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ZFX (zinc finger protein, X-linked)

Written2014-10Modjtaba Emadi-Baygi
Dept of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)ZNF926
Other alias
HGNC (Hugo) ZFX
LocusID (NCBI) 7543
Atlas_Id 43623
Location Xp22.11  [Link to chromosome band Xp22]
Location_base_pair Starts at 24167841 and ends at 24234372 bp from pter ( according to hg19-Feb_2009)  [Mapping ZFX.png]
Fusion genes
(updated 2016)
PDZK1 (1q21.1) / ZFX (Xp22.11)ZFX (Xp22.11) / APOO (Xp22.11)ZFX (Xp22.11) / KLHL15 (Xp22.11)
ZFX (Xp22.11) / MTA3 (2p21)

DNA/RNA

Note Differential splicing of a single ZFX transcript results in five variants. Variants 1, 2 and 3 result in isoform I, variant 4 results in isoform II and variant 5 results in isoform III.
 
  Structure of the human ZFX gene. Exon positions (green) and sizes (nt-nucleotides) are labelled.
Description ZFX gene is a human X- chromosome gene that escapes X inactivation (Schneider-Gadicke et al.,1989a) and is composed of 10 exons, ranging in size from 57 to 6062 nt. Exons 1 to 5 in isoform 2 and exons 1 to 6 in isoform 1 comprise the 5' UTR and encodes N-terminal acidic domain. Exon 10 contains 3' UTR and AATAAA polyadenylation signal and encodes C-terminal zinc - finger domain for isoforms 1 and 2 (Schneider-Gadicke et al.,1989a).
Transcription Transcription initiation sites were not exactly identified, but there is same ORF with the first ATG codon at nucleotide 1 in cDNAs (Schneider-Gadicke et al.,1989b).
Pseudogene Pseudogenes were not exactly identified.

Protein

 
  Structure of the human ZFX isoforms. Acidic domain (orange), nuclear localisation signal (blue) and zinc finger domain (green) are labelled.
Description The ZFX isoform I, the longest isoform, contains 805 amino acids (130 kDa). Isoforms II (91 kDa) and III contain 576 and 432 amino acids, respectively. Isoform II binds to the AGGGCCCCA and AGGCCCCGA sequences located at HLA-A11 promoter (L'Haridon et al.,1996) and in accompanying with isoform I could play a role as co-activators in HIV-1 LTR induction (Nikpour et al., 2012). Isoforms I and II contain three domains: acidic domain (transcription activation region), nuclear localization signal (NLS) and 13 zinc finger domains, that differ in the length of their N-terminal (acidic) domain resulting in qualitatively and quantitatively different regulatory properties (Schneider-Gadicke et al., 1989b).
Expression ZFX gene escapes X inactivation in humans (Schneider-Gadicke et al., 1989a) and is expressed in a wide range of human tissues (Schneider-Gadicke et al.,1989b).
Localisation It was shown that ZFX isoform I is concentrated in the nucleus of glioma cell line, while ZFX isoform II is found in the cytoplasm (Zhu et al., 2013).
Function ZFX gene is differentially expressed in tissues and may have separate functions in gonadal and somatic tissues (Lau and Chan, 1989). It may play a role as a sex determination factor in mammals (Zhu et al., 2013). ZFX acts as a transcriptional regulator in self renewal and differentiation mechanisms in human embryonic and hematopoietic stem cells (Galan-Caridad et al., 2007; Harel et al., 2012). ZFX has an important role in cell cycle progression and cell growth control (Jiang et al., 2012b).
Homology In mammals, ZFX gene is highly conserved (Ashworth et al., 1990; Lau and Chan, 1989; Palmer et al., 1990). Zinc finger protein X linked is one of the members of ZFY family comprised of three members: ZFX, ZFY and ZFA (Palmer et al., 1990).

Mutations

Note A novel Xp22.11 deletion causing a syndrome of craniosynostosis and periventricular nodular heterotopias affecting all or part of three annotated genes, ZFX, PDK3, and PCYT1B has recently been reported in a male subject (van Kogelenberg et al., 2011). Furthermore, Zfx mutation results in small animal size and reduced germ cell number in male and female mice (Luoh et al., 1997). Moreover, molecular cytogenetic analysis of a male infant with severe mental retardation and autism shows that there is a duplication in Xp in this subject (Rao et al., 1994).

Implicated in

Note
  
Entity Glioma cell and cell lines
Note In human glioma cell lines, knocking down of ZFX expression by lentivirus-mediated RNA interference (RNAi) shows that ZFX plays an important role in glioma cell proliferation, survival and growth potential in both subcutaneous and intracranial models in mice (Zhu et al., 2013). Furthermore, Zhou et al. detected ZFX expression in U251 cells using semi- quantitative PCR. They showed that expression of ZFX is significantly higher in glioma tissues compared to non glioma tissues using real-time RT-PCR. In the same vein, Knocking down of ZFX gene expression in U251 cells results in disturbed cell proliferation and increased apoptosis and arrested cells in S phase (Zhou et al., 2011).
  
  
Entity Gastric cancer tissues and cells
Note ZFX gene expression was examined by quantitative real-time RT-PCR in 30 paired gastric tissue samples. Result shows that ZFX gene has differential expression in gastric tissues. There is a statistically significant association between the ZFX expression and different tumour types and grades (Nikpour et al., 2012). Furthermore, ZFX silencing inhibits gastric cancer cell growth in both in vitro and in vivo via modulating extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK-MAPK) pathway (Wu et al., 2013).
  
  
Entity Non - small cell lung cancer (NSCLC)
Note ZFX overexpresses in NSCLC and its expression is correlated with lymph node metastasis. Knocking down of ZFX gene by short hairpin RNA interference (shRNA) in NSCLC cell line reduces cell viability and colony formation and causes cell cycle arrest (Jiang et al., 2012b).
  
  
Entity Laryngeal squamous cell carcinoma (LSCC)
Note ZFX expression up-regulates in LSCC tissues compared to the non- tumoral tissues. Knock-down of ZFX by shRNA results in suppression of proliferation and colony-forming potential of infected Hep-2 human LSCC cells and induces enhancing of cell apoptosis. Furthermore, high expression of ZFX associates with LSCC progression and its decreased expression associates with declined tumor cell growth (Fang et al., 2012).
  
  
Entity Osteosarcoma cells
Note Inhibition of ZFX expression by siRNA results in decreased proliferation, colony formation and invasion of Saos-2 cells. Silencing of ZFX gene expression causes cell cycle arrest in which greater portion of the cells existed in G1 phase and minor portion in S and G2/M phases (Jiang et al., 2013; Jiang et al., 2012a).
  
  
Entity Prostate cancer
Note Prostate cancer tissues show higher expression of ZFX than that observed in normal adjacent tissues and BPH tissues. Furthermore, silencing the expression of ZFX in the prostate cancer cells effectively abolishes the cellular proliferation and colony-formation ability, and results in G1 phase cell cycle arrest. Moreover, inhibition of ZFX induces apoptosis by activating caspase-1, caspase-3 and caspase-9. (Jiang et al., 2012c).
  
  
Entity Childhood B lineage acute lymphoblastic leukemia
Note ZFX protein expresses in human leukemia cell lines REH, HL-60, NB(4) and K562. Furthermore, ZFX mRNA expression increases in the newly-diagnosed ALL group while in the ALL complete remission group was significantly reduces. Moreover, ZFX mRNA level is significantly higher in Children with a poor prognosis than those with a good prognosis at diagnosis (Wang et al., 2013).
  

Bibliography

Zfa is an expressed retroposon derived from an alternative transcript of the Zfx gene.
Ashworth A, Skene B, Swift S, Lovell-Badge R.
EMBO J. 1990 May;9(5):1529-34.
PMID 1691708
 
Knockdown of zinc finger protein, X-linked (ZFX) inhibits cell proliferation and induces apoptosis in human laryngeal squamous cell carcinoma.
Fang J, Yu Z, Lian M, Ma H, Tai J, Zhang L, Han D.
Mol Cell Biochem. 2012 Jan;360(1-2):301-7. doi: 10.1007/s11010-011-1069-x. Epub 2011 Oct 19.
PMID 22009483
 
Zfx controls the self-renewal of embryonic and hematopoietic stem cells.
Galan-Caridad JM, Harel S, Arenzana TL, Hou ZE, Doetsch FK, Mirny LA, Reizis B.
Cell. 2007 Apr 20;129(2):345-57.
PMID 17448993
 
ZFX controls the self-renewal of human embryonic stem cells.
Harel S, Tu EY, Weisberg S, Esquilin M, Chambers SM, Liu B, Carson CT, Studer L, Reizis B, Tomishima MJ.
PLoS One. 2012;7(8):e42302. doi: 10.1371/journal.pone.0042302. Epub 2012 Aug 3.
PMID 22879936
 
Knockdown of zinc finger protein X-linked inhibits prostate cancer cell proliferation and induces apoptosis by activating caspase-3 and caspase-9.
Jiang H, Zhang L, Liu J, Chen Z, Na R, Ding G, Zhang H, Ding Q.
Cancer Gene Ther. 2012c Oct;19(10):684-9. doi: 10.1038/cgt.2012.53. Epub 2012 Aug 17.
PMID 22898899
 
The role of ZFX in non-small cell lung cancer development.
Jiang M, Xu S, Yue W, Zhao X, Zhang L, Zhang C, Wang Y.
Oncol Res. 2012b;20(4):171-8.
PMID 23461064
 
Zinc finger X-chromosomal protein promotes growth and tumorigenesis in human osteosarcoma cells.
Jiang R, Gao ZL, Sun M, Zhang XY, Wang JC, Wu H.
Pak J Med Sci. 2013 Jul;29(4):997-1002.
PMID 24353675
 
Zinc finger X-chromosomal protein (ZFX) promotes solid agar colony growth of osteosarcoma cells.
Jiang R, Wang JC, Sun M, Zhang XY, Wu H.
Oncol Res. 2012a;20(12):565-70. doi: 10.3727/096504013X13775486749290.
PMID 24139414
 
Transcriptional regulation of the MHC class I HLA-A11 promoter by the zinc finger protein ZFX.
L'Haridon M, Paul P, Xerri JG, Dastot H, Dolliger C, Schmid M, de Angelis N, Grollet L, Sigaux F, Degos L, Gazin C.
Nucleic Acids Res. 1996 May 15;24(10):1928-35.
PMID 8657576
 
The putative testis-determining factor and related genes are expressed as discrete-sized transcripts in adult gonadal and somatic tissues.
Lau YF, Chan KM.
Am J Hum Genet. 1989 Dec;45(6):942-52.
PMID 2511751
 
Zfx mutation results in small animal size and reduced germ cell number in male and female mice.
Luoh SW, Bain PA, Polakiewicz RD, Goodheart ML, Gardner H, Jaenisch R, Page DC.
Development. 1997 Jun;124(11):2275-84.
PMID 9187153
 
Differential expression of ZFX gene in gastric cancer.
Nikpour P, Emadi-Baygi M, Mohammad-Hashem F, Maracy MR, Haghjooy-Javanmard S.
J Biosci. 2012 Mar;37(1):85-90.
PMID 22357206
 
Comparison of human ZFY and ZFX transcripts.
Palmer MS, Berta P, Sinclair AH, Pym B, Goodfellow PN.
Proc Natl Acad Sci U S A. 1990 Mar;87(5):1681-5.
PMID 2308929
 
Molecular cytogenetic analysis of a duplication Xp in a male: further delineation of a possible sex influencing region on the X chromosome.
Rao PN, Klinepeter K, Stewart W, Hayworth R, Grubs R, Pettenati MJ.
Hum Genet. 1994 Aug;94(2):149-53.
PMID 8045561
 
ZFX has a gene structure similar to ZFY, the putative human sex determinant, and escapes X inactivation.
Schneider-Gadicke A, Beer-Romero P, Brown LG, Nussbaum R, Page DC.
Cell. 1989 Jun 30;57(7):1247-58.
PMID 2500252
 
[Expression of zinc finger protein X-linked in childhood B lineage acute lymphoblastic leukemia].
Wang Z, Liang HH, Li BS, Huang XH, Zhang J, Wang X, Ding LX, Jiang H.
Zhongguo Dang Dai Er Ke Za Zhi. 2013 Jul;15(7):509-13.
PMID 23866268
 
Knockdown of ZFX inhibits gastric cancer cell growth in vitro and in vivo via downregulating the ERK-MAPK pathway.
Wu S, Lao XY, Sun TT, Ren LL, Kong X, Wang JL, Wang YC, Du W, Yu YN, Weng YR, Hong J, Fang JY.
Cancer Lett. 2013 Sep 1;337(2):293-300. doi: 10.1016/j.canlet.2013.04.003. Epub 2013 Apr 13.
PMID 23587796
 
The Zfx gene is expressed in human gliomas and is important in the proliferation and apoptosis of the human malignant glioma cell line U251.
Zhou Y, Su Z, Huang Y, Sun T, Chen S, Wu T, Chen G, Xie X, Li B, Du Z.
J Exp Clin Cancer Res. 2011 Dec 20;30:114. doi: 10.1186/1756-9966-30-114.
PMID 22185393
 
ZFX regulates glioma cell proliferation and survival in vitro and in vivo.
Zhu Z, Li K, Xu D, Liu Y, Tang H, Xie Q, Xie L, Liu J, Wang H, Gong Y, Hu Z, Zheng J.
J Neurooncol. 2013 Mar;112(1):17-25. doi: 10.1007/s11060-012-1032-z. Epub 2013 Jan 16.
PMID 23322077
 
A novel Xp22.11 deletion causing a syndrome of craniosynostosis and periventricular nodular heterotopia.
van Kogelenberg M, Lerone M, De Toni T, Divizia MT, de Brouwer AP, Veltman JA, van Bokhoven H, Robertson SP.
Am J Med Genet A. 2011 Dec;155A(12):3144-7. doi: 10.1002/ajmg.a.34311. Epub 2011 Nov 3.
PMID 22052819
 

Citation

This paper should be referenced as such :
Emadi-Baygi M
ZFX (zinc finger protein, X-linked);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/ZFXID43623chXp22.html


