BioPAX pathway converted from "TRIM27 polyubiquitinates PTEN" in the Reactome database.LEFT-TO-RIGHTTRIM27 polyubiquitinates PTENTRIM27 (RFP) is an E3 ubiquitin ligase for PTEN. TRIM27 polyubiquitinates PTEN on multiple lysines in the C2 domain of PTEN using K27-linkage between ubiquitin molecules. TRIM27-mediated ubiquitination inhibits PTEN lipid phosphatase activity, but does not affect PTEN protein localization or stability (Lee et al. 2013).Authored: Orlic-Milacic, Marija, 2016-01-04Reviewed: Leslie, Nicholas, 2016-09-30Reviewed: Kriplani, Nisha, 2016-09-30Reviewed: Carracedo, Arkaitz, 2016-08-11Reviewed: Salmena, Leonardo, 2016-08-11Edited: Orlic-Milacic, Marija, 2017-05-09Converted from EntitySet in ReactomeUbubiquitinReactome DB_ID: 113595RPS27ARPS27A(1-76)ubiquitin (RPS27A)Reactome DB_ID: 939205cytosolGENE ONTOLOGYGO:0005829UniProt:P62979 RPS27ARPS27AUBA80UBCEP1FUNCTION Ubiquitin: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.FUNCTION 40S Ribosomal protein S27a: Component of the 40S subunit of the ribosome.SUBUNIT Ribosomal protein S27a is part of the 40S ribosomal subunit.PTM Ubiquitin: Phosphorylated at Ser-65 by PINK1 during mitophagy. Phosphorylated ubiquitin specifically binds and activates parkin (PRKN), triggering mitophagy (PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25527291). Phosphorylation does not affect E1-mediated E2 charging of ubiquitin but affects discharging of E2 enzymes to form polyubiquitin chains. It also affects deubiquitination by deubiquitinase enzymes such as USP30 (PubMed:25527291).PTM Ubiquitin: Mono-ADP-ribosylated at the C-terminus by PARP9, a component of the PPAR9-DTX3L complex. ADP-ribosylation requires processing by E1 and E2 enzymes and prevents ubiquitin conjugation to substrates such as histones.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.Homo sapiensNCBI Taxonomy9606UniProtP629791EQUAL76EQUALReactome Database ID Release 71939205Database identifier. Use 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-939205.1Reactomehttp://www.reactome.orgUBA52UBA52(1-76)ubiquitin (UBA52)Reactome DB_ID: 939203UniProt:P62987 UBA52UBA52UBCEP2FUNCTION Ubiquitin: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.FUNCTION 60S ribosomal protein L40: Component of the 60S subunit of the ribosome. Ribosomal protein L40 is essential for translation of a subset of cellular transcripts, and especially for cap-dependent translation of vesicular stomatitis virus mRNAs.SUBUNIT Ribosomal protein L40 is part of the 60S ribosomal subunit. Interacts with UBQLN1 (via UBA domain).PTM Ubiquitin: Phosphorylated at Ser-65 by PINK1 during mitophagy. Phosphorylated ubiquitin specifically binds and activates parkin (PRKN), triggering mitophagy (PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25527291). Phosphorylation does not affect E1-mediated E2 charging of ubiquitin but affects discharging of E2 enzymes to form polyubiquitin chains. It also affects deubiquitination by deubiquitinase enzymes such as USP30 (PubMed:25527291).PTM Ubiquitin: Mono-ADP-ribosylated at the C-terminus by PARP9, a component of the PPAR9-DTX3L complex. ADP-ribosylation requires processing by E1 and E2 enzymes and prevents ubiquitin conjugation to substrates such as histones.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 71939203Database identifier. Use 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 UBBUBBFUNCTION Ubiquitin: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.PTM Ubiquitin: Phosphorylated at Ser-65 by PINK1 during mitophagy. Phosphorylated ubiquitin specifically binds and activates parkin (PRKN), triggering mitophagy (PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25527291). Phosphorylation does not affect E1-mediated E2 charging of ubiquitin but affects discharging of E2 enzymes to form polyubiquitin chains. It also affects deubiquitination by deubiquitinase enzymes such as USP30 (PubMed:25527291).PTM Ubiquitin: Mono-ADP-ribosylated at the C-terminus by PARP9, a component of the PPAR9-DTX3L complex. ADP-ribosylation requires processing by E1 and E2 enzymes and prevents ubiquitin conjugation to substrates such as histones.