Protein: P98170

UniprotKB AC UniprotKB ID Gene name Full name Species Curated set
P98170 (Uniprot) XIAP_HUMAN XIAP E3 ubiquitin-protein ligase XIAP human No
Uniprot: 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. more..
MoonDB Dissimilar Functions
GO ID 1 Function 1 Module ID 1 GO ID 2 Function 2 Module ID 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0009056 catabolic process 125 GO:0009059 macromolecule biosynthetic process 270 6.37e-04 1.88e-40
Biological Processes
Module ID (MoonGO) GO ID (BP) GO Name
125 GO:0044248 cellular catabolic process
125 GO:0016567 protein ubiquitination
125 GO:0060255 regulation of macromolecule metabolic process
131 GO:0070647 protein modification by small protein conjugation or removal
131 GO:0006355 regulation of transcription, DNA-templated
270 GO:0034645 cellular macromolecule biosynthetic process
270 GO:0010467 gene expression
270 GO:0090304 nucleic acid metabolic process
270 GO:0032446 protein modification by small protein conjugation
270 GO:0060255 regulation of macromolecule metabolic process
270 GO:0007165 signal transduction
375 GO:0070647 protein modification by small protein conjugation or removal
375 GO:0060255 regulation of macromolecule metabolic process
450 GO:0051252 regulation of RNA metabolic process
450 GO:0010646 regulation of cell communication
450 GO:2000112 regulation of cellular macromolecule biosynthetic process
450 GO:0010468 regulation of gene expression
450 GO:0023051 regulation of signaling
450 GO:0007165 signal transduction
565 GO:0008283 cell proliferation
565 GO:0022607 cellular component assembly
565 GO:0071310 cellular response to organic substance
565 GO:0097191 extrinsic apoptotic signaling pathway
565 GO:0010467 gene expression
565 GO:0043066 negative regulation of apoptotic process
565 GO:0032270 positive regulation of cellular protein metabolic process
565 GO:0044093 positive regulation of molecular function
565 GO:0009967 positive regulation of signal transduction
565 GO:0006508 proteolysis
565 GO:0050790 regulation of catalytic activity
565 GO:1902531 regulation of intracellular signal transduction
565 GO:1901700 response to oxygen-containing compound
620 GO:0019538 protein metabolic process
620 GO:0006355 regulation of transcription, DNA-templated
620 GO:0006366 transcription from RNA polymerase II promoter
652 GO:0044267 cellular protein metabolic process
652 GO:0060255 regulation of macromolecule metabolic process
Cellular Components
Module ID (MoonGO) GO ID (CC) GO Name
125 GO:0005829 cytosol
125 GO:0005634 nucleus
131 GO:0005829 cytosol
131 GO:0043232 intracellular non-membrane-bounded organelle
131 GO:0005634 nucleus
270 GO:0005829 cytosol
270 GO:0070013 intracellular organelle lumen
270 GO:0005634 nucleus
375 GO:0005829 cytosol
375 GO:0005634 nucleus
450 GO:0005634 nucleus
565 GO:0005829 cytosol
565 GO:0005634 nucleus
565 GO:0098805 whole membrane
620 GO:0031981 nuclear lumen
652 GO:0005829 cytosol
652 GO:0005634 nucleus
652 GO:0031982 vesicle
GO ID (BP) GO Name Evidence Code (GO EC)
GO:0006915 apoptotic process IEA
GO:0006974 cellular response to DNA damage stimulus IEP
GO:0016055 Wnt signaling pathway IEA
GO:0016567 protein ubiquitination IEA
GO:0030510 regulation of BMP signaling pathway TAS
GO:0031398 positive regulation of protein ubiquitination IDA
GO:0042127 regulation of cell proliferation TAS
GO:0043066 negative regulation of apoptotic process IMP
GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process IDA
GO:0045088 regulation of innate immune response TAS
GO:0050727 regulation of inflammatory response TAS
GO:0055070 copper ion homeostasis TAS
GO:0070424 regulation of nucleotide-binding oligomerization domain containing signaling pathway TAS
GO:0090263 positive regulation of canonical Wnt signaling pathway IMP
GO:0090307 mitotic spindle assembly IBA
GO:1902530 positive regulation of protein linear polyubiquitination IDA
GO:1990001 inhibition of cysteine-type endopeptidase activity involved in apoptotic process IBA
GO ID (CC) GO Name Evidence Code (GO EC)
GO:0005634 nucleus IDA
GO:0005654 nucleoplasm TAS
GO:0005737 cytoplasm IDA
GO:0005829 cytosol TAS
No pairs of PrOnto dissimilar CC GO terms found.
