GENERAL INFORMATIONi
Gene namei CDKN1A
Synonyms CAP20, CDKN1, CIP1, P21, p21CIP1, p21Cip1/Waf1, SDI1, WAF1
Gene descriptioni Cyclin dependent kinase inhibitor 1A
Protein classi Cancer-related genes
Human disease related genes
Predicted locationi Intracellular
Protein evidence Evidence at protein level (all genes)
GENE INFORMATIONi
Chromosome 6
Cytoband p21.2
Chromosome location (bp) 36676460 - 36687337
Number of transcriptsi 5
Ensembl ENSG00000124762 (version 109)
Entrez gene 1026
HGNC HGNC:1784
UniProt P38936 (UniProt - Evidence at protein level)
neXtProt NX_P38936
GeneCards CDKN1A
Antibodypedia CDKN1A antibodies


PROTEIN FUNCTION
Protein function (UniProt)i Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest 1. Involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Also involved in p53-independent DNA damage-induced G2 arrest mediated by CREB3L1 in astrocytes and osteoblasts (By similarity). Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding 2. Negatively regulates the CDK4- and CDK6-driven phosphorylation of RB1 in keratinocytes, thereby resulting in the release of E2F1 and subsequent transcription of E2F1-driven G1/S phase promoting genes (By similarity). show less
Molecular function (UniProt)i Protein kinase inhibitor
Biological process (UniProt)i Cell cycle
Ligand (UniProt)i Metal-binding, Zinc
Gene summary (Entrez)i 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] show less
PROTEIN INFORMATIONi
Splice variant SwissProt TrEMBL Protein class Gene ontology Length & mass Signal peptide
(predicted)		 Transmembrane regions
(predicted)
CDKN1A-201
ENSP00000244741
ENST00000244741
P38936
[Direct mapping] Cyclin-dependent kinase inhibitor 1
Show all
A0A024RCX5
[Target identity:100%; Query identity:100%] Cyclin-dependent kinase inhibitor 1A (P21, Cip1), isoform CRA_a
Show all
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Cancer-related genes
   Candidate cancer biomarkers
   Mutated cancer genes
   Mutational cancer driver genes
Human disease related genes
   Cancers
   Cancers of the breast and female genital organs
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000079 [regulation of cyclin-dependent protein serine/threonine kinase activity]
GO:0000082 [G1/S transition of mitotic cell cycle]
GO:0000307 [cyclin-dependent protein kinase holoenzyme complex]
GO:0001933 [negative regulation of protein phosphorylation]
GO:0001934 [positive regulation of protein phosphorylation]
GO:0004860 [protein kinase inhibitor activity]
GO:0004861 [cyclin-dependent protein serine/threonine kinase inhibitor activity]
GO:0005515 [protein binding]
GO:0005634 [nucleus]
GO:0005654 [nucleoplasm]
GO:0005730 [nucleolus]
GO:0005737 [cytoplasm]
GO:0005829 [cytosol]
GO:0006606 [protein import into nucleus]
GO:0006974 [cellular response to DNA damage stimulus]
GO:0006977 [DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest]
GO:0006978 [DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator]
GO:0007049 [cell cycle]
GO:0007095 [mitotic G2 DNA damage checkpoint signaling]
GO:0007265 [Ras protein signal transduction]
GO:0007346 [regulation of mitotic cell cycle]
GO:0007507 [heart development]
GO:0008285 [negative regulation of cell population proliferation]
GO:0009411 [response to UV]
GO:0010389 [regulation of G2/M transition of mitotic cell cycle]
GO:0010629 [negative regulation of gene expression]
GO:0016301 [kinase activity]
GO:0016310 [phosphorylation]
GO:0016604 [nuclear body]
GO:0019901 [protein kinase binding]
GO:0019912 [cyclin-dependent protein kinase activating kinase activity]
GO:0030308 [negative regulation of cell growth]
GO:0030332 [cyclin binding]
GO:0030890 [positive regulation of B cell proliferation]
GO:0031625 [ubiquitin protein ligase binding]
GO:0031668 [cellular response to extracellular stimulus]
GO:0032091 [negative regulation of protein binding]
GO:0032991 [protein-containing complex]
GO:0034198 [cellular response to amino acid starvation]
GO:0042060 [wound healing]
GO:0042246 [tissue regeneration]
GO:0042326 [negative regulation of phosphorylation]
