CDK6_HUMAN
ID CDK6_HUMAN Reviewed; 326 AA.
AC Q00534; A4D1G0;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 227.
DE RecName: Full=Cyclin-dependent kinase 6;
DE EC=2.7.11.22;
DE AltName: Full=Cell division protein kinase 6;
DE AltName: Full=Serine/threonine-protein kinase PLSTIRE;
GN Name=CDK6; Synonyms=CDKN6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1639063; DOI=10.1002/j.1460-2075.1992.tb05360.x;
RA Meyerson M., Enders G.H., Wu C.-L., Su L.-K., Gorka C., Nelson C.,
RA Harlow E., Tsai L.-H.;
RT "A family of human cdc2-related protein kinases.";
RL EMBO J. 11:2909-2917(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Tongue;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION AS PRB/RB1 KINASE, TISSUE SPECIFICITY, AND INTERACTION WITH D-TYPE
RP CYCLINS.
RX PubMed=8114739; DOI=10.1128/mcb.14.3.2077-2086.1994;
RA Meyerson M., Harlow E.;
RT "Identification of G1 kinase activity for cdk6, a novel cyclin D partner.";
RL Mol. Cell. Biol. 14:2077-2086(1994).
RN [9]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH D-TYPE CYCLINS; CDKN2D; HSP90AB1
RP AND CDC37.
RX PubMed=9482106; DOI=10.1038/sj.onc.1201570;
RA Mahony D., Parry D.A., Lees E.;
RT "Active cdk6 complexes are predominantly nuclear and represent only a
RT minority of the cdk6 in T cells.";
RL Oncogene 16:603-611(1998).
RN [10]
RP FUNCTION IN DIFFERENTIATION, AND ACTIVITY REGULATION.
RX PubMed=12833137; DOI=10.1038/sj.onc.1206484;
RA Matushansky I., Radparvar F., Skoultchi A.I.;
RT "CDK6 blocks differentiation: coupling cell proliferation to the block to
RT differentiation in leukemic cells.";
RL Oncogene 22:4143-4149(2003).
RN [11]
RP FUNCTION IN CELL PROLIFERATION.
RX PubMed=14985467;
RA Lucas J.J., Domenico J., Gelfand E.W.;
RT "Cyclin-dependent kinase 6 inhibits proliferation of human mammary
RT epithelial cells.";
RL Mol. Cancer Res. 2:105-114(2004).
RN [12]
RP FUNCTION IN DIFFERENTIATION.
RX PubMed=15254224; DOI=10.1128/mcb.24.15.6560-6568.2004;
RA Ogasawara T., Kawaguchi H., Jinno S., Hoshi K., Itaka K., Takato T.,
RA Nakamura K., Okayama H.;
RT "Bone morphogenetic protein 2-induced osteoblast differentiation requires
RT Smad-mediated down-regulation of Cdk6.";
RL Mol. Cell. Biol. 24:6560-6568(2004).
RN [13]
RP INTERACTION WITH FBXO7, AND SUBCELLULAR LOCATION.
RX PubMed=16096642; DOI=10.1038/sj.emboj.7600775;
RA Laman H., Funes J.M., Ye H., Henderson S., Galinanes-Garcia L., Hara E.,
RA Knowles P., McDonald N., Boshoff C.;
RT "Transforming activity of Fbxo7 is mediated specifically through regulation
RT of cyclin D/cdk6.";
RL EMBO J. 24:3104-3116(2005).
RN [14]
RP FUNCTION AS PRB/RB1 KINASE.
RX PubMed=15809340; DOI=10.1093/jb/mvi050;
RA Takaki T., Fukasawa K., Suzuki-Takahashi I., Semba K., Kitagawa M.,
RA Taya Y., Hirai H.;
RT "Preferences for phosphorylation sites in the retinoblastoma protein of D-
RT type cyclin-dependent kinases, Cdk4 and Cdk6, in vitro.";
RL J. Biochem. 137:381-386(2005).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-13 AND TYR-24, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [16]
RP INDUCTION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16548883; DOI=10.1111/j.1462-5822.2005.00644.x;
RA Leong W.F., Chow V.T.;
RT "Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal
RT differential cellular gene expression in response to enterovirus 71
RT infection.";
RL Cell. Microbiol. 8:565-580(2006).
RN [17]
RP FUNCTION IN MYELOID DIFFERENTIATION, AND INTERACTION WITH RUNX1.
RX PubMed=17431401; DOI=10.1038/sj.emboj.7601675;
RA Fujimoto T., Anderson K., Jacobsen S.E., Nishikawa S.I., Nerlov C.;
RT "Cdk6 blocks myeloid differentiation by interfering with Runx1 DNA binding
RT and Runx1-C/EBPalpha interaction.";
RL EMBO J. 26:2361-2370(2007).
RN [18]
RP FUNCTION IN SENESCENCE.
RX PubMed=17420273; DOI=10.1128/mcb.02286-06;
RA Ruas M., Gregory F., Jones R., Poolman R., Starborg M., Rowe J.,
RA Brookes S., Peters G.;
RT "CDK4 and CDK6 delay senescence by kinase-dependent and p16INK4a-
RT independent mechanisms.";
RL Mol. Cell. Biol. 27:4273-4282(2007).
RN [19]
RP INDUCTION BY NANOG.
RX PubMed=19139263; DOI=10.1083/jcb.200801009;
RA Zhang X., Neganova I., Przyborski S., Yang C., Cooke M., Atkinson S.P.,
RA Anyfantis G., Fenyk S., Keith W.N., Hoare S.F., Hughes O., Strachan T.,
RA Stojkovic M., Hinds P.W., Armstrong L., Lako M.;
RT "A role for NANOG in G1 to S transition in human embryonic stem cells
RT through direct binding of CDK6 and CDC25A.";
RL J. Cell Biol. 184:67-82(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-24; THR-49; THR-70 AND
RP THR-325, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-264, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA 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 [23]
RP FUNCTION IN BETA-CELL PROLIFERATION, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=20668294; DOI=10.2337/db09-1776;
RA Fiaschi-Taesch N.M., Salim F., Kleinberger J., Troxell R.,
RA Cozar-Castellano I., Selk K., Cherok E., Takane K.K., Scott D.K.,
RA Stewart A.F.;
RT "Induction of human beta-cell proliferation and engraftment using a single
RT G1/S regulatory molecule, cdk6.";
RL Diabetes 59:1926-1936(2010).
RN [24]
RP FUNCTION AS NPM1 KINASE, AND INTERACTION WITH KSHV V-CYCLIN.
RX PubMed=20333249; DOI=10.1371/journal.ppat.1000818;
RA Sarek G., Jaerviluoma A., Moore H.M., Tojkander S., Vartia S.,
RA Biberfeld P., Laiho M., Ojala P.M.;
RT "Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency.";
RL PLoS Pathog. 6:E1000818-E1000818(2010).
RN [25]
RP REVIEW ON CELL DIFFERENTIATION.
RX PubMed=16294322; DOI=10.1002/jcb.20712;
RA Grossel M.J., Hinds P.W.;
RT "Beyond the cell cycle: a new role for Cdk6 in differentiation.";
RL J. Cell. Biochem. 97:485-493(2006).
RN [26]
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 [27]
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., Buerckstuemmer T.,
RA 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 [28]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [29]
RP FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN MCPH12, AND VARIANT MCPH12
RP THR-197.
RX PubMed=23918663; DOI=10.1093/hmg/ddt374;
RA Hussain M.S., Baig S.M., Neumann S., Peche V.S., Szczepanski S.,
RA Nurnberg G., Tariq M., Jameel M., Khan T.N., Fatima A., Malik N.A.,
RA Ahmad I., Altmuller J., Frommolt P., Thiele H., Hohne W., Yigit G.,
RA Wollnik B., Neubauer B.A., Nurnberg P., Noegel A.A.;
RT "CDK6 associates with the centrosome during mitosis and is mutated in a
RT large Pakistani family with primary microcephaly.";
RL Hum. Mol. Genet. 22:5199-5214(2013).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF COMPLEXES WITH INK4A AND INK4D.
