CDN1A_HUMAN
ID CDN1A_HUMAN Reviewed; 164 AA.
AC P38936; Q14010; Q6FI05; Q9BUT4;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 236.
DE RecName: Full=Cyclin-dependent kinase inhibitor 1;
DE AltName: Full=CDK-interacting protein 1;
DE AltName: Full=Melanoma differentiation-associated protein 6;
DE Short=MDA-6;
DE AltName: Full=p21;
GN Name=CDKN1A; Synonyms=CAP20, CDKN1, CIP1, MDA6, PIC1, SDI1, WAF1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INDUCTION.
RX PubMed=8242751; DOI=10.1016/0092-8674(93)90499-g;
RA Harper J.W., Adami G.R., Wei N., Keyomarsi K., Elledge S.J.;
RT "The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-
RT dependent kinases.";
RL Cell 75:805-816(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RX PubMed=8242752; DOI=10.1016/0092-8674(93)90500-p;
RA El-Deiry W.S., Tokino T., Velculescu V.E., Levy D.B., Parsons R.,
RA Trent J.M., Lin D., Mercer W.E., Kinzler K.W., Vogelstein B.;
RT "WAF1, a potential mediator of p53 tumor suppression.";
RL Cell 75:817-825(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8259214; DOI=10.1038/366701a0;
RA Xiong Y., Hannon G.J., Zhang H., Casso D., Kobayashi R., Beach D.;
RT "p21 is a universal inhibitor of cyclin kinases.";
RL Nature 366:701-704(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Jiang H., Fisher P.B.;
RT "Use of a sensitive and efficient subtraction hybridization protocol for
RT the identification of genes differentially regulated during the induction
RT of differentiation in human melanoma cells.";
RL Mol. Cell. Differ. 1:285-299(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7753561;
RA Jiang H., Lin J., Su Z.Z., Herlyn M., Kerbel R.S., Weissman B.E.,
RA Welch D.R., Fisher P.B.;
RT "The melanoma differentiation-associated gene mda-6, which encodes the
RT cyclin-dependent kinase inhibitor p21, is differentially expressed during
RT growth, differentiation and progression in human melanoma cells.";
RL Oncogene 10:1855-1864(1995).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8125163; DOI=10.1006/excr.1994.1063;
RA Noda A., Ning Y., Venable S.F., Pereira-Smith O.M., Smith J.R.;
RT "Cloning of senescent cell-derived inhibitors of DNA synthesis using an
RT expression screen.";
RL Exp. Cell Res. 211:90-98(1994).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-31.
RX PubMed=7655464; DOI=10.1093/hmg/4.6.1089;
RA Mousses S., Oezcelik H., Lee P.D., Malkin D., Bull S.B., Andrulis I.L.;
RT "Two variants of the CIP1/WAF1 gene occur together and are associated with
RT human cancer.";
RL Hum. Mol. Genet. 4:1089-1092(1995).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-31.
RG NIEHS SNPs program;
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-31.
RC TISSUE=Eye, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [15]
RP PROTEIN SEQUENCE OF 2-16, ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=15574338; DOI=10.1016/j.molcel.2004.11.011;
RA Chen X., Chi Y., Bloecher A., Aebersold R., Clurman B.E., Roberts J.M.;
RT "N-acetylation and ubiquitin-independent proteasomal degradation of
RT p21(Cip1).";
RL Mol. Cell 16:839-847(2004).
RN [16]
RP PROTEIN SEQUENCE OF 136-148, PHOSPHORYLATION AT THR-145; SER-146 AND
RP SER-160, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=10753973; DOI=10.1074/jbc.275.15.11529;
RA Scott M.T., Morrice N., Ball K.L.;
RT "Reversible phosphorylation at the C-terminal regulatory domain of
RT p21(Waf1/Cip1) modulates proliferating cell nuclear antigen binding.";
RL J. Biol. Chem. 275:11529-11537(2000).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CDK4 AND CCND1 IN THE
RP CYCLIN D-CDK4-CDKN1A COMPLEX.
RX PubMed=9106657; DOI=10.1101/gad.11.7.847;
RA LaBaer J., Garrett M.D., Stevenson L.F., Slingerland J.M., Sandhu C.,
RA Chou H.S., Fattaey A., Harlow E.;
RT "New functional activities for the p21 family of CDK inhibitors.";
RL Genes Dev. 11:847-862(1997).
RN [18]
RP INTERACTION WITH PSMA3.
RX PubMed=11350925; DOI=10.1093/emboj/20.10.2367;
RA Touitou R., Richardson J., Bose S., Nakanishi M., Rivett J., Allday M.J.;
RT "A degradation signal located in the C-terminus of p21WAF1/CIP1 is a
RT binding site for the C8 alpha-subunit of the 20S proteasome.";
RL EMBO J. 20:2367-2375(2001).
RN [19]
RP FUNCTION, AND INTERACTION WITH PCNA.
RX PubMed=11595739; DOI=10.1074/jbc.m106990200;
RA Ducoux M., Urbach S., Baldacci G., Huebscher U., Koundrioukoff S.,
RA Christensen J., Hughes P.;
RT "Mediation of proliferating cell nuclear antigen (PCNA)-dependent DNA
RT replication through a conserved p21(Cip1)-like PCNA-binding motif present
RT in the third subunit of human DNA polymerase delta.";
RL J. Biol. Chem. 276:49258-49266(2001).
