RBCC Red Blood Cell Collection

CDK2 (CDKN2) [Confidence: low (only semi-automatic identification from reviews)]
Cyclin-dependent kinase 2; 2.7.11.22 (Cell division protein kinase 2; p33 protein kinase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

UniProt P24941
ID CDK2_HUMAN Reviewed; 298 AA.
AC P24941; A8K7C6; O75100;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-AUG-1992, sequence version 2.
DT 22-JAN-2014, entry version 182.
DE RecName: Full=Cyclin-dependent kinase 2;
DE EC=2.7.11.22;
DE AltName: Full=Cell division protein kinase 2;
DE AltName: Full=p33 protein kinase;
GN Name=CDK2; Synonyms=CDKN2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1714386;
RA Elledge S.J., Spottswood M.R.;
RT "A new human p34 protein kinase, CDK2, identified by complementation
RT of a cdc28 mutation in Saccharomyces cerevisiae, is a homolog of
RT Xenopus Eg1.";
RL EMBO J. 10:2653-2659(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1653904; DOI=10.1038/353174a0;
RA Tsai L.-H., Harlow E., Meyerson M.;
RT "Isolation of the human cdk2 gene that encodes the cyclin A- and
RT adenovirus E1A-associated p33 kinase.";
RL Nature 353:174-177(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1717994; DOI=10.1073/pnas.88.20.9006;
RA Ninomiya-Tsuji J., Nomoto S., Yasuda H., Reed S.I., Matsumoto K.;
RT "Cloning of a human cDNA encoding a CDC2-related kinase by
RT complementation of a budding yeast cdc28 mutation.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:9006-9010(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE (ISOFORM 2).
RA Nishikawa T., Ohta T., Fukuda M., Ogata H., Okamoto K., Isohashi F.,
RA Arima K., Yamaguchi S.;
RT "Sequence of deletion type cdk2 variant in human breast cancer.";
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-290.
RG NIEHS SNPs program;
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP PHOSPHORYLATION AT THR-14; TYR-15 AND THR-160, AND MUTAGENESIS OF
RP THR-14; TYR-15 AND THR-160.
RX PubMed=1396589;
RA Gu Y., Rosenblatt J., O'Morgan D.O.;
RT "Cell cycle regulation of CDK2 activity by phosphorylation of Thr160
RT and Tyr15.";
RL EMBO J. 11:3995-4005(1992).
RN [12]
RP ENZYME REGULATION BY ROSCOVITINE AND OLOMOUCINE.
RX PubMed=9030781; DOI=10.1111/j.1432-1033.1997.t01-2-00527.x;
RA Meijer L., Borgne A., Mulner O., Chong J.P.J., Blow J.J., Inagaki N.,
RA Inagaki M., Delcros J.-G., Moulinoux J.-P.;
RT "Biochemical and cellular effects of roscovitine, a potent and
RT selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and
RT cdk5.";
RL Eur. J. Biochem. 243:527-536(1997).
RN [13]
RP FUNCTION AS RB1 KINASE, AND INTERACTION WITH CYCLIN E.
RX PubMed=10499802; DOI=10.1016/S0092-8674(00)81519-6;
RA Harbour J.W., Luo R.X., Dei Santi A., Postigo A.A., Dean D.C.;
RT "Cdk phosphorylation triggers sequential intramolecular interactions
RT that progressively block Rb functions as cells move through G1.";
RL Cell 98:859-869(1999).
RN [14]
RP FUNCTION AS NPM1 KINASE.
RX PubMed=11051553; DOI=10.1016/S0092-8674(00)00093-3;
RA Okuda M., Horn H.F., Tarapore P., Tokuyama Y., Smulian A.G.,
RA Chan P.K., Knudsen E.S., Hofmann I.A., Snyder J.D., Bove K.E.,
RA Fukasawa K.;
RT "Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome
RT duplication.";
RL Cell 103:127-140(2000).
RN [15]
RP FUNCTION AS NPAT KINASE.
RX PubMed=10995386; DOI=10.1101/gad.827700;
RA Zhao J., Kennedy B.K., Lawrence B.D., Barbie D.A., Matera A.G.,
RA Fletcher J.A., Harlow E.;
RT "NPAT links cyclin E-Cdk2 to the regulation of replication-dependent
RT histone gene transcription.";
RL Genes Dev. 14:2283-2297(2000).
RN [16]
RP FUNCTION AS NPAT KINASE, AND SUBCELLULAR LOCATION.
RX PubMed=10995387; DOI=10.1101/gad.829500;
RA Ma T., Van Tine B.A., Wei Y., Garrett M.D., Nelson D., Adams P.D.,
RA Wang J., Qin J., Chow L.T., Harper J.W.;
RT "Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2
RT in Cajal bodies promotes histone gene transcription.";
RL Genes Dev. 14:2298-2313(2000).
RN [17]
RP FUNCTION AS P53/TP53 KINASE, AND INTERACTION WITH CYCLIN A AND CYCLIN
RP B1.
RX PubMed=10884347; DOI=10.1006/jmbi.2000.3830;
RA Luciani M.G., Hutchins J.R.A., Zheleva D., Hupp T.R.;
RT "The C-terminal regulatory domain of p53 contains a functional docking
RT site for cyclin A.";
RL J. Mol. Biol. 300:503-518(2000).
RN [18]
RP FUNCTION AS CDK7 KINASE, AND PHOSPHORYLATION BY CDK7.
RX PubMed=11113184; DOI=10.1128/MCB.21.1.88-99.2001;
RA Garrett S., Barton W.A., Knights R., Jin P., Morgan D.O., Fisher R.P.;
RT "Reciprocal activation by cyclin-dependent kinases 2 and 7 is directed
RT by substrate specificity determinants outside the T loop.";
RL Mol. Cell. Biol. 21:88-99(2001).
RN [19]
RP INTERACTION WITH CCNB3.
RX PubMed=12185076; DOI=10.1074/jbc.M203951200;
RA Nguyen T.B., Manova K., Capodieci P., Lindon C., Bottega S.,
RA Wang X.-Y., Refik-Rogers J., Pines J., Wolgemuth D.J., Koff A.;
RT "Characterization and expression of mammalian cyclin b3, a
RT prepachytene meiotic cyclin.";
RL J. Biol. Chem. 277:41960-41969(2002).
RN [20]
RP INTERACTION WITH SPDYA.
RX PubMed=11980914; DOI=10.1083/jcb.200109045;
RA Porter L.A., Dellinger R.W., Tynan J.A., Barnes E.A., Kong M.,
RA Lenormand J.-L., Donoghue D.J.;
RT "Human Speedy: a novel cell cycle regulator that enhances
RT proliferation through activation of Cdk2.";
RL J. Cell Biol. 157:357-366(2002).
RN [21]
RP INTERACTION WITH SPDYA.
RX PubMed=12839962;
RA Barnes E.A., Porter L.A., Lenormand J.-L., Dellinger R.W.,
RA Donoghue D.J.;
RT "Human Spy1 promotes survival of mammalian cells following DNA
RT damage.";
RL Cancer Res. 63:3701-3707(2003).
RN [22]
RP INTERACTION WITH SPDYA, AND IDENTIFICATION IN A COMPLEX WITH CDKN1B
RP AND SPDYA.
RX PubMed=12972555; DOI=10.1091/mbc.E02-12-0820;
RA Porter L.A., Kong-Beltran M., Donoghue D.J.;
RT "Spy1 interacts with p27Kip1 to allow G1/S progression.";
RL Mol. Biol. Cell 14:3664-3674(2003).
RN [23]
RP INTERACTION WITH UHRF2, AND IDENTIFICATION IN A COMPLEX WITH UHRF2 AND
RP CCNE1.
RX PubMed=15178429; DOI=10.1016/j.bbrc.2004.04.190;
RA Li Y., Mori T., Hata H., Homma Y., Kochi H.;
RT "NIRF induces G1 arrest and associates with Cdk2.";
RL Biochem. Biophys. Res. Commun. 319:464-468(2004).
RN [24]
RP PHOSPHORYLATION AT THR-160.
RX PubMed=14597612; DOI=10.1074/jbc.M309995200;
RA Liu Y., Wu C., Galaktionov K.;
RT "p42, a novel cyclin-dependent kinase-activating kinase in mammalian
RT cells.";
RL J. Biol. Chem. 279:4507-4514(2004).
RN [25]
RP INTERACTION WITH SPDYA AND SPDYC.
RX PubMed=15611625;
RA Cheng A., Xiong W., Ferrell J.E. Jr., Solomon M.J.;
RT "Identification and comparative analysis of multiple mammalian
RT Speedy/Ringo proteins.";
RL Cell Cycle 4:155-165(2005).
RN [26]
RP FUNCTION AS BRCA2 KINASE.
RX PubMed=15800615; DOI=10.1038/nature03404;
RA Esashi F., Christ N., Gannon J., Liu Y., Hunt T., Jasin M., West S.C.;
RT "CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for
RT recombinational repair.";
RL Nature 434:598-604(2005).
RN [27]
RP PHOSPHORYLATION BY CAK, MUTAGENESIS OF LYS-9; 88-LYS-LYS-89 AND
RP LEU-166, AND INTERACTION WITH CDK7.
RX PubMed=17373709; DOI=10.1002/prot.21370;
RA Lolli G., Johnson L.N.;
RT "Recognition of Cdk2 by Cdk7.";
RL Proteins 67:1048-1059(2007).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [29]
RP FUNCTION IN MITOSE REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=18372919; DOI=10.1038/onc.2008.74;
RA De Boer L., Oakes V., Beamish H., Giles N., Stevens F.,
RA Somodevilla-Torres M., Desouza C., Gabrielli B.;
RT "Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events.";
RL Oncogene 27:4261-4268(2008).
RN [30]
RP INTERACTION WITH CACUL1.
RX PubMed=19829063;
RA Kong Y., Nan K., Yin Y.;
RT "Identification and characterization of CAC1 as a novel CDK2-
RT associated cullin.";
RL Cell Cycle 8:3544-3553(2009).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-19, AND MASS
RP SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-15, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [33]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND LYS-6, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [34]
RP FUNCTION IN VITAMIN D-MEDIATED GROWTH INHIBITION, SUBCELLULAR
RP LOCATION, ENZYME REGULATION, AND PHOSPHORYLATION AT THR-160.
RX PubMed=20147522; DOI=10.1210/en.2009-1116;
RA Flores O., Wang Z., Knudsen K.E., Burnstein K.L.;
RT "Nuclear targeting of cyclin-dependent kinase 2 reveals essential
RT roles of cyclin-dependent kinase 2 localization and cyclin E in
RT vitamin D-mediated growth inhibition.";
RL Endocrinology 151:896-908(2010).
RN [35]
RP FUNCTION, AND NITROSYLATION.
RX PubMed=20079829; DOI=10.1016/j.freeradbiomed.2010.01.004;
RA Kumar S., Barthwal M.K., Dikshit M.;
RT "Cdk2 nitrosylation and loss of mitochondrial potential mediate NO-
RT dependent biphasic effect on HL-60 cell cycle.";
RL Free Radic. Biol. Med. 48:851-861(2010).
RN [36]
RP PHOSPHORYLATION AT THR-160 BY CAK, AND DEPHOSPHORYLATION BY CDC25A.
RX PubMed=20360007; DOI=10.1074/jbc.M109.096552;
RA Timofeev O., Cizmecioglu O., Settele F., Kempf T., Hoffmann I.;
RT "Cdc25 phosphatases are required for timely assembly of CDK1-cyclin B
RT at the G2/M transition.";
RL J. Biol. Chem. 285:16978-16990(2010).
RN [37]
RP FUNCTION AS EZH2 KINASE.
RX PubMed=20935635; DOI=10.1038/ncb2116;
RA Chen S., Bohrer L.R., Rai A.N., Pan Y., Gan L., Zhou X., Bagchi A.,
RA Simon J.A., Huang H.;
RT "Cyclin-dependent kinases regulate epigenetic gene silencing through
RT phosphorylation of EZH2.";
RL Nat. Cell Biol. 12:1108-1114(2010).
RN [38]
RP FUNCTION IN DNA DAMAGE CHECKPOINT.
RX PubMed=20195506; DOI=10.1371/journal.pgen.1000863;
RA Chung J.H., Bunz F.;
RT "Cdk2 is required for p53-independent G2/M checkpoint control.";
RL PLoS Genet. 6:E1000863-E1000863(2010).
RN [39]
RP FUNCTION AS MYC KINASE.
RX PubMed=19966300; DOI=10.1073/pnas.0900121106;
RA Hydbring P., Bahram F., Su Y., Tronnersjoe S., Hoegstrand K.,
RA von der Lehr N., Sharifi H.R., Lilischkis R., Hein N., Wu S.,
RA Vervoorts J., Henriksson M., Grandien A., Luescher B., Larsson L.-G.;
RT "Phosphorylation by Cdk2 is required for Myc to repress Ras-induced
RT senescence in cotransformation.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:58-63(2010).
RN [40]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [41]
RP INTERACTION WITH CEP63.
RX PubMed=21406398; DOI=10.1158/0008-5472.CAN-10-2684;
RA Loffler H., Fechter A., Matuszewska M., Saffrich R., Mistrik M.,
RA Marhold J., Hornung C., Westermann F., Bartek J., Kramer A.;
RT "Cep63 recruits Cdk1 to the centrosome: implications for regulation of
RT mitotic entry, centrosome amplification, and genome maintenance.";
RL Cancer Res. 71:2129-2139(2011).
RN [42]
RP FUNCTION AS CTNNB1 KINASE, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP PTPN6 AND CTNNB1.
RX PubMed=21262353; DOI=10.1016/j.cellsig.2011.01.019;
RA Fiset A., Xu E., Bergeron S., Marette A., Pelletier G.,
RA Siminovitch K.A., Olivier M., Beauchemin N., Faure R.L.;
RT "Compartmentalized CDK2 is connected with SHP-1 and beta-catenin and
RT regulates insulin internalization.";
RL Cell. Signal. 23:911-919(2011).
RN [43]
RP INHIBITORS.
RX PubMed=21684737; DOI=10.1016/j.bmcl.2011.05.081;
RA Lee J., Kim K.H., Jeong S.;
RT "Discovery of a novel class of 2-aminopyrimidines as CDK1 and CDK2
RT inhibitors.";
RL Bioorg. Med. Chem. Lett. 21:4203-4205(2011).
RN [44]
RP FUNCTION AS USP37 KINASE.
RX PubMed=21596315; DOI=10.1016/j.molcel.2011.03.027;
RA Huang X., Summers M.K., Pham V., Lill J.R., Liu J., Lee G.,
RA Kirkpatrick D.S., Jackson P.K., Fang G., Dixit V.M.;
RT "Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and
RT promote S phase entry.";
RL Mol. Cell 42:511-523(2011).
RN [45]
RP FUNCTION IN CELL CYCLE REGULATION.
RX PubMed=21319273; DOI=10.1002/stem.620;
RA Neganova I., Vilella F., Atkinson S.P., Lloret M., Passos J.F.,
RA von Zglinicki T., O'Connor J.-E., Burks D., Jones R., Armstrong L.,
RA Lako M.;
RT "An important role for CDK2 in G1 to S checkpoint activation and DNA
RT damage response in human embryonic stem cells.";
RL Stem Cells 29:651-659(2011).
RN [46]
RP REVIEW ON DNA REPAIR, AND INTERACTION WITH CDKN1A/P21.
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 [47]
RP REVIEW ON CELL CYCLE CONTROL, INHIBITORS, AND GENE FAMILY.
RX PubMed=19238148; DOI=10.1038/nrc2602;
RA Malumbres M., Barbacid M.;
RT "Cell cycle, CDKs and cancer: a changing paradigm.";
RL Nat. Rev. Cancer 9:153-166(2009).
RN [48]
RP REVIEW, AND GENE FAMILY.
RX PubMed=19561645; DOI=10.1038/onc.2009.170;
RA Satyanarayana A., Kaldis P.;
RT "Mammalian cell-cycle regulation: several Cdks, numerous cyclins and
RT diverse compensatory mechanisms.";
RL Oncogene 28:2925-2939(2009).
RN [49]
RP REVIEW ON SENESCENCE.
RX PubMed=20713526; DOI=10.1158/0008-5472.CAN-10-1383;
RA Hydbring P., Larsson L.-G.;
RT "Tipping the balance: Cdk2 enables Myc to suppress senescence.";
RL Cancer Res. 70:6687-6691(2010).
RN [50]
RP REVIEW ON INHIBITORS.
RX PubMed=21517772; DOI=10.2174/092986711795590110;
RA Wang Q., Su L., Liu N., Zhang L., Xu W., Fang H.;
RT "Cyclin dependent kinase 1 inhibitors: a review of recent progress.";
RL Curr. Med. Chem. 18:2025-2043(2011).
RN [51]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [52]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=8510751; DOI=10.1038/363595a0;
RA de Bondt H.L., Rosenblatt J., Jancarik J., Jones H.D., Morgan D.O.,
RA Kim S.-H.;
RT "Crystal structure of cyclin-dependent kinase 2.";
RL Nature 363:595-602(1993).
RN [53]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH CYCLIN A.
RX PubMed=7630397; DOI=10.1038/376313a0;
RA Jeffrey P.D., Russo A.A., Polyak K., Gibbs E., Hurwitz J.,
RA Massague J., Pavletich N.P.;
RT "Mechanism of CDK activation revealed by the structure of a cyclinA-
RT CDK2 complex.";
RL Nature 376:313-320(1995).
RN [54]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITG CKS1.
RX PubMed=8601310; DOI=10.1016/S0092-8674(00)81065-X;
RA Bourne Y., Watson M.H., Hickey M.J., Holmes W., Rocque W., Reed S.I.,
RA Tainer J.A.;
RT "Crystal structure and mutational analysis of the human CDK2 kinase
RT complex with cell cycle-regulatory protein CksHs1.";
RL Cell 84:863-874(1996).
RN [55]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
RX PubMed=8917641; DOI=10.1021/jm960402a;
RA Schulze-Gahmen U., de Bondt H.L., Kim S.-H.;
RT "High-resolution crystal structures of human cyclin-dependent kinase 2
RT with and without ATP: bound waters and natural ligand as guides for
RT inhibitor design.";
RL J. Med. Chem. 39:4540-4546(1996).
RN [56]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH CG2A AND KIP1.
RX PubMed=8684460; DOI=10.1038/382325a0;
RA Russo A.A., Jeffrey P.D., Patten A.K., Massague J., Pavletich N.P.;
RT "Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor
RT bound to the cyclin A-Cdk2 complex.";
RL Nature 382:325-331(1996).
RN [57]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH CG2A.
RX PubMed=8756328; DOI=10.1038/nsb0896-696;
RA Russo A.A., Jeffrey P.D., Pavletich N.P.;
RT "Structural basis of cyclin-dependent kinase activation by
RT phosphorylation.";
RL Nat. Struct. Biol. 3:696-700(1996).
RN [58]
RP X-RAY CRYSTALLOGRAPHY (2.33 ANGSTROMS) IN COMPLEX WITH L868276.
RX PubMed=8610110; DOI=10.1073/pnas.93.7.2735;
RA de Azevedo W.F. Jr., Mueller-Dieckmann H.-J., Schulze-Gahmen U.,
RA Worland P.J., Sausville E., Kim S.-H.;
RT "Structural basis for specificity and potency of a flavonoid inhibitor
RT of human CDK2, a cell cycle kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:2735-2740(1996).
RN [59]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH STAUROSPORINE,
RP AND ENZYME REGULATION.
RX PubMed=9334743; DOI=10.1038/nsb1097-796;
RA Lawrie A.M., Noble M.E.M., Tunnah P., Brown N.R., Johnson L.N.,
RA Endicott J.A.;
RT "Protein kinase inhibition by staurosporine revealed in details of the
RT molecular interaction with CDK2.";
RL Nat. Struct. Biol. 4:796-801(1997).
RN [60]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS).
RX PubMed=9677190; DOI=10.1126/science.281.5376.533;
RA Gray N.S., Wodicka L., Thunnissen A.-M.W.H., Norman T.C., Kwon S.,
RA Espinoza F.H., Morgan D.O., Barnes G., Leclerc S., Meijer L.,
RA Kim S.H., Lockhart D.J., Schultz P.G.;
RT "Exploiting chemical libraries, structure, and genomics in the search
RT for kinase inhibitors.";
RL Science 281:533-538(1998).
RN [61]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP PHOSPHORYLATION AT THR-160.
RX PubMed=16325401; DOI=10.1016/j.bmcl.2005.11.048;
RA Richardson C.M., Williamson D.S., Parratt M.J., Borgognoni J.,
RA Cansfield A.D., Dokurno P., Francis G.L., Howes R., Moore J.D.,
RA Murray J.B., Robertson A., Surgenor A.E., Torrance C.J.;
RT "Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: protein
RT structure-guided design and SAR.";
RL Bioorg. Med. Chem. Lett. 16:1353-1357(2006).
RN [62]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH INHIBITORS, AND
RP PHOSPHORYLATION AT THR-160.
RX PubMed=17570665; DOI=10.1016/j.bmcl.2007.04.110;
RA Richardson C.M., Nunns C.L., Williamson D.S., Parratt M.J.,
RA Dokurno P., Howes R., Borgognoni J., Drysdale M.J., Finch H.,
RA Hubbard R.E., Jackson P.S., Kierstan P., Lentzen G., Moore J.D.,
RA Murray J.B., Simmonite H., Surgenor A.E., Torrance C.J.;
RT "Discovery of a potent CDK2 inhibitor with a novel binding mode, using
RT virtual screening and initial, structure-guided lead scoping.";
RL Bioorg. Med. Chem. Lett. 17:3880-3885(2007).
RN [63]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 1-288 IN COMPLEX WITH CCNB1,
RP AND FUNCTION.
RX PubMed=17495531;
RA Brown N.R., Lowe E.D., Petri E., Skamnaki V., Antrobus R.,
RA Johnson L.N.;
RT "Cyclin B and cyclin A confer different substrate recognition
RT properties on CDK2.";
RL Cell Cycle 6:1350-1359(2007).
RN [64]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH ATP, AND
RP PHOSPHORYLATION AT THR-14; TYR-15 AND THR-160.
RX PubMed=17095507; DOI=10.1074/jbc.M609151200;
RA Welburn J.P.I., Tucker J.A., Johnson T., Lindert L., Morgan M.,
RA Willis A., Noble M.E.M., Endicott J.A.;
RT "How tyrosine 15 phosphorylation inhibits the activity of cyclin-
RT dependent kinase 2-cyclin A.";
RL J. Biol. Chem. 282:3173-3181(2007).
RN [65]
RP X-RAY CRYSTALLOGRAPHY (1.28 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=17937404; DOI=10.1002/bip.20868;
RA Fischmann T.O., Hruza A., Duca J.S., Ramanathan L., Mayhood T.,
RA Windsor W.T., Le H.V., Guzi T.J., Dwyer M.P., Paruch K., Doll R.J.,
RA Lees E., Parry D., Seghezzi W., Madison V.;
RT "Structure-guided discovery of cyclin-dependent kinase inhibitors.";
RL Biopolymers 89:372-379(2008).
RN [66]
RP X-RAY CRYSTALLOGRAPHY (1.68 ANGSTROMS) IN COMPLEX WITH INHIBITORS.
RX PubMed=18656911; DOI=10.1021/jm800382h;
RA Wyatt P.G., Woodhead A.J., Berdini V., Boulstridge J.A., Carr M.G.,
RA Cross D.M., Davis D.J., Devine L.A., Early T.R., Feltell R.E.,
RA Lewis E.J., McMenamin R.L., Navarro E.F., O'Brien M.A., O'Reilly M.,
RA Reule M., Saxty G., Seavers L.C., Smith D.M., Squires M.S.,
RA Trewartha G., Walker M.T., Woolford A.J.;
RT "Identification of N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-
RT pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase
RT inhibitor using fragment-based X-ray crystallography and structure
RT based drug design.";
RL J. Med. Chem. 51:4986-4999(2008).
RN [67]
RP X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) OF 1-296 IN COMPLEX WITH ATP
RP AND MAGNESIUM, AND PHOSPHORYLATION AT THR-160.
RX PubMed=21565702; DOI=10.1016/j.str.2011.02.016;
RA Bao Z.Q., Jacobsen D.M., Young M.A.;
RT "Briefly bound to activate: transient binding of a second catalytic
RT magnesium activates the structure and dynamics of CDK2 kinase for
RT catalysis.";
RL Structure 19:675-690(2011).
RN [68]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-45 AND SER-290.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Serine/threonine-protein kinase involved in the control
CC of the cell cycle; essential for meiosis, but dispensable for
CC mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1,
CC BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E.
CC Triggers duplication of centrosomes and DNA. Acts at the G1-S
CC transition to promote the E2F transcriptional program and the
CC initiation of DNA synthesis, and modulates G2 progression;
CC controls the timing of entry into mitosis/meiosis by controlling
CC the subsequent activation of cyclin B/CDK1 by phosphorylation, and
CC coordinates the activation of cyclin B/CDK1 at the centrosome and
CC in the nucleus. Crucial role in orchestrating a fine balance
CC between cellular proliferation, cell death, and DNA repair in
CC human embryonic stem cells (hESCs). Activity of CDK2 is maximal
CC during S phase and G2; activated by interaction with cyclin E
CC during the early stages of DNA synthesis to permit G1-S
CC transition, and subsequently activated by cyclin A2 (cyclin A1 in
CC germ cells) during the late stages of DNA replication to drive the
CC transition from S phase to mitosis, the G2 phase. EZH2
CC phosphorylation promotes H3K27me3 maintenance and epigenetic gene
CC silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2
CC prevents oxidative stress-mediated Ras-induced senescence by
CC phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint
CC that prevents cells with damaged DNA from initiating mitosis;
CC regulates homologous recombination-dependent repair by
CC phosphorylating BRCA2, this phosphorylation is low in S phase when
CC recombination is active, but increases as cells progress towards
CC mitosis. In response to DNA damage, double-strand break repair by
CC homologous recombination a reduction of CDK2-mediated BRCA2
CC phosphorylation. Phosphorylation of RB1 disturbs its interaction
CC with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its
CC dissociates from unduplicated centrosomes, thus initiating
CC centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of
CC NPAT at G1-S transition and until prophase stimulates the NPAT-
CC mediated activation of histone gene transcription during S phase.
CC Required for vitamin D-mediated growth inhibition by being itself
CC inactivated. Involved in the nitric oxide- (NO) mediated signaling
CC in a nitrosylation/activation-dependent manner. USP37 is activated
CC by phosphorylation and thus triggers G1-S transition. CTNNB1
CC phosphorylation regulates insulin internalization.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- ENZYME REGULATION: Phosphorylation at Thr-14 or Tyr-15 inactivates
CC the enzyme, while phosphorylation at Thr-160 activates it.
CC Inhibited by 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), AG-
CC 024322, N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-
CC pyrazole-3-carboxamide (AT7519), R547 (Ro-4584820), purine,
CC pyrimidine and pyridine derivatives, 2-aminopyrimidines,
CC paullones, thiazo derivatives, macrocyclic quinoxalin-2-one,
CC pyrazolo[1,5-a]-1,3,5-triazine, pyrazolo[1,5-a]pyrimidine, 2-(1-
CC ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine
CC (roscovitine, seliciclib and CYC202), SNS-032 (BMS-387032),
CC triazolo[1,5-a]pyrimidines, staurosporine and olomoucine.
CC Stimulated by MYC. Inactivated by CDKN1A (p21).
CC -!- SUBUNIT: Found in a complex with CABLES1, CCNA1 and CCNE1.
CC Interacts with CABLES1 (By similarity). Interacts with UHRF2. Part
CC of a complex consisting of UHRF2, CDK2 and CCNE1. Interacts with
CC the Speedy/Ringo proteins SPDYA and SPDYC. Found in a complex with
CC both SPDYA and CDKN1B/KIP1. Binds to RB1 and CDK7. Binding to
CC CDKN1A (p21) leads to CDK2/cyclin E inactivation at the G1-S phase
CC DNA damage checkpoint, thereby arresting cells at the G1-S
CC transition during DNA repair. Associated with PTPN6 and beta-
CC catenin/CTNNB1. Interacts with CACUL1. May interact with CEP63.
CC -!- INTERACTION:
CC P20248:CCNA2; NbExp=19; IntAct=EBI-375096, EBI-457097;
CC O95067:CCNB2; NbExp=2; IntAct=EBI-375096, EBI-375024;
CC P24864:CCNE1; NbExp=12; IntAct=EBI-375096, EBI-519526;
CC O96020:CCNE2; NbExp=7; IntAct=EBI-375096, EBI-375033;
CC P51946:CCNH; NbExp=2; IntAct=EBI-375096, EBI-741406;
CC P38936:CDKN1A; NbExp=13; IntAct=EBI-375096, EBI-375077;
CC P46527:CDKN1B; NbExp=15; IntAct=EBI-375096, EBI-519280;
CC Q16667:CDKN3; NbExp=3; IntAct=EBI-375096, EBI-1031527;
CC P61024:CKS1B; NbExp=3; IntAct=EBI-375096, EBI-456371;
CC Q09472:EP300; NbExp=5; IntAct=EBI-375096, EBI-447295;
CC Q969H0-4:FBXW7; NbExp=2; IntAct=EBI-375096, EBI-6502391;
CC Q08619:Ifi205b (xeno); NbExp=2; IntAct=EBI-375096, EBI-8064290;
CC Q9Y6K9:IKBKG; NbExp=4; IntAct=EBI-375096, EBI-81279;
CC P06400:RB1; NbExp=3; IntAct=EBI-375096, EBI-491274;
CC Q9UBI4:STOML1; NbExp=2; IntAct=EBI-375096, EBI-2681162;
CC Q96PU4:UHRF2; NbExp=5; IntAct=EBI-375096, EBI-625304;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome. Nucleus, Cajal body. Cytoplasm.
CC Endosome. Note=Localized at the centrosomes in late G2 phase after
CC separation of the centrosomes but before the start of prophase.
CC Nuclear-cytoplasmic trafficking is mediated during the inhibition
CC by 1,25-(OH)(2)D(3).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P24941-1; Sequence=Displayed;
CC Name=2; Synonyms=CDK2deltaT;
CC IsoId=P24941-2; Sequence=VSP_041998;
CC -!- INDUCTION: Induced transiently by TGFB1 at an early phase of
CC TGFB1-mediated apoptosis.
CC -!- PTM: Phosphorylated at Thr-160 by CDK7 in a CAK complex.
CC Phosphorylation at Thr-160 promotes kinase activity, whereas
CC phosphorylation at Tyr-15 by WEE1 reduces slightly kinase
CC activity. Phosphorylated on Thr-14 and Tyr-15 during S and G2
CC phases before being dephosphorylated by CDC25A.
CC -!- PTM: Nitrosylated after treatment with nitric oxide (DETA-NO).
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC
CC Ser/Thr protein kinase family. CDC2/CDKX subfamily.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cdk2/";
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DR EMBL; X61622; CAA43807.1; -; mRNA.
DR EMBL; X62071; CAA43985.1; -; mRNA.
DR EMBL; M68520; AAA35667.1; -; mRNA.
DR EMBL; AB012305; BAA32794.1; -; mRNA.
DR EMBL; BT006821; AAP35467.1; -; mRNA.
DR EMBL; AF512553; AAM34794.1; -; Genomic_DNA.
DR EMBL; AK291941; BAF84630.1; -; mRNA.
DR EMBL; AC025162; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC034102; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW96858.1; -; Genomic_DNA.
DR EMBL; BC003065; AAH03065.1; -; mRNA.
DR PIR; A41227; A41227.
DR RefSeq; NP_001789.2; NM_001798.3.
DR RefSeq; NP_439892.2; NM_052827.2.
DR UniGene; Hs.19192; -.
DR UniGene; Hs.689624; -.
DR PDB; 1AQ1; X-ray; 2.00 A; A=1-298.
DR PDB; 1B38; X-ray; 2.00 A; A=1-298.
DR PDB; 1B39; X-ray; 2.10 A; A=1-298.
DR PDB; 1BUH; X-ray; 2.60 A; A=1-298.
DR PDB; 1CKP; X-ray; 2.05 A; A=1-298.
DR PDB; 1DI8; X-ray; 2.20 A; A=1-298.
DR PDB; 1DM2; X-ray; 2.10 A; A=1-298.
DR PDB; 1E1V; X-ray; 1.95 A; A=1-298.
DR PDB; 1E1X; X-ray; 1.85 A; A=1-298.
DR PDB; 1E9H; X-ray; 2.50 A; A/C=1-296.
DR PDB; 1F5Q; X-ray; 2.50 A; A/C=1-298.
DR PDB; 1FIN; X-ray; 2.30 A; A/C=1-298.
DR PDB; 1FQ1; X-ray; 3.00 A; B=1-298.
DR PDB; 1FVT; X-ray; 2.20 A; A=1-298.
DR PDB; 1FVV; X-ray; 2.80 A; A/C=1-298.
DR PDB; 1G5S; X-ray; 2.61 A; A=1-298.
DR PDB; 1GIH; X-ray; 2.80 A; A=1-298.
DR PDB; 1GII; X-ray; 2.00 A; A=1-298.
DR PDB; 1GIJ; X-ray; 2.20 A; A=1-298.
DR PDB; 1GY3; X-ray; 2.70 A; A/C=1-296.
DR PDB; 1GZ8; X-ray; 1.30 A; A=1-298.
DR PDB; 1H00; X-ray; 1.60 A; A=1-298.
DR PDB; 1H01; X-ray; 1.79 A; A=1-298.
DR PDB; 1H07; X-ray; 1.85 A; A=1-298.
DR PDB; 1H08; X-ray; 1.80 A; A=1-298.
DR PDB; 1H0V; X-ray; 1.90 A; A=1-298.
DR PDB; 1H0W; X-ray; 2.10 A; A=1-298.
DR PDB; 1H1P; X-ray; 2.10 A; A/C=1-298.
DR PDB; 1H1Q; X-ray; 2.50 A; A/C=1-298.
DR PDB; 1H1R; X-ray; 2.00 A; A/C=1-298.
DR PDB; 1H1S; X-ray; 2.00 A; A/C=1-298.
DR PDB; 1H24; X-ray; 2.50 A; A/C=1-298.
DR PDB; 1H25; X-ray; 2.50 A; A/C=1-298.
DR PDB; 1H26; X-ray; 2.24 A; A/C=1-298.
DR PDB; 1H27; X-ray; 2.20 A; A/C=1-298.
DR PDB; 1H28; X-ray; 2.80 A; A/C=1-298.
DR PDB; 1HCK; X-ray; 1.90 A; A=1-298.
DR PDB; 1HCL; X-ray; 1.80 A; A=1-298.
DR PDB; 1JST; X-ray; 2.60 A; A/C=1-298.
DR PDB; 1JSU; X-ray; 2.30 A; A=1-298.
DR PDB; 1JSV; X-ray; 1.96 A; A=1-298.
DR PDB; 1JVP; X-ray; 1.53 A; P=1-298.
DR PDB; 1KE5; X-ray; 2.20 A; A=1-298.
DR PDB; 1KE6; X-ray; 2.00 A; A=1-298.
DR PDB; 1KE7; X-ray; 2.00 A; A=1-298.
DR PDB; 1KE8; X-ray; 2.00 A; A=1-298.
DR PDB; 1KE9; X-ray; 2.00 A; A=1-298.
DR PDB; 1OGU; X-ray; 2.60 A; A/C=1-298.
DR PDB; 1OI9; X-ray; 2.10 A; A/C=1-298.
DR PDB; 1OIQ; X-ray; 2.31 A; A=1-298.
DR PDB; 1OIR; X-ray; 1.91 A; A=1-298.
DR PDB; 1OIT; X-ray; 1.60 A; A=1-298.
DR PDB; 1OIU; X-ray; 2.00 A; A/C=1-298.
DR PDB; 1OIY; X-ray; 2.40 A; A/C=1-298.
DR PDB; 1OKV; X-ray; 2.40 A; A/C=1-298.
DR PDB; 1OKW; X-ray; 2.50 A; A/C=1-298.
DR PDB; 1OL1; X-ray; 2.90 A; A/C=1-298.
DR PDB; 1OL2; X-ray; 2.60 A; A/C=1-298.
DR PDB; 1P2A; X-ray; 2.50 A; A=1-298.
DR PDB; 1P5E; X-ray; 2.22 A; A/C=1-298.
DR PDB; 1PF8; X-ray; 2.51 A; A=1-298.
DR PDB; 1PKD; X-ray; 2.30 A; A/C=1-296.
DR PDB; 1PW2; X-ray; 1.95 A; A=1-298.
DR PDB; 1PXI; X-ray; 1.95 A; A=1-298.
DR PDB; 1PXJ; X-ray; 2.30 A; A=1-298.
DR PDB; 1PXK; X-ray; 2.80 A; A=1-298.
DR PDB; 1PXL; X-ray; 2.50 A; A=1-298.
DR PDB; 1PXM; X-ray; 2.53 A; A=1-298.
DR PDB; 1PXN; X-ray; 2.50 A; A=1-298.
DR PDB; 1PXO; X-ray; 1.96 A; A=1-298.
DR PDB; 1PXP; X-ray; 2.30 A; A=1-298.
DR PDB; 1PYE; X-ray; 2.00 A; A=1-298.
DR PDB; 1QMZ; X-ray; 2.20 A; A/C=1-298.
DR PDB; 1R78; X-ray; 2.00 A; A=1-298.
DR PDB; 1URC; X-ray; 2.60 A; A/C=1-298.
DR PDB; 1URW; X-ray; 1.60 A; A=1-298.
DR PDB; 1V1K; X-ray; 2.31 A; A=1-298.
DR PDB; 1VYW; X-ray; 2.30 A; A/C=1-298.
DR PDB; 1VYZ; X-ray; 2.21 A; A=1-298.
DR PDB; 1W0X; X-ray; 2.20 A; C=1-298.
DR PDB; 1W8C; X-ray; 2.05 A; A=1-298.
DR PDB; 1W98; X-ray; 2.15 A; A=1-297.
DR PDB; 1WCC; X-ray; 2.20 A; A=1-298.
DR PDB; 1Y8Y; X-ray; 2.00 A; A=1-298.
DR PDB; 1Y91; X-ray; 2.15 A; A=1-298.
DR PDB; 1YKR; X-ray; 1.80 A; A=1-298.
DR PDB; 2A0C; X-ray; 1.95 A; X=1-298.
DR PDB; 2A4L; X-ray; 2.40 A; A=1-298.
DR PDB; 2B52; X-ray; 1.88 A; A=1-298.
DR PDB; 2B53; X-ray; 2.00 A; A=1-298.
DR PDB; 2B54; X-ray; 1.85 A; A=1-298.
DR PDB; 2B55; X-ray; 1.85 A; A=1-298.
DR PDB; 2BHE; X-ray; 1.90 A; A=1-298.
DR PDB; 2BHH; X-ray; 2.60 A; A=1-298.
DR PDB; 2BKZ; X-ray; 2.60 A; A/C=1-298.
DR PDB; 2BPM; X-ray; 2.40 A; A/C=1-298.
DR PDB; 2BTR; X-ray; 1.85 A; A=1-298.
DR PDB; 2BTS; X-ray; 1.99 A; A=1-298.
DR PDB; 2C4G; X-ray; 2.70 A; A/C=1-298.
DR PDB; 2C5N; X-ray; 2.10 A; A/C=1-298.
DR PDB; 2C5O; X-ray; 2.10 A; A/C=1-298.
DR PDB; 2C5V; X-ray; 2.90 A; A/C=1-298.
DR PDB; 2C5X; X-ray; 2.90 A; A/C=1-298.
DR PDB; 2C5Y; X-ray; 2.25 A; A=1-298.
DR PDB; 2C68; X-ray; 1.95 A; A=1-298.
DR PDB; 2C69; X-ray; 2.10 A; A=1-298.
DR PDB; 2C6I; X-ray; 1.80 A; A=1-298.
DR PDB; 2C6K; X-ray; 1.90 A; A=1-298.
DR PDB; 2C6L; X-ray; 2.30 A; A=1-298.
DR PDB; 2C6M; X-ray; 1.90 A; A=1-298.
DR PDB; 2C6O; X-ray; 2.10 A; A=1-298.
DR PDB; 2C6T; X-ray; 2.61 A; A/C=1-298.
DR PDB; 2CCH; X-ray; 1.70 A; A/C=1-298.
DR PDB; 2CCI; X-ray; 2.70 A; A/C=1-298.
DR PDB; 2CJM; X-ray; 2.30 A; A/C=1-298.
DR PDB; 2CLX; X-ray; 1.80 A; A=1-298.
DR PDB; 2DS1; X-ray; 2.00 A; A=1-298.
DR PDB; 2DUV; X-ray; 2.20 A; A=1-298.
DR PDB; 2EXM; X-ray; 1.80 A; A=1-298.
DR PDB; 2FVD; X-ray; 1.85 A; A=1-298.
DR PDB; 2G9X; X-ray; 2.50 A; A/C=1-298.
DR PDB; 2HIC; Model; -; A=1-298.
DR PDB; 2I40; X-ray; 2.80 A; A/C=1-298.
DR PDB; 2IW6; X-ray; 2.30 A; A/C=1-298.
DR PDB; 2IW8; X-ray; 2.30 A; A/C=1-298.
DR PDB; 2IW9; X-ray; 2.00 A; A/C=1-298.
DR PDB; 2J9M; X-ray; 2.50 A; A=1-298.
DR PDB; 2JGZ; X-ray; 2.90 A; A=1-288.
DR PDB; 2R3F; X-ray; 1.50 A; A=1-298.
DR PDB; 2R3G; X-ray; 1.55 A; A=1-298.
DR PDB; 2R3H; X-ray; 1.50 A; A=1-298.
DR PDB; 2R3I; X-ray; 1.28 A; A=1-298.
DR PDB; 2R3J; X-ray; 1.65 A; A=1-298.
DR PDB; 2R3K; X-ray; 1.70 A; A=1-298.
DR PDB; 2R3L; X-ray; 1.65 A; A=1-298.
DR PDB; 2R3M; X-ray; 1.70 A; A=1-298.
DR PDB; 2R3N; X-ray; 1.63 A; A=1-298.
DR PDB; 2R3O; X-ray; 1.80 A; A=1-298.
DR PDB; 2R3P; X-ray; 1.66 A; A=1-298.
DR PDB; 2R3Q; X-ray; 1.35 A; A=1-298.
DR PDB; 2R3R; X-ray; 1.47 A; A=1-298.
DR PDB; 2R64; X-ray; 2.30 A; A=1-298.
DR PDB; 2UUE; X-ray; 2.06 A; A/C=1-298.
DR PDB; 2UZB; X-ray; 2.70 A; A/C=1-298.
DR PDB; 2UZD; X-ray; 2.72 A; A/C=1-298.
DR PDB; 2UZE; X-ray; 2.40 A; A/C=1-298.
DR PDB; 2UZL; X-ray; 2.40 A; A/C=1-298.
DR PDB; 2UZN; X-ray; 2.30 A; A=1-298.
DR PDB; 2UZO; X-ray; 2.30 A; A=1-298.
DR PDB; 2V0D; X-ray; 2.20 A; A=1-298.
DR PDB; 2V22; X-ray; 2.60 A; A/C=1-298.
DR PDB; 2VTA; X-ray; 2.00 A; A=1-298.
DR PDB; 2VTH; X-ray; 1.90 A; A=1-298.
DR PDB; 2VTI; X-ray; 2.00 A; A=1-298.
DR PDB; 2VTJ; X-ray; 2.20 A; A=1-298.
DR PDB; 2VTL; X-ray; 2.00 A; A=1-298.
DR PDB; 2VTM; X-ray; 2.25 A; A=1-298.
DR PDB; 2VTN; X-ray; 2.20 A; A=1-298.
DR PDB; 2VTO; X-ray; 2.19 A; A=1-298.
DR PDB; 2VTP; X-ray; 2.15 A; A=1-298.
DR PDB; 2VTQ; X-ray; 1.90 A; A=1-298.
DR PDB; 2VTR; X-ray; 1.90 A; A=1-298.
DR PDB; 2VTS; X-ray; 1.90 A; A=1-298.
DR PDB; 2VTT; X-ray; 1.68 A; A=1-298.
DR PDB; 2VU3; X-ray; 1.85 A; A=1-298.
DR PDB; 2VV9; X-ray; 1.90 A; A=1-298.
DR PDB; 2W05; X-ray; 1.90 A; A=1-298.
DR PDB; 2W06; X-ray; 2.04 A; A=1-298.
DR PDB; 2W17; X-ray; 2.15 A; A=1-298.
DR PDB; 2W1H; X-ray; 2.15 A; A=1-298.
DR PDB; 2WEV; X-ray; 2.30 A; A/C=1-298.
DR PDB; 2WFY; X-ray; 2.53 A; A/C=1-298.
DR PDB; 2WHB; X-ray; 2.90 A; A/C=1-298.
DR PDB; 2WIH; X-ray; 2.50 A; A/C=1-298.
DR PDB; 2WIP; X-ray; 2.80 A; A/C=1-298.
DR PDB; 2WMA; X-ray; 2.80 A; A/C=1-298.
DR PDB; 2WMB; X-ray; 2.60 A; A/C=1-298.
DR PDB; 2WPA; X-ray; 2.51 A; A/C=1-298.
DR PDB; 2WXV; X-ray; 2.60 A; A/C=1-298.
DR PDB; 2X1N; X-ray; 2.75 A; A/C=1-298.
DR PDB; 2XMY; X-ray; 1.90 A; A=1-298.
DR PDB; 2XNB; X-ray; 1.85 A; A=1-298.
DR PDB; 3BHT; X-ray; 2.00 A; A/C=1-298.
DR PDB; 3BHU; X-ray; 2.30 A; A/C=1-298.
DR PDB; 3BHV; X-ray; 2.10 A; A/C=1-298.
DR PDB; 3DDP; X-ray; 2.70 A; A/C=1-298.
DR PDB; 3DDQ; X-ray; 1.80 A; A/C=1-298.
DR PDB; 3DOG; X-ray; 2.70 A; A/C=1-298.
DR PDB; 3EID; X-ray; 3.15 A; A/C=1-298.
DR PDB; 3EJ1; X-ray; 3.22 A; A/C=1-298.
DR PDB; 3EOC; X-ray; 3.20 A; A/C=1-298.
DR PDB; 3EZR; X-ray; 1.90 A; A=1-298.
DR PDB; 3EZV; X-ray; 1.99 A; A=1-298.
DR PDB; 3F5X; X-ray; 2.40 A; A/C=1-298.
DR PDB; 3FZ1; X-ray; 1.90 A; A=1-298.
DR PDB; 3IG7; X-ray; 1.80 A; A=1-298.
DR PDB; 3IGG; X-ray; 1.80 A; A=1-298.
DR PDB; 3LE6; X-ray; 2.00 A; A=1-298.
DR PDB; 3LFN; X-ray; 2.28 A; A=1-298.
DR PDB; 3LFQ; X-ray; 2.03 A; A=1-298.
DR PDB; 3LFS; X-ray; 2.40 A; A=1-298.
DR PDB; 3MY5; X-ray; 2.10 A; A/C=1-298.
DR PDB; 3NS9; X-ray; 1.78 A; A=1-298.
DR PDB; 3PJ8; X-ray; 1.96 A; A=1-298.
DR PDB; 3PXF; X-ray; 1.80 A; A=1-298.
DR PDB; 3PXQ; X-ray; 1.90 A; A=1-298.
DR PDB; 3PXR; X-ray; 2.00 A; A=1-298.
DR PDB; 3PXY; X-ray; 1.80 A; A=1-298.
DR PDB; 3PXZ; X-ray; 1.70 A; A=1-298.
DR PDB; 3PY0; X-ray; 1.75 A; A=1-298.
DR PDB; 3PY1; X-ray; 2.05 A; A=1-298.
DR PDB; 3QHR; X-ray; 2.17 A; A/C=1-296.
DR PDB; 3QHW; X-ray; 1.91 A; A/C=1-296.
DR PDB; 3QL8; X-ray; 1.90 A; A=1-298.
DR PDB; 3QQF; X-ray; 1.75 A; A=1-298.
DR PDB; 3QQG; X-ray; 1.90 A; A=1-298.
DR PDB; 3QQH; X-ray; 1.87 A; A=1-298.
DR PDB; 3QQJ; X-ray; 1.70 A; A=1-298.
DR PDB; 3QQK; X-ray; 1.86 A; A=1-298.
DR PDB; 3QQL; X-ray; 1.85 A; A=1-298.
DR PDB; 3QRT; X-ray; 1.75 A; A=1-298.
DR PDB; 3QRU; X-ray; 1.95 A; A=1-298.
DR PDB; 3QTQ; X-ray; 1.80 A; A=1-298.
DR PDB; 3QTR; X-ray; 1.85 A; A=1-298.
DR PDB; 3QTS; X-ray; 1.90 A; A=1-298.
DR PDB; 3QTU; X-ray; 1.82 A; A=1-298.
DR PDB; 3QTW; X-ray; 1.85 A; A=1-298.
DR PDB; 3QTX; X-ray; 1.95 A; A=1-298.
DR PDB; 3QTZ; X-ray; 2.00 A; A=1-298.
DR PDB; 3QU0; X-ray; 1.95 A; A=1-298.
DR PDB; 3QWJ; X-ray; 1.75 A; A=1-298.
DR PDB; 3QWK; X-ray; 1.85 A; A=1-298.
DR PDB; 3QX2; X-ray; 1.75 A; A=1-298.
DR PDB; 3QX4; X-ray; 1.92 A; A=1-298.
DR PDB; 3QXO; X-ray; 1.75 A; A=1-298.
DR PDB; 3QXP; X-ray; 1.75 A; A=1-298.
DR PDB; 3QZF; X-ray; 2.00 A; A=1-298.
DR PDB; 3QZG; X-ray; 1.75 A; A=1-298.
DR PDB; 3QZH; X-ray; 1.95 A; A=1-298.
DR PDB; 3QZI; X-ray; 1.75 A; A=1-298.
DR PDB; 3R1Q; X-ray; 1.85 A; A=1-298.
DR PDB; 3R1S; X-ray; 1.80 A; A=1-298.
DR PDB; 3R1Y; X-ray; 1.80 A; A=1-298.
DR PDB; 3R28; X-ray; 1.75 A; A=1-298.
DR PDB; 3R6X; X-ray; 1.75 A; A=1-298.
DR PDB; 3R71; X-ray; 1.75 A; A=1-298.
DR PDB; 3R73; X-ray; 1.70 A; A=1-298.
DR PDB; 3R7E; X-ray; 1.90 A; A=1-298.
DR PDB; 3R7I; X-ray; 1.85 A; A=1-298.
DR PDB; 3R7U; X-ray; 1.75 A; A=1-298.
DR PDB; 3R7V; X-ray; 1.95 A; A=1-298.
DR PDB; 3R7Y; X-ray; 1.90 A; A=1-298.
DR PDB; 3R83; X-ray; 1.75 A; A=1-298.
DR PDB; 3R8L; X-ray; 1.90 A; A=1-298.
DR PDB; 3R8M; X-ray; 1.80 A; A=1-298.
DR PDB; 3R8P; X-ray; 1.80 A; A=1-298.
DR PDB; 3R8U; X-ray; 2.00 A; A=1-298.
DR PDB; 3R8V; X-ray; 1.90 A; A=1-298.
DR PDB; 3R8Z; X-ray; 1.85 A; A=1-298.
DR PDB; 3R9D; X-ray; 1.95 A; A=1-298.
DR PDB; 3R9H; X-ray; 2.10 A; A=1-298.
DR PDB; 3R9N; X-ray; 1.75 A; A=1-298.
DR PDB; 3R9O; X-ray; 1.90 A; A=1-298.
DR PDB; 3RAH; X-ray; 1.75 A; A=1-298.
DR PDB; 3RAI; X-ray; 1.70 A; A=1-298.
DR PDB; 3RAK; X-ray; 1.75 A; A=1-298.
DR PDB; 3RAL; X-ray; 1.75 A; A=1-298.
DR PDB; 3RJC; X-ray; 1.85 A; A=1-298.
DR PDB; 3RK5; X-ray; 2.00 A; A=1-298.
DR PDB; 3RK7; X-ray; 1.80 A; A=1-298.
DR PDB; 3RK9; X-ray; 1.85 A; A=1-298.
DR PDB; 3RKB; X-ray; 2.00 A; A=1-298.
DR PDB; 3RM6; X-ray; 1.60 A; A=1-298.
DR PDB; 3RM7; X-ray; 1.85 A; A=1-298.
DR PDB; 3RMF; X-ray; 1.75 A; A=1-298.
DR PDB; 3RNI; X-ray; 1.95 A; A=1-298.
DR PDB; 3ROY; X-ray; 1.75 A; A=1-298.
DR PDB; 3RPO; X-ray; 1.75 A; A=1-298.
DR PDB; 3RPR; X-ray; 1.75 A; A=1-298.
DR PDB; 3RPV; X-ray; 1.80 A; A=1-298.
DR PDB; 3RPY; X-ray; 1.90 A; A=1-298.
DR PDB; 3RZB; X-ray; 1.90 A; A=1-298.
DR PDB; 3S00; X-ray; 1.80 A; A=1-298.
DR PDB; 3S0O; X-ray; 2.00 A; A=1-298.
DR PDB; 3S1H; X-ray; 1.75 A; A=1-298.
DR PDB; 3S2P; X-ray; 2.30 A; A=1-298.
DR PDB; 3SQQ; X-ray; 1.85 A; A=1-298.
DR PDB; 3SW4; X-ray; 1.70 A; A=1-298.
DR PDB; 3SW7; X-ray; 1.80 A; A=1-298.
DR PDB; 3TI1; X-ray; 1.99 A; A=1-298.
DR PDB; 3TIY; X-ray; 1.84 A; A=1-298.
DR PDB; 3TIZ; X-ray; 2.02 A; A=1-298.
DR PDB; 3TNW; X-ray; 2.00 A; A/C=1-298.
DR PDB; 3ULI; X-ray; 2.00 A; A=1-298.
DR PDB; 3UNJ; X-ray; 1.90 A; A=1-298.
DR PDB; 3UNK; X-ray; 2.10 A; A=1-298.
DR PDB; 3WBL; X-ray; 2.00 A; A=1-298.
DR PDB; 4ACM; X-ray; 1.63 A; A=1-298.
DR PDB; 4BCK; X-ray; 2.05 A; A/C=1-298.
DR PDB; 4BCM; X-ray; 2.45 A; A/C=1-298.
DR PDB; 4BCN; X-ray; 2.10 A; A/C=1-298.
DR PDB; 4BCO; X-ray; 2.05 A; A/C=1-298.
DR PDB; 4BCP; X-ray; 2.26 A; A/C=1-298.
DR PDB; 4BCQ; X-ray; 2.40 A; A/C=1-298.
DR PDB; 4BGH; X-ray; 1.95 A; A=1-298.
DR PDB; 4EK3; X-ray; 1.34 A; A=1-298.
DR PDB; 4EK4; X-ray; 1.26 A; A=1-298.
DR PDB; 4EK5; X-ray; 1.60 A; A=1-298.
DR PDB; 4EK6; X-ray; 1.52 A; A=1-298.
DR PDB; 4EK8; X-ray; 1.70 A; A=1-298.
DR PDB; 4EOI; X-ray; 2.00 A; A/C=1-298.
DR PDB; 4EOJ; X-ray; 1.65 A; A/C=1-298.
DR PDB; 4EOK; X-ray; 2.57 A; A/C=1-297.
DR PDB; 4EOL; X-ray; 2.40 A; A/C=1-297.
DR PDB; 4EOM; X-ray; 2.10 A; A/C=1-297.
DR PDB; 4EON; X-ray; 2.40 A; A/C=1-298.
DR PDB; 4EOO; X-ray; 2.10 A; A/C=1-297.
DR PDB; 4EOP; X-ray; 1.99 A; A/C=1-297.
DR PDB; 4EOQ; X-ray; 2.15 A; A/C=1-297.
DR PDB; 4EOR; X-ray; 2.20 A; A/C=1-297.
DR PDB; 4EOS; X-ray; 2.57 A; A/C=1-297.
DR PDB; 4ERW; X-ray; 2.00 A; A=1-298.
DR PDB; 4EZ3; X-ray; 2.00 A; A=1-298.
DR PDB; 4EZ7; X-ray; 2.49 A; A=1-298.
DR PDB; 4FKG; X-ray; 1.51 A; A=1-298.
DR PDB; 4FKI; X-ray; 1.60 A; A=1-298.
DR PDB; 4FKJ; X-ray; 1.63 A; A=1-298.
DR PDB; 4FKL; X-ray; 1.26 A; A=1-298.
DR PDB; 4FKO; X-ray; 1.55 A; A=1-298.
DR PDB; 4FKP; X-ray; 1.60 A; A=1-298.
DR PDB; 4FKQ; X-ray; 1.75 A; A=1-298.
DR PDB; 4FKR; X-ray; 1.90 A; A=1-298.
DR PDB; 4FKS; X-ray; 1.55 A; A=1-298.
DR PDB; 4FKT; X-ray; 1.60 A; A=1-298.
DR PDB; 4FKU; X-ray; 1.47 A; A=1-298.
DR PDB; 4FKV; X-ray; 1.70 A; A=1-298.
DR PDB; 4FKW; X-ray; 1.80 A; A=1-298.
DR PDB; 4FX3; X-ray; 2.75 A; A/C=1-298.
DR PDB; 4GCJ; X-ray; 1.42 A; A=1-298.
DR PDB; 4I3Z; X-ray; 2.05 A; A/C=1-296.
DR PDB; 4II5; X-ray; 2.15 A; A/C=1-298.
DR PDB; 4KD1; X-ray; 1.70 A; A=1-298.
DR PDB; 4LYN; X-ray; 2.00 A; A=1-298.
DR PDBsum; 1AQ1; -.
DR PDBsum; 1B38; -.
DR PDBsum; 1B39; -.
DR PDBsum; 1BUH; -.
DR PDBsum; 1CKP; -.
DR PDBsum; 1DI8; -.
DR PDBsum; 1DM2; -.
DR PDBsum; 1E1V; -.
DR PDBsum; 1E1X; -.
DR PDBsum; 1E9H; -.
DR PDBsum; 1F5Q; -.
DR PDBsum; 1FIN; -.
DR PDBsum; 1FQ1; -.
DR PDBsum; 1FVT; -.
DR PDBsum; 1FVV; -.
DR PDBsum; 1G5S; -.
DR PDBsum; 1GIH; -.
DR PDBsum; 1GII; -.
DR PDBsum; 1GIJ; -.
DR PDBsum; 1GY3; -.
DR PDBsum; 1GZ8; -.
DR PDBsum; 1H00; -.
DR PDBsum; 1H01; -.
DR PDBsum; 1H07; -.
DR PDBsum; 1H08; -.
DR PDBsum; 1H0V; -.
DR PDBsum; 1H0W; -.
DR PDBsum; 1H1P; -.
DR PDBsum; 1H1Q; -.
DR PDBsum; 1H1R; -.
DR PDBsum; 1H1S; -.
DR PDBsum; 1H24; -.
DR PDBsum; 1H25; -.
DR PDBsum; 1H26; -.
DR PDBsum; 1H27; -.
DR PDBsum; 1H28; -.
DR PDBsum; 1HCK; -.
DR PDBsum; 1HCL; -.
DR PDBsum; 1JST; -.
DR PDBsum; 1JSU; -.
DR PDBsum; 1JSV; -.
DR PDBsum; 1JVP; -.
DR PDBsum; 1KE5; -.
DR PDBsum; 1KE6; -.
DR PDBsum; 1KE7; -.
DR PDBsum; 1KE8; -.
DR PDBsum; 1KE9; -.
DR PDBsum; 1OGU; -.
DR PDBsum; 1OI9; -.
DR PDBsum; 1OIQ; -.
DR PDBsum; 1OIR; -.
DR PDBsum; 1OIT; -.
DR PDBsum; 1OIU; -.
DR PDBsum; 1OIY; -.
DR PDBsum; 1OKV; -.
DR PDBsum; 1OKW; -.
DR PDBsum; 1OL1; -.
DR PDBsum; 1OL2; -.
DR PDBsum; 1P2A; -.
DR PDBsum; 1P5E; -.
DR PDBsum; 1PF8; -.
DR PDBsum; 1PKD; -.
DR PDBsum; 1PW2; -.
DR PDBsum; 1PXI; -.
DR PDBsum; 1PXJ; -.
DR PDBsum; 1PXK; -.
DR PDBsum; 1PXL; -.
DR PDBsum; 1PXM; -.
DR PDBsum; 1PXN; -.
DR PDBsum; 1PXO; -.
DR PDBsum; 1PXP; -.
DR PDBsum; 1PYE; -.
DR PDBsum; 1QMZ; -.
DR PDBsum; 1R78; -.
DR PDBsum; 1URC; -.
DR PDBsum; 1URW; -.
DR PDBsum; 1V1K; -.
DR PDBsum; 1VYW; -.
DR PDBsum; 1VYZ; -.
DR PDBsum; 1W0X; -.
DR PDBsum; 1W8C; -.
DR PDBsum; 1W98; -.
DR PDBsum; 1WCC; -.
DR PDBsum; 1Y8Y; -.
DR PDBsum; 1Y91; -.
DR PDBsum; 1YKR; -.
DR PDBsum; 2A0C; -.
DR PDBsum; 2A4L; -.
DR PDBsum; 2B52; -.
DR PDBsum; 2B53; -.
DR PDBsum; 2B54; -.
DR PDBsum; 2B55; -.
DR PDBsum; 2BHE; -.
DR PDBsum; 2BHH; -.
DR PDBsum; 2BKZ; -.
DR PDBsum; 2BPM; -.
DR PDBsum; 2BTR; -.
DR PDBsum; 2BTS; -.
DR PDBsum; 2C4G; -.
DR PDBsum; 2C5N; -.
DR PDBsum; 2C5O; -.
DR PDBsum; 2C5V; -.
DR PDBsum; 2C5X; -.
DR PDBsum; 2C5Y; -.
DR PDBsum; 2C68; -.
DR PDBsum; 2C69; -.
DR PDBsum; 2C6I; -.
DR PDBsum; 2C6K; -.
DR PDBsum; 2C6L; -.
DR PDBsum; 2C6M; -.
DR PDBsum; 2C6O; -.
DR PDBsum; 2C6T; -.
DR PDBsum; 2CCH; -.
DR PDBsum; 2CCI; -.
DR PDBsum; 2CJM; -.
DR PDBsum; 2CLX; -.
DR PDBsum; 2DS1; -.
DR PDBsum; 2DUV; -.
DR PDBsum; 2EXM; -.
DR PDBsum; 2FVD; -.
DR PDBsum; 2G9X; -.
DR PDBsum; 2HIC; -.
DR PDBsum; 2I40; -.
DR PDBsum; 2IW6; -.
DR PDBsum; 2IW8; -.
DR PDBsum; 2IW9; -.
DR PDBsum; 2J9M; -.
DR PDBsum; 2JGZ; -.
DR PDBsum; 2R3F; -.
DR PDBsum; 2R3G; -.
DR PDBsum; 2R3H; -.
DR PDBsum; 2R3I; -.
DR PDBsum; 2R3J; -.
DR PDBsum; 2R3K; -.
DR PDBsum; 2R3L; -.
DR PDBsum; 2R3M; -.
DR PDBsum; 2R3N; -.
DR PDBsum; 2R3O; -.
DR PDBsum; 2R3P; -.
DR PDBsum; 2R3Q; -.
DR PDBsum; 2R3R; -.
DR PDBsum; 2R64; -.
DR PDBsum; 2UUE; -.
DR PDBsum; 2UZB; -.
DR PDBsum; 2UZD; -.
DR PDBsum; 2UZE; -.
DR PDBsum; 2UZL; -.
DR PDBsum; 2UZN; -.
DR PDBsum; 2UZO; -.
DR PDBsum; 2V0D; -.
DR PDBsum; 2V22; -.
DR PDBsum; 2VTA; -.
DR PDBsum; 2VTH; -.
DR PDBsum; 2VTI; -.
DR PDBsum; 2VTJ; -.
DR PDBsum; 2VTL; -.
DR PDBsum; 2VTM; -.
DR PDBsum; 2VTN; -.
DR PDBsum; 2VTO; -.
DR PDBsum; 2VTP; -.
DR PDBsum; 2VTQ; -.
DR PDBsum; 2VTR; -.
DR PDBsum; 2VTS; -.
DR PDBsum; 2VTT; -.
DR PDBsum; 2VU3; -.
DR PDBsum; 2VV9; -.
DR PDBsum; 2W05; -.
DR PDBsum; 2W06; -.
DR PDBsum; 2W17; -.
DR PDBsum; 2W1H; -.
DR PDBsum; 2WEV; -.
DR PDBsum; 2WFY; -.
DR PDBsum; 2WHB; -.
DR PDBsum; 2WIH; -.
DR PDBsum; 2WIP; -.
DR PDBsum; 2WMA; -.
DR PDBsum; 2WMB; -.
DR PDBsum; 2WPA; -.
DR PDBsum; 2WXV; -.
DR PDBsum; 2X1N; -.
DR PDBsum; 2XMY; -.
DR PDBsum; 2XNB; -.
DR PDBsum; 3BHT; -.
DR PDBsum; 3BHU; -.
DR PDBsum; 3BHV; -.
DR PDBsum; 3DDP; -.
DR PDBsum; 3DDQ; -.
DR PDBsum; 3DOG; -.
DR PDBsum; 3EID; -.
DR PDBsum; 3EJ1; -.
DR PDBsum; 3EOC; -.
DR PDBsum; 3EZR; -.
DR PDBsum; 3EZV; -.
DR PDBsum; 3F5X; -.
DR PDBsum; 3FZ1; -.
DR PDBsum; 3IG7; -.
DR PDBsum; 3IGG; -.
DR PDBsum; 3LE6; -.
DR PDBsum; 3LFN; -.
DR PDBsum; 3LFQ; -.
DR PDBsum; 3LFS; -.
DR PDBsum; 3MY5; -.
DR PDBsum; 3NS9; -.
DR PDBsum; 3PJ8; -.
DR PDBsum; 3PXF; -.
DR PDBsum; 3PXQ; -.
DR PDBsum; 3PXR; -.
DR PDBsum; 3PXY; -.
DR PDBsum; 3PXZ; -.
DR PDBsum; 3PY0; -.
DR PDBsum; 3PY1; -.
DR PDBsum; 3QHR; -.
DR PDBsum; 3QHW; -.
DR PDBsum; 3QL8; -.
DR PDBsum; 3QQF; -.
DR PDBsum; 3QQG; -.
DR PDBsum; 3QQH; -.
DR PDBsum; 3QQJ; -.
DR PDBsum; 3QQK; -.
DR PDBsum; 3QQL; -.
DR PDBsum; 3QRT; -.
DR PDBsum; 3QRU; -.
DR PDBsum; 3QTQ; -.
DR PDBsum; 3QTR; -.
DR PDBsum; 3QTS; -.
DR PDBsum; 3QTU; -.
DR PDBsum; 3QTW; -.
DR PDBsum; 3QTX; -.
DR PDBsum; 3QTZ; -.
DR PDBsum; 3QU0; -.
DR PDBsum; 3QWJ; -.
DR PDBsum; 3QWK; -.
DR PDBsum; 3QX2; -.
DR PDBsum; 3QX4; -.
DR PDBsum; 3QXO; -.
DR PDBsum; 3QXP; -.
DR PDBsum; 3QZF; -.
DR PDBsum; 3QZG; -.
DR PDBsum; 3QZH; -.
DR PDBsum; 3QZI; -.
DR PDBsum; 3R1Q; -.
DR PDBsum; 3R1S; -.
DR PDBsum; 3R1Y; -.
DR PDBsum; 3R28; -.
DR PDBsum; 3R6X; -.
DR PDBsum; 3R71; -.
DR PDBsum; 3R73; -.
DR PDBsum; 3R7E; -.
DR PDBsum; 3R7I; -.
DR PDBsum; 3R7U; -.
DR PDBsum; 3R7V; -.
DR PDBsum; 3R7Y; -.
DR PDBsum; 3R83; -.
DR PDBsum; 3R8L; -.
DR PDBsum; 3R8M; -.
DR PDBsum; 3R8P; -.
DR PDBsum; 3R8U; -.
DR PDBsum; 3R8V; -.
DR PDBsum; 3R8Z; -.
DR PDBsum; 3R9D; -.
DR PDBsum; 3R9H; -.
DR PDBsum; 3R9N; -.
DR PDBsum; 3R9O; -.
DR PDBsum; 3RAH; -.
DR PDBsum; 3RAI; -.
DR PDBsum; 3RAK; -.
DR PDBsum; 3RAL; -.
DR PDBsum; 3RJC; -.
DR PDBsum; 3RK5; -.
DR PDBsum; 3RK7; -.
DR PDBsum; 3RK9; -.
DR PDBsum; 3RKB; -.
DR PDBsum; 3RM6; -.
DR PDBsum; 3RM7; -.
DR PDBsum; 3RMF; -.
DR PDBsum; 3RNI; -.
DR PDBsum; 3ROY; -.
DR PDBsum; 3RPO; -.
DR PDBsum; 3RPR; -.
DR PDBsum; 3RPV; -.
DR PDBsum; 3RPY; -.
DR PDBsum; 3RZB; -.
DR PDBsum; 3S00; -.
DR PDBsum; 3S0O; -.
DR PDBsum; 3S1H; -.
DR PDBsum; 3S2P; -.
DR PDBsum; 3SQQ; -.
DR PDBsum; 3SW4; -.
DR PDBsum; 3SW7; -.
DR PDBsum; 3TI1; -.
DR PDBsum; 3TIY; -.
DR PDBsum; 3TIZ; -.
DR PDBsum; 3TNW; -.
DR PDBsum; 3ULI; -.
DR PDBsum; 3UNJ; -.
DR PDBsum; 3UNK; -.
DR PDBsum; 3WBL; -.
DR PDBsum; 4ACM; -.
DR PDBsum; 4BCK; -.
DR PDBsum; 4BCM; -.
DR PDBsum; 4BCN; -.
DR PDBsum; 4BCO; -.
DR PDBsum; 4BCP; -.
DR PDBsum; 4BCQ; -.
DR PDBsum; 4BGH; -.
DR PDBsum; 4EK3; -.
DR PDBsum; 4EK4; -.
DR PDBsum; 4EK5; -.
DR PDBsum; 4EK6; -.
DR PDBsum; 4EK8; -.
DR PDBsum; 4EOI; -.
DR PDBsum; 4EOJ; -.
DR PDBsum; 4EOK; -.
DR PDBsum; 4EOL; -.
DR PDBsum; 4EOM; -.
DR PDBsum; 4EON; -.
DR PDBsum; 4EOO; -.
DR PDBsum; 4EOP; -.
DR PDBsum; 4EOQ; -.
DR PDBsum; 4EOR; -.
DR PDBsum; 4EOS; -.
DR PDBsum; 4ERW; -.
DR PDBsum; 4EZ3; -.
DR PDBsum; 4EZ7; -.
DR PDBsum; 4FKG; -.
DR PDBsum; 4FKI; -.
DR PDBsum; 4FKJ; -.
DR PDBsum; 4FKL; -.
DR PDBsum; 4FKO; -.
DR PDBsum; 4FKP; -.
DR PDBsum; 4FKQ; -.
DR PDBsum; 4FKR; -.
DR PDBsum; 4FKS; -.
DR PDBsum; 4FKT; -.
DR PDBsum; 4FKU; -.
DR PDBsum; 4FKV; -.
DR PDBsum; 4FKW; -.
DR PDBsum; 4FX3; -.
DR PDBsum; 4GCJ; -.
DR PDBsum; 4I3Z; -.
DR PDBsum; 4II5; -.
DR PDBsum; 4KD1; -.
DR PDBsum; 4LYN; -.
DR ProteinModelPortal; P24941; -.
DR SMR; P24941; 1-298.
DR DIP; DIP-161N; -.
DR IntAct; P24941; 61.
DR MINT; MINT-96328; -.
DR STRING; 9606.ENSP00000266970; -.
DR BindingDB; P24941; -.
DR ChEMBL; CHEMBL1907605; -.
DR GuidetoPHARMACOLOGY; 1973; -.
DR PhosphoSite; P24941; -.
DR DMDM; 116051; -.
DR PaxDb; P24941; -.
DR PRIDE; P24941; -.
DR DNASU; 1017; -.
DR Ensembl; ENST00000266970; ENSP00000266970; ENSG00000123374.
DR Ensembl; ENST00000354056; ENSP00000243067; ENSG00000123374.
DR GeneID; 1017; -.
DR KEGG; hsa:1017; -.
DR UCSC; uc001sit.4; human.
DR CTD; 1017; -.
DR GeneCards; GC12P056360; -.
DR HGNC; HGNC:1771; CDK2.
DR HPA; CAB013115; -.
DR MIM; 116953; gene.
DR neXtProt; NX_P24941; -.
DR PharmGKB; PA101; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000233024; -.
DR HOVERGEN; HBG014652; -.
DR InParanoid; P24941; -.
DR KO; K02206; -.
DR OrthoDB; EOG7966H8; -.
DR PhylomeDB; P24941; -.
DR BRENDA; 2.7.11.22; 2681.
DR Reactome; REACT_111183; Meiosis.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_120956; Cellular responses to stress.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR Reactome; REACT_383; DNA Replication.
DR Reactome; REACT_604; Hemostasis.
DR SignaLink; P24941; -.
DR ChiTaRS; CDK2; human.
DR EvolutionaryTrace; P24941; -.
DR GeneWiki; Cyclin-dependent_kinase_2; -.
DR GenomeRNAi; 1017; -.
DR NextBio; 4273; -.
DR PRO; PR:P24941; -.
DR ArrayExpress; P24941; -.
DR Bgee; P24941; -.
DR CleanEx; HS_CDK2; -.
DR Genevestigator; P24941; -.
DR GO; GO:0015030; C:Cajal body; IDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; TAS:UniProtKB.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:Ensembl.
DR GO; GO:0000793; C:condensed chromosome; IEA:Ensembl.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription factor complex; IEA:Ensembl.
DR GO; GO:0000805; C:X chromosome; IEA:Ensembl.
DR GO; GO:0000806; C:Y chromosome; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0030332; F:cyclin binding; IDA:UniProtKB.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031145; P:anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; TAS:Reactome.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0071732; P:cellular response to nitric oxide; TAS:UniProtKB.
DR GO; GO:0051298; P:centrosome duplication; TAS:UniProtKB.
DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; TAS:Reactome.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0006260; P:DNA replication; TAS:UniProtKB.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; NAS:UniProtKB.
DR GO; GO:0016572; P:histone phosphorylation; IDA:GOC.
DR GO; GO:0007126; P:meiosis; TAS:UniProtKB.
DR GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW.
DR GO; GO:0000085; P:mitotic G2 phase; TAS:Reactome.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IDA:UniProtKB.
DR GO; GO:0032298; P:positive regulation of DNA-dependent DNA replication initiation; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; IEA:Ensembl.
DR GO; GO:0006813; P:potassium ion transport; IEA:Ensembl.
DR GO; GO:0007265; P:Ras protein signal transduction; IEP:BHF-UCL.
DR GO; GO:0060968; P:regulation of gene silencing; IDA:UniProtKB.
DR GO; GO:0051439; P:regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle; TAS:Reactome.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Cell cycle; Cell division; Complete proteome; Cytoplasm; Cytoskeleton;
KW DNA damage; DNA repair; Endosome; Kinase; Magnesium; Meiosis;
KW Metal-binding; Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Polymorphism; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1 298 Cyclin-dependent kinase 2.
FT /FTId=PRO_0000085769.
FT DOMAIN 4 286 Protein kinase.
FT NP_BIND 10 18 ATP.
FT NP_BIND 81 83 ATP.
FT NP_BIND 129 132 ATP.
FT ACT_SITE 127 127 Proton acceptor.
FT METAL 132 132 Magnesium; catalytic.
FT METAL 145 145 Magnesium; catalytic.
FT BINDING 33 33 ATP.
FT BINDING 86 86 ATP.
FT BINDING 145 145 ATP.
FT SITE 9 9 CDK7 binding.
FT SITE 88 89 CDK7 binding.
FT SITE 166 166 CDK7 binding.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 6 6 N6-acetyllysine.
FT MOD_RES 14 14 Phosphothreonine.
FT MOD_RES 15 15 Phosphotyrosine; by WEE1.
FT MOD_RES 19 19 Phosphotyrosine.
FT MOD_RES 160 160 Phosphothreonine; by CAK and CCRK.
FT VAR_SEQ 163 196 Missing (in isoform 2).
FT /FTId=VSP_041998.
FT VARIANT 15 15 Y -> S (in dbSNP:rs3087335).
FT /FTId=VAR_016157.
FT VARIANT 18 18 V -> L (in dbSNP:rs11554376).
FT /FTId=VAR_053927.
FT VARIANT 45 45 P -> L (in a glioblastoma multiforme
FT sample; somatic mutation).
FT /FTId=VAR_041972.
FT VARIANT 290 290 T -> S (in dbSNP:rs2069413).
FT /FTId=VAR_019988.
FT MUTAGEN 9 9 K->F: Reduced phosphorylation by CAK.
FT MUTAGEN 14 14 T->A: 2-fold increase in activity.
FT MUTAGEN 15 15 Y->F: 2-fold increase in activity.
FT MUTAGEN 88 89 KK->EV: Reduced phosphorylation by CAK.
FT MUTAGEN 160 160 T->A: Abolishes activity.
FT MUTAGEN 166 166 L->R: Reduced phosphorylation by CAK and
FT reduced kinase activity.
FT CONFLICT 8 12 EKIGE -> AQIGQ (in Ref. 5; BAA32794).
FT CONFLICT 25 29 LTGEV -> STGQM (in Ref. 5; BAA32794).
FT CONFLICT 272 277 NKRISA -> YKRFST (in Ref. 5; BAA32794).
FT CONFLICT 286 287 FQ -> LE (in Ref. 5; BAA32794).
FT HELIX 1 3
FT STRAND 4 12
FT STRAND 14 23
FT TURN 24 26
FT STRAND 29 35
FT STRAND 39 41
FT STRAND 42 44
FT HELIX 46 54
FT HELIX 55 57
FT STRAND 66 72
FT STRAND 75 81
FT STRAND 84 86
FT HELIX 87 93
FT TURN 94 97
FT HELIX 101 120
FT HELIX 130 132
FT STRAND 133 135
FT TURN 137 139
FT STRAND 141 143
FT HELIX 148 152
FT HELIX 156 158
FT STRAND 159 161
FT HELIX 162 168
FT HELIX 171 174
FT STRAND 178 180
FT HELIX 183 198
FT HELIX 208 219
FT TURN 224 226
FT HELIX 230 232
FT HELIX 248 251
FT STRAND 252 254
FT HELIX 257 266
FT TURN 271 273
FT HELIX 277 281
FT HELIX 284 286
FT TURN 287 289
SQ SEQUENCE 298 AA; 33930 MW; F90A0F4E70910B51 CRC64;
MENFQKVEKI GEGTYGVVYK ARNKLTGEVV ALKKIRLDTE TEGVPSTAIR EISLLKELNH
PNIVKLLDVI HTENKLYLVF EFLHQDLKKF MDASALTGIP LPLIKSYLFQ LLQGLAFCHS
HRVLHRDLKP QNLLINTEGA IKLADFGLAR AFGVPVRTYT HEVVTLWYRA PEILLGCKYY
STAVDIWSLG CIFAEMVTRR ALFPGDSEID QLFRIFRTLG TPDEVVWPGV TSMPDYKPSF
PKWARQDFSK VVPPLDEDGR SLLSQMLHYD PNKRISAKAA LAHPFFQDVT KPVPHLRL
//