RX PubMed=9751050; DOI=10.1038/26155;
RA Russo A.A., Tong L., Lee J.O., Jeffrey P.D., Pavletich N.P.;
RT "Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the
RT tumour suppressor p16INK4a.";
RL Nature 395:237-243(1998).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) IN COMPLEX WITH INHIBITOR
RP CDKN2C/P18-INK4C.
RX PubMed=11124804; DOI=10.1101/gad.851100;
RA Jeffrey P.D., Tong L., Pavletich N.P.;
RT "Structural basis of inhibition of CDK-cyclin complexes by INK4
RT inhibitors.";
RL Genes Dev. 14:3115-3125(2000).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 1-308 IN COMPLEX WITH HERPESVIRUS
RP SAIMIRI V-CYCLIN/ECLF2, AND PHOSPHORYLATION AT THR-177.
RX PubMed=11828325; DOI=10.1038/nsb756;
RA Schulze-Gahmen U., Kim S.-H.;
RT "Structural basis for CDK6 activation by a virus-encoded cyclin.";
RL Nat. Struct. Biol. 9:177-181(2002).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 1-308 IN COMPLEX WITH INHIBITOR.
RX PubMed=15689157; DOI=10.1021/jm049353p;
RA Lu H., Chang D.J., Baratte B., Meijer L., Schulze-Gahmen U.;
RT "Crystal structure of a human cyclin-dependent kinase 6 complex with a
RT flavonol inhibitor, fisetin.";
RL J. Med. Chem. 48:737-743(2005).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 1-308 IN COMPLEX WITH INHIBITORS
RP AND V-CYCLIN.
RX PubMed=16789739; DOI=10.1021/jm0600388;
RA Lu H., Schulze-Gahmen U.;
RT "Toward understanding the structural basis of cyclin-dependent kinase 6
RT specific inhibition.";
RL J. Med. Chem. 49:3826-3831(2006).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 1-301 IN COMPLEX WITH INHIBITORS.
RX PubMed=21038853; DOI=10.1021/jm100571n;
RA Cho Y.S., Borland M., Brain C., Chen C.H.-T., Cheng H., Chopra R.,
RA Chung K., Groarke J., He G., Hou Y., Kim S., Kovats S., Lu Y., O'Reilly M.,
RA Shen J., Smith T., Trakshel G., Voegtle M., Xu M., Xu M., Sung M.J.;
RT "4-(Pyrazol-4-yl)-pyrimidines as selective inhibitors of cyclin-dependent
RT kinase 4/6.";
RL J. Med. Chem. 53:7938-7957(2010).
RN [36]
RP VARIANTS [LARGE SCALE ANALYSIS] ASN-110 AND LEU-199.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA 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 of
CC the cell cycle and differentiation; promotes G1/S transition.
CC Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins
CC during interphase at G1 to form a pRB/RB1 kinase and controls the
CC entrance into the cell cycle. Involved in initiation and maintenance of
CC cell cycle exit during cell differentiation; prevents cell
CC proliferation and regulates negatively cell differentiation, but is
CC required for the proliferation of specific cell types (e.g. erythroid
CC and hematopoietic cells). Essential for cell proliferation within the
CC dentate gyrus of the hippocampus and the subventricular zone of the
CC lateral ventricles. Required during thymocyte development. Promotes the
CC production of newborn neurons, probably by modulating G1 length.
