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Symbol BIRC2 contributors: mct - updated : 05-05-2016
HGNC name baculoviral IAP repeat-containing 2
HGNC id 590
Location 11q22.1      Physical location : 102.217.965 - 102.249.394
Synonym name
  • apoptosis inhibitor 1
  • NFR2-TRAF signaling complex protein
  • RING finger protein 48
  • apoptosis inhibitor 1
  • IAP homolog B
  • Synonym symbol(s) MIHB, HIAP2, BIR2, CIAP, API1, HIAP2, Hiap-2, RNF48, cIAP1
    TYPE functioning gene
    SPECIAL FEATURE arranged in tandem
    text arranged in tandem with BIRC3
    STRUCTURE 31.44 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    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
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 3753 69.8 618 - 2009 19223549
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Hearing/Equilibriumear   highly
    Lymphoid/Immunespleen   highly
    Respiratoryrespiratory tracttrachea  highly
    Urinarybladder   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunemacrophage Homo sapiens
    cell lineage
    cell lines
    at STAGE
    physiological period fetal
    Text lung, kidney
  • N-terminal (BIR1) and C-terminal (BIR3) domains necessary and sufficient for binding TRAF2 and DIABLO
  • three baculovirus IAP repeats (BIR)
  • one CARD domain, and CARD-mediated autoregulation is necessary to maximally suppress CASP8-dependent apoptosis and vascular tree degeneration (
  • a C-terminal RING zinc finger domain, E3 ligase RING domain targeting RING-bearing IAPs for proteasomal degradation by ubiquitin-dependent and -independent pathways , sequestered within a compact, monomeric structure that prevents RING dimerization
  • mono polymer heteromer
    interspecies homolog to murine Birc2
    intraspecies paralog to NAIP
  • IAP family
  • CATEGORY regulatory , receptor membrane G
    SUBCELLULAR LOCALIZATION     intracellular
  • localized almost exclusively to nuclei in cells
  • was released into the cytosol early in mitosis, then reaccumulated in nuclei in late anaphase and in telophase, with the exception of a pool of BIRC2 that associated with the midbody
  • migration from the nucleus to the Golgi apparatus in monocytes undergoing differentiation into macrophages
  • in the nucleus appears to be part of the molecular machinery that regulates the transcriptional activity of E2F1 on CCNE and CCNA promoters
  • VGLL4 triggers a relocalization of BIRC2 from the cytoplasm to the nucleus
  • basic FUNCTION
  • inhibiting apoptosis induced by serum deprivation and menadione, a potent inducer of free radicals
  • playing an essential role in the cell death mechanism of injured motoneurons in collaboration with XIAP, BIRC3, BIRC4BP
  • modulating the cell cycle
  • playing an essential role for maintaining endothelial cell survival and blood vessel homeostasis during vascular development
  • positively regulating the formation of the TNF receptor complex I in endothelial cells, thereby promoting NF-B activation and maintaining vessel integrity and stabilization
  • in the cytoplasm, involved in the degradation of the adaptor protein tumor necrosis factor receptor-associated factor 2 (TRAF2) by the proteosomal machinery
  • 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
  • BIRC2, BIRC3, and MAP3K7 protect cells from TNF-induced necrosis by preventing RIPK1/RIPK3-dependent ROS production
  • BIRC2 and UBE2D1 promote K11-linked polyubiquitination of RIPK1 in TNF signalling
  • potent regulator of the tumor necrosis factor (TNF) receptor family and NFKB signaling pathways in the cytoplasm
  • one of the functions of BIRC2 when localized in the nucleus is to regulate E2F1 transcriptional activity
  • ability of BIRC2 to promote E2F1-mediated transcription activity of CCN genes, whose overexpression was associated with poor prognosis in several tumor types, could account for its oncogenic properties
  • acts in collaboration with the TRAF2 protein to regulate the TNFR signaling pathway
  • XIAP, BIRC2, BIRC3 are important regulators of inflammatory processes in endothelial cells
  • critical effector of the inflammasome and required for efficient caspase-1 activation
  • acts on both secretion of PCSK9 and its lysosomal localization
  • XIAP and BIRC2 induce autophagy by upregulating the transcription of BECN1, an essential autophagy gene
  • 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
  • heterodimeric complex with TRAF1 and TRAF2
  • part of antiapoptotic protein complex associated with death receptors that contains DDX3X and GSK3B
    RNA interaction with TRAF2 (ubiquitination and degradation of TRAF2)
    small molecule
  • inhibitor of caspase 9, DIABLO releasing this inhibition
  • interacting with DIABLO and with PRSS25 (interactions inhibit apoptotic suppressor activity)
  • interact with FBXO7 (can mediate its ubiquitination by SCF ubiquitin protein ligase and thus have important implication in the regulation of BIRC2 function)
  • is a client protein of the stress protein HSP90AB1 that prevents auto-ubiquitination and degradation of BIRC2, whose depletion would be sufficient to inhibit cell differentiation
  • interacting with TRAF2 (BIRC2-dependent TRAF2 degradation regulates the differentiation of monocytes into macrophages and their response to CD40 ligand)
  • acting cooperatively with BIRC3 and XIAP via nonredundant pathways to regulate genotoxic stress-induced nuclear factor-kappaB activation
  • cooperatively interacts with oligomerized processed CASP9 in the apoptosome and blocks procaspase-3 activation
  • dramatically increases the transcriptional activity of E2F1 on synthetic and CCNE promoters
  • VGLL4 triggers a relocalization of BIRC2 from the cytoplasm to the nucleus
  • USP19, a deubiquitinating enzyme, interacts with cellular BIRC2, BIRC3
  • binding and ubiquitinating CASP3 and CASP7
  • RIPK4 interacts with BIRC2 (Lys51 and Lys145 of RIPK4 are two critical AAs for BIRC2-mediated ubiquitination and NFKB activation)
  • BIRC2, BIRC3 and the adaptor protein TRAF2 interacted with caspase-1-containing complexes
  • a ubiquitin-regulated signaling network centered on ITCH and BIRC2 controls the strength of NOD2 signaling
  • XIAP and, to a lesser extent, BIRC2 were found to directly interact with RHOA independently of the RHOA activation status
  • 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
    Other self-ubiquitin ligase activity of BIRC2, BIRC3 is inhibited by USP19 and deubiquitinating enzymes are impicated in the regulation of IAP stability
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in esophageal squamous cell carcinoma in progression
    tumoral     --over  
    in lung cancer and NPM-ALK positive anaplastic large cells lymphoma
    Variant & Polymorphism
    Candidate gene
    Therapy target
    therapeutic opportunities in the treatment of cancer