MIM 116953
*RECORD*
*FIELD* NO
116953
*FIELD* TI
*116953 CYCLIN-DEPENDENT KINASE 2; CDK2
;;CELL DIVISION KINASE 2;;
p33(CDK2)
*FIELD* TX
read more
CLONING

Ninomiya-Tsuji et al. (1991) cloned 2 different cDNAs that can
complement cdc28 mutations of budding yeast Saccharomyces cerevisiae.
One corresponded to a gene encoding human p34(CDC2) kinase (116940), and
the other to a gene that had not been characterized previously, CDK2
(cell division kinase-2). The CDK2 protein was highly homologous to
p34(CDC2) kinase and more significantly homologous to Xenopus Eg1
kinase, suggesting that CDK2 is the human homolog of Eg1. The human CDC2
and CDK2 genes were both able to complement the inviability of a null
allele of S. cerevisiae, CDC28. However, CDK2 was unable to complement
cdc2 mutants in fission yeast Schizosaccharomyces pombe under the
condition where the human CDC2 gene could complement them. CDK2 mRNA
appeared late in G1 or in early S phase, slightly before CDC2 mRNA,
after growth stimulation in the normal human fibroblast cells. Thus, 2
different CDC2-like kinases appear to regulate the human cell cycle at
different stages.

