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P98170 (XIAP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase XIAP

EC=6.3.2.-
Alternative name(s):
Baculoviral IAP repeat-containing protein 4
IAP-like protein
Short name=ILP
Short name=hILP
Inhibitor of apoptosis protein 3
Short name=IAP-3
Short name=hIAP-3
Short name=hIAP3
X-linked inhibitor of apoptosis protein
Short name=X-linked IAP
Gene names
Name:XIAP
Synonyms:API3, BIRC4, IAP3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length497 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.7 Ref.8 Ref.10 Ref.12 Ref.14 Ref.20 Ref.22 Ref.26 Ref.27 Ref.30 Ref.36 Ref.44

Subunit structure

Monomer, and homodimer. Interacts with DIABLO/SMAC and with PRSS25; these interactions inhibit apoptotic suppressor activity. Interacts with TAB1/MAP3K7IP1 and AIFM1. Interaction with SMAC hinders binding of TAB1/MAP3K7IP1 and AIFM1. Interacts with TCF25 and COMMD1. Interacts with SEPT4 isoform 6 but not with other SEPT4 isoforms. Interacts with RIP1, RIP2, RIP3, RIP4, CCS and USP19. Interacts (via BIR 2 domain and BIR 3 domain) with HAX1 (via C-terminus) and this interaction blocks ubiquitination of XIAP/BIRC4. Interacts with the monomeric form of BIRC5/survivin. Interacts with TLE3 and TCF7L2/TCF4. Ref.12 Ref.13 Ref.18 Ref.20 Ref.22 Ref.23 Ref.27 Ref.32 Ref.33 Ref.34 Ref.36 Ref.43

Subcellular location

Cytoplasm. Nucleus. Note: TLE3 promotes its nuclear localization. Ref.15 Ref.36

Tissue specificity

Ubiquitous, except peripheral blood leukocytes.

Domain

The first BIR domain is involved in interaction with TAB1/MAP3K7IP1 and is important for dimerization. The second BIR domain is sufficient to inhibit CASP3 and CASP7, while the third BIR is involved in CASP9 inhibition. The interactions with DIABLO/SMAC and PRSS25 are mediated by the second and third BIR domains.

Post-translational modification

S-Nitrosylation down-regulates its E3 ubiquitin-protein ligase activity.

Autoubiquitinated and degraded by the proteasome in apoptotic cells.

Phosphorylation by PKB/AKT protects XIAP against ubiquitination and protects the protein against proteasomal degradation.

Involvement in disease

Lymphoproliferative syndrome, X-linked, 2 (XLP2) [MIM:300635]: A rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16

Sequence similarities

Belongs to the IAP family.

Contains 3 BIR repeats.

Contains 1 RING-type zinc finger.

Ontologies

Keywords
   Biological processApoptosis
Ubl conjugation pathway
Wnt signaling pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DomainRepeat
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionLigase
Protease inhibitor
Thiol protease inhibitor
   PTMIsopeptide bond
Phosphoprotein
S-nitrosylation
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

apoptotic process

Traceable author statement. Source: Reactome

cellular response to DNA damage stimulus

Inferred from expression pattern PubMed 18049476. Source: UniProtKB

copper ion homeostasis

Traceable author statement Ref.17. Source: UniProtKB

intrinsic apoptotic signaling pathway

Traceable author statement. Source: Reactome

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 18049476PubMed 22173242. Source: UniProtKB

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 11583623. Source: UniProtKB

positive regulation of canonical Wnt signaling pathway

Inferred from mutant phenotype Ref.36. Source: UniProtKB

positive regulation of protein linear polyubiquitination

Inferred from direct assay Ref.34. Source: UniProtKB

positive regulation of protein ubiquitination

Inferred from direct assay Ref.34. Source: UniProtKB

protein ubiquitination

Inferred from direct assay Ref.22Ref.27Ref.34Ref.36. Source: GOC

regulation of BMP signaling pathway

Traceable author statement Ref.19. Source: UniProtKB

regulation of cell proliferation

Traceable author statement Ref.19. Source: UniProtKB

regulation of inflammatory response

Traceable author statement Ref.31. Source: UniProtKB

regulation of innate immune response

Traceable author statement Ref.31. Source: UniProtKB

regulation of nucleotide-binding oligomerization domain containing signaling pathway

Traceable author statement Ref.24. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay Ref.15Ref.36. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.36. Source: UniProtKB

   Molecular_functioncysteine-type endopeptidase inhibitor activity involved in apoptotic process

Inferred from direct assay Ref.7. Source: ProtInc

ubiquitin-protein ligase activity

Inferred from direct assay Ref.22Ref.27Ref.34Ref.36. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 497497E3 ubiquitin-protein ligase XIAP
PRO_0000122352

Regions

Repeat26 – 9368BIR 1
Repeat163 – 23068BIR 2
Repeat265 – 33066BIR 3
Zinc finger450 – 48536RING-type
Region141 – 1499Interaction with caspase-7

Sites

Metal binding3001Zinc By similarity
Metal binding3031Zinc By similarity
Metal binding3201Zinc By similarity
Metal binding3271Zinc By similarity

Amino acid modifications

Modified residue871Phosphoserine; by PKB Ref.14 Ref.43
Modified residue4501S-nitrosocysteine Ref.25
Cross-link322Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.11
Cross-link328Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.11

Natural variations

Natural variant1071N → S. Ref.3
Corresponds to variant rs28382721 [ dbSNP | Ensembl ].
VAR_022282
Natural variant1331S → F. Ref.3
Corresponds to variant rs28382722 [ dbSNP | Ensembl ].
VAR_022283
Natural variant2421D → E. Ref.3
Corresponds to variant rs28382723 [ dbSNP | Ensembl ].
VAR_022284
Natural variant4231Q → P. Ref.1 Ref.3
Corresponds to variant rs5956583 [ dbSNP | Ensembl ].
VAR_022285

Experimental info

Mutagenesis751Y → G: Loss of interaction with TAB1/MAP3K7IP1; when associated with G-75. Ref.44
Mutagenesis801V → A: Strongly reduced interaction with TAB1/MAP3K7IP1. Reduced activation of MAP3K7/TAK1. Reduced activation of NF-kappa-B. Ref.44
Mutagenesis801V → D: Loss of interaction with TAB1/MAP3K7IP1. Reduced activation of MAP3K7/TAK1. Strongly reduced activation of NF-kappa-B. Ref.44
Mutagenesis861V → E: Loss of dimerization. Reduces activation of NF-kappa-B. Ref.44
Mutagenesis871S → A: No effect on dimerization. Ref.43
Mutagenesis871S → D or E: Abolishes dimerization. Interferes with ubiquitination. Ref.43
Mutagenesis981L → G: Loss of interaction with TAB1/MAP3K7IP1; when associated with G-75. Ref.44
Mutagenesis1411L → A: Reduced inhibition of caspase-3. Ref.37
Mutagenesis1471V → A: Reduced inhibition of caspase-3. Ref.37
Mutagenesis1481D → A: Abolishes inhibition of caspase-3. Reduced interaction with PRSS25; when associated with S-214. Ref.9 Ref.37
Mutagenesis1491I → A: Reduced inhibition of caspase-3. Ref.37
Mutagenesis1511D → A: Reduced inhibition of caspase-3. Ref.37
Mutagenesis1671L → A: Reduced inhibition of caspase-3. Ref.37
Mutagenesis1961D → A: Reduced inhibition of caspase-3. May affect protein folding and stability. Ref.37
Mutagenesis2141D → S: Reduced interaction with PRSS25. Reduced interaction with PRSS25; when associated with A-148. Ref.9
Mutagenesis2591N → D: Reduced interaction with PRSS25; when associated with S-314. Ref.9
Mutagenesis3101W → R: Reduced interaction with PRSS25; when associated with S-314. Ref.9
Mutagenesis3141E → S: Decreased interaction with DIABLO/SMAC and with PRSS25. Decreases interaction with PRSS25; when associated with D-259 or A-310. Ref.9
Mutagenesis4501C → A or S: Inhibits degradation of active caspase-3. Ref.8
Mutagenesis4671H → A: Loss of E3 ubiquitin-protein ligase activity. Ref.20
Sequence conflict1621S → C in AAC50373. Ref.2

Secondary structure

..................................................................................................... 497
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P98170 [UniParc].

