CENPW (centromere protein W)

2013-06-01   Seyoung Jeon , Soojin Lee 

Department of Microbiology, Molecular Biology, Chungnam National Institute, 305-764, Daejeon, Republic of Korea

Identity

HGNC
LOCATION
6q22.32
LOCUSID
ALIAS
C6orf173,CENP-W,CUG2

DNA/RNA

Atlas Image
Figure 1. A genomic structure of the CENPW gene.

Description

Exons: 3, coding exons: 3, introns: 2.

Transcription

Transcript length: 750 bps, open reading frame: 264 bps.

Pseudogene

No pseudogene.

Proteins

Atlas Image
Figure 2. Schematic representation of CENPW protein. Each domain is represented with the unique color and name. One nuclear localization signal (NLS) sequence of 17 amino acids starts at amino acid 13.

Description

CENP-W gene encodes 88-amino acid protein which shows ~27% of amino acid sequence similarity to a general transcription repressor, human DR1. It contains a typical NLS sequence and histone fold region which is critical for binding to centromeric DNA.

Expression

Widely expressed; kidney, colon, breast, liver, lung, ovary, prostate, thyroid, etc.

Localisation

Intracellular, nucleus, centromere, kinetochore, nucleus matrix, nucleolus.

Function

CENP-W was originally identified as a cancer-upregulated gene 2 (CUG2) which is commonly overexpressed in various human cancer tissues. Although it has high oncogenic activities, CENP-W also induces cell apoptosis when overexpressed in certain cell lines. After it was revealed that CENP-W forms a stable heterodimer with CENP-T and is localized in kinetochores during mitosis, CENP-W become recognized as a new member of the inner centromere protein complex. Subsequent studies have also shown that CENP-T-W-S-X forms a unique centromeric nucleosome-like heterotetramer structure which binds to and supercoils DNA. As a nucleolus-associated protein, CENP-W may play critical role in the formation of functional kinetochore, possibly by facilitating the recruitment of other centromeric components during interphase, which is required for proper chromosome segregation during mitosis.

Homology

According to NCBI-HomoloGene:
Pan troglodytes (chimpanzee): centromere protein W (NP_001012525.1, 88 aa)
Macacamulatta (Rhesus monkey): centromere protein W (XP_001107034.2, 88 aa)
Canis lupus familiaris (dog): centromere protein W-like (XP_003638832.1, 88 aa)
Bostaurus (cattle): centromere protein W (NP_001104731.1, 88 aa)
Mus musculus (house mouse): centromere protein W (NP_001103217.1, 86 aa)
Rattus norvegicus (Norway rat): centromere protein W (XP_001070657.1, 86 aa).

Mutations

Note

Over expressed in various cancer tissues; notably high in the ovary (6.3-fold), liver (6.0), lung (4.9), and pancreas (3.8).
Atlas Image
Figure 3. mRNA expression of CUG2 in various tumors. DNA chip microarray profile in tumors (closed bar) and normal (open bar) tissues from the Gene Express Oncology DatasuiteTM of Gene Logic Inc.

Implicated in

Entity name
Various human cancers
Oncogenesis
CENP-W has been found to be upregulated in several tumor tissues. When the expression level of CENP-W was examined by DNA chip microarray and RT-PCR in tumors, six tissues (ovary, liver, lung, pancreas, colon, and stomach) showed high-fold increases in expression profiles. Also, CENP-W-transformed NIH3T3 cells exhibited exceptionally prominent cancerous phenotypes in vitro as well as in vivo tumor forming assays.

Bibliography

Pubmed IDLast YearTitleAuthors
220020612011New centromeric component CENP-W is an RNA-associated nuclear matrix protein that interacts with nucleophosmin/B23 protein.Chun Y et al
195330402009Cancer-upregulated gene 2 (CUG2), a new component of centromere complex, is required for kinetochore function.Kim H et al
201800242010Sp1 and Sp3 mediate basal and serum-induced expression of human CENP-W.Kim H et al
218389322011Cug2 is essential for normal mitotic control and CNS development in zebrafish.Kim HT et al
176108442007Molecular cloning and functional analysis of a novel oncogene, cancer-upregulated gene 2 (CUG2).Lee S et al
206486952010Cancer-upregulated gene 2 (CUG2) overexpression induces apoptosis in SKOV-3 cells.Lee S et al
223049172012CENP-T-W-S-X forms a unique centromeric chromatin structure with a histone-like fold.Nishino T et al
200759842010CUG2, a novel oncogene confers reoviral replication through Ras and p38 signaling pathway.Park EH et al
216951102011Premitotic assembly of human CENPs -T and -W switches centromeric chromatin to a mitotic state.Prendergast L et al

Other Information

Locus ID:

NCBI: 387103
MIM: 611264
HGNC: 21488
Ensembl: ENSG00000203760

Variants:

dbSNP: 387103
ClinVar: 387103
TCGA: ENSG00000203760
COSMIC: CENPW

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000203760ENST00000368325Q5EE01
ENSG00000203760ENST00000368326A0A0A0MRK5
ENSG00000203760ENST00000368328Q5EE01

Expression (GTEx)

0
10
20
30
40
50
60
70

Pathways

PathwaySourceExternal ID
Cell CycleREACTOMER-HSA-1640170
Chromosome MaintenanceREACTOMER-HSA-73886
Nucleosome assemblyREACTOMER-HSA-774815
Deposition of new CENPA-containing nucleosomes at the centromereREACTOMER-HSA-606279

References

Pubmed IDYearTitleCitations
190705752008CCAN makes multiple contacts with centromeric DNA to provide distinct pathways to the outer kinetochore.166
192660772009Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966.48
216951102011Premitotic assembly of human CENPs -T and -W switches centromeric chromatin to a mitotic state.32
221313682012Replication of loci influencing ages at menarche and menopause in Hispanic women: the Women's Health Initiative SHARe Study.29
205466122010The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature.19
272841632016The CENP-T/-W complex is a binding partner of the histone chaperone FACT.15
220020612011New centromeric component CENP-W is an RNA-associated nuclear matrix protein that interacts with nucleophosmin/B23 protein.8
233066142013Cancer upregulated gene 2, a novel oncogene, confers resistance to oncolytic vesicular stomatitis virus through STAT1-OASL2 signaling.8
208462172010Association of linear growth impairment in pediatric Crohn's disease and a known height locus: a pilot study.7
239173552013Cancer upregulated gene 2, a novel oncogene, enhances migration and drug resistance of colon cancer cells via STAT1 activation.7

Citation

Seyoung Jeon ; Soojin Lee

CENPW (centromere protein W)

Atlas Genet Cytogenet Oncol Haematol. 2013-06-01

Online version: http://atlasgeneticsoncology.org/gene/51452/cenpw