GENE FUNCTION

The complex formed of p34(cdc2) (116940) and cyclin B (176740) is
required for the G2-to-M transition in cell division. Human cyclin A
(123835) binds independently to 2 kinases, p34(cdc2) or p33. In
adenovirus-transformed cells, the viral E1A oncoprotein seems to
associate with p33/cyclin A but not with p34(cdc2)/cyclin A. Tsai et al.
(1991) isolated the gene for p33, which shares 65% sequence identity
with p34(cdc2). They suggested that p33(cdk2) plays a unique role in
cell cycle regulation of vertebrate cells.

CDK (e.g., CDK2) activation requires association with cyclins (e.g.,
CCNE1; 123837) and phosphorylation by CAK (CCNH; 601953), and leads to
cell proliferation. Inhibition of cellular proliferation occurs upon
association of CDK inhibitor (e.g., CDKN1B; 600778) with a cyclin-CDK
complex. Sheaff et al. (1997) showed that expression of CCNE1-CDK2 at
physiologic levels of ATP results in phosphorylation of CDKN1B at
thr187, leading to elimination of CDKN1B from the cell and progression
of the cell cycle from G1 to S phase. At low ATP levels, the inhibitory
functions of CDKN1B are enhanced, thereby arresting cell proliferation.

Apoptosis of human endothelial cells after growth factor deprivation is
associated with rapid and dramatic upregulation of cyclin A-associated
CDK2 activity. Levkau et al. (1998) showed that in apoptotic cells the
carboxyl-termini of the CDK inhibitors CDKN1A (116899) and CDKN1B are
truncated by specific cleavage. The enzyme involved in this cleavage is
CASP3 (600636) and/or a CASP3-like caspase. After cleavage, CDKN1A loses
its nuclear localization sequence and exits the nucleus. Cleavage of
CDKN1A and CDKN1B resulted in a substantial reduction in their
association with nuclear cyclin-CDK2 complexes, leading to a dramatic
induction of CDK2 activity. Dominant-negative CDK2, as well as a mutant
CDKN1A resistant to caspase cleavage, partially suppressed apoptosis.
These data suggested that CDK2 activation, through caspase-mediated
cleavage of CDK inhibitors, may be instrumental in the execution of
apoptosis following caspase activation.

Hinchcliffe et al. (1999) developed a Xenopus egg extract arrested in S
phase that supported repeated assembly of daughter centrosomes. Multiple
rounds of centrosome reproduction were blocked by selective inactivation
of CDK2-cyclin E (123837) and were restored by addition of purified
CDK2-cyclin E. Confocal microscopy revealed that cyclin E was localized
at the centrosome. The authors concluded that CDK2-cyclin E activity is
required for centrosome duplication during S phase and that these
results suggested a mechanism that could coordinate centrosome
reproduction with cycles of DNA synthesis and mitosis.

Falck et al. (2002) demonstrated that experimental blockade of either
the NBS1 (602667)-MRE11 (600814) function or the CHK2 (604373)-triggered
events leads to a partial radioresistant DNA synthesis phenotype in
human cells. In contrast, concomitant interference with NBS1-MRE11 and
the CHK2-CDC25A (116947)-CDK2 pathways entirely abolishes inhibition of
DNA synthesis induced by ionizing radiation, resulting in complete RDS
analogous to that caused by defective ATM (607585). In addition,
CDK2-dependent loading of CDC45 (603465) onto replication origins, a
prerequisite for recruitment of DNA polymerase, was prevented upon
irradiation of normal or NBS1/MRE11-defective cells but not cells with
defective ATM. Falck et al. (2002) concluded that in response to
ionizing radiation, phosphorylation of NBS1 and CHK2 by ATM triggers 2
parallel branches of the DNA damage-dependent S-phase checkpoint that
cooperate by inhibiting distinct steps of DNA replication.

