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FLASH GENE
Symbol BIRC3 contributors: mct/pgu - updated : 05-05-2015
HGNC name baculoviral IAP repeat-containing 3
HGNC id 591
Location 11q22.2      Physical location : 102.188.193 - 102.208.464
Synonym name
  • apoptosis inhibitor 2
  • TNFR2-TRAF signaling complex protein
  • mammalian IAP homolog C
  • inhibitor of apoptosis protein 1
  • cellular inhibitor of apoptosis 2
  • RING finger protein 49
  • Synonym symbol(s) MIHC, cIAP2, IAP-1, AIP1, API2, HAIP1, HIAP1, MALT2, RNF49
    DNA
    TYPE functioning gene
    SPECIAL FEATURE
    text arranged in tandem with BIRC2
    STRUCTURE 20.27 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   enhancer
    motif
    text structure
  • enhancer element
  • a bipartite CDE (cell cycle-dependent element)/CHR (cell cycle gene homology region) element in the promoter mediates BIRC3 gene activation in G2/M phase
  • MAPPING cloned Y linked N status confirmed
    Physical map
    TRPC6 11q21-q22 transient receptor potential cation channel, subfamily C, member 6 ANGPTL5 11q22.2 angiopoietin-like 5 MGC13040 11q22.2 hypothetical protein MGC13040 YAP1 11q13 Yes-associated protein 1, 65kDa LOC120318 11q22.2 similar to 40S ribosomal protein S6 (Phosphoprotein NP33) BIRC3 11q25 baculoviral IAP repeat-containing 3 BIRC2 11q22 baculoviral IAP repeat-containing 2 PORIMIN 11q22.1 Homo sapiens pro-oncosis receptor inducing membrane injury gene (PORIMIN), mRNA. MMP7 11q22.2-q22.3 matrix metalloproteinase 7 (matrilysin, uterine) MMP20 11q22.2-q22.3 matrix metalloproteinase 20 (enamelysin) MMP27 11q24 matrix metalloproteinase 27 MMP8 11q22.2-q22.3 matrix metalloproteinase 8 (neutrophil collagenase) LOC390248 11 similar to matrix metalloproteinase 1 precursor MMP10 11q22.2-q22.3 matrix metalloproteinase 10 (stromelysin 2) MMP1 11q22.2-q22.3 matrix metalloproteinase 1 (interstitial collagenase) LOC120321 11q22.2 similar to casein kinase 1, alpha 1 MMP3 11q22.2-q22.3 matrix metalloproteinase 3 (stromelysin 1, progelatinase) MMP12 11q22.3 matrix metalloproteinase 12 (macrophage elastase) MMP13 11q22.2-q22.3 matrix metalloproteinase 13 (collagenase 3) MGC2714 11q22.2 hypothetical protein MGC2714 DNCH2 11q21-q22.1 dynein, cytoplasmic, heavy polypeptide 2
    RNA
    TRANSCRIPTS type messenger
    text variants 1 and 2 encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 5243 68.2 604 - 2008 18784070
    10 - 2683 68.2 604 - 2008 18784070
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus    
    Digestiveintestinelarge intestinecolon highly
    Endocrinepancreas    
     parathyroid   highly
    Lymphoid/Immunelymph node   highly
    Reproductivefemale systemovary   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunemacrophage Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text tissues
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 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)
  • HOMOLOGY
    intraspecies homolog to NAIP
    Homologene
    FAMILY
  • IAP family
  • CATEGORY regulatory , receptor membrane G
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text
  • 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
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • heteromeric complex with TRAF1, TRAF2, recruited to TBFR
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • 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
    REGULATION
    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)
    ASSOCIATED DISORDERS
    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
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    therapeutic opportunities in the treatment of cancer
    ANIMAL & CELL MODELS