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CDKN1A (cyclin-dependent kinase inhibitor 1A)

Written2001-04Delphine Javelaud, Françoise Besançon
Institut Curie, Pavillon Pasteur, Unité INSERM 365, 26 rue d'Ulm, 75231 Paris cedex 05, France

(Note : for Links provided by Atlas : click)

Identity

Alias (NCBI)p21
WAF1 (Wild type p53 activated protein-1)
CIP1 (CDK- interacting protein)
SDI1 (Senescence cell- derived inhibitor-1)
CAP20
MDA-6 (melanoma differentiation-asssociated protein-1)
HGNC (Hugo) CDKN1A
HGNC Alias symbP21
CIP1
WAF1
SDI1
CAP20
p21CIP1
p21Cip1/Waf1
p21
HGNC Previous nameCDKN1
HGNC Previous namecyclin-dependent kinase inhibitor 1A (p21, Cip1)
LocusID (NCBI) 1026
Atlas_Id 139
Location 6p21.2  [Link to chromosome band 6p21]
Location_base_pair Starts at 36676463 and ends at 36687332 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping CDKN1A.png]
 
  CDKN1A (6p21) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CDKN1A (6p21.2)::CD9 (12p13.31)CDKN1A (6p21.2)::CDKN1A (6p21.2)CDKN1A (6p21.2)::GAPDH (12p13.31)
CREB3L2 (7q33)::CDKN1A (6p21.2)RCN2 (15q24.3)::CDKN1A (6p21.2)UBR4 (1p36.13)::CDKN1A (6p21.2)

DNA/RNA

Description 3 exons (68, 450, 1600 pb ; the first exon is not translated)
Transcription 2,1 kb mRNA, expression regulated at both transcriptional and post-transcriptional levels.

Protein

 
Description 164 amino acids, 18 kDa. Contains interacting domains with several proteins (see Figure) and a nuclear localization signal.
Expression in all adult human tissues. CDKN1A expression in the developing mouse embryo is correlated with cell-cycle arrest that precedes terminal differentiation in a variety of tissues.
Localisation nuclear and cytoplasmic.
  • located predominantly in the nucleus.
  • relocalization to the cytoplasm during the differentiation of immature monocytes.
  • Function can interact with cytoplasmic proteins ( pro-caspase-3, ASK-1, JNK, CaM, cyclinD-CDK4).
  • CDKN1A is implicated in regulation of cell growth and cell response to DNA damage. It inhibits cell cycle progression in G1 by binding to G1 cyclin-CDK complexes and to PCNA antigen and may also induce G2 arrest. In response to DNA damage p53 induces CDKN1A expression, which is responsible for the cell cycle arrest at the G1 checkpoint. CDKN1A plays also a role in the protection of cells against apoptosis and its expression is essential to maintain cell survival during differentiation of several cell lineages.
  • Homology with p27kip1 and p57kip2 in the N- terminal.

    Mutations

    Somatic Analysis of normal and tumor cells revealed two common variants in the CDKN1A gene which were not unique to tumors: a C to A substitution at codon 31 (Ser 31-to-Arg) which does not result in loss of activity and a C to T change in the 3' untranslated region of the CDKN1A gene, 20 bp following the stop codon. In prostate cancer, a single base insertion at codon 35, resulting in frameshift, protein troncation and impairement of activity, has been identified. A Phe to Leu change at codon 63, an Arg to Trp change at position 94 and an Asn to Ser change at position 50 were observed in a Burkitt's lymphoma, a human breast carcinoma and a malignant melanoma cell line, respectively.

    Bibliography

    Apoptosis inhibitory activity of cytoplasmic p21(Cip1/WAF1) in monocytic differentiation.
    Asada M, Yamada T, Ichijo H, Delia D, Miyazono K, Fukumuro K, Mizutani S
    The EMBO journal. 1999 ; 18 (5) : 1223-1234.
    PMID 10064589
     
    A single nucleotide substitution at codon 31 (Ser/Arg) defines a polymorphism in a highly conserved region of the p53-inducible gene WAF1/CIP1.
    Chedid M, Michieli P, Lengel C, Huppi K, Givol D
    Oncogene. 1994 ; 9 (10) : 3021-3024.
    PMID 8084608
     
    p21(WAF1/Cip1): more than a break to the cell cycle?
    Dotto GP
    Biochimica et biophysica acta. 2000 ; 1471 (1) : M43-M56.
    PMID 10967424
     
    Transcriptional regulation of the p21((WAF1/CIP1)) gene.
    Gartel AL, Tyner AL
    Experimental cell research. 1999 ; 246 (2) : 280-289.
    PMID 9925742
     
    The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.
    Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ
    Cell. 1993 ; 75 (4) : 805-816.
    PMID 8242751
     
    Two variants of the CIP1/WAF1 gene occur together and are associated with human cancer.
    Mousses S, Ozçelik H, Lee PD, Malkin D, Bull SB, Andrulis IL
    Human molecular genetics. 1995 ; 4 (6) : 1089-1092.
    PMID 7655464
     
    p53-independent expression of p21Cip1 in muscle and other terminally differentiating cells.
    Parker SB, Eichele G, Zhang P, Rawls A, Sands AT, Bradley A, Olson EN, Harper JW, Elledge SJ
    Science (New York, N.Y.). 1995 ; 267 (5200) : 1024-1027.
    PMID 7863329
     

    Citation

    This paper should be referenced as such :
    Javelaud, D ; Besanè_on, F
    CDKN1A (cyclin-dependent kinase inhibitor 1A)
    Atlas Genet Cytogenet Oncol Haematol. 2001;5(3):170-171.
    Free journal version : [ pdf ]   [ DOI ]


    Other Leukemias implicated (Data extracted from papers in the Atlas) [ 7 ]
      del(6p) (loss of JARID2 and DTNBP1) in myeloid malignances
    t(1;9)(p13;p12) PAX5::HIPK1
    inv(7)(p15q34) TRB::HOXA10::t(7;7)(p15;q34) TRB::HOXA10
    t(8;9)(q24;p13) ?::MYC
    t(10;10)(p12;q21) CTNNA3::ARHGAP21
    t(20;21)(q13.2;q22.12) ZFP64::RUNX1
    TAL1 (1p32) deletion in lymphoid malignancies


    External links

     

