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Q00534 (CDK6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 160. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length326 AA.
Sequence statusComplete.
Protein existenceEvidence 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.8 Ref.10 Ref.11 Ref.12 Ref.14 Ref.17 Ref.18 Ref.23 Ref.24

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.10

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.8 Ref.9 Ref.13 Ref.17 Ref.24

Subcellular location

Cytoplasm. Nucleus. Cell projectionruffle. Note: Localized to the ruffling edge of spreading fibroblasts. Kinase activity only in nucleus. Ref.9 Ref.13 Ref.23

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.8 Ref.23

Induction

Down-regulated in response to enterovirus 71 (EV71) infection. Induced by NANOG during S-phase entry. Ref.10 Ref.16 Ref.19

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 processCell cycle
Cell division
Differentiation
   Cellular componentCell projection
Cytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG1/S transition of mitotic cell cycle

Traceable author statement Ref.25. Source: UniProtKB

astrocyte development

Inferred from sequence or structural similarity PubMed 16767702. Source: UniProtKB

cell cycle arrest

Traceable author statement Ref.25. 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

gliogenesis

Inferred from mutant phenotype PubMed 12861051. Source: BHF-UCL

lateral ventricle development

Inferred from sequence or structural similarity PubMed 21319271. Source: UniProtKB

mitotic cell cycle

Traceable author statement. Source: Reactome

negative regulation of cell cycle

Inferred from direct assay Ref.11. Source: UniProtKB

negative regulation of cell differentiation

Traceable author statement Ref.25. Source: UniProtKB

negative regulation of cell proliferation

Traceable author statement Ref.25. Source: UniProtKB

negative regulation of cellular senescence

Inferred from direct assay Ref.18. Source: UniProtKB

negative regulation of epithelial cell proliferation

Inferred from mutant phenotype Ref.11. Source: BHF-UCL

negative regulation of myeloid cell differentiation

Inferred from direct assay Ref.17. Source: UniProtKB

negative regulation of osteoblast differentiation

Inferred from direct assay Ref.12. 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.18. Source: BHF-UCL

protein phosphorylation

Inferred from direct assay Ref.8. Source: BHF-UCL

regulation of cell motility

Inferred from sequence or structural similarity PubMed 16767702. Source: UniProtKB

regulation of erythrocyte differentiation

Inferred from mutant phenotype Ref.10. Source: BHF-UCL

regulation of gene expression

Inferred from direct assay Ref.12. Source: BHF-UCL

response to virus

Inferred from expression pattern Ref.16. Source: UniProtKB

type B pancreatic cell development

Inferred from direct assay Ref.23. Source: UniProtKB

   Cellular_componentcyclin-dependent protein kinase holoenzyme complex

Inferred from direct assay Ref.18. Source: BHF-UCL

cytoplasm

Inferred from direct assay Ref.11. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.11. Source: BHF-UCL

ruffle

Inferred from direct assay PubMed 10205165. Source: BHF-UCL

   Molecular_functionATP binding

Inferred from direct assay Ref.29. Source: BHF-UCL

cyclin binding

Inferred from physical interaction Ref.8. Source: BHF-UCL

cyclin-dependent protein serine/threonine kinase activity

Inferred from direct assay Ref.8. Source: BHF-UCL

protein binding

Inferred from physical interaction PubMed 15232106Ref.17PubMed 17517622PubMed 17909018PubMed 17955473PubMed 18394558PubMed 21516116PubMed 22094256PubMed 22939624PubMed 23602568PubMed 8840966PubMed 9150368Ref.29. Source: IntAct

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 326326Cyclin-dependent kinase 6
PRO_0000085789

Regions

Domain13 – 300288Protein kinase
Nucleotide binding19 – 279ATP By similarity

Sites

Active site1451Proton acceptor
Binding site431ATP By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.28
Modified residue131Phosphotyrosine Ref.15
Modified residue241Phosphotyrosine Ref.15 Ref.20
Modified residue491Phosphothreonine Ref.20
Modified residue701Phosphothreonine Ref.20
Modified residue1771Phosphothreonine Ref.31
Modified residue2641N6-acetyllysine Ref.22
Modified residue3251Phosphothreonine Ref.20

Natural variations

Natural variant1101D → N. Ref.35
Corresponds to variant rs35654944 [ dbSNP | Ensembl ].
VAR_041978
Natural variant1991P → L in a metastatic melanoma sample; somatic mutation. Ref.35
VAR_041979

Secondary structure

....................................................... 326
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q00534 [UniParc].

Last modified April 1, 1993. Version 1.
Checksum: 571733EE6BE7FD4A

FASTA32636,938
        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 

« Hide

References

« Hide '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]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Tongue.
[4]"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. expand/collapse author list , 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].
[5]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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.
[8]"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.
[9]"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.
[10]"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.
[11]"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.
[12]"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.
[13]"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.
[14]"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.
[15]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"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, IDENTIFICATION BY MASS SPECTROMETRY.
[17]"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.
[18]"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.
[19]"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.
[20]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]"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.
[22]"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-264, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"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.
[24]"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.
[25]"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.
[26]"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.
[27]"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].
[28]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[29]"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.
[30]"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.
[31]"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.
[32]"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.
[33]"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.
[34]"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. expand/collapse author list , 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.
[35]"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. expand/collapse author list , 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

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X66365 mRNA. Translation: CAA47008.1.
AY128534 Genomic DNA. Translation: AAM76970.1.
AK313491 mRNA. Translation: BAG36273.1.
AC000065 Genomic DNA. No translation available.
AC004128 Genomic DNA. No translation available.
AC004011 Genomic DNA. No translation available.
CH236949 Genomic DNA. Translation: EAL24146.1.
CH471091 Genomic DNA. Translation: EAW76827.1.
BC052264 mRNA. Translation: AAH52264.1.
CCDSCCDS5628.1.
PIRS23387.
RefSeqNP_001138778.1. NM_001145306.1.
NP_001250.1. NM_001259.6.
XP_006715898.1. XM_006715835.1.
UniGeneHs.119882.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1BI7X-ray3.40A1-326[»]
1BI8X-ray2.80A/C1-326[»]
1BLXX-ray1.90A1-326[»]
1G3NX-ray2.90A/E1-326[»]
1JOWX-ray3.10B1-308[»]
1XO2X-ray2.90B1-308[»]
2EUFX-ray3.00B1-308[»]
2F2CX-ray2.80B1-308[»]
3NUPX-ray2.60A1-301[»]
3NUXX-ray2.70A1-301[»]
4AUAX-ray2.31A1-301[»]
4EZ5X-ray2.70A1-301[»]
4P41X-ray2.90B1-326[»]
ProteinModelPortalQ00534.
SMRQ00534. Positions 5-309.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107456. 103 interactions.
DIPDIP-687N.
IntActQ00534. 91 interactions.
MINTMINT-232049.
STRING9606.ENSP00000265734.

Chemistry

BindingDBQ00534.
ChEMBLCHEMBL2111448.
GuidetoPHARMACOLOGY1978.

PTM databases

PhosphoSiteQ00534.

Polymorphism databases

DMDM266423.

Proteomic databases

MaxQBQ00534.
PaxDbQ00534.
PeptideAtlasQ00534.
PRIDEQ00534.

Protocols and materials databases

DNASU1021.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265734; ENSP00000265734; ENSG00000105810.
ENST00000424848; ENSP00000397087; ENSG00000105810.
GeneID1021.
KEGGhsa:1021.
UCSCuc010lez.3. human.

Organism-specific databases

CTD1021.
GeneCardsGC07M092234.
GeneReviewsCDK6.
HGNCHGNC:1777. CDK6.
HPACAB004363.
HPA002637.
MIM603368. gene.
612223. phenotype.
neXtProtNX_Q00534.
Orphanet2512. Autosomal recessive primary microcephaly.
PharmGKBPA103.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233024.
HOVERGENHBG014652.
InParanoidQ00534.
KOK02091.
OMAFHSKSPQ.
OrthoDBEOG73JKVV.
PhylomeDBQ00534.
TreeFamTF101022.

Enzyme and pathway databases

BRENDA2.7.11.22. 2681.
ReactomeREACT_115566. Cell Cycle.
REACT_120956. Cellular responses to stress.
SignaLinkQ00534.

Gene expression databases

ArrayExpressQ00534.
BgeeQ00534.
CleanExHS_CDK6.
GenevestigatorQ00534.

Family and domain databases

InterProIPR028788. CDK6.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERPTHR24056:SF130. PTHR24056:SF130. 1 hit.
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCDK6. human.
EvolutionaryTraceQ00534.
GeneWikiCyclin-dependent_kinase_6.
GenomeRNAi1021.
NextBio4291.
PROQ00534.
SOURCESearch...

Entry information

Entry nameCDK6_HUMAN
AccessionPrimary (citable) accession number: Q00534
Secondary accession number(s): A4D1G0
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: July 9, 2014
This is version 160 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM