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Aliases for XIAP Gene

Aliases for XIAP Gene

  • X-Linked Inhibitor Of Apoptosis, E3 Ubiquitin Protein Ligase 2 3
  • BIRC4 3 4 6
  • API3 3 4 6
  • Baculoviral IAP Repeat-Containing Protein 4 3 4
  • Inhibitor Of Apoptosis Protein 3 3 4
  • IAP-Like Protein 3 4
  • X-Linked IAP 3 4
  • HIAP-3 3 4
  • IAP-3 3 4
  • HIAP3 3 4
  • XLP2 3 6
  • X-Linked Inhibitor Of Apoptosis Protein 4
  • Baculoviral IAP Repeat-Containing 4 2
  • E3 Ubiquitin-Protein Ligase XIAP 3
  • X-Linked Inhibitor Of Apoptosis 2
  • EC 6.3.2.- 4
  • ILP1 3
  • MIHA 3
  • IAP3 4
  • HILP 4
  • ILP 4

External Ids for XIAP Gene

Previous Symbols for XIAP Gene

  • API3
  • BIRC4

Summaries for XIAP Gene

Entrez Gene Summary for XIAP Gene

  • This gene encodes a protein that belongs to a family of apoptotic suppressor proteins. Members of this family share a conserved motif termed, baculovirus IAP repeat, which is necessary for their anti-apoptotic function. This protein functions through binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2 and inhibits apoptosis induced by menadione, a potent inducer of free radicals, and interleukin 1-beta converting enzyme. This protein also inhibits at least two members of the caspase family of cell-death proteases, caspase-3 and caspase-7. Mutations in this gene are the cause of X-linked lymphoproliferative syndrome. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 2 and 11.[provided by RefSeq, Feb 2011]

GeneCards Summary for XIAP Gene

XIAP (X-Linked Inhibitor Of Apoptosis, E3 Ubiquitin Protein Ligase) is a Protein Coding gene. Diseases associated with XIAP include lymphoproliferative syndrome, x-linked, 2 and chronic neutrophilic leukemia. Among its related pathways are Pathways in cancer and Akt Signaling. GO annotations related to this gene include ubiquitin-protein transferase activity and cysteine-type endopeptidase inhibitor activity involved in apoptotic process. An important paralog of this gene is NAIP.

UniProtKB/Swiss-Prot for XIAP Gene

  • 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.

Tocris Summary for XIAP Gene

  • Inhibitor of apoptosis (IAPs) are a family of proteins that are the major regulators of apoptosis through their interaction with the various components of the apoptotic signalling cascades. Originally discovered in baculovirus, the human homologues are sometimes described as baculovirus IAP repeat containing (BIRC) proteins. There are a number of different IAPs including neuronal apoptosis inhibitory protein (NAIP or BIRC1), cellular IAPs (c-IAP-1 and c-IAP-2, or BIRC2 and BIRC3 respectively), X-chromosome linked IAP (XIAP or BIRC4) and survivin (BIRC5). cIAP-1 and 2 function through interaction with TNF receptors and by binding to the mitochondrial protein, SMAC, preventing it binding to XIAP. Thought to be the most potent apoptosis suppressor, XIAP, directly binds and inhibits caspases -3, -7 and -9. Survivin, which also binds to several caspases, is up-regulated in a many tumour cell types.

Gene Wiki entry for XIAP Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for XIAP Gene

Genomics for XIAP Gene

Genomic Location for XIAP Gene

Start:
123,859,724 bp from pter
End:
123,913,979 bp from pter
Size:
54,256 bases
Orientation:
Plus strand

Genomic View for XIAP Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for XIAP Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for XIAP Gene

Regulatory Elements for XIAP Gene

Proteins for XIAP Gene

  • Protein details for XIAP Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P98170-XIAP_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase XIAP
    Protein Accession:
    P98170
    Secondary Accessions:
    • D3DTF2
    • Q9NQ14

    Protein attributes for XIAP Gene

    Size:
    497 amino acids
    Molecular mass:
    56685 Da
    Quaternary 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.

    Three dimensional structures from OCA and Proteopedia for XIAP Gene

neXtProt entry for XIAP Gene

Proteomics data for XIAP Gene at MOPED

Post-translational modifications for XIAP Gene

  • Autoubiquitinated and degraded by the proteasome in apoptotic cells.
  • Phosphorylation by PKB/AKT protects XIAP against ubiquitination and protects the protein against proteasomal degradation.
  • S-Nitrosylation down-regulates its E3 ubiquitin-protein ligase activity.
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys10, Lys31, Lys116, Lys168, Lys208, Lys322, Lys328, and Lys358

Other Protein References for XIAP Gene

No data available for DME Specific Peptides for XIAP Gene

Domains for XIAP Gene

Gene Families for XIAP Gene

HGNC:
  • BIRC :Baculoviral IAP repeat containing

Protein Domains for XIAP Gene

UniProtKB/Swiss-Prot:

XIAP_HUMAN
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:
    • P98170
Family:
  • Belongs to the IAP family.:
    • P98170
Similarity:
  • Contains 3 BIR repeats.:
    • P98170
  • Contains 1 RING-type zinc finger.:
    • P98170
genes like me logo Genes that share domains with XIAP: view

Function for XIAP Gene

Molecular function for XIAP Gene

UniProtKB/Swiss-Prot 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.

