BioPAX pathway converted from "PIAS4 SUMOylates IKBKG with SUMO1" in the Reactome database. PIAS4 SUMOylates IKBKG with SUMO1 PIAS4 SUMOylates IKBKG with SUMO1 This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 9884348 1 nucleoplasm GO 0005654 UniProt:O88522 Reactome http://www.reactome.org Mus musculus NCBI Taxonomy 10090 UniProt O88522 Chain Coordinates 1 EQUAL 419 EQUAL Reactome DB_ID: 9879547 2 SUMO1:C93-UBE2I [nucleoplasm] SUMO1:C93-UBE2I Reactome DB_ID: 9879542 1 UniProt:P63280 Ube2i Ube2i Ubce9 Ube2i Ubce2i Ubc9 FUNCTION Accepts the ubiquitin-like proteins SUMO1, SUMO2 and SUMO3 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2, CBX4 and ZNF451. Can catalyze the formation of poly-SUMO chains. Essential for nuclear architecture, chromosome segregation and embryonic viability. Necessary for sumoylation of FOXL2 and KAT5 (By similarity). Sumoylates p53/TP53 at 'Lys-386'. Mediates sumoylation of ERCC6 which is essential for its transcription-coupled nucleotide excision repair activity (By similarity).PATHWAY Protein modification; protein sumoylation.SUBUNIT Forms a complex with SENP6 and UBE2I in response to UV irradiation (By similarity). Forms a tight complex with RANGAP1 and RANBP2 (By similarity). Identified in a complex with SUMO2 and UBE2I, where one ZNF451 interacts with one UBE2I and two SUMO2 chains, one bound to the UBE2I active site and the other to another region of the same UBE2I molecule (By similarity). Interacts with SETX (By similarity). Interacts with HIPK1 and HIPK2 (PubMed:10535925). Interacts with PPM1J (PubMed:12633878). Interacts with RASD2 (By similarity). Interacts with TCF3 (PubMed:9409784). Interacts with NR2C1; the interaction promotes its sumoylation (PubMed:17187077). Interacts with SIAH1 (By similarity). Interacts with PARP (By similarity). Interacts with various transcription factors such as TFAP2A, TFAP2B, and TFAP2C (By similarity). Interacts with AR (By similarity). Interacts with ETS1 (By similarity). Interacts with SOX4 (By similarity). Interacts with RWDD3; the interaction enhances the sumoylation of a number of proteins such as HIF1A and I-kappa-B (By similarity). Interacts with FOXL2 (By similarity). Interacts with DNM1l (via its GTPase and B domains); the interaction promotes sumoylation of DNM1L, mainly in its B domain (By similarity). Interacts with NFATC2IP; this inhibits formation of poly-SUMO chains (By similarity). Interacts with FHIT (By similarity). Interacts with PRKRA and p53/TP53 (PubMed:22214662). Interacts with UHRF2 (By similarity). Interacts with NR3C1 and this interaction is enhanced in the presence of RWDD3 (By similarity). Interacts with MTA1 (By similarity). Interacts with ZNF451 (By similarity). Interacts with CPEB3 (PubMed:26074071). Interacts with SUMO1, SUMO2, and SUMO3 (By similarity). Interacts with IPO13 (By similarity). Interacts with DNMT1 (By similarity).TISSUE SPECIFICITY Present in spleen, kidney, lung, brain, heart and testis (at protein level).PTM Phosphorylation at Ser-71 significantly enhances SUMOylation activity.DISRUPTION PHENOTYPE Death prior to E7.5 due to major defects in nuclear organization.SIMILARITY Belongs to the ubiquitin-conjugating enzyme family. UniProt P63280 Inter-chain Crosslink via S-(glycyl)-L-cysteine (Cys-Gly) at 93 and 97 (in Homo sapiens) 93 EQUAL S-(glycyl)-L-cysteine (Cys-Gly) ChEBI 24411 modification 1 EQUAL 158 EQUAL Reactome DB_ID: 9879545 1 UniProt:P63166 Sumo1 Sumo1 Smt3h3 Sumo1 Ubl1 Smt3c FUNCTION Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by E3 ligases such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved for instance in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Covalently attached to the voltage-gated potassium channel KCNB1; this modulates the gating characteristics of KCNB1. Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. May also regulate a network of genes involved in palate development. Covalently attached to ZFHX3 (By similarity).SUBUNIT Covalently attached to KCNB1; UBE2I increases cross-linking with KCNB1 and PIAS1 decreases cross-links with KCNB1 (By similarity). Interacts with SAE2, RANBP2, PIAS1 and PIAS2 (By similarity). Interacts with PRKN (By similarity). Covalently attached to a number of proteins such as IKFZ1, PML, RANGAP1, HIPK2, SP100, p53, p73-alpha, MDM2, JUN, DNMT3B and TDG (By similarity). Also interacts with HIF1A, HIPK2, HIPK3, CHD3, EXOSC9, RAD51 and RAD52 (By similarity). Interacts with USP25 (via ts SIM domain); the interaction weakly sumoylates USP25 (By similarity). Interacts with SIMC1, CASP8AP2, RNF111 AND SOBP (via SIM domains) (By similarity). Interacts with BHLHE40/DEC1 (By similarity). Interacts with RWDD3 (By similarity). Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3 (By similarity). Interacts with MTA1 (By similarity). Interacts with SENP2 (By similarity). Interacts with HINT1 (PubMed:31088288).TISSUE SPECIFICITY Ubiquitous.DEVELOPMENTAL STAGE Expressed at 13.5 dpc strongly in the upper lip, primary palate and medial edge epithelia of the secondary palate. At 14.5 dpc expression could be seen in the medial edge epithelial seam.INDUCTION By hypoxia.PTM Cleavage of precursor form by SENP1 or SENP2 is necessary for function.PTM Polymeric SUMO1 chains undergo polyubiquitination by RNF4.SIMILARITY Belongs to the ubiquitin family. SUMO subfamily. UniProt P63166 Inter-chain Crosslink via S-(glycyl)-L-cysteine (Cys-Gly) at 97 and 93 (in Homo sapiens) 97 EQUAL ChEBI 23511 modification 2 EQUAL 97 EQUAL Reactome Database ID Release 82 9879547 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9879547 Reactome R-MMU-2993783 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2993783.1 Reactome DB_ID: 912483 2 1 EQUAL 158 EQUAL Reactome DB_ID: 9884352 1 sumoylated lysine (monoSUMO1 [nucleoplasm]) at 277 (in Homo sapiens) 277 EQUAL sumoylated lysine sumoylated lysine (monoSUMO1 [nucleoplasm]) at 309 (in Homo sapiens) 309 EQUAL 1 EQUAL 419 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 9816660 UniProt:Q9JM05 Pias4 Pias4 Pias4 Piasg FUNCTION Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Mediates sumoylation of CEBPA, PARK7, HERC2, MYB, TCF4 and RNF168. Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway, the p53/TP53 pathway, the Wnt pathway and the steroid hormone signaling pathway. Involved in gene silencing. In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations. Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation (By similarity). Binds to AT-rich DNA sequences, known as matrix or scaffold attachment regions (MARs/SARs) (PubMed:11731474). Catalyzes conjugation of SUMO2 to KAT5 in response to DNA damage, facilitating repair of DNA double-strand breaks (DSBs) via homologous recombination (HR) (By similarity).PATHWAY Protein modification; protein sumoylation.SUBUNIT Interacts with AR, AXIN1, GATA2, TP53 and STAT1 (IFNG-induced) (By similarity). Interacts with LEF1 (PubMed:11731474). Interacts with TICAM1 (By similarity). Interacts with KLF8; the interaction results in SUMO ligation and repression of KLF8 transcriptional activity and of its cell cycle progression into G(1) phase (By similarity). Interacts with MTA1 (By similarity). Interacts with PRDM1/Blimp-1 (By similarity). Interacts with TRIM32 upon treatment with UVB and TNF-alpha (PubMed:16816390).SUBUNIT (Microbial infection) Interacts ewith Moloney murine leukemia virus Capsid protein p30.TISSUE SPECIFICITY Widely expressed, with highest levels in testis. Also expressed in vascular endothelial cells, in primary keratinocytes and in the CNS, including cortex, olfactory bulb, spinal cord, thalamus and trigeminal ganglion. Low expression, if any, in liver and lung.DEVELOPMENTAL STAGE At 8.5 dpc, expressed primarily in the anterior part of the neural tube. At 10.5 dpc, expressed in the neuroepithelium of the forebrain and hindbrain. At 11.5 dpc, detected in the neural tube, eye, limb buds and brachial arches. At 12.5 dpc, expressed in the hindlimbs and forelimbs, as well as in the forebrain. At 12.5 and 13.5 dpc, detected in single cells in the marginal zone of the developing cortex, as well as in other developing tissues and organs. At 13.5 dpc, expressed in the developing limb buds, in single cells in the mesenchyme surrounding future digit structures. At 15.5 dpc, detected in the inner root sheath of vibrissa hair follicle. Expression in the inner root sheath of the hair follicle continues later in life as it can also be detected in the back skin of newborn at postnatal day 3. At 16.5 dpc, expressed in the epithelium of olfactory and in the retina.DOMAIN The LXXLL motif is a coregulator signature that is essential for transcriptional corepression.PTM Sumoylated. Lys-35 is the main site of sumoylation. Sumoylation is required for TCF4 sumoylation and transcriptional activation. Represses LEF1 transcriptional activity. SUMO1 is the preferred conjugate.PTM Ubiquitinated by TRIM32 upon treatment with UVB and TNF-alpha.SIMILARITY Belongs to the PIAS family. UniProt Q9JM05 2 EQUAL 510 EQUAL GO 0019789 GO molecular function Reactome Database ID Release 82 9879736 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9879736 Reactome Database ID Release 82 9884354 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9884354 Reactome R-MMU-4755411 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-4755411.1 PIAS4 SUMOylates IKBKG with SUMO1 at lysine-277 and lysine-309 (Huang et al. 2003, Mabb et al. 2006). SUMOylation occurs in the nucleus when IKBKG is unbound to IKK. The interaction between PIAS4 and IKBKG is increased by genotoxic stress. SUMOylation is independent of ATM. 14651848 Pubmed 2003 Sequential modification of NEMO/IKKgamma by SUMO-1 and ubiquitin mediates NF-kappaB activation by genotoxic stress Huang, TT Wuerzberger-Davis, Shelly M Wu, Zhao-Hui Miyamoto, Shigeki Cell 115:565-76 16906147 Pubmed 2006 PIASy mediates NEMO sumoylation and NF-kappaB activation in response to genotoxic stress Mabb, Angela M Wuerzberger-Davis, Shelly M Miyamoto, Shigeki Nat. Cell Biol. 8:986-93 inferred by electronic annotation IEA GO IEA