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    CDKN1A cyclin dependent kinase inhibitor 1A [ Homo sapiens (human) ]

    Gene ID: 1026, updated on 5-Feb-2023

    Summary

    Official Symbol
    CDKN1Aprovided by HGNC
    Official Full Name
    cyclin dependent kinase inhibitor 1Aprovided by HGNC
    Primary source
    HGNC:HGNC:1784
    See related
    Ensembl:ENSG00000124762 MIM:116899; AllianceGenome:HGNC:1784
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    P21; CIP1; SDI1; WAF1; CAP20; CDKN1; MDA-6; p21CIP1
    Summary
    This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin-cyclin-dependent kinase2 or -cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This protein can interact with proliferating cell nuclear antigen, a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of cyclin-dependent kinase2, and may be instrumental in the execution of apoptosis following caspase activation. Mice that lack this gene have the ability to regenerate damaged or missing tissue. Multiple alternatively spliced variants have been found for this gene. [provided by RefSeq, Sep 2015]
    Expression
    Ubiquitous expression in colon (RPKM 71.4), gall bladder (RPKM 68.8) and 24 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See CDKN1A in Genome Data Viewer
    Location:
    6p21.2
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    110 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (36676463..36687332)
    110 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (36497108..36508013)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (36644240..36655109)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:36634735-36635516 Neighboring gene promoter of CDKN1A antisense DNA damage activated RNA Neighboring gene leucine aminopeptidase 3 pseudogene 2 Neighboring gene damage induced long noncoding RNA Neighboring gene RAB44, member RAS oncogene family Neighboring gene G protein-coupled receptor 166 pseudogene

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    EBI GWAS Catalog

    Description
    Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction.
    EBI GWAS Catalog
    Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk.
    EBI GWAS Catalog
    Genome- and phenome-wide analyses of cardiac conduction identifies markers of arrhythmia risk.
    EBI GWAS Catalog
    Identification of three novel genetic variations associated with electrocardiographic traits (QRS duration and PR interval) in East Asians.
    EBI GWAS Catalog
    Several common variants modulate heart rate, PR interval and QRS duration.
    EBI GWAS Catalog

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    HIV-1 infection in CD4+ T cells induces higher expression of CDKN1A (p21) PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 upregulates the expression of cyclin-dependent kinase inhibitor 1A (CDKN1A; p21; Cip1) in human B cells PubMed
    env HIV-1 gp120 induces NF-kappaB activation and increases p21(cip1/waf1) and p27(kip1) protein levels in human mesangial cells PubMed
    Nef nef HIV-1 Nef upregulates the expression of p21/WAF1 protein in human mesenchymal stem cells PubMed
    Tat tat HIV-1 Tat upregulates the expression of p21/WAF1 protein in human mesenchymal stem cells PubMed
    tat Treatment with HIV-Tat and morphine activates extracellular signal-regulated kinase-1/2 (ERK1/2), upregulates p53 and p21 levels, and downregulates cyclin D1 and Akt levels in human fetal brain-derived neural precursor cells PubMed
    tat HIV-1 Tat inhibits SIRT1 and increases acetylation of p53, which leads to activation of p21 and BAX in HeLa-CD4+ cells PubMed
    tat A p53 fusion protein with the HIV-1 Tat basic domain at its N terminus activates the expression of p21and downregulates the levels of caspase-3 and Bcl-2 PubMed
    Vif vif HIV-1 Vif upregulates the expression of cyclin-dependent kinase inhibitor 1A (CDKN1A, p21, Cip1) in Vif-expression T cells PubMed
    Vpr vpr Activation of p21/Waf1/Cip1 by HIV-1 Vpr appears to be dependent upon p53 PubMed
    vpr COUP-TF-interacting protein 2 (CTIP2) abolishes Vpr-mediated stimulation of p21 by cooperating with SUV39H1 and HDAC1/HDAC2 to silence the p21 gene transcription PubMed
    vpr Results from GST pull-down assays show the association of Vpr with p53 in extracts containing Sp1, suggesting the physical interaction of Vpr with Sp1 and p53 could modulate transcriptional activity of p21 PubMed
    vpr HIV-1 Vpr activates promoter activity of p21/Cip1/Waf1 through the GC-rich region located between nucleotides -84 and -74 in a manner that requires cooperativity of Sp1, which binds to the DNA sequence spanning -84 to -74 PubMed
    vpr HIV-1 Vpr activates the expression and transcription of the cyclin-dependent kinase inhibitor p21/Waf1/Cip1, an inhibitor of the G1 and G2/M phase transitions in T lymphoid and myeloid cells PubMed
    integrase gag-pol Cyclin-dependent kinase inhibitor (CKI) p21 (Waf1/Cip1/Sdi1) blocks viral infection by complexing with HIV-1 integrase and aborting chromosomal integration in hematopoietic stem cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Process Evidence Code Pubs
    involved_in DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest TAS
    Traceable Author Statement
    more info
     
    involved_in DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in G1/S transition of mitotic cell cycle TAS
    Traceable Author Statement
    more info
     
    involved_in Ras protein signal transduction IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in cellular response to DNA damage stimulus IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in cellular response to DNA damage stimulus IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cellular response to UV-B ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cellular response to amino acid starvation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cellular response to extracellular stimulus IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cellular response to gamma radiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to ionizing radiation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cellular senescence IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cellular senescence TAS
    Traceable Author Statement
    more info
     
    involved_in heart development ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in intrinsic apoptotic signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in mitotic G2 DNA damage checkpoint signaling IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of DNA biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    acts_upstream_of_or_within negative regulation of G1/S transition of mitotic cell cycle IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in negative regulation of cardiac muscle tissue regeneration ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in negative regulation of cell growth IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of cell population proliferation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of cell population proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of cyclin-dependent protein kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of cyclin-dependent protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in negative regulation of gene expression IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of protein binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of protein phosphorylation IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in negative regulation of vascular associated smooth muscle cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of B cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of fibroblast proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of programmed cell death IEA
    Inferred from Electronic Annotation
    more info
     
    acts_upstream_of_or_within positive regulation of protein kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of protein phosphorylation IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in positive regulation of reactive oxygen species metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in protein import into nucleus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of G1/S transition of mitotic cell cycle IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in regulation of G1/S transition of mitotic cell cycle IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of G2/M transition of mitotic cell cycle IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of cell cycle IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of cell cycle IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of cell cycle ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in regulation of cell cycle G1/S phase transition IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of cyclin-dependent protein serine/threonine kinase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in replicative senescence IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in stress-induced premature senescence TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in tissue regeneration IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in wound healing IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    part_of PCNA-p21 complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of PCNA-p21 complex IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    part_of cyclin-dependent protein kinase holoenzyme complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    part_of cyclin-dependent protein kinase holoenzyme complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in nuclear body IDA
    Inferred from Direct Assay
    more info
     
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
     
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    cyclin-dependent kinase inhibitor 1
    Names
    CDK-interacting protein 1
    CDK-interaction protein 1
    DNA synthesis inhibitor
    cyclin-dependent kinase inhibitor 1A (p21, Cip1)
    melanoma differentiation associated protein 6
    wild-type p53-activated fragment 1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_009364.2 RefSeqGene

      Range
      7253..15871
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000389.5NP_000380.1  cyclin-dependent kinase inhibitor 1 isoform 1

      See identical proteins and their annotated locations for NP_000380.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) differs in the 5' UTR, lacks an in-frame portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 3. The resulting isoform (1) has a shorter N-terminus, compared to isoform 2. Variants 1, 2, 4, 5, and 10 all encode the same isoform (1).
      Source sequence(s)
      Z85996
      Consensus CDS
      CCDS4824.1
      UniProtKB/Swiss-Prot
      P38936, Q9BUT4
      UniProtKB/TrEMBL
      A0A024RCX5
      Related
      ENSP00000244741.6, ENST00000244741.10
      Conserved Domains (1) summary
      pfam02234
      Location:2166
      CDI; Cyclin-dependent kinase inhibitor
    2. NM_001220777.2NP_001207706.1  cyclin-dependent kinase inhibitor 1 isoform 1

      See identical proteins and their annotated locations for NP_001207706.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR, lacks an in-frame portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 3. The resulting isoform (1) has a shorter N-terminus, compared to isoform 2. Variants 1, 2, 4, 5, and 10 all encode the same isoform (1).
      Source sequence(s)
      Z85996
      Consensus CDS
      CCDS4824.1
      UniProtKB/Swiss-Prot
      P38936, Q9BUT4
      UniProtKB/TrEMBL
      A0A024RCX5
      Related
      ENSP00000482768.1, ENST00000615513.4
      Conserved Domains (1) summary
      pfam02234
      Location:2166
      CDI; Cyclin-dependent kinase inhibitor
    3. NM_001220778.2NP_001207707.1  cyclin-dependent kinase inhibitor 1 isoform 1

      See identical proteins and their annotated locations for NP_001207707.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR, lacks an in-frame portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 3. The resulting isoform (1) has a shorter N-terminus, compared to isoform 2. Variants 1, 2, 4, 5, and 10 all encode the same isoform (1).
      Source sequence(s)
      Z85996
      Consensus CDS
      CCDS4824.1
      UniProtKB/Swiss-Prot
      P38936, Q9BUT4
      UniProtKB/TrEMBL
      A0A024RCX5
      Related
      ENSP00000384849.1, ENST00000405375.5
      Conserved Domains (1) summary
      pfam02234
      Location:2166
      CDI; Cyclin-dependent kinase inhibitor
    4. NM_001291549.3NP_001278478.1  cyclin-dependent kinase inhibitor 1 isoform 2

      See identical proteins and their annotated locations for NP_001278478.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) encodes the longest isoform (2). Variants 3 and 6 both encode the same isoform (2).
      Source sequence(s)
      Z85996
      UniProtKB/Swiss-Prot
      P38936
      Conserved Domains (1) summary
      pfam02234
      Location:55100
      CDI; Cyclin-dependent kinase inhibitor
    5. NM_001374509.1NP_001361438.1  cyclin-dependent kinase inhibitor 1 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6), as well as variant 3, encodes isoform 2.
      Source sequence(s)
      Z85996
      Conserved Domains (1) summary
      pfam02234
      Location:55100
      CDI; Cyclin-dependent kinase inhibitor
    6. NM_001374510.1NP_001361439.1  cyclin-dependent kinase inhibitor 1 isoform 3

      Status: REVIEWED

      Source sequence(s)
      Z85996
      Conserved Domains (1) summary
      pfam02234
      Location:3479
      CDI; Cyclin-dependent kinase inhibitor
    7. NM_001374511.1NP_001361440.1  cyclin-dependent kinase inhibitor 1 isoform 4

      Status: REVIEWED

      Source sequence(s)
      Z85996
      Conserved Domains (1) summary
      pfam02234
      Location:2166
      CDI; Cyclin-dependent kinase inhibitor
    8. NM_001374512.1NP_001361441.1  cyclin-dependent kinase inhibitor 1 isoform 5

      Status: REVIEWED

      Source sequence(s)
      Z85996
      Conserved Domains (1) summary
      pfam02234
      Location:2166
      CDI; Cyclin-dependent kinase inhibitor
    9. NM_001374513.1NP_001361442.1  cyclin-dependent kinase inhibitor 1 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (10), as well as variants 1, 2, 4, and 5, encodes isoform 1.
      Source sequence(s)
      Z85996
      Consensus CDS
      CCDS4824.1
      UniProtKB/Swiss-Prot
      Q9BUT4
      UniProtKB/TrEMBL
      A0A024RCX5
      Conserved Domains (1) summary
      pfam02234
      Location:2166
      CDI; Cyclin-dependent kinase inhibitor
    10. NM_078467.3NP_510867.1  cyclin-dependent kinase inhibitor 1 isoform 1

      See identical proteins and their annotated locations for NP_510867.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, lacks an in-frame portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 3. The resulting isoform (1) has a shorter N-terminus, compared to isoform 2. Variants 1, 2, 4, 5, and 10 all encode the same isoform (1).
      Source sequence(s)
      Z85996
      Consensus CDS
      CCDS4824.1
      UniProtKB/Swiss-Prot
      P38936, Q9BUT4
      UniProtKB/TrEMBL
      A0A024RCX5
      Related
      ENSP00000409259.3, ENST00000448526.6
      Conserved Domains (1) summary
      pfam02234
      Location:2166
      CDI; Cyclin-dependent kinase inhibitor

    RNA

    1. NR_164655.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      Z85996
    2. NR_164656.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      Z85996
      Related
      ENST00000462537.3

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 110 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      36676463..36687332
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      36497108..36508013
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)