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Q64261

- CDK6_MOUSE

UniProt

Q64261 - CDK6_MOUSE

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Protein

Cyclin-dependent kinase 6

Gene

Cdk6

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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

GO - Biological processi

  1. cell cycle Source: UniProtKB-KW
  2. cell dedifferentiation Source: Ensembl
  3. cell division Source: UniProtKB-KW
  4. gliogenesis Source: Ensembl
  5. hematopoietic progenitor cell differentiation Source: MGI
  6. hematopoietic stem cell differentiation Source: MGI
  7. hemopoiesis Source: BHF-UCL
  8. negative regulation of cell cycle Source: Ensembl
  9. negative regulation of cellular senescence Source: Ensembl
  10. negative regulation of epithelial cell proliferation Source: Ensembl
  11. negative regulation of myeloid cell differentiation Source: Ensembl
  12. negative regulation of osteoblast differentiation Source: Ensembl
  13. Notch signaling pathway Source: MGI
  14. positive regulation of cell-matrix adhesion Source: Ensembl
  15. positive regulation of fibroblast proliferation Source: Ensembl
  16. positive regulation of gene expression Source: MGI
  17. regulation of erythrocyte differentiation Source: Ensembl
  18. response to virus Source: Ensembl
  19. T cell differentiation in thymus Source: MGI
  20. type B pancreatic cell development Source: Ensembl
Complete GO annotation...

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. cyclin-dependent protein kinase holoenzyme complex Source: Ensembl
  2. cytoplasm Source: UniProtKB-KW
  3. nucleus Source: UniProtKB-KW
  4. ruffle Source: Ensembl
Complete GO annotation...

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

BgeeiQ64261.
CleanExiMM_CDK6.
ExpressionAtlasiQ64261. baseline and differential.
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.
GeneTreeiENSGT00760000119154.
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.
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 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MEKDSLSRAD QQYECVAEIG EGAYGKVFKA RDLKNGGRFV ALKRVRVQTS
60 70 80 90 100
EEGMPLSTIR EVAVLRHLET FEHPNVVRLF DVCTVSRTDR ETKLTLVFEH
110 120 130 140 150
VDQDLTTYLD KVPEPGVPTE TIKDMMFQLL RGLDFLHSHR VVHRDLKPQN
160 170 180 190 200
ILVTSSGQIK LADFGLARIY SFQMALTSVV VTLWYRAPEV LLQSSYATPV
210 220 230 240 250
DLWSVGCIFA EMFRRKPLFR GSSDVDQLGK ILDIIGLPGE EDWPRDVALP
260 270 280 290 300
RQAFHSKSAQ PIEKFVTDID ELGKDLLLKC LTFNPAKRIS AYGALNHPYF
310 320
QDLERYKDNL NSHLPSNQST SELNTA
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 ENSGT00760000119154.
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

Bgeei Q64261.
CleanExi MM_CDK6.
ExpressionAtlasi Q64261. baseline and differential.
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.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 133 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