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Q00534

- CDK6_HUMAN

UniProt

Q00534 - CDK6_HUMAN

Protein

Cyclin-dependent kinase 6

Gene

CDK6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 162 (01 Oct 2014)
      Sequence version 1 (01 Apr 1993)
      Previous versions | rss
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    Functioni

    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.9 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Enzyme regulationi

    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).By similarity1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei43 – 431ATPPROSITE-ProRule annotation
    Active sitei145 – 1451Proton acceptor

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi19 – 279ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: BHF-UCL
    2. cyclin binding Source: BHF-UCL
    3. cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
    4. protein binding Source: IntAct

    GO - Biological processi

    1. astrocyte development Source: UniProtKB
    2. cell cycle arrest Source: UniProtKB
    3. cell dedifferentiation Source: BHF-UCL
    4. cell division Source: UniProtKB-KW
    5. dentate gyrus development Source: UniProtKB
    6. G1/S transition of mitotic cell cycle Source: UniProtKB
    7. generation of neurons Source: UniProtKB
    8. gliogenesis Source: BHF-UCL
    9. lateral ventricle development Source: UniProtKB
    10. mitotic cell cycle Source: Reactome
    11. negative regulation of cell cycle Source: UniProtKB
    12. negative regulation of cell differentiation Source: UniProtKB
    13. negative regulation of cell proliferation Source: UniProtKB
    14. negative regulation of cellular senescence Source: UniProtKB
    15. negative regulation of epithelial cell proliferation Source: BHF-UCL
    16. negative regulation of myeloid cell differentiation Source: UniProtKB
    17. negative regulation of osteoblast differentiation Source: BHF-UCL
    18. positive regulation of cell-matrix adhesion Source: BHF-UCL
    19. positive regulation of fibroblast proliferation Source: BHF-UCL
    20. protein phosphorylation Source: BHF-UCL
    21. regulation of cell motility Source: UniProtKB
    22. regulation of erythrocyte differentiation Source: BHF-UCL
    23. regulation of gene expression Source: BHF-UCL
    24. response to virus Source: UniProtKB
    25. type B pancreatic cell development Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Cell cycle, Cell division, Differentiation

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.22. 2681.
    ReactomeiREACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_169325. Oncogene Induced Senescence.
    REACT_169436. Oxidative Stress Induced Senescence.
    REACT_821. Cyclin D associated events in G1.
    SignaLinkiQ00534.

    Names & Taxonomyi

    Protein namesi
    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 namesi
    Name:CDK6
    Synonyms:CDKN6
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:1777. CDK6.

    Subcellular locationi

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

    GO - Cellular componenti

    1. cyclin-dependent protein kinase holoenzyme complex Source: BHF-UCL
    2. cytoplasm Source: BHF-UCL
    3. cytosol Source: Reactome
    4. nucleus Source: BHF-UCL
    5. ruffle Source: BHF-UCL

    Keywords - Cellular componenti

    Cell projection, Cytoplasm, Nucleus

    Pathology & Biotechi

    Organism-specific databases

    MIMi612223. phenotype.
    Orphaneti2512. Autosomal recessive primary microcephaly.
    PharmGKBiPA103.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 326326Cyclin-dependent kinase 6PRO_0000085789Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine1 Publication
    Modified residuei13 – 131Phosphotyrosine1 Publication
    Modified residuei24 – 241Phosphotyrosine2 Publications
    Modified residuei49 – 491Phosphothreonine1 Publication
    Modified residuei70 – 701Phosphothreonine1 Publication
    Modified residuei177 – 1771Phosphothreonine1 Publication
    Modified residuei264 – 2641N6-acetyllysine1 Publication
    Modified residuei325 – 3251Phosphothreonine1 Publication

    Post-translational modificationi

    Thr-177 phosphorylation and Tyr-24 dephosphorylation promotes kinase activity.3 Publications

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiQ00534.
    PaxDbiQ00534.
    PeptideAtlasiQ00534.
    PRIDEiQ00534.

    PTM databases

    PhosphoSiteiQ00534.

    Expressioni

    Tissue specificityi

    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.2 Publications

    Inductioni

    Down-regulated in response to enterovirus 71 (EV71) infection. Induced by NANOG during S-phase entry.2 Publications

    Gene expression databases

    ArrayExpressiQ00534.
    BgeeiQ00534.
    CleanExiHS_CDK6.
    GenevestigatoriQ00534.

    Organism-specific databases

    HPAiCAB004363.
    HPA002637.

    Interactioni

    Subunit structurei

    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.By similarity10 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CCND1P243852EBI-295663,EBI-375001
    CCND3P302814EBI-295663,EBI-375013
    CDC37Q165433EBI-295663,EBI-295634
    CDKN2AP4277110EBI-295663,EBI-375053
    CDKN2BP427723EBI-295663,EBI-711280
    CDKN2CP427733EBI-295663,EBI-711290
    CDKN2DP552732EBI-295663,EBI-745859
    FOXM1Q08050-12EBI-295663,EBI-866499
    HSP90AB1P082382EBI-295663,EBI-352572
    RUNX1Q011965EBI-295663,EBI-925904

    Protein-protein interaction databases

    BioGridi107456. 103 interactions.
    DIPiDIP-687N.
    IntActiQ00534. 95 interactions.
    MINTiMINT-232049.
    STRINGi9606.ENSP00000265734.

    Structurei

    Secondary structure

    1
    326
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi9 – 113
    Beta strandi13 – 2210
    Beta strandi25 – 328
    Turni33 – 375
    Beta strandi39 – 4911
    Helixi58 – 7013
    Beta strandi79 – 879
    Beta strandi89 – 9911
    Beta strandi102 – 1043
    Helixi105 – 1117
    Turni113 – 1153
    Helixi119 – 13820
    Helixi148 – 1503
    Beta strandi151 – 1533
    Beta strandi159 – 1613
    Helixi172 – 1765
    Beta strandi180 – 1823
    Helixi183 – 1853
    Helixi188 – 1914
    Helixi199 – 21416
    Helixi224 – 23512
    Helixi240 – 2423
    Beta strandi245 – 2495
    Helixi251 – 2533
    Helixi262 – 2643
    Beta strandi266 – 2683
    Helixi271 – 28010
    Turni285 – 2873
    Helixi291 – 2955
    Helixi298 – 3003

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliQ00534.
    SMRiQ00534. Positions 5-309.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ00534.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini13 – 300288Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000233024.
    HOVERGENiHBG014652.
    InParanoidiQ00534.
    KOiK02091.
    OMAiFHSKSPQ.
    OrthoDBiEOG73JKVV.
    PhylomeDBiQ00534.
    TreeFamiTF101022.

    Family and domain databases

    InterProiIPR028788. 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]
    PANTHERiPTHR24056:SF130. PTHR24056:SF130. 1 hit.
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q00534-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEKDGLCRAD QQYECVAEIG EGAYGKVFKA RDLKNGGRFV ALKRVRVQTG    50
    EEGMPLSTIR EVAVLRHLET FEHPNVVRLF DVCTVSRTDR ETKLTLVFEH 100
    VDQDLTTYLD KVPEPGVPTE TIKDMMFQLL RGLDFLHSHR VVHRDLKPQN 150
    ILVTSSGQIK LADFGLARIY SFQMALTSVV VTLWYRAPEV LLQSSYATPV 200
    DLWSVGCIFA EMFRRKPLFR GSSDVDQLGK ILDVIGLPGE EDWPRDVALP 250
    RQAFHSKSAQ PIEKFVTDID ELGKDLLLKC LTFNPAKRIS AYSALSHPYF 300
    QDLERCKENL DSHLPPSQNT SELNTA 326
    Length:326
    Mass (Da):36,938
    Last modified:April 1, 1993 - v1
    Checksum:i571733EE6BE7FD4A
    GO

    Polymorphismi

    Genetic variations in CDK6 may influence stature as a quantitative trait, contributing to the stature quantitative trait locus 11 (STQTL11) [MIMi: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.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti110 – 1101D → N.1 Publication
    Corresponds to variant rs35654944 [ dbSNP | Ensembl ].
    VAR_041978
    Natural varianti199 – 1991P → L in a metastatic melanoma sample; somatic mutation. 1 Publication
    VAR_041979

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS5628.1.
    PIRiS23387.
    RefSeqiNP_001138778.1. NM_001145306.1.
    NP_001250.1. NM_001259.6.
    XP_006715898.1. XM_006715835.1.
    UniGeneiHs.119882.

