ID:BIRC3_HUMAN DESCRIPTION: RecName: Full=Baculoviral IAP repeat-containing protein 3; EC=6.3.2.-; AltName: Full=Apoptosis inhibitor 2; Short=API2; AltName: Full=C-IAP2; AltName: Full=IAP homolog C; AltName: Full=Inhibitor of apoptosis protein 1; Short=IAP-1; Short=hIAP-1; Short=hIAP1; AltName: Full=RING finger protein 49; AltName: Full=TNFR2-TRAF-signaling complex protein 1; FUNCTION: Multi-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, TRAF1, and BCL10. 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. ENZYME REGULATION: USP19 regulates the stability of BIRC3/c-IAP2 by preventing its ubiquitination. SUBUNIT: Interacts with DIABLO/SMAC and with PRSS25; these interactions inhibit apoptotic suppressor activity. The BIR motifs region interacts with TNF receptor associated factors 1 and 2 (TRAF1 and TRAF2) to form a heteromeric complex, which is then recruited to the tumor necrosis factor receptor 2 (TNFR2). Interacts with RIP1, RIP2, RIP3, RIP4 and USP19. INTERACTION: Q9NR28:DIABLO; NbExp=2; IntAct=EBI-517709, EBI-517508; Q13546:RIPK1; NbExp=3; IntAct=EBI-517709, EBI-358507; O43353:RIPK2; NbExp=3; IntAct=EBI-517709, EBI-358522; Q9Y572:RIPK3; NbExp=3; IntAct=EBI-517709, EBI-298250; P57078:RIPK4; NbExp=3; IntAct=EBI-517709, EBI-4422308; Q12933:TRAF2; NbExp=5; IntAct=EBI-517709, EBI-355744; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. TISSUE SPECIFICITY: Highly expressed in fetal lung, and kidney. In the adult, expression is mainly seen in lymphoid tissues, including spleen, thymus and peripheral blood lymphocytes. PTM: Auto-ubiquitinated and degraded by the proteasome in apoptotic cells. DISEASE: Note=A chromosomal aberration involving BIRC3 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(11;18)(q21;q21) with MALT1. This translocation is found in approximately 50% of cytogenetically abnormal low-grade MALT lymphoma. SIMILARITY: Belongs to the IAP family. SIMILARITY: Contains 3 BIR repeats. SIMILARITY: Contains 1 CARD domain. SIMILARITY: Contains 1 RING-type zinc finger. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/BIRC3ID239.html"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/birc3/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13489
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004842 ubiquitin-protein transferase activity GO:0005515 protein binding GO:0016740 transferase activity GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process GO:0046872 metal ion binding
Biological Process: GO:0006915 apoptotic process GO:0007166 cell surface receptor signaling pathway GO:0007249 I-kappaB kinase/NF-kappaB signaling GO:0007283 spermatogenesis GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway GO:0016567 protein ubiquitination GO:0016579 protein deubiquitination GO:0031398 positive regulation of protein ubiquitination GO:0033209 tumor necrosis factor-mediated signaling pathway GO:0034121 regulation of toll-like receptor signaling pathway GO:0038061 NIK/NF-kappaB signaling GO:0039535 regulation of RIG-I signaling pathway GO:0042981 regulation of apoptotic process GO:0043066 negative regulation of apoptotic process GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0045088 regulation of innate immune response GO:0050727 regulation of inflammatory response GO:0051291 protein heterooligomerization GO:0060544 regulation of necroptotic process GO:0060546 negative regulation of necroptotic process GO:0070424 regulation of nucleotide-binding oligomerization domain containing signaling pathway GO:1990001 inhibition of cysteine-type endopeptidase activity involved in apoptotic process GO:2000116 regulation of cysteine-type endopeptidase activity GO:0090307 mitotic spindle assembly
