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Symbol BIRC3 contributors: mct/pgu - updated : 05-05-2015
HGNC name baculoviral IAP repeat-containing 3
HGNC id 591
  • the baculovirus IAP repeat (three BIR domains)
  • a carboxyterminal RING zinc finger domains mediating auto-ubiquitylation (is both an active E3 ligase and a substrate for auto-ubiquitylation)
    intraspecies homolog to NAIP
  • IAP family
  • CATEGORY regulatory , receptor membrane G
    SUBCELLULAR LOCALIZATION     intracellular
  • VGLL4 triggers a relocalization of BIRC3 from the cytoplasm to the nucleus
  • basic FUNCTION
  • antagonizing cell death and regulating the cell cycle
  • playing an essential role in the cell death mechanism of injured motoneurons in collaboration with XIAP, BIRC4BP, BIRC2
  • playing a critical role in the maintenance of a normal innate immune inflammatory response
  • recruits two UBE2B molecules, through the RING domains (specific contacts between UBE2B and RING are required for activity)
  • through its E3 ubiquitin ligase activities, promote proteasomal degradation of NIK (NF-kappaB-inducing kinase) and regulate the non-canonical NF-kappaB pathway
  • promote cancer cell survival by functioning as E3 ubiquitin ligases that maintain constitutive ubiquitination of the RIPK1 adaptor protein
  • BIRC2, BIRC3, and XIAP act cooperatively via nonredundant pathways to regulate genotoxic stress-induced nuclear factor-kappaB activation
  • likely suppress apoptosis, at least in part, by facilitating the ubiquitination and turnover of active effector caspases in cells
  • a key regulator of programmed cell death and the NFKB pathway
  • BIRC2, BIRC3, and MAP3K7 protect cells from TNF-induced necrosis by preventing RIPK1/RIPK3-dependent ROS production
  • XIAP, BIRC2, BIRC3 are important regulators of inflammatory processes in endothelial cells
  • roles for TNFSF12, BIRC3, and noncanonical NFKB1 signaling in the regulation of myoblast fusion and highlight a role for cytokine signaling during adult skeletal myogenesis
  • NAIP is abundantly expressed in M2 macrophages, while BIRC2 and BIRC3 show an inverse pattern of expression in polarized macrophages, with elevated expression levels of BIRC2 in M2 and BIRC3 preferentially expressed in M1
  • CELLULAR PROCESS cell life, antiapoptosis
    a component
  • heteromeric complex with TRAF1, TRAF2, recruited to TBFR
    small molecule
  • inhibitor of caspases 3, 7, 9
  • SMAC releasing this inhibition
  • binds to UBE2D1, UBE2B, UBE2D3, and UBE2G1 but not to UBE2E2
  • acting cooperatively with BIRC2 and XIAP via nonredundant pathways to regulate genotoxic stress-induced nuclear factor-kappaB activation
  • NF-kappaB-independent G2/M-phase-specific expression will help in further understanding the molecular basis of BIRC3 over-expression in a variety of cancers
  • because TRAF1 is upregulated by many stimuli, it may modulate the interaction of TRAF2 with BIRC2, BIRC3, which explains regulatory roles of TRAF1 in TNF signaling
  • USP19, a deubiquitinating enzyme, interacts with cellular BIRC2, BIRC3
  • VGLL4 triggers a relocalization of BIRC3 from the cytoplasm to the nucleus
  • BIRC2, BIRC3 are direct E3 ubiquitin ligases for all four RIP proteins and BIRC2 is capable of conjugating the RIPs with diverse types of ubiquitin chains, including linear chains
  • BIRC2, BIRC3 and the adaptor protein TRAF2 interacted with caspase-1-containing complexes
  • TNFSF10 -induced lysosomal membrane permeabilization is mediated by the multifunctional sorting protein PACS2 and repressed by the E3 ligases BIRC2 and BIRC3
  • BIRC2, BIRC3 constitutively downregulate PACS2 by polyubiquitination and proteasomal degradation, thereby restraining TNFSF10-induced killing of liver cancer cells
  • cell & other
    activated by severe hypoxia
    induced by NF-kappaB (nuclear factor kappaB) when cells need to respond quickly to different apoptotic stimuli
    Other self-ubiquitin ligase activity of BIRC2, BIRC3 is inhibited by USP19 and deubiquitinating enzymes are impicated in the regulation of IAP stability
    post-transcriptional regulation of BIRC3 expression by tristetraprolin (ZFP36)
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    rearranged with MALT1 :t(11;18)(q21;q21) in marginal zone cell lymphoma
    tumoral     --over  
    in lung cancer and malignant pleural mesothelioma and promoting tumor cell survival
    tumoral     --other  
    is a common mechanism across marginal zone B-cell lymphomagenesis
    Variant & Polymorphism
    Candidate gene
    Therapy target
    therapeutic opportunities in the treatment of cancer