Reviewed, UniProtKB/Swiss-Prot Q6GPH4 (XAF1_HUMAN)

Names and origin

Protein names

Recommended name:
    XIAP-associated factor 1
Alternative name(s):
    BIRC4-binding protein

Gene names

Name:	XAF1
Synonyms:	BIRC4BP, XIAPAF1

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 cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrion Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred 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

	Sequence		Length	Mass (Da)
	Isoform 1 (XAF1(A)) [UniParc]. Last modified July 19, 2004. Version 1. Checksum: FC9D48BD07BE541D	FASTA	301	34,626
	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
	Isoform 2 (XAF1B) [UniParc]. Checksum: 6EAC4F7EC6F8E64A		282	32,471
	10 20 30 40 50 60 MEGDFSVCRN CKRHVVSANF TLHEAYCLRF LVLCPECEEP VPKETMEEHC KLEHQQANEC 70 80 90 100 110 120 QERPVECKFC KLDMQLSKLE LHESYCGSRT ELCQGCGQFI MHRMLAQHRD VCRSEQAQLG 130 140 150 160 170 180 KGERISAPER EIYCHYCNQM IPENKYFHHM GKCCPDSEFK KHFPVGNPEI LPSSLPSQAA 190 200 210 220 230 240 ENQTSTMEKD VRPKTRSINR FPLHSESSSK KAPRSKNKTL DPLLMSEPKP RTSSPRGDKA 250 260 270 280 AYDILRRCSQ CGILLPLPIL NQHQEKCRWL ASSKGKQVRN FS
	Isoform 3 (D) [UniParc]. Checksum: B286A33BC34A10A2		141	16,322
	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 HRMLAQHRDV CRSEQAQLGK G
	Isoform 4 (E) [UniParc]. Checksum: 36CC8B71B4DCCD8A		122	14,167
	10 20 30 40 50 60 MEGDFSVCRN CKRHVVSANF TLHEAYCLRF LVLCPECEEP VPKETMEEHC KLEHQQANEC 70 80 90 100 110 120 QERPVECKFC KLDMQLSKLE LHESYCGSRT ELCQGCGQFI MHRMLAQHRD VCRSEQAQLG KG
	Isoform 5 (XAF1C) [UniParc]. Checksum: 0EDD81DA26C30B50		166	18,960
	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 HRMLAQHRDV CRSEQAQLGK ETSPDPGKCL SITVAAALSA HLWPFT
	Isoform 6 [UniParc]. Checksum: FCA89ECA5FB0ED46		199	22,507
	10 20 30 40 50 60 MSLHYGCCCP ECTSVAIKEM MWVIRPRVAC VVKDAGSAGE RISAPEREIY CHYCNQMIPE 70 80 90 100 110 120 NKYFHHMGKC CPDSEFKKHF PVGNPEILPS SLPSQAAENQ TSTMEKDVRP KTRSINRFPL 130 140 150 160 170 180 HSESSSKKAP RSKNKTLDPL LMSEPKPRTS SPRGDKAAYD ILRRCSQCGI LLPLPILNQH 190 QEKCRWLASS KGKQVRNFS
	Isoform 7 [UniParc]. Checksum: 556947EBEFD6B84E		301	34,543
	10 20 30 40 50 60 MEGDFSVCRN CKRHVVSANF TLHEAYCLRF LVLCPECEEP VPKETMEEHC KLEHQQGKEF 70 80 90 100 110 120 QLLKGKSTVI IATKKANECQ 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

References

	« Hide 'large scale' referencesShow '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. , 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: 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. , 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: 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
EMBLGenBankDDBJ	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 , A2T932, A8K2L1, A8K9Y3, Q6MZE8, Q8N557, Q99982

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 8, 2008
Last sequence update:	July 19, 2004
Last modified:	November 25, 2008
This is version 32 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)