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MGP000163

UniProt Annotations

Entry Information
Gene Namebaculoviral IAP repeat containing 2
Protein EntryBIRC2_HUMAN
UniProt IDQ13490
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q13490-1; Sequence=Displayed; Name=2; IsoId=Q13490-2; Sequence=VSP_045314;
DomainThe BIR domains mediate nuclear localization. {ECO:0000269|PubMed:21549626}.
DomainThe CARD domain is necessary to stabilize the protein and inhibit the activation of E3 ubiquitin-protein ligase activity of BIRC2/c-IAP1 by preventing RING domain dimerization and E2 ubiquitin donor binding and activation. {ECO:0000269|PubMed:21549626}.
Enzyme RegulationThe CARD domain inhibits the activation of E3 ubiquitin ligase activity by preventing RING domain dimerization and E2 ubiquitin donor binding and activation. The CARD domain- mediated autoinhibition of the E3 ubiquitin-protein ligase activity suppresses cell proliferation and migration. USP19 regulates the stability of BIRC2/c-IAP1 by preventing its ubiquitination. {ECO:0000269|PubMed:21549626, ECO:0000269|PubMed:21849505}.
FunctionMulti-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling, and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin- protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin- protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, TRAF2, DIABLO/SMAC, MAP3K14/NIK, MAP3K5/ASK1, IKBKG/NEMO, IKBKE and MXD1/MAD1. Can also function as an E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase- dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Can stimulate the transcriptional activity of E2F1. Plays a role in the modulation of the cell cycle. {ECO:0000269|PubMed:15665297, ECO:0000269|PubMed:18082613, ECO:0000269|PubMed:21145488, ECO:0000269|PubMed:21653699, ECO:0000269|PubMed:21931591, ECO:0000269|PubMed:23453969}.
InteractionP55210:CASP7; NbExp=2; IntAct=EBI-514538, EBI-523958; P55211:CASP9; NbExp=4; IntAct=EBI-514538, EBI-516799; Q9NR28:DIABLO; NbExp=5; IntAct=EBI-514538, EBI-517508; Q96FW1:OTUB1; NbExp=3; IntAct=EBI-514538, EBI-1058491; P63000:RAC1; NbExp=2; IntAct=EBI-514538, EBI-413628; Q13546:RIPK1; NbExp=3; IntAct=EBI-514538, EBI-358507; O43353:RIPK2; NbExp=3; IntAct=EBI-514538, EBI-358522; Q9Y572:RIPK3; NbExp=3; IntAct=EBI-514538, EBI-298250; P57078:RIPK4; NbExp=3; IntAct=EBI-514538, EBI-4422308; Q9NP84:TNFRSF12A; NbExp=2; IntAct=EBI-514538, EBI-2851995; Q12933:TRAF2; NbExp=10; IntAct=EBI-514538, EBI-355744;
PtmAuto-ubiquitinated and degraded by the proteasome in apoptotic cells.
SimilarityBelongs to the IAP family. {ECO:0000305}.
SimilarityContains 1 CARD domain. {ECO:0000255|PROSITE- ProRule:PRU00046}.
SimilarityContains 1 RING-type zinc finger. {ECO:0000255|PROSITE-ProRule:PRU00175}.
SimilarityContains 3 BIR repeats. {ECO:0000255|PROSITE- ProRule:PRU00029}.
Subcellular LocationCytoplasm. Nucleus. Note=Agents that induce either the extrinsic or intrinsic apoptotic pathways promote its redistribution from the nuclear compartment to the cytoplasmic compartment. Associated with the midbody in telophase cells, and found diffusely in the nucleus of interphase cells.
SubunitInteracts with DIABLO/SMAC and with PRSS25; these interactions inhibit apoptotic suppressor activity. Interacts with CASP9. Interacts (via BIR domains) with TRAF2; the interaction is required for IKBKE ubiquitination. Interacts with E2F1, RIPK1, RIPK2, RIPK3, RIPK4, BIRC5/survivin and USP19. {ECO:0000269|PubMed:15665297, ECO:0000269|PubMed:19153467, ECO:0000269|PubMed:21653699, ECO:0000269|PubMed:21849505, ECO:0000269|PubMed:21931591}.
Tissue SpecificityPresent in many fetal and adult tissues. Mainly expressed in adult skeletal muscle, thymus, testis, ovary, and pancreas, low or absent in brain and peripheral blood leukocytes.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/BIRC2ID795ch11q22.html";
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/birc2/";
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