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CKS1B (CDC28 protein kinase regulatory subunit 1B)

Written2009-09Yongyou Zhang
Case Western Reserve University, 2103 Cornell Rd, WRB-3101, Cleveland, Ohio 44106, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesCDC28 protein kinase 1B
Alias_symbol (synonym)ckshs1
CKS1
Other aliasCKS-1
PNAS-143
PNAS-16
PNAS-18
HGNC (Hugo) CKS1B
LocusID (NCBI) 1163
Atlas_Id 40092
Location 1q21.3  [Link to chromosome band 1q21]
Location_base_pair Starts at 154974642 and ends at 154979249 bp from pter ( according to hg19-Feb_2009)  [Mapping CKS1B.png]

DNA/RNA

 
  Genomic organization of the CKS1B gene.
Description Three exons, spans approximately 4.61 kb of genomic DNA in the centromere-to-telomere orientation. The translation initiation codon ATG is located in exon 1, and the stop codon in exon 3.
Transcription mRNA of approximately 1.8 kb. There are two transcript variants for CKS1B gene. The variant 2 uses a different splice site at the 3' end of the first exon compared to variant 1. There is no evidence that variant 2 encodes a protein.
Pseudogene 4 processed, non-expressed, pseudogenes in human genome.

Protein

 
  The side chains of residues of CKS1b in the binding sites for Cdk2, Skp2 and phosphorylated substrate are shown, with residues in the Cdk2-binding site in green, in the phosphate-binding site in blue, and the Skp2-binding site in red. (The structure figure modified from the origin paper: Markus A. Seeliger et al, Role of Conformational Heterogeneity in Domain Swapping and Adapter Function of the Cks Proteins. J. Biol. Chem., Vol. 280, Issue 34, 30448-30459, August 26, 2005).
Description The open reading frame encodes a 79 amino acid protein, with an estimated molecular weight of approximately 9660 Da.
Expression Basical level expression in all mammalian cell and aberrant expression in cancer cell.
Localisation Cytoplasm and nucleus.
Function CKS1B protein binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function of cell cycle control.
 
  Schematic of the regulation of cell cycle by the CKS1B. CKS1B associates with the p27kip1-Cdk/cyclin complex, induces the formation of the p27kip1-SCF ubiquitin ligase complex, triggers degradation of p27kip1, and signals cells to undergo the G1/S transition by releasing and activating the Cdk/cyclin A/E complexes. CycE/A, cyclin E or Cyclin A; Ub, ubiquitin.
Homology The CKS1B proteins are evolutionary conserved. Mammalian cells express two well-conserved members, like the human CKS1B and CKS2 proteins. The CKSB1B protein is highly conserved across species.

Implicated in

Note
  
Entity Cancer
Note The expression of CKS1B is elevaled in multiple cancer, including breast cancer, lymphoma, myeloma, colon cancer, prostate cancer, lung cancer, renal carcinoma, oesophageal squamous cell carcinoma, salivary cancer, serous ovarian cancer, bladder cancer, urothelial carcinoma et al.
Prognosis Overexpression of CKS1B is associated with poor prognosis in multiple cancer, including myeloma, breast cancer, lymphoma, renal carcinoma, ovarian cancer et al.
Oncogenesis Amplification and overexpression of CKS1B were strongly associated with lymph node metastasis and poor prognosis in breast, salivary cancer and oesophageal squamous cell carcinoma. Generally, CKS1B is an essential factor in facilitating Skp2-dependent degradation of p27. In breast cancer cell, overexpression of CKS1B may inhibit the apoptosis through the MEK-Erk pathway. All of these suggest that CKS1B alterations may have a significant biological role in the tumorigenesis in different tissue and the novel therapeutic strategy for cancer through inhibiting the CKS1B activity. Therefore, disruption of Skp2-CKS1B assembly or down-regulation of CKS1B expression may be used for cancer therapy.
  

