CXXC5 (CXXC finger protein 5)

2014-04-01   Pelin Yaşar , Mesut Muyan 

Department of Biological Sciences, Middle East Technical University, Ankara, Turkey

Identity

HGNC
LOCATION
5q31.2
IMAGE
Atlas Image
LEGEND
Local order of CXXC5 is shown together with leading and subsequent genes on chromosome 5. The direction of arrows indicates transcriptional directions on the chromosome and arrow sizes approximate gene sizes.
LOCUSID
ALIAS
CF5,HSPC195,RINF,WID
FUSION GENES

DNA/RNA

Atlas Image
Boxes are exons. The lines are introns. Shaded parts of the exon boxes are coding regions. Unshaded parts are noncoding regions.

Description

The gene is on the plus strand and encompasses 35 kb of DNA. The exon number of gene is 3 and parts of the second and third exons encode the protein (ENSP00000302543).

Transcription

1447 bp long mRNA; 969 bp long open reading frame.

Pseudogene

No reported pseudogenes.

Proteins

Atlas Image
CXXC5 contains a nuclear localization signal adjacent to the CXXC-zinc finger domain.

Description

CXXC5 encodes a 322 amino-acid protein with a molecular mass of 33 kDa. Amino-acid sequence suggests that CXXC5 contains a number of phosphorylation and acetylation sites. By homology, CXXC5 is considered to be a member of CXXC-type zinc finger protein family, which binds to non-methylated CpG dinuclotide containing DNA.

Expression

CXXC5 is expressed in various tissues.

Localisation

CXXC5 protein is mainly in the nucleus. CXXC5 protein may also be localized in the cytoplasm coupled with Dishevelled (Dvl) protein (Andersson et al., 2009).

Function

CXXC5 can be induced by retinoid signaling and is required for myelopoiesis (Pendino et al., 2009). CXXC5 protein is involved in the DNA-damage induced p53 activation as well as in the regulation of cell cycle and apoptosis (Zhang et al., 2009). CXXC5 protein participates in the TNF-a-induced apoptosis through association with SMAD (Wang et al., 2013). CXXC5 protein is a critical modulator of BMP4-regulated Wnt-signaling in neural stem cells (Andersson et al., 2009). CXXC5 protein is shown to repress TET2 gene expression (Ko et al., 2013).

Homology

CXXC domain is a highly conserved domain of a class of proteins that interact with non-methylated CpG dinucleotides (CpGs). The CXXC domain of CXXC5 displays a significant homology to CXXC domains of CXXC4 and TET3 proteins (Ko et al., 2013).

Mutations

Note

Not defined yet.

Implicated in

Entity name
Acute myeloid leukemia (AML) and Myelodysplastic syndrome (MDS)
Disease
Acute myeloid leukemia (AML) is a disease manifested by cytogenetic anomalies affecting cell proliferation, death and differentiation (Renneville et al., 2008). Myelodysplastic syndrome (MDS) defines a hematological condition with insufficient hematopoiesis. MDS results from chromosomal deletions, inversions and translocations giving rise to trilineage dysplasia (Mhawech and Saleem, 2001).
Oncogenesis
The region on the chromosome 5 which also contains CXXC5 gene (5q31.2) is often deleted in AML and MDS (Treppendahl et al., 2013). Low survival rate has been observed in intensive chemotherapy treated patients with AML who show a high level of CXXC5 gene expression (Astori et al., 2013).
Disease
APL, which is characterized by the translocation event of the retinoic acid receptor alpha gene, is a rare subtype of AML in which leukemia cells are sensitive to anthracyclines (Tallman and Altman, 2008).
Oncogenesis
Terminal maturation of premyelocytic leukemia cells requires the expression of CXXC5 (Pendino et al., 2009).
Entity name
Breast cancer
Disease
Breast cancer is a disease which is mainly originated in the lining of the milk ducts and/or the lobules.
Oncogenesis
It has been shown that CXXC5 is transcriptionally upregulated in some solid tumors including melanoma, thyroid and breast cancer. In addition, overexpression of CXXC5 in breast cancer is suggested to be associated with poor prognosis (Knappskog et al., 2011).

