FunctionApoptotic suppressor. Has E3 ubiquitin-protein ligase activity. Mediates the proteasomal degradation of target proteins, such as caspase-3, SMAC or AIFM1. Inhibitor of caspase-3, -7 and -9. Mediates activation of MAP3K7/TAK1, leading to the activation of NF-kappa-B.
Involvement in diseaseDefects in XIAP are the cause of lymphoproliferative syndrome X-linked type 2 (XLP2) [MIM:300635]. XLP is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.
Sequence similaritiesBelongs to the IAP family. Contains 3 BIR repeats. Contains 1 RING-type zinc finger.
DomainThe first BIR domain is involved in interaction with TAB1/MAP3K7IP1 and is important for dimerization. The second BIR domain is sufficient to inhibit caspase-3 and caspase-7, while the third BIR is involved in caspase-9 inhibition. The interactions with SMAC and PRSS25 are mediated by the second and third BIR domains.
Post-translational modificationsUbiquitinated and degraded by the proteasome in apoptotic cells. Phosphorylation by PKB/AKT protects XIAP against ubiquitination and protects the protein against proteasomal degradation.