Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q6GPH4 (XAF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 82. 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·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
XIAP-associated factor 1
Alternative name(s):
BIRC4-binding protein
Gene names
Name:XAF1
Synonyms:BIRC4BP, XIAPAF1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length301 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Ref.1 Ref.7 Ref.9 Ref.10 Ref.11

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. Interacts with RNF114, the interaction increases XAF1 stability and proapoptotic effects, and may regulate IFN signaling. Ref.1 Ref.9 Ref.10 Ref.12

Subcellular location

Cytoplasm. Nucleus. Mitochondrion. Note: Found in the cytoplasm and nucleus of placental syncytiotrophoblasts. Translocates to mitochondria upon TNF-alpha treatment. Ref.1 Ref.8 Ref.11

Isoform 1: Nucleus Ref.1 Ref.8 Ref.11.

Isoform 5: Nucleus Ref.1 Ref.8 Ref.11.

Tissue specificity

Widely expressed. Expression is frequently down-regulated in cancer cell lines. Isoform 5 is widely expressed. Expressed in placenta (at protein level). Ref.1 Ref.2 Ref.8 Ref.11

Developmental stage

Selectively expressed in third trimester placenta. Ref.11

Induction

Up-regulated by IFNB1/IFN-beta in cell lines sensitive to the proapoptotic effects of IFNB1 but not in apoptosis-resistant cells. Up-regulated by TNF in trophoblast cells. Ref.7 Ref.11

Sequence similarities

Contains 1 TRAF-type zinc finger.

Sequence caution

The sequence AAH32776.1 differs from that shown. Reason: Erroneous initiation.

The sequence CAA68030.1 differs from that shown. Reason: Frameshift at position 294.

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
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 301301XIAP-associated factor 1
PRO_0000329028

Regions

Zinc finger22 – 9978TRAF-type

Natural variations

Alternative sequence1 – 102102Missing in isoform 6.
VSP_032918
Alternative sequence57 – 7519Missing in isoform 2 and isoform 4.
VSP_032919
Alternative sequence57 – 7418VGCTM…SLEFH → GKEFQLLKGKSTVIIATK in isoform 7.
VSP_032920
Alternative sequence103 – 14038SYCGS…AQLGK → MSLHYGCCCPECTSVAIKEM MWVIRPRVACVVKDAGSA in isoform 6.
VSP_032921
Alternative sequence141 – 301161GERIS…VRNFS → ETSPDPGKCLSITVAAALSA HLWPFT in isoform 5.
VSP_032922
Alternative sequence142 – 301160Missing in isoform 3 and isoform 4.
VSP_032923
Natural variant851E → G.
Corresponds to variant rs34195599 [ dbSNP | Ensembl ].
VAR_042616
Natural variant1321R → H.
Corresponds to variant rs2271232 [ dbSNP | Ensembl ].
VAR_042617
Natural variant1881E → K.
Corresponds to variant rs34625877 [ dbSNP | Ensembl ].
VAR_042618
Natural variant2191R → I.
Corresponds to variant rs3736433 [ dbSNP | Ensembl ].
VAR_042619

Experimental info

Sequence conflict1321R → Q in BAF85537. Ref.3
Sequence conflict1381L → R in BAF85537. Ref.3
Sequence conflict1961S → R in BAF85537. Ref.3

Secondary structure

........ 301
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (XAF1(A)) [UniParc].

Last modified July 19, 2004. Version 1.
Checksum: FC9D48BD07BE541D

FASTA30134,626
        10         20         30         40         50         60 
MEGDFSVCRN CKRHVVSANF TLHEAYCLRF LVLCPECEEP VPKETMEEHC KLEHQQVGCT 

        70         80         90        100        110        120 
MCQQSMQKSS LEFHKANECQ ERPVECKFCK LDMQLSKLEL HESYCGSRTE LCQGCGQFIM 

       130        140        150        160        170        180 
HRMLAQHRDV CRSEQAQLGK GERISAPERE IYCHYCNQMI PENKYFHHMG KCCPDSEFKK 

       190        200        210        220        230        240 
HFPVGNPEIL PSSLPSQAAE NQTSTMEKDV RPKTRSINRF PLHSESSSKK APRSKNKTLD 

       250        260        270        280        290        300 
PLLMSEPKPR TSSPRGDKAA YDILRRCSQC GILLPLPILN QHQEKCRWLA SSKGKQVRNF 


S 

« Hide

Isoform 2 (XAF1B) [UniParc].