    Nomenclature
    HGNC (Hugo)CDKN1A   1784
    Cards
    AtlasCDKN1AID139
    Entrez_Gene (NCBI)CDKN1A    cyclin dependent kinase inhibitor 1A
    AliasesCAP20; CDKN1; CIP1; MDA-6; 
    P21; SDI1; WAF1; p21CIP1
    GeneCards (Weizmann)CDKN1A
    Ensembl hg19 (Hinxton)ENSG00000124762 [Gene_View]
    Ensembl hg38 (Hinxton)ENSG00000124762 [Gene_View]  ENSG00000124762 [Sequence]  chr6:36676463-36687332 [Contig_View]  CDKN1A [Vega]
    ICGC DataPortalENSG00000124762
    TCGA cBioPortalCDKN1A
    AceView (NCBI)CDKN1A
    Genatlas (Paris)CDKN1A
    SOURCE (Princeton)CDKN1A
    Genetics Home Reference (NIH)CDKN1A
    Genomic and cartography
    GoldenPath hg38 (UCSC)CDKN1A  -     chr6:36676463-36687332 +  6p21.2   [Description]    (hg38-Dec_2013)
    GoldenPath hg19 (UCSC)CDKN1A  -     6p21.2   [Description]    (hg19-Feb_2009)
    GoldenPathCDKN1A - 6p21.2 [CytoView hg19]  CDKN1A - 6p21.2 [CytoView hg38]
    ImmunoBaseENSG00000124762
    Genome Data Viewer NCBICDKN1A [Mapview hg19]  
    OMIM116899   
    Gene and transcription
    Genbank (Entrez)AA534613 AB209881 AB451290 AB451422 AI973138
    RefSeq transcript (Entrez)NM_000389 NM_001220777 NM_001220778 NM_001291549 NM_001374509 NM_001374510 NM_001374511 NM_001374512 NM_001374513 NM_078467
    Consensus coding sequences : CCDS (NCBI)CDKN1A
    Gene ExpressionCDKN1A [ NCBI-GEO ]   CDKN1A [ EBI - ARRAY_EXPRESS ]   CDKN1A [ SEEK ]   CDKN1A [ MEM ]
    Gene Expression Viewer (FireBrowse)CDKN1A [ Firebrowse - Broad ]
    GenevisibleExpression of CDKN1A in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)1026
    GTEX Portal (Tissue expression)CDKN1A
    Human Protein AtlasENSG00000124762-CDKN1A [pathology]   [cell]   [tissue]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtP38936   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
    NextProtP38936  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProP38936
    PhosPhoSitePlusP38936
    Domains : Interpro (EBI)CDI    CDKN1A   
    Domain families : Pfam (Sanger)CDI (PF02234)   
    Domain families : Pfam (NCBI)pfam02234   
    Conserved Domain (NCBI)CDKN1A
    PDB (RSDB)1AXC    2ZVV    2ZVW    4RJF    5E0U    6CBI    6CEJ    6CIV    6CIX    6P8H   
    PDB Europe1AXC    2ZVV    2ZVW    4RJF    5E0U    6CBI    6CEJ    6CIV    6CIX    6P8H   
    PDB (PDBSum)1AXC    2ZVV    2ZVW    4RJF    5E0U    6CBI    6CEJ    6CIV    6CIX    6P8H   
    PDB (IMB)1AXC    2ZVV    2ZVW    4RJF    5E0U    6CBI    6CEJ    6CIV    6CIX    6P8H   
    Structural Biology KnowledgeBase1AXC    2ZVV    2ZVW    4RJF    5E0U    6CBI    6CEJ    6CIV    6CIX    6P8H   
    SCOP (Structural Classification of Proteins)1AXC    2ZVV    2ZVW    4RJF    5E0U    6CBI    6CEJ    6CIV    6CIX    6P8H   
    CATH (Classification of proteins structures)1AXC    2ZVV    2ZVW    4RJF    5E0U    6CBI    6CEJ    6CIV    6CIX    6P8H   
    SuperfamilyP38936
    AlphaFold pdb e-kbP38936   
    Human Protein Atlas [tissue]ENSG00000124762-CDKN1A [tissue]
    HPRD00298
    Protein Interaction databases
    DIP (DOE-UCLA)P38936
    IntAct (EBI)P38936
    BioGRIDCDKN1A
    STRING (EMBL)CDKN1A
    ZODIACCDKN1A
    Ontologies - Pathways
    QuickGOP38936
    Ontology : AmiGOregulation of cyclin-dependent protein serine/threonine kinase activity  G1/S transition of mitotic cell cycle  G1/S transition of mitotic cell cycle  G2/M transition of mitotic cell cycle  cyclin-dependent protein kinase holoenzyme complex  protein kinase inhibitor activity  cyclin-dependent protein serine/threonine kinase inhibitor activity  protein binding  nucleus  nucleoplasm  nucleoplasm  nucleolus  cytosol  regulation of transcription by RNA polymerase II  protein import into nucleus  cellular response to DNA damage stimulus  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator  mitotic G2 DNA damage checkpoint signaling  Ras protein signal transduction  heart development  negative regulation of cell population proliferation  negative regulation of cell population proliferation  response to toxic substance  response to X-ray  response to organonitrogen compound  negative regulation of gene expression  nuclear body  cytokine-mediated signaling pathway  protein kinase binding  cyclin-dependent protein kinase activating kinase activity  negative regulation of