Reviewed,
UniProtKB/Swiss-Prot Q6GPH4 (XAF1_HUMAN)
Last modified
November 25, 2008.
Version 32.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: XIAP-associated factor 1 Alternative name(s): BIRC4-binding protein | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 301 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Seems to function as a negative regulator of members of the IAP (inhibitor of apoptosis protein) family. Inhibits anti-caspase activity of BIRC4. Induces cleavage and inactivation of BIRC4 independent of caspase activation. Mediates TNF-alpha-induced apoptosis and is involved in apoptosis in trophoblast cells. May inhibit BIRC4 indirectly by activating the mitochondrial apoptosis pathway. After translocation to mitochondra, promotes translocation of BAX to mitochondria and cytochrome c release from mitochondria. Seems to promote the redistribution of BIRC4 from the cytoplasm to the nucleus, probably independent of BIRC4 inactivation which seems to occur in the cytoplasm. The BIRC4-XAF1 complex mediates down-regulation of BIRC5/survivin; the process requires the E3 ligase activity of BIRC4. Seems to be involved in cellular sensitivity to the proapoptotic actions of TRAIL. May be a tumor suppressor by mediating apoptosis resistance of cancer cells. |
| Subunit structure | Interacts with BIRC4; the interaction is not detected in (Ref.9). Interacts with BIRC1, BIRC2, BIRC3, BIRC7 and BIRC8. Part of an complex consisting of BIRC4, XAF1 and BIRC5; the complex formation requires IFN-beta stimulation. |
| Subcellular location | Cytoplasm. Nucleus. Mitochondrion. Note= Found in the cytoplasm and nucleus of placental syncytiotrophoblasts. Translocates to mitochondria upon TNF-alpha treatment. Isoform 1: Nucleus. Isoform 5: Nucleus. |
| Tissue specificity | Widely expressed. Expression is frequently down-regulated in cancer cell lines. Isoform 5 is widely expressed. Expressed in placenta (at protein level). |
| Developmental stage | Selectively expressed in third trimester placenta. |
| Induction | Up-regulated by IFN-beta in cell lines sensitive to the proapoptotic effects of IFN-beta but not in apoptosis-resistant cells. Up-regulated by TNF-alhpa in trophoblast cells. |
| Sequence similarities | Contains 1 TRAF-type zinc finger. |
| Sequence caution | The sequence CAA68030.1 differs from that shown. Reason: Frameshift at position 294. |
Ontologies
Keywords | |
|---|---|
| Biological process | Apoptosis Cell cycle |
| Cellular component | Cytoplasm Mitochondrion Nucleus |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Domain | Zinc-finger |
| Ligand | Metal-binding Zinc |
| Molecular function | Anti-oncogene |
Gene Ontology (GO) | |
| Biological process | apoptosis Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell cycleInferred from electronic annotation. Source: UniProtKB-KW |
| Cellular component | mitochondrion Inferred from electronic annotation. Source: UniProtKB-KW nucleusInferred from electronic annotation. Source: UniProtKB-KW |
| Molecular function | zinc ion binding Inferred from electronic annotation. Source: InterPro |
| Complete GO annotation... | |
Alternative products
| This entry describes 7 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q6GPH4-1) Also known as: XAF1(A); This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: Q6GPH4-2) Also known as: XAF1B; The sequence of this isoform differs from the canonical sequence as follows: 57-75: Missing. | ||||||
| Isoform 3 (identifier: Q6GPH4-3) Also known as: D; The sequence of this isoform differs from the canonical sequence as follows: 142-301: Missing. | ||||||
| Isoform 4 (identifier: Q6GPH4-4) Also known as: E; The sequence of this isoform differs from the canonical sequence as follows: 57-75: Missing. 142-301: Missing. | ||||||
| Isoform 5 (identifier: Q6GPH4-5) Also known as: XAF1C; The sequence of this isoform differs from the canonical sequence as follows: 141-301: GERISAPERE...SKGKQVRNFS → ETSPDPGKCLSITVAAALSAHLWPFT | ||||||
| Isoform 6 (identifier: Q6GPH4-6) The sequence of this isoform differs from the canonical sequence as follows: 1-102: Missing. 103-140: SYCGSRTELC...CRSEQAQLGK → MSLHYGCCCP...ACVVKDAGSA | ||||||
| Isoform 7 (identifier: Q6GPH4-7) The sequence of this isoform differs from the canonical sequence as follows: 57-74: VGCTMCQQSMQKSSLEFH → GKEFQLLKGKSTVIIATK | ||||||
| Notes: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 301 | 301 | XIAP-associated factor 1 | PRO_0000329028 | |||||
Regions | |||||||||
| Zinc finger | 22 – 99 | 78 | TRAF-type | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 102 | 102 | Missing in isoform 6. | VSP_032918 | |||||
| Alternative sequence | 57 – 75 | 19 | Missing in isoform 2 and isoform 4. | VSP_032919 | |||||
| Alternative sequence | 57 – 74 | 18 | VGCTM…SLEFH → GKEFQLLKGKSTVIIATK in isoform 7. | VSP_032920 | |||||
| Alternative sequence | 103 – 140 | 38 | SYCGS…AQLGK → MSLHYGCCCPECTSVAIKEM MWVIRPRVACVVKDAGSA in isoform 6. | VSP_032921 | |||||
| Alternative sequence | 141 – 301 | 161 | GERIS…VRNFS → ETSPDPGKCLSITVAAALSA HLWPFT in isoform 5. | VSP_032922 | |||||
| Alternative sequence | 142 – 301 | 160 | Missing in isoform 3 and isoform 4. | VSP_032923 | |||||
| Natural variant | 85 | 1 | E → G: dbSNP rs34195599. | VAR_042616 | |||||
| Natural variant | 132 | 1 | R → H: dbSNP rs2271232. | VAR_042617 | |||||
| Natural variant | 188 | 1 | E → K: dbSNP rs34625877. | VAR_042618 | |||||
| Natural variant | 219 | 1 | R → I: dbSNP rs3736433. | VAR_042619 | |||||
Experimental info | |||||||||
| Sequence conflict | 132 | 1 | R → Q in BAF85537. Ref.3 | ||||||
| Sequence conflict | 138 | 1 | L → R in BAF85537. Ref.3 | ||||||
| Sequence conflict | 196 | 1 | S → R in BAF85537. Ref.3 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Identification of XAF1 as an antagonist of XIAP anti-Caspase activity." Liston P., Fong W.G., Kelly N.L., Toji S., Miyazaki T., Conte D., Tamai K., Craig C.G., McBurney M.W., Korneluk R.G. Nat. Cell Biol. 3:128-133(2001) [PubMed: 11175744] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH BIRC4, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Placenta. |
| [2] | "Frequent alteration of XAF1 in human colorectal cancers: implication for tumor cell resistance to apoptotic stresses." Chung S.K., Lee M.G., Ryu B.K., Lee J.H., Han J., Byun D.S., Chae K.S., Lee K.Y., Jang J.Y., Kim H.J., Chi S.G. Gastroenterology 132:2459-2477(2007) [PubMed: 17570219] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), TISSUE SPECIFICITY. |
| [3] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 6). Tissue: Thymus. |
| [4] | 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. Venter J.C.Submitted (SEP-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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 7). Tissue: Testis. |
| [6] | The German cDNA consortium Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-57. Tissue: Endometrium. |
| [7] | "Identification of X-linked inhibitor of apoptosis-associated factor-1 as an interferon-stimulated gene that augments TRAIL Apo2L-induced apoptosis." Leaman D.W., Chawla-Sarkar M., Vyas K., Reheman M., Tamai K., Toji S., Borden E.C. J. Biol. Chem. 277:28504-28511(2002) [PubMed: 12029096] [Abstract] Cited for: FUNCTION, INDUCTION. |
| [8] | "Identification of a novel splice variant of X-linked inhibitor of apoptosis-associated factor 1." Yin W., Cheepala S., Clifford J.L. Biochem. Biophys. Res. Commun. 339:1148-1154(2006) [PubMed: 16343440] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORM 5), SUBCELLULAR LOCATION, TISSUE SPECIFICITY. |
| [9] | "Xaf1 can cooperate with TNFalpha in the induction of apoptosis, independently of interaction with XIAP." Xia Y., Novak R., Lewis J., Duckett C.S., Phillips A.C. Mol. Cell. Biochem. 286:67-76(2006) [PubMed: 16432762] [Abstract] Cited for: FUNCTION IN TNF-ALPHA-INDUCED APOPTOSIS, NEGATIVE INTERACTION WITH BIRC4. |
| [10] | "Degradation of survivin by the X-linked inhibitor of apoptosis (XIAP)-XAF1 complex." Arora V., Cheung H.H., Plenchette S., Micali O.C., Liston P., Korneluk R.G. J. Biol. Chem. 282:26202-26209(2007) [PubMed: 17613533] [Abstract] Cited for: FUNCTION IN BIRC5 DEGRADATION, INTERACTION WITH BIRC1; BIRC2; BIRC3; BIRC4; BIRC7 AND BIRC8. |
| [11] | "XAF1 mediates tumor necrosis factor-alpha-induced apoptosis and X-linked inhibitor of apoptosis cleavage by acting through the mitochondrial pathway." Straszewski-Chavez S.L., Visintin I.P., Karassina N., Los G., Liston P., Halaban R., Fadiel A., Mor G. J. Biol. Chem. 282:13059-13072(2007) [PubMed: 17329253] [Abstract] Cited for: FUNCTION IN TNF-ALPHA-INDUCED APOPTOSIS, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| X99699 mRNA. Translation: CAA68030.1. Frameshift. EF028165 mRNA. Translation: ABM74556.1. EF028166 mRNA. Translation: ABM74557.1. AK290276 mRNA. Translation: BAF82965.1. AK292710 mRNA. Translation: BAF85399.1. AK292848 mRNA. Translation: BAF85537.1. CH471108 Genomic DNA. Translation: EAW90288.1. BC032776 mRNA. Translation: AAH32776.1. Different initiation. BC073156 mRNA. Translation: AAH73156.1. BX649188 mRNA. Translation: CAE46206.1. | |
| RefSeq | NP_059993.2. |
| UniGene | Hs.441975 |
3D structure databases | |
| ModBase | Search... |
Genome annotation databases | |
| Ensembl | ENSG00000132530. Homo sapiens. [Contig view] |
| GeneID | 54739. |
| KEGG | hsa:54739. |
Organism-specific databases | |
| HGNC | HGNC:30932. XAF1. |
| MIM | 606717. gene. |
| GenAtlas | Search... |
| GeneCards | Search... |
Phylogenomic databases | |
| HOVERGEN | Q6GPH4. |
Gene expression databases | |
| ArrayExpress | Q6GPH4. |
| CleanEx | HS_XAF1. |
Family and domain databases | |
| InterPro | IPR001293. Znf_TRAF. [Graphical view] |
| Pfam | PF02176. zf-TRAF. 1 hit. [Graphical view] |
| PROSITE | PS50145. ZF_TRAF. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 57333. |
| SOURCE | Search... |
Entry information
| Entry name | XAF1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q6GPH4 Secondary accession number(s): A2T931 Q99982 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 17 Human chromosome 17: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


