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O08863

- BIRC3_MOUSE

UniProt

O08863 - BIRC3_MOUSE

Protein

Baculoviral IAP repeat-containing protein 3

Gene

Birc3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    Functioni

    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, IKBKE, 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 CASP8.1 Publication

    Enzyme regulationi

    USP19 regulates the stability of BIRC3/c-IAP2 by preventing its ubiquitination.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi290 – 2901ZincPROSITE-ProRule annotation
    Metal bindingi293 – 2931ZincPROSITE-ProRule annotation
    Metal bindingi310 – 3101ZincPROSITE-ProRule annotation
    Metal bindingi317 – 3171ZincPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri553 – 58836RING-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. ligase activity Source: UniProtKB-KW
    2. protein binding Source: IntAct
    3. ubiquitin-protein transferase activity Source: Ensembl
    4. zinc ion binding Source: InterPro

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. necroptotic process Source: UniProtKB
    3. negative regulation of necroptotic process Source: UniProtKB
    4. negative regulation of phosphorylation Source: UniProtKB
    5. negative regulation of reactive oxygen species metabolic process Source: UniProtKB
    6. positive regulation of protein ubiquitination Source: Ensembl
    7. protein heterooligomerization Source: Ensembl
    8. regulation of apoptotic process Source: Ensembl
    9. spermatogenesis Source: Ensembl

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Apoptosis, Ubl conjugation pathway

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_226192. IKK complex recruitment mediated by RIP1.

    Protein family/group databases

    MEROPSiI32.003.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Baculoviral IAP repeat-containing protein 3 (EC:6.3.2.-)
    Alternative name(s):
    Inhibitor of apoptosis protein 1
    Short name:
    IAP-1
    Short name:
    mIAP-1
    Short name:
    mIAP1
    Gene namesi
    Name:Birc3
    Synonyms:Birc2, Iap1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Unplaced

    Organism-specific databases

    MGIiMGI:1197007. Birc3.

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. membrane raft Source: Ensembl
    3. nucleus Source: UniProtKB
    4. protein complex Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 600600Baculoviral IAP repeat-containing protein 3PRO_0000122350Add
    BLAST

    Post-translational modificationi

    Auto-ubiquitinated and degraded by the proteasome in apoptotic cells.By similarity

    Keywords - PTMi

    Ubl conjugation

    Proteomic databases

    PaxDbiO08863.
    PRIDEiO08863.

    PTM databases

    PhosphoSiteiO08863.

    Expressioni

    Gene expression databases

    ArrayExpressiO08863.
    BgeeiO08863.
    CleanExiMM_BIRC2.
    MM_BIRC3.
    GenevestigatoriO08863.

    Interactioni

    Subunit structurei

    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). Interaction with TRAF2 is required for ubiquitination of IKBKE, degradation of NFKBIA and activation of NF-kappa-B. Interacts with RIP1, RIP2, RIP3, RIP4 and USP19 By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Traf2P394297EBI-642236,EBI-520016

    Protein-protein interaction databases

    BioGridi198147. 14 interactions.
    DIPiDIP-43742N.
    IntActiO08863. 3 interactions.
    MINTiMINT-1581324.

    Structurei

    3D structure databases

    ProteinModelPortaliO08863.
    SMRiO08863. Positions 24-96, 159-600.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati27 – 9468BIR 1Add
    BLAST
    Repeati167 – 23367BIR 2Add
    BLAST
    Repeati253 – 32068BIR 3Add
    BLAST
    Domaini436 – 52590CARDPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the IAP family.Curated
    Contains 3 BIR repeats.PROSITE-ProRule annotation
    Contains 1 CARD domain.PROSITE-ProRule annotation
    Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri553 – 58836RING-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiNOG243347.
    HOGENOMiHOG000232059.
    HOVERGENiHBG004848.
    InParanoidiO08863.
    KOiK16060.

    Family and domain databases

    Gene3Di1.10.1170.10. 4 hits.
    1.10.533.10. 1 hit.
    InterProiIPR001370. BIR.
    IPR001315. CARD.
    IPR011029. DEATH-like_dom.
    IPR001841. Znf_RING.
    [Graphical view]
    PfamiPF00653. BIR. 3 hits.
    PF00619. CARD. 1 hit.
    [Graphical view]
    SMARTiSM00238. BIR. 3 hits.
    SM00114. CARD. 1 hit.
    SM00184. RING. 1 hit.
    [Graphical view]
    SUPFAMiSSF47986. SSF47986. 1 hit.
    PROSITEiPS01282. BIR_REPEAT_1. 3 hits.
    PS50143. BIR_REPEAT_2. 3 hits.
    PS50209. CARD. 1 hit.
    PS50089. ZF_RING_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O08863-1 [UniParc]FASTAAdd to Basket