Enzyme Numbers (IUBMB) for XIAP Gene

Gene Ontology (GO) - Molecular Function for XIAP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 ubiquitin-protein transferase activity IDA 19473982
GO:0005515 protein binding IPI 11257230
GO:0008270 zinc ion binding IEA --
GO:0016874 ligase activity IEA --
GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process IDA 9230442
genes like me logo Genes that share ontologies with XIAP: view
genes like me logo Genes that share phenotypes with XIAP: view

Animal Models for XIAP Gene

MGI Knock Outs for XIAP:

No data available for Transcription Factor Targeting and HOMER Transcription for XIAP Gene

Localization for XIAP Gene

Subcellular locations from UniProtKB/Swiss-Prot for XIAP Gene

Cytoplasm. Nucleus. Note=TLE3 promotes its nuclear localization.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for XIAP Gene COMPARTMENTS Subcellular localization image for XIAP gene
Compartment Confidence
nucleus 5
cytosol 4
mitochondrion 3
plasma membrane 2
cytoskeleton 1
endoplasmic reticulum 1
extracellular 1

Gene Ontology (GO) - Cellular Components for XIAP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 22304967
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IDA 15665297
GO:0005829 cytosol TAS --
GO:0005876 NOT spindle microtubule IBA --
genes like me logo Genes that share ontologies with XIAP: view

Pathways for XIAP Gene

genes like me logo Genes that share pathways with XIAP: view

Gene Ontology (GO) - Biological Process for XIAP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006915 apoptotic process TAS --
GO:0006974 cellular response to DNA damage stimulus IEP 18049476
GO:0012501 programmed cell death TAS --
GO:0016055 Wnt signaling pathway IEA --
GO:0016567 protein ubiquitination IDA 19473982
genes like me logo Genes that share ontologies with XIAP: view

Compounds for XIAP Gene

(6) ApexBio Compounds for XIAP Gene

Compound Action Cas Number
AT-406 (SM-406) antagonist of the IAPs [1071992-99-8]
Birinapant (TL32711) inhibitor of IAP family proteins [1260251-31-7]
Embelin Cell-permeable, non-peptide inhibitor of XIAP [550-24-3]
GDC-0152 potent small-molecule antagonist of IAP proteins [873652-48-3]
LCL161 oral small molecule antagonist of IAPs [1005342-46-0]
YM155 smallest member of IAP gene family. [781661-94-7]

(1) Tocris Compounds for XIAP Gene

Compound Action Cas Number
Embelin Inhibitor of X-linked inhibitor of apoptosis (XIAP); cell-permeable and antitumor [550-24-3]

(80) Novoseek inferred chemical compound relationships for XIAP Gene

Compound -log(P) Hits PubMed IDs
ciap2 86.5 16
miha 85.4 20
ciap1 77.1 5
phenoxodiol 64.4 7
tab-1 61.5 7
genes like me logo Genes that share compounds with XIAP: view

Transcripts for XIAP Gene

Unigene Clusters for XIAP Gene

X-linked inhibitor of apoptosis:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for XIAP Gene

No ASD Table

Relevant External Links for XIAP Gene

GeneLoc Exon Structure for
XIAP
ECgene alternative splicing isoforms for
XIAP

Expression for XIAP Gene

mRNA expression in normal human tissues for XIAP Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for XIAP Gene

SOURCE GeneReport for Unigene cluster for XIAP Gene Hs.356076

mRNA Expression by UniProt/SwissProt for XIAP Gene

P98170-XIAP_HUMAN
Tissue specificity: Ubiquitous, except peripheral blood leukocytes
genes like me logo Genes that share expressions with XIAP: view

Orthologs for XIAP Gene

This gene was present in the common ancestor of animals.

Orthologs for XIAP Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia XIAP 36
  • 98.93 (n)
  • 98.39 (a)
XIAP 37
  • 98 (a)
OneToOne
cow
(Bos Taurus)
Mammalia XIAP 36
  • 91.75 (n)
  • 87.73 (a)
XIAP 37
  • 88 (a)
OneToMany
dog
(Canis familiaris)
Mammalia BIRC4 37
  • 87 (a)
OneToMany
XIAP 36
  • 91.14 (n)
  • 87.42 (a)
mouse
(Mus musculus)
Mammalia Xiap 36
  • 90.05 (n)
  • 89.52 (a)
Xiap 16
Xiap 37
  • 90 (a)
OneToMany
oppossum
(Monodelphis domestica)
Mammalia -- 37
  • 78 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia -- 37
  • 62 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Xiap 36
  • 89.78 (n)
  • 89.92 (a)
chicken
(Gallus gallus)
Aves IAP3 37
  • 56 (a)
OneToMany
XIAP 36
  • 66.67 (n)
  • 59.18 (a)
lizard
(Anolis carolinensis)
Reptilia -- 37
  • 49 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia xiap 36
  • 61.71 (n)
  • 53.02 (a)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.4242 36
zebrafish
(Danio rerio)
Actinopterygii xiap 36
  • 55.56 (n)
  • 51.06 (a)
xiap 37
  • 42 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP012677 36
  • 52.07 (n)
  • 42.98 (a)
fruit fly
(Drosophila melanogaster)
Insecta Iap2 37
  • 30 (a)
ManyToMany
th 37
  • 25 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 19 (a)
ManyToMany
-- 37
  • 26 (a)
ManyToMany
-- 37
  • 56 (a)
ManyToMany
-- 37
  • 22 (a)
ManyToMany
-- 37
  • 48 (a)
ManyToMany
-- 37
  • 29 (a)
ManyToMany
-- 37
  • 38 (a)
ManyToMany
-- 37
  • 23 (a)
ManyToMany
Species with no ortholog for XIAP:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for XIAP Gene

ENSEMBL:
Gene Tree for XIAP (if available)
TreeFam:
Gene Tree for XIAP (if available)

Paralogs for XIAP Gene

Paralogs for XIAP Gene

Selected SIMAP similar genes for XIAP Gene using alignment to 3 proteins:

Pseudogenes.org Pseudogenes for XIAP Gene

genes like me logo Genes that share paralogs with XIAP: view

Variants for XIAP Gene

Sequence variations from dbSNP and Humsavar for XIAP Gene

SNP ID Clin Chr 0X pos Sequence Context AA Info Type MAF
rs8371 -- 123,912,065(+) AACTA(C/T)TCTTT utr-variant-3-prime, nc-transcript-variant
rs9856 -- 123,911,791(+) CACTT(C/T)AATAA utr-variant-3-prime, nc-transcript-variant
rs1474593 -- 123,861,754(+) ATATA(C/T)GTATT intron-variant
rs1474594 -- 123,861,867(+) ATTGC(C/T)CTCTC intron-variant
rs1535222 -- 123,895,291(+) ctttt(C/T)tattg intron-variant

Structural Variations from Database of Genomic Variants (DGV) for XIAP Gene

Variant ID Type Subtype PubMed ID
dgv2471e1 CNV Complex 17122850
nsv507991 CNV Insertion 20534489

Relevant External Links for XIAP Gene

HapMap Linkage Disequilibrium report
XIAP
Human Gene Mutation Database (HGMD)
XIAP
Locus Specific Mutation Databases (LSDB)
XIAP

Disorders for XIAP Gene

(1) OMIM Diseases for XIAP Gene (300079)

UniProtKB/Swiss-Prot

XIAP_HUMAN
  • 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. {ECO:0000269 PubMed:17080092}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(2) University of Copenhagen DISEASES for XIAP Gene

(64) Novoseek inferred disease relationships for XIAP Gene

Disease -log(P) Hits PubMed IDs
leukemia b-cell 66.6 1
cancer 62.4 80
tumors 60.2 112
leukemia 57.7 18
necrosis 57.1 13

Relevant External Links for XIAP

GeneTests
XIAP
GeneReviews
XIAP
Genetic Association Database (GAD)
XIAP
Human Genome Epidemiology (HuGE) Navigator
XIAP
genes like me logo Genes that share disorders with XIAP: view

Publications for XIAP Gene

  1. 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. (PMID: 11447297) Suzuki Y. … Takahashi R. (Proc. Natl. Acad. Sci. U.S.A. 2001) 3 4 23
  2. Proteasome-mediated degradation of Smac during apoptosis: XIAP promotes Smac ubiquitination in vitro. (PMID: 12121969) MacFarlane M. … Cohen G.M. (J. Biol. Chem. 2002) 3 4 23
  3. Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis protein (XIAP). (PMID: 14645242) Dan H.C. … Cheng J.Q. (J. Biol. Chem. 2004) 3 4 23
  4. cIAP1 Localizes to the nuclear compartment and modulates the cell cycle. (PMID: 15665297) Samuel T. … Reed J.C. (Cancer Res. 2005) 3 4 23
  5. XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome. (PMID: 17080092) Rigaud S. … Latour S. (Nature 2006) 3 4 23

Products for XIAP Gene

  • Addgene plasmids for XIAP

Sources for XIAP Gene

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