Bibliography

Control of the SCF(Skp2-Cks1) ubiquitin ligase by the APC/C(Cdh1) ubiquitin ligase.
Bashir T, Dorrello NV, Amador V, Guardavaccaro D, Pagano M.
Nature. 2004 Mar 11;428(6979):190-3.
PMID 15014502
 
Crystal structure and mutational analysis of the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1.
Bourne Y, Watson MH, Hickey MJ, Holmes W, Rocque W, Reed SI, Tainer JA.
Cell. 1996 Mar 22;84(6):863-74.
PMID 8601310
 
The degradation of cell cycle regulators by SKP2/CKS1 ubiquitin ligase is genetically controlled in rodent liver cancer and contributes to determine the susceptibility to the disease.
Calvisi DF, Pinna F, Ladu S, Muroni MR, Frau M, Demartis I, Tomasi ML, Sini M, Simile MM, Seddaiu MA, Feo F, Pascale RM.
Int J Cancer. 2009 Jun 16.
PMID 19533683
 
Chromosomal mapping of the human genes CKS1 to 8q21 and CKS2 to 9q22.
Demetrick DJ, Zhang H, Beach DH.
Cytogenet Cell Genet. 1996;73(3):250-4.
PMID 8697818
 
Increased SKP2 and CKS1 gene expression contributes to the progression of human urothelial carcinoma.
Kawakami K, Enokida H, Tachiwada T, Nishiyama K, Seki N, Nakagawa M.
J Urol. 2007 Jul;178(1):301-7. Epub 2007 May 17.
PMID 17499794
 
Role of Cks1 overexpression in oral squamous cell carcinomas: cooperation with Skp2 in promoting p27 degradation.
Kitajima S, Kudo Y, Ogawa I, Bashir T, Kitagawa M, Miyauchi M, Pagano M, Takata T.
Am J Pathol. 2004 Dec;165(6):2147-55.
PMID 15579456
 
Fluoxetine mediates G0/G1 arrest by inducing functional inhibition of cyclin dependent kinase subunit (CKS)1.
Krishnan A, Hariharan R, Nair SA, Pillai MR.
Biochem Pharmacol. 2008 May 15;75(10):1924-34. Epub 2008 Feb 17.
PMID 18371935
 
Aberrant expression of Cks1 and Cks2 contributes to prostate tumorigenesis by promoting proliferation and inhibiting programmed cell death.
Lan Y, Zhang Y, Wang J, Lin C, Ittmann MM, Wang F.
Int J Cancer. 2008 Aug 1;123(3):543-51.
PMID 18498131
 
Prognostic implication of p27Kip1, Skp2 and Cks1 expression in renal cell carcinoma: a tissue microarray study.
Liu Z, Fu Q, Lv J, Wang F, Ding K.
J Exp Clin Cancer Res. 2008 Oct 15;27:51.
PMID 18922157
 
Cyclin-dependent kinase-associated proteins Cks1 and Cks2 are essential during early embryogenesis and for cell cycle progression in somatic cells.
Martinsson-Ahlzen HS, Liberal V, Grunenfelder B, Chaves SR, Spruck CH, Reed SI.
Mol Cell Biol. 2008 Sep;28(18):5698-709. Epub 2008 Jul 14.
PMID 18625720
 
Cks1-dependent proteasome recruitment and activation of CDC20 transcription in budding yeast.
Morris MC, Kaiser P, Rudyak S, Baskerville C, Watson MH, Reed SI.
Nature. 2003 Jun 26;423(6943):1009-13.
PMID 12827207
 
The expression and prognostic significance of Cks1 in salivary cancer.
Nagler RM, Ben-Izhak O, Ostrovsky D, Golz A, Hershko DD.
Cancer Invest. 2009 Jun;27(5):512-20.
PMID 19296297
 
Tissue array analysis of expression microarray candidates identifies markers associated with tumor grade and outcome in serous epithelial ovarian cancer.
Ouellet V, Guyot MC, Le Page C, Filali-Mouhim A, Lussier C, Tonin PN, Provencher DM, Mes-Masson AM.
Int J Cancer. 2006 Aug 1;119(3):599-607.
PMID 16572426
 
Human cDNAs encoding homologs of the small p34Cdc28/Cdc2-associated protein of Saccharomyces cerevisiae and Schizosaccharomyces pombe.
Richardson HE, Stueland CS, Thomas J, Russell P, Reed SI.
Genes Dev. 1990 Aug;4(8):1332-44.
PMID 2227411
 
The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma.
Shapira M, Ben-Izhak O, Linn S, Futerman B, Minkov I, Hershko DD.
Cancer. 2005 Apr 1;103(7):1336-46.
PMID 15717322
 
The expression of the ubiquitin ligase subunit Cks1 in human breast cancer.
Slotky M, Shapira M, Ben-Izhak O, Linn S, Futerman B, Tsalic M, Hershko DD.
Breast Cancer Res. 2005;7(5):R737-44. Epub 2005 Jul 19.
PMID 16168119
 
A CDK-independent function of mammalian Cks1: targeting of SCF(Skp2) to the CDK inhibitor p27Kip1.
Spruck C, Strohmaier H, Watson M, Smith AP, Ryan A, Krek TW, Reed SI.
Mol Cell. 2001 Mar;7(3):639-50.
PMID 11463388
 
Role of Cks1 amplification and overexpression in breast cancer.
Wang XC, Tian J, Tian LL, Wu HL, Meng AM, Ma TH, Xiao J, Xiao XL, Li CH.
Biochem Biophys Res Commun. 2009 Feb 20;379(4):1107-13. Epub 2009 Jan 20.
PMID 19161979
 
Cks1 regulates cdk1 expression: a novel role during mitotic entry in breast cancer cells.
Westbrook L, Manuvakhova M, Kern FG, Estes NR 2nd, Ramanathan HN, Thottassery JV.
Cancer Res. 2007 Dec 1;67(23):11393-401.
PMID 18056467
 
Direct cell cycle regulation by the fibroblast growth factor receptor (FGFR) kinase through phosphorylation-dependent release of Cks1 from FGFR substrate 2.
Zhang Y, Lin Y, Bowles C, Wang F.
J Biol Chem. 2004 Dec 31;279(53):55348-54. Epub 2004 Oct 27.
PMID 15513912
 

Citation

This paper should be referenced as such :
Zhang, Y
CKS1B (CDC28 protein kinase regulatory subunit 1B)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(7):676-678.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CKS1BID40092ch1q21.html


