BIRC2_MOUSE
ID BIRC2_MOUSE Reviewed; 612 AA.
AC Q62210; A6H6S7; O08864;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Baculoviral IAP repeat-containing protein 2;
DE EC=2.3.2.27 {ECO:0000269|PubMed:18621737};
DE AltName: Full=Cellular inhibitor of apoptosis 1;
DE Short=C-IAP1 {ECO:0000303|PubMed:8548810};
DE AltName: Full=Inhibitor of apoptosis protein 2 {ECO:0000303|PubMed:9441758};
DE Short=mIAP2 {ECO:0000303|PubMed:9441758};
DE AltName: Full=RING-type E3 ubiquitin transferase BIRC2 {ECO:0000305};
GN Name=Birc2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=8548810; DOI=10.1016/0092-8674(95)90149-3;
RA Rothe M., Pan M.-G., Henzel W.J., Ayres T.M., Goeddel D.V.;
RT "The TNFR2-TRAF signaling complex contains two novel proteins related to
RT baculoviral inhibitor of apoptosis proteins.";
RL Cell 83:1243-1252(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=9441758; DOI=10.1006/geno.1997.5059;
RA Liston P., Lefebvre C., Fong W.G., Xuan J.Y., Korneluk R.G.;
RT "Genomic characterization of the mouse inhibitor of apoptosis protein 1 and
RT 2 genes.";
RL Genomics 46:495-503(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, AND CATALYTIC ACTIVITY.
RX PubMed=18621737; DOI=10.1074/jbc.c800128200;
RA Varfolomeev E., Goncharov T., Fedorova A.V., Dynek J.N., Zobel K.,
RA Deshayes K., Fairbrother W.J., Vucic D.;
RT "c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha
RT (TNFalpha)-induced NF-kappaB activation.";
RL J. Biol. Chem. 283:24295-24299(2008).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-143, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Multi-functional protein which regulates not only caspases
CC and apoptosis, but also modulates inflammatory signaling and immunity,
CC mitogenic kinase signaling, and cell proliferation, as well as cell
CC invasion and metastasis. Acts as an E3 ubiquitin-protein ligase
CC regulating NF-kappa-B signaling and regulates both canonical and non-
CC canonical NF-kappa-B signaling by acting in opposite directions: acts
CC as a positive regulator of the canonical pathway and suppresses
CC constitutive activation of non-canonical NF-kappa-B signaling. The
CC target proteins for its E3 ubiquitin-protein ligase activity include:
CC RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, TRAF2, DIABLO/SMAC,
CC MAP3K14/NIK, MAP3K5/ASK1, IKBKG/NEMO, IKBKE and MXD1/MAD1. Can also
CC function as an E3 ubiquitin-protein ligase of the NEDD8 conjugation
CC pathway, targeting effector caspases for neddylation and inactivation.
CC Acts as an important regulator of innate immune signaling via
CC regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and
CC RIG-I like receptors (RLRs), collectively referred to as pattern
CC recognition receptors (PRRs). Protects cells from spontaneous formation
CC of the ripoptosome, a large multi-protein complex that has the
CC capability to kill cancer cells in a caspase-dependent and caspase-
CC independent manner. Suppresses ripoptosome formation by ubiquitinating
CC RIPK1 and CASP8. Can stimulate the transcriptional activity of E2F1.
CC Plays a role in the modulation of the cell cycle.
CC {ECO:0000269|PubMed:18621737}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:18621737};
CC -!- ACTIVITY REGULATION: The CARD domain inhibits the activation of E3
CC ubiquitin ligase activity by preventing RING domain dimerization and E2
CC ubiquitin donor binding and activation. The CARD domain-mediated
CC autoinhibition of the E3 ubiquitin-protein ligase activity suppresses
CC cell proliferation and migration. USP19 regulates the stability of
CC BIRC2/c-IAP1 by preventing its ubiquitination (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with DIABLO/SMAC and with PRSS25; these interactions
CC inhibit apoptotic suppressor activity. Interacts with CASP9. Interacts
CC (via BIR domains) with TRAF2; the interaction is required for IKBKE
CC ubiquitination. Interacts with E2F1, RIPK1, RIPK2, RIPK3, RIPK4,
CC BIRC5/survivin and USP19 (By similarity). Interacts with HSP90AB1 (By
CC similarity). Interacts with several death receptors, inclusing FAS,
CC TNFRSF10A and TNFRSF10B (By similarity). Recruited to TNFRSF10B in the
CC absence of receptor stimulation. When TNFRSF10B is stimulated, further
CC recruited to the receptor and cleaved by caspases. Proteolytic
CC fragments remain associated with TNFRSF10B (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:Q13490}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Agents that induce either the extrinsic or intrinsic apoptotic
CC pathways promote its redistribution from the nuclear compartment to the
CC cytoplasmic compartment. Associated with the midbody in telophase
CC cells, and found diffusely in the nucleus of interphase cells (By
CC similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in heart, brain, spleen, lung, liver,
CC skeletal muscle, kidney and testis.