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 71939214Database identifier. Use 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 71939213Database identifier. Use 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 71939230Database identifier. Use 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 UBCUBCFUNCTION Ubiquitin: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.PTM Ubiquitin: Phosphorylated at Ser-65 by PINK1 during mitophagy. Phosphorylated ubiquitin specifically binds and activates parkin (PRKN), triggering mitophagy (PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25527291). Phosphorylation does not affect E1-mediated E2 charging of ubiquitin but affects discharging of E2 enzymes to form polyubiquitin chains. It also affects deubiquitination by deubiquitinase enzymes such as USP30 (PubMed:25527291).PTM Ubiquitin: Mono-ADP-ribosylated at the C-terminus by PARP9, a component of the PPAR9-DTX3L complex. ADP-ribosylation requires processing by E1 and E2 enzymes and prevents ubiquitin conjugation to substrates such as histones.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 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 71939188Database identifier. Use 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 71939164Database identifier. Use 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 71939258Database identifier. Use 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 71939192Database identifier. Use 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 71939232Database identifier. Use 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 71939191Database identifier. Use 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 71939184Database identifier. Use 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 71939239Database identifier. Use 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 71939165Database identifier. Use 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 71113595Database identifier. Use 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-113595.13PTEN:RFPPTEN:TRIM27Reactome DB_ID: 8851000RFPTRIM27Zinc finger protein RFPTripartite motif-containing protein 27RING finger protein 76RNF76Ret finger proteinReactome DB_ID: 8851002UniProt:P14373 TRIM27TRIM27RFPRNF76FUNCTION E3 ubiquitin-protein ligase that mediates ubiquitination of PIK3C2B and inhibits its activity; mediates the formation of 'Lys-48'-linked polyubiquitin chains; the function inhibits CD4 T-cell activation. Acts as a regulator of retrograde transport: together with MAGEL2, mediates the formation of 'Lys-63'-linked polyubiquitin chains at 'Lys-220' of WASHC1, leading to promote endosomal F-actin assembly (PubMed:23452853). Has a transcriptional repressor activity by cooperating with EPC1. Induces apoptosis by activating Jun N-terminal kinase and p38 kinase and also increases caspase-3-like activity independently of mitochondrial events. May function in male germ cell development. Has DNA-binding activity and preferentially bound to double-stranded DNA.SUBUNIT Homomultimerizes. Interacts with PML, EIF3S6, EPC1, CHD4 and EID1. Interacts with MAGED4, MAGEF1 and MAGEL2. Interacts with herpes simplex virus protein ICP0.TISSUE SPECIFICITY Expressed in testis namely within the seminiferous tubules.DOMAIN The coiled-coil region mediates interaction with EPC1 and CHD4. The B box and coiled-coil domains mediate interaction with PML. The B box and the distal coiled-coil domains mediate homomultimerisation. The B30.2 domain mediates interaction with EIF3S6.DISEASE A chromosomal aberration involving TRIM27/RFP is found in papillary thyroid carcinomas (PTCs). Translocation t(6;10)(p21.3;q11.2) with RET. The translocation generates TRIM27/RET and delta TRIM27/RET oncogenes.SIMILARITY Belongs to the TRIM/RBCC family.UniProtP143731EQUAL513EQUALReactome Database ID Release 718851002Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8851002ReactomeR-HSA-88510021Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8851002.11PTENPhosphatidylinositol-3,4,5-trisphosphate 3-phosphatase PTENPTEN_HUMANMMAC1TEP1Reactome DB_ID: 199420UniProt:P60484 PTENPTENMMAC1TEP1FUNCTION Tumor suppressor. Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4 (PubMed:26504226, PubMed:16824732). The lipid phosphatase activity is critical for its tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form cooperates with AIP1 to suppress AKT1 activation. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation. Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement.FUNCTION Isoform alpha: Functional kinase, like isoform 1 it antagonizes the PI3K-AKT/PKB signaling pathway. Plays a role in mitochondrial energetic metabolism by promoting COX activity and ATP production, via collaboration with isoform 1 in increasing protein levels of PINK1.ACTIVITY REGULATION Enzymatic activity is enhanced in the presence of phosphatidylserine.SUBUNIT Monomer. The unphosphorylated form interacts with the second PDZ domain of AIP1 and with DLG1 and MAST2 in vitro (PubMed:10646847, PubMed:10760291, PubMed:11707428). Interacts with MAGI2, MAGI3, MAST1 and MAST3, but neither with MAST4 nor with DLG5; interaction with MAGI2 increases protein stability (PubMed:10748157, PubMed:15951562). Interacts with NEDD4 (PubMed:17218260). Interacts with NDFIP1 and NDFIP2; in the presence of NEDD4 or ITCH, this interaction promotes PTEN ubiquitination (PubMed:25801959, PubMed:20534535). Interacts (via C2 domain) with FRK (PubMed:19345329). Interacts with USP7; the interaction is direct (PubMed:18716620). Interacts with ROCK1 (By similarity). Interacts with XIAP/BIRC4 (PubMed:19473982). Interacts with STK11; the interaction phosphorylates PTEN (PubMed:15987703). Interacts with PPP1R16B (PubMed:25007873). Interacts with NOP53; regulates PTEN phosphorylation and increases its stability (PubMed:15355975).TISSUE SPECIFICITY Expressed at a relatively high level in all adult tissues, including heart, brain, placenta, lung, liver, muscle, kidney and pancreas.INDUCTION Down-regulated by TGFB1.DOMAIN The C2 domain binds phospholipid membranes in vitro in a Ca(2+)-independent manner; this binding is important for its tumor suppressor function.PTM Constitutively phosphorylated by CK2 under normal conditions. Phosphorylated in vitro by MAST1, MAST2, MAST3 and STK11. Phosphorylation results in an inhibited activity towards PIP3. Phosphorylation can both inhibit or promote PDZ-binding. Phosphorylation at Tyr-336 by FRK/PTK5 protects this protein from ubiquitin-mediated degradation probably by inhibiting its binding to NEDD4. Phosphorylation by ROCK1 is essential for its stability and activity. Phosphorylation by PLK3 promotes its stability and prevents its degradation by the proteasome.PTM Monoubiquitinated; monoubiquitination is increased in presence of retinoic acid. Deubiquitinated by USP7; leading to its nuclear exclusion. Monoubiquitination of one of either Lys-13 and Lys-289 amino acid is sufficient to modulate PTEN compartmentalization. Ubiquitinated by XIAP/BIRC4.DISEASE PTEN mutations are found in a subset of patients with Proteus syndrome, a genetically heterogeneous condition. The molecular diagnosis of PTEN mutation positive cases classifies Proteus syndrome patients as part of the PTEN hamartoma syndrome spectrum. As such, patients surviving the early years of Proteus syndrome are likely at a greater risk of developing malignancies.DISEASE A microdeletion of chromosome 10q23 involving BMPR1A and PTEN is a cause of chromosome 10q23 deletion syndrome, which shows overlapping features of the following three disorders: Bannayan-Zonana syndrome, Cowden disease and juvenile polyposis syndrome.SIMILARITY Belongs to the PTEN phosphatase protein family.UniProtP604842EQUAL403EQUALReactome Database ID Release 71199420Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=199420ReactomeR-HSA-1994202Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-199420.21Reactome Database ID Release 718851000Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8851000ReactomeR-HSA-88510001Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8851000.1K27polyUb-PTENReactome DB_ID: 8851009ubiquitinylated lysineMODMOD:011482EQUAL403EQUALReactome Database ID Release 718851009Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8851009ReactomeR-HSA-88510091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8851009.1ACTIVATIONactiveUnit: #Protein16GENE ONTOLOGYGO:0061630gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 718851010Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8851010Reactome Database ID Release 718851011Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8851011ReactomeR-HSA-88510113Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8851011.323419514Pubmed2013RFP-mediated ubiquitination of PTEN modulates its effect on AKT activationLee, James TShan, JingZhong, JiayunLi, MuyangZhou, BrendaZhou, AmandaParsons, RGu, WeiCell Res. 23:552-64