External links

Nomenclature
HGNC (Hugo)CKS1B   19083
Cards
AtlasCKS1BID40092ch1q21
Entrez_Gene (NCBI)CKS1B  1163  CDC28 protein kinase regulatory subunit 1B
AliasesCKS1; PNAS-16; PNAS-18; ckshs1
GeneCards (Weizmann)CKS1B
Ensembl hg19 (Hinxton)ENSG00000173207 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000173207 [Gene_View]  chr1:154974642-154979249 [Contig_View]  CKS1B [Vega]
ICGC DataPortalENSG00000173207
TCGA cBioPortalCKS1B
AceView (NCBI)CKS1B
Genatlas (Paris)CKS1B
WikiGenes1163
SOURCE (Princeton)CKS1B
Genetics Home Reference (NIH)CKS1B
Genomic and cartography
GoldenPath hg38 (UCSC)CKS1B  -     chr1:154974642-154979249 +  1q21.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CKS1B  -     1q21.3   [Description]    (hg19-Feb_2009)
EnsemblCKS1B - 1q21.3 [CytoView hg19]  CKS1B - 1q21.3 [CytoView hg38]
Mapping of homologs : NCBICKS1B [Mapview hg19]  CKS1B [Mapview hg38]
OMIM116900   
Gene and transcription
Genbank (Entrez)AF274941 AF274943 AF279897 AK307066 AK311769
RefSeq transcript (Entrez)NM_001826
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CKS1B
Cluster EST : UnigeneHs.374378 [ NCBI ]
CGAP (NCI)Hs.374378
Alternative Splicing GalleryENSG00000173207
Gene ExpressionCKS1B [ NCBI-GEO ]   CKS1B [ EBI - ARRAY_EXPRESS ]   CKS1B [ SEEK ]   CKS1B [ MEM ]
Gene Expression Viewer (FireBrowse)CKS1B [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1163
GTEX Portal (Tissue expression)CKS1B
Protein : pattern, domain, 3D structure
UniProt/SwissProtP61024   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP61024  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP61024
Splice isoforms : SwissVarP61024
PhosPhoSitePlusP61024
Domaine pattern : Prosite (Expaxy)CKS_1 (PS00944)    CKS_2 (PS00945)   
Domains : Interpro (EBI)Cyclin-dep_kinase_reg-sub   
Domain families : Pfam (Sanger)CKS (PF01111)   
Domain families : Pfam (NCBI)pfam01111   
Domain families : Smart (EMBL)CKS (SM01084)  
Conserved Domain (NCBI)CKS1B
DMDM Disease mutations1163
Blocks (Seattle)CKS1B
PDB (SRS)1BUH    1DKS    1DKT    2ASS    2AST    4YC6   
PDB (PDBSum)1BUH    1DKS    1DKT    2ASS    2AST    4YC6   
PDB (IMB)1BUH    1DKS    1DKT    2ASS    2AST    4YC6   
PDB (RSDB)1BUH    1DKS    1DKT    2ASS    2AST    4YC6   
Structural Biology KnowledgeBase1BUH    1DKS    1DKT    2ASS    2AST    4YC6   
SCOP (Structural Classification of Proteins)1BUH    1DKS    1DKT    2ASS    2AST    4YC6   
CATH (Classification of proteins structures)1BUH    1DKS    1DKT    2ASS    2AST    4YC6   
SuperfamilyP61024
Human Protein AtlasENSG00000173207
Peptide AtlasP61024
HPRD00299
IPIIPI00015104   IPI00643512   IPI00514250   
Protein Interaction databases
DIP (DOE-UCLA)P61024
IntAct (EBI)P61024
FunCoupENSG00000173207
BioGRIDCKS1B
STRING (EMBL)CKS1B
ZODIACCKS1B
Ontologies - Pathways
QuickGOP61024
Ontology : AmiGOcyclin-dependent protein kinase holoenzyme complex  protein binding  nucleoplasm  regulation of mitotic cell cycle  cell proliferation  SCF ubiquitin ligase complex  protein kinase binding  histone binding  ubiquitin binding  mitotic cell cycle phase transition  positive regulation of cyclin-dependent protein serine/threonine kinase activity  positive regulation of transcription, DNA-templated  cell division  cyclin-dependent protein serine/threonine kinase activator activity  
Ontology : EGO-EBIcyclin-dependent protein kinase holoenzyme complex  protein binding  nucleoplasm  regulation of mitotic cell cycle  cell proliferation  SCF ubiquitin ligase complex  protein kinase binding  histone binding  ubiquitin binding  mitotic cell cycle phase transition  positive regulation of cyclin-dependent protein serine/threonine kinase activity  positive regulation of transcription, DNA-templated  cell division  cyclin-dependent protein serine/threonine kinase activator activity  
Pathways : BIOCARTARegulation of p27 Phosphorylation during Cell Cycle Progression [Genes]   
Pathways : KEGGPathways in cancer    Small cell lung cancer   
REACTOMEP61024 [protein]
REACTOME PathwaysR-HSA-69231 [pathway]   
NDEx NetworkCKS1B
Atlas of Cancer Signalling NetworkCKS1B
Wikipedia pathwaysCKS1B
Orthology - Evolution
OrthoDB1163
GeneTree (enSembl)ENSG00000173207
Phylogenetic Trees/Animal Genes : TreeFamCKS1B
HOVERGENP61024
HOGENOMP61024
Homologs : HomoloGeneCKS1B
Homology/Alignments : Family Browser (UCSC)CKS1B
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCKS1B [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CKS1B
dbVarCKS1B
ClinVarCKS1B
1000_GenomesCKS1B 
Exome Variant ServerCKS1B
ExAC (Exome Aggregation Consortium)CKS1B (select the gene name)
Genetic variants : HAPMAP1163
Genomic Variants (DGV)CKS1B [DGVbeta]
DECIPHERCKS1B [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCKS1B 
Mutations
ICGC Data PortalCKS1B 
TCGA Data PortalCKS1B 
Broad Tumor PortalCKS1B
OASIS PortalCKS1B [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCKS1B  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCKS1B
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CKS1B
DgiDB (Drug Gene Interaction Database)CKS1B
DoCM (Curated mutations)CKS1B (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CKS1B (select a term)
intoGenCKS1B
NCG5 (London)CKS1B
Cancer3DCKS1B(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM116900   
Orphanet
MedgenCKS1B
Genetic Testing Registry CKS1B
NextProtP61024 [Medical]
TSGene1163
GENETestsCKS1B
Target ValidationCKS1B
Huge Navigator CKS1B [HugePedia]
snp3D : Map Gene to Disease1163
BioCentury BCIQCKS1B
ClinGenCKS1B
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD1163
Chemical/Pharm GKB GenePA38791
Clinical trialCKS1B
Miscellaneous
canSAR (ICR)CKS1B (select the gene name)
Probes
Litterature
PubMed81 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCKS1B
EVEXCKS1B
GoPubMedCKS1B
iHOPCKS1B
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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