Q00534 (CDK6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-dependent kinase 6
EC=2.7.11.22

Alternative name(s):
Cell division protein kinase 6
Serine/threonine-protein kinase PLSTIRE

Gene names

Name:	CDK6
Synonyms:	CDKN6

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	326 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. Ref.5 Ref.7 Ref.8 Ref.9 Ref.11 Ref.14 Ref.15 Ref.20 Ref.21
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Inhibited by INK4 proteins (CDKN2C/p18-INK4c), aminopurvalanol, PD0332991, 4-(Pyrazol-4-yl)-pyrimidines and fisetin, a flavonol inhibitor. Activated by Thr-177 phosphorylation and Tyr-24 dephosphorylation By similarity. Stimulated by cyclin from herpesvirus saimiri (V-cyclin/ECLF2). Rapidly down-regulated prior to cell differentiation (e.g. erythroid and osteoblast). Ref.7
Subunit structure	Interaction with D-type G1 cyclins. Cyclin binding promotes enzyme activation by phosphorylation at Thr-177 By similarity. Binds to RUNX1, CDKN2D, FBXO7 and CDKN2C/p18-INK4c. Forms a cytoplasmic complex with Hsp90/HSP90AB1 and CDC37. FBXO7-binding promotes D-type cyclin binding. Interacts with Kaposi's sarcoma herpesvirus (KSHV) V-cyclin and herpesvirus saimiri (V-cyclin/ECLF2); the CDK6/V-cyclin complex phosphorylates NPM1 and thus lead to viral reactivation by reducing viral LANA levels. Ref.5 Ref.6 Ref.10 Ref.14 Ref.21
Subcellular location	Cytoplasm. Nucleus. Cell projection › ruffle. Note: Localized to the ruffling edge of spreading fibroblasts. Kinase activity only in nucleus. Ref.6 Ref.10 Ref.20
Tissue specificity	Expressed ubiquitously. Accumulates in squamous cell carcinomas, proliferating hematopoietic progenitor cells, beta-cells of pancreatic islets of Langerhans, and neuroblastomas. Reduced levels in differentiating cells. Ref.5 Ref.20
Induction	Down-regulated in response to enterovirus 71 (EV71) infection. Induced by NANOG during S-phase entry. Ref.7 Ref.13 Ref.16
Post-translational modification	Thr-177 phosphorylation and Tyr-24 dephosphorylation promotes kinase activity.
Polymorphism	Genetic variations in CDK6 may influence stature as a quantitative trait, contributing to the stature quantitative trait locus 11 (STQTL11) [MIM:612223]. Adult height is an easily observable and highly heritable complex continuous trait. Because of this, it is a model trait for studying genetic influence on quantitative traits.
Miscellaneous	Over-expressed in some leukemias and malignancies (including sarcoma, glioma, breast tumors, lymphoma and melanoma) as a consequence of nearby translocations. Enhances beta-cells engraftment in pancreatic islets of Langerhans of diabetic patients.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Cell cycle Cell division Differentiation
Cellular component	Cell projection Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G1 phase of mitotic cell cycle Inferred from expression pattern Ref.5. Source: BHF-UCL G1/S transition of mitotic cell cycle Traceable author statement Ref.22. Source: UniProtKB Notch signaling pathway Inferred from electronic annotation. Source: Compara T cell differentiation in thymus Inferred from electronic annotation. Source: Compara astrocyte development Inferred from sequence or structural similarity PubMed 16767702. Source: UniProtKB cell cycle arrest Traceable author statement Ref.22. Source: UniProtKB cell dedifferentiation Inferred from mutant phenotype PubMed 12861051. Source: BHF-UCL cell division Inferred from electronic annotation. Source: UniProtKB-KW dentate gyrus development Inferred from sequence or structural similarity PubMed 21319271. Source: UniProtKB generation of neurons Inferred from sequence or structural similarity PubMed 21319271. Source: UniProtKB hematopoietic progenitor cell differentiation Inferred from electronic annotation. Source: Compara hematopoietic stem cell differentiation Inferred from electronic annotation. Source: Compara lateral ventricle development Inferred from sequence or structural similarity PubMed 21319271. Source: UniProtKB negative regulation of cellular senescence Inferred from direct assay Ref.15. Source: UniProtKB negative regulation of epithelial cell proliferation Inferred from mutant phenotype Ref.8. Source: BHF-UCL negative regulation of myeloid cell differentiation Inferred from direct assay Ref.14. Source: UniProtKB negative regulation of osteoblast differentiation Inferred from direct assay Ref.9. Source: BHF-UCL positive regulation of cell-matrix adhesion Inferred from direct assay PubMed 10205165. Source: BHF-UCL positive regulation of fibroblast proliferation Inferred from mutant phenotype Ref.15. Source: BHF-UCL positive regulation of gene expression Inferred from electronic annotation. Source: Compara regulation of cell motility Inferred from sequence or structural similarity PubMed 16767702. Source: UniProtKB regulation of erythrocyte differentiation Inferred from mutant phenotype Ref.7. Source: BHF-UCL regulation of gene expression Inferred from direct assay Ref.9. Source: BHF-UCL response to virus Inferred from expression pattern Ref.13. Source: UniProtKB type B pancreatic cell development Inferred from direct assay Ref.20. Source: UniProtKB
Cellular_component	cyclin-dependent protein kinase holoenzyme complex Inferred from direct assay Ref.15. Source: BHF-UCL cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay Ref.8. Source: BHF-UCL ruffle Inferred from direct assay PubMed 10205165. Source: BHF-UCL
Molecular_function	ATP binding Inferred from direct assay Ref.25. Source: BHF-UCL cyclin-dependent protein serine/threonine kinase activity Inferred from direct assay Ref.5. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CCND1	P24385	2	EBI-295663,EBI-375001
CCND3	P30281	2	EBI-295663,EBI-375013
CDC37	Q16543	2	EBI-295663,EBI-295634
CDKN2A	P42771	9	EBI-295663,EBI-375053
FOXM1	Q08050-1	2	EBI-295663,EBI-866499
HSP90AB1	P08238	2	EBI-295663,EBI-352572

