ZNF217 (zinc finger protein 217)

2005-09-01 Paul Yaswen , Colin Collins Affiliation

Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Bldg 977-225A, Berkeley, CA 94720-8174, USA

Identity

HGNC

ZNF217

LOCATION

20q13.2

LOCUSID

7764

ALIAS

ZABC1

FUSION GENES

Show Gene Fusions

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

Proteins

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, multiple adjacent, 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

Breast cancer

Note

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.

Bibliography

Pubmed ID	Last Year	Title	Authors
15300252	2004	In situ analyses of genome instability in breast cancer.	Chin K et al
9671742	1998	Positional cloning of ZNF217 and NABC1: genes amplified at 20q13.2 and overexpressed in breast carcinoma.	Collins C et al
11245413	2001	The ZNF217 gene amplified in breast cancers promotes immortalization of human mammary epithelial cells.	Nonet GH et al
15476264	2004	The candidate oncogene ZNF217 is frequently amplified in colon cancer.	Rooney PH et al
15756435	2005	Detection of Her2/neu, c-MYC and ZNF217 gene amplification during breast cancer progression using fluorescence in situ hybridization.	Shimada M et al

Other Information

Locus ID:

NCBI: 7764
MIM: 602967
HGNC: 13009
Ensembl: ENSG00000171940

Variants:

dbSNP: 7764
ClinVar: 7764
TCGA: ENSG00000171940
COSMIC: ZNF217

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000171940	ENST00000302342	O75362
ENSG00000171940	ENST00000371471	O75362
ENSG00000171940	ENST00000431687	A2A326
ENSG00000171940	ENST00000437222	Q9BZ31

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
27590511	2016	Hypoxia-inducible factors regulate pluripotency factor expression by ZNF217- and ALKBH5-mediated modulation of RNA methylation in breast cancer cells.	69
17130829	2007	Biochemical characterization of the zinc-finger protein 217 transcriptional repressor complex: identification of a ZNF217 consensus recognition sequence.	48
16940172	2006	Specific recognition of ZNF217 and other zinc finger proteins at a surface groove of C-terminal binding proteins.	43
24615544	2014	MiR-200c suppresses TGF-β signaling and counteracts trastuzumab resistance and metastasis by targeting ZNF217 and ZEB1 in breast cancer.	43
22593193	2012	ZNF217 is a marker of poor prognosis in breast cancer that drives epithelial-mesenchymal transition and invasion.	40
19242095	2009	The ZNF217 oncogene is a candidate organizer of repressive histone modifiers.	34
17572303	2007	Amplification of zinc finger gene 217 (ZNF217) and cancer: when good fingers go bad.	30
22815235	2013	Identification of ZNF217, hnRNP-K, VEGF-A and IPO7 as targets for microRNAs that are downregulated in prostate carcinoma.	29
22728437	2012	The transcription factor ZNF217 is a prognostic biomarker and therapeutic target during breast cancer progression.	28
16203743	2005	ZNF217 suppresses cell death associated with chemotherapy and telomere dysfunction.	25

Citation

Paul Yaswen ; Colin Collins

ZNF217 (zinc finger protein 217)

Atlas Genet Cytogenet Oncol Haematol. 2005-09-01

Online version: http://atlasgeneticsoncology.org/gene/42875/znf217