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Protein

E3 ubiquitin-protein ligase XIAP

Gene

Xiap

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi299 – 2991ZincPROSITE-ProRule annotation
Metal bindingi302 – 3021ZincPROSITE-ProRule annotation
Metal bindingi319 – 3191ZincPROSITE-ProRule annotation
Metal bindingi326 – 3261ZincPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri449 – 48436RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Apoptosis, Ubl conjugation pathway, Wnt signaling pathway

Keywords - Ligandi

Metal-binding, Zinc

Protein family/group databases

MEROPSiI32.004.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase XIAP (EC:6.3.2.-)
Alternative name(s):
Baculoviral IAP repeat-containing protein 4
IAP homolog A
Inhibitor of apoptosis protein 3
Short name:
IAP-3
Short name:
mIAP-3
Short name:
mIAP3
X-linked inhibitor of apoptosis protein
Short name:
X-linked IAP
Gene namesi
Name:Xiap
Synonyms:Aipa, Api3, Birc4, Miha
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:107572. Xiap.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: TLE3 promotes its nuclear localization.By similarity

GO - Cellular componenti

  • cytoplasm Source: MGI
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 496496E3 ubiquitin-protein ligase XIAPPRO_0000122353Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei87 – 871Phosphoserine; by PKBBy similarity
Cross-linki321 – 321Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki327 – 327Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei449 – 4491S-nitrosocysteineBy similarity

Post-translational modificationi

S-Nitrosylation down-regulates its E3 ubiquitin-protein ligase activity.By similarity
Autoubiquitinated and degraded by the proteasome in apoptotic cells.By similarity
Phosphorylation by PKB/AKT protects XIAP against ubiquitination and protects the protein against proteasomal degradation.By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, S-nitrosylation, Ubl conjugation

Proteomic databases

EPDiQ60989.
MaxQBiQ60989.
PaxDbiQ60989.
PeptideAtlasiQ60989.
PRIDEiQ60989.

PTM databases

iPTMnetiQ60989.
PhosphoSiteiQ60989.

Expressioni

Gene expression databases

BgeeiQ60989.
CleanExiMM_XIAP.
ExpressionAtlasiQ60989. baseline and differential.
GenevisibleiQ60989. MM.

Interactioni

Subunit structurei

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 (By similarity). Interacts with TLE3 and TCF7L2/TCF4 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
HccsP537025EBI-517478,EBI-8579982
Htra2Q9JIY52EBI-517478,EBI-2365838

Protein-protein interaction databases

BioGridi198149. 7 interactions.
DIPiDIP-33721N.
IntActiQ60989. 7 interactions.
MINTiMINT-141707.
STRINGi10090.ENSMUSP00000026978.

Structurei

3D structure databases

ProteinModelPortaliQ60989.
SMRiQ60989. Positions 22-99, 127-237, 256-345, 351-495.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati26 – 9368BIR 1Add
BLAST
Repeati163 – 23068BIR 2Add
BLAST
Repeati264 – 32966BIR 3Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni141 – 1499Interaction with caspase-7By similarity

Domaini

The first BIR domain is involved in interaction with TAB1/MAP3K7IP1 and is important for dimerization. The second BIR domain is sufficient to inhibit caspase-3 and caspase-7, while the third BIR is involved in caspase-9 inhibition. The interactions with DIABLO/SMAC and PRSS25 are mediated by the second and third BIR domains (By similarity).By similarity

Sequence similaritiesi

Belongs to the IAP family.Curated
Contains 3 BIR repeats.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri449 – 48436RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1101. Eukaryota.
ENOG410YPNM. LUCA.
GeneTreeiENSGT00500000044782.
HOGENOMiHOG000232059.
HOVERGENiHBG004848.
InParanoidiQ60989.
KOiK04725.
OMAiPRNPAMY.
OrthoDBiEOG78H3TF.
TreeFamiTF105356.

Family and domain databases

Gene3Di1.10.1170.10. 3 hits.
3.30.40.10. 1 hit.
InterProiIPR001370. BIR_rpt.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF00653. BIR. 3 hits.
[Graphical view]
SMARTiSM00238. BIR. 3 hits.
SM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS01282. BIR_REPEAT_1. 3 hits.
PS50143. BIR_REPEAT_2. 3 hits.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q60989-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTFNSFEGTR TFVLADTNKD EEFVEEFNRL KTFANFPSSS PVSASTLARA
60 70 80 90 100
GFLYTGEGDT VQCFSCHAAI DRWQYGDSAV GRHRRISPNC RFINGFYFEN
110 120 130 140 150
GAAQSTNPGI QNGQYKSENC VGNRNPFAPD RPPETHADYL LRTGQVVDIS
160 170 180 190 200
DTIYPRNPAM CSEEARLKSF QNWPDYAHLT PRELASAGLY YTGADDQVQC
210 220 230 240 250
FCCGGKLKNW EPCDRAWSEH RRHFPNCFFV LGRNVNVRSE SGVSSDRNFP
260 270 280 290 300
NSTNSPRNPA MAEYEARIVT FGTWTSSVNK EQLARAGFYA LGEGDKVKCF
310 320 330 340 350
HCGGGLTDWK PSEDPWEQHA KWYPGCKYLL DEKGQEYINN IHLTHSLEES
360 370 380 390 400
LGRTAEKTPS LTKKIDDTIF QNPMVQEAIR MGFSFKDIKK TMEEKIQTSG
410 420 430 440 450
SSYLSLEVLI ADLVSAQKDN TEDESSQTSL QKDISTEEQL RRLQEEKLCK
460 470 480 490
ICMDRNIAIV FVPCGHLVTC KQCAEAVDKC PMCYTVITFK QKIFMS
Length:496
Mass (Da):56,079
Last modified:July 27, 2011 - v2
Checksum:iEE5D242D3C3DF12E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti208 – 2081K → E in AAC52594 (PubMed:8643514).Curated
Sequence conflicti317 – 3171E → D in AAB58376 (Ref. 2) Curated
Sequence conflicti322 – 3221W → C in AAB58376 (Ref. 2) Curated
Sequence conflicti346 – 3461S → P in AAB58376 (Ref. 2) Curated
Sequence conflicti360 – 3601S → P in AAB58376 (Ref. 2) Curated
Sequence conflicti388 – 3881I → L in AAB58376 (Ref. 2) Curated
Sequence conflicti449 – 4491C → S in AAB58376 (Ref. 2) Curated
Sequence conflicti462 – 4621V → F in AAB58376 (Ref. 2) Curated
Sequence conflicti468 – 4681V → A in AAB58376 (Ref. 2) Curated
Sequence conflicti490 – 4901K → N in AAB58376 (Ref. 2) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U36842 mRNA. Translation: AAC52594.1.
U88990 mRNA. Translation: AAB58376.1.
BX530028 Genomic DNA. Translation: CAM17468.1.
CH466570 Genomic DNA. Translation: EDL29039.1.
CH466570 Genomic DNA. Translation: EDL29040.1.
BC138528 mRNA. Translation: AAI38529.1.
BC145861 mRNA. Translation: AAI45862.1.
CCDSiCCDS30098.1.
RefSeqiNP_001288568.1. NM_001301639.1.
NP_001288570.1. NM_001301641.1.
NP_033818.2. NM_009688.3.
XP_006541488.1. XM_006541425.1.
XP_006541490.1. XM_006541427.1.
XP_011249279.1. XM_011250977.1.
UniGeneiMm.259879.