Last modified January 24, 2001. Version 2.
Checksum: 9D394C16D45EB635

FASTA49756,685
        10         20         30         40         50         60 
MTFNSFEGSK TCVPADINKE EEFVEEFNRL KTFANFPSGS PVSASTLARA GFLYTGEGDT 

        70         80         90        100        110        120 
VRCFSCHAAV DRWQYGDSAV GRHRKVSPNC RFINGFYLEN SATQSTNSGI QNGQYKVENY 

       130        140        150        160        170        180 
LGSRDHFALD RPSETHADYL LRTGQVVDIS DTIYPRNPAM YSEEARLKSF QNWPDYAHLT 

       190        200        210        220        230        240 
PRELASAGLY YTGIGDQVQC FCCGGKLKNW EPCDRAWSEH RRHFPNCFFV LGRNLNIRSE 

       250        260        270        280        290        300 
SDAVSSDRNF PNSTNLPRNP SMADYEARIF TFGTWIYSVN KEQLARAGFY ALGEGDKVKC 

       310        320        330        340        350        360 
FHCGGGLTDW KPSEDPWEQH AKWYPGCKYL LEQKGQEYIN NIHLTHSLEE CLVRTTEKTP 

       370        380        390        400        410        420 
SLTRRIDDTI FQNPMVQEAI RMGFSFKDIK KIMEEKIQIS GSNYKSLEVL VADLVNAQKD 

       430        440        450        460        470        480 
SMQDESSQTS LQKEISTEEQ LRRLQEEKLC KICMDRNIAI VFVPCGHLVT CKQCAEAVDK 