CC -!- DOMAIN: The BIR domains mediate nuclear localization. {ECO:0000250}.
CC -!- DOMAIN: The CARD domain is necessary to stabilize the protein and
CC inhibit the activation of E3 ubiquitin-protein ligase activity of
CC BIRC2/c-IAP1 by preventing RING domain dimerization and E2 ubiquitin
CC donor binding and activation. {ECO:0000250}.
CC -!- PTM: Auto-ubiquitinated and degraded by the proteasome in apoptotic
CC cells. {ECO:0000250}.
CC -!- PTM: Upon stimulation of death receptors, including TNFRSF10B,
CC recruited to receptors and cleaved by caspases. Proteolytic fragments
CC remain associated with the receptors. This cleavage presumably
CC inactivates the protein. {ECO:0000250|UniProtKB:Q13490}.
CC -!- SIMILARITY: Belongs to the IAP family. {ECO:0000305}.
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DR EMBL; L49433; AAC42078.1; -; mRNA.
DR EMBL; U88909; AAC53532.1; -; mRNA.
DR EMBL; BC145985; AAI45986.1; -; mRNA.
DR CCDS; CCDS22811.1; -.
DR RefSeq; NP_001278432.1; NM_001291503.1.
DR RefSeq; NP_031491.2; NM_007465.3.
DR RefSeq; XP_017168599.1; XM_017313110.1.
DR AlphaFoldDB; Q62210; -.
DR SMR; Q62210; -.
DR BioGRID; 198148; 16.
DR CORUM; Q62210; -.
DR IntAct; Q62210; 3.
DR MINT; Q62210; -.
DR STRING; 10090.ENSMUSP00000140049; -.
DR MEROPS; I32.002; -.
DR MEROPS; I32.007; -.
DR iPTMnet; Q62210; -.
DR PhosphoSitePlus; Q62210; -.
DR EPD; Q62210; -.
DR jPOST; Q62210; -.
DR MaxQB; Q62210; -.
DR PaxDb; Q62210; -.
DR PRIDE; Q62210; -.
DR ProteomicsDB; 273617; -.
DR Antibodypedia; 1043; 486 antibodies from 41 providers.
DR DNASU; 11797; -.
DR Ensembl; ENSMUST00000074246; ENSMUSP00000091422; ENSMUSG00000057367.
DR Ensembl; ENSMUST00000190341; ENSMUSP00000140049; ENSMUSG00000057367.
DR GeneID; 11797; -.
DR KEGG; mmu:11797; -.
DR UCSC; uc009ocz.2; mouse.
DR CTD; 329; -.
DR MGI; MGI:1197009; Birc2.
DR VEuPathDB; HostDB:ENSMUSG00000057367; -.
DR eggNOG; KOG1101; Eukaryota.
DR GeneTree; ENSGT00940000154175; -.
DR HOGENOM; CLU_016347_1_1_1; -.
DR InParanoid; Q62210; -.
DR OMA; SEYMYTE; -.
DR OrthoDB; 1340284at2759; -.
DR PhylomeDB; Q62210; -.
DR TreeFam; TF105356; -.
DR Reactome; R-MMU-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-MMU-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-MMU-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-MMU-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-MMU-5668541; TNFR2 non-canonical NF-kB pathway.
DR Reactome; R-MMU-5675482; Regulation of necroptotic cell death.
DR Reactome; R-MMU-5676594; TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-937041; IKK complex recruitment mediated by RIP1.
DR BioGRID-ORCS; 11797; 9 hits in 77 CRISPR screens.
DR ChiTaRS; Birc2; mouse.
DR PRO; PR:Q62210; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q62210; protein.
