. 106:14530-525242263Pubmed2015USP33 mediates Slit-Robo signaling in inhibiting colorectal cancer cell migrationHuang, ZhaohuiWen, PushuaiKong, RuiruiCheng, HaipengZhang, BinbinQuan, CaoBian, ZehuaChen, MengmengZhang, ZhenfengChen, XiaopingDu, XiangLiu, JianghongZhu, LiFushimi, KazuoHua, DongWu, Jane YInt. J. Cancer 136:1792-802LEFT-TO-RIGHTHOXA2 binds ROBO2 gene promoterBased on studies in mice, the homeobox transcription factor HOXA2 binds to an evolutionarily conserved (also present in the human gene) HOX-PBX binding site in the second intron of the ROBO2 gene (Geisen et al. 2008). The heterodimerization partner of HOXA2 at the ROBO2 gene binding site is not known.Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04ROBO2 geneReactome DB_ID: 9010496ENSEMBL:ENSG00000185008 ROBO2ROBO2KIAA1568ENSEMBLENSG00000185008Reactome Database ID Release 759010496Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010496ReactomeR-HSA-90104961Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010496.1HOXA2Homeobox protein Hox-A2HXA2_HUMANReactome DB_ID: 5617494UniProt:O43364 HOXA2HOXA2HOX1KFUNCTION Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.SIMILARITY Belongs to the Antp homeobox family. Proboscipedia subfamily.UniProtO433641EQUAL376EQUALReactome Database ID Release 755617494Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617494ReactomeR-HSA-56174941Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5617494.1HOXA2:ROBO2 geneReactome DB_ID: 901050411Reactome Database ID Release 759010504Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010504ReactomeR-HSA-90105041Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010504.1Reactome Database ID Release 759010503Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010503ReactomeR-HSA-90105031Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010503.118547144Pubmed2008Hox paralog group 2 genes control the migration of mouse pontine neurons through slit-robo signalingGeisen, Marc JDi Meglio, ThomasPasqualetti, MassimoDucret, SebastienBrunet, Jean-FranƧoisChĆ©dotal, AlainRijli, Filippo MPLoS Biol. 6:e142LEFT-TO-RIGHTLHX2 binds to ROBO2 gene locusBased on studies in mice, a LIM-homeodomain transcription factor LHX2 binds to evolutionarily conserved LHX2 binding elements about 50 kb downstream from the ROBO2 gene transcription start site (Marcos-Mondejar et al. 2012).Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04LHX2:ROBO2 geneReactome DB_ID: 901110811Reactome Database ID Release 759011108Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011108ReactomeR-HSA-90111081Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011108.1Reactome Database ID Release 759011077Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011077ReactomeR-HSA-90110771Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011077.1LEFT-TO-RIGHTROBO2 gene transcription is stimulated by HOXA2 and inhibited by LHX2Based on studies in mice, the homeobox transcription factor HOXA2, which directly binds to an evolutionarily conserved site in the second intron of the ROBO2 gene, is needed for the maintenance of ROBO2 expression during pontine neuron migration (Geisen et al. 2008).<p>Also based on mouse studies, LHX2, a LIM-homeodomain transcription factor, directly represses transcription of the ROBO2 gene by binding to evolutionarily conserved LHX2 binding sites about 50 kb downstream from the ROBO2 gene transcription start site. LHX2 is involved in thalamocortical axon guidance (Marcos-Mondejar et al. 2012). In commissural relay neurons of the dorsal spinal cord, however, ROBO2 expression is not affected by LHX2 (Wilson et al. 2008).<p>In zebrafish, transcription of Robo2 is directly stimulated by Mecp2 (Leong et al. 2015).Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04ROBO2Roundabout homolog 2ROB2_HUMANReactome DB_ID: 197747UniProt:Q9HCK4 ROBO2ROBO2KIAA1568FUNCTION Receptor for SLIT2, and probably SLIT1, which are thought to act as molecular guidance cue in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development.SUBUNIT Interacts with SLIT2.DISEASE A chromosomal aberration involving ROBO2 is a cause of multiple congenital abnormalities, including severe bilateral VUR with ureterovesical junction defects. Translocation t(Y;3)(p11;p12) with PCDH11Y. This translocation disrupts ROBO2 and produces dominant-negative ROBO2 proteins that abrogate SLIT-ROBO signaling in vitro.SIMILARITY Belongs to the immunoglobulin superfamily. ROBO family.UniProtQ9HCK422EQUAL1378EQUALReactome Database ID Release 75197747Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=197747ReactomeR-HSA-1977471Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-197747.1Reactome Database ID Release 759010523Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010523ReactomeR-HSA-90105232Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010523.226733807Pubmed2015Methyl-CpG Binding Protein 2 (Mecp2) Regulates Sensory Function Through Sema5b and Robo2Leong, Wan YLim, Zhi HKorzh, VladimirPietri, ThomasGoh, Eyleen L KFront Cell Neurosci 9:481INHIBITIONactiveUnit: #Protein22Reactome Database ID Release 759011104Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011104ReactomeR-HSA-90111041Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011104.1ACTIVATIONactiveUnit: #Protein41Reactome Database ID Release 759010524Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9010524ReactomeR-HSA-90105241Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9010524.1LEFT-TO-RIGHTLHX2,(LHX9) binds the ROBO3 gene promoterBased on studies in mice, a LIM-homeodomain transcription factor LHX2, and possibly LHX9, binds to conserved LHX2 binding elements in the promoter region of the ROBO3 gene (Wilson et al. 2008).Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04ROBO3 geneReactome DB_ID: 9011166ENSEMBL:ENSG00000154134 ROBO3ROBO3ENSEMBLENSG00000154134Reactome Database ID Release 759011166Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011166ReactomeR-HSA-90111661Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011166.1Converted from EntitySet in ReactomeLHX2,(LHX9)Reactome DB_ID: 9011165LHX9LIM/homeobox protein Lhx9LHX9_HUMANReactome DB_ID: 9011158UniProt:Q9NQ69 LHX9LHX9FUNCTION Involved in gonadal development.SUBUNIT Interacts with LDB1 and LDB2.UniProtQ9NQ691EQUAL397EQUALReactome Database ID Release 759011158Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011158ReactomeR-HSA-90111581Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011158.1Reactome Database ID Release 759011165Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011165ReactomeR-HSA-90111651Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011165.1LHX2,(LHX9):ROBO3 geneReactome DB_ID: 901116411Reactome Database ID Release 759011164Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011164ReactomeR-HSA-90111641Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011164.1Reactome Database ID Release 759011145Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011145ReactomeR-HSA-90111451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011145.1LEFT-TO-RIGHTROBO3.1 expression is stimulated by LHX2,(LHX9)Based on studies in mice, expression of the ROBO3.1 isoform from the ROBO3 gene is directly stimulated by LHX2 and possibly LHX9. LHX2/9-mediated regulation of ROBO3.1 levels is involved in midline crossing by commissural relay neurons of the dorsal spinal cord (Wilson et al. 2008). ROBO3.1 levels, however, seem to be unaffected by LHX2 in thalamocortical neurons (Marcos-Mondejar et al. 2012).Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04ROBO3.1 mRNAReactome DB_ID: 9011385ENSEMBL:ENST00000397801 ROBO3.1ROBO3.1ENSEMBLENST000003978011EQUAL4569EQUALReactome Database ID Release 759011385Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011385ReactomeR-HSA-90113851Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011385.1Reactome Database ID Release 759011143Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011143ReactomeR-HSA-90111432Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011143.2ACTIVATIONactiveUnit: #Protein43Reactome Database ID Release 759011163Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011163ReactomeR-HSA-90111631Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011163.1LEFT-TO-RIGHTMSI1 binds ROBO3.1 mRNABased on studies in mice, MSI1, and RNA-binding protein, binds to ROBO3.1 mRNA (Kuwako et al. 2010).Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04MSI1RNA-binding protein Musashi homolog 1Musashi-1Reactome DB_ID: 9011403UniProt:O43347 MSI1MSI1FUNCTION RNA binding protein that regulates the expression of target mRNAs at the translation level. Regulates expression of the NOTCH1 antagonist NUMB. Binds RNA containing the sequence 5'-GUUAGUUAGUUAGUU-3' and other sequences containing the pattern 5'-[GA]U(1-3)AGU-3'. May play a role in the proliferation and maintenance of stem cells in the central nervous system (By similarity).TISSUE SPECIFICITY Detected in fetal kidney, brain, liver and lung, and in adult brain and pancreas. Detected in hepatoma cell lines.DOMAIN The first RNA recognition motif binds more strongly to RNA compared to the second one.SIMILARITY Belongs to the Musashi family.UniProtO433471EQUAL362EQUALReactome Database ID Release 759011403Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011403ReactomeR-HSA-90114031Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011403.1ROBO3.1 mRNA:MSI1Reactome DB_ID: 901140111Reactome Database ID Release 759011401Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011401ReactomeR-HSA-90114011Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011401.1Reactome Database ID Release 759011346Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011346ReactomeR-HSA-90113462Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011346.220696379Pubmed2010Neural RNA-binding protein Musashi1 controls midline crossing of precerebellar neurons through posttranscriptional regulation of Robo3/Rig-1 expressionKuwako, Ken-ichiroKakumoto, KyokoImai, TakaoIgarashi, ManaHamakubo, TakaoSakakibara, Shin-ichiTessier-Lavigne, MarcOkano, Hirotaka JamesOkano, HNeuron 67:407-21LEFT-TO-RIGHTROBO3.1 mRNA translation is positively regulated by MSI1Based on studies in mice, binding of MSI1 to ROBO3.1 mRNA positively regulates ROBO3.1 mRNA translation, resulting in increased levels of ROBO3.1 protein. Similar to Robo3 knockout mice, Msi1 knockout mice also show sever abnormalities in axonal midline crossing and migration of precerebellar neurons (Kuwako et al. 2010).Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04ROBO3.1ROBO3-1ROBO3A.1Roundabout homolog 3 isoform AROBO3 isoform 1Reactome DB_ID: 426410UniProt:Q96MS0-1 ROBO3ROBO3FUNCTION Thought to be involved during neural development in axonal navigation at the ventral midline of the neural tube (By similarity). In spinal chord development plays a role in guiding commissural axons probably by preventing premature sensitivity to Slit proteins thus inhibiting Slit signaling through ROBO1 (By similarity). Required for hindbrain axon midline crossing (PubMed:15105459).SUBUNIT Probably interacts with SLIT2.SIMILARITY Belongs to the immunoglobulin superfamily. ROBO family.UniProt IsoformQ96MS0-121EQUAL1386EQUALReactome Database ID Release 75426410Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=426410ReactomeR-HSA-4264102Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-426410.2Reactome Database ID Release 759011347Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011347ReactomeR-HSA-90113473Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011347.3ACTIVATIONactiveUnit: #Protein45Reactome Database ID Release 759011411Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011411ReactomeR-HSA-90114111Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011411.1LEFT-TO-RIGHTZSWIM8 binds ROBO3.1Based on studies in C. elegans and with recombinant human and mouse proteins, ZSWIM8 and its C. elegans orthologue EBAX-1 are predicted to be an E3 ubiquitin ligase component of the CUL2 ubiquitin ligase complex. ZSWIM8 co-immunoprecipitates with the CUL2 ubiquitin ligase complex components Elongin-B (ELOB) and Elongin-C (ELOC). The BC-box and Cul2-box of ZSWIM8 are needed for interaction with ELOB and ELOC, implying the presence of other CUL2 complex components in the complex of ZSWIM8, ELOB and ELOC. ZSWIM8 binds to wild-type ROBO3.1, but preferentially associates with misfolded or mutant ROBO3.1 proteins, suggesting that it is involved in the quality control of ROBO3.1 (Wang et al. 2013).Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04ZSWIM8-CUL2 E3 ubiquitin ligaseReactome DB_ID: 9011265ELOCTCEB1Transcription elongation factor B polypeptide 1RNA polymerase II transcription factor SIII subunit CSIII p15Elongin-CEloCElongin 15 kDa subunitReactome DB_ID: 180535UniProt:Q15369 ELOCELOCTCEB1FUNCTION SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex) (PubMed:7821821). In embryonic stem cells, the elongin BC complex is recruited by EPOP to Polycomb group (PcG) target genes in order generate genomic region that display both active and repressive chromatin properties, an important feature of pluripotent stem cells (By similarity).FUNCTION The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.SUBUNIT Heterotrimer of an A (ELOA, ELOA2 or ELOA3P), ELOB and ELOC subunit (PubMed:17997974). The elongin BC complex interacts with EPOP; leading to recruit the elongin BC complex to Polycomb group (PcG) target genes, thereby restricting excessive activity of the PRC2/EED-EZH2 complex (By similarity). Part of E3 ubiquitin ligase complexes with CUL5 or CUL2, RBX1 and a substrate adapter protein that can be either SOCS1, SOCS5, ELOA, VHL or WSB1 (PubMed:15590694). The elongin BC complex is part of a complex with VHL and hydroxylated HIF1A (PubMed:12050673, PubMed:12004076). Part of an E3 ubiquitin-protein ligase complex including ZYG11B, CUL2 and Elongin BC. Part of an E3 ubiquitin-protein ligase complex including ZER1, CUL2 and Elongin BC (PubMed:17304241). Interacts with VHL (PubMed:10205047, PubMed:12050673, PubMed:11006129). Interacts with TMF1 (PubMed:15467733). Interacts with SPSB1 (PubMed:17189197). Interacts with SPSB1. Interacts with KLHDC10; which may be an E3 ubiquitin ligase complex substrate recognition component (PubMed:23102700). Interacts with NOS2 in the presence of SPSB1 or SPSB2 or SPSB4 (PubMed:21199876).SUBUNIT (Microbial infection) Substrate adapter protein can be a viral protein such as HIV Vif.SUBUNIT (Microbial infection) Interacts with human respiratory syncytial virus (HRSV) protein NS1.SUBUNIT (Microbial infection) Interacts with molluscum contagiosum virus MC132.SUBUNIT (Microbial infection) Interacts with herpes virus 8 virus protein LANA1.TISSUE SPECIFICITY Overexpressed in prostate cancer cell line PC-3 and breast cancer cell line SK-BR-3.SIMILARITY Belongs to the SKP1 family.UniProtQ153691EQUAL112EQUALReactome Database ID Release 75180535Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=180535ReactomeR-HSA-1805353Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-180535.31RBX1ROC1Reactome DB_ID: 180582UniProt:P62877 RBX1RBX1RNF75ROC1FUNCTION E3 ubiquitin ligase component of multiple cullin-RING-based E3 ubiquitin-protein ligase (CRLs) complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins, including proteins involved in cell cycle progression, signal transduction, transcription and transcription-coupled nucleotide excision repair (PubMed:10230407, PubMed:10579999, PubMed:15983046, PubMed:16678110, PubMed:19112177, PubMed:19679664, PubMed:23455478, PubMed:27565346, PubMed:29769719, PubMed:11961546, PubMed:22748924). CRLs complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, ARIH1 mediating addition of the first ubiquitin on CRLs targets (PubMed:27565346). The functional specificity of the E3 ubiquitin-protein ligase complexes depends on the variable substrate recognition components. As a component of the CSA complex promotes the ubiquitination of ERCC6 resulting in proteasomal degradation. Recruits the E2 ubiquitin-conjugating enzyme CDC34 to the complex and brings it into close proximity to the substrate. Probably also stimulates CDC34 autoubiquitination. May be required for histone H3 and histone H4 ubiquitination in response to ultraviolet and for subsequent DNA repair. Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41. In concert with ATF2 and CUL3, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Part of a SCF complex consisting of CUL1, RBX1, SKP1 and SKP2 (PubMed:11961546). Part of a SCF-like complex consisting of CUL7, RBX1, SKP1 and FBXW8. Part of CBC(VHL) complexes with elongin BC complex (ELOB and ELOC), CUL2 or CUL5 and VHL. Part of the CSA complex (DCX(ERCC8) complex), a DCX E3 ubiquitin-protein ligase complex containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II. Part of multisubunit E3 ubiquitin ligase complexes with elongin BC complex (ELOB and ELOC), CUL2 and MED8; elongin BC complex (ELOB and ELOC), CUL5 and MUF1. Part of multisubunit complexes with elongin BC complex (ELOB and ELOC), elongin A/ELOA or SOCS1 or WSB1 and CUL5. Interacts directly with CUL1 and probably also with CUL2, CUL3, CUL4A, CUL4B, CUL5 and CUL7. Interacts with CDC34 (PubMed:22748924). Interacts with GLMN. GLMN competes for the binding site of the E2 ubiquitin-conjugating enzyme CDC34 and disrupts CDC34 binding (PubMed:22748924). Interacts with COPS6. Component of the DCX DET1-COP1 ubiquitin ligase complex at least composed of RBX1, DET1, DDB1, CUL4A and COP1. Part of an E3 ligase complex composed of RBX1, DDB1, DDB2 and CUL4A or CUL4B. Interacts with UBE2M. Part of a SCF complex consisting of CUL1, FBXO3, RBX1 and SKP1; this complex interacts with PML via FBXO3. Component of the SCF(Cyclin F) complex consisting of CUL1, RBX1, SKP1 and CCNF. Identified in a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex together with HINT1 and CDC34. Component of multiple BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes formed of CUL3, RBX1 and a variable BTB domain-containing protein. Part of the BCR(ENC1) complex containing ENC1. Part of the BCR(GAN) complex containing GAN. Part of the BCR(KLHL41) complex containing KLHL41. Part of the BCR(KEAP1) complex containing KEAP1. Interacts with DCUN1D3. Interacts with SESN1 and SESN2 (PubMed:23274085). Interacts with NOTCH2 (PubMed:29149593). Component of the BCR(KLHL22) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL22 and RBX1 (PubMed:23455478).SUBUNIT (Microbial infection) Interacts with human adenovirus 5 protein E1A; this interaction inhibits RBX1-CUL1-dependent elongation reaction of ubiquitin chains by the SCF(FBW7) complex.TISSUE SPECIFICITY Widely expressed.DOMAIN The RING-type zinc finger domain is essential for ubiquitin ligase activity (PubMed:10230407). It coordinates an additional third zinc ion (PubMed:11961546, PubMed:22748924).SIMILARITY Belongs to the RING-box family.UniProtP628772EQUAL108EQUALReactome Database ID Release 75180582Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=180582ReactomeR-HSA-1805821Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-180582.11ZSWIM8Reactome DB_ID: 9011266UniProt:A7E2V4 ZSWIM8ZSWIM8KIAA0913SIMILARITY Contains 1 SWIM-type zinc finger.UniProtA7E2V41EQUAL1837EQUALReactome Database ID Release 759011266Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011266ReactomeR-HSA-90112661Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011266.11ELOBTCEB2Transcription elongation factor B polypeptide 2RNA polymerase II transcription factor SIII subunit BSIII p18Elongin-BElongin 18 kDa subunitReactome DB_ID: 180551UniProt:Q15370 ELOBELOBTCEB2FUNCTION SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex) (PubMed:7638163). In embryonic stem cells, the elongin BC complex is recruited by EPOP to Polycomb group (PcG) target genes in order generate genomic region that display both active and repressive chromatin properties, an important feature of pluripotent stem cells (By similarity).FUNCTION The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Heterotrimer of an A (ELOA, ELOA2 or ELOA3), ELOB and ELOC subunit (PubMed:10205047, PubMed:17997974). The elongin BC complex interacts with EPOP; leading to recruit the elongin BC complex to Polycomb group (PcG) target genes, thereby restricting excessive activity of the PRC2/EED-EZH2 complex (By similarity). Part of E3 ubiquitin ligase complexes with CUL5 or CUL2, RBX1 and a substrate adapter protein that can be either SOCS1, SOCS5, ELOA, VHL or WSB1 (PubMed:15590694, PubMed:22286099). Interacts with VHL (PubMed:10205047, PubMed:11006129). Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. Interacts with SPSB1 (PubMed:17189197). Interacts with KLHDC10; which may be an E3 ubiquitin ligase complex substrate recognition component (PubMed:23102700).SUBUNIT (Microbial infection) Substrate adapter protein can be a viral protein such as HIV Vif.SUBUNIT (Microbial infection) Interacts with molluscum contagiosum virus MC132.SUBUNIT (Microbial infection) Interacts with herpes virus 8 virus protein LANA1.UniProtQ153701EQUAL118EQUALReactome Database ID Release 75180551Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=180551ReactomeR-HSA-1805513Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-180551.31CUL2Cullin-2CUL2_HUMANReactome DB_ID: 416982UniProt:Q13617 CUL2CUL2FUNCTION Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. ECS complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). May serve as a rigid scaffold in the complex and may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the ECS complex depends on the substrate recognition component. ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor (HIF).PATHWAY Protein modification; protein ubiquitination.SUBUNIT Component of multiple ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes formed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and a variable substrate-specific adapter. Component of the ECS(VHL) or CBC(VHL) complex containing VHL. Component of the ECS(MED8) complex with the probable substrate recognition component MED8. Component of the ECS(LRR1) complex with the probable substrate recognition component LRR1. Component of a probable ECS E3 ubiquitin-protein ligase complex containing CUL2, RBX1, ELOB, ELOC and FEM1B. Part of an E3 ubiquitin-protein ligase complex including ZYG11B, CUL2 and Elongin BC. Part of an E3 ubiquitin-protein ligase complex including ZER1, CUL2 and Elongin BC. Interacts with RBX1, RNF7, FEM1B and TIP120A/CAND1. Interacts with COPS2, and MED8. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. Interacts with KLHDC10; which may be an E3 ubiquitin ligase complex substrate recognition component. Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1 (PubMed:24076655, PubMed:27565346).SUBUNIT (Microbial infection) Interacts with human respiratory syncytial virus (HRSV) protein NS1.PTM Neddylated; which enhances the ubiquitination activity of ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes. CBC(VHL) complex formation seems to promote neddylation. Deneddylated via its interaction with the COP9 signalosome (CSN) complex (By similarity).SIMILARITY Belongs to the cullin family.UniProtQ136171EQUAL745EQUALReactome Database ID Release 75416982Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=416982ReactomeR-HSA-4169821Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-416982.11Reactome Database ID Release 759011265Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011265ReactomeR-HSA-90112651Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011265.1ROBO3.1:ZSWIM8-CUL2Reactome DB_ID: 901128611Reactome Database ID Release 759011286Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011286ReactomeR-HSA-90112861Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011286.1Reactome Database ID Release 759011289Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011289ReactomeR-HSA-90112892Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011289.224012004Pubmed2013The EBAX-type Cullin-RING E3 ligase and Hsp90 guard the protein quality of the SAX-3/Robo receptor in developing neuronsWang, ZhipingHou, YanliGuo, Xingvan der Voet, MoniqueBoxem, MikeDixon, JEChisholm, Andrew DJin, YishiNeuron 79:903-16LEFT-TO-RIGHTZSWIM8 ubiquitinates ROBO3.1Based on studies with C. elegans proteins, ZSWIM8 (orthologue of C. elegans EBAX-1) promotes ubiquitination of ROBO3.1 (orthologue of C. elegans SAX-3) (Wang et al. 2013).Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04Ub-ROBO3.1:ZSWIM8-CUL2Reactome DB_ID: 90113091Ub-ROBO3.1Ub-ROBO3A.1Reactome DB_ID: 901130121EQUAL1386EQUALReactome Database ID Release 759011301Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011301ReactomeR-HSA-90113011Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011301.11Reactome Database ID Release 759011309Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011309ReactomeR-HSA-90113091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011309.1ACTIVATIONactiveUnit: #Complex14GENE ONTOLOGYGO:0061630Reactome Database ID Release 759011307Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011307Reactome Database ID Release 759011300Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011300ReactomeR-HSA-90113001Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011300.1LEFT-TO-RIGHTProteasome degrades ubiquitinated ROBO3.1Based on studies using recombinant C. elegans proteins expressed in human 293T cells, ZSWIM8-mediated ubiquitination of ROBO3.1 targets ROBO3.1 for proteasome-mediated degradation (Wang et al. 2013).Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04ACTIVATION26S proteasomeReactome DB_ID: 68819AFPSMD426S proteasome non-ATPase regulatory subunit 426S proteasome regulatory subunit S5ARpn10Multiubiquitin chain binding proteinAntisecretory factor-1ASFReactome DB_ID: 68800UniProt:P55036 PSMD4PSMD4MCB1FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMD4 acts as an ubiquitin receptor subunit through ubiquitin-interacting motifs and selects ubiquitin-conjugates for destruction. Displays a preferred selectivity for longer polyubiquitin chains.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases and few additional components including PSMD4 (PubMed:27428775, PubMed:27342858). Interacts with NUB1 (PubMed:11585840). Interacts with SQSTM1 (PubMed:15340068). Interacts with UBQLN4 (PubMed:15280365). Interacts with UBE3A (PubMed:22645313). Interacts with UBQLN1 (via ubiquitin-like domain) (PubMed:15147878). Interacts with DDI2 (PubMed:29290612).DOMAIN The 2 UIM motifs are involved in the binding to a multi-ubiquitin chain in a cooperative way.SIMILARITY Belongs to the proteasome subunit S5A family.UniProtP550361EQUAL377EQUALReactome Database ID Release 7568800Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68800ReactomeR-HSA-688002Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68800.21PSMD526S proteasome non-ATPase regulatory subunit 526S proteasome subunit S5B26S protease subunit S5 basicReactome DB_ID: 68802UniProt:Q16401 PSMD5PSMD5KIAA0072FUNCTION Acts as a chaperone during the assembly of the 26S proteasome, specifically of the base subcomplex of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD5:PSMC2:PSMC1:PSMD2 module which probably assembles with a PSMD10:PSMC4:PSMC5:PAAF1 module followed by dissociation of PSMD5.SUBUNIT Interacts with PSMC1, PSMC2, PSMD1 and PSMD6. Part of transient complex containing PSMD5, PSMC2, PSMC1 and PSMD2 formed during the assembly of the 26S proteasome.DOMAIN Rich in dileucine repeats, which have been implicated in trafficking of a variety of transmembrane proteins.SIMILARITY Belongs to the proteasome subunit S5B/HSM3 family.CAUTION Was initially identified as a genuine component of the 26S proteasome.UniProtQ164012EQUAL504EQUALReactome Database ID Release 7568802Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68802ReactomeR-HSA-688022Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68802.21PSMD926S proteasome non-ATPase regulatory subunit 926S proteasome regulatory subunit p27Reactome DB_ID: 68810UniProt:O00233 PSMD9PSMD9FUNCTION Acts as a chaperone during the assembly of the 26S proteasome, specifically of the base subcomplex of the PA700/19S regulatory complex (RC). During the base subcomplex assembly is part of an intermediate PSMD9:PSMC6:PSMC3 module, also known as modulator trimer complex; PSMD9 is released during the further base assembly process.SUBUNIT Interacts with PSMC3. Part of a transient complex (modulator) containing PSMD9, PSMC6 and PSMC3 formed during the assembly of the 26S proteasome.TISSUE SPECIFICITY Expressed in all tissues tested, highly expressed in liver and kidney.SIMILARITY Belongs to the proteasome subunit p27 family.CAUTION Was initially identified as a component of the 26S proteasome.UniProtO002331EQUAL223EQUALReactome Database ID Release 7568810Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68810ReactomeR-HSA-688102Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68810.21PSMB11Proteasome subunit beta type-11PSB11_HUMANReactome DB_ID: 947607UniProt:A5LHX3 PSMB11PSMB11FUNCTION The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. Incorporated instead of PSMB5 or PSMB8, this unit reduces the chymotrypsin-like activity of the proteasome (By similarity). Plays a pivotal role in development of CD8-positive T cells (By similarity).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Incorporated instead of PSMB5 and PSMB8.SIMILARITY Belongs to the peptidase T1B family.UniProtA5LHX350EQUAL300EQUALReactome Database ID Release 75947607Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=947607ReactomeR-HSA-9476071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-947607.11PSMA8Proteasome subunit alpha type-7-likePSA7L_HUMANReactome DB_ID: 947610UniProt:Q8TAA3 PSMA8PSMA8PSMA7LFUNCTION Component of the spermatoproteasome, a proteasome specifically found in testis that promotes acetylation-dependent degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis. The proteasome is a protein complexe that degrades unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Required for 20S core proteasome assembly, essential for the degradation of meiotic proteins RAD51 and RPA1 at late prophase I and the progression of meiosis I during spermatogenesis. Localizes to the synaptonemal complex, a 'zipper'-like structure that holds homologous chromosome pairs in synapsis during meiotic prophase I.SUBUNIT Component of the outer alpha-ring of the 20S proteasome core which is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The catalytic chamber with the active sites is on the inside of the barrel. Interacts with canonical subunits of the spermatoproteasome, including proteasome activators PSME4 (also called PA200) and PSME3 (also called PA28-gamma). Interacts with proteasome-interacting proteins chaperones, ubiquitin ligases and ubiquitin specific proteases. Interacts with meiotic proteins cyclin dependent kinase CDK1 and the ATPase TRIP13 as well as proteins of the synaptonemal complex SIX6OS1 and SYCE3.SIMILARITY Belongs to the peptidase T1A family.UniProtQ8TAA31EQUAL256EQUALReactome Database ID Release 75947610Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=947610ReactomeR-HSA-9476101Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-947610.11PSMC226S protease regulatory subunit 7MSS1 proteinReactome DB_ID: 68771UniProt:P35998 PSMC2PSMC2MSS1FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC2 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC2 and few additional components (PubMed:27428775, PubMed:27342858). Interacts with NDC80/HEC; this interaction is detected only during M phase. Interacts and SQSTM1 (PubMed:15340068). Interacts with PAAF1 (PubMed:15831487). Directly interacts with TRIM5 (PubMed:22078707).INDUCTION Expression is not cell cycle-dependent and occurs throughout the cell cycle.SIMILARITY Belongs to the AAA ATPase family.UniProtP359982EQUAL433EQUALReactome Database ID Release 7568771Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68771ReactomeR-HSA-687712Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68771.21p42APSMD626S proteasome non-ATPase regulatory subunit 626S proteasome regulatory subunit S10Proteasome regulatory particle subunit p44S10Reactome DB_ID: 68804UniProt:Q15008 PSMD6PSMD6KIAA0107PFAAP4FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD6, a base containing 6 ATPases and few additional components.SIMILARITY Belongs to the proteasome subunit S10 family.UniProtQ150081EQUAL389EQUALReactome Database ID Release 7568804Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68804ReactomeR-HSA-688042Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68804.21PSME4Proteasome activator complex subunit 4PSME4_HUMANReactome DB_ID: 947606UniProt:Q14997 PSME4PSME4KIAA0077FUNCTION Associated component of the proteasome that specifically recognizes acetylated histones and promotes ATP- and ubiquitin-independent degradation of core histones during spermatogenesis and DNA damage response. Recognizes and binds acetylated histones via its bromodomain-like (BRDL) region and activates the proteasome by opening the gated channel for substrate entry. Binds to the core proteasome via its C-terminus, which occupies the same binding sites as the proteasomal ATPases, opening the closed structure of the proteasome via an active gating mechanism. Component of the spermatoproteasome, a form of the proteasome specifically found in testis: binds to acetylated histones and promotes degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis. Also involved in DNA damage response in somatic cells, by promoting degradation of histones following DNA double-strand breaks.SUBUNIT Homodimer. Interacts with the 20S and 26S proteasomes. Component of the spermatoproteasome, a form of the proteasome specifically found in testis.DOMAIN The bromodomain-like (BRDL) region specifically recognizes and binds acetylated histones.SIMILARITY Belongs to the BLM10 family.UniProtQ149971EQUAL1843EQUALReactome Database ID Release 75947606Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=947606ReactomeR-HSA-9476061Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-947606.11RPN2PSMD126S proteasome non-ATPase regulatory subunit 126S proteasome regulatory subunit S126S proteasome subunit p112Reactome DB_ID: 68786UniProt:Q99460 PSMD1PSMD1FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases and few additional components including PSMD1 (PubMed:27428775, PubMed:27342858). Interacts with ADRM1 (PubMed:16990800, PubMed:16906146). Interacts with ZFAND1 (PubMed:29804830).SIMILARITY Belongs to the proteasome subunit S1 family.UniProtQ994601EQUAL953EQUALReactome Database ID Release 7568786Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68786ReactomeR-HSA-687862Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68786.21PSMD326S proteasome non-ATPase regulatory subunit 326S proteasome regulatory subunit S3Proteasome subunit p58Reactome DB_ID: 68798UniProt:O43242 PSMD3PSMD3FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD3, a base containing 6 ATPases and few additional components (PubMed:27428775, PubMed:27342858). Interacts with UBQLN1 (via ubiquitin-like domain) (PubMed:15147878). Interacts with ERCC6 (PubMed:26030138).SIMILARITY Belongs to the proteasome subunit S3 family.UniProtO432421EQUAL534EQUALReactome Database ID Release 7568798Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68798ReactomeR-HSA-687982Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68798.21PSME2Proteasome activator complex subunit 2Proteasome activator 28-beta subunitPA28betaPA28bActivator of multicatalytic protease subunit 211S regulator complex beta subunitREG-betaReactome DB_ID: 68814UniProt:Q9UL46 PSME2PSME2FUNCTION Implicated in immunoproteasome assembly and required for efficient antigen processing. The PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern of the proteasome.SUBUNIT Heterodimer of PSME1 and PSME2, which forms a hexameric ring.INDUCTION By IFNG/IFN-gamma.SIMILARITY Belongs to the PA28 family.UniProtQ9UL462EQUAL239EQUALReactome Database ID Release 7568814Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68814ReactomeR-HSA-688142Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68814.21SHFM126S proteasome complex subunit DSS1DSS1_HUMANReactome DB_ID: 8866674UniProt:P60896 SEM1SEM1DSS1SHFDG1SHFM1C7orf76FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair (PubMed:15117943). Component of the TREX-2 complex (transcription and export complex 2), composed of at least ENY2, GANP, PCID2, SEM1, and either centrin CETN2 or CETN3 (PubMed:22307388). The TREX-2 complex functions in docking export-competent ribonucleoprotein particles (mRNPs) to the nuclear entrance of the nuclear pore complex (nuclear basket). TREX-2 participates in mRNA export and accurate chromatin positioning in the nucleus by tethering genes to the nuclear periphery. Binds and stabilizes BRCA2 and is thus involved in the control of R-loop-associated DNA damage and thus transcription-associated genomic instability. R-loop accumulation increases in SEM1-depleted cells.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including SEM1, a base containing 6 ATPases and few additional components (PubMed:27428775, PubMed:27342858). Belongs to the TREX-2 complex (transcription and export complex 2), composed of at least ENY2, GANP, PCID2, SEM1, and either centrin CETN2 or CETN3 (PubMed:22307388). Interacts with the C-terminal of BRCA2 (PubMed:10373512, PubMed:21719596).TISSUE SPECIFICITY Expressed in limb bud, craniofacial primordia and skin.SIMILARITY Belongs to the DSS1/SEM1 family.UniProtP608961EQUAL70EQUALReactome Database ID Release 758866674Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8866674ReactomeR-HSA-88666742Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8866674.21PSMB9Proteasome subunit beta type 9Proteasome subunit beta type 9 precursor Proteasome chain 7Macropain chain 7Multicatalytic endopeptidase complex chain 7RING12 proteinLow molecular mass protein 2Reactome DB_ID: 68765UniProt:P28065 PSMB9PSMB9LMP2PSMB6iRING12FUNCTION The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB6 by PSMB9 increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Component of the immunoproteasome, where it displaces the equivalent housekeeping subunit PSMB6. Component of the spermatoproteasome, a form of the proteasome specifically found in testis.SUBUNIT (Microbial infection) Interacts with HIV-1 TAT protein.DEVELOPMENTAL STAGE Highly expressed in immature dendritic cells (at protein level).INDUCTION Up-regulated by interferon gamma (at protein level). Up-regulated by IRF1. Up-regulated by tumor necrosis factor-alpha (at protein level). Up-regulated by tetrodotoxin (TTX) in glial cells. Up-regulated in Crohn's bowel disease (CD). Up-regulated by heat shock treatment. Up-regulated by CD40L via the NFKB1 pathway in cancer cells.PTM Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity.MISCELLANEOUS Encoded in the MHC class II region.MISCELLANEOUS A model for self-activation in which residue Thr-21 serves as nucleophile and Lys-53 as proton donor/acceptor has been proposed. Subunit processing of mammalian beta-subunits proceeds via a novel ordered two-step mechanism involving autocatalysis.SIMILARITY Belongs to the peptidase T1B family.UniProtP2806521EQUAL219EQUALReactome Database ID Release 7568765Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68765ReactomeR-HSA-687652Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68765.21PSMD1226S proteasome non-ATPase regulatory subunit 1226S proteasome regulatory subunit p55Reactome DB_ID: 68792UniProt:O00232 PSMD12PSMD12FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.SUBUNIT Component of the 19S proteasome regulatory particle complex (PubMed:27428775,PubMed:27342858). The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP) (PubMed:27428775,PubMed:27342858). The regulatory particle is made of a lid composed of 9 subunits including PSMD12, a base containing 6 ATPases and few additional components (PubMed:27428775,PubMed:27342858). Interacts with ERCC6 (PubMed:26030138).SIMILARITY Belongs to the proteasome subunit p55 family.UniProtO002322EQUAL456EQUALReactome Database ID Release 7568792Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68792ReactomeR-HSA-687922Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68792.21PSMF1Proteasome inhibitor PI31 subunithPI31Reactome DB_ID: 68818UniProt:Q92530 PSMF1PSMF1FUNCTION Plays an important role in control of proteasome function. Inhibits the hydrolysis of protein and peptide substrates by the 20S proteasome. Also inhibits the activation of the proteasome by the proteasome regulatory proteins PA700 and PA28.SUBUNIT Monomer and homodimer. Interacts with FBXO7. Interacts with the 20S proteasome.SIMILARITY Belongs to the proteasome inhibitor PI31 family.UniProtQ925301EQUAL271EQUALReactome Database ID Release 7568818Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68818ReactomeR-HSA-688182Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68818.21PSMA5Proteasome subunit alpha type 5 Proteasome zeta chainMacropain zeta chainMulticatalytic endopeptidase complex zeta chainReactome DB_ID: 68732UniProt:P28066 PSMA5PSMA5FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. PSMA5 interacts directly with the PSMG1-PSMG2 heterodimer which promotes 20S proteasome assembly.TISSUE SPECIFICITY Expressed in fetal brain (at protein level).INDUCTION Up-regulated in colon cancer cell lines. Up-regulated in fetal Down syndrome (DS) brain (at protein level). May be the target of the transcriptional activator NFE2L2.SIMILARITY Belongs to the peptidase T1A family.UniProtP280661EQUAL241EQUALReactome Database ID Release 7568732Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68732ReactomeR-HSA-687322Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68732.21PSMC426S protease regulatory subunit 6BMIP224MB67 interacting proteinTAT-binding protein-7TBP-7Reactome DB_ID: 68777UniProt:P43686 PSMC4PSMC4MIP224TBP7FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC4 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC4 and few additional components (PubMed:27428775,PubMed:27342858). Interacts with NR1I3. Interacts with PAAF1 (PubMed:15831487). Interacts with TRIM5 (PubMed:22078707). Interacts with ZFAND1 (PubMed:29804830).SIMILARITY Belongs to the AAA ATPase family.UniProtP436861EQUAL418EQUALReactome Database ID Release 7568777Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68777ReactomeR-HSA-687772Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68777.21PSMB7Proteasome subunit beta type 7Proteasome subunit beta type 7 precursor Proteasome subunit ZMacropain chain ZMulticatalytic endopeptidase complex chain ZReactome DB_ID: 68759UniProt:Q99436 PSMB7PSMB7ZFUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB7 displays a trypsin-like activity.