XIAP (Homo sapiens)
Description [+]
- Synonyms: XIAP, HILP
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Baculoviral IAP repeat-containing protein 4 (EC 6.3.2.-)(E3 ubiquitin-protein ligase XIAP)(Inhibitor of apoptosis protein 3)(X-linked inhibitor of apoptosis protein)(X-linked IAP)(IAP-like protein)(HILP) [Source:UniProtKB/Swiss-Prot;Acc:P98170]
- Family: BIR-containing protein : IAP
- Process: apoptosis,
- Pathways: intrinsic pathway, extrinsic pathway,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Xiap
- WIKI: XIAP-H_sapiens
References [+]
- X-linked IAP is a direct inhibitor of cell-death proteases.
- Deveraux QL, Takahashi R, Salvesen GS, Reed JC
- The inhibitor-of-apoptosis (IAP) family of genes has an evolutionarily conserved role in regulating programmed cell death in animals ranging from insects to humans. Ectopic expression of human IAP proteins can suppress cell death induced by a variety of stimuli, but the mechanism of this inhibition was previously unknown. Here we show that human X-chromosome-linked IAP directly inhibits at least two members of the caspase family of cell-death proteases, caspase-3 and caspase-7. As the caspases are highly conserved throughout the animal kingdom and are the principal effectors of apoptosis, our findings suggest how IAPs might inhibit cell death, providing evidence for a mechanism of action for these mammalian cell-death suppressors. Nature. 1997 Jul 17;388(6639):300-4.
- References from Mouse ortholog(s):
- Characterization of XIAP-deficient mice.
- Harlin H, Reffey SB, Duckett CS, Lindsten T, Thompson CB
- The inhibitor of apoptosis protein (IAP) family consists of a number of evolutionarily conserved proteins that function to inhibit programmed cell death. X-linked IAP (XIAP) was cloned due to its sequence homology with other family members and has previously been shown to prevent apoptosis by binding to active caspases 3, 7, and 9 in vitro. XIAP transcripts can be found in a variety of tissues, and the protein levels are regulated both transcriptionally and posttranscriptionally. To better understand the function of XIAP in normal cells, we generated mice deficient in XIAP through homologous gene targeting. The resulting mice were viable, and histopathological analysis did not reveal any differences between XIAP-deficient and wild-type mice. We were unable to detect any defects in induction of caspase-dependent or -independent apoptosis in cells from the gene-targeted mice. One change was observed in cells derived from XIAP-deficient mice: the levels of c-IAP1 and c-IAP2 protein were increased. This suggests that there exists a compensatory mechanism that leads to upregulation of other family members when XIAP expression is lost. The changes in c-IAP1 and c-IAP2 expression may provide functional compensation for loss of XIAP during development or in the induction of apoptosis. Mol Cell Biol. 2001 May;21(10):3604-8.
- IAP family proteins--suppressors of apoptosis.
- Deveraux QL, Reed JC
- Genes Dev. 1999 Feb 1;13(3):239-52.
- XIAP discriminates between type I and type II FAS-induced apoptosis.