RN [20]
RP PHOSPHORYLATION AT THR-145, MUTAGENESIS OF THR-145 AND SER-146, AND
RP SUBCELLULAR LOCATION.
RX PubMed=11463845; DOI=10.1128/mcb.21.16.5644-5657.2001;
RA Roessig L., Jadidi A.S., Urbich C., Badorff C., Zeiher A.M., Dimmeler S.;
RT "Akt-dependent phosphorylation of p21(Cip1) regulates PCNA binding and
RT proliferation of endothelial cells.";
RL Mol. Cell. Biol. 21:5644-5657(2001).
RN [21]
RP PHOSPHORYLATION AT THR-145 BY PIM1, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH PIM1.
RX PubMed=12431783; DOI=10.1016/s0167-4889(02)00347-6;
RA Wang Z., Bhattacharya N., Mixter P.F., Wei W., Sedivy J., Magnuson N.S.;
RT "Phosphorylation of the cell cycle inhibitor p21Cip1/WAF1 by Pim-1
RT kinase.";
RL Biochim. Biophys. Acta 1593:45-55(2002).
RN [22]
RP UBIQUITINATION AT SER-2.
RX PubMed=15226418; DOI=10.1128/mcb.24.14.6140-6150.2004;
RA Coulombe P., Rodier G., Bonneil E., Thibault P., Meloche S.;
RT "N-Terminal ubiquitination of extracellular signal-regulated kinase 3 and
RT p21 directs their degradation by the proteasome.";
RL Mol. Cell. Biol. 24:6140-6150(2004).
RN [23]
RP PHOSPHORYLATION AT THR-145.
RX PubMed=16982699; DOI=10.1128/mcb.00201-06;
RA Heron-Milhavet L., Franckhauser C., Rana V., Berthenet C., Fisher D.,
RA Hemmings B.A., Fernandez A., Lamb N.J.;
RT "Only Akt1 is required for proliferation, while Akt2 promotes cell cycle
RT exit through p21 binding.";
RL Mol. Cell. Biol. 26:8267-8280(2006).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [25]
RP UBIQUITINATION, DOMAIN PIP-BOX K+4 MOTIF, INTERACTION WITH PCNA,
RP MUTAGENESIS OF SER-114 AND 144-GLN--PHE-150, AND PHOSPHORYLATION AT
RP SER-114.
RX PubMed=18794347; DOI=10.1101/gad.1676108;
RA Abbas T., Sivaprasad U., Terai K., Amador V., Pagano M., Dutta A.;
RT "PCNA-dependent regulation of p21 ubiquitylation and degradation via the
RT CRL4Cdt2 ubiquitin ligase complex.";
RL Genes Dev. 22:2496-2506(2008).
RN [26]
RP UBIQUITINATION.
RX PubMed=18794348; DOI=10.1101/gad.1703708;
RA Kim Y., Starostina N.G., Kipreos E.T.;
RT "The CRL4Cdt2 ubiquitin ligase targets the degradation of p21Cip1 to
RT control replication licensing.";
RL Genes Dev. 22:2507-2519(2008).
RN [27]
RP UBIQUITINATION, DOMAIN PIP-BOX K+4 MOTIF, MUTAGENESIS OF 147-MET--TYR-151
RP AND 154-LYS--ARG-156, AND INTERACTION WITH PCNA.
RX PubMed=18703516; DOI=10.1074/jbc.m806045200;
RA Nishitani H., Shiomi Y., Iida H., Michishita M., Takami T., Tsurimoto T.;
RT "CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-
RT coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation.";
RL J. Biol. Chem. 283:29045-29052(2008).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [29]
RP REVIEW ON DNA REPAIR, AND INTERACTION WITH CDK2.
RX PubMed=19445729; DOI=10.1186/1747-1028-4-9;
RA Satyanarayana A., Kaldis P.;
RT "A dual role of Cdk2 in DNA damage response.";
RL Cell Div. 4:9-9(2009).
RN [30]
RP UBIQUITINATION, AND INTERACTION WITH MKRN1.
RX PubMed=19536131; DOI=10.1038/emboj.2009.164;
RA Lee E.-W., Lee M.-S., Camus S., Ghim J., Yang M.-R., Oh W., Ha N.-C.,
RA Lane D.P., Song J.;
RT "Differential regulation of p53 and p21 by MKRN1 E3 ligase controls cell
RT cycle arrest and apoptosis.";
RL EMBO J. 28:2100-2113(2009).
RN [31]
RP UBIQUITINATION.
RX PubMed=19332548; DOI=10.1074/jbc.m808810200;
RA Stuart S.A., Wang J.Y.;
RT "Ionizing radiation induces ATM-independent degradation of p21Cip1 in
RT transformed cells.";
RL J. Biol. Chem. 284:15061-15070(2009).
RN [32]
RP PHOSPHORYLATION AT THR-145 BY PIM2.
