Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  E3 ubiquitin-protein ligase XIAP  

UniProtKB / Swiss-Prot ID :  XIAP_HUMAN

Gene Name (Synonyms) : 
XIAP, API3, BIRC4, IAP3  

Species :  Homo sapiens (Human). 

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

Protein 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. 

Protein Sequence MTFNSFEGSKTCVPADINKEEEFVEEFNRLKTFANFPSGSPVSASTLARAGFLYTGEGDTVRCFSCHAAV...
Predicted Secondary Structure  -
Protein Variant
LocationDescription
107N -> S (in dbSNP:rs28382721). VAR_022282
133S -> F (in dbSNP:rs28382722). VAR_022283
242D -> E (in dbSNP:rs28382723). VAR_022284
423Q -> P (in dbSNP:rs5956583). VAR_022285
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
10Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)FEGSKTCVP
57.72Phosphositeplus
Link-
12S-nitrosocysteineGSKTCVPAD
3.87dbSNO
Link-
31Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)FNRLKTFAN
38.06Phosphositeplus
Link-
40PhosphoserineFPSGSPVSA
26.85HPRD
Link-
40PhosphoserineFPSGSPVSA
26.85PhosphoELM
Link-
87PhosphoserineHRKVSPNCR
17.27Phosphositeplus
Link-
87Phosphoserine (AKT1)HRKVSPNCR
17.27HPRD
Link-
87Phosphoserine (AKT2)HRKVSPNCR
17.27HPRD
Link-
87Phosphoserine (PKB_group;PKB_beta)HRKVSPNCR
17.27PhosphoELM
Link-
87Phosphoserine; by PKB.HRKVSPNCR
17.27UniProtKB
Link-
90S-nitrosocysteineVSPNCRFIN
4.22dbSNO
Link-
116Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)NGQYKVENY
34.87Phosphositeplus
Link-
123PhosphoserineNYLGSRDHF
31.75Phosphositeplus
Link
139PhosphotyrosineTHADYLLRT
14.39Phosphositeplus
Link
139Phosphotyrosine.THADYLLRT
14.39UniProtKB
Link
168Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)EARLKSFQN
43.61Phosphositeplus
Link
213S-nitrosocysteineNWEPCDRAW
3.61dbSNO
Link
300S-nitrosocysteineDKVKCFHCG
2.93dbSNO
Link-
303S-nitrosocysteineKCFHCGGGL
2.44dbSNO
Link-
322Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)EQHAKWYPG
45.17Phosphositeplus
Link-
322Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)EQHAKWYPG
45.17UbiProtDB
Link-
322Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin).EQHAKWYPG
45.17UniProtKB
Link-
327S-nitrosocysteineWYPGCKYLL
1.95dbSNO
Link-
328Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)YPGCKYLLE
44.86Phosphositeplus
Link-
328Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)YPGCKYLLE
44.86UbiProtDB
Link-
328Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin).YPGCKYLLE
44.86UniProtKB
Link-
351S-nitrosocysteineSLEECLVRT
2.88dbSNO
Link-
355PhosphothreonineCLVRTTEKT
31.65HPRD
Link-
356PhosphothreonineLVRTTEKTP
25.56HPRD
Link-
358Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)RTTEKTPSL
64.74Phosphositeplus
Link-
430PhosphoserineSSQTSLQKE
22.59Phosphositeplus
Link-
433Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)TSLQKEIST
63.41Phosphositeplus
Link-
436PhosphoserineQKEISTEEQ
30.75HPRD
Link-
450S-nitrosocysteine.EEKLCKICM
4.07UniProtKB
Link-
470PhosphothreonineGHLVTCKQC
21.98HPRD
Link-
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
There are no Protein-Protein Interactions.
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Disease Reference
Kegg disease
OMIM disease
300635Lymphoproliferative syndrome, X-linked, 2 (XLP2)
Drug Reference
There are no disease associations of PTM sites.
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Related Literatures of Post-Translational Modification
Phosphorylation
ReferencePubMed
"Akt phosphorylation and stabilization of X-linked inhibitor ofapoptosis protein (XIAP).";
Dan H.C., Sun M., Kaneko S., Feldman R.I., Nicosia S.V., Wang H.-G.,Tsang B.K., Cheng J.Q.;
J. Biol. Chem. 279:5405-5412(2004).
Cited for: FUNCTION, PHOSPHORYLATION AT SER-87, UBIQUITINATION, AND PROTEASOMALDEGRADATION.
"Tyrosine phosphorylated Par3 regulates epithelial tight junctionassembly promoted by EGFR signaling.";
Wang Y., Du D., Fang L., Yang G., Zhang C., Zeng R., Ullrich A.,Lottspeich F., Chen Z.;
EMBO J. 25:5058-5070(2006).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-139, AND MASSSPECTROMETRY.
"Crystal structure of the BIR1 domain of XIAP in two crystal forms.";
Lin S.-C., Huang Y., Lo Y.-C., Lu M., Wu H.;
J. Mol. Biol. 372:847-854(2007).
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 10-99, PHOSPHORYLATION ATSER-87, MUTAGENESIS OF SER-87, AND SUBUNIT.
S-nitrosylation
ReferencePubMed
"Transnitrosylation of XIAP regulates caspase-dependent neuronal celldeath.";
Nakamura T., Wang L., Wong C.C., Scott F.L., Eckelman B.P., Han X.,Tzitzilonis C., Meng F., Gu Z., Holland E.A., Clemente A.T.,Okamoto S., Salvesen G.S., Riek R., Yates J.R. III, Lipton S.A.;
Mol. Cell 39:184-195(2010).
Cited for: S-NITROSYLATION AT CYS-450.
Ubiquitylation
ReferencePubMed
"Identification of ubiquitination sites on the X-linked inhibitor ofapoptosis protein.";
Shin H., Okada K., Wilkinson J.C., Solomon K.M., Duckett C.S.,Reed J.C., Salvesen G.S.;
Biochem. J. 373:965-971(2003).
Cited for: AUTOUBIQUITINATION AT LYS-322 AND LYS-328.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures