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Protein

XIAP-associated factor 1

Gene

XAF1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.5 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri22 – 99TRAF-typePROSITE-ProRule annotationAdd BLAST78

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-909733. Interferon alpha/beta signaling.
SIGNORiQ6GPH4.

Names & Taxonomyi

Protein namesi
Recommended name:
XIAP-associated factor 1
Alternative name(s):
BIRC4-binding protein
Gene namesi
Name:XAF1
Synonyms:BIRC4BP, XIAPAF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:30932. XAF1.

Subcellular locationi

  • Cytoplasm
  • Nucleus
  • Mitochondrion

  • Note: Found in the cytoplasm and nucleus of placental syncytiotrophoblasts. Translocates to mitochondria upon TNF-alpha treatment.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi54739.
OpenTargetsiENSG00000132530.
PharmGKBiPA162409299.

Polymorphism and mutation databases

BioMutaiXAF1.
DMDMi74736479.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003290281 – 301XIAP-associated factor 1Add BLAST301

Proteomic databases

MaxQBiQ6GPH4.
PaxDbiQ6GPH4.
PeptideAtlasiQ6GPH4.
PRIDEiQ6GPH4.

PTM databases

iPTMnetiQ6GPH4.
PhosphoSitePlusiQ6GPH4.

Expressioni

Tissue specificityi

Widely expressed. Expression is frequently down-regulated in cancer cell lines. Isoform 5 is widely expressed. Expressed in placenta (at protein level).4 Publications

Developmental stagei

Selectively expressed in third trimester placenta.1 Publication

Inductioni

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.2 Publications

Gene expression databases

BgeeiENSG00000132530.
CleanExiHS_XAF1.
ExpressionAtlasiQ6GPH4. baseline and differential.
GenevisibleiQ6GPH4. HS.

Organism-specific databases

HPAiHPA057302.

Interactioni

Subunit structurei

Interacts with BIRC4; the interaction is not detected in (PubMed:16432762). 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.4 Publications

Protein-protein interaction databases

BioGridi120121. 11 interactors.
IntActiQ6GPH4. 6 interactors.
MINTiMINT-216123.
STRINGi9606.ENSP00000354822.

Structurei

Secondary structure

1301
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni261 – 263Combined sources3
Beta strandi264 – 266Combined sources3
Turni268 – 270Combined sources3
Helixi279 – 292Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LXWNMR-A251-301[»]
ProteinModelPortaliQ6GPH4.
SMRiQ6GPH4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Contains 1 TRAF-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri22 – 99TRAF-typePROSITE-ProRule annotationAdd BLAST78

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IK96. Eukaryota.
ENOG4110HW5. LUCA.
GeneTreeiENSGT00530000063869.
HOVERGENiHBG108681.
InParanoidiQ6GPH4.
OMAiHYCNQMI.
OrthoDBiEOG091G0OSL.
PhylomeDBiQ6GPH4.
TreeFamiTF331416.

Family and domain databases

InterProiIPR031220. XAF1.
IPR001293. Znf_TRAF.
[Graphical view]
PANTHERiPTHR16295:SF17. PTHR16295:SF17. 1 hit.
PROSITEiPS50145. ZF_TRAF. 1 hit.
[Graphical view]

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6GPH4-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MEGDFSVCRN CKRHVVSANF TLHEAYCLRF LVLCPECEEP VPKETMEEHC
60 70 80 90 100
KLEHQQVGCT MCQQSMQKSS LEFHKANECQ ERPVECKFCK LDMQLSKLEL
110 120 130 140 150
HESYCGSRTE LCQGCGQFIM HRMLAQHRDV CRSEQAQLGK GERISAPERE
160 170 180 190 200
IYCHYCNQMI PENKYFHHMG KCCPDSEFKK HFPVGNPEIL PSSLPSQAAE
210 220 230 240 250
NQTSTMEKDV RPKTRSINRF PLHSESSSKK APRSKNKTLD PLLMSEPKPR
260 270 280 290 300
TSSPRGDKAA YDILRRCSQC GILLPLPILN QHQEKCRWLA SSKGKQVRNF

S
Length:301
Mass (Da):34,626
Last modified:July 19, 2004 - v1
Checksum:iFC9D48BD07BE541D
GO
Isoform 2 (identifier: Q6GPH4-2) [UniParc]FASTAAdd to basket
Also known as: XAF1B

The sequence of this isoform differs from the canonical sequence as follows:
     57-75: Missing.

