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Symbol XIAP contributors: shn/mct - updated : 19-10-2017
HGNC name X-linked inhibitor of apoptosis
HGNC id 592
Corresponding disease
XLP2 lymphoproliferative syndrome, 2
Location Xq25      Physical location : 122.994.047 - 123.047.821
Synonym name
  • baculoviral IAP repeat-containing 4
  • apoptosis inhibitor 3
  • IAP-like protein
  • X-linked inhibitor of apoptosis protein
  • E3 ubiquitin-protein ligase XIAP
  • mammalian IAP Homolog A
  • Synonym symbol(s) API3, ILP1, MIHA, BIRC4, HILP, XLP2, FLJ26913, IAP-3, hIAP-3
    TYPE functioning gene
    STRUCTURE 54.17 kb     7 Exon(s)
    text structure an internal ribosome entry site (IRES) in the 5'UTR
    MAPPING cloned Y linked N status confirmed
    Map cen - DXS9909 - DXS8098 - XIAP - DXS8057 - DXS8093 - qter
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 8413 57 497 - 2017 28040451
    7 - 8427 - 497 - 2017 28040451
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
     intestinelarge intestinecolon  
    Endocrinepancreas   highly
    Lymphoid/Immunelymph node   highly
    Reproductivemale systemprostate   
    Urinarykidney   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
  • three baculovirus IAP repeat (BIR1-2 domains required for inhibition of caspase 3/7)
  • the BIR1 domain directly interacts with MA1P3K7IP1 to induce NF-kappaB activation
  • a C-terminal RING zinc finger domain (BIR3 Ring inhibitor of caspase 9), mediating MAP3K7 polyubiquitination, which then targets this molecule for proteosomal degradation, and is essential for NOD2 signaling
  • BIR and RING finger domains of XIAP contain multiple cysteine residues and are potential targets for S-nitrosylation
  • conjugated ubiquitinated
    mono polymer homomer , monomer , dimer
    interspecies ortholog to Xiap, Mus musculus
    ortholog to Xiap, Rattus norvegicus
    ortholog to xiap, Danio rerio
    ortholog to XIAP, Pan troglodytes
    intraspecies homolog to NAIP
  • IAP family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
  • VGLL4 triggers a relocalization of XIAP from the cytoplasm to the nucleus
  • basic FUNCTION
  • a direct inhibitor of cell-death proteases
  • inhibitor of apoptosis through binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2
  • antiapoptosis activity in a variety of apoptosis inducing conditions
  • has a ubiquitin protein ligase activity in response to apoptotic stimuli
  • involved in the protection of the neonatal brain against hypoxia-ischemia
  • potent suppressor of apoptosis that directly inhibits specific members of the caspase family (caspase 3, 7, 9) of cysteine proteases, playing a role in the control of intracellular copper levels
  • playing an essential role in the cell death mechanism of injured motoneurons in collaboration with BIRC4BP, BIRC3, BIRC2
  • required for the survival and/or differentiation of NKT cells, and potent regulator of lymphocyte homeostasis
  • functioning as ubiquitin ligase toward mature CASP9 and DIABLO to inhibit apoptosis
  • inhibits c-Jun N-terminal kinase 1 (MAPK8) activation by transforming growth factor beta1 (TGF-beta1) through ubiquitin-mediated proteosomal degradation of the TGF-beta1-activated kinase 1 (MAP3K7)
  • can function as a cofactor in the regulation of gene expression by transforming growth factor-beta (TGF-beta)
  • having a role in control of oxidative stress and mitochondrial antioxidants that may contribute to cell protection after various injuries
  • mediating activation of MAP3K7/TAK1, leading to the activation of NF Kappa B
  • is essential for the shear stress-stimulated SRC/PTK2/ERK signaling pathway
  • is a nonredundant modulator of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
  • has a role in copper metabolism
  • critical controller of apoptotic susceptibility of effector T cell function
  • plays a novel role in endothelial cells and acting as a regulator of vascular antiatherogenic function
  • promoting the binding of STUB1 to the RAF1/Hsp90 complex
  • acting as an E3 ubiquitin ligase for PTEN, promoting Akt activity by regulating PTEN content and compartimentalization