GO:0042771 [intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator]
GO:0043068 [positive regulation of programmed cell death]
GO:0044877 [protein-containing complex binding]
GO:0045736 [negative regulation of cyclin-dependent protein serine/threonine kinase activity]
GO:0045860 [positive regulation of protein kinase activity]
GO:0046872 [metal ion binding]
GO:0048146 [positive regulation of fibroblast proliferation]
GO:0051726 [regulation of cell cycle]
GO:0060255 [regulation of macromolecule metabolic process]
GO:0070557 [PCNA-p21 complex]
GO:0071479 [cellular response to ionizing radiation]
GO:0071480 [cellular response to gamma radiation]
GO:0071493 [cellular response to UV-B]
GO:0072331 [signal transduction by p53 class mediator]
GO:0090398 [cellular senescence]
GO:0090399 [replicative senescence]
GO:0090400 [stress-induced premature senescence]
GO:0097193 [intrinsic apoptotic signaling pathway]
GO:0140311 [protein sequestering activity]
GO:0140677 [molecular function activator activity]
GO:0140678 [molecular function inhibitor activity]
GO:1902806 [regulation of cell cycle G1/S phase transition]
GO:1904030 [negative regulation of cyclin-dependent protein kinase activity]
GO:1904706 [negative regulation of vascular associated smooth muscle cell proliferation]
GO:1905179 [negative regulation of cardiac muscle tissue regeneration]
GO:2000045 [regulation of G1/S transition of mitotic cell cycle]
GO:2000134 [negative regulation of G1/S transition of mitotic cell cycle]
GO:2000278 [regulation of DNA biosynthetic process]
GO:2000279 [negative regulation of DNA biosynthetic process]
GO:2000379 [positive regulation of reactive oxygen species metabolic process]
Show all
 164 aa
18.1 kDa 		No 0
CDKN1A-202
ENSP00000362815
ENST00000373711
P38936
[Direct mapping] Cyclin-dependent kinase inhibitor 1
Show all
A0A024RCX5
[Target identity:100%; Query identity:100%] Cyclin-dependent kinase inhibitor 1A (P21, Cip1), isoform CRA_a
Show all
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Cancer-related genes
   Candidate cancer biomarkers
   Mutated cancer genes
   Mutational cancer driver genes
Human disease related genes
   Cancers
   Cancers of the breast and female genital organs
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000079 [regulation of cyclin-dependent protein serine/threonine kinase activity]
GO:0000082 [G1/S transition of mitotic cell cycle]
GO:0000307 [cyclin-dependent protein kinase holoenzyme complex]
GO:0001933 [negative regulation of protein phosphorylation]
GO:0001934 [positive regulation of protein phosphorylation]
GO:0004860 [protein kinase inhibitor activity]
GO:0004861 [cyclin-dependent protein serine/threonine kinase inhibitor activity]
GO:0005515 [protein binding]
GO:0005634 [nucleus]
GO:0005654 [nucleoplasm]
GO:0005730 [nucleolus]
GO:0005737 [cytoplasm]
GO:0005829 [cytosol]
GO:0006974 [cellular response to DNA damage stimulus]
GO:0006977 [DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest]
GO:0007049 [cell cycle]
GO:0007095 [mitotic G2 DNA damage checkpoint signaling]
GO:0007265 [Ras protein signal transduction]
GO:0007346 [regulation of mitotic cell cycle]
GO:0007507 [heart development]
GO:0008285 [negative regulation of cell population proliferation]
GO:0010389 [regulation of G2/M transition of mitotic cell cycle]
GO:0016301 [kinase activity]
GO:0016310 [phosphorylation]
GO:0016604 [nuclear body]
GO:0019901 [protein kinase binding]
GO:0019912 [cyclin-dependent protein kinase activating kinase activity]
GO:0030308 [negative regulation of cell growth]
GO:0030332 [cyclin binding]
GO:0031625 [ubiquitin protein ligase binding]
GO:0031668 [cellular response to extracellular stimulus]
GO:0032091 [negative regulation of protein binding]
GO:0032991 [protein-containing complex]
GO:0034198 [cellular response to amino acid starvation]
GO:0042326 [negative regulation of phosphorylation]
GO:0044877 [protein-containing complex binding]
GO:0045736 [negative regulation of cyclin-dependent protein serine/threonine kinase activity]
GO:0045860 [positive regulation of protein kinase activity]
GO:0046872 [metal ion binding]
GO:0048146 [positive regulation of fibroblast proliferation]
GO:0051726 [regulation of cell cycle]
GO:0060255 [regulation of macromolecule metabolic process]
GO:0070557 [PCNA-p21 complex]
GO:0071479 [cellular response to ionizing radiation]
GO:0071493 [cellular response to UV-B]
GO:0072331 [signal transduction by p53 class mediator]
GO:0090398 [cellular senescence]
GO:0090400 [stress-induced premature senescence]
GO:0097193 [intrinsic apoptotic signaling pathway]
GO:0140311 [protein sequestering activity]
GO:0140677 [molecular function activator activity]
GO:0140678 [molecular function inhibitor activity]
GO:1902806 [regulation of cell cycle G1/S phase transition]
GO:1904030 [negative regulation of cyclin-dependent protein kinase activity]
GO:1904706 [negative regulation of vascular associated smooth muscle cell proliferation]
GO:1905179 [negative regulation of cardiac muscle tissue regeneration]
GO:2000045 [regulation of G1/S transition of mitotic cell cycle]
GO:2000134 [negative regulation of G1/S transition of mitotic cell cycle]
GO:2000279 [negative regulation of DNA biosynthetic process]
GO:2000379 [positive regulation of reactive oxygen species metabolic process]
Show all
 164 aa
18.1 kDa 		No 0
CDKN1A-203
ENSP00000384849
ENST00000405375
P38936
[Direct mapping] Cyclin-dependent kinase inhibitor 1
Show all
A0A024RCX5
[Target identity:100%; Query identity:100%] Cyclin-dependent kinase inhibitor 1A (P21, Cip1), isoform CRA_a
Show all
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Cancer-related genes
   Candidate cancer biomarkers
   Mutated cancer genes
   Mutational cancer driver genes
Human disease related genes
   Cancers
   Cancers of the breast and female genital organs
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000079 [regulation of cyclin-dependent protein serine/threonine kinase activity]
GO:0000082 [G1/S transition of mitotic cell cycle]
GO:0000307 [cyclin-dependent protein kinase holoenzyme complex]
GO:0001933 [negative regulation of protein phosphorylation]
GO:0001934 [positive regulation of protein phosphorylation]
GO:0004860 [protein kinase inhibitor activity]
GO:0004861 [cyclin-dependent protein serine/threonine kinase inhibitor activity]
GO:0005515 [protein binding]
GO:0005634 [nucleus]
GO:0005654 [nucleoplasm]
GO:0005730 [nucleolus]
GO:0005737 [cytoplasm]
GO:0005829 [cytosol]
GO:0006974 [cellular response to DNA damage stimulus]
GO:0006977 [DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest]
GO:0007049 [cell cycle]
GO:0007095 [mitotic G2 DNA damage checkpoint signaling]
GO:0007265 [Ras protein signal transduction]
GO:0007346 [regulation of mitotic cell cycle]
GO:0007507 [heart development]
GO:0008285 [negative regulation of cell population proliferation]
GO:0010389 [regulation of G2/M transition of mitotic cell cycle]
GO:0016301 [kinase activity]
GO:0016310 [phosphorylation]
GO:0016604 [nuclear body]
GO:0019901 [protein kinase binding]
GO:0019912 [cyclin-dependent protein kinase activating kinase activity]
GO:0030308 [negative regulation of cell growth]
GO:0030332 [cyclin binding]
GO:0031625 [ubiquitin protein ligase binding]
GO:0031668 [cellular response to extracellular stimulus]
GO:0032091 [negative regulation of protein binding]
GO:0032991 [protein-containing complex]
GO:0034198 [cellular response to amino acid starvation]
GO:0042326 [negative regulation of phosphorylation]
GO:0044877 [protein-containing complex binding]
GO:0045736 [negative regulation of cyclin-dependent protein serine/threonine kinase activity]
GO:0045860 [positive regulation of protein kinase activity]
GO:0046872 [metal ion binding]
GO:0048146 [positive regulation of fibroblast proliferation]
GO:0051726 [regulation of cell cycle]
GO:0060255 [regulation of macromolecule metabolic process]
GO:0070557 [PCNA-p21 complex]
GO:0071479 [cellular response to ionizing radiation]
GO:0071493 [cellular response to UV-B]
GO:0072331 [signal transduction by p53 class mediator]
GO:0090398 [cellular senescence]
