ID:BIRC2_HUMAN DESCRIPTION: RecName: Full=Baculoviral IAP repeat-containing protein 2; EC=6.3.2.-; AltName: Full=C-IAP1; AltName: Full=IAP homolog B; AltName: Full=Inhibitor of apoptosis protein 2; Short=IAP-2; Short=hIAP-2; Short=hIAP2; AltName: Full=RING finger protein 48; AltName: Full=TNFR2-TRAF-signaling complex protein 2; 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, TRAF2, DIABLO/SMAC, MAP3K14/NIK, MAP3K5/ASK1, IKBKG/NEMO 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. ENZYME REGULATION: The 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. SUBUNIT: Interacts with DIABLO/SMAC and with PRSS25; these interactions inhibit apoptotic suppressor activity. Interacts with CASP9. Interacts (via BIR domains) with TRAF2. Interacts with E2F1, RIPK1, RIPK2, RIPK3, RIPK4, BIRC5/survivin and USP19. INTERACTION: P55210:CASP7; NbExp=2; IntAct=EBI-514538, EBI-523958; Q9NR28:DIABLO; NbExp=4; IntAct=EBI-514538, EBI-517508; 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=8; IntAct=EBI-514538, EBI-355744; SUBCELLULAR LOCATION: Cytoplasm. 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. TISSUE SPECIFICITY: Present 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. DOMAIN: The BIR domains mediate nuclear localization. DOMAIN: The 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. PTM: Auto-ubiquitinated and degraded by the proteasome in apoptotic cells. 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=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/birc2/";
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 Q13490
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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:0003713 transcription coactivator activity GO:0004842 ubiquitin-protein transferase activity GO:0005515 protein binding GO:0008270 zinc ion binding GO:0016740 transferase activity GO:0042802 identical protein binding GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process GO:0043130 ubiquitin binding GO:0046872 metal ion binding GO:0047485 protein N-terminus binding GO:0051087 chaperone binding GO:0098770 FBXO family protein binding
Biological Process: GO:0000209 protein polyubiquitination GO:0001666 response to hypoxia GO:0001890 placenta development GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006915 apoptotic process GO:0007166 cell surface receptor signaling pathway GO:0007249 I-kappaB kinase/NF-kappaB signaling GO:0010243 response to organonitrogen compound GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway GO:0014070 response to organic cyclic compound GO:0016579 protein deubiquitination 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:0042127 regulation of cell proliferation 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:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0045088 regulation of innate immune response GO:0045471 response to ethanol GO:0045595 regulation of cell differentiation GO:0050727 regulation of inflammatory response GO:0051291 protein heterooligomerization GO:0051591 response to cAMP GO:0051726 regulation of cell cycle GO:0060544 regulation of necroptotic process GO:0060546 negative regulation of necroptotic process GO:0070266 necroptotic process GO:0070424 regulation of nucleotide-binding oligomerization domain containing signaling pathway GO:0071356 cellular response to tumor necrosis factor GO:1901222 regulation of NIK/NF-kappaB signaling GO:1902443 negative regulation of ripoptosome assembly involved in necroptotic process GO:1902523 positive regulation of protein K63-linked ubiquitination GO:1902524 positive regulation of protein K48-linked ubiquitination GO:1902527 positive regulation of protein monoubiquitination GO:1902916 positive regulation of protein polyubiquitination GO:1990001 inhibition of cysteine-type endopeptidase activity involved in apoptotic process GO:2000116 regulation of cysteine-type endopeptidase activity GO:2000377 regulation of reactive oxygen species metabolic process GO:0090307 mitotic spindle assembly
AK303197 - Homo sapiens cDNA FLJ57692 complete cds. BX647978 - Homo sapiens mRNA; cDNA DKFZp686H2452 (from clone DKFZp686H2452). LP895223 - Sequence 87 from Patent EP3253886. AF207599 - Homo sapiens pRb-interacting protein RbBP-36 mRNA, complete cds. BC028578 - Homo sapiens baculoviral IAP repeat-containing 2, mRNA (cDNA clone MGC:26517 IMAGE:4831062), complete cds. U37547 - Homo sapiens dev-stage fetal MIHB (MIHB) mRNA, complete cds. AK225856 - Homo sapiens mRNA for baculoviral IAP repeat-containing protein 2 variant, clone: FCC125E05. AK313446 - Homo sapiens cDNA, FLJ93988, highly similar to Homo sapiens baculoviral IAP repeat-containing 2 (BIRC2), mRNA. U45879 - Human inhibitor of apoptosis protein 2 mRNA, complete cds. L49431 - Homo sapiens TNFR2-TRAF signalling complex protein mRNA, complete cds. BC016174 - Homo sapiens baculoviral IAP repeat-containing 2, mRNA (cDNA clone MGC:17185 IMAGE:3908352), complete cds. DQ895596 - Synthetic construct Homo sapiens clone IMAGE:100010056; FLH185802.01L; RZPDo839F03147D baculoviral IAP repeat-containing 2 (BIRC2) gene, encodes complete protein. DQ892384 - Synthetic construct clone IMAGE:100005014; FLH185806.01X; RZPDo839F03148D baculoviral IAP repeat-containing 2 (BIRC2) gene, encodes complete protein. AB384744 - Synthetic construct DNA, clone: pF1KB3090, Homo sapiens BIRC2 gene for baculoviral IAP repeat-containing protein 2, complete cds, without stop codon, in Flexi system. KJ890684 - Synthetic construct Homo sapiens clone ccsbBroadEn_00078 BIRC2 gene, encodes complete protein. JD345462 - Sequence 326486 from Patent EP1572962. JD545564 - Sequence 526588 from Patent EP1572962. JD509561 - Sequence 490585 from Patent EP1572962. JD049152 - Sequence 30176 from Patent EP1572962. JD284320 - Sequence 265344 from Patent EP1572962. JD508272 - Sequence 489296 from Patent EP1572962. JD490025 - Sequence 471049 from Patent EP1572962. JD250287 - Sequence 231311 from Patent EP1572962. JD315472 - Sequence 296496 from Patent EP1572962. JD333586 - Sequence 314610 from Patent EP1572962. JD263530 - Sequence 244554 from Patent EP1572962. JD082429 - Sequence 63453 from Patent EP1572962. JD223308 - Sequence 204332 from Patent EP1572962. CU677583 - Synthetic construct Homo sapiens gateway clone IMAGE:100020396 5' read BIRC2 mRNA. JD021293 - Sequence 2317 from Patent EP1572962. JD028127 - Sequence 9151 from Patent EP1572962. JD232354 - Sequence 213378 from Patent EP1572962. JD060460 - Sequence 41484 from Patent EP1572962. JD546518 - Sequence 527542 from Patent EP1572962. JD237277 - Sequence 218301 from Patent EP1572962. JD525456 - Sequence 506480 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_mitochondriaPathway - Role of Mitochondria in Apoptotic Signaling h_HivnefPathway - HIV-I Nef: negative effector of Fas and TNF h_caspasePathway - Caspase Cascade in Apoptosis h_deathPathway - Induction of apoptosis through DR3 and DR4/5 Death Receptors
Reactome (by CSHL, EBI, and GO)
Protein Q13490 (Reactome details) participates in the following event(s):
R-HSA-202960 Caspase mediated cleavage of C-IAP1 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-111465 Apoptotic cleavage of cellular proteins 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-75153 Apoptotic execution phase 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-109581 Apoptosis 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-5357801 Programmed Cell Death R-HSA-937061 TRIF(TICAM1)-mediated TLR4 signaling R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade R-HSA-162582 Signal Transduction 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 