CC Promotes, at least in astrocytes, changes in patterns of gene
CC expression, changes in the actin cytoskeleton including loss of stress
CC fibers, and enhanced motility during cell differentiation. Prevents
CC myeloid differentiation by interfering with RUNX1 and reducing its
CC transcription transactivation activity, but promotes proliferation of
CC normal myeloid progenitors. Delays senescence. Promotes the
CC proliferation of beta-cells in pancreatic islets of Langerhans. May
CC play a role in the centrosome organization during the cell cycle phases
CC (PubMed:23918663). {ECO:0000269|PubMed:12833137,
CC ECO:0000269|PubMed:14985467, ECO:0000269|PubMed:15254224,
CC ECO:0000269|PubMed:15809340, ECO:0000269|PubMed:17420273,
CC ECO:0000269|PubMed:17431401, ECO:0000269|PubMed:20333249,
CC ECO:0000269|PubMed:20668294, ECO:0000269|PubMed:23918663,
CC ECO:0000269|PubMed:8114739}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.22;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.22;
CC -!- ACTIVITY REGULATION: Inhibited by INK4 proteins (CDKN2C/p18-INK4c),
CC aminopurvalanol, PD0332991, 4-(Pyrazol-4-yl)-pyrimidines and fisetin, a
CC flavonol inhibitor. Activated by Thr-177 phosphorylation and Tyr-24
CC dephosphorylation (By similarity). Stimulated by cyclin from
CC herpesvirus saimiri (V-cyclin/ECLF2). Rapidly down-regulated prior to
CC cell differentiation (e.g. erythroid and osteoblast). {ECO:0000250,
CC ECO:0000269|PubMed:12833137}.
CC -!- SUBUNIT: Interaction with D-type G1 cyclins. Cyclin binding promotes
CC enzyme activation by phosphorylation at Thr-177 (By similarity). Binds
CC to RUNX1, CDKN2D, FBXO7 and CDKN2C/p18-INK4c. Forms a cytoplasmic
CC complex with Hsp90/HSP90AB1 and CDC37. FBXO7-binding promotes D-type
CC cyclin binding. Interacts with Kaposi's sarcoma herpesvirus (KSHV) V-
CC cyclin and herpesvirus saimiri (V-cyclin/ECLF2); the CDK6/V-cyclin
CC complex phosphorylates NPM1 and thus lead to viral reactivation by
CC reducing viral LANA levels. {ECO:0000250, ECO:0000269|PubMed:11124804,
CC ECO:0000269|PubMed:11828325, ECO:0000269|PubMed:15689157,
CC ECO:0000269|PubMed:16096642, ECO:0000269|PubMed:16789739,
CC ECO:0000269|PubMed:17431401, ECO:0000269|PubMed:20333249,
CC ECO:0000269|PubMed:21038853, ECO:0000269|PubMed:8114739,
CC ECO:0000269|PubMed:9482106}.
CC -!- INTERACTION:
CC Q00534; P41238: APOBEC1; NbExp=3; IntAct=EBI-295663, EBI-12819523;
CC Q00534; P24385: CCND1; NbExp=4; IntAct=EBI-295663, EBI-375001;
CC Q00534; P30281: CCND3; NbExp=28; IntAct=EBI-295663, EBI-375013;
CC Q00534; P51946: CCNH; NbExp=5; IntAct=EBI-295663, EBI-741406;
CC Q00534; Q14094: CCNI; NbExp=3; IntAct=EBI-295663, EBI-1104653;
CC Q00534; Q16543: CDC37; NbExp=3; IntAct=EBI-295663, EBI-295634;
CC Q00534; P38936: CDKN1A; NbExp=2; IntAct=EBI-295663, EBI-375077;
CC Q00534; P42771: CDKN2A; NbExp=16; IntAct=EBI-295663, EBI-375053;
CC Q00534; P42772: CDKN2B; NbExp=16; IntAct=EBI-295663, EBI-711280;
CC Q00534; P42773: CDKN2C; NbExp=25; IntAct=EBI-295663, EBI-711290;
CC Q00534; P55273: CDKN2D; NbExp=22; IntAct=EBI-295663, EBI-745859;
CC Q00534; Q08050-1: FOXM1; NbExp=2; IntAct=EBI-295663, EBI-866499;
CC Q00534; P08238: HSP90AB1; NbExp=2; IntAct=EBI-295663, EBI-352572;
CC Q00534; Q5XKR4: OTP; NbExp=3; IntAct=EBI-295663, EBI-12865884;
CC Q00534; Q01196: RUNX1; NbExp=5; IntAct=EBI-295663, EBI-925904;
CC Q00534; Q9C019: TRIM15; NbExp=3; IntAct=EBI-295663, EBI-2342111;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell projection, ruffle.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:23918663}. Note=Localized to the ruffling edge of
CC spreading fibroblasts. Kinase activity only in nucleus. Localized to
CC the cytosol of neurons and showed prominent staining around either side
CC of the nucleus (By similarity). Present in the cytosol and in the
CC nucleus in interphase cells and at the centrosome during mitosis from
CC prophase to telophase (PubMed:23918663). {ECO:0000250|UniProtKB:Q64261,
CC ECO:0000269|PubMed:23918663}.
