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

Gene ID: 1026, updated on 20-Sep-2020

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
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

Genomic context

See CDKN1A in Genome Data Viewer
Location:
6p21.2
Exon count:
6
Annotation release Status Assembly Chr Location
109.20200815 current GRCh38.p13 (GCF_000001405.39) 6 NC_000006.12 (36676463..36687332)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (36644237..36655116)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene Sharpr-MPRA regulatory region 2703 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

Associated conditions

Description Tests
Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction.
GeneReviews: Not available
Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk.
GeneReviews: Not available
Genome- and phenome-wide analyses of cardiac conduction identifies markers of arrhythmia risk.
GeneReviews: Not available
Identification of three novel genetic variations associated with electrocardiographic traits (QRS duration and PR interval) in East Asians.
GeneReviews: Not available
Several common variants modulate heart rate, PR interval and QRS duration.
GeneReviews: Not available

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

Function Evidence Code Pubs
cyclin binding ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
cyclin-dependent protein kinase activating kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
cyclin-dependent protein serine/threonine kinase inhibitor activity TAS
Traceable Author Statement
more info
PubMed 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase inhibitor activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein-containing complex binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest IDA
Inferred from Direct Assay
more info
PubMed 
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest TAS
Traceable Author Statement
more info
 
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator IEA
Inferred from Electronic Annotation
more info
 
G1/S transition of mitotic cell cycle IDA
Inferred from Direct Assay
more info
PubMed 
G1/S transition of mitotic cell cycle TAS
Traceable Author Statement
more info
 
G2/M transition of mitotic cell cycle IMP
Inferred from Mutant Phenotype
more info
PubMed 
Ras protein signal transduction IEP
Inferred from Expression Pattern
more info
PubMed 
animal organ regeneration IEA
Inferred from Electronic Annotation
more info
 
cell cycle arrest IDA
Inferred from Direct Assay
more info
PubMed 
cell cycle arrest IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to DNA damage stimulus IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to UV-B ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to amino acid starvation IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to extracellular stimulus IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to gamma radiation IEA
Inferred from Electronic Annotation
more info
 
cellular response to heat IEA
Inferred from Electronic Annotation
more info
 
cellular response to ionizing radiation IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular senescence IMP
Inferred from Mutant Phenotype
more info
PubMed 
cytokine-mediated signaling pathway TAS
Traceable Author Statement
more info
 
heart development ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
intestinal epithelial cell maturation IEA
Inferred from Electronic Annotation
more info
 
intrinsic apoptotic signaling pathway TAS
Traceable Author Statement
more info
PubMed 
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator IEA
Inferred from Electronic Annotation
more info
 
mitotic G2 DNA damage checkpoint IMP
Inferred from Mutant Phenotype
more info
PubMed 
mitotic cell cycle arrest ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
negative regulation of DNA biosynthetic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of G1/S transition of mitotic cell cycle IGI
Inferred from Genetic Interaction
more info
PubMed 
negative regulation of apoptotic process IEA
Inferred from Electronic Annotation
more info
 
negative regulation of cardiac muscle tissue regeneration ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
negative regulation of cell growth IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of cyclin-dependent protein kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of cyclin-dependent protein serine/threonine kinase activity IEA
Inferred from Electronic Annotation
more info
 
negative regulation of gene expression IEA
Inferred from Electronic Annotation
more info
 
negative regulation of phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of protein binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of vascular smooth muscle cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of B cell proliferation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of cyclin-dependent protein kinase activity IEA
Inferred from Electronic Annotation
more info
 
positive regulation of fibroblast proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of programmed cell death IEA
Inferred from Electronic Annotation
more info
 
positive regulation of protein kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of reactive oxygen species metabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein import into nucleus IEA
Inferred from Electronic Annotation
more info
 
protein stabilization TAS
Traceable Author Statement
more info
 
regulation of cell cycle G1/S phase transition IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of cyclin-dependent protein serine/threonine kinase activity TAS
Traceable Author Statement
more info
PubMed 
regulation of transcription by RNA polymerase II TAS
Traceable Author Statement
more info
 
replicative senescence IEA
Inferred from Electronic Annotation
more info
 
response to X-ray IEA
Inferred from Electronic Annotation
more info
 
response to arsenic-containing substance IEA
Inferred from Electronic Annotation
more info
 
response to corticosterone IEA
Inferred from Electronic Annotation
more info
 
response to drug IEA
Inferred from Electronic Annotation
more info
 
response to hyperoxia IEA
Inferred from Electronic Annotation
more info
 
response to organonitrogen compound IEA
Inferred from Electronic Annotation
more info
 
response to toxic substance IEA
Inferred from Electronic Annotation
more info
 
stress-induced premature senescence TAS
Traceable Author Statement
more info
PubMed 
tissue regeneration IEA
Inferred from Electronic Annotation
more info
 
transcription initiation from RNA polymerase II promoter TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
PCNA-p21 complex IDA
Inferred from Direct Assay
more info
PubMed 
PCNA-p21 complex IMP
Inferred from Mutant Phenotype
more info
PubMed 
cyclin-dependent protein kinase holoenzyme complex IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
nuclear body IDA
Inferred from Direct Assay
more info
 
nucleolus IDA
Inferred from Direct Assay
more info
PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
PubMed 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
perinuclear region of cytoplasm IEA
Inferred from Electronic Annotation
more info
 
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)

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_009364.1 RefSeqGene

    Range
    2809..13658
    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
    UniProtKB/TrEMBL
    A0A024RCX5
    Related
    ENSP00000244741.5, ENST00000244741.9
    Conserved Domains (1) summary
    pfam02234
    Location:2163
    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
    UniProtKB/TrEMBL
    A0A024RCX5
    Related
    ENSP00000482768.1, ENST00000615513.4
    Conserved Domains (1) summary
    pfam02234
    Location:2163
    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
    UniProtKB/TrEMBL
    A0A024RCX5
    Related
    ENSP00000384849.1, ENST00000405375.5
    Conserved Domains (1) summary
    pfam02234
    Location:2163
    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:5597
    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
  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
  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
  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
    UniProtKB/TrEMBL
    A0A024RCX5
    Related
    ENSP00000409259.3, ENST00000448526.6
    Conserved Domains (1) summary
    pfam02234
    Location:2163
    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 Updated Annotation Release 109.20200815

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p13 Primary Assembly

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