Genome annotation databases

EnsembliENSMUST00000026978; ENSMUSP00000026978; ENSMUSG00000025860.
ENSMUST00000055483; ENSMUSP00000061074; ENSMUSG00000025860.
ENSMUST00000115094; ENSMUSP00000110746; ENSMUSG00000025860.
ENSMUST00000115095; ENSMUSP00000110747; ENSMUSG00000025860.
GeneIDi11798.
KEGGimmu:11798.
UCSCiuc009tas.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U36842 mRNA. Translation: AAC52594.1.
U88990 mRNA. Translation: AAB58376.1.
BX530028 Genomic DNA. Translation: CAM17468.1.
CH466570 Genomic DNA. Translation: EDL29039.1.
CH466570 Genomic DNA. Translation: EDL29040.1.
BC138528 mRNA. Translation: AAI38529.1.
BC145861 mRNA. Translation: AAI45862.1.
CCDSiCCDS30098.1.
RefSeqiNP_001288568.1. NM_001301639.1.
NP_001288570.1. NM_001301641.1.
NP_033818.2. NM_009688.3.
XP_006541488.1. XM_006541425.1.
XP_006541490.1. XM_006541427.1.
XP_011249279.1. XM_011250977.1.
UniGeneiMm.259879.

3D structure databases

ProteinModelPortaliQ60989.
SMRiQ60989. Positions 22-99, 127-237, 256-345, 351-495.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198149. 7 interactions.
DIPiDIP-33721N.
IntActiQ60989. 7 interactions.
MINTiMINT-141707.
STRINGi10090.ENSMUSP00000026978.

Protein family/group databases

MEROPSiI32.004.

PTM databases

iPTMnetiQ60989.
PhosphoSiteiQ60989.

Proteomic databases

EPDiQ60989.
MaxQBiQ60989.
PaxDbiQ60989.
PeptideAtlasiQ60989.
PRIDEiQ60989.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000026978; ENSMUSP00000026978; ENSMUSG00000025860.
ENSMUST00000055483; ENSMUSP00000061074; ENSMUSG00000025860.
ENSMUST00000115094; ENSMUSP00000110746; ENSMUSG00000025860.
ENSMUST00000115095; ENSMUSP00000110747; ENSMUSG00000025860.
GeneIDi11798.
KEGGimmu:11798.
UCSCiuc009tas.2. mouse.

Organism-specific databases

CTDi331.
MGIiMGI:107572. Xiap.

Phylogenomic databases

eggNOGiKOG1101. Eukaryota.
ENOG410YPNM. LUCA.
GeneTreeiENSGT00500000044782.
HOGENOMiHOG000232059.
HOVERGENiHBG004848.
InParanoidiQ60989.
KOiK04725.
OMAiPRNPAMY.
OrthoDBiEOG78H3TF.
TreeFamiTF105356.

Miscellaneous databases

ChiTaRSiXiap. mouse.
PROiQ60989.
SOURCEiSearch...

Gene expression databases

BgeeiQ60989.
CleanExiMM_XIAP.
ExpressionAtlasiQ60989. baseline and differential.
GenevisibleiQ60989. MM.

Family and domain databases

Gene3Di1.10.1170.10. 3 hits.
3.30.40.10. 1 hit.
InterProiIPR001370. BIR_rpt.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF00653. BIR. 3 hits.
[Graphical view]
SMARTiSM00238. BIR. 3 hits.
SM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS01282. BIR_REPEAT_1. 3 hits.
PS50143. BIR_REPEAT_2. 3 hits.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors."
    Uren A.G., Pakusch M., Hawkins C.J., Puls K.L., Vaux D.L.
    Proc. Natl. Acad. Sci. U.S.A. 93:4974-4978(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6 X CBA.
    Tissue: Liver.
  2. Farahani R., Lefebvre C., Korneluk R.G., Mackenzie A.E.
    Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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: Brain.
  6. "XIAP regulates bi-phasic NF-kappaB induction involving physical interaction and ubiquitination of MEKK2."
    Winsauer G., Resch U., Hofer-Warbinek R., Schichl Y.M., de Martin R.
    Cell. Signal. 20:2107-2112(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN THE UBIQUITINATION OF MAP3K2/MEKK2, INTERACTION WITH MAP3K2/MEKK2.
  7. "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.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain and Spleen.

Entry informationi

Entry nameiXIAP_MOUSE
AccessioniPrimary (citable) accession number: Q60989
Secondary accession number(s): A2BGY6, O08865
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: July 6, 2016
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.