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously. Accumulates in squamous
CC cell carcinomas, proliferating hematopoietic progenitor cells, beta-
CC cells of pancreatic islets of Langerhans, and neuroblastomas. Reduced
CC levels in differentiating cells. {ECO:0000269|PubMed:20668294,
CC ECO:0000269|PubMed:8114739}.
CC -!- INDUCTION: Down-regulated in response to enterovirus 71 (EV71)
CC infection. Induced by NANOG during S-phase entry.
CC {ECO:0000269|PubMed:16548883, ECO:0000269|PubMed:19139263}.
CC -!- PTM: Thr-177 phosphorylation and Tyr-24 dephosphorylation promotes
CC kinase activity. {ECO:0000269|PubMed:11828325}.
CC -!- POLYMORPHISM: Genetic variations in CDK6 may influence stature as a
CC quantitative trait, contributing to the stature quantitative trait
CC locus 11 (STQTL11) [MIM:612223]. Adult height is an easily observable
CC and highly heritable complex continuous trait. Because of this, it is a
CC model trait for studying genetic influence on quantitative traits.
CC -!- DISEASE: Microcephaly 12, primary, autosomal recessive (MCPH12)
CC [MIM:616080]: A form of microcephaly, a disease defined as a head
CC circumference more than 3 standard deviations below the age-related
CC mean. Brain weight is markedly reduced and the cerebral cortex is
CC disproportionately small. {ECO:0000269|PubMed:23918663}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: Over-expressed in some leukemias and malignancies
CC (including sarcoma, glioma, breast tumors, lymphoma and melanoma) as a
CC consequence of nearby translocations.
CC -!- MISCELLANEOUS: Enhances beta-cells engraftment in pancreatic islets of
CC Langerhans of diabetic patients.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cdk6/";
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DR EMBL; X66365; CAA47008.1; -; mRNA.
DR EMBL; AY128534; AAM76970.1; -; Genomic_DNA.
DR EMBL; AK313491; BAG36273.1; -; mRNA.
DR EMBL; AC000065; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC004128; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC004011; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236949; EAL24146.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76827.1; -; Genomic_DNA.
DR EMBL; BC052264; AAH52264.1; -; mRNA.
DR CCDS; CCDS5628.1; -.
DR PIR; S23387; S23387.
DR RefSeq; NP_001138778.1; NM_001145306.1.
DR RefSeq; NP_001250.1; NM_001259.6.
DR RefSeq; XP_006715898.1; XM_006715835.2.
DR PDB; 1BI7; X-ray; 3.40 A; A=1-326.
DR PDB; 1BI8; X-ray; 2.80 A; A/C=1-326.
DR PDB; 1BLX; X-ray; 1.90 A; A=1-326.
DR PDB; 1G3N; X-ray; 2.90 A; A/E=1-326.
DR PDB; 1JOW; X-ray; 3.10 A; B=1-308.
DR PDB; 1XO2; X-ray; 2.90 A; B=1-308.
DR PDB; 2EUF; X-ray; 3.00 A; B=1-308.
DR PDB; 2F2C; X-ray; 2.80 A; B=1-308.
DR PDB; 3NUP; X-ray; 2.60 A; A=1-301.
DR PDB; 3NUX; X-ray; 2.70 A; A=1-301.
DR PDB; 4AUA; X-ray; 2.31 A; A=1-301.
DR PDB; 4EZ5; X-ray; 2.70 A; A=1-301.
DR PDB; 4TTH; X-ray; 2.90 A; B=1-326.
DR PDB; 5L2I; X-ray; 2.75 A; A=1-301.
DR PDB; 5L2S; X-ray; 2.27 A; A=1-301.
DR PDB; 5L2T; X-ray; 2.37 A; A=1-301.
DR PDB; 6OQL; X-ray; 2.71 A; A=11-301.
DR PDB; 6OQO; X-ray; 1.98 A; A=11-301.
DR PDBsum; 1BI7; -.
DR PDBsum; 1BI8; -.
DR PDBsum; 1BLX; -.
DR PDBsum; 1G3N; -.
DR PDBsum; 1JOW; -.
DR PDBsum; 1XO2; -.
DR PDBsum; 2EUF; -.
DR PDBsum; 2F2C; -.
DR PDBsum; 3NUP; -.
DR PDBsum; 3NUX; -.
DR PDBsum; 4AUA; -.
DR PDBsum; 4EZ5; -.
DR PDBsum; 4TTH; -.
DR PDBsum; 5L2I; -.
DR PDBsum; 5L2S; -.
DR PDBsum; 5L2T; -.
DR PDBsum; 6OQL; -.
DR PDBsum; 6OQO; -.
DR AlphaFoldDB; Q00534; -.
DR SMR; Q00534; -.
DR BioGRID; 107456; 197.
DR ComplexPortal; CPX-2013; Cyclin D3-CDK6 complex.
DR ComplexPortal; CPX-2014; Cyclin D1-CDK6 complex.
DR CORUM; Q00534; -.
DR DIP; DIP-687N; -.
DR IntAct; Q00534; 117.
DR MINT; Q00534; -.
DR STRING; 9606.ENSP00000265734; -.
DR BindingDB; Q00534; -.
DR ChEMBL; CHEMBL2508; -.
DR DrugBank; DB07379; (2S)-2-({6-[(3-Amino-5-chlorophenyl)amino]-9-isopropyl-9H-purin-2-yl}amino)-3-methyl-1-butanol.
DR DrugBank; DB12001; Abemaciclib.
DR DrugBank; DB03496; Alvocidib.
DR DrugBank; DB07795; Fisetin.
DR DrugBank; DB09073; Palbociclib.
DR DrugBank; DB11730; Ribociclib.
DR DrugBank; DB15442; Trilaciclib.
DR DrugCentral; Q00534; -.
DR GuidetoPHARMACOLOGY; 1978; -.
DR MoonDB; Q00534; Predicted.
DR iPTMnet; Q00534; -.
DR MetOSite; Q00534; -.
DR PhosphoSitePlus; Q00534; -.
DR BioMuta; CDK6; -.
DR DMDM; 266423; -.
DR EPD; Q00534; -.
DR jPOST; Q00534; -.
DR MassIVE; Q00534; -.
DR MaxQB; Q00534; -.
DR PaxDb; Q00534; -.
DR PeptideAtlas; Q00534; -.
DR PRIDE; Q00534; -.
DR ProteomicsDB; 57851; -.
DR Antibodypedia; 1130; 1004 antibodies from 43 providers.
DR DNASU; 1021; -.
DR Ensembl; ENST00000265734.8; ENSP00000265734.4; ENSG00000105810.10.
DR Ensembl; ENST00000424848.3; ENSP00000397087.3; ENSG00000105810.10.
DR GeneID; 1021; -.
DR KEGG; hsa:1021; -.
DR MANE-Select; ENST00000424848.3; ENSP00000397087.3; NM_001145306.2; NP_001138778.1.
DR UCSC; uc010lez.4; human.
DR CTD; 1021; -.
DR DisGeNET; 1021; -.
DR GeneCards; CDK6; -.
DR HGNC; HGNC:1777; CDK6.
DR HPA; ENSG00000105810; Tissue enhanced (lymphoid).
DR MalaCards; CDK6; -.
DR MIM; 603368; gene.
DR MIM; 612223; phenotype.
DR MIM; 616080; phenotype.
DR neXtProt; NX_Q00534; -.
DR OpenTargets; ENSG00000105810; -.
DR Orphanet; 2512; Autosomal recessive primary microcephaly.
DR PharmGKB; PA103; -.
DR VEuPathDB; HostDB:ENSG00000105810; -.
DR eggNOG; KOG0594; Eukaryota.
DR GeneTree; ENSGT00940000157957; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; Q00534; -.
DR OMA; QWNSGEE; -.
DR OrthoDB; 988547at2759; -.
DR PhylomeDB; Q00534; -.
DR TreeFam; TF101022; -.
DR BRENDA; 2.7.11.22; 2681.
DR PathwayCommons; Q00534; -.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-HSA-2559585; Oncogene Induced Senescence.
DR Reactome; R-HSA-69231; Cyclin D associated events in G1.
DR Reactome; R-HSA-8934593; Regulation of RUNX1 Expression and Activity.
DR Reactome; R-HSA-9630794; Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6.
DR Reactome; R-HSA-9632700; Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6.
DR Reactome; R-HSA-9661069; Defective binding of RB1 mutants to E2F1,(E2F2, E2F3).
DR Reactome; R-HSA-9754119; Drug-mediated inhibition of CDK4/CDK6 activity.
DR SignaLink; Q00534; -.
DR SIGNOR; Q00534; -.
DR BioGRID-ORCS; 1021; 351 hits in 1134 CRISPR screens.
DR ChiTaRS; CDK6; human.
DR EvolutionaryTrace; Q00534; -.
DR GeneWiki; Cyclin-dependent_kinase_6; -.
DR GenomeRNAi; 1021; -.
DR Pharos; Q00534; Tclin.
DR PRO; PR:Q00534; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q00534; protein.
DR Bgee; ENSG00000105810; Expressed in adrenal tissue and 182 other tissues.
DR Genevisible; Q00534; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0097132; C:cyclin D2-CDK6 complex; IEA:Ensembl.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016592; C:mediator complex; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0001726; C:ruffle; IDA:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IDA:BHF-UCL.
DR GO; GO:0030332; F:cyclin binding; IPI:BHF-UCL.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IDA:BHF-UCL.
DR GO; GO:0098770; F:FBXO family protein binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IBA:GO_Central.
DR GO; GO:0014002; P:astrocyte development; ISS:UniProtKB.
DR GO; GO:0043697; P:cell dedifferentiation; IMP:BHF-UCL.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0021542; P:dentate gyrus development; ISS:UniProtKB.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:UniProtKB.
DR GO; GO:0048699; P:generation of neurons; ISS:UniProtKB.
DR GO; GO:0042063; P:gliogenesis; IMP:BHF-UCL.
DR GO; GO:0060218; P:hematopoietic stem cell differentiation; IEA:Ensembl.
DR GO; GO:0021670; P:lateral ventricle development; ISS:UniProtKB.
DR GO; GO:0045786; P:negative regulation of cell cycle; IDA:UniProtKB.
DR GO; GO:0045596; P:negative regulation of cell differentiation; TAS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:UniProtKB.
DR GO; GO:2000773; P:negative regulation of cellular senescence; IDA:UniProtKB.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:BHF-UCL.
DR GO; GO:0045656; P:negative regulation of monocyte differentiation; IDA:UniProtKB.
DR GO; GO:0045638; P:negative regulation of myeloid cell differentiation; IDA:UniProtKB.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; IDA:BHF-UCL.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0051726; P:regulation of cell cycle; IBA:GO_Central.
DR GO; GO:2000145; P:regulation of cell motility; ISS:UniProtKB.
DR GO; GO:0045646; P:regulation of erythrocyte differentiation; IMP:BHF-UCL.
DR GO; GO:0010468; P:regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:1902036; P:regulation of hematopoietic stem cell differentiation; IEA:Ensembl.
DR GO; GO:0009615; P:response to virus; IEP:UniProtKB.
DR GO; GO:0033077; P:T cell differentiation in thymus; IEA:Ensembl.
DR GO; GO:0003323; P:type B pancreatic cell development; IDA:UniProtKB.
DR CDD; cd07862; STKc_CDK6; 1.
DR InterPro; IPR028788; CDK6.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
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; ATP-binding; Cell cycle; Cell division;
KW Cell projection; Cytoplasm; Cytoskeleton; Differentiation; Disease variant;
KW Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Primary microcephaly;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..326
FT /note="Cyclin-dependent kinase 6"
FT /id="PRO_0000085789"
FT DOMAIN 13..300
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 145
FT /note="Proton acceptor"
FT BINDING 19..27
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 43
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 13
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 24
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 49
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 70
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 177
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:11828325"
FT MOD_RES 264
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 325
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT VARIANT 110
FT /note="D -> N (in dbSNP:rs35654944)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041978"
FT VARIANT 197
FT /note="A -> T (in MCPH12; dbSNP:rs606231255)"
FT /evidence="ECO:0000269|PubMed:23918663"
FT /id="VAR_072638"
FT VARIANT 199
FT /note="P -> L (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041979"
FT HELIX 9..11
FT /evidence="ECO:0007829|PDB:1BLX"
FT STRAND 13..22
FT /evidence="ECO:0007829|PDB:1BLX"
FT STRAND 25..32
FT /evidence="ECO:0007829|PDB:1BLX"
FT TURN 33..37
FT /evidence="ECO:0007829|PDB:1BLX"
FT STRAND 39..49
FT /evidence="ECO:0007829|PDB:1BLX"
FT HELIX 58..70
FT /evidence="ECO:0007829|PDB:1BLX"
FT STRAND 79..87
FT /evidence="ECO:0007829|PDB:1BLX"
FT STRAND 89..99
FT /evidence="ECO:0007829|PDB:1BLX"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:6OQO"
FT HELIX 105..111
FT /evidence="ECO:0007829|PDB:1BLX"
FT TURN 113..115
FT /evidence="ECO:0007829|PDB:4TTH"
FT HELIX 119..138
FT /evidence="ECO:0007829|PDB:1BLX"
FT HELIX 148..150
FT /evidence="ECO:0007829|PDB:1BLX"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:1BLX"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:1BLX"
FT HELIX 172..176
FT /evidence="ECO:0007829|PDB:1BLX"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:1BI8"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:2F2C"
FT HELIX 188..191
FT /evidence="ECO:0007829|PDB:1BLX"
FT HELIX 199..214
FT /evidence="ECO:0007829|PDB:1BLX"
FT HELIX 224..235
FT /evidence="ECO:0007829|PDB:1BLX"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:1BLX"
FT STRAND 245..249
FT /evidence="ECO:0007829|PDB:1XO2"
FT HELIX 251..253
FT /evidence="ECO:0007829|PDB:1BLX"
FT HELIX 262..264
FT /evidence="ECO:0007829|PDB:1BLX"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:1XO2"
FT HELIX 271..280
FT /evidence="ECO:0007829|PDB:1BLX"
FT TURN 285..287
FT /evidence="ECO:0007829|PDB:1BLX"
FT HELIX 291..295
FT /evidence="ECO:0007829|PDB:1BLX"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:1BLX"
SQ SEQUENCE 326 AA; 36938 MW; 571733EE6BE7FD4A CRC64;
MEKDGLCRAD QQYECVAEIG EGAYGKVFKA RDLKNGGRFV ALKRVRVQTG EEGMPLSTIR
EVAVLRHLET FEHPNVVRLF DVCTVSRTDR ETKLTLVFEH VDQDLTTYLD KVPEPGVPTE
TIKDMMFQLL RGLDFLHSHR VVHRDLKPQN ILVTSSGQIK LADFGLARIY SFQMALTSVV
VTLWYRAPEV LLQSSYATPV DLWSVGCIFA EMFRRKPLFR GSSDVDQLGK ILDVIGLPGE
EDWPRDVALP RQAFHSKSAQ PIEKFVTDID ELGKDLLLKC LTFNPAKRIS AYSALSHPYF
QDLERCKENL DSHLPPSQNT SELNTA
