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CDK20 (cell cycle related kinase)

Written2009-07Marie Lin, William Cheung
Department of Chemistry, Open Laboratory of Chemical Biology, The University of Hong Kong, Pokfulam, Hong Kong, China.

(Note : for Links provided by Atlas : click)

Identity

Alias_namesCCRK
cell cycle related kinase
Alias_symbol (synonym)p42
Other aliasCDCH
P42
EC 2.7.11.22
PNQALRE
HGNC (Hugo) CDK20
LocusID (NCBI) 23552
Atlas_Id 43196
Location 9q22.1  [Link to chromosome band 9q22]
Location_base_pair Starts at 87966444 and ends at 87974780 bp from pter ( according to hg19-Feb_2009)  [Mapping CDK20.png]
Local_order 235kb telomeric to cathepsin L1 (CTSL1).
Fusion genes
(updated 2016)
CDK20 (9q22.1) / ACO2 (22q13.2)

DNA/RNA

 
  (A) Chromosomal location of human CCRK gene. (B) Genomic organization of four CCRK transcript variants.
Description Human CCRK gene spans around 8.3kb of genomic DNA on the chromosome 9q22.2 in telomere-to-centromere orientation. This gene locates within the locus tag RP11-350E12.2. A block of hypermethylated CpGs has been identified in the CCRK promoter and is associated with its high expression in adult human brain cortex (Farcas et al., 2009).
Transcription Four alternative spliced transcript variants of CCRK gene are known. The generic variant 3 (GenBank#: NM_001039803) consists of 8 exons, with the start codon on exon 1 and stop codon on exon 8. Both transcript variant 1 (GenBank#: NM_178432) and variant 2 (GenBank#: NM_012119) have had their exon 5 deleted. Variant 1 also differs from the other variants by an additional 39nt on exon 2. The cardiac splice variant (GenBank#: AY904367) lacks both the exons 5 and 6, and has truncated 5'- and 3'-untranslated regions.
Pseudogene No pseudogenes for CCRK are known.

Protein

Note There has been controversy over whether CCRK functions as a second cyclin-dependent kinase (CDK)-activating kinase (CAK) (i.e., in addition to CDK7). Inconsistent with other studies, Wohlbold and colleagues (2006) reported that monomeric CCRK has no intrinsic CAK activity.
Description The open reading frame encodes a 346-amino acid protein, with molecular weight of 42kDa. CCRK protein has a protein kinase domain extending from residues 4-288, in which typical ATP-binding region and serine/threonine kinase active site can be identified. Its interacting proteins include CDK2, cyclin H and casein kinase 2.
Expression In human tissues, the 2.2kb CCRK transcript is expressed predominantly in the brain and kidney, and to lesser extent in the liver, heart and placenta. The cardiac CCRK isoform is detectable only in heart, liver and kidney. CCRK is also widely expressed in cell lines originating from glioblastoma (U87, U118, U138, U373 and SW1088), cervical adenocarcinoma (HeLa), colorectal carcinoma (HCT116), osteogenic sarcoma (U2OS), breast adenocarcinoma (MCF-7), ovarian carcinoma (UACC-1598, UACC-326, OVCAR-3, HO-8910 and TOV-21G), lung fibroblast (WI-38), myoblast (C2C12), and lymphocyte (GM08336).
Localisation Mainly in nucleus and perinuclear region. Relative low expression in cytoplasm.
Function CCRK is an important regulator of G1- to S-phase transition in cell cycle and is indispensable for cell growth. It possesses CDK-activating kinase activity that is essential for the phosphorylation of CDK2 at Thr160 (Liu et al., 2004) and male germ cell-associated kinase-related kinase (MRK) at Thr157 in mammalian cells (Fu et al., 2006). CCRK also acts as a negative regulator of apoptosis and may confer cells with drug resistance (MacKeigan et al., 2005). Moreover, CCRK splice variant expressing in the heart has been shown to promote cardiac cell growth and survival (Qiu et al., 2008).
Homology CCRK belongs to the CDK family. Among the other 10 CDK members, human CCRK shares the highest sequence identity (43%) with a well known CAK, CDK7. Orthologs of CCRK are found in orangutans, Old World monkeys, bovine, dog, boar, mouse, rat, fishes, frog, budding yeast and fission yeast.