cell growth  cyclin binding  granulocyte differentiation  positive regulation of B cell proliferation  animal organ regeneration  ubiquitin protein ligase binding  cellular response to extracellular stimulus  negative regulation of protein binding  protein-containing complex  cellular response to amino acid starvation  cellular response to heat  wound healing  tissue regeneration  negative regulation of phosphorylation  response to drug  intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator  negative regulation of apoptotic process  positive regulation of programmed cell death  protein-containing complex binding  negative regulation of cyclin-dependent protein serine/threonine kinase activity  positive regulation of protein kinase activity  response to arsenic-containing substance  metal ion binding  positive regulation of fibroblast proliferation  perinuclear region of cytoplasm  protein stabilization  response to corticosterone  regulation of cell cycle  regulation of cell cycle  regulation of cell cycle  response to hyperoxia  regulation of transcription initiation from RNA polymerase II promoter  intestinal epithelial cell maturation  PCNA-p21 complex  PCNA-p21 complex  cellular response to ionizing radiation  cellular response to gamma radiation  cellular response to UV-B  cellular senescence  replicative senescence  stress-induced premature senescence  intrinsic apoptotic signaling pathway  protein sequestering activity  regulation of cell cycle G1/S phase transition  negative regulation of cyclin-dependent protein kinase activity  positive regulation of cyclin-dependent protein kinase activity  negative regulation of vascular associated smooth muscle cell proliferation  negative regulation of cardiac muscle tissue regeneration  negative regulation of G1/S transition of mitotic cell cycle  negative regulation of DNA biosynthetic process  positive regulation of reactive oxygen species metabolic process  
    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  G2/M transition of mitotic cell cycle  cyclin-dependent protein kinase holoenzyme complex  protein kinase inhibitor activity  cyclin-dependent protein serine/threonine kinase inhibitor activity  protein binding  nucleus  nucleoplasm  nucleoplasm  nucleolus  cytosol  regulation of transcription by RNA polymerase II  protein import into nucleus  cellular response to DNA damage stimulus  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator  mitotic G2 DNA damage checkpoint signaling  Ras protein signal transduction  heart development  negative regulation of cell population proliferation  negative regulation of cell population proliferation  response to toxic substance  response to X-ray  response to organonitrogen compound  negative regulation of gene expression  nuclear body  cytokine-mediated signaling pathway  protein kinase binding  cyclin-dependent protein kinase activating kinase activity  negative regulation of cell growth  cyclin binding  granulocyte differentiation  positive regulation of B cell proliferation  animal organ regeneration  ubiquitin protein ligase binding  cellular response to extracellular stimulus  negative regulation of protein binding  protein-containing complex  cellular response to amino acid starvation  cellular response to heat  wound healing  tissue regeneration  negative regulation of phosphorylation  response to drug  intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator  negative regulation of apoptotic process  positive regulation of programmed cell death  protein-containing complex binding  negative regulation of cyclin-dependent protein serine/threonine kinase activity  positive regulation of protein kinase activity  response to arsenic-containing substance  metal ion binding  positive regulation of fibroblast proliferation  perinuclear region of cytoplasm  protein stabilization  response to corticosterone  regulation of cell cycle  regulation of cell cycle  regulation of cell cycle  response to hyperoxia  regulation of transcription initiation from RNA polymerase II promoter  intestinal epithelial cell maturation  PCNA-p21 complex  PCNA-p21 complex  cellular response to ionizing radiation  cellular response to gamma radiation  cellular response to UV-B  cellular senescence  replicative senescence  stress-induced premature senescence  intrinsic apoptotic signaling pathway  protein sequestering activity  regulation of cell cycle G1/S phase transition  negative regulation of cyclin-dependent protein kinase activity  positive regulation of cyclin-dependent protein kinase activity  negative regulation of vascular associated smooth muscle cell proliferation  negative regulation of cardiac muscle tissue regeneration  negative regulation of G1/S transition of mitotic cell cycle  negative regulation of DNA biosynthetic process  positive regulation of reactive oxygen species metabolic process  