    Genome annotation databases

    EnsembliENST00000265734; ENSP00000265734; ENSG00000105810.
    ENST00000424848; ENSP00000397087; ENSG00000105810.
    GeneIDi1021.
    KEGGihsa:1021.
    UCSCiuc010lez.3. human.

    Polymorphism databases

    DMDMi266423.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS5628.1.
    PIRi S23387.
    RefSeqi NP_001138778.1. NM_001145306.1.
    NP_001250.1. NM_001259.6.
    XP_006715898.1. XM_006715835.1.
    UniGenei Hs.119882.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    4P41 X-ray 2.90 B 1-326 [» ]
    ProteinModelPortali Q00534.
    SMRi Q00534. Positions 5-309.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107456. 103 interactions.
    DIPi DIP-687N.
    IntActi Q00534. 95 interactions.
    MINTi MINT-232049.
    STRINGi 9606.ENSP00000265734.

    Chemistry

    BindingDBi Q00534.
    ChEMBLi CHEMBL2111448.
    GuidetoPHARMACOLOGYi 1978.

    PTM databases

    PhosphoSitei Q00534.

    Polymorphism databases

    DMDMi 266423.

    Proteomic databases

    MaxQBi Q00534.
    PaxDbi Q00534.
    PeptideAtlasi Q00534.
    PRIDEi Q00534.

    Protocols and materials databases

    DNASUi 1021.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000265734 ; ENSP00000265734 ; ENSG00000105810 .
    ENST00000424848 ; ENSP00000397087 ; ENSG00000105810 .
    GeneIDi 1021.
    KEGGi hsa:1021.
    UCSCi uc010lez.3. human.

    Organism-specific databases

    CTDi 1021.
    GeneCardsi GC07M092234.
    GeneReviewsi CDK6.
    HGNCi HGNC:1777. CDK6.
    HPAi CAB004363.
    HPA002637.
    MIMi 603368. gene.
    612223. phenotype.
    neXtProti NX_Q00534.
    Orphaneti 2512. Autosomal recessive primary microcephaly.
    PharmGKBi PA103.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    InParanoidi Q00534.
    KOi K02091.
    OMAi FHSKSPQ.
    OrthoDBi EOG73JKVV.
    PhylomeDBi Q00534.
    TreeFami TF101022.

    Enzyme and pathway databases

    BRENDAi 2.7.11.22. 2681.
    Reactomei REACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_169325. Oncogene Induced Senescence.
    REACT_169436. Oxidative Stress Induced Senescence.
    REACT_821. Cyclin D associated events in G1.
    SignaLinki Q00534.

    Miscellaneous databases

    ChiTaRSi CDK6. human.
    EvolutionaryTracei Q00534.
    GeneWikii Cyclin-dependent_kinase_6.
    GenomeRNAii 1021.
    NextBioi 4291.
    PROi Q00534.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q00534.
    Bgeei Q00534.
    CleanExi HS_CDK6.
    Genevestigatori Q00534.

    Family and domain databases

    InterProi IPR028788. 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 ]
    PANTHERi PTHR24056:SF130. PTHR24056:SF130. 1 hit.
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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.
      , 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.
      , 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. 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. 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. 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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    28. 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. 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.
      , 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.

    Entry informationi

    Entry nameiCDK6_HUMAN
    AccessioniPrimary (citable) accession number: Q00534
    Secondary accession number(s): A4D1G0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1993
    Last sequence update: April 1, 1993
    Last modified: October 1, 2014
    This is version 162 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    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.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3