CDKN1A
Cyclin-dependent kinase inhibitor 1
Also known as: CAP20, CDKN1, CDN1A_HUMAN, CIP1, P21, p21CIP1, p21Cip1/Waf1, SDI1, WAF1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P38936
- Gene
- CDKN1A
- Ensembl
- ENSG00000124762
- Chromosome
- 6
- Canonical length
- 164 aa
- Protein class
- Cancer-related genes, Human disease related genes, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Nuclear bodies
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
164 residues, UniProt reviewed canonical sequence.
>P38936|CDKN1A
1 MSEPAGDVRQ NPCGSKACRR LFGPVDSEQL SRDCDALMAG CIQEARERWN FDFVTETPLE
61 GDFAWERVRG LGLPKLYLPT GPRRGRDELG GGRRPGTSPA LLQGTAEEDH VDLSLSCTLV
121 PRSGEQAEGS PGGPGDSQGR KRRQTSMTDF YHSKRRLIFS KRKPLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CDKN1A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.65
- Highest tissue expression
- 340 nTPM
Expression across tissuesHPA
Tissue
- blood vessel: 340 nTPM
- adipose tissue: 316 nTPM
- choroid plexus: 301 nTPM
- skeletal muscle: 236 nTPM
- skin: 222 nTPM
- esophagus: 202 nTPM
Single-cell type
- epididymal basal cells: 861 nCPM
- ocular epithelial cells: 839 nCPM
- urothelial cells: 765 nCPM
- vascular smooth muscle cells: 707 nCPM
- esophageal apical cells: 585 nCPM
- esophageal suprabasal cells: 572 nCPM
Immune cell
- non-classical monocyte: 75 nTPM
- intermediate monocyte: 52 nTPM
- total PBMC: 34 nTPM
- classical monocyte: 23 nTPM
- plasmacytoid DC: 22 nTPM
- memory B-cell: 21 nTPM
Brain region
- choroid plexus: 106 nTPM
- medulla oblongata: 59 nTPM
- midbrain: 44 nTPM
- spinal cord: 43 nTPM
- white matter: 39 nTPM
- pons: 39 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CDKN1A.
Disease | GeneticClinVar
1 pathogenic / likely-pathogenic of 47 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
Disease | ImmuneIEDB
Conditions an epitope on CDKN1A was assayed in.
- skin melanoma T cell
- melanoma T cell
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.38
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.42
- DepMap mean gene effect
- 0.29
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cellular response to amino acid starvation
- cellular response to cell-matrix adhesion
- cellular response to gamma radiation
- cellular response to ionizing radiation
- cellular response to UV-B
- cellular senescence
- DNA damage response
- DNA damage response, signal transduction by p53 class mediator
- fibroblast proliferation
- G1/S transition of mitotic cell cycle
- heart development
- import into nucleus
- in utero embryonic development
- intrinsic apoptotic signaling pathway
- intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
- keratinocyte differentiation
- keratinocyte proliferation
- mitotic G1 DNA damage checkpoint signaling
- mitotic G2 DNA damage checkpoint signaling
- negative regulation of cardiac muscle tissue regeneration
- negative regulation of cell growth
- negative regulation of cell population proliferation
- negative regulation of DNA biosynthetic process
- negative regulation of G1/S transition of mitotic cell cycle
- negative regulation of gene expression
- negative regulation of vascular associated smooth muscle cell proliferation
- oncogene-induced cell senescence
- positive regulation of B cell proliferation
- positive regulation of DNA replication
- positive regulation of fibroblast proliferation
- positive regulation of programmed cell death
- positive regulation of protein kinase activity
- positive regulation of reactive oxygen species metabolic process
- protein import into nucleus
- Ras protein signal transduction
- regulation of cell cycle
- regulation of cell cycle G1/S phase transition
- regulation of G1/S transition of mitotic cell cycle
- regulation of G2/M transition of mitotic cell cycle
- replicative senescence
- stress-induced premature senescence
- tissue regeneration
- wound healing
Molecular functions
- cyclin binding
- cyclin-dependent protein serine/threonine kinase inhibitor activity
- molecular function activator activity
- molecular function inhibitor activity
- protein kinase binding
- protein kinase inhibitor activity
- protein sequestering activity
- protein serine/threonine kinase binding
- protein-containing complex binding
- ubiquitin protein ligase binding
- zinc ion binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Cyclin-dependent kinase inhibitor domain
- Cyclin-dependent kinase inhibitor domain superfamily
- Cyclin-dependent kinase inhibitor
- Cyclin-dependent kinase inhibitor 1
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CDKN1A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CDKN1A as an antibody target. Whether an autoantibody or antibody against CDKN1A could matter depends on whether native CDKN1A is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CDKN1A is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label CDKN1A as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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