    Pathways : BIOCARTAInfluence of Ras and Rho proteins on G1 to S Transition [Genes]    Cell Cycle: G1/S Check Point [Genes]    p53 Signaling Pathway [Genes]    Erythropoietin mediated neuroprotection through NF-kB [Genes]    Hypoxia and p53 in the Cardiovascular system [Genes]    ATM Signaling Pathway [Genes]    Effects of calcineurin in Keratinocyte Differentiation [Genes]    Cell Cycle: G2/M Checkpoint [Genes]    Cyclins and Cell Cycle Regulation [Genes]   
    Pathways : KEGGErbB signaling pathway    HIF-1 signaling pathway    FoxO signaling pathway    Cell cycle    p53 signaling pathway    PI3K-Akt signaling pathway    Hepatitis C    Hepatitis B    HTLV-I infection    Epstein-Barr virus infection    Pathways in cancer    Transcriptional misregulation in cancer    Viral carcinogenesis    Proteoglycans in cancer    MicroRNAs in cancer    Glioma    Prostate cancer    Melanoma    Bladder cancer    Chronic myeloid leukemia   
    REACTOMEP38936 [protein]
    REACTOME PathwaysR-HSA-9617828 [pathway]   
    NDEx NetworkCDKN1A
    Atlas of Cancer Signalling NetworkCDKN1A
    Wikipedia pathwaysCDKN1A
    Orthology - Evolution
    OrthoDB1026
    GeneTree (enSembl)ENSG00000124762
    Phylogenetic Trees/Animal Genes : TreeFamCDKN1A
    Homologs : HomoloGeneCDKN1A
    Homology/Alignments : Family Browser (UCSC)CDKN1A
    Gene fusions - Rearrangements
    Fusion : MitelmanCDKN1A::CD9 [6p21.2/12p13.31]  
    Fusion : QuiverCDKN1A
    Polymorphisms : SNP and Copy number variants
    NCBI Variation ViewerCDKN1A [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)CDKN1A
    dbVarCDKN1A
    ClinVarCDKN1A
    MonarchCDKN1A
    1000_GenomesCDKN1A 
    Exome Variant ServerCDKN1A
    GNOMAD BrowserENSG00000124762
    Varsome BrowserCDKN1A
    ACMGCDKN1A variants
    VarityP38936
    Genomic Variants (DGV)CDKN1A [DGVbeta]
    DECIPHERCDKN1A [patients]   [syndromes]   [variants]   [genes]  
    CONAN: Copy Number AnalysisCDKN1A 
    Mutations
    ICGC Data PortalCDKN1A 
    TCGA Data PortalCDKN1A 
    Broad Tumor PortalCDKN1A
    OASIS PortalCDKN1A [ Somatic mutations - Copy number]
    Cancer Gene: CensusCDKN1A 
    Somatic Mutations in Cancer : COSMICCDKN1A  [overview]  [genome browser]  [tissue]  [distribution]  
    Somatic Mutations in Cancer : COSMIC3DCDKN1A
    Mutations and Diseases : HGMDCDKN1A
    intOGen PortalCDKN1A
    LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
    BioMutaCDKN1A
    DgiDB (Drug Gene Interaction Database)CDKN1A
    DoCM (Curated mutations)CDKN1A
    CIViC (Clinical Interpretations of Variants in Cancer)CDKN1A
    OncoKBCDKN1A
    NCG (London)CDKN1A
    Cancer3DCDKN1A
    Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
    Diseases
    OMIM116899   
    Orphanet121   
    DisGeNETCDKN1A
    MedgenCDKN1A
    Genetic Testing Registry CDKN1A
    NextProtP38936 [Medical]
    GENETestsCDKN1A
    Target ValidationCDKN1A
    Huge Navigator CDKN1A [HugePedia]
    ClinGenCDKN1A
    Clinical trials, drugs, therapy
    MyCancerGenomeCDKN1A
    Protein Interactions : CTDCDKN1A
    Pharm GKB GenePA104
    Pharm GKB PathwaysPA152241951   
    PharosP38936
    Clinical trialCDKN1A
    Miscellaneous
    canSAR (ICR)CDKN1A
    HarmonizomeCDKN1A
    DataMed IndexCDKN1A
    Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=CDKN1A
    Probes
    Litterature
    PubMed499 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    EVEXCDKN1A
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

    Search in all EBI   NCBI

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    indexed on : Fri Oct 8 21:14:44 CEST 2021

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