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.SUBUNIT (Microbial infection) Interacts with HIV-1 Tat protein.TISSUE SPECIFICITY Expressed at a low level in colonic mucosa. Up-regulated in colorectal cancer tissues.SIMILARITY Belongs to the peptidase T1B family.UniProtQ9943644EQUAL277EQUALReactome Database ID Release 7568759Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68759ReactomeR-HSA-687592Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68759.21PSMC5Probable 26S protease regulatory subunit 8Reactome DB_ID: 68780UniProt:P62195 PSMC5PSMC5SUG1FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC5 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC5 and few additional components (PubMed:27428775, PubMed:27342858). Component of a complex with USP49 and RUVBL1 (PubMed:23824326). Interacts with PRPF19. Interacts with TRIM5 (PubMed:22078707). Interacts with NDC80 (PubMed:9295362, PubMed:10409732). Interacts with PAAF1 (PubMed:15831487). Interacts, in vitro, with the thyroid hormone receptor (in a thyroid hormone T3-dependent manner) and with retinoid X receptor (RXR) (By similarity). Interacts with ERCC6 (PubMed:26030138).SIMILARITY Belongs to the AAA ATPase family.UniProtP621952EQUAL406EQUALReactome Database ID Release 7568780Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68780ReactomeR-HSA-687802Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68780.21PSME3Proteasome activator complex subunit 3Proteasome activator 28-gamma subunitPA28gammaPA28gActivator of multicatalytic protease subunit 311S regulator complex gamma subunitREG-gammaKi nuclear autoantigenReactome DB_ID: 68816UniProt:P61289 PSME3PSME3FUNCTION Subunit of the 11S REG-gamma (also called PA28-gamma) proteasome regulator, a doughnut-shaped homoheptamer which associates with the proteasome. 11S REG-gamma activates the trypsin-like catalytic subunit of the proteasome but inhibits the chymotrypsin-like and postglutamyl-preferring (PGPH) subunits. Facilitates the MDM2-p53/TP53 interaction which promotes ubiquitination- and MDM2-dependent proteasomal degradation of p53/TP53, limiting its accumulation and resulting in inhibited apoptosis after DNA damage. May also be involved in cell cycle regulation. Mediates CCAR2 and CHEK2-dependent SIRT1 inhibition (PubMed:25361978).SUBUNIT Homoheptamer; the stability of the heptamer is essential for the specific activation of the trypsine-like subunit and inhibition of the chymotrypsin-like and postglutamyl-preferring (PGPH) subunits of the proteasome. Interacts with p53/TP53 and MDM2. Interacts with MAP3K3 (By similarity). Associates with the proteasome. Interacts with CCAR2. Interacts with PSME3IP1 (via C-terminus); the interaction is direct and promotes the association of PSME3 with the 20S proteasome (PubMed:29934401). Interacts with COIL; the interaction is inhibited by PSME3IP1 (PubMed:29934401).SUBUNIT (Microbial infection) Interacts with human cytomegalovirus UL27.INDUCTION Up-regulated in thyroid carcinoma cells.DOMAIN The C-terminal sequences affect heptamer stability and proteasome affinity.PTM Phosphorylated by MAP3K3 (By similarity). Phosphorylation at Ser-247 promotes its association with CCAR2.PTM Acetylation at the major site Lys-195 is important for oligomerization and ability to degrade its target substrates. Deacetylated by SIRT1.SIMILARITY Belongs to the PA28 family.UniProtP612892EQUAL254EQUALReactome Database ID Release 7568816Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68816ReactomeR-HSA-688162Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68816.21PSMA7Proteasome subunit alpha type 7 Proteasome subunit RC6-1Proteasome subunit XAPC7Reactome DB_ID: 68736UniProt:O14818 PSMA7PSMA7HSPCFUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Inhibits the transactivation function of HIF-1A under both normoxic and hypoxia-mimicking conditions. The interaction with EMAP2 increases the proteasome-mediated HIF-1A degradation under the hypoxic conditions. Plays a role in hepatitis C virus internal ribosome entry site-mediated translation. Mediates nuclear translocation of the androgen receptor (AR) and thereby enhances androgen-mediated transactivation. Promotes MAVS degradation and thereby negatively regulates MAVS-mediated innate immune response.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. PSMA7 interacts directly with the PSMG1-PSMG2 heterodimer which promotes 20S proteasome assembly (PubMed:16251969). Interacts with HIF1A. Interacts with RAB7A (PubMed:14998988). Interacts with PRKN (PubMed:15987638). Interacts with ABL1 and ABL2 (PubMed:16678104). Interacts with EMAP2 (PubMed:19362550). Interacts with MAVS (PubMed:19734229).SUBUNIT (Microbial infection) Interacts with HIV-1 TAT protein.SUBUNIT (Microbial infection) Interacts with hepatitis B virus X protein (HBX).INDUCTION Down-regulated by the ribozyme Rz3'X. Up-regulated in colorectal cancer tissues.PTM Phosphorylation by ABL1 or ABL2 leads to an inhibition of proteasomal activity and cell cycle transition blocks.SIMILARITY Belongs to the peptidase T1A family.UniProtO148181EQUAL248EQUALReactome Database ID Release 7568736Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68736ReactomeR-HSA-687362Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68736.21PSMC326S protease regulatory subunit 6ATAT-binding protein 1TBP-1Proteasome subunit P50Reactome DB_ID: 68774UniProt:P17980 PSMC3PSMC3TBP1FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC3 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC3 and few additional components (PubMed:27428775, PubMed:27342858). Interacts with PAAF1 (PubMed:15831487).SUBUNIT (Microbial infection) Interacts with HIV-1 Tat.PTM Sumoylated by UBE2I in response to MEKK1-mediated stimuli.SIMILARITY Belongs to the AAA ATPase family.UniProtP179801EQUAL439EQUALReactome Database ID Release 7568774Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68774ReactomeR-HSA-687742Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68774.21PSMC126S protease regulatory subunit 4P26s4Reactome DB_ID: 68768UniProt:P62191 PSMC1PSMC1FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC1 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC1 and few additional components (PubMed:27428775, PubMed:27342858). Interacts with SCA7 (PubMed:11734547). Interacts with NGLY1 (PubMed:15358861). Interacts with PAAF1 (PubMed:15831487).SIMILARITY Belongs to the AAA ATPase family.UniProtP621912EQUAL440EQUALReactome Database ID Release 7568768Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68768ReactomeR-HSA-687682Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68768.21PSMD1326S proteasome non-ATPase regulatory subunit 1326S proteasome regulatory subunit S1126S proteasome regulatory subunit p40.5Reactome DB_ID: 68794UniProt:Q9UNM6 PSMD13PSMD13FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD13, a base containing 6 ATPases and few additional components.SIMILARITY Belongs to the proteasome subunit S11 family.UniProtQ9UNM61EQUAL376EQUALReactome Database ID Release 7568794Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68794ReactomeR-HSA-687942Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68794.21PSMA1Proteasome subunit alpha type 1 Proteasome component C2Macropain subunit C2Multicatalytic endopeptidase complex subunit C2Proteasome nu chain30 kDa prosomal proteinPROS-30Reactome DB_ID: 68724UniProt:P25786 PSMA1PSMA1HC2NUPROS30PSC2FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. Interacts with NOTCH3. Interacts with ZFAND1 (PubMed:29804830).INDUCTION Induced in breast cancer tissue (at protein level). Up-regulated in liver tumor tissues.SIMILARITY Belongs to the peptidase T1A family.UniProtP257861EQUAL263EQUALReactome Database ID Release 7568724Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68724ReactomeR-HSA-687242Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68724.21PSMA2Proteasome subunit alpha type 2 Proteasome component C3Macropain subunit C3Multicatalytic endopeptidase complex subunit C3Reactome DB_ID: 68726UniProt:P25787 PSMA2PSMA2HC3PSC3FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.INDUCTION Down-regulated by antioxidants BO-653 and probucol. Down-regulated in response to enterovirus 71 (EV71) infection (at protein level).PTM Phosphorylated on tyrosine residues; which may be important for nuclear import.SIMILARITY Belongs to the peptidase T1A family.UniProtP257872EQUAL234EQUALReactome Database ID Release 7568726Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68726ReactomeR-HSA-687262Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68726.21PSMA3Proteasome subunit alpha type 3 Proteasome component C8Macropain subunit C8Multicatalytic endopeptidase complex subunit C8Reactome DB_ID: 68728UniProt:P25788 PSMA3PSMA3HC8PSC8FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Binds to the C-terminus of CDKN1A and thereby mediates its degradation. Negatively regulates the membrane trafficking of the cell-surface thromboxane A2 receptor (TBXA2R) isoform 2.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. Interacts with AURKB. Interacts with CDKN1A (PubMed:11350925). Interacts with MDM2 and RB1 (PubMed:16337594). Interacts with the C-terminus of TBXA2R isoform 2 (PubMed:17499743). Interacts with DNAJB2 (PubMed:15936278).SUBUNIT (Microbial infection) Interacts with HIV-1 Tat protein.SUBUNIT (Microbial infection) Interacts with hepatitis C virus (HCV) F protein.SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus EBNA3 proteins.INDUCTION Down-regulated by antioxidants BO-653 and probucol. Up-regulated by bacterial lipopolysaccharides (LPS) and TNF.SIMILARITY Belongs to the peptidase T1A family.UniProtP257882EQUAL255EQUALReactome Database ID Release 7568728Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68728ReactomeR-HSA-687282Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68728.21PSMD1026S proteasome non-ATPase regulatory subunit 1026S proteasome regulatory subunit p28GankyrinReactome DB_ID: 68788UniProt:O75832 PSMD10PSMD10FUNCTION Acts as a chaperone during the assembly of the 26S proteasome, specifically of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module. Independently of the proteasome, regulates EGF-induced AKT activation through inhibition of the RHOA/ROCK/PTEN pathway, leading to prolonged AKT activation. Plays an important role in RAS-induced tumorigenesis.FUNCTION Acts as an proto-oncoprotein by being involved in negative regulation of tumor suppressors RB1 and p53/TP53. Overexpression is leading to phosphorylation of RB1 and proteasomal degradation of RB1. Regulates CDK4-mediated phosphorylation of RB1 by competing with CDKN2A for binding with CDK4. Facilitates binding of MDM2 to p53/TP53 and the mono- and polyubiquitination of p53/TP53 by MDM2 suggesting a function in targeting the TP53:MDM2 complex to the 26S proteasome. Involved in p53-independent apoptosis. Involved in regulation of NF-kappa-B by retaining it in the cytoplasm. Binds to the NF-kappa-B component RELA and accelerates its XPO1/CRM1-mediated nuclear export.SUBUNIT Part of transient complex containing PSMD10, PSMC4, PSMC5 and PAAF1 formed during the assembly of the 26S proteasome. Stays associated throughout the assembly of the PA700/19S RC and is released upon association with the 20S core. Interacts with PSMC4. Interacts with RB1. Interacts with CDK4. Interacts with MDM2. Interacts with RELA. Associates with a CDK4:CCND2 serine/threonine kinase complex. Interacts with ARHGDIA and increases the interaction between ARHGDIA and RHOA, hence promotes ARHGDIA inactivation of RHOA and ROCK.TISSUE SPECIFICITY Tends to be up-regulated in cancer cells with RAS mutations, including lung cancers and adenocarconimas (at protein level).CAUTION Was initially identified as a genuine component of the 26S proteasome.UniProtO758321EQUAL226EQUALReactome Database ID Release 7568788Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68788ReactomeR-HSA-687882Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68788.21PSMA4Proteasome subunit alpha type 4 Proteasome component C9Macropain subunit C9Multicatalytic endopeptidase complex subunit C9Proteasome subunit LReactome DB_ID: 68730UniProt:P25789 PSMA4PSMA4HC9PSC9FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.SUBUNIT (Microbial infection) Interaction with HTLV-1 TAX protein favors NFKB1 activation.INDUCTION Down-regulated by antioxidants BO-653 and probucol.SIMILARITY Belongs to the peptidase T1A family.UniProtP257891EQUAL261EQUALReactome Database ID Release 7568730Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68730ReactomeR-HSA-687302Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68730.21p27KPSMA6Proteasome subunit alpha type 6 Proteasome iota chainMacropain iota chainMulticatalytic endopeptidase complex iota chain27 kDa prosomal proteinPROS-27Reactome DB_ID: 68734UniProt:P60900 PSMA6PSMA6PROS27FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. Interacts with ALKBH4 (PubMed:23145062).SIMILARITY Belongs to the peptidase T1A family.UniProtP609001EQUAL246EQUALReactome Database ID Release 7568734Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68734ReactomeR-HSA-687342Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68734.21HSN3PSMB4Proteasome subunit beta type 4Proteasome subunit beta type 4 precursor Proteasome beta chainMacropain beta chainMulticatalytic endopeptidase complex beta chainProteasome chain 3HsBPROS26Reactome DB_ID: 68750UniProt:P28070 PSMB4PSMB4PROS26FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. Forms a ternary complex with SMAD1 and OAZ1 before PSMB4 is incorporated into the 20S proteasome. Interacts with PRPF19 (PubMed:11571290, PubMed:12097147).SUBUNIT (Microbial infection) Interacts with HTLV-1 Tax protein.SUBUNIT (Microbial infection) Interacts with HIV-1 Nef and Tat proteins.INDUCTION Up-regulated in fibrolamellar carcinomas.SIMILARITY Belongs to the peptidase T1B family.CAUTION A report observed N-glycosylation at Asn-83 (PubMed:19139490). However, as the protein does not localize in an extracellular compartment of the cell, additional evidence is required to confirm this result.UniProtP2807046EQUAL264EQUALReactome Database ID Release 7568750Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68750ReactomeR-HSA-687502Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68750.21PSMB8Proteasome subunit beta type 8Proteasome subunit beta type 8 precursor Proteasome component C13Macropain subunit C13Multicatalytic endopeptidase complex subunit C13Reactome DB_ID: 68762UniProt:P28062 PSMB8PSMB8LMP7PSMB5iRING10Y2FUNCTION The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB5 by PSMB8 increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues. Involved in the generation of spliced peptides resulting from the ligation of two separate proteasomal cleavage products that are not contiguous in the parental protein (PubMed:27049119). Acts as a major component of interferon gamma-induced sensitivity. Plays a key role in apoptosis via the degradation of the apoptotic inhibitor MCL1. May be involved in the inflammatory response pathway. In cancer cells, substitution of isoform 1 (E2) by isoform 2 (E1) results in immunoproteasome deficiency. Required for the differentiation of preadipocytes into adipocytes.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Component of the immunoproteasome, where it displaces the equivalent housekeeping subunit PSMB5. Component of the spermatoproteasome, a form of the proteasome specifically found in testis. Directly interacts with POMP. Interacts with TAP1.SUBUNIT (Microbial infection) Interacts with HIV-1 TAT protein.DEVELOPMENTAL STAGE Highly expressed in immature dendritic cells (at protein level).INDUCTION Up-regulated by IFNG/IFN-gamma and IRF1 (at protein level). Up-regulated by TNF (at protein level). Up-regulated by tetrodotoxin (TTX) in glial cells. Up-regulated in Crohn's bowel disease (CD). Down-regulated by the selective inhibitor PR-957. Down-regulated in mature dendritic cells by HSV-1 infection. Up-regulated by heat shock treatment.PTM Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity.SIMILARITY Belongs to the peptidase T1B family.UniProtP2806273EQUAL276EQUALReactome Database ID Release 7568762Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68762ReactomeR-HSA-687622Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68762.21PSMD226S proteasome non-ATPase regulatory subunit 226S proteasome regulatory subunit S226S proteasome subunit p97Tumor necrosis factor type 1 receptor associated protein 255.11 proteinReactome DB_ID: 68796UniProt:Q13200 PSMD2PSMD2TRAP2FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.FUNCTION Binds to the intracellular domain of tumor necrosis factor type 1 receptor. The binding domain of TRAP1 and TRAP2 resides outside the death domain of TNFR1.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases and few additional components including PSMD2 (PubMed:27428775, PubMed:27342858). Interacts with RPGRIP1L (By similarity). Interacts with CRY1 in a KDM8-dependent manner (By similarity).TISSUE SPECIFICITY Found in skeletal muscle, liver, heart, brain, kidney, pancreas, lung and placenta.SIMILARITY Belongs to the proteasome subunit S2 family.UniProtQ132001EQUAL908EQUALReactome Database ID Release 7568796Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68796ReactomeR-HSA-687962Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68796.21RPN11PSMD1426S proteasome-associated pad1 homolog26S proteasome regulatory subunit RPN11Reactome DB_ID: 68722UniProt:O00487 PSMD14PSMD14POH1FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. The PSMD14 subunit is a metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains within the complex. Plays a role in response to double-strand breaks (DSBs): acts as a regulator of non-homologous end joining (NHEJ) by cleaving 'Lys-63'-linked polyubiquitin, thereby promoting retention of JMJD2A/KDM4A on chromatin and restricting TP53BP1 accumulation. Also involved in homologous recombination repair by promoting RAD51 loading.