  • critical discriminator between type I and type II apoptosiscritical discriminator between type I and type II apoptosis signalling
  • playing a role in regulating innate immune responses by interacting with NOD1 and NOD2 through interaction with RIPK2
  • protects gangkion cells after axotonomy of the optic nerve, increased intraocular pressure and retinal ischemia ,
  • confers structural neuroprotection of photoreceptors after retinal detachment
  • recruits focal adhesion kinase (PTK2) into integrin-associated focal adhesions, controlling cell migration
  • plays a key role in shear stress-stimulated ERK activation by maintaining the Src-accessible location of PTK2
  • important mediator for the recruitment of PTK2 into the focal adhesion site
  • may play a preventative role in cardiovascular disease
  • its inhibition are essential to limit clonogenicity of Type I tumor cells after TNFSF10 receptor stimulation )
  • negatively regulate GDI1 SUMOylation, which might affect its activity in controlling cell motility
  • has the function of regulating cell motility via regulation of beta-actin polymerization and cytoskeleton formation
  • XIAP, BIRC2, BIRC3 are important regulators of inflammatory processes in endothelial cells
  • plays a key role in vascular functions of PTK2B or PTK2B domain-mediated vascular functions of PTK2
  • is essential for functional activity of PTK2B in endothelial cells
  • regulates a diversity of vascular functions linked to PTK2 and(or) PTK2B
  • potent regulator of innate immune responses
  • co-ordinated development of the brain and face is likely dependent in part upon XIAP mediation of HH/PTCH1-regulated cell survival and apoptosis during embryogenesis
  • XIAP and BIRC2 induce autophagy by upregulating the transcription of BECN1, an essential autophagy gene
  • regulate innate immune signaling
  • plays a key role in the control of mitotic cell death
  • XIAP ubiquitinates a highly conserved Lys residue in AC isoforms and thereby accelerates the endocytosis and degradation of multiple AC isoforms in human cell lines
  • CELLULAR PROCESS cell life, cell death/apoptosis
    cell life, antiapoptosis
    a component
  • HNRPC 1/2 IRES form are part of a complex modulating BIRC4 expression
  • complexing with BIRC4BP to regulate motoneuron resistance to apoptotic cell death
  • XIAP-CCS complex implicated in apoptosis, copper metabolism, and redox regulation
    small molecule
  • DIABLO (direct IAP binding protein with low pI)
  • TRAF1 and TRAF2
  • COMMD1, a factor recently implicated in copper homeostasis (functioning through COMMD1 to regulate copper homeostasis)
  • MAP3K7IP1 and AIFM1
  • acting cooperatively with BIRC3 and BIRC2 via nonredundant pathways to regulate genotoxic stress-induced nuclear factor-kappaB activation
  • KCNJ6/MAP3K7IP1 interaction is crucial for BIRK4-induced MAP3K7 and NF-kappaB activation
  • RIPK2 via its BIR2 domain, which could be disrupted by XIAP antagonists SMAC and SMAC-mimicking compounds
  • inhibitor of caspase-3, -7 and -9
  • mediates activation of MAP3K7/TAK1, leading to the activation of NF-kappa-B
  • GSPT1/eRF3 protein
  • HtrA2, mammalian homologue of the Escherichia coli heat shock-inducible protein HtrA
  • neurotrophin receptor-interacting MAGE homologue (NRAGE)
  • ILPIP (hILP-Interacting Protein)
  • TAB1-TAK1 receptors
  • XIAP-associated factor 1 (XAF1)
  • survivin (BIRC5)
  • checkpoint kinase Chk1
  • enhances NF-kappaB activity
  • interacts with and ubiquitinates MEKK2
  • binds strongly to C-RAF and promotes the ubiquitylation of C-RAF in vivo through the Hsp90-mediated quality control system
  • interacting with AIFM1 (role for XIAP in regulating cellular reactive oxygen species)
  • caveolin-1 (CAV1)
  • role for XIAP in regulating innate immune responses by interacting with NOD1 and NOD2 through interaction with RIPK2
  • interacting with HAX1, that enhances the stability of XIAP against proteosomal degradation and thus contributing to inhibition of apoptosis
  • regulates actin polymerization and cell motility through its interaction with GDI1
  • VGLL4 triggers a relocalization of XIAP from the cytoplasm to the nucleus
