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Database: UniProt
Entry: Q00534
LinkDB: Q00534
Original site: Q00534 
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-JUL-2019, entry version 211.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1639063;
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.,
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   [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.,
RA   Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA   Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA   Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA   Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA   Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA   Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA   Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA   Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA   Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA   Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA   Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA   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.,
RA   Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA   Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA   Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA   Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA   Waterston R.H., 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.,
RA   Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA   Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA   Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA   Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA   Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA   Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA   Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA   Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA   Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA   Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA   Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA   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.,
RA   Mural R.J., 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.,
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 (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
RT   project: 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
RP   D-TYPE CYCLINS.
RX   PubMed=8114739; DOI=10.1128/MCB.14.3.2077;
RA   Meyerson M., Harlow E.;
RT   "Identification of G1 kinase activity for cdk6, a novel cyclin D
RT   partner.";
RL   Mol. Cell. Biol. 14:2077-2086(1994).
RN   [9]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH D-TYPE CYCLINS; CDKN2D;
RP   HSP90AB1 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
RT   to 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
RT   requires 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.,
RA   Hara E., Knowles P., McDonald N., Boshoff C.;
RT   "Transforming activity of Fbxo7 is mediated specifically through
RT   regulation 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
RT   of D-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
RT   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
RT   reveal differential cellular gene expression in response to
RT   enterovirus 71 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
RT   binding 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.,
RA   Atkinson S.P., Anyfantis G., Fenyk S., Keith W.N., Hoare S.F.,
RA   Hughes O., Strachan T., Stojkovic M., Hinds P.W., Armstrong L.,
RA   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
RP   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
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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   [23]
RP   FUNCTION IN BETA-CELL PROLIFERATION, TISSUE SPECIFICITY, AND
RP   SUBCELLULAR 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
RT   single 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
RT   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.,
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   [28]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA   Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA   Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-
RT   terminal acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [29]
RP   FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN MCPH12, AND VARIANT
RP   MCPH12 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
RT   a 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
RP   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
RT   by the 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
RP   HERPESVIRUS 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
RP   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
RP   INHIBITORS 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
RT   6 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
RP   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.,
RA   O'Reilly M., Shen J., Smith T., Trakshel G., Voegtle M., Xu M., Xu M.,
RA   Sung M.J.;
RT   "4-(Pyrazol-4-yl)-pyrimidines as selective inhibitors of cyclin-
RT   dependent 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.,
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 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
CC       maintenance of cell cycle exit during cell differentiation;
CC       prevents cell proliferation and regulates negatively cell
CC       differentiation, but is required for the proliferation of specific
CC       cell types (e.g. erythroid and hematopoietic cells). Essential for
CC       cell proliferation within the dentate gyrus of the hippocampus and
CC       the subventricular zone of the lateral ventricles. Required during
CC       thymocyte development. Promotes the production of newborn neurons,
CC       probably by modulating G1 length. Promotes, at least in
CC       astrocytes, changes in patterns of gene expression, changes in the
CC       actin cytoskeleton including loss of stress fibers, and enhanced
CC       motility during cell differentiation. Prevents myeloid
CC       differentiation by interfering with RUNX1 and reducing its
CC       transcription transactivation activity, but promotes proliferation
CC       of normal myeloid progenitors. Delays senescence. Promotes the
CC       proliferation of beta-cells in pancreatic islets of Langerhans.
CC       May play a role in the centrosome organization during the cell
CC       cycle phases (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,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216;
CC         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-
CC       INK4c), aminopurvalanol, PD0332991, 4-(Pyrazol-4-yl)-pyrimidines
CC       and fisetin, a flavonol inhibitor. Activated by Thr-177
CC       phosphorylation and Tyr-24 dephosphorylation (By similarity).
CC       Stimulated by cyclin from herpesvirus saimiri (V-cyclin/ECLF2).
CC       Rapidly down-regulated prior to cell differentiation (e.g.
CC       erythroid and osteoblast). {ECO:0000250,
CC       ECO:0000269|PubMed:12833137}.
CC   -!- SUBUNIT: Interaction with D-type G1 cyclins. Cyclin binding
CC       promotes enzyme activation by phosphorylation at Thr-177 (By
CC       similarity). Binds to RUNX1, CDKN2D, FBXO7 and CDKN2C/p18-INK4c.
CC       Forms a cytoplasmic complex with Hsp90/HSP90AB1 and CDC37. FBXO7-
CC       binding promotes D-type cyclin binding. Interacts with Kaposi's
CC       sarcoma herpesvirus (KSHV) V-cyclin and herpesvirus saimiri (V-
CC       cyclin/ECLF2); the CDK6/V-cyclin complex phosphorylates NPM1 and
CC       thus lead to viral reactivation by reducing viral LANA levels.
