Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q64261

- CDK6_MOUSE

UniProt

Q64261 - CDK6_MOUSE

Protein

Cyclin-dependent kinase 6

Gene

Cdk6

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 132 (01 Oct 2014)
      Sequence version 2 (30 Apr 2003)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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.3 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Enzyme regulationi

    Activated by Thr-177 phosphorylation and Tyr-24 dephosphorylation By similarity. Rapidly down-regulated prior to cell differentiation (e.g. erythroid and osteoblast) By similarity.By similarity

    Sites

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

    Regions

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

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB-EC
    3. kinase activity Source: MGI
    4. protein binding Source: IntAct

    GO - Biological processi

    1. cell cycle Source: UniProtKB-KW
    2. cell dedifferentiation Source: InterPro
    3. cell division Source: UniProtKB-KW
    4. hematopoietic progenitor cell differentiation Source: MGI
    5. hematopoietic stem cell differentiation Source: MGI
    6. hemopoiesis Source: BHF-UCL
    7. Notch signaling pathway Source: MGI
    8. positive regulation of gene expression Source: MGI
    9. regulation of cell proliferation Source: InterPro
    10. T cell differentiation in thymus Source: MGI

    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

    ReactomeiREACT_188970. Oxidative Stress Induced Senescence.
    REACT_188971. Oncogene Induced Senescence.
    REACT_206033. Senescence-Associated Secretory Phenotype (SASP).

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cyclin-dependent kinase 6 (EC:2.7.11.22)
    Alternative name(s):
    CR2 protein kinase
    Short name:
    CRK2
    Cell division protein kinase 6
    Serine/threonine-protein kinase PLSTIRE
    Gene namesi
    Name:Cdk6
    Synonyms:Cdkn6, Crk2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 5

    Organism-specific databases

    MGIiMGI:1277162. Cdk6.

    Subcellular locationi

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

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell
    3. ruffle Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell projection, Cytoplasm, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Slight anemia and defective proliferation of some hematopoietic cells, thymocytes and progenitor cells. Females are reduced in size and often sterile. Prevents the expansion of neuronally committed precursors by prematurely exiting the cell cycle and lengthening G1 phase duration, reducing concomitantly the production of newborn neurons.3 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi31 – 311R → C: Enhanced kinase activity. Over-production of thymocytes and hematopoietic stem cells and progenitor cells. 1 Publication
    Mutagenesisi43 – 431K → M: Loss of kinase activity. Pronounced reduction in thymocytes and hematopoietic stem cells and progenitor cells. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 326326Cyclin-dependent kinase 6PRO_0000085790Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineBy similarity
    Modified residuei13 – 131PhosphotyrosineBy similarity
    Modified residuei24 – 241PhosphotyrosineBy similarity
    Modified residuei49 – 491PhosphothreonineBy similarity
    Modified residuei70 – 701PhosphothreonineBy similarity
    Modified residuei177 – 1771PhosphothreonineBy similarity
    Modified residuei264 – 2641N6-acetyllysineBy similarity
    Modified residuei325 – 3251PhosphothreonineBy similarity

    Post-translational modificationi

    Thr-177 phosphorylation and Tyr-24 dephosphorylation promotes kinase activity.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiQ64261.
    PaxDbiQ64261.
    PRIDEiQ64261.

    PTM databases

    PhosphoSiteiQ64261.

    Expressioni

    Tissue specificityi

    Expressed in subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ) of the lateral ventricles whose neural precursor cells (NPC) give rise to dentate granule neurons and olfactory bulb (OB) interneurons, respectively.1 Publication

    Gene expression databases

    ArrayExpressiQ64261.
    BgeeiQ64261.
    CleanExiMM_CDK6.
    GenevestigatoriQ64261.

    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 By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Ccnd3P302822EBI-847380,EBI-847337
    JunP056272EBI-847380,EBI-764369
    Stat3P422273EBI-847380,EBI-602878

    Protein-protein interaction databases

    BioGridi198649. 10 interactions.
    DIPiDIP-24175N.
    IntActiQ64261. 7 interactions.
    MINTiMINT-4090464.

    Structurei

    3D structure databases

    ProteinModelPortaliQ64261.
    SMRiQ64261. Positions 9-301.
    ModBaseiSearch...
    MobiDBiSearch...

    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.
    GeneTreeiENSGT00720000108415.
    HOGENOMiHOG000233024.
    HOVERGENiHBG014652.
    InParanoidiQ64261.
    KOiK02091.
    OMAiFHSKSPQ.
    OrthoDBiEOG73JKVV.
    PhylomeDBiQ64261.
    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.