- Jost PJ, Grabow S, Gray D, McKenzie MD, Nachbur U, Huang DC, Bouillet P, Thomas HE, Borner C, Silke J, Strasser A, Kaufmann T
- FAS (also called APO-1 and CD95) and its physiological ligand, FASL, regulate apoptosis of unwanted or dangerous cells, functioning as a guardian against autoimmunity and cancer development. Distinct cell types differ in the mechanisms by which the 'death receptor' FAS triggers their apoptosis. In type I cells, such as lymphocytes, activation of 'effector caspases' by FAS-induced activation of caspase-8 suffices for cell killing, whereas in type II cells, including hepatocytes and pancreatic beta-cells, caspase cascade amplification through caspase-8-mediated activation of the pro-apoptotic BCL-2 family member BID (BH3 interacting domain death agonist) is essential. Here we show that loss of XIAP (X-chromosome linked inhibitor of apoptosis protein) function by gene targeting or treatment with a second mitochondria-derived activator of caspases (SMAC, also called DIABLO; direct IAP-binding protein with low pI) mimetic drug in mice rendered hepatocytes and beta-cells independent of BID for FAS-induced apoptosis. These results show that XIAP is the critical discriminator between type I and type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions. Nature. 2009 Aug 20;460(7258):1035-9. Epub 2009 Jul 22.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | BIR | 29 | 94 |
| PFAM A | BIR | 166 | 231 |
| PFAM A | BIR | 268 | 331 |
Protein sequence [+]
XIAP | Homo sapiens | 9606 | length:497
MTFNSFEGSKTCVPADINKEEEFVEEFNRLKTFANFPSGSPVSASTLARAGFLYTGEGDT
VRCFSCHAAVDRWQYGDSAVGRHRKVSPNCRFINGFYLENSATQSTNSGIQNGQYKVENY
LGSRDHFALDRPSETHADYLLRTGQVVDISDTIYPRNPAMYSEEARLKSFQNWPDYAHLT
PRELASAGLYYTGIGDQVQCFCCGGKLKNWEPCDRAWSEHRRHFPNCFFVLGRNLNIRSE
SDAVSSDRNFPNSTNLPRNPSMADYEARIFTFGTWIYSVNKEQLARAGFYALGEGDKVKC
FHCGGGLTDWKPSEDPWEQHAKWYPGCKYLLEQKGQEYINNIHLTHSLEECLVRTTEKTP
SLTRRIDDTIFQNPMVQEAIRMGFSFKDIKKIMEEKIQISGSNYKSLEVLVADLVNAQKD
SMQDESSQTSLQKEISTEEQLRRLQEEKLCKICMDRNIAIVFVPCGHLVTCKQCAEAVDK
CPMCYTVITFKQKIFMS
VRCFSCHAAVDRWQYGDSAVGRHRKVSPNCRFINGFYLENSATQSTNSGIQNGQYKVENY
LGSRDHFALDRPSETHADYLLRTGQVVDISDTIYPRNPAMYSEEARLKSFQNWPDYAHLT
PRELASAGLYYTGIGDQVQCFCCGGKLKNWEPCDRAWSEHRRHFPNCFFVLGRNLNIRSE
SDAVSSDRNFPNSTNLPRNPSMADYEARIFTFGTWIYSVNKEQLARAGFYALGEGDKVKC
FHCGGGLTDWKPSEDPWEQHAKWYPGCKYLLEQKGQEYINNIHLTHSLEECLVRTTEKTP
SLTRRIDDTIFQNPMVQEAIRMGFSFKDIKKIMEEKIQISGSNYKSLEVLVADLVNAQKD
SMQDESSQTSLQKEISTEEQLRRLQEEKLCKICMDRNIAIVFVPCGHLVTCKQCAEAVDK
CPMCYTVITFKQKIFMS
Structure links:
- Smartdomain prediction information: SM00238
- Smartdomain prediction information: SM00184
- Prosite motif and domain information: PS01282
- Profile motif and domain profile information: PS50143
- Profile motif and domain profile information: PS50089
- Interpro domain information: P98170
- PFAM domain and domain family information: P98170
- Protein 3D structures from PDB: 3CM2 3CM7 3EYL 2QRA 2VSL 3CLX 2OPY 2OPZ 2POI 1TFT 2ECG 2JK7 1F9X 1TFQ 1C9Q 2POP 1G3F 1G73 1NW9 1KMC 1I4O 1I51 1I3O
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| A_aegypti_AAEL006633-PA | orthology | Aedes |
| Q5MM83_AEDAE | orthology | Aedes |
| IAP4 | orthology | Anopheles |
| IAP3 | orthology | Anopheles |
| A_gambiae_AGAP007293-PA | orthology | Anopheles |
| IAP1 | orthology | Anopheles |
| IAP2 | orthology | Anopheles |
| IAP4 | orthology | Anopheles |
| NP_989919.1 | orthology | Chicken |
| NP_989919.1 | orthology | Chicken |
| XIAP | orthology | Chimpanzee |
| XIAP | orthology | Chimpanzee |
| C_intestinalis_ENSCINP00000000510 | orthology | Ciona |
| C_intestinalis_ENSCINP00000002256 | orthology | Ciona |
| C_intestinalis_ENSCINP00000002312 | orthology | Ciona |
| C_intestinalis_ENSCINP00000005161 | orthology | Ciona |
| C_intestinalis_ENSCINP00000009820 | orthology | Ciona |
| C_intestinalis_ENSCINP00000010449 | orthology | Ciona |
| C_intestinalis_ENSCINP00000011648 | orthology | Ciona |
| C_intestinalis_ENSCINP00000020067 | orthology | Ciona |
| NA | orthology | Ciona |
| C_intestinalis_ENSCINP00000021651 | orthology | Ciona |
| C_intestinalis_ENSCINP00000000045 | orthology | Ciona |
| C_intestinalis_ENSCINP00000000047 | orthology | Ciona |
| C_intestinalis_ENSCINP00000000466 | orthology | Ciona |
| NA | orthology | Ciona |
| C_intestinalis_ENSCINP00000000487 | orthology | Ciona |
| Q8WMY4_BOVIN | orthology | Cow |
| Q8WMY4_BOVIN | orthology | Cow |
| Q38IV1_CANFA | orthology | Dog |
| Q38IV1_CANFA | orthology | Dog |
| th | orthology | Fly |
| Iap2 | orthology | Fly |
| Iap2 | orthology | Fly |
| BIRC8 | orthology | Fugu |
| XIAP | orthology | Fugu |
| XIAP | orthology | Gasterosteus |
| BIRC8 | orthology | Gasterosteus |
| XIAP | orthology | Gorilla |
| XIAP | orthology | Gorilla |
| BIRC8 | orthology | Horse |
| XIAP | orthology | Horse |
| A_carolinensis_ENSACAP00000011315 | orthology | Lyzard |
| A_carolinensis_ENSACAP00000011315 | orthology | Lyzard |
| BIRC8 | orthology | Medaka |
| XIAP | orthology | Medaka |
| XM_001364568.1 | orthology | Monodelphis |
| M_domestica_ENSMODP00000018715 | orthology | Monodelphis |
| Xiap | orthology | Mouse |
| Xiap | orthology | Mouse |
| XIAP | orthology | Orangutan |
| XIAP | orthology | Orangutan |
| O_anatinus_ENSOANP00000006435 | orthology | Ornithorhynchus |
| O_anatinus_ENSOANP00000006435 | orthology | Ornithorhynchus |
| O_cuniculus_ENSOCUP00000008505 | orthology | Rabbit |
| XIAP | orthology | Rabbit |
| Birc4 | orthology | Rat |
| XIAP_RAT | orthology | Rat |
| BIRC8 | orthology | Tetraodon |
| XIAP | orthology | Tetraodon |
| birc4 | orthology | Xenopus |
| birc4 | orthology | Xenopus |
| T_guttata_ENSTGUP00000003825 | orthology | Zebra finch |
| XIAP | orthology | Zebra finch |
| birc4 | orthology | Zebrafish |
| xiap | orthology | Zebrafish |
| A_aegypti_AAEL000590-PA | paralogy | Aedes |
| IAP6 | paralogy | Anopheles |
| BIRC7 | paralogy | Chicken |
| IPI00603248.2 | paralogy | Chicken |
| BIR_CHICK | paralogy | Chicken |
| BIR_CHICK | paralogy | Chicken |