CC       {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       P24385:CCND1; NbExp=4; IntAct=EBI-295663, EBI-375001;
CC       P30281:CCND3; NbExp=17; IntAct=EBI-295663, EBI-375013;
CC       P51946:CCNH; NbExp=4; IntAct=EBI-295663, EBI-741406;
CC       Q16543:CDC37; NbExp=3; IntAct=EBI-295663, EBI-295634;
CC       P42771:CDKN2A; NbExp=14; IntAct=EBI-295663, EBI-375053;
CC       P42772:CDKN2B; NbExp=10; IntAct=EBI-295663, EBI-711280;
CC       P42773:CDKN2C; NbExp=19; IntAct=EBI-295663, EBI-711290;
CC       P55273:CDKN2D; NbExp=14; IntAct=EBI-295663, EBI-745859;
CC       Q08050-1:FOXM1; NbExp=2; IntAct=EBI-295663, EBI-866499;
CC       P08238:HSP90AB1; NbExp=2; IntAct=EBI-295663, EBI-352572;
CC       Q01196:RUNX1; NbExp=5; IntAct=EBI-295663, EBI-925904;
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
CC       of spreading fibroblasts. Kinase activity only in nucleus.
CC       Localized to the cytosol of neurons and showed prominent staining
CC       around either side of the nucleus (By similarity). Present in the
CC       cytosol and in the nucleus in interphase cells and at the
CC       centrosome during mitosis from prophase to telophase
CC       (PubMed:23918663). {ECO:0000250|UniProtKB:Q64261,
CC       ECO:0000269|PubMed:23918663}.
CC   -!- TISSUE SPECIFICITY: Expressed ubiquitously. Accumulates in
CC       squamous cell carcinomas, proliferating hematopoietic progenitor
CC       cells, beta-cells of pancreatic islets of Langerhans, and
CC       neuroblastomas. Reduced levels in differentiating cells.
CC       {ECO:0000269|PubMed:20668294, 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
CC       a quantitative trait, contributing to the stature quantitative
CC       trait locus 11 (STQTL11) [MIM:612223]. Adult height is an easily
CC       observable and highly heritable complex continuous trait. Because
CC       of this, it is a model trait for studying genetic influence on
CC       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-
CC       related mean. Brain weight is markedly reduced and the cerebral
CC       cortex is disproportionately small. {ECO:0000269|PubMed:23918663}.
CC       Note=The disease is caused by mutations affecting the gene
CC       represented in this entry.
CC   -!- MISCELLANEOUS: Over-expressed in some leukemias and malignancies
CC       (including sarcoma, glioma, breast tumors, lymphoma and melanoma)
CC       as a consequence of nearby translocations.
CC   -!- MISCELLANEOUS: Enhances beta-cells engraftment in pancreatic
CC       islets of Langerhans of diabetic patients.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC
CC       Ser/Thr protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/cdk6/";
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   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   SMR; Q00534; -.
DR   BioGrid; 107456; 164.
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; 102.
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-methylbutan-1-ol.
DR   DrugBank; DB03496; Flavopiridol.
DR   DrugBank; DB09073; Palbociclib.
DR   DrugBank; DB11730; Ribociclib.
DR   GuidetoPHARMACOLOGY; 1978; -.
DR   MoonDB; Q00534; Predicted.
DR   iPTMnet; Q00534; -.
DR   PhosphoSitePlus; Q00534; -.
DR   BioMuta; CDK6; -.
DR   DMDM; 266423; -.
DR   EPD; Q00534; -.
DR   jPOST; Q00534; -.
DR   MaxQB; Q00534; -.
DR   PaxDb; Q00534; -.
DR   PeptideAtlas; Q00534; -.
DR   PRIDE; Q00534; -.
DR   ProteomicsDB; 57851; -.
DR   DNASU; 1021; -.
DR   Ensembl; ENST00000265734; ENSP00000265734; ENSG00000105810.
DR   Ensembl; ENST00000424848; ENSP00000397087; ENSG00000105810.
DR   GeneID; 1021; -.
DR   KEGG; hsa:1021; -.
DR   UCSC; uc010lez.4; human.
DR   CTD; 1021; -.
DR   DisGeNET; 1021; -.
DR   GeneCards; CDK6; -.
DR   HGNC; HGNC:1777; CDK6.
DR   HPA; CAB004363; -.
DR   HPA; HPA002637; -.
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   eggNOG; KOG0594; Eukaryota.
DR   eggNOG; ENOG410XPP3; LUCA.
DR   GeneTree; ENSGT00940000157957; -.
DR   HOGENOM; HOG000233024; -.
DR   InParanoid; Q00534; -.
DR   KO; K02091; -.
DR   OMA; HDLERCK; -.
DR   OrthoDB; 1597535at2759; -.
DR   PhylomeDB; Q00534; -.
DR   TreeFam; TF101022; -.
DR   BRENDA; 2.7.11.22; 2681.
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   SignaLink; Q00534; -.
DR   SIGNOR; Q00534; -.
DR   ChiTaRS; CDK6; human.
DR   EvolutionaryTrace; Q00534; -.
DR   GeneWiki; Cyclin-dependent_kinase_6; -.