    Q64261-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEKDSLSRAD QQYECVAEIG EGAYGKVFKA RDLKNGGRFV ALKRVRVQTS    50
    EEGMPLSTIR EVAVLRHLET FEHPNVVRLF DVCTVSRTDR ETKLTLVFEH 100
    VDQDLTTYLD KVPEPGVPTE TIKDMMFQLL RGLDFLHSHR VVHRDLKPQN 150
    ILVTSSGQIK LADFGLARIY SFQMALTSVV VTLWYRAPEV LLQSSYATPV 200
    DLWSVGCIFA EMFRRKPLFR GSSDVDQLGK ILDIIGLPGE EDWPRDVALP 250
    RQAFHSKSAQ PIEKFVTDID ELGKDLLLKC LTFNPAKRIS AYGALNHPYF 300
    QDLERYKDNL NSHLPSNQST SELNTA 326
    Length:326
    Mass (Da):37,028
    Last modified:April 30, 2003 - v2
    Checksum:i127B7ECFFC54C3AC
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti321 – 3211S → A in strain: SPRET/Ei.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF132483 mRNA. Translation: AAD43504.1.
    AF132482 mRNA. Translation: AAD43503.1.
    AK078973 mRNA. Translation: BAC37489.1.
    X65068 mRNA. Translation: CAA46201.1.
    CCDSiCCDS19062.1.
    PIRiPN0483.
    RefSeqiNP_034003.1. NM_009873.2.
    XP_006503606.1. XM_006503543.1.
    UniGeneiMm.31672.
    Mm.389058.
    Mm.399714.

    Genome annotation databases

    EnsembliENSMUST00000042410; ENSMUSP00000037925; ENSMUSG00000040274.
    ENSMUST00000165117; ENSMUSP00000126024; ENSMUSG00000040274.
    GeneIDi12571.
    KEGGimmu:12571.
    UCSCiuc008wgu.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF132483 mRNA. Translation: AAD43504.1 .
    AF132482 mRNA. Translation: AAD43503.1 .
    AK078973 mRNA. Translation: BAC37489.1 .
    X65068 mRNA. Translation: CAA46201.1 .
    CCDSi CCDS19062.1.
    PIRi PN0483.
    RefSeqi NP_034003.1. NM_009873.2.
    XP_006503606.1. XM_006503543.1.
    UniGenei Mm.31672.
    Mm.389058.
    Mm.399714.

    3D structure databases

    ProteinModelPortali Q64261.
    SMRi Q64261. Positions 9-301.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 198649. 10 interactions.
    DIPi DIP-24175N.
    IntActi Q64261. 7 interactions.
    MINTi MINT-4090464.

    PTM databases

    PhosphoSitei Q64261.

    Proteomic databases

    MaxQBi Q64261.
    PaxDbi Q64261.
    PRIDEi Q64261.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000042410 ; ENSMUSP00000037925 ; ENSMUSG00000040274 .
    ENSMUST00000165117 ; ENSMUSP00000126024 ; ENSMUSG00000040274 .
    GeneIDi 12571.
    KEGGi mmu:12571.
    UCSCi uc008wgu.1. mouse.

    Organism-specific databases

    CTDi 1021.
    MGIi MGI:1277162. Cdk6.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00720000108415.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    InParanoidi Q64261.
    KOi K02091.
    OMAi FHSKSPQ.
    OrthoDBi EOG73JKVV.
    PhylomeDBi Q64261.
    TreeFami TF101022.

    Enzyme and pathway databases

    Reactomei REACT_188970. Oxidative Stress Induced Senescence.
    REACT_188971. Oncogene Induced Senescence.
    REACT_206033. Senescence-Associated Secretory Phenotype (SASP).

    Miscellaneous databases

    NextBioi 281678.
    PROi Q64261.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q64261.
    Bgeei Q64261.
    CleanExi MM_CDK6.
    Genevestigatori Q64261.

    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. "Human-mouse comparative mapping of the genomic region containing CDK6: localization of an evolutionary breakpoint."
      Thomas J.W., Lee-Lin S.Q., Green E.D.
      Mamm. Genome 10:764-767(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: BALB/c, C57BL/6J and SPRET/Ei.
      Tissue: Testis.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Cecum.
    3. "Novel CDC2-related protein kinases produced in murine hematopoietic stem cells."
      Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V.
      Gene 124:305-306(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 149-183.
      Strain: CBA.
      Tissue: Bone marrow.
    4. "Identification of new protein kinase genes, similar to kinases of the cdc2 family and expressed in murine hematopoietic stem cells."
      Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V.
      Dokl. Akad. Nauk SSSR 324:893-897(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 149-183.
      Strain: CBA.
      Tissue: Bone marrow.
    5. "Mammalian cells cycle without the D-type cyclin-dependent kinases Cdk4 and Cdk6."
      Malumbres M., Sotillo R., Santamaria D., Galan J., Cerezo A., Ortega S., Dubus P., Barbacid M.
      Cell 118:493-504(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    6. "Changes in motility, gene expression and actin dynamics: Cdk6-induced cytoskeletal changes associated with differentiation in mouse astrocytes."
      Slomiany P., Baker T., Elliott E.R., Grossel M.J.
      J. Cell. Biochem. 99:635-646(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CELL DIFFERENTIATION.
    7. Cited for: FUNCTION IN THYMOCYTE DEVELOPMENT, DISRUPTION PHENOTYPE, MUTAGENESIS OF ARG-31 AND LYS-43.
    8. Cited for: FUNCTION IN NEURON PRODUCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiCDK6_MOUSE
    AccessioniPrimary (citable) accession number: Q64261
    Secondary accession number(s): Q9R1D2, Q9R1D3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: April 30, 2003
    Last modified: October 1, 2014
    This is version 132 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3