DR Bgee; ENSMUSG00000057367; Expressed in spermatocyte and 276 other tissues.
DR ExpressionAtlas; Q62210; baseline and differential.
DR Genevisible; Q62210; MM.
DR GO; GO:0035631; C:CD40 receptor complex; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0001741; C:XY body; ISO:MGI.
DR GO; GO:0051087; F:chaperone binding; ISO:MGI.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0098770; F:FBXO family protein binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0016740; F:transferase activity; ISO:MGI.
DR GO; GO:0043130; F:ubiquitin binding; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IGI:MGI.
DR GO; GO:0070266; P:necroptotic process; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0060546; P:negative regulation of necroptotic process; IGI:MGI.
DR GO; GO:1902443; P:negative regulation of ripoptosome assembly involved in necroptotic process; IGI:MGI.
DR GO; GO:0001890; P:placenta development; IMP:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:1902524; P:positive regulation of protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:1902523; P:positive regulation of protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:1902527; P:positive regulation of protein monoubiquitination; ISO:MGI.
DR GO; GO:1902916; P:positive regulation of protein polyubiquitination; IGI:MGI.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IBA:GO_Central.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0060544; P:regulation of necroptotic process; ISO:MGI.
DR GO; GO:1901222; P:regulation of NIK/NF-kappaB signaling; IGI:MGI.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IMP:MGI.
DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR CDD; cd00022; BIR; 3.
DR CDD; cd14394; UBA_BIRC2_3; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR001370; BIR_rpt.
DR InterPro; IPR041933; BIRC2/BIRC3_UBA.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR001841; Znf_RING.
DR Pfam; PF00653; BIR; 3.
DR Pfam; PF00619; CARD; 1.
DR SMART; SM00238; BIR; 3.
DR SMART; SM00114; CARD; 1.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR PROSITE; PS01282; BIR_REPEAT_1; 3.
DR PROSITE; PS50143; BIR_REPEAT_2; 3.
DR PROSITE; PS50209; CARD; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Activator; Apoptosis; Cytoplasm; Direct protein sequencing; Metal-binding;
KW Methylation; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Transcription; Transcription regulation; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..612
FT /note="Baculoviral IAP repeat-containing protein 2"
FT /id="PRO_0000122348"
FT REPEAT 46..113
FT /note="BIR 1"
FT REPEAT 177..243
FT /note="BIR 2"
FT REPEAT 262..329
FT /note="BIR 3"
FT DOMAIN 447..537
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT ZN_FING 565..600
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT BINDING 299
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00029"
FT BINDING 302
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00029"
FT BINDING 319
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00029"
FT BINDING 326
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00029"
FT MOD_RES 143
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 153
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 380
FT /note="E -> K (in Ref. 2; AAC53532)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 612 AA; 69676 MW; E08969D93C6C610D CRC64;
MDKTVSQRLG QGTLHQKLKR IMEKSTILSN WTKESEEKMK FDFSCELYRM STYSAFPRGV
PVSERSLARA GFYYTGVNDK VKCFCCGLML DNWKQGDSPV EKHRQFYPSC SFVQTLLSAS
LQSPSKNMSP VKSRFAHSSP LERGGIHSNL CSSPLNSRAV EDFSSRMDPC SYAMSTEEAR
FLTYSMWPLS FLSPAELARA GFYYIGPGDR VACFACGGKL SNWEPKDDAM SEHRRHFPHC
PFLENTSETQ RFSISNLSMQ THSARLRTFL YWPPSVPVQP EQLASAGFYY VDRNDDVKCF
CCDGGLRCWE PGDDPWIEHA KWFPRCEFLI RMKGQEFVDE IQARYPHLLE QLLSTSDTPG
EENADPTETV VHFGPGESSE DVVMMSTPVV KAALEMGFSR SLVRQTVQRQ ILATGENYRT
VNDIVSVLLN AEDERREEEK ERQTEEMASG DLSLIRKNRM ALFQQLTHVL PILDNLLEAS
VITKQEHDII RQKTQIPLQA RELIDTVLVK GNAAANIFKN SLKEIDSTLY ENLFVEKNMK
YIPTEDVSGL SLEEQLRRLQ EERTCKVCMD REVSIVFIPC GHLVVCQECA PSLRKCPICR
GTIKGTVRTF LS
