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CDKN1B (cyclin-dependent kinase inhibitor 1 B)

Identity

Other namesKIP1
P27KIP1
HGNC (Hugo) CDKN1B
LocusID (NCBI) 1027
Location 12p13.1
Location_base_pair Starts at 12870204 and ends at 12875316 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order centromere - CDNK1B - ETV6 - PRB - KCNA5 - CACNL1A1 - telomere
 
  CDK1B (12p3) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

DNA/RNA

Description coding region from two exons
Transcription 2.5 Kb mRNA; CDKN1B gene regulation by extracellular antiproliferative signals occurs at a post-transcriptional level

Protein

Description 198 amino-acids; 22 kDa; homology to WAF1, limited to a 60 amino acid segment in the N-term half of the protein (residues 28-88); putative bipartite nuclear localization signal near the C-term (153-169); C-term extension of 23 amino acids that contains a consensus Cdc2 phosphorylation site.
Expression expressed in all tissues tested; high levels in skeletal muscle, low levels in liver and kidney.
Localisation nuclear.
Function - CDKN1B is a negative regulator implicated in G1 arrest mediated by TGFb, cell-cell contact, agents that elevate cyclic AMP and rapamycin; CDKN1B binds to and acts as a stoichiometric inhibitor of G1-cyclin-cyclin dependent kinase complexes (cyclin E-Cdk2, cyclin A-Cdk2, cyclin D-Cdk4 (restriction point), controlling G1 to S phase transition or exit from the cell cycle; CDKN1B coordinates the varied inputs from the extracellular environment; post-translational ubiquitin-mediated proteasomal proteolysis represents the major regulatory influence of CDKN1B protein level. - in CDKN1B knockout mouse, CDKN1B defect causes multi-organ hyperplasia with features of gigantism, abnormalities of thymus, retina, pituitary, adrenal glands and gonadal organs (ovulatory defect and female sterility).
Homology Cip1/WAF1

Implicated in

Entity haematological malignancies.
Note hemizygous interstitial deletion is found in 10% of cytogenetically normal ANLL; monoallelic deletion found in 5% ANLL cases, but not described in ALL; no case so far of CDKN1B mutations in leukemia samples.
  
Entity primary breast cancers
Prognosis a low nuclear expression of CDKN1B protein is a significant predictor of poor disease-free survival; in contrary, high level of CDKN1B protein expression combined with low level expression of its target (cyclin E-Cdk2) correlates with about 90% 10-yr overall survival in the lymph node-negative subgroup.
  
Entity primary colorectal carcinomas
Prognosis CDKN1B is an independent prognostic marker: low levels are significantly correlated with a poor prognosis.
  

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias 11q23ChildAMLID1615 11q23ID1030 11q23secondLeukID1131

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945 MedulloblastomaID5065 rhab5004

External links

Nomenclature
HGNC (Hugo)CDKN1B   1785
Cards
AtlasCDKN1BID116
Entrez_Gene (NCBI)CDKN1B  1027  cyclin-dependent kinase inhibitor 1B (p27, Kip1)
GeneCards (Weizmann)CDKN1B
Ensembl (Hinxton)ENSG00000111276 [Gene_View]  chr12:12870204-12875316 [Contig_View]  CDKN1B [Vega]
ICGC DataPortalENSG00000111276
cBioPortalCDKN1B
AceView (NCBI)CDKN1B
Genatlas (Paris)CDKN1B
WikiGenes1027
SOURCE (Princeton)NM_004064
Genomic and cartography
GoldenPath (UCSC)CDKN1B  -  12p13.1   chr12:12870204-12875316 +  12p13.1-p12   [Description]    (hg19-Feb_2009)
EnsemblCDKN1B - 12p13.1-p12 [CytoView]
Mapping of homologs : NCBICDKN1B [Mapview]
OMIM600778   610755   
Gene and transcription
Genbank (Entrez)AA833962 AB451291 AB451423 AF247551 AJ616234
RefSeq transcript (Entrez)NM_004064
RefSeq genomic (Entrez)AC_000144 NC_000012 NC_018923 NG_016341 NT_009714 NW_001838052 NW_004929383
Consensus coding sequences : CCDS (NCBI)CDKN1B
Cluster EST : UnigeneHs.238990 [ NCBI ]
CGAP (NCI)Hs.238990
Alternative Splicing : Fast-db (Paris)GSHG0006492
Alternative Splicing GalleryENSG00000111276
Gene ExpressionCDKN1B [ NCBI-GEO ]     CDKN1B [ SEEK ]   CDKN1B [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP46527 (Uniprot)
NextProtP46527  [Medical]
With graphics : InterProP46527
Splice isoforms : SwissVarP46527 (Swissvar)
Domains : Interpro (EBI)CDI [organisation]  
Related proteins : CluSTrP46527
Domain families : Pfam (Sanger)CDI (PF02234)   
Domain families : Pfam (NCBI)pfam02234   
DMDM Disease mutations1027
Blocks (Seattle)P46527
PDB (SRS)1H27    1JSU    2AST   
PDB (PDBSum)1H27    1JSU    2AST   
PDB (IMB)1H27    1JSU    2AST   
PDB (RSDB)1H27    1JSU    2AST   
Human Protein AtlasENSG00000111276 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP46527
HPRD02867
IPIIPI00006991   IPI01011627   IPI00852705   IPI00853130   
Protein Interaction databases
DIP (DOE-UCLA)P46527
IntAct (EBI)P46527
FunCoupENSG00000111276
BioGRIDCDKN1B
InParanoidP46527
Interologous Interaction database P46527
IntegromeDBCDKN1B
STRING (EMBL)CDKN1B
Ontologies - Pathways
Ontology : AmiGOregulation of cyclin-dependent protein serine/threonine kinase activity  G1/S transition of mitotic cell cycle  G1/S transition of mitotic cell cycle  mitotic cell cycle  response to hypoxia  cyclin-dependent protein serine/threonine kinase inhibitor activity  transforming growth factor beta receptor, cytoplasmic mediator activity  protein binding  nucleus  nucleoplasm  cytoplasm  endosome  cytosol  potassium ion transport  activation of cysteine-type endopeptidase activity involved in apoptotic process  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  cell cycle arrest  epidermal growth factor receptor signaling pathway  sensory perception of sound  positive regulation of cell proliferation  negative regulation of cell proliferation  negative regulation of cell proliferation  fibroblast growth factor receptor signaling pathway  cysteine-type endopeptidase activator activity involved in apoptotic process  response to glucose  positive regulation of cell death  protein phosphatase binding  negative regulation of cell growth  Hsp70 protein binding  positive regulation of microtubule polymerization  response to estradiol  protein complex binding  negative regulation of kinase activity  Fc-epsilon receptor signaling pathway  negative regulation of phosphorylation  response to drug  negative regulation of apoptotic process  response to amino acid  protein complex  response to peptide hormone  innate immune response  positive regulation of protein catabolic process  negative regulation of cyclin-dependent protein serine/threonine kinase activity  negative regulation of transcription, DNA-templated  negative regulation of mitotic cell cycle  response to cadmium ion  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  autophagic cell death  inner ear development  chaperone binding  negative regulation of cellular component movement  negative regulation of epithelial cell proliferation involved in prostate gland development  cellular response to antibiotic  cellular response to lithium ion  cellular response to organic cyclic compound  mitotic cell cycle arrest  
Ontology : EGO-EBIregulation of cyclin-dependent protein serine/threonine kinase activity  G1/S transition of mitotic cell cycle  G1/S transition of mitotic cell cycle  mitotic cell cycle  response to hypoxia  cyclin-dependent protein serine/threonine kinase inhibitor activity  transforming growth factor beta receptor, cytoplasmic mediator activity  protein binding  nucleus  nucleoplasm  cytoplasm  endosome  cytosol  potassium ion transport  activation of cysteine-type endopeptidase activity involved in apoptotic process  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  cell cycle arrest  epidermal growth factor receptor signaling pathway  sensory perception of sound  positive regulation of cell proliferation  negative regulation of cell proliferation  negative regulation of cell proliferation  fibroblast growth factor receptor signaling pathway  cysteine-type endopeptidase activator activity involved in apoptotic process  response to glucose  positive regulation of cell death  protein phosphatase binding  negative regulation of cell growth  Hsp70 protein binding  positive regulation of microtubule polymerization  response to estradiol  protein complex binding  negative regulation of kinase activity  Fc-epsilon receptor signaling pathway  negative regulation of phosphorylation  response to drug  negative regulation of apoptotic process  response to amino acid  protein complex  response to peptide hormone  innate immune response  positive regulation of protein catabolic process  negative regulation of cyclin-dependent protein serine/threonine kinase activity  negative regulation of transcription, DNA-templated  negative regulation of mitotic cell cycle  response to cadmium ion  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  autophagic cell death  inner ear development  chaperone binding  negative regulation of cellular component movement  negative regulation of epithelial cell proliferation involved in prostate gland development  cellular response to antibiotic  cellular response to lithium ion  cellular response to organic cyclic compound  mitotic cell cycle arrest  
Pathways : BIOCARTARegulation of p27 Phosphorylation during Cell Cycle Progression [Genes]    Cyclins and Cell Cycle Regulation [Genes]    CTCF: First Multivalent Nuclear Factor [Genes]    Cell Cycle: G1/S Check Point [Genes]    CDK Regulation of DNA Replication [Genes]    PTEN dependent cell cycle arrest and apoptosis [Genes]    Influence of Ras and Rho proteins on G1 to S Transition [Genes]   
Pathways : KEGGErbB signaling pathway    HIF-1 signaling pathway    FoxO signaling pathway    Cell cycle    PI3K-Akt signaling pathway    Hepatitis B    Measles    Epstein-Barr virus infection    Pathways in cancer    Transcriptional misregulation in cancer    Viral carcinogenesis    MicroRNAs in cancer    Prostate cancer    Chronic myeloid leukemia    Small cell lung cancer   
Protein Interaction DatabaseCDKN1B
Wikipedia pathwaysCDKN1B
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)CDKN1B
snp3D : Map Gene to Disease1027
SNP (GeneSNP Utah)CDKN1B
SNP : HGBaseCDKN1B
Genetic variants : HAPMAPCDKN1B
Exome VariantCDKN1B
1000_GenomesCDKN1B 
ICGC programENSG00000111276 
Somatic Mutations in Cancer : COSMICCDKN1B 
CONAN: Copy Number AnalysisCDKN1B 
Mutations and Diseases : HGMDCDKN1B
Mutations and Diseases : intOGenCDKN1B
Genomic VariantsCDKN1B  CDKN1B [DGVbeta]
dbVarCDKN1B
ClinVarCDKN1B
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM600778    610755   
MedgenCDKN1B
GENETestsCDKN1B
Disease Genetic AssociationCDKN1B
Huge Navigator CDKN1B [HugePedia]  CDKN1B [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneCDKN1B
Homology/Alignments : Family Browser (UCSC)CDKN1B
Phylogenetic Trees/Animal Genes : TreeFamCDKN1B
Chemical/Protein Interactions : CTD1027
Chemical/Pharm GKB GenePA105
Clinical trialCDKN1B
Cancer Resource (Charite)ENSG00000111276
Other databases
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=CDKN1B
Probes
ProbeCancer Cytogenetics (Bari)
Litterature
PubMed499 Pubmed reference(s) in Entrez
CoreMineCDKN1B
iHOPCDKN1B
OncoSearchCDKN1B

