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Q64261 (CDK6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Cdk6
Synonyms:Cdkn6, Crk2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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.6 Ref.7 Ref.8

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

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.

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 By similarity.

Subcellular location

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.

Tissue specificity

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. Ref.8

Post-translational modification

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

Disruption phenotype

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. Ref.5 Ref.7 Ref.8

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
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNotch signaling pathway

Inferred from direct assay Ref.7. Source: MGI

T cell differentiation in thymus

Inferred from mutant phenotype Ref.7. Source: MGI

cell dedifferentiation

Inferred from electronic annotation. Source: InterPro

cell division

Inferred from electronic annotation. Source: UniProtKB-KW

hematopoietic progenitor cell differentiation

Inferred from mutant phenotype Ref.7. Source: MGI

hematopoietic stem cell differentiation

Inferred from mutant phenotype Ref.7. Source: MGI

hemopoiesis

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

positive regulation of gene expression

Inferred from direct assay Ref.7. Source: MGI

regulation of cell proliferation

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

ruffle

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

cyclin-dependent protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

kinase activity

Inferred from direct assay Ref.7. Source: MGI

protein binding

Inferred from physical interaction PubMed 23079656PubMed 23948297. Source: IntAct

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 326326Cyclin-dependent kinase 6
PRO_0000085790

Regions

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

Sites

Active site1451Proton acceptor By similarity
Binding site431ATP By similarity

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue131Phosphotyrosine By similarity
Modified residue241Phosphotyrosine By similarity
Modified residue491Phosphothreonine By similarity
Modified residue701Phosphothreonine By similarity
Modified residue1771Phosphothreonine By similarity
Modified residue2641N6-acetyllysine By similarity
Modified residue3251Phosphothreonine By similarity

Natural variations

Natural variant3211S → A in strain: SPRET/Ei.

Experimental info

Mutagenesis311R → C: Enhanced kinase activity. Over-production of thymocytes and hematopoietic stem cells and progenitor cells. Ref.7
Mutagenesis431K → M: Loss of kinase activity. Pronounced reduction in thymocytes and hematopoietic stem cells and progenitor cells. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Q64261 [UniParc].

Last modified April 30, 2003. Version 2.
Checksum: 127B7ECFFC54C3AC

FASTA32637,028
        10         20         30         40         50         60 
MEKDSLSRAD QQYECVAEIG EGAYGKVFKA RDLKNGGRFV ALKRVRVQTS 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 ILDIIGLPGE 

       250        260        270        280        290        300 
EDWPRDVALP RQAFHSKSAQ PIEKFVTDID ELGKDLLLKC LTFNPAKRIS AYGALNHPYF 

       310        320 
QDLERYKDNL NSHLPSNQST SELNTA 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"CDK6 kinase activity is required for thymocyte development."
Hu M.G., Deshpande A., Schlichting N., Hinds E.A., Mao C., Dose M., Hu G.F., Van Etten R.A., Gounari F., Hinds P.W.
Blood 117:6120-6131(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THYMOCYTE DEVELOPMENT, DISRUPTION PHENOTYPE, MUTAGENESIS OF ARG-31 AND LYS-43.
[8]"Cdk6-dependent regulation of G(1) length controls adult neurogenesis."
Beukelaers P., Vandenbosch R., Caron N., Nguyen L., Belachew S., Moonen G., Kiyokawa H., Barbacid M., Santamaria D., Malgrange B.
Stem Cells 29:713-724(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN NEURON PRODUCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF132483 mRNA. Translation: AAD43504.1.
AF132482 mRNA. Translation: AAD43503.1.
AK078973 mRNA. Translation: BAC37489.1.
X65068 mRNA. Translation: CAA46201.1.
CCDSCCDS19062.1.
PIRPN0483.
RefSeqNP_034003.1. NM_009873.2.
XP_006503606.1. XM_006503543.1.
UniGeneMm.31672.
Mm.389058.
Mm.399714.

3D structure databases

ProteinModelPortalQ64261.
SMRQ64261. Positions 9-301.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198649. 10 interactions.
DIPDIP-24175N.
IntActQ64261. 7 interactions.
MINTMINT-4090464.

PTM databases

PhosphoSiteQ64261.

Proteomic databases

MaxQBQ64261.
PaxDbQ64261.
PRIDEQ64261.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000042410; ENSMUSP00000037925; ENSMUSG00000040274.
ENSMUST00000165117; ENSMUSP00000126024; ENSMUSG00000040274.
GeneID12571.
KEGGmmu:12571.
UCSCuc008wgu.1. mouse.

Organism-specific databases

CTD1021.
MGIMGI:1277162. Cdk6.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00720000108415.
HOGENOMHOG000233024.
HOVERGENHBG014652.
InParanoidQ64261.
KOK02091.
OMAFHSKSPQ.
OrthoDBEOG73JKVV.
PhylomeDBQ64261.
TreeFamTF101022.

Gene expression databases

ArrayExpressQ64261.
BgeeQ64261.
CleanExMM_CDK6.
GenevestigatorQ64261.

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

NextBio281678.
PROQ64261.
SOURCESearch...

Entry information

Entry nameCDK6_MOUSE
AccessionPrimary (citable) accession number: Q64261
Secondary accession number(s): Q9R1D2, Q9R1D3
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: April 30, 2003
Last modified: July 9, 2014
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot