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ZNF217

Identity

Other names13009
FLJ14031
ZABC1
HGNC (Hugo) ZNF217
Location 20q13.2
Location_base_pair Starts at 51617017 and ends at 51633043 bp from pter ( according to hg18-Mar_2006)  [Mapping]

DNA/RNA

 
  Genomic organization of ZNF217. (A) The genomic organization of the five exons with encoded initiation and termination codons that make up ZNF217. Hatched boxes represent known 59- and 39-untranslated regions (UTR) in the cDNA. The sizes of exons and introns appear below and above the map, respectively. (B) The map of the 5632-bp ZNF217 cDNA. Vertical bars represent exon boundaries. The relative positions of the predicted eight C2H2 Kruppel-like zinc finger motifs are indicated by white circles. The position of the proline-rich putative transcription activator domain is shown as a hatched oval. AUUUA motifs are indicated in the 39-untranslated region. The relative locations of three ESTs are shown in boxes.
Description 5 exons
Transcription Exon 4 encodes a TGA termination codon and is alternatively processed.
Pseudogene None

Protein

 
  Eight C2H2 zinc fingers and a proline-rich domain. Conserved linker sequence, TGEKP, reported to bind DNA with high affinity
Description Full-length ZNF217 cDNAs encode two open reading frames of 1,062 and 1,108 amino acids, due to alternative splicing of exon 4.  Each predicted protein has eight C2H2 zinc fingers and a proline-rich domain.  Sequence analysis of ZNF217 indicates a strong resemblance to members of the Kruppel-like family of zinc finger proteins. The eight zinc finger domains in ZNF217 are interspersed throughout the ZNF217 sequence and their pattern does not appear to fall into one of the three classes of C2H2 zinc finger proteins; triple-C2H2, multiple­adjacent, and separated-paired fingers. The sixth and seventh zinc fingers in ZNF217 are separated by the conserved linker sequence, TGEKP, reported to bind DNA with high affinity.  Database analysis indicates that this paired zinc finger region aligns with those in several members of the Delta-EF1/ZFH-1 family of two-handed zinc-finger homeodomain proteins, including Smad-Interacting Protein 1 (SIP-1).
Expression ZNF217 is expressed at low levels in normal tissues.
Localisation Nuclear
Function ZNF217 protein localizes to the nucleus and co-immunoprecipitates with complexes containing the transcriptional corepressors CoREST and CtBP, histone deacetylases HDAC1 and HDAC2, and histone methyltransferases G9a and Eu-HMTase1.  This strongly suggests that ZNF217 may function as part of a transcriptional repressor complex.

Implicated in

Entity The findings that ZNF217 can immortalize human mammary epithelial cells, and that its amplification is associated with poor prognosis, suggest that it may play roles in both early and late stage breast cancer. ZNF217 can attenuate apoptotic signals resulting from telomere dysfunction as well as from doxorubicin-induced DNA damage, while silencing ZNF217 with siRNA restores sensitivity to doxorubicin. Moreover, elevated ZNF217 leads to increased phosphorylation of Akt, whereas inhibition of the phosphatidylinositol 3 kinase pathway and Akt phosphorylation decreases ZNF217 protein levels and increases sensitivity to doxorubicin. These results suggest that ZNF217 may promote neoplastic transformation by increasing cell survival during telomeric crisis, and may promote later stages of malignancy by increasing cell survival during chemotherapy.
  