AF070674 - Homo sapiens inhibitor of apoptosis protein-1 (MIHC) mRNA, complete cds. L49432 - Homo sapiens TNFR2-TRAF signalling complex protein mRNA, complete cds. BC027485 - Homo sapiens baculoviral IAP repeat-containing 3, mRNA (cDNA clone IMAGE:4339454), partial cds. U37546 - Human IAP homolog C (MIHC) mRNA, complete cds. L43346 - Homo sapiens mRNA fragment. JD171466 - Sequence 152490 from Patent EP1572962. JD281145 - Sequence 262169 from Patent EP1572962. U45878 - Human inhibitor of apoptosis protein 1 mRNA, complete cds. BC037420 - Homo sapiens baculoviral IAP repeat-containing 3, mRNA (cDNA clone MGC:46142 IMAGE:5497880), complete cds. JD459608 - Sequence 440632 from Patent EP1572962. CU691496 - Synthetic construct Homo sapiens gateway clone IMAGE:100021219 5' read BIRC3 mRNA. AB590788 - Synthetic construct DNA, clone: pFN21AB6172, Homo sapiens BIRC3 gene for baculoviral IAP repeat-containing 3, without stop codon, in Flexi system. JD299458 - Sequence 280482 from Patent EP1572962. JD528525 - Sequence 509549 from Patent EP1572962. JD529822 - Sequence 510846 from Patent EP1572962. JD421385 - Sequence 402409 from Patent EP1572962. JD533001 - Sequence 514025 from Patent EP1572962. JD431030 - Sequence 412054 from Patent EP1572962. JD443024 - Sequence 424048 from Patent EP1572962. JD251482 - Sequence 232506 from Patent EP1572962. JD402024 - Sequence 383048 from Patent EP1572962. JD170749 - Sequence 151773 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_caspasePathway - Caspase Cascade in Apoptosis h_HivnefPathway - HIV-I Nef: negative effector of Fas and TNF h_soddPathway - SODD/TNFR1 Signaling Pathway h_mitochondriaPathway - Role of Mitochondria in Apoptotic Signaling h_deathPathway - Induction of apoptosis through DR3 and DR4/5 Death Receptors
Reactome (by CSHL, EBI, and GO)
Protein Q13489 (Reactome details) participates in the following event(s):
R-HSA-5357780 TNF:TNFR1:TRADD:TRAF2:RIPK1 recruits BIRC2/3 (cIAP1/2) R-HSA-6781797 USP19 binds HIF1A,BIRC2,BIRC3 R-HSA-5357860 TNF:TNFR1:TRADD:TRAF2:K63polyUb-RIPK1:BIRC2/3 recruits TAK1 complex R-HSA-5357904 TNF:TNFR1:TRADD:TRAF2:RIPK1 binds LUBAC R-HSA-5357928 CLIP3 and CYLD bind TNF signaling complex R-HSA-5693055 TAX1BP1:TNFAIP3(A20) binds RIPK1-containing complexes R-HSA-5357757 BIRC(cIAP1/2) ubiquitinates RIPK1 R-HSA-5668543 TRAF3:NIK binds TRAF2:cIAP1/2 R-HSA-688137 RIP2 is K63 polyubiquitinated R-HSA-168915 K63-linked ubiquitination of RIP1 bound to the activated TLR complex R-HSA-9014342 K63-linked ubiquitination of RIP1 bound to the activated TLR complex R-HSA-5357776 TNF:TNFR1:TRADD:TRAF2:K63polyUb-RIPK1:BIRC2,3:LUBAC recruits IKKA:IKBKB:IKBKG R-HSA-5693108 TNFAIP3 (A20) ubiquitinates RIPK1 with K48-linked Ub chains R-HSA-5668417 cIAP1,2:TRAF2:TRAF3:NIK complex binds TNFR2 trimer R-HSA-5676593 TRAF2:TRAF1:cIAP1,2:TRAF3:NIK regulatory complex binds LTBR R-HSA-5676595 TRAFs bind RANK:RANKL R-HSA-5676596 TRAF3 binds BAFFR:BAFF R-HSA-5676597 TRAF2:TRAF1:cIAP1,2:TRAF3:NIK regulatory complex binds CD40 R-HSA-5676598 TRAF2:cIAP1/2 complex binds FN14:TWEAK R-HSA-5357956 TNFR1-induced NFkappaB signaling pathway R-HSA-5675482 Regulation of necroptotic cell death R-HSA-5689880 Ub-specific processing proteases R-HSA-5357905 Regulation of TNFR1 signaling R-HSA-75893 TNF signaling R-HSA-5213460 RIPK1-mediated regulated necrosis R-HSA-5668541 TNFR2 non-canonical NF-kB pathway R-HSA-5688426 Deubiquitination R-HSA-168638 NOD1/2 Signaling Pathway R-HSA-937041 IKK complex recruitment mediated by RIP1 R-HSA-168927 TICAM1, RIP1-mediated IKK complex recruitment R-HSA-73887 Death Receptor Signalling R-HSA-5218859 Regulated Necrosis R-HSA-5676594 TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-597592 Post-translational protein modification R-HSA-168643 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways R-HSA-937061 TRIF(TICAM1)-mediated TLR4 signaling R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade R-HSA-162582 Signal Transduction R-HSA-5357801 Programmed Cell Death R-HSA-168256 Immune System R-HSA-392499 Metabolism of proteins R-HSA-168249 Innate Immune System R-HSA-166166 MyD88-independent TLR4 cascade R-HSA-168898 Toll-Like Receptors Cascades R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
