InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Xiap

Summary

InnateDB Protein

IDBP-141326.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Xiap

Protein Name

X-linked inhibitor of apoptosis

Synonyms

1110015C02Rik; Aipa; Api3; Birc4; IAP3; ILP-1; MIHA;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000061074

InnateDB Gene

IDBG-141324 (Xiap)

Protein Structure

UniProt Annotation

Function

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. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. 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, CASP3, CASP7, CASP8, CASP9, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS and BIRC5/survivin. Ubiquitinion of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. Ubiquitinion of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation. Plays a role in copper homeostasis by ubiquitinationg COMMD1 and promoting its proteasomal degradation. Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation. Acts as an important regulator of innate immune signaling via regulation of Nodlike receptors (NLRs). 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. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and AES. 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. {ECO:0000269PubMed:18761086, ECO:0000269PubMed:19473982}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. Note=TLE3 promotes its nuclear localization. {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 19 experimentally validated interaction(s) in this database.
They are also associated with 119 interaction(s) predicted by orthology.

Experimentally validated
Total	19 [view]
Protein-Protein	19 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	119 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0002020	protease binding
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0016874	ligase activity
GO:0097110	scaffold protein binding

Biological Process

GO:0016055	Wnt signaling pathway
GO:0016567	protein ubiquitination
GO:0043066	negative regulation of apoptotic process
GO:0043154	negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043524	negative regulation of neuron apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0051402	neuron apoptotic process
GO:1990001	inhibition of cysteine-type endopeptidase activity involved in apoptotic process