RX PubMed=20307683; DOI=10.1016/j.biocel.2010.03.012;
RA Wang Z., Zhang Y., Gu J.J., Davitt C., Reeves R., Magnuson N.S.;
RT "Pim-2 phosphorylation of p21(Cip1/WAF1) enhances its stability and
RT inhibits cell proliferation in HCT116 cells.";
RL Int. J. Biochem. Cell Biol. 42:1030-1038(2010).
RN [33]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [34]
RP FUNCTION, INTERACTION WITH TRIM39 AND DTL, SUBCELLULAR LOCATION,
RP UBIQUITINATION, PROTEASOMAL DEGRADATION, AND MUTAGENESIS OF LYS-154.
RX PubMed=23213251; DOI=10.1073/pnas.1214156110;
RA Zhang L., Mei Y., Fu N.Y., Guan L., Xie W., Liu H.H., Yu C.D., Yin Z.,
RA Yu V.C., You H.;
RT "TRIM39 regulates cell cycle progression and DNA damage responses via
RT stabilizing p21.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:20937-20942(2012).
RN [35]
RP UBIQUITINATION BY RNF114.
RX PubMed=23645206; DOI=10.1038/cdd.2013.33;
RA Han J., Kim Y.L., Lee K.W., Her N.G., Ha T.K., Yoon S., Jeong S.I.,
RA Lee J.H., Kang M.J., Lee M.G., Ryu B.K., Baik J.H., Chi S.G.;
RT "ZNF313 is a novel cell cycle activator with an E3 ligase activity
RT inhibiting cellular senescence by destabilizing p21(WAF1.).";
RL Cell Death Differ. 20:1055-1067(2013).
RN [36]
RP FUNCTION, INTERACTION WITH STK11 AND NUAK1, PHOSPHORYLATION AT THR-80 AND
RP SER-146, AND MUTAGENESIS OF THR-80 AND SER-146.
RX PubMed=25329316; DOI=10.1371/journal.pgen.1004721;
RA Esteve-Puig R., Gil R., Gonzalez-Sanchez E., Bech-Serra J.J., Grueso J.,
RA Hernandez-Losa J., Moline T., Canals F., Ferrer B., Cortes J., Bastian B.,
RA Cajal S.R.Y., Martin-Caballero J., Flores J.M., Vivancos A.,
RA Garcia-Patos V., Recio J.A.;
RT "A mouse model uncovers LKB1 as an UVB-induced DNA damage sensor mediating
RT CDKN1A (p21WAF1/CIP1) degradation.";
RL PLoS Genet. 10:E1004721-E1004721(2014).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 139-160 IN COMPLEX WITH PCNA.
RX PubMed=8861913; DOI=10.1016/s0092-8674(00)81347-1;
RA Gulbis J.M., Kelman Z., Hurwitz J., O'Donnell M., Kuriyan J.;
RT "Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human
RT PCNA.";
RL Cell 87:297-306(1996).
CC -!- FUNCTION: May be involved in p53/TP53 mediated inhibition of cellular
CC proliferation in response to DNA damage. Binds to and inhibits cyclin-
CC dependent kinase activity, preventing phosphorylation of critical
CC cyclin-dependent kinase substrates and blocking cell cycle progression.
CC Functions in the nuclear localization and assembly of cyclin D-CDK4
CC complex and promotes its kinase activity towards RB1. At higher
CC stoichiometric ratios, inhibits the kinase activity of the cyclin D-
CC CDK4 complex. Inhibits DNA synthesis by DNA polymerase delta by
CC competing with POLD3 for PCNA binding (PubMed:11595739). Plays an
CC important role in controlling cell cycle progression and DNA damage-
CC induced G2 arrest (PubMed:9106657). {ECO:0000269|PubMed:11595739,
CC ECO:0000269|PubMed:8242751, ECO:0000269|PubMed:9106657}.
CC -!- SUBUNIT: Interacts with HDAC1; the interaction is prevented by
CC competitive binding of C10orf90/FATS to HDAC1 facilitating acetylation
CC and protein stabilization of CDKN1A/p21 (By similarity). Interacts with
CC MKRN1 (PubMed:19536131). Interacts with PSMA3 (PubMed:11350925).
CC Interacts with PCNA (PubMed:11595739, PubMed:18794347, PubMed:18703516,
CC PubMed:8861913). Component of the ternary complex, cyclin D-CDK4-
CC CDKN1A. Interacts (via its N-terminal domain) with CDK4; the
CC interaction promotes the assembly of the cyclin D-CDK4 complex, its
CC nuclear translocation and promotes the cyclin D-dependent enzyme
CC activity of CDK4 (PubMed:9106657). Binding to CDK2 leads to CDK2/cyclin
CC E inactivation at the G1-S phase DNA damage checkpoint, thereby
CC arresting cells at the G1-S transition during DNA repair
CC (PubMed:19445729). Interacts with PIM1 (PubMed:12431783). Interacts
CC with STK11 and NUAK1 (PubMed:25329316). Interacts wih DTL
CC (PubMed:23213251). Interacts with isoform 1 and isoform 2 of TRIM39
CC (PubMed:23213251). {ECO:0000250|UniProtKB:P39689,
CC ECO:0000269|PubMed:11350925, ECO:0000269|PubMed:11595739,
CC ECO:0000269|PubMed:12431783, ECO:0000269|PubMed:18703516,
CC ECO:0000269|PubMed:18794347, ECO:0000269|PubMed:19445729,
CC ECO:0000269|PubMed:19536131, ECO:0000269|PubMed:23213251,
CC ECO:0000269|PubMed:25329316, ECO:0000269|PubMed:8861913,
CC ECO:0000269|PubMed:9106657}.