External links

Nomenclature
HGNC (Hugo)ZFX   12869
Cards
AtlasZFXID43623chXp22
Entrez_Gene (NCBI)ZFX  7543  zinc finger protein, X-linked
AliasesZNF926
GeneCards (Weizmann)ZFX
Ensembl hg19 (Hinxton)ENSG00000005889 [Gene_View]  chrX:24167841-24234372 [Contig_View]  ZFX [Vega]
Ensembl hg38 (Hinxton)ENSG00000005889 [Gene_View]  chrX:24167841-24234372 [Contig_View]  ZFX [Vega]
ICGC DataPortalENSG00000005889
TCGA cBioPortalZFX
AceView (NCBI)ZFX
Genatlas (Paris)ZFX
WikiGenes7543
SOURCE (Princeton)ZFX
Genetics Home Reference (NIH)ZFX
Genomic and cartography
GoldenPath hg19 (UCSC)ZFX  -     chrX:24167841-24234372 +  Xp22.1-p21.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)ZFX  -     Xp22.1-p21.3   [Description]    (hg38-Dec_2013)
EnsemblZFX - Xp22.1-p21.3 [CytoView hg19]  ZFX - Xp22.1-p21.3 [CytoView hg38]
Mapping of homologs : NCBIZFX [Mapview hg19]  ZFX [Mapview hg38]
OMIM314980   
Gene and transcription
Genbank (Entrez)AB209892 AF454950 AF505615 AF505616 AF505617
RefSeq transcript (Entrez)NM_001178084 NM_001178085 NM_001178086 NM_001178095 NM_003410
RefSeq genomic (Entrez)NC_000023 NC_018934 NG_021253 NT_167197 NW_004929438
Consensus coding sequences : CCDS (NCBI)ZFX
Cluster EST : UnigeneHs.336681 [ NCBI ]
CGAP (NCI)Hs.336681
Alternative Splicing GalleryENSG00000005889
Gene ExpressionZFX [ NCBI-GEO ]   ZFX [ EBI - ARRAY_EXPRESS ]   ZFX [ SEEK ]   ZFX [ MEM ]
Gene Expression Viewer (FireBrowse)ZFX [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7543
GTEX Portal (Tissue expression)ZFX
Protein : pattern, domain, 3D structure
UniProt/SwissProtP17010   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP17010  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP17010
Splice isoforms : SwissVarP17010
PhosPhoSitePlusP17010
Domaine pattern : Prosite (Expaxy)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domains : Interpro (EBI)Transcrp_activ_Zfx/Zfy-dom    Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
Domain families : Pfam (Sanger)zf-C2H2 (PF00096)    Zfx_Zfy_act (PF04704)   
Domain families : Pfam (NCBI)pfam00096    pfam04704   
Domain families : Smart (EMBL)ZnF_C2H2 (SM00355)  
Conserved Domain (NCBI)ZFX
DMDM Disease mutations7543
Blocks (Seattle)ZFX
SuperfamilyP17010
Human Protein AtlasENSG00000005889
Peptide AtlasP17010
HPRD02445
IPIIPI01013198   IPI00012336   IPI01014987   IPI01015667   IPI00179465   IPI00974580   IPI00169385   
Protein Interaction databases
DIP (DOE-UCLA)P17010
IntAct (EBI)P17010
FunCoupENSG00000005889
BioGRIDZFX
STRING (EMBL)ZFX
ZODIACZFX
Ontologies - Pathways
QuickGOP17010
Ontology : AmiGORNA polymerase II regulatory region sequence-specific DNA binding  DNA binding  transcription factor activity, sequence-specific DNA binding  transcription coactivator activity  nucleus  transcription, DNA-templated  regulation of transcription, DNA-templated  multicellular organism development  metal ion binding  
Ontology : EGO-EBIRNA polymerase II regulatory region sequence-specific DNA binding  DNA binding  transcription factor activity, sequence-specific DNA binding  transcription coactivator activity  nucleus  transcription, DNA-templated  regulation of transcription, DNA-templated  multicellular organism development  metal ion binding  
NDEx NetworkZFX
Atlas of Cancer Signalling NetworkZFX
Wikipedia pathwaysZFX
Orthology - Evolution
OrthoDB7543
GeneTree (enSembl)ENSG00000005889
Phylogenetic Trees/Animal Genes : TreeFamZFX
HOVERGENP17010
HOGENOMP17010
Homologs : HomoloGeneZFX
Homology/Alignments : Family Browser (UCSC)ZFX
Gene fusions - Rearrangements
Fusion : MitelmanZFX/APOO [Xp22.11/Xp22.11]  
Fusion : MitelmanZFX/KLHL15 [Xp22.11/Xp22.11]  [t(X;X)(p22;p22)]  
Fusion: TCGAZFX Xp22.11 APOO Xp22.11 BRCA
Fusion: TCGAZFX Xp22.11 KLHL15 Xp22.11 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerZFX [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ZFX
dbVarZFX
ClinVarZFX
1000_GenomesZFX 
Exome Variant ServerZFX
ExAC (Exome Aggregation Consortium)ZFX (select the gene name)
Genetic variants : HAPMAP7543
Genomic Variants (DGV)ZFX [DGVbeta]
DECIPHER (Syndromes)X:24167841-24234372  ENSG00000005889
CONAN: Copy Number AnalysisZFX 
Mutations
ICGC Data PortalZFX 
TCGA Data PortalZFX 
Broad Tumor PortalZFX
OASIS PortalZFX [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICZFX  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDZFX
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)X-chromosome gene database
BioMutasearch ZFX
DgiDB (Drug Gene Interaction Database)ZFX
DoCM (Curated mutations)ZFX (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ZFX (select a term)
intoGenZFX
NCG5 (London)ZFX
Cancer3DZFX(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM314980   
Orphanet
MedgenZFX
Genetic Testing Registry ZFX
NextProtP17010 [Medical]
TSGene7543
GENETestsZFX
Huge Navigator ZFX [HugePedia]
snp3D : Map Gene to Disease7543
BioCentury BCIQZFX
ClinGenZFX
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7543
Chemical/Pharm GKB GenePA37458
Clinical trialZFX
Miscellaneous
canSAR (ICR)ZFX (select the gene name)
Probes
Litterature
PubMed33 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineZFX
EVEXZFX
GoPubMedZFX
iHOPZFX
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Apr 12 11:42:05 CEST 2017

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