Show »
Length:282
Mass (Da):32,471
Checksum:i6EAC4F7EC6F8E64A
GO
Isoform 3 (identifier: Q6GPH4-3) [UniParc]FASTAAdd to basket
Also known as: D

The sequence of this isoform differs from the canonical sequence as follows:
     142-301: Missing.

Show »
Length:141
Mass (Da):16,322
Checksum:iB286A33BC34A10A2
GO
Isoform 4 (identifier: Q6GPH4-4) [UniParc]FASTAAdd to basket
Also known as: E

The sequence of this isoform differs from the canonical sequence as follows:
     57-75: Missing.
     142-301: Missing.

Show »
Length:122
Mass (Da):14,167
Checksum:i36CC8B71B4DCCD8A
GO
Isoform 5 (identifier: Q6GPH4-5) [UniParc]FASTAAdd to basket
Also known as: XAF1C

The sequence of this isoform differs from the canonical sequence as follows:
     141-301: GERISAPERE...SKGKQVRNFS → ETSPDPGKCLSITVAAALSAHLWPFT

Show »
Length:166
Mass (Da):18,960
Checksum:i0EDD81DA26C30B50
GO
Isoform 6 (identifier: Q6GPH4-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-102: Missing.
     103-140: SYCGSRTELC...CRSEQAQLGK → MSLHYGCCCP...ACVVKDAGSA

Show »
Length:199
Mass (Da):22,507
Checksum:iFCA89ECA5FB0ED46
GO
Isoform 7 (identifier: Q6GPH4-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     57-74: VGCTMCQQSMQKSSLEFH → GKEFQLLKGKSTVIIATK

Note: No experimental confirmation available.
Show »
Length:301
Mass (Da):34,543
Checksum:i556947EBEFD6B84E
GO

Sequence cautioni

The sequence AAH32776 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAA68030 differs from that shown. Reason: Frameshift at position 294.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti132R → Q in BAF85537 (PubMed:14702039).Curated1
Sequence conflicti138L → R in BAF85537 (PubMed:14702039).Curated1
Sequence conflicti196S → R in BAF85537 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04261685E → G.Corresponds to variant rs34195599dbSNPEnsembl.1
Natural variantiVAR_042617132R → H.Corresponds to variant rs2271232dbSNPEnsembl.1
Natural variantiVAR_042618188E → K.Corresponds to variant rs34625877dbSNPEnsembl.1
Natural variantiVAR_042619219R → I.Corresponds to variant rs3736433dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0329181 – 102Missing in isoform 6. 1 PublicationAdd BLAST102
Alternative sequenceiVSP_03291957 – 75Missing in isoform 2 and isoform 4. 2 PublicationsAdd BLAST19
Alternative sequenceiVSP_03292057 – 74VGCTM…SLEFH → GKEFQLLKGKSTVIIATK in isoform 7. 1 PublicationAdd BLAST18
Alternative sequenceiVSP_032921103 – 140SYCGS…AQLGK → MSLHYGCCCPECTSVAIKEM MWVIRPRVACVVKDAGSA in isoform 6. 1 PublicationAdd BLAST38
Alternative sequenceiVSP_032922141 – 301GERIS…VRNFS → ETSPDPGKCLSITVAAALSA HLWPFT in isoform 5. CuratedAdd BLAST161
Alternative sequenceiVSP_032923142 – 301Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST160

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS11080.1. [Q6GPH4-1]
CCDS11081.1. [Q6GPH4-2]
RefSeqiNP_059993.2. NM_017523.3. [Q6GPH4-1]
NP_954590.1. NM_199139.2. [Q6GPH4-2]
XP_005256765.1. XM_005256708.2. [Q6GPH4-6]
UniGeneiHs.441975.