Checksum: 6EAC4F7EC6F8E64A
Show »

FASTA28232,471
Isoform 3 (D) [UniParc].

Checksum: B286A33BC34A10A2
Show »

FASTA14116,322
Isoform 4 (E) [UniParc].

Checksum: 36CC8B71B4DCCD8A
Show »

FASTA12214,167
Isoform 5 (XAF1C) [UniParc].

Checksum: 0EDD81DA26C30B50
Show »

FASTA16618,960
Isoform 6 [UniParc].

Checksum: FCA89ECA5FB0ED46
Show »

FASTA19922,507
Isoform 7 [UniParc].

Checksum: 556947EBEFD6B84E
Show »

FASTA30134,543

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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [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. 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].
[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] (ISOFORMS 1 AND 7).
Tissue: Testis.
[6]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN TNF-ALPHA-INDUCED APOPTOSIS, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION.
[12]"ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing p21(WAF1.)."
Han J., Kim Y.L., Lee K.W., Her N.G., Ha T.K., Yoon S., Jeong S.I., Lee J.H., Kang M.J., Lee M.G., Ryu B.K., Baik J.H., Chi S.G.
Cell Death Differ. 20:1055-1067(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RNF114.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CH471108 Genomic DNA. Translation: EAW90289.1.
BC032776 mRNA. Translation: AAH32776.1. Different initiation.
BC073156 mRNA. Translation: AAH73156.1.
BX649188 mRNA. Translation: CAE46206.1.
CCDSCCDS11080.1. [Q6GPH4-1]
CCDS11081.1. [Q6GPH4-2]
RefSeqNP_059993.2. NM_017523.3. [Q6GPH4-1]
NP_954590.1. NM_199139.2. [Q6GPH4-2]
XP_005256765.1. XM_005256708.1. [Q6GPH4-6]
UniGeneHs.441975.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2LXWNMR-A251-301[»]
ProteinModelPortalQ6GPH4.
SMRQ6GPH4. Positions 74-134, 251-301.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120121. 8 interactions.
IntActQ6GPH4. 2 interactions.
MINTMINT-216123.
STRING9606.ENSP00000354822.

Polymorphism databases

DMDM74736479.

Proteomic databases

MaxQBQ6GPH4.
PaxDbQ6GPH4.
PRIDEQ6GPH4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000346752; ENSP00000341029; ENSG00000132530. [Q6GPH4-2]
ENST00000361842; ENSP00000354822; ENSG00000132530. [Q6GPH4-1]
ENST00000571673; ENSP00000461196; ENSG00000132530. [Q6GPH4-4]
ENST00000574962; ENSP00000458229; ENSG00000132530. [Q6GPH4-3]
GeneID54739.
KEGGhsa:54739.
UCSCuc002gdm.1. human. [Q6GPH4-1]
uc002gdo.3. human. [Q6GPH4-2]
uc002gdp.4. human. [Q6GPH4-6]

Organism-specific databases

CTD54739.
GeneCardsGC17P006659.
HGNCHGNC:30932. XAF1.
HPAHPA057302.
MIM606717. gene.
neXtProtNX_Q6GPH4.
PharmGKBPA162409299.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG87143.
HOVERGENHBG108681.
OrthoDBEOG73806B.
PhylomeDBQ6GPH4.
TreeFamTF331416.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressQ6GPH4.
BgeeQ6GPH4.
CleanExHS_XAF1.
GenevestigatorQ6GPH4.

Family and domain databases

InterProIPR001293. Znf_TRAF.
[Graphical view]
PROSITEPS50145. ZF_TRAF. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSXAF1. human.
GeneWikiXAF1.
GenomeRNAi54739.
NextBio57333.
PROQ6GPH4.
SOURCESearch...

Entry information

Entry nameXAF1_HUMAN
AccessionPrimary (citable) accession number: Q6GPH4
Secondary accession number(s): A2T931 expand/collapse secondary AC list , A2T932, A8K2L1, A8K9Y3, D3DTM6, Q6MZE8, Q8N557, Q99982
Entry history
Integrated into UniProtKB/Swiss-Prot: April 8, 2008
Last sequence update: July 19, 2004
Last modified: July 9, 2014
This is version 82 of the entry and version 1 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 17

Human chromosome 17: entries, gene names and cross-references to MIM