DR   GenomeRNAi; 1021; -.
DR   PRO; PR:Q00534; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   Bgee; ENSG00000105810; Expressed in 208 organ(s), highest expression level in adrenal tissue.
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: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:0014002; P:astrocyte development; ISS:UniProtKB.
DR   GO; GO:0007050; P:cell cycle arrest; TAS: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:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; TAS:Reactome.
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: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; Complete proteome; Cytoplasm; Cytoskeleton;
KW   Differentiation; Disease mutation; Kinase; Nucleotide-binding;
KW   Nucleus; Phosphoprotein; Polymorphism; Primary microcephaly;
KW   Reference proteome; Serine/threonine-protein kinase; Transferase.
FT   CHAIN         1    326       Cyclin-dependent kinase 6.
FT                                /FTId=PRO_0000085789.
FT   DOMAIN       13    300       Protein kinase. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   NP_BIND      19     27       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   ACT_SITE    145    145       Proton acceptor.
FT   BINDING      43     43       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   MOD_RES       1      1       N-acetylmethionine.
FT                                {ECO:0000244|PubMed:22814378}.
FT   MOD_RES      13     13       Phosphotyrosine.
FT                                {ECO:0000244|PubMed:15592455}.
FT   MOD_RES      24     24       Phosphotyrosine.
FT                                {ECO:0000244|PubMed:15592455,
FT                                ECO:0000244|PubMed:19369195}.
FT   MOD_RES      49     49       Phosphothreonine.
FT                                {ECO:0000244|PubMed:19369195}.
FT   MOD_RES      70     70       Phosphothreonine.
FT                                {ECO:0000244|PubMed:19369195}.
FT   MOD_RES     177    177       Phosphothreonine.
FT                                {ECO:0000269|PubMed:11828325}.
FT   MOD_RES     264    264       N6-acetyllysine.
FT                                {ECO:0000244|PubMed:19608861}.
FT   MOD_RES     325    325       Phosphothreonine.
FT                                {ECO:0000244|PubMed:19369195}.
FT   VARIANT     110    110       D -> N (in dbSNP:rs35654944).
FT                                {ECO:0000269|PubMed:17344846}.
FT                                /FTId=VAR_041978.
FT   VARIANT     197    197       A -> T (in MCPH12; dbSNP:rs606231255).
FT                                {ECO:0000269|PubMed:23918663}.
FT                                /FTId=VAR_072638.
FT   VARIANT     199    199       P -> L (in a metastatic melanoma sample;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:17344846}.
FT                                /FTId=VAR_041979.
FT   HELIX         9     11       {ECO:0000244|PDB:1BLX}.
FT   STRAND       13     22       {ECO:0000244|PDB:1BLX}.
FT   STRAND       25     32       {ECO:0000244|PDB:1BLX}.
FT   TURN         33     37       {ECO:0000244|PDB:1BLX}.
FT   STRAND       39     49       {ECO:0000244|PDB:1BLX}.
FT   HELIX        58     70       {ECO:0000244|PDB:1BLX}.
FT   STRAND       79     87       {ECO:0000244|PDB:1BLX}.
FT   STRAND       89     99       {ECO:0000244|PDB:1BLX}.
FT   STRAND      102    104       {ECO:0000244|PDB:5L2S}.
FT   HELIX       105    111       {ECO:0000244|PDB:1BLX}.
FT   TURN        113    115       {ECO:0000244|PDB:4TTH}.
FT   HELIX       119    138       {ECO:0000244|PDB:1BLX}.
FT   HELIX       148    150       {ECO:0000244|PDB:1BLX}.
FT   STRAND      151    153       {ECO:0000244|PDB:1BLX}.
FT   STRAND      159    161       {ECO:0000244|PDB:1BLX}.
FT   HELIX       172    176       {ECO:0000244|PDB:1BLX}.
FT   STRAND      180    182       {ECO:0000244|PDB:1BI8}.
FT   HELIX       183    185       {ECO:0000244|PDB:2F2C}.
FT   HELIX       188    191       {ECO:0000244|PDB:1BLX}.
FT   HELIX       199    214       {ECO:0000244|PDB:1BLX}.
FT   HELIX       224    235       {ECO:0000244|PDB:1BLX}.
FT   HELIX       240    242       {ECO:0000244|PDB:1BLX}.
FT   STRAND      245    249       {ECO:0000244|PDB:1XO2}.
FT   HELIX       251    253       {ECO:0000244|PDB:1BLX}.
FT   HELIX       262    264       {ECO:0000244|PDB:1BLX}.
FT   STRAND      266    268       {ECO:0000244|PDB:1XO2}.
FT   HELIX       271    280       {ECO:0000244|PDB:1BLX}.
FT   TURN        285    287       {ECO:0000244|PDB:1BLX}.
FT   HELIX       291    295       {ECO:0000244|PDB:1BLX}.
FT   HELIX       298    300       {ECO:0000244|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
//
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