Matsuura et al. (2004) showed that SMAD3 (603109) is a major physiologic
substrate of the G1 cyclin-dependent kinases CDK4 (123829) and CDK2.
Except for the retinoblastoma protein family, SMAD3 was the only CDK4
substrate demonstrated to that time. Matsuura et al. (2004) mapped CDK4
and CDK2 phosphorylation sites to thr8, thr178, and ser212 in SMAD3.
Mutation of the CDK phosphorylation sites increased Smad3
transcriptional activity, leading to higher expression of the CDK
inhibitor p15 (600431). Mutation of the CDK phosphorylation sites of
Smad3 also increased its ability to downregulate the expression of c-myc
(190080). Using Smad3 knockout mouse embryonic fibroblasts and other
epithelial cell lines, Matsuura et al. (2004) further showed that Smad3
inhibits cell cycle progression from G1 to S phase and that mutation of
the CDK phosphorylation sites in Smad3 increases this ability. They
concluded that CDK phosphorylation of SMAD3 inhibits its transcriptional
activity and antiproliferative function.

Matsumoto and Maller (2004) identified 20 amino acids in cyclin E as a
centrosomal localization signal (CLS) essential for both centrosomal
targeting and promoting DNA synthesis. Expressed wildtype, but not
mutant, CLS peptides localized on the centrosome, prevented endogenous
cyclin E and cyclin A from localizing to the centrosome, and inhibited
DNA synthesis. Ectopic cyclin E localized to the centrosome and
accelerated S phase entry even with mutations that abolished Cdk2
binding, but not with a mutation in the CLS. Matsumoto and Maller (2004)
concluded that cyclin E has a modular centrosomal-targeting domain
essential for promoting S phase entry in a Cdk2-independent manner.

Huang et al. (2006) found that CDK2 specifically phosphorylated FOXO1
(136533) at ser249 in vitro and in vivo. Phosphorylation of ser249
resulted in cytoplasmic localization and inhibition of FOXO1. This
phosphorylation was abrogated upon DNA damage through the cell cycle
checkpoint pathway that is dependent on the protein kinases CHK1
(603078) and CHK2. Moreover, silencing of FOXO1 by small interfering RNA
diminished DNA damage-induced death in both p53 (191170)-deficient and
p53-proficient cells. This effect was reversed by restored expression of
FOXO1 in a manner depending on phosphorylation of ser249. Huang et al.
(2006) concluded that functional interaction between CDK2 and FOXO1
provides a mechanism that regulates apoptotic cell death after DNA
strand breakage.

GENE STRUCTURE

Shiffman et al. (1996) described the cloning of an approximately 2.4-kb
genomic DNA fragment from the upstream region of the CDK2 gene. This
fragment was found to contain 5 transcription initiation sites within a
72-bp stretch. A 200-bp subfragment that confers 70% of maximal basal
promoter activity was shown to contain 2 synergistically acting Sp1
sites. The intron-exon boundaries of 7 exons in this gene were also
identified.

BIOCHEMICAL FEATURES

De Bondt et al. (1993) reported the crystal structure of CDK2. Bourne et
al. (1996) analyzed the crystal structure of the CDK-CKS1 (116900)
complex and defined the critical protein domains involved in the
interaction of the 2 molecules. They tested the biologic importance of
the structure-based model by constructing mutant alleles of CKS1 that
led to decreased interaction with CDK2. Bourne et al. (1996) concluded
that the structural analysis revealed the mode of CDK2 binding to CKS1,
suggested a possible mechanism of cooperativity and self regulation of
CKS proteins during the cell cycle, and implicated CKS as a targeting or
matchmaking protein for CDK and at least one other phosphoprotein.
Jeffrey et al. (1995) determined the physical structure of the human
cyclin A-CDK2-ATP complex at 2.3-angstrom resolution. Cyclin A was found
to bind to one side of CDK2's catalytic cleft, inducing large
conformational changes that activate the kinase by realigning active
site residues and relieving the steric blockage at the entrance of the
catalytic cleft.

MAPPING

By fluorescence in situ hybridization, Demetrick et al. (1994) mapped
the CDK2 gene to 12q13, the same region to which the CDK4 gene maps.

ANIMAL MODEL

In mouse embryonic stem cells, Ortega et al. (2003) targeted the locus
encoding CDK2. Embryonic fibroblasts lacking CDK2 proliferated normally
and became immortal after continuous passage in culture. Elimination of
a conditional Cdk2 allele in immortal cells did not significantly affect
proliferation. Cdk2 -/- mice were viable and survived up to 2 years of
age, indicating that CDK2 is also dispensable for proliferation and
survival of most cell types. But CDK2 was found to be essential for
completion of prophase I during meiotic cell division in male and female
germ cells, an unforeseen role for this cell cycle kinase.

Pemphigus vulgaris (PV; 169610) is an autoimmune blistering disease
affecting skin and mucous membranes. Lanza et al. (2008) found that CDK2
appeared to have a role in the development of PV lesions. Exposure of
synchronized human keratinocytes to PV serum increased the proportion of
cells in S phase, caused cell rounding and cell-cell detachment,
elevated CDK2 expression in a dose-dependent manner, and altered the
expression of over 500 genes. The most significantly enriched genes were
those involved in cell communication and cell- cell junction formation.
Small interfering RNA against CDK2 reversed PV serum-induced CDK2
overexpression and reduced cell-cell detachment. Using a neonatal mouse
model in which PV lesions were induced by a single intraperitoneal
injection of whole serum obtained from a PV patient, Lanza et al. (2008)
showed that pretreatment of mice with a pharmacologic CDK2 inhibitor
prevented the development of skin lesions and prevented PV serum-induced
changes in gene expression. Histochemical analysis of PV patient skin
revealed CDK2 overexpression around the site of the acantholytic cleft
and along suprabasal layers in perilesional sites. Lanza et al. (2008)
concluded that activation of CDK2-mediated signaling is a crucial event
in the development of PV lesions.

HISTORY

The article by Davis et al. (2001) regarding the use of a CDK2 inhibitor
compound in a rat model of chemotherapy-induced alopecia was retracted
because the authors were not able to reproduce the biological activity
of the compound.

*FIELD* RF
1. Bourne, Y.; Watson, M. H.; Hickey, M. J.; Holmes, W.; Rocque, W.;
Reed, S. I.; Turner, J. A.: Crystal structure and mutational analysis
of the human CDK2 kinase complex with cell cycle-regulatory protein
CksHs1. Cell 84: 863-874, 1996.

2. Davis, S. T.; Benson, B. G.; Bramson, H. N.; Chapman, D. E.; Dickerson,
S. H.; Dold, K. M.; Eberwein, D. J.; Edelstein, M.; Frye, S. V.; Gampe,
R. T., Jr.; Griffin, R. J.; Harris, P. A.; and 14 others: Prevention
of chemotherapy-induced alopecia in rats by CDK inhibitors. Science 291:
134-137, 2001. Note: Retraction: Science 298: 2327 only, 2002.

3. De Bondt, H. L.; Rosenblatt, J.; Jancarik, J.; Jones, H. D.; Morgan,
D. O.; Kim, S.-H.: Crystal structure of cyclin-dependent kinase 2. Nature 363:
595-602, 1993.

4. Demetrick, D. J.; Zhang, H.; Beach, D. H.: Chromosomal mapping
of human CDK2, CDK4, and CDK5 cell cycle kinase genes. Cytogenet.
Cell Genet. 66: 72-74, 1994.

5. Falck, J.; Petrini, J. H. J.; Williams, B. R.; Lukas, J.; Bartek,
J.: The DNA damage-dependent intra-S phase checkpoint is regulated
by parallel pathways. Nature Genet. 30: 290-294, 2002.

6. Hinchcliffe, E. H.; Li, C.; Thompson, E. A.; Maller, J. L.; Sluder,
G.: Requirement of Cdk2-cyclin E activity for repeated centrosome
reproduction in Xenopus egg extracts. Science 283: 851-854, 1999.

7. Huang, H.; Regan, K. M.; Lou, Z.; Chen, J.; Tindall, D. J.: CDK2-dependent
phosphorylation of FOXO1 as an apoptotic response to DNA damage. Science 314:
294-297, 2006.

8. Jeffrey, P. D.; Russo, A. A.; Polyak, K.; Gibbs, E.; Hurwitz, J.;
Massague, J.; Pavletich, N. P.: Mechanism of CDK activation revealed
by the structure of a cyclinA-CDK2 complex. Nature 376: 313-320,
1995.

9. Lanza, A.; Cirillo, N.; Rossiello, R.; Rienzo, M.; Cutillo, L.;
Casamassimi, A.; de Nigris, F.; Schiano, C.; Rossiello, L.; Femiano,
F.; Gombos, F.; Napoli, C.: Evidence of key role of Cdk2 overexpression
in pemphigus vulgaris. J. Biol. Chem 283: 8736-8745, 2008.

10. Levkau, B.; Koyama, H.; Raines, E. W.; Clurman, B. E.; Herren,
B.; Orth, K.; Roberts, J. M.; Ross, R.: Cleavage of p21(Cip1/Waf1)
and p27(Kip1) mediates apoptosis in endothelial cells through activation
of Cdk2: role of a caspase cascade. Molec. Cell 1: 553-563, 1998.

11. Matsumoto, Y.; Maller, J. L.: A centrosomal localization signal
in cyclin E required for Cdk2-independent S phase entry. Science 306:
885-888, 2004.

12. Matsuura, I.; Denissova, N. G.; Wang, G.; He, D.; Long, J.; Liu,
F.: Cyclin-dependent kinases regulate the antiproliferative function
of Smads. Nature 430: 226-231, 2004.

13. Ninomiya-Tsuji, J.; Nomoto, S.; Yasuda, H.; Reed, S. I.; Matsumoto,
K.: Cloning of a human cDNA encoding a CDC2-related kinase by complementation
of a budding yeast cdc28 mutation. Proc. Nat. Acad. Sci. 88: 9006-9010,
1991.

14. Ortega, S.; Prieto, I.; Odajima, J.; Martin, A.; Dubus, P.; Sotillo,
R.; Barbero, J. L.; Malumbres, M.; Barbacid, M.: Cyclin-dependent
kinase 2 is essential for meiosis but not for mitotic cell division
in mice. Nature Genet. 35: 25-31, 2003.

15. Sheaff, R. J.; Groudine, M.; Gordon, M.; Roberts, J. M.; Clurman,
B. E.: Cyclin E-CDK2 is a regulator of p27(Kip1). Genes Dev. 11:
1464-1478, 1997.

16. Shiffman, D.; Brooks, E. E.; Brooks, A. R.; Chan, C. S.; Milner,
P. G.: Characterization of the human cyclin-dependent kinase 2 gene:
promoter analysis and gene structure. J. Biol. Chem. 271: 12199-12204,
1996.

17. Tsai, L.-H.; Harlow, E.; Meyerson, M.: Isolation of the human
cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated
p33 kinase. Nature 353: 174-177, 1991.

*FIELD* CN
Patricia A. Hartz - updated: 8/5/2008
Ada Hamosh - updated: 10/31/2006
Ada Hamosh - updated: 11/11/2004
Ada Hamosh - updated: 8/26/2004
Victor A. McKusick - updated: 8/21/2003
Ada Hamosh - updated: 3/28/2002
Paul J. Converse - updated: 4/18/2001
Ada Hamosh - updated: 1/10/2001
Ada Hamosh - updated: 2/15/1999
Stylianos E. Antonarakis - updated: 1/21/1999
Victor A. McKusick - updated: 1/20/1998
Jon B. Obray - updated: 7/13/1996
Moyra Smith - updated: 4/15/1996

*FIELD* CD
Victor A. McKusick: 8/21/1991

*FIELD* ED
carol: 03/08/2013
wwang: 8/5/2008
alopez: 11/3/2006
terry: 10/31/2006
tkritzer: 11/11/2004
tkritzer: 8/30/2004
terry: 8/26/2004
alopez: 9/2/2003
alopez: 8/22/2003
terry: 8/21/2003
ckniffin: 3/11/2003
carol: 3/29/2002
cwells: 3/29/2002
terry: 3/28/2002
terry: 11/15/2001
mgross: 4/18/2001
mgross: 1/10/2001
terry: 1/10/2001
alopez: 2/15/1999
carol: 1/21/1999
mark: 1/22/1998
terry: 1/20/1998
carol: 7/13/1996
carol: 4/19/1996
carol: 4/15/1996
carol: 4/29/1994
carol: 6/28/1993
supermim: 3/16/1992
carol: 3/2/1992
carol: 2/13/1992
carol: 11/4/1991