       490 
CPMCYTVITF KQKIFMS 

« Hide

References

« Hide 'large scale' references
[1]"A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors."
Duckett C.S., Nava V.E., Gedrich R.W., Clem R.J., van Dongen J.L., Gilfillan M.C., Shiels H., Hardwick J.M., Thompson C.B.
EMBO J. 15:2685-2694(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-423.
Tissue: Fetal heart.
[2]"Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes."
Liston P., Roy N., Tamai K., Lefebvre C., Baird S., Cherton-Horvat G., Farahani R., McLean M., Ikeda J., Mackenzie A., Korneluk R.G.
Nature 379:349-353(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal brain.
[3]NIEHS SNPs program
Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-107; PHE-133; GLU-242 AND PRO-423.
[4]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Uterus.
[7]"X-linked IAP is a direct inhibitor of cell-death proteases."
Deveraux Q.L., Takahashi R., Salvesen G.S., Reed J.C.
Nature 388:300-304(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"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."
Suzuki Y., Nakabayashi Y., Takahashi R.
Proc. Natl. Acad. Sci. U.S.A. 98:8662-8667(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF CYS-450.
[9]"HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins."
Verhagen A.M., Silke J., Ekert P.G., Pakusch M., Kaufmann H., Connolly L.M., Day C.L., Tikoo A., Burke R., Wrobel C., Moritz R.L., Simpson R.J., Vaux D.L.
J. Biol. Chem. 277:445-454(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ASP-148; ASP-214; ASN-259; TRP-310 AND GLU-314.
[10]"Proteasome-mediated degradation of Smac during apoptosis: XIAP promotes Smac ubiquitination in vitro."
MacFarlane M., Merrison W., Bratton S.B., Cohen G.M.
J. Biol. Chem. 277:36611-36616(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Identification of ubiquitination sites on the X-linked inhibitor of apoptosis 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) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOUBIQUITINATION AT LYS-322 AND LYS-328.
[12]"A novel role for XIAP in copper homeostasis through regulation of MURR1."
Burstein E., Ganesh L., Dick R.D., van De Sluis B., Wilkinson J.C., Klomp L.W., Wijmenga C., Brewer G.J., Nabel G.J., Duckett C.S.
EMBO J. 23:244-254(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH COMMD1, FUNCTION.
[13]"The mitochondrial ARTS protein promotes apoptosis through targeting XIAP."
Gottfried Y., Rotem A., Lotan R., Steller H., Larisch S.
EMBO J. 23:1627-1635(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SEPT4.
[14]"Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis 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) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-87, UBIQUITINATION, PROTEASOMAL DEGRADATION.
[15]"cIAP1 Localizes to the nuclear compartment and modulates the cell cycle."
Samuel T., Okada K., Hyer M., Welsh K., Zapata J.M., Reed J.C.
Cancer Res. 65:210-218(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[16]"XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome."
Rigaud S., Fondaneche M.-C., Lambert N., Pasquier B., Mateo V., Soulas P., Galicier L., Le Deist F., Rieux-Laucat F., Revy P., Fischer A., de Saint Basile G., Latour S.
Nature 444:110-114(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN XLP2.
[17]"XIAP: cell death regulation meets copper homeostasis."
Mufti A.R., Burstein E., Duckett C.S.
Arch. Biochem. Biophys. 463:168-174(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[18]"Nuclear localized protein-1 (Nulp1) increases cell death of human osteosarcoma cells and binds the X-linked inhibitor of apoptosis protein."
Steen H., Lindholm D.
Biochem. Biophys. Res. Commun. 366:432-437(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TCF25.
[19]"IAPs: more than just inhibitors of apoptosis proteins."
Dubrez-Daloz L., Dupoux A., Cartier J.
Cell Cycle 7:1036-1046(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[20]"Apoptosis-inducing factor is a target for ubiquitination through interaction with XIAP."
Wilkinson J.C., Wilkinson A.S., Galban S., Csomos R.A., Duckett C.S.
Mol. Cell. Biol. 28:237-247(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF HIS-467, INTERACTION WITH AIFM1.
[21]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[22]"X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization."
Van Themsche C., Leblanc V., Parent S., Asselin E.
J. Biol. Chem. 284:20462-20466(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THE UBIQUITINATION OF PTEN, INTERACTION WITH PTEN.
[23]"Molecular interaction between HAX-1 and XIAP inhibits apoptosis."
Kang Y.J., Jang M., Park Y.K., Kang S., Bae K.H., Cho S., Lee C.K., Park B.C., Chi S.W., Park S.G.
Biochem. Biophys. Res. Commun. 393:794-799(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HAX1.
[24]"To fight or die - inhibitor of apoptosis proteins at the crossroad of innate immunity and death."
Lopez J., Meier P.
Curr. Opin. Cell Biol. 22:872-881(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[25]"Transnitrosylation of XIAP regulates caspase-dependent neuronal cell death."
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) [PubMed] [Europe PMC] [Abstract]
Cited for: S-NITROSYLATION AT CYS-450.
[26]"Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3 ligases."
Broemer M., Tenev T., Rigbolt K.T., Hempel S., Blagoev B., Silke J., Ditzel M., Meier P.
Mol. Cell 40:810-822(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE OF THE NEDD8 CONJUGATION PATHWAY.
[27]"Regulation of the copper chaperone CCS by XIAP-mediated ubiquitination."
Brady G.F., Galban S., Liu X., Basrur V., Gitlin J.D., Elenitoba-Johnson K.S., Wilson T.E., Duckett C.S.
Mol. Cell. Biol. 30:1923-1936(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THE UBIQUITINATION OF CCS, INTERACTION WITH CCS.
[28]"IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer."
Gyrd-Hansen M., Meier P.
Nat. Rev. Cancer 10:561-574(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[29]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[30]"Nondegradative ubiquitination of apoptosis inducing factor (AIF) by X-linked inhibitor of apoptosis at a residue critical for AIF-mediated chromatin degradation."
