Cyclin-dependent kinase inhibitor 1

Details

Name
Cyclin-dependent kinase inhibitor 1
Synonyms
  • CAP20
  • CDK-interacting protein 1
  • CDKN1
  • CIP1
  • MDA-6
  • MDA6
  • Melanoma differentiation-associated protein 6
  • p21
  • PIC1
  • SDI1
  • WAF1
Gene Name
CDKN1A
Organism
Humans
Amino acid sequence
>lcl|BSEQ0049737|Cyclin-dependent kinase inhibitor 1
MSEPAGDVRQNPCGSKACRRLFGPVDSEQLSRDCDALMAGCIQEARERWNFDFVTETPLE
GDFAWERVRGLGLPKLYLPTGPRRGRDELGGGRRPGTSPALLQGTAEEDHVDLSLSCTLV
PRSGEQAEGSPGGPGDSQGRKRRQTSMTDFYHSKRRLIFSKRKP
Number of residues
164
Molecular Weight
18119.145
Theoretical pI
Not Available
GO Classification
Functions
cyclin binding / cyclin-dependent protein kinase activating kinase activity / cyclin-dependent protein serine/threonine kinase inhibitor activity / metal ion binding / protein complex binding / protein kinase binding / protein kinase inhibitor activity / ubiquitin protein ligase binding
Processes
animal organ regeneration / cell cycle arrest / cellular response to amino acid starvation / cellular response to DNA damage stimulus / cellular response to extracellular stimulus / cellular response to gamma radiation / cellular response to heat / cellular response to ionizing radiation / cellular response to UV-B / cellular senescence / 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 / G1/S transition of mitotic cell cycle / G2/M transition of mitotic cell cycle / intestinal epithelial cell maturation / intrinsic apoptotic signaling pathway / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / mitotic cell cycle arrest / negative regulation of apoptotic process / negative regulation of cell growth / negative regulation of cell proliferation / negative regulation of cyclin-dependent protein kinase activity / negative regulation of cyclin-dependent protein serine/threonine kinase activity / negative regulation of G1/S transition of mitotic cell cycle / negative regulation of gene expression / negative regulation of phosphorylation / positive regulation of B cell proliferation / 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 stabilization / Ras protein signal transduction / regulation of cyclin-dependent protein serine/threonine kinase activity / regulation of DNA biosynthetic process / regulation of protein import into nucleus, translocation / regulation of transcription from RNA polymerase II promoter / replicative senescence / response to arsenic-containing substance / response to corticosterone / response to drug / response to hyperoxia / response to organonitrogen compound / response to toxic substance / response to X-ray / stress-induced premature senescence
Components
cyclin-dependent protein kinase holoenzyme complex / cytosol / nuclear body / nucleolus / nucleoplasm / nucleus / PCNA-p21 complex / perinuclear region of cytoplasm / protein complex
General Function
May be involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. 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 (PubMed:11595739).
Specific Function
Cyclin binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0049738|Cyclin-dependent kinase inhibitor 1 (CDKN1A)
ATGTCAGAACCGGCTGGGGATGTCCGTCAGAACCCATGCGGCAGCAAGGCCTGCCGCCGC
CTCTTCGGCCCAGTGGACAGCGAGCAGCTGAGCCGCGACTGTGATGCGCTAATGGCGGGC
TGCATCCAGGAGGCCCGTGAGCGATGGAACTTCGACTTTGTCACCGAGACACCACTGGAG
GGTGACTTCGCCTGGGAGCGTGTGCGGGGCCTTGGCCTGCCCAAGCTCTACCTTCCCACG
GGGCCCCGGCGAGGCCGGGATGAGTTGGGAGGAGGCAGGCGGCCTGGCACCTCACCTGCT
CTGCTGCAGGGGACAGCAGAGGAAGACCATGTGGACCTGTCACTGTCTTGTACCCTTGTG
CCTCGCTCAGGGGAGCAGGCTGAAGGGTCCCCAGGTGGACCTGGAGACTCTCAGGGTCGA
AAACGGCGGCAGACCAGCATGACAGATTTCTACCACTCCAAACGCCGGCTGATCTTCTCC
AAGAGGAAGCCCTAA
Chromosome Location
6
Locus
6p21.2
External Identifiers
ResourceLink
UniProtKB IDP38936
UniProtKB Entry NameCDN1A_HUMAN
HGNC IDHGNC:1784
General References
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  2. el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B: WAF1, a potential mediator of p53 tumor suppression. Cell. 1993 Nov 19;75(4):817-25. [PubMed:8242752]
  3. Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D: p21 is a universal inhibitor of cyclin kinases. Nature. 1993 Dec 16;366(6456):701-4. [PubMed:8259214]
  4. Jiang H, Lin J, Su ZZ, Herlyn M, Kerbel RS, Weissman BE, Welch DR, Fisher PB: The melanoma differentiation-associated gene mda-6, which encodes the cyclin-dependent kinase inhibitor p21, is differentially expressed during growth, differentiation and progression in human melanoma cells. Oncogene. 1995 May 4;10(9):1855-64. [PubMed:7753561]
  5. Noda A, Ning Y, Venable SF, Pereira-Smith OM, Smith JR: Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Exp Cell Res. 1994 Mar;211(1):90-8. [PubMed:8125163]
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  11. Scott MT, Morrice N, Ball KL: Reversible phosphorylation at the C-terminal regulatory domain of p21(Waf1/Cip1) modulates proliferating cell nuclear antigen binding. J Biol Chem. 2000 Apr 14;275(15):11529-37. [PubMed:10753973]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01169Arsenic trioxideapproved, investigationalunknownDetails