AlphaFold predicted structure
XIAP · P98170
Mean pLDDT
74.3/ 100
Confident
497 residues
Confidence breakdown
- Very high(≥ 90)31%
- Confident(70–90)38%
- Low(50–70)9%
- Very low(< 50)22%
Open interactive 3D viewer
AlphaFold (Jumper et al., 2021) · CC BY 4.0
XIAP
Chr Xq25X-linked inhibitor of apoptosis
- Aliases:
- hILP, ILP-1
- MANE:
- ENST00000371199.8
Annotations refreshed 1 month ago.
Predicted protein structure
Clinical relevance (Genomics England PanelApp)
Diagnostic Grade (Green)
COVID-19 research
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)Gastrointestinal epithelial barrier disorders
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)Haemophagocytic syndrome with absent XIAP expression
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)Infantile enterocolitis & monogenic inflammatory bowel disease
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)Intestinal failure or congenital diarrhoea
X-LINKED: hemizygous mutation in males, biallelic mutations in femalesPrimary immunodeficiency or monogenic inflammatory bowel disease
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)Intellectual disability
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Disease associations (Open Targets)
X-linked lymphoproliferative disease
0.80neurodegenerative disease
0.56inflammatory bowel disease
0.48hereditary disease
0.47Splenomegaly
0.46Sepsis
0.35X-linked sideroblastic anemia 1
0.34Recurrent infections
0.34lymphoproliferative syndrome 2
0.34autoinflammatory syndrome
0.33
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
Protein function (UniProt)
E3 ubiquitin-protein ligase XIAP
Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis (PubMed:11257230, PubMed:11257231, PubMed:11447297, PubMed:12121969, PubMed:12620238, PubMed:17560374, PubMed:17967870, PubMed:19473982, PubMed:20154138, PubMed:22103349, PubMed:9230442). Acts as a direct caspase inhibitor (PubMed:11257230, PubMed:11257231, PubMed:12620238). Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry (PubMed:11257230, PubMed:11257231, PubMed:16352606, PubMed:16916640). Inactivates CASP9 by keeping it in a monomeric, inactive state (PubMed:12620238). Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS, PTEN and BIRC5/survivin (PubMed:17560374, PubMed:17967870, PubMed:19473982, PubMed:20154138, PubMed:22103349, PubMed:22607974, PubMed:29452636, PubMed:30026309). Acts as an important regulator of innate immunity by mediating 'Lys-63'-linked polyubiquitination of RIPK2 downstream of NOD1 and NOD2, thereby transforming RIPK2 into a scaffolding protein for downstream effectors, ultimately leading to activation of the NF-kappa-B and MAP kinases signaling (PubMed:19667203, PubMed:22607974, PubMed:29452636, PubMed:30026309). 'Lys-63'-linked polyubiquitination of RIPK2 also promotes recruitment of the LUBAC complex to RIPK2 (PubMed:22607974, PubMed:29452636). Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation (PubMed:17560374). Ubiquitination of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation (PubMed:20154138). Ubiquitination of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation (PubMed:17967870, PubMed:22103349). Plays a role in copper homeostasis by ubiquitinating COMMD1 and promoting its proteasomal degradation (PubMed:14685266). Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation (PubMed:21145488). Ubiquitinates and therefore mediates the proteasomal degradation of BCL2 in response to apoptosis (PubMed:29020630). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner (PubMed:22095281). Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8 (PubMed:22095281). Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and AES (PubMed:22304967). Ubiquitination of TLE3 results in inhibition of its interaction with TCF7L2/TCF4 thereby allowing efficient recruitment and binding of the transcriptional coactivator beta-catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional program (PubMed:22304967)
Diseases associated with XIAP
Curated MONDO disease pages that list XIAP among their top associated genes.