ZNF217

Identity

Other names	13009
	FLJ14031
	ZABC1
Hugo	ZNF217
Location	20q13.2

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
Hugo	ZNF217
GDB	ZNF217
Entrez_Gene	ZNF217  7764  zinc finger protein 217
	Cards
Atlas	ZNF217ID42875ch20q13
GeneCards	ZNF217
Ensembl	ZNF217 [Search_View]   ENSG00000171940 [Gene_View]
Genatlas	ZNF217
GeneLynx	ZNF217
eGenome	ZNF217
euGene	7764
	Genomic and cartography
GoldenPath	ZNF217  -  20q13.2   chr20:51617019-51633043 -  20q13.2   [Description]    (hg18-Mar_2006)
Ensembl	ZNF217 - 20q13.2 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	ZNF217
	Gene and transcription
Genbank	AF041259 [ ENTREZ ]
Genbank	BC039055 [ ENTREZ ]
Genbank	BC113427 [ ENTREZ ]
Genbank	CR598126 [ ENTREZ ]
RefSeq	NM_006526 [ SRS ]    NM_006526 [ ENTREZ ]
RefSeq	AC_000063 [ SRS ]    AC_000063 [ ENTREZ ]
RefSeq	NC_000020 [ SRS ]    NC_000020 [ ENTREZ ]
RefSeq	NT_011362 [ SRS ]    NT_011362 [ ENTREZ ]
RefSeq	NW_927339 [ SRS ]    NW_927339 [ ENTREZ ]
AceView	ZNF217 AceView - NCBI
Unigene	Hs.155040 [ SRS ]    Hs.155040 [ NCBI ]     HS155040 [ spliceNest ]
Fast-db	13584 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	O75362 [ SRS]    O75362 [ EXPASY ]     O75362 [ INTERPRO ]
Prosite	PS00028 ZINC_FINGER_C2H2_1 [ SRS ]    PS00028 ZINC_FINGER_C2H2_1 [ Expasy ]
Prosite	PS50157 ZINC_FINGER_C2H2_2 [ SRS ]    PS50157 ZINC_FINGER_C2H2_2 [ Expasy ]
Interpro	IPR007087 Znf_C2H2 [ SRS ]    IPR007087 Znf_C2H2 [ EBI ]
Interpro	IPR015880 Znf_C2H2-like [ SRS ]    IPR015880 Znf_C2H2-like [ EBI ]
Interpro	IPR013087 Znf_C2H2/integrase_DNA-bd [ SRS ]    IPR013087 Znf_C2H2/integrase_DNA-bd [ EBI ]
CluSTr	O75362
Pfam	PF00096 zf-C2H2 [ SRS ]    PF00096 zf-C2H2 [ Sanger ]    pfam00096 [ NCBI-CDD ]
Smart	SM00355 ZnF_C2H2 [EMBL]
Blocks	O75362
HPRD	04272
	Protein Interaction databases
DIP	O75362
IntAct	O75362
	Polymorphism : SNP, mutations, diseases
OMIM	602967    [ map ]
GENECLINICS	602967
SNP	ZNF217 [dbSNP-NCBI]
SNP	NM_006526 [SNP-NCI]
SNP	ZNF217 [GeneSNPs - Utah]  ZNF217] [HGBASE - SRS]
HAPMAP	ZNF217 [HAPMAP]
COSMIC	ZNF217 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	ZNF217
	General knowledge
Family Browser	ZNF217 [UCSC Family Browser]
SOURCE	NM_006526
SMD	Hs.155040
SAGE	Hs.155040
GO	transcription factor activity [Amigo]  transcription factor activity
GO	intracellular [Amigo]  intracellular
GO	nucleus [Amigo]  nucleus
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	zinc ion binding [Amigo]  zinc ion binding
GO	metal ion binding [Amigo]  metal ion binding
PubGene	ZNF217
TreeFam	ZNF217
CTD	7764 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	ZNF217 Related clones (RZPD - Berlin)
	PubMed
PubMed	14 Pubmed reference(s) in LocusLink

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 articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written	09-2005	Paul Yaswen, Colin Collins
		Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Bldg 977-225A, Berkeley, CA 94720-8174, US

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

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Jul 2 08:28:13 2008