  • interacts with PTK2B, suggesting cross-talk between XIAP and PTK2B
  • interacted with ARHGDIA via its RING domain and negatively modulated ARHGDIA SUMOylation
  • XIAP ubiquitylates RIPK2 and recruits the linear ubiquitin chain assembly complex (LUBAC) to NOD2
  • platelets have a functional intrinsic apoptotic-signalling pathway including the pro-apoptotic protease HTRA2 and its target protein XIAP
  • XIAP and, to a lesser extent, BIRC2 were found to directly interact with RHOA independently of the RHOA activation status
  • controls RIPK3-dependent cell death and IL1B secretion in response to TNF, which might contribute to hyperinflammation in patients with XLP2
  • XIAP directly interacts with MAP3K3 and competes with PB1 domain-mediated binding to MAP2K5
  • SERTAD1 may render cancer cells resistant to apoptosis through the stabilization of XIAP
  • XIAP is a target for USP11, and stabilization of XIAP due to its deubiquitylation by USP11 leads to the inhibition of cell anoikis and apoptosis, which in turn promotes tumorigenesis
  • SERTAD1 acts as an adaptor that bridges the interaction of multiple Adenylyl cyclases (ACs) isoforms with XIAP, a RING-domain E3 ubiquitin ligase
  • XIAP serves as an E3 ligase for BCL2 and SEPTIN4 is essential for this process
  • SEPTIN4 interacts with X-linked inhibitor of apoptosis (XIAP) in the ntestinal stem cell (ISC) niche to regulate stem cell survival during intestinal homeostasis and regeneration
  • cell & other
    activated by Che-1 in response to DNA damage
    inhibited by SMAC which neutralizes the ability of BIRC4 to repress active caspase 9
    interaction with PRSS25
    repressed by S-nitrosylation (does not affect its E3 ligase activity, but instead directly compromising its anticaspase-3 and antiapoptotic function, and contributes to Parkinson disease pathogenesis)
    Phosphorylated by by CDK1-CCNB1 that controls mitotic cell death
  • degraded by calpain contribution to initiation of apoptosis in neutrophils
  • neutrophils accumulation
  • ubiquitinated and degraded by the proteasome in apoptotic cells
  • phosphorylation by PKB/AKT protects against ubiquitination
  • p34SEI-1 protects the X-linked inhibitor of apoptosis protein (XIAP) from degradation
  • phosphorylated by yclic AMP-dependent protein kinase A (PKA)
  • directly ubiquitinated by TRIM32
    corresponding disease(s) XLP2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in hepatocellular carcinoma
    tumoral   deletion    
    in X-linked lymphoproliferative syndrome, and in patients with low numbers of natural killer T-lymphocytes (NKT cells)
    constitutional     --low  
    renders cells highly sensitive to oxidative stress
    tumoral     --over  
    in the majority of non-small cell lung carcinoma, together with the abundant or upregulated expression of HBXIP and BIRC5 suggest that tumours are endowed with resistance against a variety of apoptosis-inducing conditions
    tumoral     --over  
    overexpression of FOXM1, XIAP, and BIRC5 contributes to the development of drug-resistance and is associated with poor clinical outcome in breast cancer patients
    Variant & Polymorphism
    Candidate gene
    Therapy target
    for gene therapy in hepatocellular carcinoma (inhibition of the NF-kappaB/XIAP signaling pathway might selectively abolish the pro-oncogenic activity of TGF-beta1 in advanced hepatocellular carcinomas without affecting the pro-apoptotic effects of TGF-bet
    inhibition as a treatment for malignancy
    targeting CFLAR and BIRC4 may represent a therapeutic strategy for the treatment of colorectal tumors with defects in mitochondrial-regulated apoptosis
    may be target protein for the prevention of cardiovascular disease
    potential utilization of XIAP as a target for cancer prevention and therapy
    XIAP inhibitor can be therapeutically targeted, either alone or in combination, to induce efficient apoptosis in PTC with overexpression of XIAP
    mice deficient in Xiap gene were viable, histopathological analysis did not reveal any differences between IAP-deficient and wild-type mice and any defects in induction of caspase-dependent or -independent apoptosis in cells was found