CC -!- INTERACTION:
CC P38936; P78396: CCNA1; NbExp=8; IntAct=EBI-375077, EBI-375065;
CC P38936; P20248: CCNA2; NbExp=5; IntAct=EBI-375077, EBI-457097;
CC P38936; P24385: CCND1; NbExp=20; IntAct=EBI-375077, EBI-375001;
CC P38936; P30279: CCND2; NbExp=17; IntAct=EBI-375077, EBI-748789;
CC P38936; P30281: CCND3; NbExp=24; IntAct=EBI-375077, EBI-375013;
CC P38936; P24864: CCNE1; NbExp=9; IntAct=EBI-375077, EBI-519526;
CC P38936; O96020: CCNE2; NbExp=6; IntAct=EBI-375077, EBI-375033;
CC P38936; O75419: CDC45; NbExp=2; IntAct=EBI-375077, EBI-374969;
CC P38936; Q99741: CDC6; NbExp=2; IntAct=EBI-375077, EBI-374862;
CC P38936; P06493: CDK1; NbExp=7; IntAct=EBI-375077, EBI-444308;
CC P38936; O94921: CDK14; NbExp=8; IntAct=EBI-375077, EBI-1043945;
CC P38936; P24941: CDK2; NbExp=28; IntAct=EBI-375077, EBI-375096;
CC P38936; Q00526: CDK3; NbExp=6; IntAct=EBI-375077, EBI-1245761;
CC P38936; P11802: CDK4; NbExp=8; IntAct=EBI-375077, EBI-295644;
CC P38936; Q00535: CDK5; NbExp=5; IntAct=EBI-375077, EBI-1041567;
CC P38936; Q00534: CDK6; NbExp=2; IntAct=EBI-375077, EBI-295663;
CC P38936; G5E9A7: DMWD; NbExp=3; IntAct=EBI-375077, EBI-10976677;
CC P38936; P41091: EIF2S3; NbExp=3; IntAct=EBI-375077, EBI-1054228;
CC P38936; O75460-2: ERN1; NbExp=3; IntAct=EBI-375077, EBI-25852368;
CC P38936; P22607: FGFR3; NbExp=3; IntAct=EBI-375077, EBI-348399;
CC P38936; Q0VDC6: FKBP1A; NbExp=3; IntAct=EBI-375077, EBI-10226858;
CC P38936; Q9BVV2: FNDC11; NbExp=3; IntAct=EBI-375077, EBI-744935;
CC P38936; Q08379: GOLGA2; NbExp=3; IntAct=EBI-375077, EBI-618309;
CC P38936; P06396: GSN; NbExp=3; IntAct=EBI-375077, EBI-351506;
CC P38936; Q96ED9-2: HOOK2; NbExp=3; IntAct=EBI-375077, EBI-10961706;
CC P38936; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-375077, EBI-747204;
CC P38936; Q0VD86: INCA1; NbExp=3; IntAct=EBI-375077, EBI-6509505;
CC P38936; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-375077, EBI-14069005;
CC P38936; Q15323: KRT31; NbExp=6; IntAct=EBI-375077, EBI-948001;
CC P38936; Q9BYR8: KRTAP3-1; NbExp=3; IntAct=EBI-375077, EBI-9996449;
CC P38936; Q9P2M1: LRP2BP; NbExp=3; IntAct=EBI-375077, EBI-18273118;
CC P38936; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-375077, EBI-741037;
CC P38936; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-375077, EBI-16439278;
CC P38936; Q9UHC7: MKRN1; NbExp=5; IntAct=EBI-375077, EBI-373524;
CC P38936; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-375077, EBI-11522433;
CC P38936; Q9BQ15: NABP2; NbExp=7; IntAct=EBI-375077, EBI-2120336;
CC P38936; P12004: PCNA; NbExp=37; IntAct=EBI-375077, EBI-358311;
CC P38936; Q6FI35: PCNA; NbExp=2; IntAct=EBI-375077, EBI-8469539;
CC P38936; P31321: PRKAR1B; NbExp=3; IntAct=EBI-375077, EBI-2805516;
CC P38936; Q04864-2: REL; NbExp=3; IntAct=EBI-375077, EBI-10829018;
CC P38936; P49591: SARS1; NbExp=3; IntAct=EBI-375077, EBI-1053431;
CC P38936; Q9UQR0-1: SCML2; NbExp=3; IntAct=EBI-375077, EBI-16087037;
CC P38936; Q6ZSJ9: SHISA6; NbExp=3; IntAct=EBI-375077, EBI-12037847;
CC P38936; Q96FS4: SIPA1; NbExp=2; IntAct=EBI-375077, EBI-1054981;
CC P38936; P63208: SKP1; NbExp=3; IntAct=EBI-375077, EBI-307486;
CC P38936; Q13309: SKP2; NbExp=3; IntAct=EBI-375077, EBI-456291;
CC P38936; Q7Z699: SPRED1; NbExp=4; IntAct=EBI-375077, EBI-5235340;
CC P38936; P51692: STAT5B; NbExp=3; IntAct=EBI-375077, EBI-1186119;
CC P38936; P15884: TCF4; NbExp=3; IntAct=EBI-375077, EBI-533224;
CC P38936; Q8IYF3: TEX11; NbExp=4; IntAct=EBI-375077, EBI-742397;
CC P38936; Q9UBB9: TFIP11; NbExp=3; IntAct=EBI-375077, EBI-1105213;
CC P38936; Q13077: TRAF1; NbExp=3; IntAct=EBI-375077, EBI-359224;
CC P38936; Q9BYV2: TRIM54; NbExp=6; IntAct=EBI-375077, EBI-2130429;
CC P38936; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-375077, EBI-741480;
CC P38936; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-375077, EBI-739895;
CC P38936; Q9Y649; NbExp=3; IntAct=EBI-375077, EBI-25900580;
CC P38936; PRO_0000037566 [P27958]; Xeno; NbExp=3; IntAct=EBI-375077, EBI-6377335;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11463845}. Nucleus
CC {ECO:0000269|PubMed:11463845, ECO:0000269|PubMed:23213251}.
CC -!- TISSUE SPECIFICITY: Expressed in all adult tissues, with 5-fold lower
CC levels observed in the brain.
CC -!- INDUCTION: Activated by p53/TP53, mezerein (antileukemic compound) and
CC IFNB1. Repressed by HDAC1. {ECO:0000269|PubMed:8242751,
CC ECO:0000269|PubMed:8242752}.
CC -!- DOMAIN: The PIP-box K+4 motif mediates both the interaction with PCNA
CC and the recruitment of the DCX(DTL) complex: while the PIP-box
CC interacts with PCNA, the presence of the K+4 submotif, recruits the
CC DCX(DTL) complex, leading to its ubiquitination.
CC -!- DOMAIN: The C-terminal is required for nuclear localization of the
CC cyclin D-CDK4 complex.
CC -!- PTM: Phosphorylation of Thr-145 by Akt or of Ser-146 by PKC impairs
CC binding to PCNA. Phosphorylation at Ser-114 by GSK3-beta enhances
CC ubiquitination by the DCX(DTL) complex. Phosphorylation of Thr-145 by
CC PIM2 enhances CDKN1A stability and inhibits cell proliferation.
CC Phosphorylation of Thr-145 by PIM1 results in the relocation of CDKN1A
CC to the cytoplasm and enhanced CDKN1A protein stability. UV radiation-
CC induced phosphorylation at Thr-80 by LKB1 and at Ser-146 by NUAK1 leads
CC to its degradation. {ECO:0000269|PubMed:10753973,
CC ECO:0000269|PubMed:11463845, ECO:0000269|PubMed:12431783,
CC ECO:0000269|PubMed:16982699, ECO:0000269|PubMed:18794347,
CC ECO:0000269|PubMed:20307683, ECO:0000269|PubMed:25329316}.
CC -!- PTM: Ubiquitinated by MKRN1; leading to polyubiquitination and 26S
CC proteasome-dependent degradation. Ubiquitinated by the DCX(DTL)
CC complex, also named CRL4(CDT2) complex, leading to its degradation
CC during S phase or following UV irradiation. Ubiquitination by the
CC DCX(DTL) complex is essential to control replication licensing and is
CC PCNA-dependent: interacts with PCNA via its PIP-box, while the presence
CC of the containing the 'K+4' motif in the PIP box, recruit the DCX(DTL)
CC complex, leading to its degradation. Ubiquitination at Ser-2 leads to
CC degradation by the proteasome pathway. Ubiquitinated by RNF114; leading
CC to proteasomal degradation. {ECO:0000269|PubMed:15226418,
CC ECO:0000269|PubMed:23213251}.
CC -!- PTM: Acetylation leads to protein stability. Acetylated in vitro on
CC Lys-141, Lys-154, Lys-161 and Lys-163. Deacetylation by HDAC1 is
CC prevented by competitive binding of C10orf90/FATS to HDAC1 (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the CDI family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB59559.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAB59560.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CDKN1AID139.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cdkn1a/";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L25610; AAA16109.1; -; mRNA.
DR EMBL; S67388; AAB29246.1; -; mRNA.
DR EMBL; U09579; AAA85641.1; -; mRNA.
DR EMBL; U03106; AAC04313.1; -; mRNA.
DR EMBL; L26165; AAA19811.1; -; mRNA.
DR EMBL; L47232; AAB59559.1; ALT_INIT; mRNA.
DR EMBL; L47233; AAB59560.1; ALT_INIT; mRNA.
DR EMBL; AF497972; AAM11787.1; -; Genomic_DNA.
DR EMBL; BT006719; AAP35365.1; -; mRNA.
DR EMBL; AB451290; BAG70104.1; -; mRNA.
DR EMBL; AB451422; BAG70236.1; -; mRNA.
DR EMBL; CR536533; CAG38770.1; -; mRNA.