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD4, a base containing 6 ATPases and few additional components (PubMed:27428775, PubMed:27342858). Within the complex, PSMD4 interacts with subunit PSMD7 through their respective MPN domain. Interacts with TXNL1 (PubMed:19349277).TISSUE SPECIFICITY Widely expressed. Highest levels in heart and skeletal muscle.SIMILARITY Belongs to the peptidase M67A family. PSMD14 subfamily.UniProtO004871EQUAL310EQUALReactome Database ID Release 7568722Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68722ReactomeR-HSA-687223Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68722.31PSMB6Proteasome subunit beta type 6Proteasome subunit beta type 6 precursor Proteasome delta chainMacropain delta chainMulticatalytic endopeptidase complex delta chainProteasome subunit YReactome DB_ID: 68756UniProt:P28072 PSMB6PSMB6LMPYYFUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB6 displays a peptidylglutamyl-hydrolizing activity also termed postacidic or caspase-like activity, meaning that the peptides bond hydrolysis occurs directly after acidic residues.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.SUBUNIT (Microbial infection) Interacts with HIV-1 protein Tat.INDUCTION Down-regulated by IFNG/IFN-gamma (at protein level). Up-regulated in anaplastic thyroid cancer cell lines.SIMILARITY Belongs to the peptidase T1B family.UniProtP2807235EQUAL239EQUALReactome Database ID Release 7568756Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68756ReactomeR-HSA-687562Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68756.21PSMB1Proteasome subunit beta type 1 Proteasome component C5Macropain subunit C5Multicatalytic endopeptidase complex subunit C5Proteasome gamma chainReactome DB_ID: 68738UniProt:P20618 PSMB1PSMB1PSC5FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. Interacts with SERPINB2. Interacts with RFPL4A (By similarity).SUBUNIT (Microbial infection) Interacts with HIV-1 protein Tat.SIMILARITY Belongs to the peptidase T1B family.UniProtP2061829EQUAL241EQUALReactome Database ID Release 7568738Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68738ReactomeR-HSA-687382Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68738.21PSMD726S proteasome non-ATPase regulatory subunit 726S proteasome regulatory subunit S12Proteasome subunit p40Mov34 protein homologReactome DB_ID: 68806UniProt:P51665 PSMD7PSMD7MOV34LFUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD7, a base containing 6 ATPases and few additional components (PubMed:27428775, PubMed:27342858). Within the complex, PSMD7 interacts with subunit PSMD4 through their respective MPN domain. Interacts with TRIM5 (PubMed:22078707).MISCELLANEOUS Does not bind a metal ion.SIMILARITY Belongs to the peptidase M67A family.UniProtP516651EQUAL324EQUALReactome Database ID Release 7568806Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68806ReactomeR-HSA-688062Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68806.21PSMD1126S proteasome non-ATPase regulatory subunit 1126S proteasome regulatory subunit S926S proteasome regulatory subunit p44.5Reactome DB_ID: 68790UniProt:O00231 PSMD11PSMD11FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. In the complex, PSMD11 is required for proteasome assembly. Plays a key role in increased proteasome activity in embryonic stem cells (ESCs): its high expression in ESCs promotes enhanced assembly of the 26S proteasome, followed by higher proteasome activity.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD11, a base containing 6 ATPases and few additional components.TISSUE SPECIFICITY Highly expressed in embryonic stem cells (ESCs). Expression decreases as ESCs differentiate.INDUCTION By FOXO4; expression in embryonic stem cells (ESCs) is mediated by FOXO4.PTM Phosphorylated by AMPK.SIMILARITY Belongs to the proteasome subunit S9 family.UniProtO002312EQUAL422EQUALReactome Database ID Release 7568790Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68790ReactomeR-HSA-687902Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68790.21PSMB2Proteasome subunit beta type 2 Proteasome component C7-IMacropain subunit C7-IMulticatalytic endopeptidase complex subunit C7-IReactome DB_ID: 68744UniProt:P49721 PSMB2PSMB2FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.SUBUNIT (Microbial infection) Interacts with HIV-1 protein Tat.INDUCTION Up-regulated in ovarian cancer cell lines.SIMILARITY Belongs to the peptidase T1B family.UniProtP497211EQUAL201EQUALReactome Database ID Release 7568744Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68744ReactomeR-HSA-687442Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68744.21PSMB10Proteasome subunit beta type 10Proteasome subunit beta type 10 precursor Proteasome MECl-1Macropain subunit MECl-1Multicatalytic endopeptidase complex subunit MECl-1Reactome DB_ID: 68741UniProt:P40306 PSMB10PSMB10LMP10MECL1FUNCTION The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Component of the immunoproteasome, where it displaces the equivalent housekeeping subunit PSMB7. Component of the spermatoproteasome, a form of the proteasome specifically found in testis.SUBUNIT (Microbial infection) Interacts with HIV-1 TAT protein.DEVELOPMENTAL STAGE Highly expressed in immature dendritic cells (at protein level).INDUCTION Up-regulated by IFNG/IFN-gamma (at protein level). Up-regulated by IRF1. Up-regulated by TNF (at protein level). Up-regulated by tetrodotoxin (TTX) in glial cells. Up-regulated in Crohn's bowel disease (CD). Up-regulated by CD40L via the NFKB1 pathway in cancer cells.PTM Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity.SIMILARITY Belongs to the peptidase T1B family.UniProtP4030640EQUAL273EQUALReactome Database ID Release 7568741Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68741ReactomeR-HSA-687412Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68741.21p44PSMC626S protease regulatory subunit S10BProteasome subunit p42Conserved ATPase domain protein 44CADp44Reactome DB_ID: 68783UniProt:P62333 PSMC6PSMC6SUG2FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC6 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC6 and few additional components (PubMed:27428775, PubMed:27342858). Interacts with PAAF1 (PubMed:15831487).SIMILARITY Belongs to the AAA ATPase family.CAUTION Alternative initiation from an upstream conserved methionine cannot be fully excluded but is not experimentally supported while initiation from the displayed methionine is supported by PubMed:17323924.UniProtP623331EQUAL389EQUALReactome Database ID Release 7568783Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68783ReactomeR-HSA-687832Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68783.21p31PSMD826S proteasome non-ATPase regulatory subunit 826S proteasome regulatory subunit S14Reactome DB_ID: 68808UniProt:P48556 PSMD8PSMD8FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD8, a base containing 6 ATPases and few additional components. Interacts with DDI2 (PubMed:29290612). Interacts with TASOR (By similarity).SIMILARITY Belongs to the proteasome subunit S14 family.CAUTION It is uncertain whether Met-1 or Met-64 is the initiator.UniProtP485561EQUAL350EQUALReactome Database ID Release 7568808Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68808ReactomeR-HSA-688082Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68808.21PSME1Proteasome activator complex subunit 1Proteasome activator 28-alpha subunitPA28alphaPA28aActivator of multicatalytic protease subunit 111S regulator complex alpha subunitREG-alphaInterferon gamma up-regulated I-5111 proteinIGUP I-5111Reactome DB_ID: 68812UniProt:Q06323 PSME1PSME1IFI5111FUNCTION Implicated in immunoproteasome assembly and required for efficient antigen processing. The PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern of the proteasome.SUBUNIT Heterodimer of PSME1 and PSME2, which forms a hexameric ring. PSME1 can form homoheptamers.INDUCTION By IFNG/IFN-gamma.SIMILARITY Belongs to the PA28 family.UniProtQ063231EQUAL249EQUALReactome Database ID Release 7568812Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68812ReactomeR-HSA-688122Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68812.21PSMB3Proteasome subunit beta type 3 Proteasome theta chainProteasome chain 13Proteasome component C10-IIReactome DB_ID: 68747UniProt:P49720 PSMB3PSMB3FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.SUBUNIT (Microbial infection) Interacts with HIV-1 TAT protein.INDUCTION Up-regulated in asthenozoospermic sperm.SIMILARITY Belongs to the peptidase T1B family.UniProtP497202EQUAL205EQUALReactome Database ID Release 7568747Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68747ReactomeR-HSA-687472Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68747.21PSMB5Proteasome subunit beta type 5Proteasome subunit beta type 5 precursor Proteasome epsilon chainMacropain epsilon chainMulticatalytic endopeptidase complex epsilon chainProteasome subunit XProteasome chain 6Proteasome subunit MB1Reactome DB_ID: 68753UniProt:P28074 PSMB5PSMB5LMPXMB1XFUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB5 displays a chymotrypsin-like activity.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. Directly interacts with POMP (PubMed:15944226). Interacts with ABCB1 and TAP1 (PubMed:15488952).SUBUNIT (Microbial infection) Interacts with HIV-1 TAT protein.INDUCTION Down-regulated by IFNG/IFN-gamma (at protein level). Induced in breast cancer tissue. Up-regulated by sulforaphane in breast cancer cells.SIMILARITY Belongs to the peptidase T1B family.UniProtP2807460EQUAL263EQUALReactome Database ID Release 7568753Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68753ReactomeR-HSA-687532Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68753.21Reactome Database ID Release 7568819Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68819ReactomeR-HSA-688192Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68819.2GENE ONTOLOGYGO:0004175Reactome Database ID Release 7568824Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68824Reactome Database ID Release 759011313Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9011313ReactomeR-HSA-90113131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9011313.1LEFT-TO-RIGHTTranscription of ROBO3.2 mRNABased on studies in mice, a transcript variant ROBO3.2 is produced from nascent ROBO3 mRNA by alternative splicing. Existence of this splicing isoform is predicted to be conserved in humans and rats. The alternative splicing results in retention of the intronic sequence between exons 26 and 27, which creates a premature stop codon. While Robo3.1 mouse mRNA is expressed in the pre-crossing and crossing commissural axons, Robo3.2 mRNA is expressed after midline crossing and thought to block midline re-crossing (Chen et al. 2008).Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04ROBO3.2 mRNAReactome DB_ID: 9014585Reactome Database ID Release 759014585Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9014585ReactomeR-HSA-90145852Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9014585.2ChEBI33699Reactome Database ID Release 759014587Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9014587ReactomeR-HSA-90145871Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9014587.118466743Pubmed2008Alternative splicing of the Robo3 axon guidance receptor governs the midline switch from attraction to repulsionChen, ZGore, BBLong, HMa, LTessier-Lavigne, MNeuron 58:325-32LEFT-TO-RIGHTTranslation of ROBO3.2 mRNA initiates NMDBased on studies in mice, ROBO3.2 mRNA, which contains a premature stop codon, is recognized by components of the nonsense mediated decay (NMD) machinery during translation. Association of ROBO3.2 mRNA with UPF2 and UPF1 was directly demonstrated in mouse cells, and presence of other translation and NMD components is assumed (Colak et al. 2013). In this step, we only show association of ROBO3.2 mRNA with the UPF2-containing exon junction complex. For detailed representation of UPF2 and UPF1 in NMD, please refer to the Reactome pathway 'Nonsense Mediated Decay (NMD)'.Authored: Orlic-Milacic, Marija, 2017-06-23Reviewed: Jaworski, Alexander, 2017-07-31Edited: Orlic-Milacic, Marija, 2017-08-04Exon Junction:UPF2:UPF3 ComplexReactome DB_ID: 927798Core Exon Junction Complex (Core EJC)Reactome DB_ID: 927869CASC3Protein CASC3CASC3_HUMANReactome DB_ID: 927807UniProt:O15234 CASC3CASC3MLN51FUNCTION Required for pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:29301961). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Stimulates the ATPase and RNA-helicase activities of EIF4A3. Plays a role in the stress response by participating in cytoplasmic stress granules assembly and by favoring cell recovery following stress. Component of the dendritic ribonucleoprotein particles (RNPs) in hippocampal neurons. May play a role in mRNA transport. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Binds poly(G) and poly(U) RNA homopolymer.SUBUNIT Identified in the spliceosome C complex (PubMed:28502770, PubMed:29301961). Component of the mRNA splicing-dependent exon junction complex (EJC), which contains at least CASC3, EIF4A3, MAGOH, NXF1 and RBM8A/Y14 (PubMed:15166247, PubMed:16170325, PubMed:16314458, PubMed:16923391, PubMed:16931718, PubMed:19033377, PubMed:20479275). Identified in a complex composed of the EJC core, UPF3B and UPF2. The EJC core can also interact with UPF3A (in vitro) (PubMed:20479275). Forms homooligomers (By similarity). Interacts with STAU in an RNA-dependent manner (By similarity).TISSUE SPECIFICITY Widely expressed. Overexpressed in breast cancers and metastasis, as well as in gastric cancers.DOMAIN The coiled coil domain may be involved in oligomerization.PTM ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination.PTM Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation.SIMILARITY Belongs to the CASC3 family.UniProtO152341EQUAL703EQUALReactome Database ID Release 75927807Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=927807ReactomeR-HSA-9278071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-927807.11EIF4A3Eukaryotic initiation factor 4A-IIIIF4A3_HUMANReactome DB_ID: 927868UniProt:P38919 EIF4A3EIF4A3DDX48KIAA0111FUNCTION ATP-dependent RNA helicase (PubMed:16170325). Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:22961380, PubMed:28502770, PubMed:28076346, PubMed:29301961). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs (PubMed:16209946, PubMed:16170325, PubMed:16314458, PubMed:16923391, PubMed:16931718, PubMed:19033377, PubMed:20479275). The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Its RNA-dependent ATPase and RNA-helicase activities are induced by CASC3, but abolished in presence of the MAGOH-RBM8A heterodimer, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The inhibition of ATPase activity by the MAGOH-RBM8A heterodimer increases the RNA-binding affinity of the EJC. Involved in translational enhancement of spliced mRNAs after formation of the 80S ribosome complex. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Shows higher affinity for single-stranded RNA in an ATP-bound core EJC complex than after the ATP is hydrolyzed. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the function is different from the established EJC assembly (PubMed:22203037). Involved in craniofacial development (PubMed:24360810).ACTIVITY REGULATION The ATPase activity is increased some 4-fold in the presence of RNA.SUBUNIT Identified in the spliceosome C complex (PubMed:11991638, PubMed:22961380, PubMed:28502770, PubMed:28076346, PubMed:29301961). Core component of the mRNA splicing-dependent exon junction complex (EJC); the core complex contains CASC3, EIF4A3, MAGOH or MAGOHB, and RBM8A (PubMed:15034551, PubMed:14730019, PubMed:16170325, PubMed:16314458, PubMed:23917022, PubMed:16923391, PubMed:16931718, PubMed:19033377, PubMed:20479275). Interacts with CASC3, MAGOH, NXF1, RBM8A and ALYREF/THOC4 (PubMed:14730019, PubMed:16170325, PubMed:16495234, PubMed:22961380). May interact with NOM1. Interacts with POLDIP3 (PubMed:18423201). Interacts with CWC22 and PRPF19 in an RNA-independent manner (PubMed:22959432, PubMed:22961380, PubMed:23236153, PubMed:24218557). Direct interaction with CWC22 is mediated by the helicase C-terminal domain (PubMed:22959432, PubMed:24218557). Full interaction with CWC22 occurs only when EIF4A3 is not part of the EJC and prevents EIF4A3 binding to RNA. Identified in a complex composed of the EJC core, UPF3B and UPF2. The EJC core can also interact with UPF3A (in vitro) (PubMed:20479275). Interacts with NCBP3 (PubMed:26382858).TISSUE SPECIFICITY Ubiquitously expressed.SIMILARITY Belongs to the DEAD box helicase family. eIF4A subfamily.UniProtP389192EQUAL411EQUALReactome Database ID Release 75927868Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=927868ReactomeR-HSA-9278681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-927868.11Magoh-Y14 complexReactome DB_ID: 162463RBM8ARBM8A/Y14Reactome DB_ID: 162462UniProt:Q9Y5S9 RBM8ARBM8ARBM8HSPC114MDS014FUNCTION Required for pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:29301961). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). The MAGOH-RBM8A heterodimer inhibits the ATPase activity of EIF4A3, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The MAGOH-RBM8A heterodimer interacts with the EJC key regulator PYM1 leading to EJC disassembly in the cytoplasm and translation enhancement of EJC-bearing spliced mRNAs by recruiting them to the ribosomal 48S preinitiation complex. Its removal from cytoplasmic mRNAs requires translation initiation from EJC-bearing spliced mRNAs. Associates preferentially with mRNAs produced by splicing. Does not interact with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. Associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs. The MAGOH-RBM8A heterodimer is a component of the nonsense mediated decay (NMD) pathway. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the function is different from the established EJC assembly.SUBUNIT Heterodimer with either MAGOH or MAGOHB (PubMed:10662555, PubMed:12730685, PubMed:23917022, PubMed:12781131). Part of the mRNA splicing-dependent exon junction complex (EJC) complex; the core complex contains CASC3, EIF4A3, MAGOH or MAGOHB, and RBM8A (PubMed:11707413, PubMed:16170325, PubMed:16314458, PubMed:23917022, PubMed:16923391, PubMed:16931718, PubMed:19033377, PubMed:20479275). Interacts with PYM1; the interaction is direct and dissociates the EJC from spliced mRNAs (PubMed:14968132, PubMed:18026120, PubMed:19410547). Part of a complex that contains the EJC core components CASC3, EIF4A3, MAGOH and RBM8A plus proteins involved in nonsense-mediated mRNA decay, such as UPF1, UPF2, UPF3A and UPF3B (PubMed:11546873, PubMed:12718880, PubMed:20479275). Found in a post-splicing complex with NXF1, MAGOH, UPF1, UPF2, UPF3A, UPF3B and RNPS1 (PubMed:11546874). Interacts with BAT1, MAGOH, DPH1, UPF3B, RNPS1, SRRM1 and ALYREF/THOC4 (PubMed:11013075, PubMed:11118221, PubMed:11707413, PubMed:12944400). Interacts with IPO13; the interaction mediates the nuclear import of the MAGOH-RBM8A heterodimer (PubMed:11447110). Identified in the spliceosome C complex (PubMed:11991638, PubMed:28502770, PubMed:29301961). Associates with polysomes (PubMed:12121612).TISSUE SPECIFICITY Ubiquitous.SIMILARITY Belongs to the RBM8A family.UniProtQ9Y5S92EQUAL174EQUALReactome Database ID Release 75162462Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=162462ReactomeR-HSA-1624621Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-162462.11Converted from EntitySet in ReactomeMAGOH,MAGOHBReactome DB_ID: 8868752MAGOHmagohReactome DB_ID: 156658UniProt:P61326 MAGOHMAGOHMAGOHAFUNCTION Required for pre-mRNA splicing as component of the spliceosome (PubMed:11991638). Plays a redundant role with MAGOHB as core component of the exon junction complex (EJC) and in the nonsense-mediated decay (NMD) pathway (PubMed:23917022). The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). The MAGOH-RBM8A heterodimer inhibits the ATPase activity of EIF4A3, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The MAGOH-RBM8A heterodimer interacts with the EJC key regulator PYM1 leading to EJC disassembly in the cytoplasm and translation enhancement of EJC-bearing spliced mRNAs by recruiting them to the ribosomal 48S preinitiation complex. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the function is different from the established EJC assembly.SUBUNIT Heterodimer with RBM8A (PubMed:12730685, PubMed:12781131, PubMed:23917022). Core component of the mRNA splicing-dependent exon junction complex (EJC); the core complex contains CASC3, EIF4A3, MAGOH or MAGOHB, and RBM8A (PubMed:11991638, PubMed:16170325, PubMed:16314458, PubMed:23917022, PubMed:16923391, PubMed:16931718, PubMed:19033377, PubMed:20479275). Interacts with PYM1; the interaction is direct and dissociates the EJC from spliced mRNAs (PubMed:14968132, PubMed:18026120, PubMed:19410547). Identified in a complex composed of the EJC core, UPF3B and UPF2. The EJC core can also interact with UPF3A (in vitro) (PubMed:20479275). Identified in the spliceosome C complex (PubMed:11991638).TISSUE SPECIFICITY Ubiquitous.SIMILARITY Belongs to the mago nashi family.UniProtP613261EQUAL146EQUALReactome Database ID Release 75156658Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=156658ReactomeR-HSA-1566581Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-156658.1MAGOHBProtein mago nashi homolog 2MGN2_HUMANReactome DB_ID: 8867888UniProt:Q96A72 MAGOHBMAGOHBMAGOH2FUNCTION Required for pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:29301961, PubMed:30705154). Plays a redundant role with MAGOH in the exon junction complex and in the nonsense-mediated decay (NMD) pathway (PubMed:23917022).SUBUNIT Component of the pre-catalytic, catalytic and post-catalytic spliceosome complexes (PubMed:28502770, PubMed:29301961, PubMed:30705154). Heterodimer with RBM8A. Core component of the mRNA splicing-dependent exon junction complex (EJC); the core complex contains CASC3, EIF4A3, MAGOH or MAGOHB, and RBM8A (PubMed:23917022).TISSUE SPECIFICITY Ubiquitous.SIMILARITY Belongs to the mago nashi family.UniProtQ96A722EQUAL148EQUALReactome Database ID Release 758867888Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8867888ReactomeR-HSA-88678882Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8867888.2Reactome Database ID Release 758868752Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8868752ReactomeR-HSA-88687522Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8868752.21Reactome Database ID Release 75162463Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=162463ReactomeR-HSA-1624632Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-162463.21Reactome Database ID Release 75927869Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=927869ReactomeR-HSA-9278691Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-927869.11RNPS1Reactome DB_ID: 159256UniProt:Q15287 RNPS1RNPS1LDC2FUNCTION Part of pre- and post-splicing multiprotein mRNP complexes. Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP and PSAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets. The ASAP complex can inhibit RNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Enhances the formation of the ATP-dependent A complex of the spliceosome. Involved in both constitutive splicing and, in association with SRP54 and TRA2B/SFRS10, in distinctive modulation of alternative splicing in a substrate-dependent manner. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Participates in mRNA 3'-end cleavage. Involved in UPF2-dependent nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Also mediates increase of mRNA abundance and translational efficiency. Binds spliced mRNA 20-25 nt upstream of exon-exon junctions.SUBUNIT Found in mRNA splicing-dependent exon junction complexes (EJC). Found in a post-splicing complex with NXF1, RBM8A, UPF1, UPF2, UPF3A, UPF3B and RNPS1. Component of the heterotrimeric ASAP (apoptosis- and splicing-associated protein) and PSAP complexes consisting of RNPS1, SAP18 and either ACIN1 or PNN, respectively; the ASAP and PSAP complexes probably are formed mutually exclusive. Component of the active spliceosome. Associates with polysomes. Interacts with the cleaved p110 isoform of CDC2L1, CSNK2A1, PNN, SART3, SRP54, SRRM1 and TRA2B/SFRS10.TISSUE SPECIFICITY Ubiquitous.DOMAIN The RRM domain is required for the formation of the ASAP complex.PTM Phosphorylated on one or more of the four Ser/Thr residues (Ser-43, Thr-49, Ser-52 or Ser-53). Ser-53 phosphorylation site is important for splicing and translation stimulation activity in vitro.SIMILARITY Belongs to the splicing factor SR family.UniProtQ152871EQUAL305EQUALReactome Database ID Release 75159256Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159256ReactomeR-HSA-1592561Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-159256.11UPF2Regulator of nonsense transcripts 2RENT2_HUMANReactome DB_ID: 927799UniProt:Q9HAU5 UPF2UPF2KIAA1408RENT2FUNCTION Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC). Recruited by UPF3B associated with the EJC core at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF3B stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA.SUBUNIT Found in a post-splicing messenger ribonucleoprotein (mRNP) complex. Associates with the exon junction complex (EJC). Interacts with SMG1, EST1A, UPF1, UPF3A, UPF3B, EIF4A1 and EIF1.TISSUE SPECIFICITY Ubiquitous.UniProtQ9HAU51EQUAL1272EQUALReactome Database ID Release 75927799Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=927799ReactomeR-HSA-9277991Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-927799.11Converted from EntitySet in ReactomeUPF3Reactome DB_ID: 927833UPF3ARegulator of nonsense transcripts 3AREN3A_HUMANReactome DB_ID: 927801UniProt:Q9H1J1 UPF3AUPF3ARENT3AUPF3FUNCTION Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. However, UPF3A is shown to be only marginally active in NMD as compared to UPF3B. Binds spliced mRNA upstream of exon-exon junctions. In vitro, weakly stimulates translation.SUBUNIT Found in a post-splicing messenger ribonucleoprotein (mRNP) complex. Associates with the exon junction complex (EJC). Interacts with UPF2 and RBM8A.TISSUE SPECIFICITY Isoform 1 is strongly expressed in testis, uterus, muscle, fetal brain and spinal cord. Isoform 2 is strongly expressed in fetal brain and spinal cord.SIMILARITY Belongs to the RENT3 family.UniProtQ9H1J11EQUAL476EQUALReactome Database ID Release 75927801Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=927801ReactomeR-HSA-9278011Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-927801.1UPF3BhUpf3BUPf3BReactome DB_ID: 159258UniProt:Q9BZI7 UPF3BUPF3BRENT3BUPF3XFUNCTION Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF2 stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA upstream of exon-exon junctions. In vitro, stimulates translation; the function is independent of association with UPF2 and components of the EJC core.SUBUNIT Found in a post-splicing messenger ribonucleoprotein (mRNP) complex. Core component of the mRNA splicing-dependent exon junction complex (EJC); the core complex contains CASC3, EIF4A3, MAGOH or MAGOHB, and RBM8A. The EJC core components EIF4A3 and the MAGOH-RBM8A dimer form a composite binding site for UPF3B which overlaps with the EJC binding site for WIBG (PubMed:16601204, PubMed:18066079, PubMed:23917022, PubMed:20479275). Interacts with EST1A, UPF2 and RBM8A (PubMed:12554878, PubMed:18066079, PubMed:15004547). Interacts with CPSF6 (PubMed:19864460).TISSUE SPECIFICITY Expressed in testis, uterus, prostate, heart, muscle, brain, spinal cord and placenta.SIMILARITY Belongs to the RENT3 family.UniProtQ9BZI71EQUAL483EQUALReactome Database ID Release 75159258Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159258ReactomeR-HSA-1592581Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-159258.1Reactome Database ID Release 75927833Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=927833ReactomeR-HSA-9278331Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-927833.11Reactome Database ID Release 75927798Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=927798ReactomeR-HSA-9277981Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-927798.1ETF1Eukaryotic peptide chain release factor subunit 1eRF1Eukaryotic release factor 1TB3-1C11 proteinReactome DB_ID: 54433UniProt:P62495 ETF1ETF1ERF1RF1SUP45L1FUNCTION Directs the termination of nascent peptide synthesis (translation) in response to the termination codons UAA, UAG and UGA (PubMed:7990965, PubMed:24486019). Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Required for SHFL-mediated translation termination which inhibits programmed ribosomal frameshifting (-1PRF) of mRNA from viruses and cellular genes (PubMed:30682371).SUBUNIT Heterodimer of two subunits, one of which binds GTP (PubMed:19417104). Component of the transient SURF (SMG1-UPF1-eRF1-eRF3) complex (PubMed:19417104). Interacts with JMJD4 (PubMed:24486019). The ETF1-GSPT1 complex interacts with JMJD4 (PubMed:24486019).PTM Methylated at Gln-185 by N6AMT1.PTM Hydroxylation at Lys-63 by JMJD4 promotes its translational termination efficiency.SIMILARITY Belongs to the eukaryotic release factor 1 family.UniProtP624952EQUAL437EQUALReactome Database ID Release 7554433Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=54433ReactomeR-HSA-544331Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-54433.1Cap Binding Complex (CBC)Reactome DB_ID: 162460NCBP1CBP8080 kDa nuclear cap binding protein (NCBP 80 kDa subunit) (CBP80)80 kDa nuclear cap binding proteinNCBP 80 kDa subunitReactome DB_ID: 162459UniProt:Q09161 NCBP1NCBP1CBP80NCBPFUNCTION Component of the cap-binding complex (CBC), which binds cotranscriptionally to the 5'-cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus via its interaction with ALYREF/THOC4/ALY, leading to the recruitment of the mRNA export machinery to the 5'-end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC) via its interaction with UPF1, promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2 and is required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of PARN, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, NCBP1/CBP80 does not bind directly capped RNAs (m7GpppG-capped RNA) but is required to stabilize the movement of the N-terminal loop of NCBP2/CBP20 and lock the CBC into a high affinity cap-binding state with the cap structure. Associates with NCBP3 to form an alternative cap-binding complex (CBC) which plays a key role in mRNA export and is particularly important in cellular stress situations such as virus infections. The conventional CBC with NCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus whereas the alternative CBC with NCBP3 does not bind snRNA and associates only with mRNA thereby playing a role only in mRNA export. NCBP1/CBP80 is required for cell growth and viability (PubMed:26382858).SUBUNIT Component of the nuclear cap-binding complex (CBC), a heterodimer composed of NCBP1/CBP80 and NCBP2/CBP20 that interacts with m7GpppG-capped RNA. Found in a U snRNA export complex containing PHAX/RNUXA, NCBP1/CBP80, NCBP2/CBP20, RAN, XPO1 and m7G-capped RNA. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with PHAX/RNUXA, SRRT/ARS2, EIF4G2, IGF2BP1, HNRNPF, HNRNPH1, KIAA0427/CTIF, PARN, DROSHA, UPF1 and ALYREF/THOC4. May interact with EIF4G1; the interaction is however controversial since it is reported by PubMed:11340157, PubMed:15059963 and PubMed:15361857, but is not observed by PubMed:19648179. The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1/CBP80 and POLR2A. Component of an alternative nuclear cap-binding complex (CBC) composed of NCBP1/CBP80 and NCBP3 (PubMed:26382858). Interacts with METTL3 (PubMed:27117702). Interacts with ZFC3H1 in a RNase-insensitive manner (PubMed:27871484). Interacts with MTREX (PubMed:30842217). Interacts with TASOR (By similarity).SIMILARITY Belongs to the NCBP1 family.UniProtQ091611EQUAL790EQUALReactome Database ID Release 75162459Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=162459ReactomeR-HSA-1624591Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-162459.11NIP1NCBP2CBP2020 kDa nuclear cap binding protein (NCBP 20 kDa subunit) (CBP20) (NCBP interacting protein 1) (NIP1)20 kDa nuclear cap binding proteinNCBP 20 kDa subunitNCBP interacting protein 1Reactome DB_ID: 162458UniProt:P52298 NCBP2NCBP2CBP20PIG55FUNCTION Component of the cap-binding complex (CBC), which binds co-transcriptionally to the 5' cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus via its interaction with ALYREF/THOC4/ALY, leading to the recruitment of the mRNA export machinery to the 5' end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC) via its interaction with UPF1, promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2, thereby being required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of PARN, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, NCBP2/CBP20 recognizes and binds capped RNAs (m7GpppG-capped RNA) but requires NCBP1/CBP80 to stabilize the movement of its N-terminal loop and lock the CBC into a high affinity cap-binding state with the cap structure. The conventional cap-binding complex with NCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus (PubMed:26382858).SUBUNIT Component of the nuclear cap-binding complex (CBC), a heterodimer composed of NCBP1/CBP80 and NCBP2/CBP20 that interacts with m7GpppG-capped RNA (PubMed:26382858). Found in a U snRNA export complex with PHAX/RNUXA, NCBP1/CBP80, NCBP2/CBP20, RAN, XPO1 and m7G-capped RNA. Interacts with PHAX/RNUXA, EIF4G1, HNRNPF, HNRNPH1 and ALYREF/THOC4/ALY. Interacts with SRRT/ARS2 and KPNA3 (PubMed:26382858).SIMILARITY Belongs to the RRM NCBP2 family.UniProtP522981EQUAL156EQUALReactome Database ID Release 75162458Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=162458ReactomeR-HSA-1624581Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-162458.11Reactome Database ID Release 75162460Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=162460ReactomeR-HSA-1624601Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-162460.1ComplexPortalCPX-1427PABPPABPC1Reactome DB_ID: 156803UniProt:P11940 PABPC1PABPC1PAB1PABP1PABPC2FUNCTION Binds the poly(A) tail of mRNA, including that of its own transcript, and regulates processes of mRNA metabolism such as pre-mRNA splicing and mRNA stability (PubMed:11051545, PubMed:17212783, PubMed:25480299). Its function in translational initiation regulation can either be enhanced by PAIP1 or repressed by PAIP2 (PubMed:11051545, PubMed:20573744). Can probably bind to cytoplasmic RNA sequences other than poly(A) in vivo. Involved in translationally coupled mRNA turnover (PubMed:11051545). Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain (PubMed:11051545). Involved in regulation of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons; for the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed (PubMed:18447585). By binding to long poly(A) tails, may protect them from uridylation by ZCCHC6/ZCCHC11 and hence contribute to mRNA stability (PubMed:25480299).FUNCTION (Microbial infection) Positively regulates the replication of dengue virus (DENV).SUBUNIT May interact with SETX (PubMed:21700224). May form homodimers. Component of a multisubunit autoregulatory ribonucleoprotein complex (ARC), at least composed of IGF2BP1, PABPC1 and CSDE1 (PubMed:16356927). Directly interacts with IGF2BP1. Part of a complex associated with the FOS mCRD domain and consisting of HNRPD, SYNCRIP, PAIP1 and CSDE1/UNR (PubMed:11051545). Interacts with the PABPC1-interacting motif-1 (PAM1) and -2 (PAM2) of PAIP1 and PAIP2 (PubMed:9548260, PubMed:11172725, PubMed:11438674, PubMed:11997512, PubMed:11287632, PubMed:20096703). Interacts with PAIP1 with a 1:1 stoichiometry and with PAIP2 with a 1:2 stoichiometry. The interaction with CSDE1 is direct and RNA-independent. Found in a mRNP complex with YBX2 (By similarity). Interacts with TENT2/GLD2 (By similarity). Identified in the spliceosome C complex (PubMed:11991638). Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. The interaction with DDX3X is direct and RNA-independent (PubMed:18596238, PubMed:21883093, PubMed:22872150). This interaction increases in stressed cells and decreases during cell recovery (PubMed:21883093). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with NXF1/TAP (PubMed:17267499, PubMed:18596238). Interacts with PIWIL1 (By similarity). Interacts with AGO1, AGO2, GSPT1 and GSPT2 (PubMed:17932509, PubMed:18447585, Ref.57). Interacts with LARP4B (Ref.59). Interacts (via the second and third RRM domains and the C-terminus) with PAIP2B (via central acidic portion and C-terminus) (PubMed:16804161, PubMed:11287632). Forms a complex with LARP1 and SHFL (PubMed:20430826, PubMed:24532714, PubMed:25940091, PubMed:26735137). Interacts with LARP4 (PubMed:21098120). Interacts with ZFC3H1 in a RNase-sensitive manner (PubMed:27871484). Interacts with TRIM71 (via NHL repeats) in an RNA-dependent manner (PubMed:23125361). Interacts with TENT5C; the interaction has no effect on TENT5C poly(A) polymerase function (PubMed:28931820). Interacts with G3BP1 and G3BP2 (PubMed:23279204). Interacts with ENDOV; the interaction is RNA-dependent and stimulates ENDOV activity (PubMed:27573237).SUBUNIT (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL69.TISSUE SPECIFICITY Ubiquitous.DOMAIN The RNA-binding domains RRM1 and RRM2 and the C-terminus (last 138 amino acids) regions interact with the PABPC1-interacting motif-1 (PAM1) and -2 (PAM2) of PAIP1, respectively.DOMAIN The RNA-binding domains RRM2 and RRM3 and the C-terminus (last 138 amino acids) regions interact with the PABPC1-interacting motif-1 (PAM1) and -2 (PAM2) of PAIP2, respectively.PTM Phosphorylated by MAPKAPK2.PTM Methylated by CARM1. Arg-493 is dimethylated, probably to asymmetric dimethylarginine.MISCELLANEOUS Many viruses shutoff host mRNA translational machinery by inhibiting cellular PABPC1 activity using different mechanisms. Picornaviruses, caliciviruses or lentiviruses encode proteases that cleave PABPC1 at several defined sites in the proline-rich linker region between RRMs and the C-terminal domain. Rotaviruses, gammherpesviruses and bunyamwera virus relocalize PABPC1 from the cytoplasm to the nucleus thus altering its function. Many of these viruses translate their mRNA in a PABPC1-independent manner and are unaffected by host PABPC1 inhibition.SIMILARITY Belongs to the polyadenylate-binding protein type-1 family.CAUTION Was termed (Ref.5) polyadenylate binding protein II.UniProtP119401EQUAL636EQUALReactome Database ID Release 75156803Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=156803ReactomeR-HSA-1568031Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-156803.1eRF3:GDPReactome DB_ID: 143378GDPGuanosine 5'-diphosphateGuanosine diphosphateReactome DB_ID: 29420GDP [ChEBI:17552]GDPGuanosine 5'-diphosphateGuanosine diphosphateChEBICHEBI:17552Reactome Database ID Release 7529420Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29420ReactomeR-ALL-294202Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29420.2COMPOUNDC000351Converted from EntitySet in ReactomeeRF3GSPT1,GSPT2eRF3a,eRF3bReactome DB_ID: 8865793GSPT1Eukaryotic peptide chain release factor GTP-binding subunit ERF3AeRF3aEukaryotic peptide chain release factor subunit 3aERF3AG1 to S phase transition protein 1 homologERF3A_HUMANReactome DB_ID: 8865759UniProt:P15170 GSPT1GSPT1ERF3AFUNCTION Involved in translation termination in response to the termination codons UAA, UAG and UGA (By similarity). Stimulates the activity of ETF1 (By similarity). Involved in regulation of mammalian cell growth (PubMed:2511002). Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons (PubMed:24486019). Required for SHFL-mediated translation termination which inhibits programmed ribosomal frameshifting (-1PRF) of mRNA from viruses and cellular genes (PubMed:30682371).SUBUNIT Component of the transient SURF (SMG1-UPF1-eRF1-eRF3) complex (PubMed:19417104). The ETF1-GSPT1 complex interacts with JMJD4 (PubMed:24486019). Interacts with PABPC1 (By similarity). Interacts with SHFL (PubMed:30682371).SIMILARITY Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. ERF3 subfamily.CAUTION eRF3 antibodies used in PubMed:19417104 do not differentiate between GSPT1/ERF3A and GSPT2/ERF3B.UniProtP151701EQUAL499EQUALReactome Database ID Release 758865759Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8865759ReactomeR-HSA-88657592Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8865759.2eRF3GSPT2Reactome DB_ID: 143379UniProt:Q8IYD1 GSPT2GSPT2ERF3BFUNCTION Involved in translation termination in response to the termination codons UAA, UAG and UGA. May play a role as a potent stimulator of the release factor activity of ETF1. Exhibits GTPase activity, which is ribosome- and ETF1-dependent. May play a role in cell cycle progression. Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons.SUBUNIT Interacts with ETF1 (By similarity). Component of the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. Interacts with UPF1 and PABPC1.TISSUE SPECIFICITY Highly expressed in IUCC stage II colorectal cancer (CRC).SIMILARITY Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. ERF3 subfamily.UniProtQ8IYD11EQUAL628EQUALReactome Database ID Release 75143379Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=143379ReactomeR-HSA-1433791Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-143379.1Reactome Database ID Release 758865793Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8865793ReactomeR-HSA-88657932Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8865793.21Reactome Database ID Release 75143378Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=143378ReactomeR-HSA-1433782Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-143378.280S ribosome80S monosomeReactome DB_ID: 7250040S ribosomal complexReactome DB_ID: 72392RPS940S small ribosomal protein 9P4678140S ribosomal protein S9Reactome DB_ID: 72387UniProt:P46781 RPS9RPS9SUBUNIT Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs.SIMILARITY Belongs to the universal ribosomal protein uS4 family.UniProtP467812EQUAL194EQUALReactome Database ID Release 7572387Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72387ReactomeR-HSA-723871Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72387.11RPS2940S small ribosomal protein 29P3005440S ribosomal protein S29Reactome DB_ID: 72367UniProt:P62273 RPS29RPS29SUBUNIT Component of the 40S small ribosomal subunit.SIMILARITY Belongs to the universal ribosomal protein uS14 family.UniProtP622732EQUAL56EQUALReactome Database ID Release 7572367Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72367ReactomeR-HSA-723671Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72367.11RPS340S small ribosomal protein 3P2339640S ribosomal protein S3Reactome DB_ID: 72369UniProt:P23396 RPS3RPS3OK/SW-cl.26FUNCTION Involved in translation as a component of the 40S small ribosomal subunit (PubMed:8706699). Has endonuclease activity and plays a role in repair of damaged DNA (PubMed:7775413). Cleaves phosphodiester bonds of DNAs containing altered bases with broad specificity and cleaves supercoiled DNA more efficiently than relaxed DNA (PubMed:15707971). Displays high binding affinity for 7,8-dihydro-8-oxoguanine (8-oxoG), a common DNA lesion caused by reactive oxygen species (ROS) (PubMed:14706345). Has also been shown to bind with similar affinity to intact and damaged DNA (PubMed:18610840). Stimulates the N-glycosylase activity of the base excision protein OGG1 (PubMed:15518571). Enhances the uracil excision activity of UNG1 (PubMed:18973764). Also stimulates the cleavage of the phosphodiester backbone by APEX1 (PubMed:18973764). When located in the mitochondrion, reduces cellular ROS levels and mitochondrial DNA damage (PubMed:23911537). Has also been shown to negatively regulate DNA repair in cells exposed to hydrogen peroxide (PubMed:17049931). Plays a role in regulating transcription as part of the NF-kappa-B p65-p50 complex where it binds to the RELA/p65 subunit, enhances binding of the complex to DNA and promotes transcription of target genes (PubMed:18045535). Represses its own translation by binding to its cognate mRNA (PubMed:20217897). Binds to and protects TP53/p53 from MDM2-mediated ubiquitination (PubMed:19656744). Involved in spindle formation and chromosome movement during mitosis by regulating microtubule polymerization (PubMed:23131551). Involved in induction of apoptosis through its role in activation of CASP8 (PubMed:14988002). Induces neuronal apoptosis by interacting with the E2F1 transcription factor and acting synergistically with it to up-regulate pro-apoptotic proteins BCL2L11/BIM and HRK/Dp5 (PubMed:20605787). Interacts with TRADD following exposure to UV radiation and induces apoptosis by caspase-dependent JNK activation (PubMed:22510408).ACTIVITY REGULATION Endonuclease activity is inhibited by MgCl2 on apurinic/apyrimidinic DNA but not on UV-irradiated DNA.SUBUNIT Component of the 40S small ribosomal subunit (PubMed:8706699). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661). Interacts with HNRPD (PubMed:24423872). Interacts with PRMT1; the interaction methylates RPS3 (PubMed:19460357). Interacts with SUMO1; the interaction sumoylates RPS3 (PubMed:21968017). Interacts with UBC9 (PubMed:21968017). Interacts with CDK1; the interaction phosphorylates RPS3 (PubMed:21871177). Interacts with PRKCD; the interaction phosphorylates RPS3 (PubMed:19059439). Interacts with PKB/AKT; the interaction phosphorylates RPS3 (PubMed:20605787). Interacts with E2F1; the interaction occurs in the absence of nerve growth factor and increases transcription of pro-apoptotic proteins BCL2L11/BIM and HRK/Dp5 (PubMed:20605787). Interacts with the base excision repair proteins APEX1 and OGG1; interaction with OGG1 increases OGG1 N-glycosylase activity (PubMed:15518571). Interacts with UNG; the interaction increases the uracil excision activity of UNG1 (PubMed:18973764). Interacts with HSP90; the interaction prevents the ubiquitination and proteasome-dependent degradation of RPS3 and is suppressed by increased ROS levels (PubMed:16314389). Interacts with TOM70; the interaction promotes translocation of RPS3 to the mitochondrion (PubMed:23911537). Interacts (via N-terminus) with RELA (via N-terminus); the interaction enhances the DNA-binding activity of the NF-kappa-B p65-p50 complex (PubMed:18045535). Interacts with NFKBIA; the interaction is direct and may bridge the interaction between RPS3 and RELA (PubMed:24457201). Interacts with IKKB; the interaction phosphorylates RPS3 and enhances its translocation to the nucleus (PubMed:21399639). Interacts (via KH domain) with MDM2 and TP53 (PubMed:19656744). Interacts with TRADD (PubMed:22510408). Interacts (via N-terminus) with E.coli O157:H7 (strain EDL933) nleH1 and nleH2; the interaction with nleH1 inhibits phosphorylation by IKKB, reduces RPS3 nuclear abundance and inhibits transcriptional activation by the NF-kappa-B p65-p50 complex (PubMed:20041225, PubMed:21399639). Identified in a HCV IRES-mediated translation complex, at least composed of EIF3C, IGF2BP1, RPS3 and HCV RNA-replicon (PubMed:19541769). Interacts with CRY1 (By similarity).PTM Methylation by PRMT1 is required for import into the nucleolus and for ribosome assembly.PTM Sumoylation by SUMO1 enhances protein stability through increased resistance to proteolysis. Sumoylation occurs at one or more of the three consensus sites, Lys-18, Lys-214 and Lys-230.PTM Phosphorylation at Thr-221 by CDK1 occurs mainly in G2/M phase (PubMed:21871177). Phosphorylation by PRKCD occurs on a non-ribosomal-associated form which results in translocation of RPS3 to the nucleus and enhances its endonuclease activity (PubMed:19059439). Phosphorylated on Ser-209 by IKKB in response to activation of the NF-kappa-B p65-p50 complex which enhances the association of RPS3 with importin-alpha and mediates the nuclear translocation of RPS3 (PubMed:21399639). Phosphorylation by MAPK is required for translocation to the nucleus following exposure of cells to DNA damaging agents such as hydrogen peroxide (PubMed:17560175). Phosphorylation by PKB/AKT mediates RPS3 nuclear translocation, enhances RPS3 endonuclease activity and suppresses RPS3-induced neuronal apoptosis (PubMed:20605787).PTM Ubiquitinated (PubMed:16314389). This is prevented by interaction with HSP90 which stabilizes the protein (PubMed:16314389). Monoubiquitinated at Lys-214 by ZNF598 when a ribosome has stalled during translation of poly(A) sequences, leading to preclude synthesis of a long poly-lysine tail and initiate the ribosome quality control (RQC) pathway to degrade the potentially detrimental aberrant nascent polypeptide (PubMed:28065601, PubMed:28132843).PTM Ufmylated by UFL1.SIMILARITY Belongs to the universal ribosomal protein uS3 family.UniProtP233962EQUAL243EQUALReactome Database ID Release 7572369Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72369ReactomeR-HSA-723691Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72369.11S8RPS740S small ribosomal protein 7P2382140S ribosomal protein S7Reactome DB_ID: 72383UniProt:P62081 RPS7RPS7FUNCTION Required for rRNA maturation.SUBUNIT Binds IPO9 with high affinity (PubMed:11823430). Interacts with NEK6 (PubMed:20873783). Interacts with DESI2 (PubMed:28483520).PTM Phosphorylated by NEK6.PTM Ubiquitinated. Deubiquitinated by DESI2, leading to its stabilization.SIMILARITY Belongs to the eukaryotic ribosomal protein eS7 family.UniProtP620811EQUAL194EQUALReactome Database ID Release 7572383Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72383ReactomeR-HSA-723831Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72383.11RPS2040S small ribosomal protein 20P1707540S ribosomal protein S20Reactome DB_ID: 72349UniProt:P60866 RPS20RPS20SUBUNIT Component of the 40S small ribosomal subunit.PTM Monoubiquitinated by ZNF598 when a ribosome has stalled during translation of poly(A) sequences, leading to preclude synthesis of a long poly-lysine tail and initiate the ribosome quality control (RQC) pathway to degrade the potentially detrimental aberrant nascent polypeptide (PubMed:28065601, PubMed:28132843).PTM Ufmylated by UFL1.SIMILARITY Belongs to the universal ribosomal protein uS10 family.UniProtP608662EQUAL119EQUALReactome Database ID Release 7572349Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72349ReactomeR-HSA-723491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72349.11RPS1040S small ribosomal protein 10P4678340S ribosomal protein S10Reactome DB_ID: 72325UniProt:P46783 RPS10RPS10FUNCTION Component of the 40S ribosomal subunit.SUBUNIT Component of the small ribosomal subunit. Interacts with PRMT5. The methylated form interacts with NPM1.PTM Methylated by PRMT5. Methylation is necessary for its interaction with NPS1, its localization in the granular component (GC) region of the nucleolus, for the proper assembly of ribosomes, protein synthesis and optimal cell proliferation.PTM Monoubiquitinated by ZNF598 when a ribosome has stalled during translation of poly(A) sequences, leading to preclude synthesis of a long poly-lysine tail and initiate the ribosome quality control (RQC) pathway to degrade the potentially detrimental aberrant nascent polypeptide (PubMed:28065601, PubMed:28132843).SIMILARITY Belongs to the eukaryotic ribosomal protein eS10 family.UniProtP467831EQUAL165EQUALReactome Database ID Release 7572325Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72325ReactomeR-HSA-723251Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72325.11RPS1740S small ribosomal protein 17P0870840S ribosomal protein S17Reactome DB_ID: 72339UniProt:P08708 RPS17RPS17RPS17LSIMILARITY Belongs to the eukaryotic ribosomal protein eS17 family.UniProtP087082EQUAL135EQUALReactome Database ID Release 7572339Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72339ReactomeR-HSA-723391Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72339.11RPS2640S small ribosomal protein 26P0238340S ribosomal protein S26Reactome DB_ID: 72359UniProt:P62854 RPS26RPS26SUBUNIT Component of the 40S small ribosomal subunit.SIMILARITY Belongs to the eukaryotic ribosomal protein eS26 family.UniProtP628542EQUAL115EQUALReactome Database ID Release 7572359Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72359ReactomeR-HSA-723591Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72359.11RPS1340S small ribosomal protein 13Q0254640S ribosomal protein S13Reactome DB_ID: 72331UniProt:P62277 RPS13RPS13SIMILARITY Belongs to the universal ribosomal protein uS15 family.UniProtP622772EQUAL151EQUALReactome Database ID Release 7572331Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72331ReactomeR-HSA-723311Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72331.11P40RPSA40S small ribosomal protein P4P0886540S ribosomal protein SA34/67 kDa laminin receptorColon carcinoma laminin-binding proteinNEM/1CHD4Multidrug resistance- associated protein MGr1-AgReactome DB_ID: 72389UniProt:P08865 RPSARPSALAMBRLAMR1FUNCTION Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits. Also functions as a cell surface receptor for laminin. Plays a role in cell adhesion to the basement membrane and in the consequent activation of signaling transduction pathways. May play a role in cell fate determination and tissue morphogenesis. Acts as a PPP1R16B-dependent substrate of PPP1CA.FUNCTION (Microbial infection) Acts as a receptor for the Adeno-associated viruses 2,3,8 and 9.FUNCTION (Microbial infection) Acts as a receptor for the Dengue virus.FUNCTION (Microbial infection) Acts as a receptor for the Sindbis virus.FUNCTION (Microbial infection) Acts as a receptor for the Venezuelan equine encephalitis virus.FUNCTION (Microbial infection) Acts as a receptor for the pathogenic prion protein.FUNCTION (Microbial infection) Acts as a receptor for bacteria.SUBUNIT Monomer (37LRP) and homodimer (67LR). Component of the small ribosomal subunit. Mature ribosomes consist of a small (40S) and a large (60S) subunit. The 40S subunit contains about 33 different proteins and 1 molecule of RNA (18S). The 60S subunit contains about 49 different proteins and 3 molecules of RNA (28S, 5.8S and 5S). Interacts with RPS21. Interacts with several laminins including at least LAMB1. Interacts with MDK (By similarity). The mature dimeric form interacts with PPP1R16B (via its fourth ankyrin repeat). Interacts with PPP1CA only in the presence of PPP1R16B.SUBUNIT (Microbial infection) 67LR interacts with capsid protein of Adeno-associated virus 2,3,8 and 9.SUBUNIT (Microbial infection) 67LR interacts with envelope protein of dengue virus.SUBUNIT (Microbial infection) 6s7LR interacts with E2 glycoprotein of Sindbis and Venezuelan equine encephalitis virus (PubMed:8764073, PubMed:1385835).PTM Acylated. Acylation may be a prerequisite for conversion of the monomeric 37 kDa laminin receptor precursor (37LRP) to the mature dimeric 67 kDa laminin receptor (67LR), and may provide a mechanism for membrane association (PubMed:9581863).PTM Cleaved by stromelysin-3 (ST3) at the cell surface. Cleavage by stromelysin-3 may be a mechanism to alter cell-extracellular matrix interactions.MISCELLANEOUS This protein appears to have acquired a second function as a laminin receptor specifically in the vertebrate lineage.MISCELLANEOUS It is thought that in vertebrates 37/67 kDa laminin receptor acquired a dual function during evolution. It developed from the ribosomal protein SA, playing an essential role in the protein biosynthesis lacking any laminin binding activity, to a cell surface receptor with laminin binding activity.SIMILARITY Belongs to the universal ribosomal protein uS2 family.UniProtP088652EQUAL295EQUALReactome Database ID Release 7572389Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72389ReactomeR-HSA-723891Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72389.11RPS15A40S small ribosomal protein 1AP3902740S ribosomal protein S15aReactome DB_ID: 72345UniProt:P62244 RPS15ARPS15AOK/SW-cl.82FUNCTION Structural component of the ribosome (PubMed:23636399). Required for proper erythropoiesis (PubMed:27909223).SUBUNIT Component of the 40S ribosomal subunit.SIMILARITY Belongs to the universal ribosomal protein uS8 family.UniProtP622442EQUAL130EQUALReactome Database ID Release 7572345Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72345ReactomeR-HSA-723451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72345.11RPS640S small ribosomal protein 6P1066040S ribosomal protein S6Phosphoprotein NP33Reactome DB_ID: 72381UniProt:P62753 RPS6RPS6OK/SW-cl.2FUNCTION May play an important role in controlling cell growth and proliferation through the selective translation of particular classes of mRNA.PTM Ribosomal protein S6 is the major substrate of protein kinases in eukaryote ribosomes. The phosphorylation is stimulated by growth factors, tumor promoting agents, and mitogens. It is dephosphorylated at growth arrest. Phosphorylated at Ser-235 and Ser-236 by RPS6KA1 and RPS6KA3; phosphorylation at these sites facilitates the assembly of the preinitiation complex.PTM Specifically hydroxylated (with R stereochemistry) at C-3 of Arg-137 by KDM8.SIMILARITY Belongs to the eukaryotic ribosomal protein eS6 family.UniProtP627531EQUAL249EQUALReactome Database ID Release 7572381Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72381ReactomeR-HSA-723811Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72381.11RPS540S small ribosomal protein 5P4678240S ribosomal protein S5Reactome DB_ID: 72379UniProt:P46782 RPS5RPS5SIMILARITY Belongs to the universal ribosomal protein uS7 family.UniProtP467821EQUAL204EQUALReactome Database ID Release 7572379Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72379ReactomeR-HSA-723791Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72379.11KE3RPS1840S small ribosomal protein 18P2523240S ribosomal protein S18KE-3Reactome DB_ID: 72341UniProt:P62269 RPS18RPS18D6S218EFUNCTION Located at the top of the head of the 40S subunit, it contacts several helices of the 18S rRNA.SIMILARITY Belongs to the universal ribosomal protein uS13 family.UniProtP622692EQUAL152EQUALReactome Database ID Release 7572341Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72341ReactomeR-HSA-723411Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72341.11RPS1140S small ribosomal protein 11P0464340S ribosomal protein S11Reactome DB_ID: 72327UniProt:P62280 RPS11RPS11PTM Citrullinated by PADI4.SIMILARITY Belongs to the universal ribosomal protein uS17 family.UniProtP622802EQUAL158EQUALReactome Database ID Release 7572327Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72327ReactomeR-HSA-723271Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72327.11RPS1940S small ribosomal protein 19P3901940S ribosomal protein S19Reactome DB_ID: 72343UniProt:P39019 RPS19RPS19FUNCTION Required for pre-rRNA processing and maturation of 40S ribosomal subunits.SUBUNIT Interacts with RPS19BP1.TISSUE SPECIFICITY Higher level expression is seen in the colon carcinoma tissue than normal colon tissue.SIMILARITY Belongs to the eukaryotic ribosomal protein eS19 family.UniProtP390192EQUAL145EQUALReactome Database ID Release 7572343Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72343ReactomeR-HSA-723431Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72343.11RPS840S small ribosomal protein 8P0905840S ribosomal protein S8Reactome DB_ID: 72385UniProt:P62241 RPS8RPS8OK/SW-cl.83SUBUNIT Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs.SIMILARITY Belongs to the eukaryotic ribosomal protein eS8 family.UniProtP622412EQUAL208EQUALReactome Database ID Release 7572385Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72385ReactomeR-HSA-723851Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72385.11RPS2540S small ribosomal protein 25P2511140S ribosomal protein S25Reactome DB_ID: 72357UniProt:P62851 RPS25RPS25SIMILARITY Belongs to the eukaryotic ribosomal protein eS25 family.UniProtP628511EQUAL125EQUALReactome Database ID Release 7572357Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72357ReactomeR-HSA-723571Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72357.11RPS1540S small ribosomal protein 15P1117440S ribosomal protein S15RIG proteinReactome DB_ID: 72335UniProt:P62841 RPS15RPS15RIGSIMILARITY Belongs to the universal ribosomal protein uS19 family.UniProtP628412EQUAL145EQUALReactome Database ID Release 7572335Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72335ReactomeR-HSA-723351Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72335.11RPS27A(77-156)40S small ribosomal protein 27A40S ribosomal protein S27aReactome DB_ID: 7236377EQUAL156EQUALReactome Database ID Release 7572363Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72363ReactomeR-HSA-723631Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72363.11RPS2840S small ribosomal protein 28P2511240S ribosomal protein S28Reactome DB_ID: 72365UniProt:P62857 RPS28RPS28SUBUNIT Component of the 40S small ribosomal subunit.SIMILARITY Belongs to the eukaryotic ribosomal protein eS28 family.UniProtP628571EQUAL69EQUALReactome Database ID Release 7572365Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72365ReactomeR-HSA-723651Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72365.1118S rRNAReactome DB_ID: 72391EMBL:X03205 18S rRNA18S rRNAEMBLX03205Reactome Database ID Release 7572391Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72391ReactomeR-HSA-723911Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72391.11RPS1240S small ribosomal protein 12P2539840S ribosomal protein S12Reactome DB_ID: 72329UniProt:P25398 RPS12RPS12SIMILARITY Belongs to the eukaryotic ribosomal protein eS12 family.UniProtP253982EQUAL132EQUALReactome Database ID Release 7572329Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72329ReactomeR-HSA-723291Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72329.11RPS3A40S small ribosomal protein 3AP4924140S ribosomal protein S3aReactome DB_ID: 72373UniProt:P61247 RPS3ARPS3AFTE1MFTLFUNCTION May play a role during erythropoiesis through regulation of transcription factor DDIT3.SUBUNIT Component of the small ribosomal subunit. Mature ribosomes consist of a small (40S) and a large (60S) subunit. The 40S subunit contains about 33 different proteins and 1 molecule of RNA (18S). The 60S subunit contains about 49 different proteins and 3 molecules of RNA (28S, 5.8S and 5S). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Binds with high affinity to IPO4. Interacts with DDIT3.SIMILARITY Belongs to the eukaryotic ribosomal protein eS1 family.UniProtP612472EQUAL264EQUALReactome Database ID Release 7572373Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72373ReactomeR-HSA-723731Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72373.11RPS1440S small ribosomal protein 14P0636640S ribosomal protein S14PRO2640Reactome DB_ID: 72333UniProt:P62263 RPS14RPS14PRO2640SIMILARITY Belongs to the universal ribosomal protein uS11 family.UniProtP622632EQUAL151EQUALReactome Database ID Release 7572333Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72333ReactomeR-HSA-723331Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72333.11FAU40S small ribosomal protein 30Q0547240S ribosomal protein S30Reactome DB_ID: 72371UniProt:P62861 FAUFAUMISCELLANEOUS This ribosomal protein is synthesized as a C-terminal extension protein (CEP) of a ubiquitin-like protein.SIMILARITY Belongs to the eukaryotic ribosomal protein eS30 family.UniProtP628611EQUAL59EQUALReactome Database ID Release 7572371Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72371ReactomeR-HSA-723711Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72371.11RPS2340S small ribosomal protein 23P3902840S ribosomal protein S23Reactome DB_ID: 72353UniProt:P62266 RPS23RPS23FUNCTION Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:28257692, PubMed:23636399, PubMed:25957688, PubMed:25901680). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (PubMed:23636399, PubMed:25957688, PubMed:25901680). Plays an important role in translational accuracy (PubMed:28257692).SUBUNIT Component of the 40S small ribosomal subunit.PTM Hydroxylation at Pro-62 affects translation termination efficiency.SIMILARITY Belongs to the universal ribosomal protein uS12 family.UniProtP622662EQUAL143EQUALReactome Database ID Release 7572353Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72353ReactomeR-HSA-723531Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72353.11RPS1640S small ribosomal protein 16P1700840S ribosomal protein S16Reactome DB_ID: 72337UniProt:P62249 RPS16RPS16SIMILARITY Belongs to the universal ribosomal protein uS9 family.UniProtP622492EQUAL146EQUALReactome Database ID Release 7572337Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72337ReactomeR-HSA-723371Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72337.11Converted from EntitySet in ReactomeRPS27,RPS27LReactome DB_ID: 8868839RPS2740S small ribosomal protein 27P4267740S ribosomal protein S27Metallopan-stimulin 1MPS-1Reactome DB_ID: 72361UniProt:P42677 RPS27RPS27MPS1FUNCTION Component of the small ribosomal subunit (PubMed:8706699). Required for proper rRNA processing and maturation of 18S rRNAs (PubMed:25424902).SUBUNIT Component of the small ribosomal subunit.TISSUE SPECIFICITY Expressed in a wide variety of actively proliferating cells and tumor tissues.SIMILARITY Belongs to the eukaryotic ribosomal protein eS27 family.CAUTION Was originally (PubMed:8407955) thought to be a protein that could have played a role as a potentially important mediator of cellular proliferative responses to various growth factors and other environmental signals. Capable of specific binding to a cAMP response element in DNA.UniProtP426772EQUAL84EQUALReactome Database ID Release 7572361Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72361ReactomeR-HSA-723611Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72361.1RPS27L40S ribosomal protein S27-likeRS27L_HUMANReactome DB_ID: 8868849UniProt:Q71UM5 RPS27LRPS27LSIMILARITY Belongs to the eukaryotic ribosomal protein eS27 family.UniProtQ71UM52EQUAL84EQUALReactome Database ID Release 758868849Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8868849ReactomeR-HSA-88688492Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8868849.2Reactome Database ID Release 758868839Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8868839ReactomeR-HSA-88688392Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8868839.21RPS2140S small ribosomal protein 21P3526540S ribosomal protein S21Reactome DB_ID: 72351UniProt:P63220 RPS21RPS21SUBUNIT Component of the 40S small ribosomal subunit.SIMILARITY Belongs to the eukaryotic ribosomal protein eS21 family.UniProtP632201EQUAL83EQUALReactome Database ID Release 7572351Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72351ReactomeR-HSA-723511Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72351.11Converted from EntitySet in ReactomeRPS4X,RPS4Y1,RPS4Y2Reactome DB_ID: 8868832RPS4X40S small ribosomal protein 4P1275040S ribosomal protein S4, X isoformSingle copy abundant mRNA proteinSCR10Reactome DB_ID: 72375UniProt:P62701 RPS4XRPS4XCCG2RPS4SCARSUBUNIT Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs.SIMILARITY Belongs to the eukaryotic ribosomal protein eS4 family.UniProtP627012EQUAL263EQUALReactome Database ID Release 7572375Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72375ReactomeR-HSA-723751Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72375.1RPS4Y140S small ribosomal protein 4YP2209040S ribosomal protein S4, Y isoformPRO2646Reactome DB_ID: 72377UniProt:P22090 RPS4Y1RPS4Y1RPS4YPRO2646SIMILARITY Belongs to the eukaryotic ribosomal protein eS4 family.UniProtP220902EQUAL263EQUALReactome Database ID Release 7572377Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72377ReactomeR-HSA-723771Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72377.1RPS4Y240S ribosomal protein S4, Y isoform 2RS4Y2_HUMANReactome DB_ID: 8868834UniProt:Q8TD47 RPS4Y2RPS4Y2RPS4Y2PSIMILARITY Belongs to the eukaryotic ribosomal protein eS4 family.UniProtQ8TD471EQUAL263EQUALReactome Database ID Release 758868834Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8868834ReactomeR-HSA-88688342Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8868834.2Reactome Database ID Release 758868832Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8868832ReactomeR-HSA-88688322Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8868832.21S4RPS240S small ribosomal protein 2P1588040S ribosomal protein S2LLREP3 proteinReactome DB_ID: 72347UniProt:P15880 RPS2RPS2RPS4PTM Citrullinated by PADI4 in the Arg/Gly-rich region.PTM Asymmetric arginine dimethylation by PRMT3 occurs at multiple sites in the Arg/Gly-rich region.SIMILARITY Belongs to the universal ribosomal protein uS5 family.UniProtP158801EQUAL293EQUALReactome Database ID Release 7572347Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72347ReactomeR-HSA-723471Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72347.11S19RPS2440S small ribosomal protein 24P1663240S ribosomal protein S24Reactome DB_ID: 72355UniProt:P62847 RPS24RPS24FUNCTION Required for processing of pre-rRNA and maturation of 40S ribosomal subunits.TISSUE SPECIFICITY Mature tissues, such as adult brain, skeletal muscle, heart, and kidney, express low levels, whereas tissues and organs with significant populations of proliferating cells, such as fetal brain, placenta, bone marrow, and various glandular organs, contain significantly higher levels.SIMILARITY Belongs to the eukaryotic ribosomal protein eS24 family.UniProtP628471EQUAL133EQUALReactome Database ID Release 7572355Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72355ReactomeR-HSA-723551Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72355.11Reactome Database ID Release 7572392Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72392ReactomeR-HSA-723922Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72392.2ComplexPortalCPX-5223160S ribosomal complexReactome DB_ID: 72499L1RPL460S ribosomal protein L4Reactome DB_ID: 72474UniProt:P36578 RPL4RPL4RPL1SUBUNIT May bind IPO9 with low affinity. Interacts with RBM3 (By similarity).PTM Citrullinated by PADI4.SIMILARITY Belongs to the universal ribosomal protein uL4 family.UniProtP365782EQUAL427EQUALReactome Database ID Release 7572474Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72474ReactomeR-HSA-724741Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72474.11RPL1560S ribosomal protein L15P39030Reactome DB_ID: 72416UniProt:P61313 RPL15RPL15EC45TCBAP0781SUBUNIT Interacts with IFIT1 (via TPR repeats 1-4).SIMILARITY Belongs to the eukaryotic ribosomal protein eL15 family.UniProtP613131EQUAL204EQUALReactome Database ID Release 7572416Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72416ReactomeR-HSA-724161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72416.11RPL3460S ribosomal protein L34P49207Reactome DB_ID: 72458UniProt:P49207 RPL34RPL34FUNCTION Component of the large ribosomal subunit.SUBUNIT Component of the large ribosomal subunit.SIMILARITY Belongs to the eukaryotic ribosomal protein eL34 family.UniProtP492072EQUAL117EQUALReactome Database ID Release 7572458Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72458ReactomeR-HSA-724581Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72458.1128S rRNAReactome DB_ID: 72498EMBL:M11167 28S rRNA28S rRNAEMBLM111671EQUAL5025EQUALReactome Database ID Release 7572498Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72498ReactomeR-HSA-724981Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72498.11RPL13A60S ribosomal protein L13a23 kDa highly basic proteinReactome DB_ID: 72412UniProt:P40429 RPL13ARPL13AFUNCTION Associated with ribosomes but is not required for canonical ribosome function and has extra-ribosomal functions. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation and subsequent phosphorylation dissociates from the ribosome and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation. In the GAIT complex interacts with m7G cap-bound eIF4G at or near the eIF3-binding site and blocks the recruitment of the 43S ribosomal complex. Involved in methylation of rRNA.SUBUNIT Component of the 60S ribosome. Component of the GAIT complex. Interacts with EIF4G1.PTM Phosphorylation at Ser-77 upon interferon-gamma treatment in monocytes involves a DAPK1-DAPK3 kinase cascade and is causing release from the ribosome, association with the GAIT complex and subsequent involvement in transcript-selective translation inhibition.PTM Citrullinated by PADI4.SIMILARITY Belongs to the universal ribosomal protein uL13 family.UniProtP404292EQUAL203EQUALReactome Database ID Release 7572412Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72412ReactomeR-HSA-724121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72412.11Converted from EntitySet in ReactomeRPL10,RPL10LReactome DB_ID: 8868854RPL1060S ribosomal protein L10QM proteinTumor suppressor QMLaminin receptor homologReactome DB_ID: 72402UniProt:P27635 RPL10RPL10DXS648EQMFUNCTION Component of the large ribosomal subunit (PubMed:26290468). Plays a role in the formation of actively translating ribosomes (PubMed:26290468). May play a role in the embryonic brain development (PubMed:25316788).SUBUNIT Component of the large ribosomal subunit. Mature ribosomes consist of a small (40S) and a large (60S) subunit. The 40S subunit contains about 33 different proteins and 1 molecule of RNA (18S). The 60S subunit contains about 49 different proteins and 3 molecules of RNA (28S, 5.8S and 5S).DEVELOPMENTAL STAGE Down-regulated during adipocyte, kidney, and heart differentiation.PTM Citrullinated by PADI4.PTM Ufmylated by UFL1.SIMILARITY Belongs to the universal ribosomal protein uL16 family.UniProtP276352EQUAL214EQUALReactome Database ID Release 7572402Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72402ReactomeR-HSA-724021Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72402.1RPL10L60S ribosomal protein L10-likeRL10L_HUMANReactome DB_ID: 8868799UniProt:Q96L21 RPL10LRPL10LFUNCTION May play a role in compensating for the inactivated X-linked gene during spermatogenesis.TISSUE SPECIFICITY Testis specific.MISCELLANEOUS This gene has no introns in its coding regions, and therefore was most likely produced by retrotransposition of the original X-linked gene during evolution.SIMILARITY Belongs to the universal ribosomal protein uL16 family.UniProtQ96L212EQUAL214EQUALReactome Database ID Release 758868799Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8868799ReactomeR-HSA-88687992Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8868799.2Reactome Database ID Release 758868854Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8868854ReactomeR-HSA-88688542Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8868854.21RPLP160S acidic ribosomal protein P1P05386Reactome DB_ID: 72398UniProt:P05386 RPLP1RPLP1RRP1FUNCTION Plays an important role in the elongation step of protein synthesis.SUBUNIT Heterodimer with RPLP2 at the lateral ribosomal stalk of the large ribosomal subunit.SIMILARITY Belongs to the eukaryotic ribosomal protein P1/P2 family.UniProtP053862EQUAL114EQUALReactome Database ID Release 7572398Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72398ReactomeR-HSA-723981Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72398.11RPL2860S ribosomal protein L28P46779Reactome DB_ID: 72444UniProt:P46779 RPL28RPL28FUNCTION Component of the large ribosomal subunit.SUBUNIT Component of the large ribosomal subunit.SIMILARITY Belongs to the eukaryotic ribosomal protein eL28 family.UniProtP467792EQUAL137EQUALReactome Database ID Release 7572444Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72444ReactomeR-HSA-724441Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72444.11L17RPL2360S ribosomal protein L23Reactome DB_ID: 72430UniProt:P62829 RPL23RPL23SIMILARITY Belongs to the universal ribosomal protein uL14 family.UniProtP628291EQUAL140EQUALReactome Database ID Release 7572430Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72430ReactomeR-HSA-724301Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72430.11L10ERPLP060S acidic ribosomal protein P0Reactome DB_ID: 72396UniProt:P05388 RPLP0RPLP0FUNCTION Ribosomal protein P0 is the functional equivalent of E.coli protein L10.SUBUNIT P0 forms a pentameric complex by interaction with dimers of P1 and P2 (PubMed:3323886). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661). Interacts with APEX1 (PubMed:19188445). Interacts with FMR1 isoform 6 (PubMed:24658146).SIMILARITY Belongs to the universal ribosomal protein uL10 family.UniProtP053881EQUAL317EQUALReactome Database ID Release 7572396Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72396ReactomeR-HSA-723961Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72396.11HG12RPL4160S ribosomal protein L41Reactome DB_ID: 72478UniProt:P62945 RPL41RPL41FUNCTION Interacts with the beta subunit of protein kinase CKII and stimulates phosphorylation of DNA topoisomerase II alpha by CKII.SIMILARITY Belongs to the eukaryotic ribosomal protein eL41 family.CAUTION There are multiple pseudogenes of this gene dispersed through the genome.UniProtP629451EQUAL25EQUALReactome Database ID Release 7572478Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72478ReactomeR-HSA-724781Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72478.11RPL3660S ribosomal protein L36Q9Y3U8Reactome DB_ID: 72464UniProt:Q9Y3U8 RPL36RPL36FUNCTION Component of the large ribosomal subunit.SUBUNIT Component of the large ribosomal subunit.SIMILARITY Belongs to the eukaryotic ribosomal protein eL36 family.UniProtQ9Y3U82EQUAL105EQUALReactome Database ID Release 7572464Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72464ReactomeR-HSA-724641Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72464.11Converted from EntitySet in ReactomeRPL26,RPL26L1Reactome DB_ID: 8868827RPL2660S ribosomal protein L26Q02877Reactome DB_ID: 72436UniProt:P61254 RPL26RPL26FUNCTION Component of the large ribosomal subunit.SUBUNIT Component of the large ribosomal subunit (Probable). Interacts with DHX33 (PubMed:26100019).PTM Ufmylated by UFL1 in response to endoplasmic reticulum stress, promoting reticulophagy of endoplasmic reticulum sheets.SIMILARITY Belongs to the universal ribosomal protein uL24 family.UniProtP612541EQUAL145EQUALReactome Database ID Release 7572436Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72436ReactomeR-HSA-724361Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72436.1Q9UNX3RPL26L160S ribosomal protein L26-like 1Reactome DB_ID: 72438UniProt:Q9UNX3 RPL26L1RPL26L1RPL26P1SIMILARITY Belongs to the universal ribosomal protein uL24 family.UniProtQ9UNX31EQUAL145EQUALReactome Database ID Release 7572438Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72438ReactomeR-HSA-724381Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72438.1Reactome Database ID Release 758868827Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8868827ReactomeR-HSA-88688272Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8868827.21RPL2760S ribosomal protein L27P08526Reactome DB_ID: 72440UniProt:P61353 RPL27RPL27FUNCTION Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:25957688, PubMed:25901680). Required for proper rRNA processing and maturation of 28S and 5.8S rRNAs (PubMed:25424902).SUBUNIT Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:25957688, PubMed:25901680). Interacts with RRP1B (PubMed:20926688). Interacts with DHX33 (PubMed:26100019).SIMILARITY Belongs to the eukaryotic ribosomal protein eL27 family.UniProtP613531EQUAL136EQUALReactome Database ID Release 7572440Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72440ReactomeR-HSA-724401Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72440.11RPL23A60S ribosomal protein L23aP29316Reactome DB_ID: 72432UniProt:P62750 RPL23ARPL23AFUNCTION Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Binds a specific region on the 26S rRNA. May promote p53/TP53 degradation possibly through the stimulation of MDM2-mediated TP53 polyubiquitination (PubMed:26203195).SUBUNIT Interacts with LYAR and GNL2 (PubMed:26203195). Interacts with MDM2; this interaction may promote MDM2-mediated p53/TP53 polyubiquitination (PubMed:26203195).INDUCTION May be down-regulated by GNL2 (at protein level).PTM N-terminus is methylated by METTL11A/NTM1.PTM Citrullinated by PADI4.SIMILARITY Belongs to the