BIRC3_MOUSE
ID BIRC3_MOUSE Reviewed; 600 AA.
AC O08863; E9QLX3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Baculoviral IAP repeat-containing protein 3;
DE EC=2.3.2.27 {ECO:0000269|PubMed:18621737};
DE AltName: Full=Cellular inhibitor of apoptosis 2;
DE Short=C-IAP2 {ECO:0000303|PubMed:18621737};
DE AltName: Full=Inhibitor of apoptosis protein 1 {ECO:0000303|PubMed:9441758};
DE Short=mIAP1 {ECO:0000303|PubMed:9441758};
DE AltName: Full=RING-type E3 ubiquitin transferase BIRC3 {ECO:0000305};
GN Name=Birc3;
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].
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
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).
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, IKBKE, TRAF1, and
CC BCL10. 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. {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: USP19 regulates the stability of BIRC3/c-IAP2 by
CC preventing its ubiquitination. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PRSS25; the interaction inhibits apoptotic
CC suppressor activity. The BIR motifs region interacts with TNF receptor
CC associated factors 1 and 2 (TRAF1 and TRAF2) to form a heteromeric
CC complex, which is then recruited to the tumor necrosis factor receptor
CC 2 (TNFR2). Interaction with TRAF2 is required for ubiquitination of
CC IKBKE, degradation of NFKBIA and activation of NF-kappa-B. Interacts
CC with RIP1, RIP2, RIP3, RIP4 and USP19 (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC O08863; P39429: Traf2; NbExp=7; IntAct=EBI-642236, EBI-520016;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- PTM: Auto-ubiquitinated and degraded by the proteasome in apoptotic
CC cells. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the IAP family. {ECO:0000305}.
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DR EMBL; U88908; AAC53531.1; -; mRNA.
DR EMBL; CT030639; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_031490.2; NM_007464.3.
DR AlphaFoldDB; O08863; -.
DR SMR; O08863; -.
DR BioGRID; 198147; 19.
DR CORUM; O08863; -.
DR DIP; DIP-43742N; -.
DR IntAct; O08863; 6.
DR MINT; O08863; -.
DR STRING; 10090.ENSMUSP00000013949; -.
DR MEROPS; I32.003; -.
DR iPTMnet; O08863; -.
DR PhosphoSitePlus; O08863; -.
DR EPD; O08863; -.
DR MaxQB; O08863; -.
DR PaxDb; O08863; -.
DR PRIDE; O08863; -.
DR ProteomicsDB; 273618; -.
DR DNASU; 11796; -.
DR GeneID; 11796; -.
DR KEGG; mmu:11796; -.
DR CTD; 330; -.
DR MGI; MGI:1197007; Birc3.
DR eggNOG; KOG1101; Eukaryota.
DR InParanoid; O08863; -.
DR OrthoDB; 1340284at2759; -.
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; 11796; 5 hits in 75 CRISPR screens.
DR ChiTaRS; Birc3; mouse.
DR PRO; PR:O08863; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O08863; protein.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0016740; F:transferase activity; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISO:MGI.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IGI:MGI.
DR GO; GO:0070266; P:necroptotic process; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0060546; P:negative regulation of necroptotic process; IMP:UniProtKB.
DR GO; GO:0042326; P:negative regulation of phosphorylation; IMP:UniProtKB.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IMP:UniProtKB.
DR GO; GO:1902916; P:positive regulation of protein polyubiquitination; IGI:MGI.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; IBA:GO_Central.
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 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 Apoptosis; Cytoplasm; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..600
FT /note="Baculoviral IAP repeat-containing protein 3"
FT /id="PRO_0000122350"
FT REPEAT 27..94
FT /note="BIR 1"
FT REPEAT 167..233
FT /note="BIR 2"
FT REPEAT 253..320
FT /note="BIR 3"
FT DOMAIN 436..525
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT ZN_FING 553..588
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT BINDING 290
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00029"
FT BINDING 293
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00029"
FT BINDING 310
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00029"
FT BINDING 317
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00029"
FT MOD_RES 138
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62210"
FT CONFLICT 398
FT /note="W -> R (in Ref. 1; AAC53531)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 600 AA; 67228 MW; 2EC9C7B567721382 CRC64;
MVQDSAFLAK LMKSADTFEL KYDFSCELYR LSTYSAFPRG VPVSERSLAR AGFYYTGAND
KVKCFCCGLM LDNWKQGDSP MEKHRKLYPS CNFVQTLNPA NSLEASPRPS LPSTAMSTMP
LSFASSENTG YFSGSYSSFP SDPVNFRANQ DCPALSTSPY HFAMNTEKAR LLTYETWPLS
FLSPAKLAKA GFYYIGPGDR VACFACDGKL SNWERKDDAM SEHQRHFPSC PFLKDLGQSA
SRYTVSNLSM QTHAARIRTF SNWPSSALVH SQELASAGFY YTGHSDDVKC FCCDGGLRCW
ESGDDPWVEH AKWFPRCEYL LRIKGQEFVS QVQAGYPHLL EQLLSTSDSP EDENADAAIV
HFGPGESSED VVMMSTPVVK AALEMGFSRS LVRQTVQWQI LATGENYRTV SDLVIGLLDA
EDEMREEQME QAAEEEESDD LALIRKNKMV LFQHLTCVTP MLYCLLSARA ITEQECNAVK
QKPHTLQAST LIDTVLAKGN TAATSFRNSL REIDPALYRD IFVQQDIRSL PTDDIAALPM
EEQLRKLQEE RMCKVCMDRE VSIVFIPCGH LVVCKDCAPS LRKCPICRGT IKGTVRTFLS