Implicated in

Note
  
Entity Colorectal carcinoma
Note Knockdown of CCRK inhibits HCT116 cell proliferation (Wohlbold et al., 2006). A small molecule kinase inhibitor (RGB-286147) that targets CCRK has been shown to promote HCT116 cell death in the absence of cell cycle progression (Caligiuri et al., 2005).
  
  
Entity Glioblastoma multiforme
Note In 14 of 19 (74%) human high-grade glioblastoma multiforme patient samples, CCRK mRNA expression levels are more than 1.5-fold higher than those of 3 normal brain tissue samples. By contrast, only 2 of 7 (29%) low-grade glioma samples have elevated CCRK expression. Knockdown of CCRK suppresses glioma tumor growth in mouse xenograft model. CCRK knockdown also inhibits glioblastoma cell proliferation via G1/S-phase arrest and reduction of CDK2 phosphorylation in vitro. Overexpression of CCRK induces malignant transformation of non-tumorigenic glioblastoma cells (U138) both in vitro and in vivo (Ng et al., 2007).
  
  
Entity Ovarian carcinoma
Note By CCRK immunohistochemical staining of CCRK in ovarian tissue microarray, CCRK is overexpressed in 65/122 (53%) invasive ovarian carcinoma patient samples, as compared with 22 normal ovarian surface epithelium samples. In 12 pairs of primary ovarian carcinoma and adjacent normal tissue specimens, CCRK expression is elevated in 6 (67%) ovarian carcinoma samples. Ectopic expression of CCRK promotes tumor growth in vivo and ovarian carcinoma cell proliferation in vitro via upregulation of cyclin D1 (Wu et al., 2009).
Prognosis CCRK expression is positively correlated with ascending histological grade and advanced clinicopathologic features. It is also an independent biomarker for shortened survival time of patients with ovarian carcinoma.
  

Bibliography

A proteome-wide CDK/CRK-specific kinase inhibitor promotes tumor cell death in the absence of cell cycle progression.
Caligiuri M, Becker F, Murthi K, Kaplan F, Dedier S, Kaufmann C, Machl A, Zybarth G, Richard J, Bockovich N, Kluge A, Kley N.
Chem Biol. 2005 Oct;12(10):1103-15.
PMID 16242653
 
Differences in DNA methylation patterns and expression of the CCRK gene in human and nonhuman primate cortices.
Farcas R, Schneider E, Frauenknecht K, Kondova I, Bontrop R, Bohl J, Navarro B, Metzler M, Zischler H, Zechner U, Daser A, Haaf T.
Mol Biol Evol. 2009 Jun;26(6):1379-89. Epub 2009 Mar 12.
PMID 19282513
 
Identification of yin-yang regulators and a phosphorylation consensus for male germ cell-associated kinase (MAK)-related kinase.
Fu Z, Larson KA, Chitta RK, Parker SA, Turk BE, Lawrence MW, Kaldis P, Galaktionov K, Cohn SM, Shabanowitz J, Hunt DF, Sturgill TW.
Mol Cell Biol. 2006 Nov;26(22):8639-54. Epub 2006 Sep 5.
PMID 16954377
 
p42, a novel cyclin-dependent kinase-activating kinase in mammalian cells.
Liu Y, Wu C, Galaktionov K.
J Biol Chem. 2004 Feb 6;279(6):4507-14. Epub 2003 Nov 3.
PMID 14597612
 
Sensitized RNAi screen of human kinases and phosphatases identifies new regulators of apoptosis and chemoresistance.
MacKeigan JP, Murphy LO, Blenis J.
Nat Cell Biol. 2005 Jun;7(6):591-600. Epub 2005 May 1.
PMID 15864305
 
Cell cycle-related kinase: a novel candidate oncogene in human glioblastoma.
Ng SS, Cheung YT, An XM, Chen YC, Li M, Li GH, Cheung W, Sze J, Lai L, Peng Y, Xia HH, Wong BC, Leung SY, Xie D, He ML, Kung HF, Lin MC.
J Natl Cancer Inst. 2007 Jun 20;99(12):936-48. Epub 2007 Jun 12.
PMID 17565152
 
Characterization of a novel cardiac isoform of the cell cycle-related kinase that is regulated during heart failure.
Qiu H, Dai H, Jain K, Shah R, Hong C, Pain J, Tian B, Vatner DE, Vatner SF, Depre C.
J Biol Chem. 2008 Aug 8;283(32):22157-65. Epub 2008 May 28.
PMID 18508765
 
The cyclin-dependent kinase (CDK) family member PNQALRE/CCRK supports cell proliferation but has no intrinsic CDK-activating kinase (CAK) activity.
Wohlbold L, Larochelle S, Liao JC, Livshits G, Singer J, Shokat KM, Fisher RP.
Cell Cycle. 2006 Mar;5(5):546-54. Epub 2006 Mar 1.
PMID 16552187
 
Cell cycle-related kinase supports ovarian carcinoma cell proliferation via regulation of cyclin D1 and is a predictor of outcome in patients with ovarian carcinoma.
Wu GQ, Xie D, Yang GF, Liao YJ, Mai SJ, Deng HX, Sze J, Guan XY, Zeng YX, Lin MC, Kung HF.
Int J Cancer. 2009 Jun 8. [Epub ahead of print].
PMID 19672860
 

Citation

This paper should be referenced as such :
Lin, M ; Cheung, W
CCRK (cell cycle related kinase)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(6):527-529.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CCRKID43196ch9q22.html