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 326

326

Cyclin-dependent kinase 6

PRO_0000085789

Regions

Domain

13 – 300

288

Protein kinase

Nucleotide binding

19 – 27

9

ATP By similarity

Sites

Active site

145

1

Proton acceptor

Binding site

43

1

ATP By similarity

Amino acid modifications

Modified residue

13

1

Phosphotyrosine Ref.12

Modified residue

24

1

Phosphotyrosine Ref.12 Ref.17

Modified residue

43

1

N6-acetyllysine Ref.19

Modified residue

49

1

Phosphothreonine Ref.17

Modified residue

70

1

Phosphothreonine Ref.17

Modified residue

177

1

Phosphothreonine Ref.27

Modified residue

264

1

N6-acetyllysine Ref.19

Modified residue

325

1

Phosphothreonine Ref.17

Natural variations

Natural variant

110

1

D → N. Ref.31
Corresponds to variant rs35654944 [ dbSNP | Ensembl ].

VAR_041978

Natural variant

199

1

P → L in a metastatic melanoma sample; somatic mutation. Ref.31

VAR_041979

Secondary structure

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326

Helix Strand Turn

Details...

Helix

9 – 11

3

Beta strand

13 – 22

10

Beta strand

25 – 32

8

Turn

33 – 37

5

Beta strand

39 – 49

11

Helix

58 – 70

13

Beta strand

79 – 87

9

Beta strand

89 – 99

11

Beta strand

102 – 104

3

Helix

105 – 111

7

Helix

119 – 138

20

Helix

148 – 150

3

Beta strand

151 – 153

3

Beta strand

159 – 161

3

Helix

172 – 176

5

Beta strand

180 – 182

3

Helix

183 – 185

3

Helix

188 – 191

4

Helix

199 – 214

16

Helix

224 – 235

12

Helix

240 – 242

3

Beta strand

245 – 249

5

Helix

251 – 253

3

Helix

262 – 264

3

Beta strand

266 – 268

3

Helix

271 – 280

10

Turn

285 – 287

3

Helix

291 – 295

5

Helix

298 – 300

3

Sequences

	Sequence		Length	Mass (Da)
	Q00534 [UniParc]. Last modified April 1, 1993. Version 1. Checksum: 571733EE6BE7FD4A	FASTA	326	36,938
	10 20 30 40 50 60 MEKDGLCRAD QQYECVAEIG EGAYGKVFKA RDLKNGGRFV ALKRVRVQTG EEGMPLSTIR 70 80 90 100 110 120 EVAVLRHLET FEHPNVVRLF DVCTVSRTDR ETKLTLVFEH VDQDLTTYLD KVPEPGVPTE 130 140 150 160 170 180 TIKDMMFQLL RGLDFLHSHR VVHRDLKPQN ILVTSSGQIK LADFGLARIY SFQMALTSVV 190 200 210 220 230 240 VTLWYRAPEV LLQSSYATPV DLWSVGCIFA EMFRRKPLFR GSSDVDQLGK ILDVIGLPGE 250 260 270 280 290 300 EDWPRDVALP RQAFHSKSAQ PIEKFVTDID ELGKDLLLKC LTFNPAKRIS AYSALSHPYF 310 320 QDLERCKENL DSHLPPSQNT SELNTA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A family of human cdc2-related protein kinases." Meyerson M., Enders G.H., Wu C.-L., Su L.-K., Gorka C., Nelson C., Harlow E., Tsai L.-H. EMBO J. 11:2909-2917(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	NIEHS SNPs program Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[5]	"Identification of G1 kinase activity for cdk6, a novel cyclin D partner." Meyerson M., Harlow E. Mol. Cell. Biol. 14:2077-2086(1994) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS PRB/RB1 KINASE, TISSUE SPECIFICITY, INTERACTION WITH D-TYPE CYCLINS.
[6]	"Active cdk6 complexes are predominantly nuclear and represent only a minority of the cdk6 in T cells." Mahony D., Parry D.A., Lees E. Oncogene 16:603-611(1998) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH D-TYPE CYCLINS; CDKN2D; HSP90AB1 AND CDC37.