DR EMBL; Z85996; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX03904.1; -; Genomic_DNA.
DR EMBL; BC000275; AAH00275.1; -; mRNA.
DR EMBL; BC000312; AAH00312.1; -; mRNA.
DR EMBL; BC001935; AAH01935.1; -; mRNA.
DR EMBL; BC013967; AAH13967.1; -; mRNA.
DR CCDS; CCDS4824.1; -.
DR PIR; I54380; I54380.
DR PIR; I68674; I68674.
DR RefSeq; NP_000380.1; NM_000389.4.
DR RefSeq; NP_001207706.1; NM_001220777.1.
DR RefSeq; NP_001207707.1; NM_001220778.1.
DR RefSeq; NP_001278478.1; NM_001291549.1.
DR RefSeq; NP_510867.1; NM_078467.2.
DR PDB; 1AXC; X-ray; 2.60 A; B/D/F=139-160.
DR PDB; 2ZVV; X-ray; 2.00 A; X/Y=139-160.
DR PDB; 2ZVW; X-ray; 2.50 A; I/J/K/L/M/N/O/P=139-160.
DR PDB; 4RJF; X-ray; 2.01 A; B/D/F=139-160.
DR PDB; 5E0U; X-ray; 1.93 A; D/E/F=139-160.
DR PDB; 6CBI; X-ray; 2.75 A; H/I/J/K=139-152.
DR PDB; 6CEJ; NMR; -; A=139-152.
DR PDB; 6CIV; NMR; -; C=139-152.
DR PDB; 6CIX; NMR; -; B=139-152.
DR PDB; 6P8H; X-ray; 3.19 A; C=9-85.
DR PDB; 7KQ0; X-ray; 2.40 A; B/D/F=141-155.
DR PDB; 7KQ1; X-ray; 3.30 A; B/D/F=141-155.
DR PDBsum; 1AXC; -.
DR PDBsum; 2ZVV; -.
DR PDBsum; 2ZVW; -.
DR PDBsum; 4RJF; -.
DR PDBsum; 5E0U; -.
DR PDBsum; 6CBI; -.
DR PDBsum; 6CEJ; -.
DR PDBsum; 6CIV; -.
DR PDBsum; 6CIX; -.
DR PDBsum; 6P8H; -.
DR PDBsum; 7KQ0; -.
DR PDBsum; 7KQ1; -.
DR AlphaFoldDB; P38936; -.
DR BMRB; P38936; -.
DR SMR; P38936; -.
DR BioGRID; 107460; 351.
DR CORUM; P38936; -.
DR DIP; DIP-246N; -.
DR IntAct; P38936; 216.
DR MINT; P38936; -.
DR STRING; 9606.ENSP00000384849; -.
DR BindingDB; P38936; -.
DR ChEMBL; CHEMBL5021; -.
DR DrugBank; DB01169; Arsenic trioxide.
DR MoonDB; P38936; Predicted.
DR GlyGen; P38936; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P38936; -.
DR PhosphoSitePlus; P38936; -.
DR BioMuta; CDKN1A; -.
DR DMDM; 729143; -.
DR SWISS-2DPAGE; P38936; -.
DR EPD; P38936; -.
DR jPOST; P38936; -.
DR MassIVE; P38936; -.
DR PaxDb; P38936; -.
DR PeptideAtlas; P38936; -.
DR PRIDE; P38936; -.
DR ProteomicsDB; 55307; -.
DR Antibodypedia; 3757; 2453 antibodies from 47 providers.
DR DNASU; 1026; -.
DR Ensembl; ENST00000244741.10; ENSP00000244741.6; ENSG00000124762.14.
DR Ensembl; ENST00000373711.3; ENSP00000362815.1; ENSG00000124762.14.
DR Ensembl; ENST00000405375.5; ENSP00000384849.1; ENSG00000124762.14.
DR Ensembl; ENST00000448526.6; ENSP00000409259.3; ENSG00000124762.14.
DR Ensembl; ENST00000615513.4; ENSP00000482768.1; ENSG00000124762.14.
DR GeneID; 1026; -.
DR KEGG; hsa:1026; -.
DR MANE-Select; ENST00000244741.10; ENSP00000244741.6; NM_000389.5; NP_000380.1.
DR UCSC; uc003omm.5; human.
DR CTD; 1026; -.
DR DisGeNET; 1026; -.
DR GeneCards; CDKN1A; -.
DR HGNC; HGNC:1784; CDKN1A.
DR HPA; ENSG00000124762; Low tissue specificity.
DR MalaCards; CDKN1A; -.
DR MIM; 116899; gene.
DR neXtProt; NX_P38936; -.
DR OpenTargets; ENSG00000124762; -.
DR Orphanet; 652; Multiple endocrine neoplasia type 1.
DR PharmGKB; PA104; -.
DR VEuPathDB; HostDB:ENSG00000124762; -.
DR eggNOG; KOG4743; Eukaryota.
DR GeneTree; ENSGT00940000159918; -.
DR HOGENOM; CLU_077692_1_1_1; -.
DR InParanoid; P38936; -.
DR OMA; KVCRRLF; -.
DR OrthoDB; 962484at2759; -.
DR PhylomeDB; P38936; -.
DR TreeFam; TF101038; -.
DR PathwayCommons; P38936; -.
DR Reactome; R-HSA-187577; SCF(Skp2)-mediated degradation of p27/p21.
DR Reactome; R-HSA-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-HSA-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-6804116; TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest.
DR Reactome; R-HSA-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-HSA-69231; Cyclin D associated events in G1.
DR Reactome; R-HSA-69563; p53-Dependent G1 DNA Damage Response.
DR Reactome; R-HSA-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR Reactome; R-HSA-69895; Transcriptional activation of cell cycle inhibitor p21.
DR Reactome; R-HSA-8852276; The role of GTSE1 in G2/M progression after G2 checkpoint.
DR Reactome; R-HSA-8866911; TFAP2 (AP-2) family regulates transcription of cell cycle factors.
DR Reactome; R-HSA-8878166; Transcriptional regulation by RUNX2.
DR Reactome; R-HSA-8941855; RUNX3 regulates CDKN1A transcription.
DR Reactome; R-HSA-9616222; Transcriptional regulation of granulopoiesis.
DR Reactome; R-HSA-9617828; FOXO-mediated transcription of cell cycle genes.
DR Reactome; R-HSA-9661069; Defective binding of RB1 mutants to E2F1,(E2F2, E2F3).
DR Reactome; R-HSA-9702518; STAT5 activation downstream of FLT3 ITD mutants.
DR Reactome; R-HSA-9703465; Signaling by FLT3 fusion proteins.
DR SignaLink; P38936; -.
DR SIGNOR; P38936; -.
DR BioGRID-ORCS; 1026; 31 hits in 1107 CRISPR screens.
DR ChiTaRS; CDKN1A; human.
DR EvolutionaryTrace; P38936; -.
DR GeneWiki; P21; -.
DR GenomeRNAi; 1026; -.
DR Pharos; P38936; Tchem.
DR PRO; PR:P38936; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P38936; protein.
DR Bgee; ENSG00000124762; Expressed in stromal cell of endometrium and 200 other tissues.
DR ExpressionAtlas; P38936; baseline and differential.
DR Genevisible; P38936; HS.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0070557; C:PCNA-p21 complex; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0030332; F:cyclin binding; ISS:BHF-UCL.
DR GO; GO:0019912; F:cyclin-dependent protein kinase activating kinase activity; IDA:UniProtKB.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; TAS:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019901; F:protein kinase binding; IPI:CAFA.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IMP:CAFA.
DR GO; GO:0140311; F:protein sequestering activity; IMP:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:CAFA.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IMP:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:BHF-UCL.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; IMP:BHF-UCL.
DR GO; GO:0071480; P:cellular response to gamma radiation; IEA:Ensembl.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IMP:BHF-UCL.
DR GO; GO:0071493; P:cellular response to UV-B; ISS:UniProtKB.
DR GO; GO:0090398; P:cellular senescence; IMP:BHF-UCL.
DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; IDA:BHF-UCL.
DR GO; GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; IEA:Ensembl.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0007507; P:heart development; ISS:BHF-UCL.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:ProtInc.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IEA:Ensembl.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:1905179; P:negative regulation of cardiac muscle tissue regeneration; ISS:BHF-UCL.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:1904030; P:negative regulation of cyclin-dependent protein kinase activity; IMP:CAFA.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:2000279; P:negative regulation of DNA biosynthetic process; IMP:UniProtKB.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IGI:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0042326; P:negative regulation of phosphorylation; IDA:BHF-UCL.
DR GO; GO:0032091; P:negative regulation of protein binding; IMP:UniProtKB.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; IMP:BHF-UCL.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:BHF-UCL.
DR GO; GO:0043068; P:positive regulation of programmed cell death; IEA:Ensembl.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:MGI.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IMP:BHF-UCL.
DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl.
DR GO; GO:0007265; P:Ras protein signal transduction; IEP:BHF-UCL.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:BHF-UCL.
DR GO; GO:1902806; P:regulation of cell cycle G1/S phase transition; IMP:UniProtKB.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; TAS:ProtInc.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IDA:BHF-UCL.
DR GO; GO:0010389; P:regulation of G2/M transition of mitotic cell cycle; IMP:BHF-UCL.
DR GO; GO:0090399; P:replicative senescence; IEA:Ensembl.
DR GO; GO:0090400; P:stress-induced premature senescence; TAS:BHF-UCL.
DR GO; GO:0042246; P:tissue regeneration; IEA:Ensembl.
DR GO; GO:0042060; P:wound healing; IEA:Ensembl.
DR DisProt; DP00016; -.
DR Gene3D; 4.10.365.10; -; 1.
DR IDEAL; IID00043; -.
DR InterPro; IPR003175; CDI_dom.
DR InterPro; IPR044898; CDI_dom_sf.
DR InterPro; IPR029841; CDKN1A.
DR PANTHER; PTHR46778; PTHR46778; 1.
DR Pfam; PF02234; CDI; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell cycle; Cytoplasm;
KW Direct protein sequencing; Metal-binding; Nucleus; Phosphoprotein;
KW Protein kinase inhibitor; Reference proteome; Ubl conjugation; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:15574338"
FT CHAIN 2..164
FT /note="Cyclin-dependent kinase inhibitor 1"
FT /id="PRO_0000190079"
FT ZN_FING 13..41
FT /note="C4-type"
FT /evidence="ECO:0000255"
FT REGION 17..24
FT /note="Required for binding cyclins"
FT REGION 53..58
FT /note="Required for binding CDKs"
FT REGION 76..164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 152..164
FT /note="Interaction with TRIM39"
FT /evidence="ECO:0000269|PubMed:23213251"
FT MOTIF 140..164
FT /note="PIP-box K+4 motif"
FT MOTIF 141..156
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|PubMed:15574338"
FT MOD_RES 80
FT /note="Phosphothreonine; by LKB1"
FT /evidence="ECO:0000269|PubMed:25329316"
FT MOD_RES 114
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000269|PubMed:18794347"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648"
FT MOD_RES 145
FT /note="Phosphothreonine; by PKA, PKB/AKT1, PIM1 and PIM2"
FT /evidence="ECO:0000269|PubMed:10753973,
FT ECO:0000269|PubMed:11463845, ECO:0000269|PubMed:12431783,
FT ECO:0000269|PubMed:16982699, ECO:0000269|PubMed:20307683"
FT MOD_RES 146
FT /note="Phosphoserine; by PKC and NUAK1"
FT /evidence="ECO:0000269|PubMed:10753973,
FT ECO:0000269|PubMed:25329316"
FT MOD_RES 160
FT /note="Phosphoserine; by PKC; in vitro"
FT /evidence="ECO:0000269|PubMed:10753973"
FT CROSSLNK 2
FT /note="Glycyl serine ester (Ser-Gly) (interchain with G-
FT Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:15226418"
FT VARIANT 4
FT /note="P -> L (in dbSNP:rs4986866)"
FT /id="VAR_048686"
FT VARIANT 31
FT /note="S -> R (in dbSNP:rs1801270)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7655464, ECO:0000269|Ref.8"
FT /id="VAR_011870"
FT VARIANT 63
FT /note="F -> L (in dbSNP:rs4986867)"
FT /id="VAR_048687"
FT MUTAGEN 80
FT /note="T->A: Abolishes UV radiation-induced phosphorylation
FT and subsequent degradation."
FT /evidence="ECO:0000269|PubMed:25329316"
FT MUTAGEN 114
FT /note="S->E: Phosphomimetic mutant, increases
FT ubiquitination by the DCX(DTL) complex."
FT /evidence="ECO:0000269|PubMed:18794347"
FT MUTAGEN 144..150
FT /note="QTSMTDF->ATSATDA: Abolishes interaction with PCNA
FT and subsequent degradation by the proteasome."
FT /evidence="ECO:0000269|PubMed:18794347"
FT MUTAGEN 145
FT /note="T->A: Reduces phosphorylation by Akt; no change in
FT interaction with PCNA, CDK2 or CDK4; no change in
FT subcellular location."
FT /evidence="ECO:0000269|PubMed:11463845"
FT MUTAGEN 145
FT /note="T->D: No interaction with PCNA; 59% inhibition of
FT CDK2 binding; modest inhibition of CDK4 binding; no change
FT in subcellular location."
FT /evidence="ECO:0000269|PubMed:11463845"
FT MUTAGEN 146
FT /note="S->A: No change in interaction with PCNA. Abolishes
FT UV radiation-induced phosphorylation and subsequent
FT degradation."
FT /evidence="ECO:0000269|PubMed:11463845,
FT ECO:0000269|PubMed:25329316"
FT MUTAGEN 146
FT /note="S->D: Reduces interaction with PCNA."
FT /evidence="ECO:0000269|PubMed:11463845"
FT MUTAGEN 147..151
FT /note="MTDFY->ATDAAA: Abolishes interaction with PCNA and
FT subsequent degradation by the proteasome."
FT /evidence="ECO:0000269|PubMed:18703516"
FT MUTAGEN 154..156
FT /note="KRR->AAA: Abolishes degradation by the proteasome
FT without affecting the interaction with PCNA."
FT /evidence="ECO:0000269|PubMed:18703516"
FT MUTAGEN 154
FT /note="K->A: Loss of interaction with TRIM39."
FT /evidence="ECO:0000269|PubMed:23213251"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:6P8H"
FT HELIX 27..46
FT /evidence="ECO:0007829|PDB:6P8H"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:6P8H"
FT TURN 53..56
FT /evidence="ECO:0007829|PDB:6P8H"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:7KQ1"
FT HELIX 147..149
FT /evidence="ECO:0007829|PDB:5E0U"
FT STRAND 153..158
FT /evidence="ECO:0007829|PDB:5E0U"
SQ SEQUENCE 164 AA; 18119 MW; 98D1E7C519ADFCA9 CRC64;
MSEPAGDVRQ NPCGSKACRR LFGPVDSEQL SRDCDALMAG CIQEARERWN FDFVTETPLE
GDFAWERVRG LGLPKLYLPT GPRRGRDELG GGRRPGTSPA LLQGTAEEDH VDLSLSCTLV
PRSGEQAEGS PGGPGDSQGR KRRQTSMTDF YHSKRRLIFS KRKP