Bibliography

Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals.
Polyak K, Lee MH, Erdjument-Bromage H, Koff A, Roberts JM, Tempst P, Massaguˆ© J
Cell. 1994 ; 78 (1) : 59-66.
PMID 8033212
 
p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21.
Toyoshima H, Hunter T
Cell. 1994 ; 78 (1) : 67-74.
PMID 8033213
 
Assignment of the human p27Kip1 gene to 12p13 and its analysis in leukemias.
Pietenpol JA, Bohlander SK, Sato Y, Papadopoulos N, Liu B, Friedman C, Trask BJ, Roberts JM, Kinzler KW, Rowley JD
Cancer research. 1995 ; 55 (6) : 1206-1210.
PMID 7882309
 
Translational control of p27Kip1 accumulation during the cell cycle.
Hengst L, Reed SI
Science (New York, N.Y.). 1996 ; 271 (5257) : 1861-1864.
PMID 8596954
 
Germline configuration of the p27(Kip1) gene in childhood acute lymphoblastic leukemia (ALL).
Seriu T, Erz D, Bartram CR
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1996 ; 10 (2) : page 345.
PMID 8637245
 
Deletions of CDKN1B and ETV6 in acute myeloid leukemia and myelodysplastic syndromes without cytogenetic evidence of 12p abnormalities.
Andreasson P, Johansson B, Arheden K, Billstrˆm R, Mitelman F, Hˆglund M
Genes, chromosomes & cancer. 1997 ; 19 (2) : 77-83.
PMID 9171997
 
Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer.
Catzavelos C, Bhattacharya N, Ung YC, Wilson JA, Roncari L, Sandhu C, Shaw P, Yeger H, Morava-Protzner I, Kapusta L, Franssen E, Pritchard KI, Slingerland JM
Nature medicine. 1997 ; 3 (2) : 227-230.
PMID 9018244
 
Molecular analysis of cyclin-dependent kinase inhibitors in human leukemias.
Hayette S, Thomas X, Bertrand Y, Tigaud I, Callanan M, Thiebaut A, Charrin C, Archimbaud E, Magaud JP, Rimokh R
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1997 ; 11 (10) : 1696-1699.
PMID 9324291
 
Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas.
Loda M, Cukor B, Tam SW, Lavin P, Fiorentino M, Draetta GF, Jessup JM, Pagano M
Nature medicine. 1997 ; 3 (2) : 231-234.
PMID 9018245
 
Expression of cell-cycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients.
Porter PL, Malone KE, Heagerty PJ, Alexander GM, Gatti LA, Firpo EJ, Daling JR, Roberts JM
Nature medicine. 1997 ; 3 (2) : 222-225.
PMID 9018243
 
Cancer prognostics: past, present and p27.
Steeg PS, Abrams JS
Nature medicine. 1997 ; 3 (2) : 152-154.
PMID 9018230
 
REVIEW articlesautomatic search in PubMed
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Contributor(s)

Written05-1998Chrystele Bilhou-Nabera

Citation

This paper should be referenced as such :
Bilhou-Nabera, C
CDKN1B (cyclin-dependent kinase inhibitor 1 B )
Atlas Genet Cytogenet Oncol Haematol. 1998;2(4):115-116.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/CDKN1BID116.html

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indexed on : Tue Aug 26 15:26:18 CEST 2014

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