[7]	"CDK6 blocks differentiation: coupling cell proliferation to the block to differentiation in leukemic cells." Matushansky I., Radparvar F., Skoultchi A.I. Oncogene 22:4143-4149(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DIFFERENTIATION, ENZYME REGULATION.
[8]	"Cyclin-dependent kinase 6 inhibits proliferation of human mammary epithelial cells." Lucas J.J., Domenico J., Gelfand E.W. Mol. Cancer Res. 2:105-114(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL PROLIFERATION.
[9]	"Bone morphogenetic protein 2-induced osteoblast differentiation requires Smad-mediated down-regulation of Cdk6." Ogasawara T., Kawaguchi H., Jinno S., Hoshi K., Itaka K., Takato T., Nakamura K., Okayama H. Mol. Cell. Biol. 24:6560-6568(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DIFFERENTIATION.
[10]	"Transforming activity of Fbxo7 is mediated specifically through regulation of cyclin D/cdk6." Laman H., Funes J.M., Ye H., Henderson S., Galinanes-Garcia L., Hara E., Knowles P., McDonald N., Boshoff C. EMBO J. 24:3104-3116(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FBXO7, SUBCELLULAR LOCATION.
[11]	"Preferences for phosphorylation sites in the retinoblastoma protein of D-type cyclin-dependent kinases, Cdk4 and Cdk6, in vitro." Takaki T., Fukasawa K., Suzuki-Takahashi I., Semba K., Kitagawa M., Taya Y., Hirai H. J. Biochem. 137:381-386(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS PRB/RB1 KINASE.
[12]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-13 AND TYR-24, MASS SPECTROMETRY.
[13]	"Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection." Leong W.F., Chow V.T. Cell. Microbiol. 8:565-580(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION, MASS SPECTROMETRY.
[14]	"Cdk6 blocks myeloid differentiation by interfering with Runx1 DNA binding and Runx1-C/EBPalpha interaction." Fujimoto T., Anderson K., Jacobsen S.E., Nishikawa S.I., Nerlov C. EMBO J. 26:2361-2370(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN MYELOID DIFFERENTIATION, INTERACTION WITH RUNX1.
[15]	"CDK4 and CDK6 delay senescence by kinase-dependent and p16INK4a-independent mechanisms." Ruas M., Gregory F., Jones R., Poolman R., Starborg M., Rowe J., Brookes S., Peters G. Mol. Cell. Biol. 27:4273-4282(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN SENESCENCE.
[16]	"A role for NANOG in G1 to S transition in human embryonic stem cells through direct binding of CDK6 and CDC25A." Zhang X., Neganova I., Przyborski S., Yang C., Cooke M., Atkinson S.P., Anyfantis G., Fenyk S., Keith W.N., Hoare S.F., Hughes O., Strachan T., Stojkovic M., Hinds P.W., Armstrong L., Lako M. J. Cell Biol. 184:67-82(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY NANOG.
[17]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-24; THR-49; THR-70 AND THR-325, MASS SPECTROMETRY.
[18]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[19]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-43 AND LYS-264, MASS SPECTROMETRY.
[20]	"Induction of human beta-cell proliferation and engraftment using a single G1/S regulatory molecule, cdk6." Fiaschi-Taesch N.M., Salim F., Kleinberger J., Troxell R., Cozar-Castellano I., Selk K., Cherok E., Takane K.K., Scott D.K., Stewart A.F. Diabetes 59:1926-1936(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN BETA-CELL PROLIFERATION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[21]	"Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency." Sarek G., Jaerviluoma A., Moore H.M., Tojkander S., Vartia S., Biberfeld P., Laiho M., Ojala P.M. PLoS Pathog. 6:E1000818-E1000818(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS NPM1 KINASE, INTERACTION WITH KSHV V-CYCLIN.
[22]	"Beyond the cell cycle: a new role for Cdk6 in differentiation." Grossel M.J., Hinds P.W. J. Cell. Biochem. 97:485-493(2006) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON CELL DIFFERENTIATION.
[23]	"Cell cycle, CDKs and cancer: a changing paradigm." Malumbres M., Barbacid M. Nat. Rev. Cancer 9:153-166(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON CELL CYCLE CONTROL, INHIBITORS, GENE FAMILY.
[24]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[25]	"Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a." Russo A.A., Tong L., Lee J.O., Jeffrey P.D., Pavletich N.P. Nature 395:237-243(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF COMPLEXES WITH INK4A AND INK4D.
[26]	"Structural basis of inhibition of CDK-cyclin complexes by INK4 inhibitors." Jeffrey P.D., Tong L., Pavletich N.P. Genes Dev. 14:3115-3125(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) IN COMPLEX WITH INHIBITOR CDKN2C/P18-INK4C.
[27]	"Structural basis for CDK6 activation by a virus-encoded cyclin." Schulze-Gahmen U., Kim S.-H. Nat. Struct. Biol. 9:177-181(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 1-308 IN COMPLEX WITH HERPESVIRUS SAIMIRI V-CYCLIN/ECLF2, PHOSPHORYLATION AT THR-177.
[28]	"Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin." Lu H., Chang D.J., Baratte B., Meijer L., Schulze-Gahmen U. J. Med. Chem. 48:737-743(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 1-308 IN COMPLEX WITH INHIBITOR.
[29]	"Toward understanding the structural basis of cyclin-dependent kinase 6 specific inhibition." Lu H., Schulze-Gahmen U. J. Med. Chem. 49:3826-3831(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 1-308 IN COMPLEX WITH INHIBITORS AND V-CYCLIN.
[30]	"4-(Pyrazol-4-yl)-pyrimidines as selective inhibitors of cyclin-dependent kinase 4/6." Cho Y.S., Borland M., Brain C., Chen C.H.-T., Cheng H., Chopra R., Chung K., Groarke J., He G., Hou Y., Kim S., Kovats S., Lu Y., O'Reilly M., Shen J., Smith T., Trakshel G., Voegtle M. , Xu M., Xu M., Sung M.J. J. Med. Chem. 53:7938-7957(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 1-301 IN COMPLEX WITH INHIBITORS.
[31]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASN-110 AND LEU-199.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X66365 mRNA. Translation: CAA47008.1.
AY128534 Genomic DNA. Translation: AAM76970.1.
AC000065 Genomic DNA. No translation available.
AC004128 Genomic DNA. No translation available.
AC004011 Genomic DNA. No translation available.
BC052264 mRNA. Translation: AAH52264.1.