External links

Nomenclature
HGNC (Hugo)ZNF217   13009
Entrez_Gene (NCBI)ZNF217  7764  zinc finger protein 217
Cards
AtlasZNF217ID42875ch20q13
GeneCards (Weizmann)ZNF217
Ensembl (Hinxton)ENSG00000171940 [Gene_View]  ZNF217 [Vega]
AceView (NCBI)ZNF217
Genatlas (Paris)ZNF217
euGene (Indiana)7764
SOURCE (Stanford)NM_006526
Genomic and cartography
GoldenPath (UCSC)ZNF217  -  20q13.2   chr20:51617017-51633043 -  20q13.2   [Description]    (hg18-Mar_2006)
EnsemblZNF217 - 20q13.2 [CytoView]
Mapping of homologs : NCBIZNF217 [Mapview]
OMIM602967   
Gene and transcription
Gene : Genbank (Entrez)AF041259 AK290350 BC039055 BC113427 CR598126
Reference sequence (RefSeq transcript) :SRSNM_006526
Reference transcript : EntrezNM_006526
RefSeq genomic : SRSAC_000063 AC_000152 NC_000020 NT_011362 NW_001838666 NW_927339
RefSeq genomic : EntrezAC_000063 AC_000152 NC_000020 NT_011362 NW_001838666 NW_927339
Consensus coding sequences : CCDS NCBIZNF217
Cluster EST : UnigeneHs.711564 [ SRS ] Hs.711564 [ NCBI ]
Alternative Splicing : Fast-db (Paris)13584
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtO75362 (SRS) O75362 (Expasy) O75362 (Uniprot)
With graphics : InterProO75362
Splice isoforms : VarSplice FASTAO75362(VarSplice FASTA)
Domaine pattern : Prosite (SRS)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domain pattern : Prosite (Expaxy)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domains : Interpro (SRS)Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
Domains : Interpro (EBI)Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
Related proteins : CluSTrO75362
Domain families : Pfam SRSzf-C2H2 (PF00096)   
Domain families : Pfam Sangerzf-C2H2 (PF00096)   
Domain families : Pfam NCBIpfam00096   
Domain families : Smart EMBLZnF_C2H2 (SM00355)
Blocks (Seattle)O75362
Crystal structure of protein : PDB SRS
Crystal structure of protein : PDBSum
Crystal structure of protein : IMB
Crystal structure of protein : PDB RSDB
HPRD04272
Protein Interaction databases
DIP (DOE-UCLA)O75362
IntAct (EBI)O75362
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIZNF217
SNP : GeneSNP UtahZNF217
SNP : HGBaseZNF217
Genetic variants : HAPMAPZNF217
Somatic Mutations in Cancer : COSMICZNF217 
Mutations and Diseases : HGMDZNF217
Hereditary diseases : OMIM602967   
Hereditary diseases : GENETests602967   
Diseases : Genetic AssociationZNF217
General knowledge
Homologs : HomoloGeneZNF217
Homology/Alignments : Family Browser UCSCZNF217
Phylogenetic Trees/Animal Genes : TreeFamZNF217
Chemical/Protein Interactions : CTD7764
Keywords Ontology : AmiGOtranscription factor activity  intracellular  nucleus  regulation of transcription, DNA-dependent  zinc ion binding  metal ion binding  
Keywords Ontology : EGO-EBItranscription factor activity  intracellular  nucleus  regulation of transcription, DNA-dependent  zinc ion binding  metal ion binding  
Pathways : BIOCARTA
Pathways : KEGG
Other databases
Probes
Probes : ImagenesZNF217 Related clones (RZPD - Berlin)
Literature
PubMed17 Pubmed reference(s) in Entrez
PubGeneZNF217

Bibliography

Positional cloning of ZNF217 and NABC1: genes amplified at 20q13.2 and overexpressed in breast carcinoma.
Collins C, Rommens JM, Kowbel D, Godfrey T, Tanner M, Hwang SI, Polikoff D, Nonet G, Cochran J, Myambo K, Jay KE, Froula J, Cloutier T, Kuo WL, Yaswen P, Dairkee S, Giovanola J, Hutchinson GB, Isola J, Kallioniemi OP, Palazzolo M, Martin C, Ericsson C, Pinkel D, Albertson D, Li WB, Gray JW
Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (15) : 8703-8708.
PMID 9671742
 
The ZNF217 gene amplified in breast cancers promotes immortalization of human mammary epithelial cells.
Nonet GH, Stampfer MR, Chin K, Gray JW, Collins CC, Yaswen P
Cancer research. 2001 ; 61 (4) : 1250-1254.
PMID 11245413
 
In situ analyses of genome instability in breast cancer.
Chin K, de Solorzano CO, Knowles D, Jones A, Chou W, Rodriguez EG, Kuo WL, Ljung BM, Chew K, Myambo K, Miranda M, Krig S, Garbe J, Stampfer M, Yaswen P, Gray JW, Lockett SJ
Nature genetics. 2004 ; 36 (9) : 984-988.
PMID 15300252
 
The candidate oncogene ZNF217 is frequently amplified in colon cancer.
Rooney PH, Boonsong A, McFadyen MC, McLeod HL, Cassidy J, Curran S, Murray GI
The Journal of pathology. 2004 ; 204 (3) : 282-288.
PMID 15476264
 
Detection of Her2/neu, c-MYC and ZNF217 gene amplification during breast cancer progression using fluorescence in situ hybridization.
Shimada M, Imura J, Kozaki T, Fujimori T, Asakawa S, Shimizu N, Kawaguchi R
Oncology reports. 2005 ; 13 (4) : 633-641.
PMID 15756435
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written09-2005Paul Yaswen, Colin Collins
Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Bldg 977-225A, Berkeley, CA 94720-8174, USA

Citation

This paper should be referenced as such :
Yaswen P, Collins C . ZNF217. Atlas Genet Cytogenet Oncol Haematol. September 2005 .
URL : http://AtlasGeneticsOncology.org/Genes/ZNF217ID42875ch20q13.html

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indexed on : Sat Jun 27 16:38:08 CEST 2009

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