External links

Nomenclature
HGNC (Hugo)CDK20   21420
Cards
AtlasCCRKID43196ch9q22
Entrez_Gene (NCBI)CDK20  23552  cyclin dependent kinase 20
AliasesCCRK; CDCH; P42; PNQALRE
GeneCards (Weizmann)CDK20
Ensembl hg19 (Hinxton)ENSG00000156345 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000156345 [Gene_View]  chr9:87966444-87974780 [Contig_View]  CDK20 [Vega]
ICGC DataPortalENSG00000156345
TCGA cBioPortalCDK20
AceView (NCBI)CDK20
Genatlas (Paris)CDK20
WikiGenes23552
SOURCE (Princeton)CDK20
Genetics Home Reference (NIH)CDK20
Genomic and cartography
GoldenPath hg38 (UCSC)CDK20  -     chr9:87966444-87974780 -  9q22.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CDK20  -     9q22.1   [Description]    (hg19-Feb_2009)
EnsemblCDK20 - 9q22.1 [CytoView hg19]  CDK20 - 9q22.1 [CytoView hg38]
Mapping of homologs : NCBICDK20 [Mapview hg19]  CDK20 [Mapview hg38]
OMIM610076   
Gene and transcription
Genbank (Entrez)AF035013 AF113130 AI479563 AK075325 AK226135
RefSeq transcript (Entrez)NM_001039803 NM_001170639 NM_001170640 NM_012119 NM_178432
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CDK20
Cluster EST : UnigeneHs.522274 [ NCBI ]
CGAP (NCI)Hs.522274
Alternative Splicing GalleryENSG00000156345
Gene ExpressionCDK20 [ NCBI-GEO ]   CDK20 [ EBI - ARRAY_EXPRESS ]   CDK20 [ SEEK ]   CDK20 [ MEM ]
Gene Expression Viewer (FireBrowse)CDK20 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)23552
GTEX Portal (Tissue expression)CDK20
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8IZL9   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8IZL9  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8IZL9
Splice isoforms : SwissVarQ8IZL9
Catalytic activity : Enzyme2.7.11.22 [ Enzyme-Expasy ]   2.7.11.222.7.11.22 [ IntEnz-EBI ]   2.7.11.22 [ BRENDA ]   2.7.11.22 [ KEGG ]   
PhosPhoSitePlusQ8IZL9
Domaine pattern : Prosite (Expaxy)PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)   
Domains : Interpro (EBI)Kinase-like_dom    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser/Thr_kinase_AS   
Domain families : Pfam (Sanger)Pkinase (PF00069)   
Domain families : Pfam (NCBI)pfam00069   
Domain families : Smart (EMBL)S_TKc (SM00220)  
Conserved Domain (NCBI)CDK20
DMDM Disease mutations23552
Blocks (Seattle)CDK20
SuperfamilyQ8IZL9
Human Protein AtlasENSG00000156345
Peptide AtlasQ8IZL9
HPRD13010
IPIIPI00218021   IPI00554807   IPI00748335   IPI00910295   IPI00015892   IPI00827564   IPI00374861   
Protein Interaction databases
DIP (DOE-UCLA)Q8IZL9
IntAct (EBI)Q8IZL9
FunCoupENSG00000156345
BioGRIDCDK20
STRING (EMBL)CDK20
ZODIACCDK20
Ontologies - Pathways
QuickGOQ8IZL9
Ontology : AmiGOcyclin-dependent protein serine/threonine kinase activity  protein binding  ATP binding  nucleus  nucleoplasm  cytoplasm  cilium  protein phosphorylation  cell cycle  multicellular organism development  cyclin-dependent protein kinase activating kinase activity  cell division  positive regulation of cyclin-dependent protein kinase activity  
Ontology : EGO-EBIcyclin-dependent protein serine/threonine kinase activity  protein binding  ATP binding  nucleus  nucleoplasm  cytoplasm  cilium  protein phosphorylation  cell cycle  multicellular organism development  cyclin-dependent protein kinase activating kinase activity  cell division  positive regulation of cyclin-dependent protein kinase activity  
NDEx NetworkCDK20
Atlas of Cancer Signalling NetworkCDK20
Wikipedia pathwaysCDK20
Orthology - Evolution
OrthoDB23552
GeneTree (enSembl)ENSG00000156345
Phylogenetic Trees/Animal Genes : TreeFamCDK20
HOVERGENQ8IZL9
HOGENOMQ8IZL9
Homologs : HomoloGeneCDK20
Homology/Alignments : Family Browser (UCSC)CDK20
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCDK20 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CDK20
dbVarCDK20
ClinVarCDK20
1000_GenomesCDK20 
Exome Variant ServerCDK20
ExAC (Exome Aggregation Consortium)CDK20 (select the gene name)
Genetic variants : HAPMAP23552
Genomic Variants (DGV)CDK20 [DGVbeta]
DECIPHERCDK20 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCDK20 
Mutations
ICGC Data PortalCDK20 
TCGA Data PortalCDK20 
Broad Tumor PortalCDK20
OASIS PortalCDK20 [ Somatic mutations - Copy number]
Mutations and Diseases : HGMDCDK20
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CDK20
DgiDB (Drug Gene Interaction Database)CDK20
DoCM (Curated mutations)CDK20 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CDK20 (select a term)
intoGenCDK20
NCG5 (London)CDK20
Cancer3DCDK20(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM610076   
Orphanet
MedgenCDK20
Genetic Testing Registry CDK20
NextProtQ8IZL9 [Medical]
TSGene23552
GENETestsCDK20
Target ValidationCDK20
Huge Navigator CDK20 [HugePedia]
snp3D : Map Gene to Disease23552
BioCentury BCIQCDK20
ClinGenCDK20
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD23552
Chemical/Pharm GKB GenePA165585688
Clinical trialCDK20
Miscellaneous
canSAR (ICR)CDK20 (select the gene name)
Probes
Litterature
PubMed22 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCDK20
EVEXCDK20
GoPubMedCDK20
iHOPCDK20
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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