GO:0090400 [stress-induced premature senescence]
GO:0097193 [intrinsic apoptotic signaling pathway]
GO:0140311 [protein sequestering activity]
GO:0140677 [molecular function activator activity]
GO:0140678 [molecular function inhibitor activity]
GO:1902806 [regulation of cell cycle G1/S phase transition]
GO:1904030 [negative regulation of cyclin-dependent protein kinase activity]
GO:1904706 [negative regulation of vascular associated smooth muscle cell proliferation]
GO:1905179 [negative regulation of cardiac muscle tissue regeneration]
GO:2000045 [regulation of G1/S transition of mitotic cell cycle]
GO:2000134 [negative regulation of G1/S transition of mitotic cell cycle]
GO:2000279 [negative regulation of DNA biosynthetic process]
GO:2000379 [positive regulation of reactive oxygen species metabolic process]
Show all
 164 aa
18.1 kDa 		No 0
CDKN1A-204
ENSP00000409259
ENST00000448526
P38936
[Direct mapping] Cyclin-dependent kinase inhibitor 1
Show all
A0A024RCX5
[Target identity:100%; Query identity:100%] Cyclin-dependent kinase inhibitor 1A (P21, Cip1), isoform CRA_a
Show all
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Cancer-related genes
   Candidate cancer biomarkers
   Mutated cancer genes
   Mutational cancer driver genes
Human disease related genes
   Cancers
   Cancers of the breast and female genital organs
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000079 [regulation of cyclin-dependent protein serine/threonine kinase activity]
GO:0000082 [G1/S transition of mitotic cell cycle]
GO:0000307 [cyclin-dependent protein kinase holoenzyme complex]
GO:0001933 [negative regulation of protein phosphorylation]
GO:0001934 [positive regulation of protein phosphorylation]
GO:0004860 [protein kinase inhibitor activity]
GO:0004861 [cyclin-dependent protein serine/threonine kinase inhibitor activity]
GO:0005515 [protein binding]
GO:0005634 [nucleus]
GO:0005654 [nucleoplasm]
GO:0005730 [nucleolus]
GO:0005737 [cytoplasm]
GO:0005829 [cytosol]
GO:0006974 [cellular response to DNA damage stimulus]
GO:0006977 [DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest]
GO:0007049 [cell cycle]
GO:0007095 [mitotic G2 DNA damage checkpoint signaling]
GO:0007265 [Ras protein signal transduction]
GO:0007346 [regulation of mitotic cell cycle]
GO:0007507 [heart development]
GO:0008285 [negative regulation of cell population proliferation]
GO:0010389 [regulation of G2/M transition of mitotic cell cycle]
GO:0016301 [kinase activity]
GO:0016310 [phosphorylation]
GO:0016604 [nuclear body]
GO:0019901 [protein kinase binding]
GO:0019912 [cyclin-dependent protein kinase activating kinase activity]
GO:0030308 [negative regulation of cell growth]
GO:0030332 [cyclin binding]
GO:0031625 [ubiquitin protein ligase binding]
GO:0031668 [cellular response to extracellular stimulus]
GO:0032091 [negative regulation of protein binding]
GO:0032991 [protein-containing complex]
GO:0034198 [cellular response to amino acid starvation]
GO:0042326 [negative regulation of phosphorylation]
GO:0044877 [protein-containing complex binding]
GO:0045736 [negative regulation of cyclin-dependent protein serine/threonine kinase activity]
GO:0045860 [positive regulation of protein kinase activity]
GO:0046872 [metal ion binding]
GO:0048146 [positive regulation of fibroblast proliferation]
GO:0051726 [regulation of cell cycle]
GO:0060255 [regulation of macromolecule metabolic process]
GO:0070557 [PCNA-p21 complex]
GO:0071479 [cellular response to ionizing radiation]
GO:0071493 [cellular response to UV-B]
GO:0072331 [signal transduction by p53 class mediator]
GO:0090398 [cellular senescence]
GO:0090400 [stress-induced premature senescence]
GO:0097193 [intrinsic apoptotic signaling pathway]
GO:0140311 [protein sequestering activity]
GO:0140677 [molecular function activator activity]
GO:0140678 [molecular function inhibitor activity]
GO:1902806 [regulation of cell cycle G1/S phase transition]
GO:1904030 [negative regulation of cyclin-dependent protein kinase activity]
GO:1904706 [negative regulation of vascular associated smooth muscle cell proliferation]