Genome annotation databases

EnsembliENST00000346752; ENSP00000341029; ENSG00000132530. [Q6GPH4-2]
ENST00000361842; ENSP00000354822; ENSG00000132530. [Q6GPH4-1]
ENST00000571673; ENSP00000461196; ENSG00000132530. [Q6GPH4-4]
ENST00000574962; ENSP00000458229; ENSG00000132530. [Q6GPH4-3]
GeneIDi54739.
KEGGihsa:54739.
UCSCiuc002gdn.4. human. [Q6GPH4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS11080.1. [Q6GPH4-1]
CCDS11081.1. [Q6GPH4-2]
RefSeqiNP_059993.2. NM_017523.3. [Q6GPH4-1]
NP_954590.1. NM_199139.2. [Q6GPH4-2]
XP_005256765.1. XM_005256708.2. [Q6GPH4-6]
UniGeneiHs.441975.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LXWNMR-A251-301[»]
ProteinModelPortaliQ6GPH4.
SMRiQ6GPH4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120121. 11 interactors.
IntActiQ6GPH4. 6 interactors.
MINTiMINT-216123.
STRINGi9606.ENSP00000354822.

PTM databases

iPTMnetiQ6GPH4.
PhosphoSitePlusiQ6GPH4.

Polymorphism and mutation databases

BioMutaiXAF1.
DMDMi74736479.

Proteomic databases

MaxQBiQ6GPH4.
PaxDbiQ6GPH4.
PeptideAtlasiQ6GPH4.
PRIDEiQ6GPH4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000346752; ENSP00000341029; ENSG00000132530. [Q6GPH4-2]
ENST00000361842; ENSP00000354822; ENSG00000132530. [Q6GPH4-1]
ENST00000571673; ENSP00000461196; ENSG00000132530. [Q6GPH4-4]
ENST00000574962; ENSP00000458229; ENSG00000132530. [Q6GPH4-3]
GeneIDi54739.
KEGGihsa:54739.
UCSCiuc002gdn.4. human. [Q6GPH4-1]

Organism-specific databases

CTDi54739.
DisGeNETi54739.
GeneCardsiXAF1.
HGNCiHGNC:30932. XAF1.
HPAiHPA057302.
MIMi606717. gene.
neXtProtiNX_Q6GPH4.
OpenTargetsiENSG00000132530.
PharmGKBiPA162409299.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IK96. Eukaryota.
ENOG4110HW5. LUCA.
GeneTreeiENSGT00530000063869.
HOVERGENiHBG108681.
InParanoidiQ6GPH4.
OMAiHYCNQMI.
OrthoDBiEOG091G0OSL.
PhylomeDBiQ6GPH4.
TreeFamiTF331416.

Enzyme and pathway databases

ReactomeiR-HSA-909733. Interferon alpha/beta signaling.
SIGNORiQ6GPH4.

Miscellaneous databases

ChiTaRSiXAF1. human.
GeneWikiiXAF1.
GenomeRNAii54739.
PROiQ6GPH4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000132530.
CleanExiHS_XAF1.
ExpressionAtlasiQ6GPH4. baseline and differential.
GenevisibleiQ6GPH4. HS.

Family and domain databases

InterProiIPR031220. XAF1.
IPR001293. Znf_TRAF.
[Graphical view]
PANTHERiPTHR16295:SF17. PTHR16295:SF17. 1 hit.
PROSITEiPS50145. ZF_TRAF. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiXAF1_HUMAN
AccessioniPrimary (citable) accession number: Q6GPH4
Secondary accession number(s): A2T931
, A2T932, A8K2L1, A8K9Y3, D3DTM6, Q6MZE8, Q8N557, Q99982
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 8, 2008
Last sequence update: July 19, 2004
Last modified: November 30, 2016
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.