ID CDK2_HUMAN Reviewed; 298 AA.
AC P24941; A8K7C6; O75100;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 2.
DT 01-MAY-2013, entry version 174.
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 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 [52]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 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 [53]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 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 [54]
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 [55]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 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 [56]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 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 [57]
RP X-RAY CRYSTALLOGRAPHY (2.33 ANGSTROMS) OF 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 [58]
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 [59]
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 [60]
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 [61]
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 [62]
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 [63]
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 [64]
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 [65]
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 [66]
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 [67]
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=17; IntAct=EBI-375096, EBI-457097;
CC O95067:CCNB2; NbExp=2; IntAct=EBI-375096, EBI-375024;
CC P24864:CCNE1; NbExp=10; IntAct=EBI-375096, EBI-519526;
CC O96020:CCNE2; NbExp=6; IntAct=EBI-375096, EBI-375033;
CC P51946:CCNH; NbExp=2; IntAct=EBI-375096, EBI-741406;
CC P38936:CDKN1A; NbExp=10; IntAct=EBI-375096, EBI-375077;
CC P46527:CDKN1B; NbExp=13; IntAct=EBI-375096, EBI-519280;
CC Q16667:CDKN3; NbExp=2; IntAct=EBI-375096, EBI-1031527;
CC Q969H0-4:FBXW7; NbExp=2; IntAct=EBI-375096, EBI-6502391;
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, centrosome.
CC Nucleus, Cajal body. Cytoplasm. Endosome. Note=Localized at the
CC centrosomes in late G2 phase after separation of the centrosomes
CC but before the start of prophase. Nuclear-cytoplasmic trafficking
CC is mediated during the inhibition 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 IPI; IPI00031681; -.
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; 3UNJ; X-ray; 1.90 A; A=1-298.
DR PDB; 3UNK; X-ray; 2.10 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; 4BCQ; X-ray; 2.40 A; A/C=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; 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 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; 3UNJ; -.
DR PDBsum; 3UNK; -.
DR PDBsum; 4ACM; -.
DR PDBsum; 4BCK; -.
DR PDBsum; 4BCM; -.
DR PDBsum; 4BCN; -.
DR PDBsum; 4BCO; -.
DR PDBsum; 4BCQ; -.
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; 4GCJ; -.
DR PDBsum; 4I3Z; -.
DR PDBsum; 4II5; -.
DR ProteinModelPortal; P24941; -.
DR DIP; DIP-161N; -.
DR IntAct; P24941; 51.
DR MINT; MINT-96328; -.
DR STRING; 9606.ENSP00000266970; -.
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; EOG4C5CJV; -.
DR PhylomeDB; P24941; -.
DR BRENDA; 2.7.11.22; 2681.
DR Pathway_Interaction_DB; bard1pathway; BARD1 signaling events.
DR Pathway_Interaction_DB; foxm1pathway; FOXM1 transcription factor network.
DR Pathway_Interaction_DB; foxopathway; FoxO family signaling.
DR Pathway_Interaction_DB; il2_1pathway; IL2-mediated signaling events.
DR Pathway_Interaction_DB; smad2_3nuclearpathway; Regulation of nuclear SMAD2/3 signaling.
DR Pathway_Interaction_DB; prlsignalingeventspathway; Signaling events mediated by PRL.
DR Reactome; REACT_111183; Meiosis.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR Reactome; REACT_383; DNA Replication.
DR Reactome; REACT_604; Hemostasis.
DR BindingDB; P24941; -.
DR ChEMBL; CHEMBL301; -.
DR ChiTaRS; CDK2; human.
DR EvolutionaryTrace; P24941; -.
DR GenomeRNAi; 1017; -.
DR NextBio; 4273; -.
DR ArrayExpress; P24941; -.
DR Bgee; P24941; -.
DR CleanEx; HS_CDK2; -.
DR Genevestigator; P24941; -.
DR GermOnline; ENSG00000123374; Homo sapiens.
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:Compara.
DR GO; GO:0000793; C:condensed chromosome; IEA:Compara.
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:Compara.
DR GO; GO:0000805; C:X chromosome; IEA:Compara.
DR GO; GO:0000806; C:Y chromosome; IEA:Compara.
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:0000085; P:G2 phase 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:0000216; P:M/G1 transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0007126; P:meiosis; TAS:UniProtKB.
DR GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW.
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:Compara.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; IEA:Compara.
DR GO; GO:0006813; P:potassium ion transport; IEA:Compara.
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 GO; GO:0000084; P:S phase of mitotic cell cycle; TAS:Reactome.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_cat_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; Kinase_like; 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 55
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 STRAND 155 157
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
//