Lewis E.M., Wilkinson A.S., Davis N.Y., Horita D.A., Wilkinson J.C.
Biochemistry 50:11084-11096(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THE UBIQUITINATION OF AIFM1.
[31]"Inhibitor of apoptosis (IAP) proteins in regulation of inflammation and innate immunity."
Damgaard R.B., Gyrd-Hansen M.
Discov. Med. 11:221-231(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[32]"Survivin monomer plays an essential role in apoptosis regulation."
Pavlyukov M.S., Antipova N.V., Balashova M.V., Vinogradova T.V., Kopantzev E.P., Shakhparonov M.I.
J. Biol. Chem. 286:23296-23307(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BIRC5/SURVIVIN.
[33]"The USP19 deubiquitinase regulates the stability of c-IAP1 and c-IAP2."
Mei Y., Hahn A.A., Hu S., Yang X.
J. Biol. Chem. 286:35380-35387(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH USP19.
[34]"cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4)."
Bertrand M.J., Lippens S., Staes A., Gilbert B., Roelandt R., De Medts J., Gevaert K., Declercq W., Vandenabeele P.
PLoS ONE 6:E22356-E22356(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RIPK1; RIPK2; RIPK3 AND RIPK4.
[35]"IAPs: guardians of RIPK1."
Darding M., Meier P.
Cell Death Differ. 19:58-66(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[36]"XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt signaling."
Hanson A.J., Wallace H.A., Freeman T.J., Beauchamp R.D., Lee L.A., Lee E.
Mol. Cell 45:619-628(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TLE3 AND TCF7L2/TCF4.
[37]"NMR structure and mutagenesis of the inhibitor-of-apoptosis protein XIAP."
Sun C., Cai M., Gunasekera A.H., Meadows R.P., Wang H., Chen J., Zhang H., Wu W., Xu N., Ng S.-C., Fesik S.W.
Nature 401:818-822(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 124-240, MUTAGENESIS OF LEU-141; VAL-147; ASP-148; ILE-149; ASP-151; LEU-167 AND ASP-196.
[38]"Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain."
Liu Z., Sun C., Olejniczak E.T., Meadows R.P., Betz S.F., Oost T., Herrmann J., Wu J.C., Fesik S.W.
Nature 408:1004-1008(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 238-358 IN COMPLEX WITH DIABLO/SMAC.
[39]"Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain."
Huang Y., Park Y.C., Rich R.L., Segal D., Myszka D.G., Wu H.
Cell 104:781-790(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 120-260 IN COMPLEX WITH CASP7.
[40]"Mechanism of XIAP-mediated inhibition of caspase-9."
Shiozaki E.N., Chai J., Rigotti D.J., Riedl S.J., Li P., Srinivasula S.M., Alnemri E.S., Fairman R., Shi Y.
Mol. Cell 11:519-527(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 253-350 IN COMPLEX WITH CASP9.
[41]"Discovery of potent antagonists of the antiapoptotic protein XIAP for the treatment of cancer."
Oost T.K., Sun C., Armstrong R.C., Al-Assaad A.-S., Betz S.F., Deckwerth T.L., Ding H., Elmore S.W., Meadows R.P., Olejniczak E.T., Oleksijew A., Oltersdorf T., Rosenberg S.H., Shoemaker A.R., Tomaselli K.J., Zou H., Fesik S.W.
J. Med. Chem. 47:4417-4426(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 241-356.
[42]"Structure-activity based study of the Smac-binding pocket within the BIR3 domain of XIAP."
Wist A.D., Gu L., Riedl S.J., Shi Y., McLendon G.L.
Bioorg. Med. Chem. 15:2935-2943(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 249-354.
[43]"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) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 10-99, PHOSPHORYLATION AT SER-87, MUTAGENESIS OF SER-87, SUBUNIT.
[44]"XIAP induces NF-kappaB activation via the BIR1/TAB1 interaction and BIR1 dimerization."
Lu M., Lin S.-C., Huang Y., Kang Y.J., Rich R., Lo Y.-C., Myszka D., Han J., Wu H.
Mol. Cell 26:689-702(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 10-99 IN COMPLEX WITH TAB1, FUNCTION, MUTAGENESIS OF TYR-75; VAL-80; VAL-86 AND LEU-98.
[45]"Solution structure of the RING domain of the baculoviral IAP repeat-containing protein 4 from Homo sapiens."
RIKEN structural genomics initiative (RSGI)
Submitted (MAR-2008) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 427-497.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U32974 mRNA. Translation: AAC50518.1.
U45880 mRNA. Translation: AAC50373.1.
AY886519 Genomic DNA. Translation: AAW62257.1.
AL121601 Genomic DNA. Translation: CAB95312.1.
CH471107 Genomic DNA. Translation: EAX11858.1.
CH471107 Genomic DNA. Translation: EAX11859.1.
CH471107 Genomic DNA. Translation: EAX11860.1.
CH471107 Genomic DNA. Translation: EAX11861.1.
BC032729 mRNA. Translation: AAH32729.1.
PIRS69544.
RefSeqNP_001158.2. NM_001167.3.
NP_001191330.1. NM_001204401.1.
UniGeneHs.356076.
Hs.736565.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1C9QNMR-A124-240[»]
1F9XNMR-A241-356[»]
1G3FNMR-A241-356[»]
1G73X-ray2.00C/D238-358[»]
1I3OX-ray2.70E/F124-240[»]
1I4OX-ray2.40C/D120-260[»]
1I51X-ray2.45E/F124-240[»]
1KMCX-ray2.90C/D124-242[»]
1NW9X-ray2.40A253-350[»]
1TFQNMR-A241-356[»]
1TFTNMR-A241-356[»]
2ECGNMR-A430-497[»]
2JK7X-ray2.82A241-356[»]
2KNANMR-A357-449[»]
2OPYX-ray2.80A249-354[»]
2OPZX-ray3.00A/B/C/D249-357[»]
2POIX-ray1.80A10-99[»]
2POPX-ray3.10B/D10-100[»]
2QRAX-ray2.50A/B/C/D10-99[»]
2VSLX-ray2.10A250-345[»]
3CLXX-ray2.70A/B/C/D241-356[»]
3CM2X-ray2.50A/B/C/D/E/F/G/H/I/J241-356[»]
3CM7X-ray3.10A/B/C/D241-356[»]
3EYLX-ray3.00A/B241-356[»]
3G76X-ray3.00A/B/C/D/E/F/G/H241-356[»]
3HL5X-ray1.80A/B256-346[»]
3UW4X-ray1.79A338-348[»]
3UW5X-ray1.71A/B296-348[»]
4EC4X-ray3.30A/B/C/D/E/F/G/J/K/L241-356[»]
4HY0X-ray2.84A/B/C/D/E/F/G/H238-357[»]
4IC2X-ray2.20A/B429-497[»]
4IC3X-ray1.78A/B429-497[»]
4J3YX-ray1.45A/C152-236[»]
4J44X-ray1.30A/C152-236[»]
4J45X-ray1.48A/C152-236[»]
4J46X-ray1.42A/C152-236[»]
4J47X-ray1.35A/C152-236[»]
4J48X-ray2.10A/C152-236[»]
4KJUX-ray1.60A/C152-236[»]
4KJVX-ray1.70A/C152-236[»]
ProteinModelPortalP98170.
SMRP98170. Positions 20-99, 124-240, 256-345, 357-497.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106828. 107 interactions.
DIPDIP-27626N.
IntActP98170. 39 interactions.
MINTMINT-141734.
STRING9606.ENSP00000347858.

