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   27-MAR-2024, entry version 185.
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; 20.
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; 10090-ENSMUSP00000013949; -.
DR   ProteomicsDB; 273618; -.
DR   DNASU; 11796; -.
DR   GeneID; 11796; -.
DR   KEGG; mmu:11796; -.
DR   AGR; MGI:1197007; -.
DR   CTD; 330; -.
DR   MGI; MGI:1197007; Birc3.
DR   eggNOG; KOG1101; Eukaryota.
DR   InParanoid; O08863; -.
DR   OrthoDB; 383715at2759; -.
DR   Reactome; R-MMU-168638; NOD1/2 Signaling Pathway.
DR   Reactome; R-MMU-5357786; TNFR1-induced proapoptotic signaling.
DR   Reactome; R-MMU-5357905; Regulation of TNFR1 signaling.
DR   Reactome; R-MMU-5357956; TNFR1-induced NF-kappa-B 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 80 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: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:0006915; P:apoptotic process; IEA:UniProtKB-KW.
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 non-canonical NF-kappaB signal transduction; IGI:MGI.
DR   CDD; cd00022; BIR; 3.
DR   CDD; cd08329; CARD_BIRC2_BIRC3; 1.
DR   CDD; cd16713; RING-HC_BIRC2_3_7; 1.
DR   CDD; cd14394; UBA_BIRC2_3; 1.
DR   Gene3D; 1.10.533.10; Death Domain, Fas; 1.
DR   Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 1.
DR   InterPro; IPR001370; BIR_rpt.
DR   InterPro; IPR048875; BIRC2-3-like_UBA.
DR   InterPro; IPR041933; BIRC2/BIRC3_UBA.
DR   InterPro; IPR001315; CARD.
DR   InterPro; IPR011029; DEATH-like_dom_sf.
DR   InterPro; IPR001841; Znf_RING.
DR   PANTHER; PTHR10044:SF178; BACULOVIRAL IAP REPEAT-CONTAINING PROTEIN 3; 1.
DR   PANTHER; PTHR10044; INHIBITOR OF APOPTOSIS; 1.
DR   Pfam; PF00653; BIR; 3.
DR   Pfam; PF21290; BIRC2-3-like_UBA; 1.
DR   Pfam; PF00619; CARD; 1.
DR   Pfam; PF13920; zf-C3HC4_3; 1.
DR   SMART; SM00238; BIR; 3.
DR   SMART; SM00114; CARD; 1.
DR   SMART; SM00184; RING; 1.
DR   SUPFAM; SSF47986; DEATH domain; 1.
DR   SUPFAM; SSF57924; Inhibitor of apoptosis (IAP) repeat; 3.
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
//