X-linked lymphoproliferative syndrome 2
The XIAP gene at Xq25 codes for the 497 amino acid E3 ubiquitin-protein ligase XIAP. This regulates or modulates caspases, apoptosis, inflammatory signaling, immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, and cell invasion and metastasis.
- Directly binds to the active site pocket of caspase-3 and caspase-7
- Inactivates caspase-9 by keeping it in a monomeric, inactive state.
- Regulates NF-kappa-B signaling with the target proteins for its E3 ubiquitin-protein ligase activity including: receptor-interacting serine/threonine-protein kinase 1, caspase-3, caspase-7, caspase-8, caspase-9, mitogen-activated protein kinase kinase kinase 2, mitochondrial diablo homolog, apoptotic protease-activating factor 1, copper chaperone for superoxide dismutase and baculoviral IAP repeat-containing protein 5.
- Ubiquitinationg COMM domain-containing protein 1, a scaffolding protein and promoting its proteasomal degradation.
- E3 ubiquitin-protein ligase in the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation.
- Regulates the bone morphogenetic protein (BMP) signaling pathway and the SMAD and mitogen-activated protein kinase kinase kinase 7dependent pathways leading to NF-kappa-B and JNK activation.
- Regulates innate immune signaling via regulation of Nodlike receptors (NLRs).
- Protects cells from spontaneous formation of the ripoptosome the key to programmed necroptosis
Mutation causes X-linked lymphoproliferative syndrome 2 (XLP2, OMIM:300635) with extreme susceptibility to infection with Epstein-Barr virus resulting in severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.