Chemistry

BindingDBP98170.
ChEMBLCHEMBL4198.

Protein family/group databases

MEROPSI32.004.

PTM databases

PhosphoSiteP98170.

Polymorphism databases

DMDM12643387.

Proteomic databases

PaxDbP98170.
PeptideAtlasP98170.
PRIDEP98170.

Protocols and materials databases

DNASU331.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000355640; ENSP00000347858; ENSG00000101966.
ENST00000371199; ENSP00000360242; ENSG00000101966.
ENST00000434753; ENSP00000395230; ENSG00000101966.
GeneID331.
KEGGhsa:331.
UCSCuc004etx.3. human.

Organism-specific databases

CTD331.
GeneCardsGC0XP122993.
HGNCHGNC:592. XIAP.
HPACAB009203.
MIM300079. gene.
300635. phenotype.
neXtProtNX_P98170.
Orphanet2442. X-linked lymphoproliferative disease.
PharmGKBPA25361.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG243347.
HOGENOMHOG000232059.
HOVERGENHBG004848.
InParanoidP98170.
KOK04725.
OMAAMYSEEA.
PhylomeDBP98170.
TreeFamTF105356.

Enzyme and pathway databases

ReactomeREACT_578. Apoptosis.
SABIO-RKP98170.
SignaLinkP98170.

Gene expression databases

ArrayExpressP98170.
BgeeP98170.
CleanExHS_XIAP.
GenevestigatorP98170.

Family and domain databases

Gene3D1.10.1170.10. 4 hits.
InterProIPR001370. BIR.
IPR001841. Znf_RING.
[Graphical view]
PfamPF00653. BIR. 3 hits.
[Graphical view]
SMARTSM00238. BIR. 3 hits.
SM00184. RING. 1 hit.
[Graphical view]
PROSITEPS01282. BIR_REPEAT_1. 3 hits.
PS50143. BIR_REPEAT_2. 3 hits.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSXIAP. human.
EvolutionaryTraceP98170.
GeneWikiXIAP.
GenomeRNAi331.
NextBio1365.
PMAP-CutDBP98170.
PROP98170.
SOURCESearch...

Entry information

Entry nameXIAP_HUMAN
AccessionPrimary (citable) accession number: P98170
Secondary accession number(s): D3DTF2, Q9NQ14
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 24, 2001
Last modified: April 16, 2014
This is version 156 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM