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Baculoviral IAP repeat-containing protein 4; E3 ubiquitin-protein ligase XIAP; inhibitor of apoptosis protein 3; X-linked inhibitor of apoptosis protein; X-linked IAP; IAP-like protein; HILP (XIAP, API3, BIRC4, IAP3)

Function: - suppressor of apoptosis - has E3 ubiquitin-protein ligase activity - mediates proteasomal degradation of target proteins, including caspase-3, SMAC & AIFM1 - inhibits caspase-3, caspase-7 & caspase-9 - mediates activation of MAP3K7/TAK1, leading to activation of NF-kappa-B - ubiquitinated & degraded by the proteasome in apoptotic cells - phosphorylation by PKB/AKT protects XIAP against ubiquitination & protects the protein against proteasomal degradation - interacts with SMAC & with PRSS25; these interactions inhibit apoptotic suppressor activity - interacts with MAP3K7IP1 & AIFM1 - interaction with SMAC hinders binding of MAP3K7IP1 & AIFM1 - interacts with TCF25 Structure: - monomer, & homodimer - the 1st BIR domain is involved in interaction with MAP3K7IP1 & is important for dimerization - the 2nd BIR domain is sufficient to inhibit caspase-3 & caspase-7, while the 3rd BIR is involved in caspase-9 inhibition - interactions with SMAC & PRSS25 are mediated by the 2nd & 3rd BIR domains - belongs to the IAP family - contains 3 BIR repeats - contains 1 RING-type Zn+2 finger Compartment: cytoplasm Expression: ubiquitous, except peripheral blood leukocytes Pathology: - defects in XIAP are the cause of X-linked lymphoproliferative syndrome type 2

General

inhibitor of apoptosis protein; baculoviral IAP repeat containing protein; BIRC protein (IAP; BIRC) phosphoprotein ring finger protein E3 ubiquitin ligase; ubiquitin-ligating enzyme E3; N end-recognizing protein

Properties

SIZE: entity length = 497 aa MW = 57 kD COMPARTMENT: cytoplasm MOTIF: BIR {26-93} MOTIF: Ser phosphorylation site {S87} Tyr phosphorylation site {Y139} caspase-7 interaction {141-149} BIR {163-230} BIR {265-330} MOTIF: Zn+2-binding site SITE: 300-300 Zn+2-binding site SITE: 303-303 Zn+2-binding site SITE: 320-320 Zn+2-binding site SITE: 327-327 RING-finger {450-485} EFFECTOR-BOUND: Zn+2 FOR-BINDING-OF: DNA motif

Database Correlations

OMIM correlations MORBIDMAP 300079 UniProt P98170 Pfam PF00653 Entrez Gene 331 KEGG correlations

References

  1. Liston P et al. Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Nature 379:349-353, 1996 PMID: 8552191
  2. Duckett CS et al. A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors. EMBO J 15:2685-94 1996 PMID: 8654366
  3. Entrez Gene :accession 331
  4. UniProt :accession P98170
  5. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=XIAP
  6. BIRC4base; Note: XIAP mutation db http://bioinf.uta.fi/BIRC4base/
  7. NIEHS-SNPs http://egp.gs.washington.edu/data/birc4/