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 27-MAR-2024, entry version 245. 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 {ECO:0000312|HGNC:HGNC:1784}; GN 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: Plays an important role in controlling cell cycle progression CC and DNA damage-induced G2 arrest (PubMed:9106657). Involved in p53/TP53 CC mediated inhibition of cellular proliferation in response to DNA CC damage. Also involved in p53-independent DNA damage-induced G2 arrest CC mediated by CREB3L1 in astrocytes and osteoblasts (By similarity). CC Binds to and inhibits cyclin-dependent kinase activity, preventing CC phosphorylation of critical cyclin-dependent kinase substrates and CC blocking cell cycle progression. Functions in the nuclear localization CC and assembly of cyclin D-CDK4 complex and promotes its kinase activity CC towards RB1. At higher stoichiometric ratios, inhibits the kinase CC activity of the cyclin D-CDK4 complex. Inhibits DNA synthesis by DNA CC polymerase delta by competing with POLD3 for PCNA binding CC (PubMed:11595739). {ECO:0000250|UniProtKB:P39689, CC ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:8242751, CC 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=23; IntAct=EBI-375077, EBI-375001; CC P38936; P30279: CCND2; NbExp=17; IntAct=EBI-375077, EBI-748789; CC P38936; P30281: CCND3; NbExp=26; 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; P04637: TP53; NbExp=5; IntAct=EBI-375077, EBI-366083; 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="https://atlasgeneticsoncology.org/gene/139/CDKN1A"; 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; 364. DR CORUM; P38936; -. DR DIP; DIP-246N; -. DR IntAct; P38936; 218. DR MINT; P38936; -. DR STRING; 9606.ENSP00000384849; -. DR BindingDB; P38936; -. DR ChEMBL; CHEMBL5021; -. DR DrugBank; DB01169; Arsenic trioxide. DR DrugBank; DB00313; Valproic acid. 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 EPD; P38936; -. DR jPOST; P38936; -. DR MassIVE; P38936; -. DR PaxDb; 9606-ENSP00000384849; -. DR PeptideAtlas; P38936; -. DR ProteomicsDB; 55307; -. DR Pumba; P38936; -. DR Antibodypedia; 3757; 2781 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 AGR; HGNC:1784; -. 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; NFAWERV; -. DR OrthoDB; 692679at2759; -. 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-8951664; Neddylation. 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 Reactome; R-HSA-9755511; KEAP1-NFE2L2 pathway. DR SignaLink; P38936; -. DR SIGNOR; P38936; -. DR BioGRID-ORCS; 1026; 36 hits in 1197 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 202 other cell types or tissues. DR ExpressionAtlas; P38936; baseline and differential. 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:MGI. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0070557; C:PCNA-p21 complex; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. 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:0140677; F:molecular function activator activity; IMP:DisProt. DR GO; GO:0140678; F:molecular function inhibitor activity; IDA:DisProt. 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:0031100; P:animal organ regeneration; IEA:Ensembl. DR GO; GO:0034198; P:cellular response to amino acid starvation; IMP:UniProtKB. 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:0034605; P:cellular response to heat; 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:0006974; P:DNA damage response; 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:0048144; P:fibroblast proliferation; 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:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0060574; P:intestinal epithelial cell maturation; IEA:Ensembl. 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:0030216; P:keratinocyte differentiation; IEA:Ensembl. DR GO; GO:0043616; P:keratinocyte proliferation; IEA:Ensembl. DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IMP:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl. 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: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:0001933; P:negative regulation of protein phosphorylation; IEP:DisProt. DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; IMP:BHF-UCL. DR GO; GO:0090402; P:oncogene-induced cell senescence; IEA:Ensembl. DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl. DR GO; GO:0045740; P:positive regulation of DNA replication; TAS:Reactome. 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:0001934; P:positive regulation of protein phosphorylation; IEP:DisProt. 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:1904044; P:response to aldosterone; IEA:Ensembl. DR GO; GO:0046685; P:response to arsenic-containing substance; IEA:Ensembl. DR GO; GO:0051412; P:response to corticosterone; IEA:Ensembl. DR GO; GO:0055093; P:response to hyperoxia; IEA:Ensembl. DR GO; GO:0010243; P:response to organonitrogen compound; IEA:Ensembl. DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl. DR GO; GO:0010165; P:response to X-ray; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; 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; p27; 1. DR IDEAL; IID00043; -. DR InterPro; IPR003175; CDI_dom. DR InterPro; IPR044898; CDI_dom_sf. DR InterPro; IPR029841; CDKN1A. DR PANTHER; PTHR46778:SF1; CYCLIN-DEPENDENT KINASE INHIBITOR 1; 1. DR PANTHER; PTHR46778; CYCLIN-DEPENDENT KINASE INHIBITOR 1-RELATED; 1. DR Pfam; PF02234; CDI; 1. DR SWISS-2DPAGE; P38936; -. DR Genevisible; P38936; HS. 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 //