IPI

IPI00023529.

PIR

S23387.

RefSeq

NP_001138778.1. NM_001145306.1.
NP_001250.1. NM_001259.6.

UniGene

Hs.119882.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BI7	X-ray	3.40	A	1-326	[»]
1BI8	X-ray	2.80	A/C	1-326	[»]
1BLX	X-ray	1.90	A	1-326	[»]
1G3N	X-ray	2.90	A/E	1-326	[»]
1JOW	X-ray	3.10	B	1-308	[»]
1XO2	X-ray	2.90	B	1-308	[»]
2EUF	X-ray	3.00	B	1-308	[»]
2F2C	X-ray	2.80	B	1-308	[»]
3NUP	X-ray	2.60	A	1-301	[»]
3NUX	X-ray	2.70	A	1-301	[»]
4AUA	X-ray	2.31	A	1-301	[»]
4EZ5	X-ray	2.70	A	1-301	[»]

ProteinModelPortal

Q00534.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-687N.

IntAct

Q00534. 82 interactions.

MINT

MINT-232049.

STRING

9606.ENSP00000265734.

PTM databases

PhosphoSite

Q00534.

Polymorphism databases

DMDM

266423.

Proteomic databases

PaxDb

Q00534.

PeptideAtlas

Q00534.

PRIDE

Q00534.

Protocols and materials databases

DNASU

1021.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000265734; ENSP00000265734; ENSG00000105810.
ENST00000424848; ENSP00000397087; ENSG00000105810.

GeneID

1021.

KEGG

hsa:1021.

UCSC

uc010lez.3. human.

Organism-specific databases

CTD

1021.

GeneCards

GC07M092234.

HGNC

HGNC:1777. CDK6.

HPA

CAB004363.
HPA002637.

MIM

603368. gene.
612223. phenotype.

neXtProt

NX_Q00534.

PharmGKB

PA103.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233024.

HOVERGEN

HBG014652.

InParanoid

Q00534.

KO

K02091.

OMA

GNSDVDQ.

OrthoDB

EOG4BZN2X.

PhylomeDB

Q00534.

Enzyme and pathway databases

BRENDA

2.7.11.22. 2681.

Pathway_Interaction_DB

ar_pathway. Coregulation of Androgen receptor activity.
il2_stat5pathway. IL2 signaling events mediated by STAT5.

Reactome

REACT_115566. Cell Cycle.

SignaLink

Q00534.

Gene expression databases

ArrayExpress

Q00534.

Bgee

Q00534.

CleanEx

HS_CDK6.

Genevestigator

Q00534.

GermOnline

ENSG00000105810. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q00534.

ChEMBL

CHEMBL2508.

ChiTaRS

CDK6. human.

EvolutionaryTrace

Q00534.

GenomeRNAi

1021.

NextBio

4291.

SOURCE

Search...

Entry information

Entry name

CDK6_HUMAN

Accession

Primary (citable) accession number: Q00534

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	April 1, 1993
Last modified:	May 29, 2013
This is version 147 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.