Bibliography

Pubmed IDLast YearTitleAuthors
190013642009CXXC5 is a novel BMP4-regulated modulator of Wnt signaling in neural stem cells.Andersson T et al
239884572013CXXC5 (retinoid-inducible nuclear factor, RINF) is a potential therapeutic target in high-risk human acute myeloid leukemia.Astori A et al
213254502011RINF (CXXC5) is overexpressed in solid tumors and is an unfavorable prognostic factor in breast cancer.Knappskog S et al
235632672013Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX.Ko M et al
117389462001Myelodysplastic syndrome: review of the cytogenetic and molecular data.Mhawech P et al
191822102009Functional involvement of RINF, retinoid-inducible nuclear factor (CXXC5), in normal and tumoral human myelopoiesis.Pendino F et al
182881312008Cooperating gene mutations in acute myeloid leukemia: a review of the literature.Renneville A et al
190741162008Curative strategies in acute promyelocytic leukemia.Tallman MS et al
231901532013Downregulation but lack of promoter hypermethylation or somatic mutations of the potential tumor suppressor CXXC5 in MDS and AML with deletion 5q.Treppendahl MB et al
239063312013CXXC5 Associates with Smads to Mediate TNF-α Induced Apoptosis.Wang X et al
195573302009The CXXC finger 5 protein is required for DNA damage-induced p53 activation.ZHANG M et al

Other Information

Locus ID:

NCBI: 51523
MIM: 612752
HGNC: 26943
Ensembl: ENSG00000171604

Variants:

dbSNP: 51523
ClinVar: 51523
TCGA: ENSG00000171604
COSMIC: CXXC5

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000171604ENST00000302517Q7LFL8
ENSG00000171604ENST00000502295D6RCN9
ENSG00000171604ENST00000502336D6RHG9
ENSG00000171604ENST00000502716D6RBE0
ENSG00000171604ENST00000503511D6RHC6
ENSG00000171604ENST00000504844D6RDY2
ENSG00000171604ENST00000504944D6R9V1
ENSG00000171604ENST00000507139D6RJC1
ENSG00000171604ENST00000509238D6RIR8
ENSG00000171604ENST00000511048Q7LFL8
ENSG00000171604ENST00000511457E7EVI8
ENSG00000171604ENST00000511591A0A1D5RMR5
ENSG00000171604ENST00000512816D6R966
ENSG00000171604ENST00000520967E7EV55

Expression (GTEx)

0
50
100
150
200
250

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
198651122010Mutual exclusion of ASXL1 and NPM1 mutations in a series of acute myeloid leukemias.34
191822102009Functional involvement of RINF, retinoid-inducible nuclear factor (CXXC5), in normal and tumoral human myelopoiesis.22
258058122015Downregulation of the Wnt inhibitor CXXC5 predicts a better prognosis in acute myeloid leukemia.22
297801662018NUDT21 negatively regulates PSMB2 and CXXC5 by alternative polyadenylation and contributes to hepatocellular carcinoma suppression.18
213254502011RINF (CXXC5) is overexpressed in solid tumors and is an unfavorable prognostic factor in breast cancer.17
239884572013CXXC5 (retinoid-inducible nuclear factor, RINF) is a potential therapeutic target in high-risk human acute myeloid leukemia.11
231901532013Downregulation but lack of promoter hypermethylation or somatic mutations of the potential tumor suppressor CXXC5 in MDS and AML with deletion 5q.9
195573302009The CXXC finger 5 protein is required for DNA damage-induced p53 activation.8
254335572014CXXC5 regulates differentiation of C2C12 myoblasts into myocytes.6
278862762016Estradiol-Estrogen Receptor α Mediates the Expression of the CXXC5 Gene through the Estrogen Response Element-Dependent Signaling Pathway.6

Citation

Pelin Yaşar ; Mesut Muyan

CXXC5 (CXXC finger protein 5)

Atlas Genet Cytogenet Oncol Haematol. 2014-04-01

Online version: http://atlasgeneticsoncology.org/gene/52549/cxxc5