    « Hide

    MVQDSAFLAK LMKSADTFEL KYDFSCELYR LSTYSAFPRG VPVSERSLAR    50
    AGFYYTGAND KVKCFCCGLM LDNWKQGDSP MEKHRKLYPS CNFVQTLNPA 100
    NSLEASPRPS LPSTAMSTMP LSFASSENTG YFSGSYSSFP SDPVNFRANQ 150
    DCPALSTSPY HFAMNTEKAR LLTYETWPLS FLSPAKLAKA GFYYIGPGDR 200
    VACFACDGKL SNWERKDDAM SEHQRHFPSC PFLKDLGQSA SRYTVSNLSM 250
    QTHAARIRTF SNWPSSALVH SQELASAGFY YTGHSDDVKC FCCDGGLRCW 300
    ESGDDPWVEH AKWFPRCEYL LRIKGQEFVS QVQAGYPHLL EQLLSTSDSP 350
    EDENADAAIV HFGPGESSED VVMMSTPVVK AALEMGFSRS LVRQTVQWQI 400
    LATGENYRTV SDLVIGLLDA EDEMREEQME QAAEEEESDD LALIRKNKMV 450
    LFQHLTCVTP MLYCLLSARA ITEQECNAVK QKPHTLQAST LIDTVLAKGN 500
    TAATSFRNSL REIDPALYRD IFVQQDIRSL PTDDIAALPM EEQLRKLQEE 550
    RMCKVCMDRE VSIVFIPCGH LVVCKDCAPS LRKCPICRGT IKGTVRTFLS 600
    Length:600
    Mass (Da):67,228
    Last modified:July 27, 2011 - v2
    Checksum:i2EC9C7B567721382
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti398 – 3981W → R in AAC53531. (PubMed:9441758)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U88908 mRNA. Translation: AAC53531.1.
    CT030639 Genomic DNA. No translation available.
    RefSeqiNP_031490.2. NM_007464.3.
    UniGeneiMm.2026.

    Genome annotation databases

    GeneIDi11796.
    KEGGimmu:11796.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U88908 mRNA. Translation: AAC53531.1 .
    CT030639 Genomic DNA. No translation available.
    RefSeqi NP_031490.2. NM_007464.3.
    UniGenei Mm.2026.

    3D structure databases

    ProteinModelPortali O08863.
    SMRi O08863. Positions 24-96, 159-600.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 198147. 14 interactions.
    DIPi DIP-43742N.
    IntActi O08863. 3 interactions.
    MINTi MINT-1581324.

    Protein family/group databases

    MEROPSi I32.003.

    PTM databases

    PhosphoSitei O08863.

    Proteomic databases

    PaxDbi O08863.
    PRIDEi O08863.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 11796.
    KEGGi mmu:11796.

    Organism-specific databases

    CTDi 330.
    MGIi MGI:1197007. Birc3.

    Phylogenomic databases

    eggNOGi NOG243347.
    HOGENOMi HOG000232059.
    HOVERGENi HBG004848.
    InParanoidi O08863.
    KOi K16060.

    Enzyme and pathway databases

    Reactomei REACT_226192. IKK complex recruitment mediated by RIP1.

    Miscellaneous databases

    NextBioi 279629.
    PROi O08863.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O08863.
    Bgeei O08863.
    CleanExi MM_BIRC2.
    MM_BIRC3.
    Genevestigatori O08863.

    Family and domain databases

    Gene3Di 1.10.1170.10. 4 hits.
    1.10.533.10. 1 hit.
    InterProi IPR001370. BIR.
    IPR001315. CARD.
    IPR011029. DEATH-like_dom.
    IPR001841. Znf_RING.
    [Graphical view ]
    Pfami PF00653. BIR. 3 hits.
    PF00619. CARD. 1 hit.
    [Graphical view ]
    SMARTi SM00238. BIR. 3 hits.
    SM00114. CARD. 1 hit.
    SM00184. RING. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47986. SSF47986. 1 hit.
    PROSITEi PS01282. BIR_REPEAT_1. 3 hits.
    PS50143. BIR_REPEAT_2. 3 hits.
    PS50209. CARD. 1 hit.
    PS50089. ZF_RING_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Genomic characterization of the mouse inhibitor of apoptosis protein 1 and 2 genes."
      Liston P., Lefebvre C., Fong W.G., Xuan J.Y., Korneluk R.G.
      Genomics 46:495-503(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Skeletal muscle.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    3. "c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation."
      Varfolomeev E., Goncharov T., Fedorova A.V., Dynek J.N., Zobel K., Deshayes K., Fairbrother W.J., Vucic D.
      J. Biol. Chem. 283:24295-24299(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE.

    Entry informationi

    Entry nameiBIRC3_MOUSE
    AccessioniPrimary (citable) accession number: O08863
    Secondary accession number(s): E9QLX3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 124 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3