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

More general terms

• E3 ubiquitin ligase
• ring finger protein
• phosphoprotein
• inhibitor of apoptosis protein

Database

• UniProt: http://www.uniprot.org/uniprot/P98170.html
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=331
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:331
• OMIM: https://mirror.omim.org/entry/300079
• OMIM: https://mirror.omim.org/entry/300635