GO:1905179 [negative regulation of cardiac muscle tissue regeneration]
GO:2000045 [regulation of G1/S transition of mitotic cell cycle]
GO:2000134 [negative regulation of G1/S transition of mitotic cell cycle]
GO:2000279 [negative regulation of DNA biosynthetic process]
GO:2000379 [positive regulation of reactive oxygen species metabolic process]
Show all
 164 aa
18.1 kDa 		No 0
CDKN1A-208
ENSP00000482768
ENST00000615513
P38936
[Direct mapping] Cyclin-dependent kinase inhibitor 1
Show all
A0A024RCX5
[Target identity:100%; Query identity:100%] Cyclin-dependent kinase inhibitor 1A (P21, Cip1), isoform CRA_a
Show all
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Cancer-related genes
   Candidate cancer biomarkers
   Mutated cancer genes
   Mutational cancer driver genes
Human disease related genes
   Cancers
   Cancers of the breast and female genital organs
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000079 [regulation of cyclin-dependent protein serine/threonine kinase activity]
GO:0000082 [G1/S transition of mitotic cell cycle]
GO:0000307 [cyclin-dependent protein kinase holoenzyme complex]
GO:0001933 [negative regulation of protein phosphorylation]
GO:0001934 [positive regulation of protein phosphorylation]
GO:0004860 [protein kinase inhibitor activity]
GO:0004861 [cyclin-dependent protein serine/threonine kinase inhibitor activity]
GO:0005515 [protein binding]
GO:0005634 [nucleus]
GO:0005654 [nucleoplasm]
GO:0005730 [nucleolus]
GO:0005737 [cytoplasm]
GO:0005829 [cytosol]
GO:0006974 [cellular response to DNA damage stimulus]
GO:0006977 [DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest]
GO:0007049 [cell cycle]
GO:0007095 [mitotic G2 DNA damage checkpoint signaling]
GO:0007265 [Ras protein signal transduction]
GO:0007346 [regulation of mitotic cell cycle]
GO:0007507 [heart development]
GO:0008285 [negative regulation of cell population proliferation]
GO:0010389 [regulation of G2/M transition of mitotic cell cycle]
GO:0016301 [kinase activity]
GO:0016310 [phosphorylation]
GO:0016604 [nuclear body]
GO:0019901 [protein kinase binding]
GO:0019912 [cyclin-dependent protein kinase activating kinase activity]
GO:0030308 [negative regulation of cell growth]
GO:0030332 [cyclin binding]
GO:0031625 [ubiquitin protein ligase binding]
GO:0031668 [cellular response to extracellular stimulus]
GO:0032091 [negative regulation of protein binding]
GO:0032991 [protein-containing complex]
GO:0034198 [cellular response to amino acid starvation]
GO:0042326 [negative regulation of phosphorylation]
GO:0044877 [protein-containing complex binding]
GO:0045736 [negative regulation of cyclin-dependent protein serine/threonine kinase activity]
GO:0045860 [positive regulation of protein kinase activity]
GO:0046872 [metal ion binding]
GO:0048146 [positive regulation of fibroblast proliferation]
GO:0051726 [regulation of cell cycle]
GO:0060255 [regulation of macromolecule metabolic process]
GO:0070557 [PCNA-p21 complex]
GO:0071479 [cellular response to ionizing radiation]
GO:0071493 [cellular response to UV-B]
GO:0072331 [signal transduction by p53 class mediator]
GO:0090398 [cellular senescence]
GO:0090400 [stress-induced premature senescence]
GO:0097193 [intrinsic apoptotic signaling pathway]
GO:0140311 [protein sequestering activity]
GO:0140677 [molecular function activator activity]
GO:0140678 [molecular function inhibitor activity]
GO:1902806 [regulation of cell cycle G1/S phase transition]
GO:1904030 [negative regulation of cyclin-dependent protein kinase activity]
GO:1904706 [negative regulation of vascular associated smooth muscle cell proliferation]
GO:1905179 [negative regulation of cardiac muscle tissue regeneration]
GO:2000045 [regulation of G1/S transition of mitotic cell cycle]
GO:2000134 [negative regulation of G1/S transition of mitotic cell cycle]
GO:2000279 [negative regulation of DNA biosynthetic process]
GO:2000379 [positive regulation of reactive oxygen species metabolic process]
Show all
 164 aa
18.1 kDa 		No 0

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