universal ribosomal protein uL23 family.UniProtP627502EQUAL156EQUALReactome Database ID Release 7572432Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72432ReactomeR-HSA-724321Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72432.11RPL27A60S ribosomal protein L27aP46776Reactome DB_ID: 72442UniProt:P46776 RPL27ARPL27APTM Hydroxylated on His-39 by MINA.SIMILARITY Belongs to the universal ribosomal protein uL15 family.UniProtP467762EQUAL148EQUALReactome Database ID Release 7572442Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72442ReactomeR-HSA-724421Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72442.11L23RPL1760S ribosomal protein L17Reactome DB_ID: 72418UniProt:P18621 RPL17RPL17FUNCTION Component of the large ribosomal subunit.SUBUNIT Component of the large ribosomal subunit.TISSUE SPECIFICITY Expressed in pancreas, lung, colon, cystic duct, gall bladder, kidney and liver. Expressed at high levels in the well differentiated pancreatic tumor cell lines HPAF, COLO 357 and Capan-1, the moderately differentiated pancreatic tumor cell lines T3M-4, AsPc-1 and BxPc-3, the poorly differentiated pancreatic tumor cell line MIA PaCa-2, and the pancreatic tumor cell lines of undefined differentiation status such as SW979. Expressed at lower levels in the poorly differentiated pancreatic tumor cell lines HCG-25 and PANC-1.SIMILARITY Belongs to the universal ribosomal protein uL22 family.UniProtP186212EQUAL184EQUALReactome Database ID Release 7572418Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72418ReactomeR-HSA-724181Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72418.11RPL960S ribosomal protein L9 P32969Reactome DB_ID: 72492UniProt:P32969 RPL9RPL9OK/SW-cl.103RPL9P7RPL9P8RPL9P9SIMILARITY Belongs to the universal ribosomal protein uL6 family.UniProtP329691EQUAL192EQUALReactome Database ID Release 7572492Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72492ReactomeR-HSA-724921Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72492.11RPL1960S ribosomal protein L19P14118Reactome DB_ID: 72424UniProt:P84098 RPL19RPL19PTM Citrullinated by PADI4.SIMILARITY Belongs to the eukaryotic ribosomal protein eL19 family.UniProtP840981EQUAL196EQUALReactome Database ID Release 7572424Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72424ReactomeR-HSA-724241Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72424.11RPL3060S ribosomal protein L30P04645Reactome DB_ID: 72452UniProt:P62888 RPL30RPL30SIMILARITY Belongs to the eukaryotic ribosomal protein eL30 family.UniProtP628881EQUAL115EQUALReactome Database ID Release 7572452Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72452ReactomeR-HSA-724521Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72452.11RPL2160S ribosomal protein L21P46778Reactome DB_ID: 72426UniProt:P46778 RPL21RPL21FUNCTION Component of the large ribosomal subunit.SUBUNIT Component of the large ribosomal subunit.SIMILARITY Belongs to the eukaryotic ribosomal protein eL21 family.UniProtP467782EQUAL160EQUALReactome Database ID Release 7572426Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72426ReactomeR-HSA-724261Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72426.11RPL860S ribosomal protein L8P25120Reactome DB_ID: 72490UniProt:P62917 RPL8RPL8FUNCTION Component of the large ribosomal subunit.SUBUNIT Component of the large ribosomal subunit (Probable). Interacts with CRY1 (By similarity).PTM Hydroxylated on His-216 by RIOX1. The modification is impaired by hypoxia.MISCELLANEOUS This protein can be partially incorporated into E.coli polysomes in vivo, indicating it can replace the endogenous protein.SIMILARITY Belongs to the universal ribosomal protein uL2 family.UniProtP629172EQUAL257EQUALReactome Database ID Release 7572490Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72490ReactomeR-HSA-724901Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72490.115S rRNAReactome DB_ID: 72494EMBL:V00589 5S rRNA5S rRNAEMBLV00589Reactome Database ID Release 7572494Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72494ReactomeR-HSA-724941Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72494.11RPL1460S ribosomal protein L14CAG-ISL 7Reactome DB_ID: 72414UniProt:P50914 RPL14RPL14FUNCTION Component of the large ribosomal subunit.SUBUNIT Component of the large ribosomal subunit.POLYMORPHISM The poly-Ala stretch is highly polymorphic.SIMILARITY Belongs to the eukaryotic ribosomal protein eL14 family.UniProtP509142EQUAL215EQUALReactome Database ID Release 7572414Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72414ReactomeR-HSA-724141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72414.11RPL1260S ribosomal protein L12P30050Reactome DB_ID: 72408UniProt:P30050 RPL12RPL12FUNCTION Binds directly to 26S ribosomal RNA.SIMILARITY Belongs to the universal ribosomal protein uL11 family.UniProtP300501EQUAL165EQUALReactome Database ID Release 7572408Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72408ReactomeR-HSA-724081Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72408.11RPL760S ribosomal protein L7P18124Reactome DB_ID: 72486UniProt:P18124 RPL7RPL7FUNCTION Component of the large ribosomal subunit (PubMed:12962325). Binds to G-rich structures in 28S rRNA and in mRNAs. Plays a regulatory role in the translation apparatus; inhibits cell-free translation of mRNAs.SUBUNIT Component of the large ribosomal subunit (Probable). Homodimer. Interacts with DHX33 (PubMed:26100019).SIMILARITY Belongs to the universal ribosomal protein uL30 family.UniProtP181241EQUAL248EQUALReactome Database ID Release 7572486Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72486ReactomeR-HSA-724861Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72486.11RPL1160S ribosomal protein L11P39026Reactome DB_ID: 72406UniProt:P62913 RPL11RPL11FUNCTION Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel. As part of the 5S RNP/5S ribonucleoprotein particle it is an essential component of the LSU, required for its formation and the maturation of rRNAs (PubMed:19061985, PubMed:12962325, PubMed:24120868). It also couples ribosome biogenesis to p53/TP53 activation. As part of the 5S RNP it accumulates in the nucleoplasm and inhibits MDM2, when ribosome biogenesis is perturbed, mediating the stabilization and the activation of TP53 (PubMed:24120868). Promotes nucleolar location of PML (By similarity).SUBUNIT Component of the large ribosomal subunit (LSU). Part of a LSU subcomplex, the 5S RNP which is composed of the 5S RNA, RPL5 and RPL11 (PubMed:24120868). Interacts with PML (By similarity). Interacts with MDM2; negatively regulates MDM2-mediated TP53 ubiquitination and degradation (PubMed:24120868). Interacts with NOP53; retains RPL11 into the nucleolus (PubMed:24556985, PubMed:27829214).SIMILARITY Belongs to the universal ribosomal protein uL5 family.UniProtP629132EQUAL178EQUALReactome Database ID Release 7572406Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72406ReactomeR-HSA-724061Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72406.11RPL660S ribosomal protein L6TAX-responsive enhancer element binding protein 107TAXREB107Neoplasm-related protein C140Reactome DB_ID: 72484UniProt:Q02878 RPL6RPL6TXREB1FUNCTION Component of the large ribosomal subunit.FUNCTION (Microbial infection) Specifically binds to domain C of the Tax-responsive enhancer element in the long terminal repeat of HTLV-I (PubMed:8457378).SUBUNIT Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:25957688, PubMed:25901680). May bind IPO9 with low affinity (By similarity).SIMILARITY Belongs to the eukaryotic ribosomal protein eL6 family.UniProtQ028782EQUAL288EQUALReactome Database ID Release 7572484Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72484ReactomeR-HSA-724841Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72484.11RPL560S ribosomal protein L5P46777Reactome DB_ID: 72482UniProt:P46777 RPL5RPL5MSTP030FUNCTION Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel. As part of the 5S RNP/5S ribonucleoprotein particle it is an essential component of the LSU, required for its formation and the maturation of rRNAs (PubMed:12962325, PubMed:19061985, PubMed:24120868, PubMed:23636399). It also couples ribosome biogenesis to p53/TP53 activation. As part of the 5S RNP it accumulates in the nucleoplasm and inhibits MDM2, when ribosome biogenesis is perturbed, mediating the stabilization and the activation of TP53 (PubMed:24120868).SUBUNIT Component of the large ribosomal subunit (LSU). Part of a LSU subcomplex, the 5S RNP which is composed of the 5S RNA, RPL5 and RPL11 (PubMed:24120868). Interacts with isoform 1 of NVL in an ATP-dependent manner (PubMed:15469983). Interacts with RRP1B (PubMed:20926688).SIMILARITY Belongs to the universal ribosomal protein uL18 family.UniProtP467772EQUAL297EQUALReactome Database ID Release 7572482Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72482ReactomeR-HSA-724821Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72482.11RPLP260S acidic ribosomal protein P2P05387Reactome DB_ID: 72400UniProt:P05387 RPLP2RPLP2D11S2243ERPP2FUNCTION Plays an important role in the elongation step of protein synthesis.SUBUNIT Heterodimer with RPLP1 at the lateral ribosomal stalk of the large ribosomal subunit.SIMILARITY Belongs to the eukaryotic ribosomal protein P1/P2 family.UniProtP053871EQUAL115EQUALReactome Database ID Release 7572400Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72400ReactomeR-HSA-724001Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72400.11Converted from EntitySet in ReactomeRPL3,RPL3LReactome DB_ID: 8868851RPL360S ribosomal protein L3HIV-1 TAR RNA binding protein BTARBP-BReactome DB_ID: 72448UniProt:P39023 RPL3RPL3OK/SW-cl.32FUNCTION The L3 protein is a component of the large subunit of cytoplasmic ribosomes.SUBUNIT Component of the large ribosomal subunit (Probable). Interacts with METTL18 (PubMed:23349634). Interacts with DHX33 (PubMed:26100019).SIMILARITY Belongs to the universal ribosomal protein uL3 family.UniProtP390232EQUAL403EQUALReactome Database ID Release 7572448Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72448ReactomeR-HSA-724481Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72448.1RPL3L60S ribosomal protein L3-likeQ92901Reactome DB_ID: 72450UniProt:Q92901 RPL3LRPL3LSIMILARITY Belongs to the universal ribosomal protein uL3 family.UniProtQ929011EQUAL407EQUALReactome Database ID Release 7572450Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72450ReactomeR-HSA-724501Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72450.1Reactome Database ID Release 758868851Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8868851ReactomeR-HSA-88688512Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8868851.21RPL3260S ribosomal protein L32P02433Reactome DB_ID: 72456UniProt:P62910 RPL32RPL32PP9932SIMILARITY Belongs to the eukaryotic ribosomal protein eL32 family.UniProtP629102EQUAL135EQUALReactome Database ID Release 7572456Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72456ReactomeR-HSA-724561Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72456.11RPL3560S ribosomal protein L35P42766Reactome DB_ID: 72460UniProt:P42766 RPL35RPL35FUNCTION Component of the large ribosomal subunit.SUBUNIT Component of the large ribosomal subunit.SIMILARITY Belongs to the universal ribosomal protein uL29 family.UniProtP427662EQUAL123EQUALReactome Database ID Release 7572460Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72460ReactomeR-HSA-724601Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72460.11RPL4060S ribosomal protein L40UBA52(77-128)CEP52Reactome DB_ID: 7247677EQUAL128EQUALReactome Database ID Release 7572476Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72476ReactomeR-HSA-724761Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72476.11Converted from EntitySet in ReactomeRPL36A,RPL36ALReactome DB_ID: 8868819L36aRPL36A60S ribosomal protein L44Reactome DB_ID: 72480UniProt:P83881 RPL36ARPL36ARPL44GIG15MIG6SIMILARITY Belongs to the eukaryotic ribosomal protein eL42 family.UniProtP838812EQUAL106EQUALReactome Database ID Release 7572480Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72480ReactomeR-HSA-724801Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72480.1RPL36AL60S ribosomal protein L36a-likeRL36L_HUMANReactome DB_ID: 8868805UniProt:Q969Q0 RPL36ALRPL36ALTISSUE SPECIFICITY Ubiquitously expressed.MISCELLANEOUS This gene has no introns in its coding regions, and therefore, was most likely produced by retrotransposition of the original X-linked gene during evolution.SIMILARITY Belongs to the eukaryotic ribosomal protein eL42 family.UniProtQ969Q01EQUAL106EQUALReactome Database ID Release 758868805Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8868805ReactomeR-HSA-88688052Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8868805.2Reactome Database ID Release 758868819Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8868819ReactomeR-HSA-88688192Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8868819.21L30RPL2460S ribosomal protein L24Reactome DB_ID: 72434UniProt:P83731 RPL24RPL24SIMILARITY Belongs to the eukaryotic ribosomal protein eL24 family.UniProtP837311EQUAL157EQUALReactome Database ID Release 7572434Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72434ReactomeR-HSA-724341Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72434.11Converted from EntitySet in ReactomeRPL22,RPL22L1Reactome DB_ID: 8868847EAPRPL2260S ribosomal protein L22Epstein-Barr virus small RNA associated proteinEBER associated proteinHeparin binding protein HBp15Reactome DB_ID: 72428UniProt:P35268 RPL22RPL22MISCELLANEOUS Binds to Epstein-Barr virus small RNAs and to heparin.SIMILARITY Belongs to the eukaryotic ribosomal protein eL22 family.UniProtP352682EQUAL128EQUALReactome Database ID Release 7572428Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72428ReactomeR-HSA-724281Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72428.1RPL22L160S ribosomal protein L22-like 1RL22L_HUMANReactome DB_ID: 8868814UniProt:Q6P5R6 RPL22L1RPL22L1SIMILARITY Belongs to the eukaryotic ribosomal protein eL22 family.UniProtQ6P5R61EQUAL122EQUALReactome Database ID Release 758868814Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8868814ReactomeR-HSA-88688142Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8868814.2Reactome Database ID Release 758868847Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8868847ReactomeR-HSA-88688472Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8868847.21RPL35A60S ribosomal protein L35aP18077Reactome DB_ID: 72462UniProt:P18077 RPL35ARPL35AGIG33FUNCTION Required for the proliferation and viability of hematopoietic cells. Plays a role in 60S ribosomal subunit formation. The protein was found to bind to both initiator and elongator tRNAs and consequently was assigned to the P site or P and A site.MISCELLANEOUS Knockdown of RPL35A in hematopoietic cell lines results in decreased cell proliferation, increased apoptosis, decreased biogenesis of mature 60S ribosomal subunit, and abnormal processing of large ribosomal subunit rRNA.SIMILARITY Belongs to the eukaryotic ribosomal protein eL33 family.UniProtP180771EQUAL110EQUALReactome Database ID Release 7572462Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72462ReactomeR-HSA-724621Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72462.11RPL3860S ribosomal protein L38P23411Reactome DB_ID: 72470UniProt:P63173 RPL38RPL38SIMILARITY Belongs to the eukaryotic ribosomal protein eL38 family.UniProtP631732EQUAL70EQUALReactome Database ID Release 7572470Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72470ReactomeR-HSA-724701Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72470.11RPL3760S ribosomal protein L37G1.16Reactome DB_ID: 72466UniProt:P61927 RPL37RPL37FUNCTION Binds to the 23S rRNA.SIMILARITY Belongs to the eukaryotic ribosomal protein eL37 family.UniProtP619272EQUAL97EQUALReactome Database ID Release 7572466Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72466ReactomeR-HSA-724661Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72466.11RPL1360S ribosomal protein L13Breast basic conserved protein 1Reactome DB_ID: 72410UniProt:P26373 RPL13RPL13BBC1OK/SW-cl.46FUNCTION Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:31630789, PubMed:23636399). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (Probable). The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain (Probable). The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (Probable). As part of the LSU, it is probably required for its formation and the maturation of rRNAs (PubMed:31630789). Plays a role in bone development (PubMed:31630789).SUBUNIT Component of the 60S large ribosomal subunit (LSU).TISSUE SPECIFICITY Higher levels of expression in benign breast lesions than in carcinomas.SIMILARITY Belongs to the eukaryotic ribosomal protein eL13 family.UniProtP263731EQUAL211EQUALReactome Database ID Release 7572410Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72410ReactomeR-HSA-724101Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72410.11RPL18A60S ribosomal protein L18aQ02543Reactome DB_ID: 72422UniProt:Q02543 RPL18ARPL18ASUBUNIT Binds IPO9 with high affinity.SIMILARITY Belongs to the eukaryotic ribosomal protein eL20 family.UniProtQ025431EQUAL176EQUALReactome Database ID Release 7572422Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72422ReactomeR-HSA-724221Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72422.11RPL10A60S ribosomal protein L10aCSA-19Reactome DB_ID: 72404UniProt:P62906 RPL10ARPL10ANEDD6FUNCTION Component of the large ribosomal subunit.SUBUNIT Component of the large ribosomal subunit.SIMILARITY Belongs to the universal ribosomal protein uL1 family.UniProtP629062EQUAL217EQUALReactome Database ID Release 7572404Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72404ReactomeR-HSA-724041Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72404.115.8S rRNAReactome DB_ID: 72496EMBL:J01866 5.8S rRNA5.8S rRNAEMBLJ01866Reactome Database ID Release 7572496Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72496ReactomeR-HSA-724961Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72496.11Converted from EntitySet in ReactomeRPL39,RPL39LReactome DB_ID: 8868812RPL3960S ribosomal protein L39P02404Reactome DB_ID: 72472UniProt:P62891 RPL39RPL39SUBUNIT Interacts with IMPACT.MISCELLANEOUS This protein is the smallest and one of the most basic of the proteins in liver ribosomes.SIMILARITY Belongs to the eukaryotic ribosomal protein eL39 family.UniProtP628912EQUAL51EQUALReactome Database ID Release 7572472Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72472ReactomeR-HSA-724721Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72472.1RPL39L60S ribosomal protein L39-likeRL39L_HUMANReactome DB_ID: 8868836UniProt:Q96EH5 RPL39LRPL39LRPL39L1TISSUE SPECIFICITY Testis specific.SIMILARITY Belongs to the eukaryotic ribosomal protein eL39 family.UniProtQ96EH51EQUAL51EQUALReactome Database ID Release 758868836Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8868836ReactomeR-HSA-88688362Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8868836.2Reactome Database ID Release 758868812Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8868812ReactomeR-HSA-88688122Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8868812.21RPL1860S ribosomal protein L18Q07020Reactome DB_ID: 72420UniProt:Q07020 RPL18RPL18FUNCTION Component of the large ribosomal subunit.SUBUNIT Component of the large ribosomal subunit.SIMILARITY Belongs to the eukaryotic ribosomal protein eL18 family.UniProtQ070202EQUAL188EQUALReactome Database ID Release 7572420Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72420ReactomeR-HSA-724201Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72420.11RPL7A60S ribosomal protein L7aSurfeit locus protein 3PLA-X polypeptideReactome DB_ID: 72488UniProt:P62424 RPL7ARPL7ASURF-3SURF3SUBUNIT Interacts with CRY1 (By similarity). Interacts with DICER1, AGO2, TARBP2, MOV10 and EIF6; they form a large RNA-induced silencing complex (RISC) (PubMed:17507929).DISEASE Chromosomal recombination involving RPL7A activates the receptor kinase domain of the TRK oncogene.SIMILARITY Belongs to the eukaryotic ribosomal protein eL8 family.UniProtP62424