Names & Taxonomy

Uniprot ID:
P98170
Entry Name:
XIAP_HUMAN
Status:
reviewed
Protein Names:
E3 ubiquitin-protein ligase XIAP (EC 6.3.2.-) (Baculoviral IAP repeat-containing protein 4) (IAP-like protein) (ILP) (hILP) (Inhibitor of apoptosis protein 3) (IAP-3) (hIAP-3) (hIAP3) (X-linked inhibitor of apoptosis protein) (X-linked IAP)
Gene Names:
XIAP API3 BIRC4 IAP3
Gene Names Primary:
XIAP
Organism:
Homo sapiens (Human)

Structure

Length:
497
Sequence:
MTFNSFEGSKTCVPADINKEEEFVEEFNRLKTFANFPSGSPVSASTLARAGFLYTGEGDTVRCFSCHAAVDRWQYGDSAVGRHRKVSPNCRFINGFYLENSATQSTNSGIQNGQYKVENYLGSRDHFALDRPSETHADYLLRTGQVVDISDTIYPRNPAMYSEEARLKSFQNWPDYAHLTPRELASAGLYYTGIGDQVQCFCCGGKLKNWEPCDRAWSEHRRHFPNCFFVLGRNLNIRSESDAVSSDRNFPNSTNLPRNPSMADYEARIFTFGTWIYSVNKEQLARAGFYALGEGDKVKCFHCGGGLTDWKPSEDPWEQHAKWYPGCKYLLEQKGQEYINNIHLTHSLEECLVRTTEKTPSLTRRIDDTIFQNPMVQEAIRMGFSFKDIKKIMEEKIQISGSNYKSLEVLVADLVNAQKDSMQDESSQTSLQKEISTEEQLRRLQEEKLCKICMDRNIAIVFVPCGHLVTCKQCAEAVDKCPMCYTVITFKQKIFMS
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm. Nucleus. Note=TLE3 promotes its nuclear localization.

Function

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.
Gene Ontology Go:
cytoplasm
cytosol
nucleoplasm
nucleus
cysteine-type endopeptidase inhibitor activity involved in apoptotic process
ligase activity
ubiquitin protein ligase activity
ubiquitin-protein transferase activity
zinc ion binding
apoptotic process
cellular response to DNA damage stimulus
copper ion homeostasis
inhibition of cysteine-type endopeptidase activity involved in apoptotic process
intrinsic apoptotic signaling pathway
negative regulation of apoptotic process
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
positive regulation of canonical Wnt signaling pathway
positive regulation of protein linear polyubiquitination
positive regulation of protein ubiquitination
programmed cell death
protein ubiquitination
regulation of BMP signaling pathway
regulation of cell proliferation
regulation of inflammatory response
regulation of innate immune response
regulation of nucleotide-binding oligomerization domain containing signaling pathway
Wnt signaling pathway
Gene Ontology Biological Process:
apoptotic process
cellular response to DNA damage stimulus
copper ion homeostasis
inhibition of cysteine-type endopeptidase activity involved in apoptotic process
intrinsic apoptotic signaling pathway
negative regulation of apoptotic process
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
positive regulation of canonical Wnt signaling pathway
positive regulation of protein linear polyubiquitination
positive regulation of protein ubiquitination
programmed cell death
protein ubiquitination
regulation of BMP signaling pathway
regulation of cell proliferation
regulation of inflammatory response
regulation of innate immune response
regulation of nucleotide-binding oligomerization domain containing signaling pathway
Wnt signaling pathway
Gene Ontology Molecular Function:
cysteine-type endopeptidase inhibitor activity involved in apoptotic process
ligase activity
ubiquitin protein ligase activity
ubiquitin-protein transferase activity
zinc ion binding
Gene Ontology Cellular Component:
cytoplasm
cytosol
nucleoplasm
nucleus
Keywords:
3D-structure
Apoptosis
Complete proteome
Cytoplasm
Isopeptide bond
Ligase
Metal-binding
Nucleus
Phosphoprotein
Polymorphism
Protease inhibitor
Reference proteome
Repeat
S-nitrosylation
Thiol protease inhibitor
Ubl conjugation
Ubl conjugation pathway
Wnt signaling pathway
Zinc
Zinc-finger
Interacts With:
Q92851; P42574; P55210; P55211; P61024; Q9NR28; P19447; O43464; Q9JIY5; Q17RB8; Q9HC98; P46531; P63000; P40937; O43353; P57078; O43236-6; Q8IUQ4; Q9Y2D8; Q9Y4K3; P0CG48; P51668; P62837; P61077; P61088; Q13404; A5D8V6

Publication

PubMed ID:
8654366 8552191 15772651 15489334 9230442 11447297 11604410 12121969 12747801 14685266 15029247 14645242 15665297 17080092 17382285 18068114 18414036 17967870 18669648 19473982 20171186 20888210 20670888 21145488 20154138 20651737 21269460 22103349 21447281 21536684 21849505 21931591 22095281 22304967 10548111 11140637 11257231 12620238 15317454 17336535 17698078 17560374