PMID Article Title
8552191 Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes.
8654366 A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors.
9230442 X-linked IAP is a direct inhibitor of cell-death proteases.
10548111 NMR structure and mutagenesis of the inhibitor-of-apoptosis protein XIAP.
11140637 Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain.
11257231 Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain.
11447297 Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death.
11604410 HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins.
12121969 Proteasome-mediated degradation of Smac during apoptosis: XIAP promotes Smac ubiquitination in vitro.
12620238 Mechanism of XIAP-mediated inhibition of caspase-9.
12747801 Identification of ubiquitination sites on the X-linked inhibitor of apoptosis protein.
14645242 Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis protein (XIAP).
14685266 A novel role for XIAP in copper homeostasis through regulation of MURR1.
15029247 The mitochondrial ARTS protein promotes apoptosis through targeting XIAP.
15317454 Discovery of potent antagonists of the antiapoptotic protein XIAP for the treatment of cancer.
15489334 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15665297 cIAP1 Localizes to the nuclear compartment and modulates the cell cycle.
15772651 The DNA sequence of the human X chromosome.
17080092 XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome.
17336535 Structure-activity based study of the Smac-binding pocket within the BIR3 domain of XIAP.
17382285 XIAP: cell death regulation meets copper homeostasis.
17560374 XIAP induces NF-kappaB activation via the BIR1/TAB1 interaction and BIR1 dimerization.
17698078 Crystal structure of the BIR1 domain of XIAP in two crystal forms.
17967870 Apoptosis-inducing factor is a target for ubiquitination through interaction with XIAP.
18068114 Nuclear localized protein-1 (Nulp1) increases cell death of human osteosarcoma cells and binds the X-linked inhibitor of apoptosis protein.
18414036 IAPs: more than just inhibitors of apoptosis proteins.
18669648 A quantitative atlas of mitotic phosphorylation.
19473982 X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization.
20154138 Regulation of the copper chaperone CCS by XIAP-mediated ubiquitination.
20171186 Molecular interaction between HAX-1 and XIAP inhibits apoptosis.
20651737 IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer.
20670888 Transnitrosylation of XIAP regulates caspase-dependent neuronal cell death.
20888210 To fight or die - inhibitor of apoptosis proteins at the crossroad of innate immunity and death.
21145488 Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3 ligases.
21269460 Initial characterization of the human central proteome.
21447281 Inhibitor of apoptosis (IAP) proteins in regulation of inflammation and innate immunity.
21536684 Survivin monomer plays an essential role in apoptosis regulation.
21849505 The USP19 deubiquitinase regulates the stability of c-IAP1 and c-IAP2.
21931591 cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).
22095281 IAPs: guardians of RIPK1.
22103349 Nondegradative ubiquitination of apoptosis inducing factor (AIF) by X-linked inhibitor of apoptosis at a residue critical for AIF-mediated chromatin degradation.
22304967 XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt signaling.
OMIM ID Disease Name
300635 Lymphoproliferative syndrome, X-linked, 2
Domain Name Domain ID Source
BIR_rpt IPR001370 InterPro
Znf_RING IPR001841 InterPro
BIR PF00653 Pfam
BIR_REPEAT_1 PS01282 PROSITE
ZF_RING_2 PS50089 PROSITE
BIR_REPEAT_2 PS50143 PROSITE
S69544 S69544 PIR
RING SM00184 SMART
BIR SM00238 SMART
BIR cd00022 CDD