| BIRC3 | paralogy | Chimpanzee |
| BIRC3 | paralogy | Chimpanzee |
| BIRC2 | paralogy | Chimpanzee |
| BIRC2 | paralogy | Chimpanzee |
| BIRC8_PANTR | paralogy | Chimpanzee |
| XR_021305.1 | paralogy | Chimpanzee |
| XR_021305.1 | paralogy | Chimpanzee |
| P_troglodytes_ENSPTRP00000048273 | paralogy | Chimpanzee |
| XM_001156604.1 | paralogy | Chimpanzee |
| IPI00689691.3 | paralogy | Cow |
| IPI00689691.3 | paralogy | Cow |
| NP_001030370.1 | paralogy | Cow |
| NP_001030370.1 | paralogy | Cow |
| IPI00824732.2 | paralogy | Cow |
| BIRC7 | paralogy | Dog |
| BIRC7 | paralogy | Dog |
| Q38JA8_CANFA | paralogy | Dog |
| Q38JA8_CANFA | paralogy | Dog |
| BIRC3_CANFA | paralogy | Dog |
| BIRC3_CANFA | paralogy | Dog |
| BIRC7 | paralogy | Fugu |
| BIRC7 | paralogy | Fugu |
| BIRC3 | paralogy | Fugu |
| BIRC3 | paralogy | Fugu |
| BIRC3 | paralogy | Gasterosteus |
| BIRC3 | paralogy | Gasterosteus |
| BIRC7 | paralogy | Gasterosteus |
| BIRC7 | paralogy | Gasterosteus |
| BIRC3 | paralogy | Gorilla |
| BIRC8 | paralogy | Gorilla |
| BIRC2 | paralogy | Gorilla |
| BIRC2 | paralogy | Gorilla |
| BIRC7 | paralogy | Gorilla |
| BIRC7 | paralogy | Gorilla |
| BIRC2 | paralogy | Horse |
| BIRC2 | paralogy | Horse |
| E_caballus_ENSECAP00000002314 | paralogy | Horse |
| XP_001504091.2 | paralogy | Horse |
| BIRC3 | paralogy | Horse |
| BIRC3 | paralogy | Horse |
| BIRC7 | paralogy | Horse |
| BIRC7 | paralogy | Horse |
| BIRC1 | paralogy | Human |
| NAIP | paralogy | Human |
| BIRC7 | paralogy | Human |
| BIRC7 | paralogy | Human |
| cIAP1 | paralogy | Human |
| BIRC2 | paralogy | Human |
| BIRC8 | paralogy | Human |
| BIRC8 | paralogy | Human |
| BIRC3 | paralogy | Human |
| BIRC3 | paralogy | Human |
| A_carolinensis_ENSACAP00000009897 | paralogy | Lyzard |
| A_carolinensis_ENSACAP00000012475 | paralogy | Lyzard |
| A_carolinensis_ENSACAP00000012475 | paralogy | Lyzard |
| BIRC7 | paralogy | Lyzard |
| BIRC7 | paralogy | Lyzard |
| A_carolinensis_ENSACAP00000009897 | paralogy | Lyzard |
| BIRC3 | paralogy | Macaca |
| BIRC3 | paralogy | Macaca |
| BIRC2 | paralogy | Macaca |
| BIRC2 | paralogy | Macaca |
| BIRC7 | paralogy | Macaca |
| BIRC7 | paralogy | Macaca |
| BIRC3 | paralogy | Medaka |
| BIRC7 | paralogy | Medaka |
| BIRC7 | paralogy | Medaka |
| BIRC7 | paralogy | Monodelphis |
| BIRC7 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000000705 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000000705 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000000728 | paralogy | Monodelphis |
| XM_001362587.1 | paralogy | Monodelphis |
| cIAP2 | paralogy | Mouse |
| Birc3 | paralogy | Mouse |
| Naip1 | paralogy | Mouse |
| Naip4 | paralogy | Mouse |
| Naip5 | paralogy | Mouse |
| Naip5 | paralogy | Mouse |
| cIAP1 | paralogy | Mouse |
| Birc2 | paralogy | Mouse |
| Birc7 | paralogy | Mouse |
| Birc7 | paralogy | Mouse |
| Birc1-rs1 | paralogy | Mouse |
| Naip6 | paralogy | Mouse |
| Naip2 | paralogy | Mouse |
| Naip2 | paralogy | Mouse |
| BIRC3 | paralogy | Orangutan |
| BIRC3 | paralogy | Orangutan |
| Q5R9T1_PONPY | paralogy | Orangutan |
| Q5R9T1_PONPY | paralogy | Orangutan |
| BIRC7 | paralogy | Orangutan |
| BIRC7 | paralogy | Orangutan |
| P_pygmaeus_ENSPPYP00000017359 | paralogy | Orangutan |
| P_pygmaeus_ENSPPYP00000017359 | paralogy | Orangutan |
| O_anatinus_ENSOANP00000016616 | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000016616 | paralogy | Ornithorhynchus |
| BIRC3 | paralogy | Rabbit |
| BIRC3 | paralogy | Rabbit |
| O_cuniculus_ENSOCUP00000011948 | paralogy | Rabbit |
| O_cuniculus_ENSOCUP00000011948 | paralogy | Rabbit |
| O_cuniculus_ENSOCUP00000014265 | paralogy | Rabbit |
| BIRC7 | paralogy | Rabbit |
| NP_076477.2 | paralogy | Rat |
| Birc2 | paralogy | Rat |
| NP_068520.2 | paralogy | Rat |
| RGD1559914_predicted | paralogy | Rat |
| Q8R4U8_RAT | paralogy | Rat |
| Birc3 | paralogy | Rat |
| BIRC7 | paralogy | Tetraodon |
| BIRC7 | paralogy | Tetraodon |
| BIRC3 | paralogy | Tetraodon |
| birc3 | paralogy | Xenopus |
| birc3 | paralogy | Xenopus |
| X_tropicalis_ENSXETP00000057704 | paralogy | Xenopus |
| X_tropicalis_ENSXETP00000016312 | paralogy | Xenopus |
| X_tropicalis_ENSXETP00000016315 | paralogy | Xenopus |
| BIRC7 | paralogy | Xenopus |
| BIRC7 | paralogy | Xenopus |
| X_tropicalis_ENSXETP00000030727 | paralogy | Xenopus |
| X_tropicalis_ENSXETP00000030727 | paralogy | Xenopus |
| X_tropicalis_ENSXETP00000034890 | paralogy | Xenopus |
| BIRC7 | paralogy | Zebra finch |
| BIRC7 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000013125 | paralogy | Zebra finch |
| BIRC2 | paralogy | Zebra finch |
| birc2 | paralogy | Zebrafish |
| birc2 | paralogy | Zebrafish |
| BIRC7 | paralogy | Zebrafish |
| zgc:165605 | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0006916 | anti-apoptosis | biological_proccess | TAS |
| GO:0006915 | apoptosis | biological_proccess | IEA |
| GO:0019941 | modification-dependent protein catabolic process | biological_proccess | IEA |
| GO:0005515 | protein binding | mollecular_function | IPI |
| GO:0043027 | caspase inhibitor activity | mollecular_function | IDA |
| GO:0016874 | ligase activity | mollecular_function | IEA |
| GO:0030414 | peptidase inhibitor activity | mollecular_function | IEA |
| GO:0046872 | metal ion binding | mollecular_function | IEA |
| GO:0008270 | zinc ion binding | mollecular_function | IEA |
| GO:0005622 | intracellular | cell_component | IEA |
| GO:0005737 | cytoplasm | cell_component | TAS |
| GO:0005829 | cytosol | cell_component | TAS |
Check GO Evidence Codes here
KEGG Pathways [+]
Curated Isoforms [+]
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- Gene info from HGNC [?] :592
- Gene related info from GeneCards [?] : XIAP
- Ensembl genome browser [?] : ENSG00000101966
- Expression info from Arrayexpress [?] : ENSG00000101966
- Protein expression from Protein Atlas: [?] ENSG00000101966
- Community gene edition from Wikigenes: [?] 331
Click on [?] for more information.
