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Protein

Cyclin-dependent kinase 6

Gene

Cdk6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 (By similarity). May play a role in the centrosome organization during the cell cycle phases.By similarity3 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)DescriptionActionsGraphical viewLength
Binding sitei43ATPPROSITE-ProRule annotation1
Active sitei145Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi19 – 27ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle, Cell division, Differentiation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-2559580 Oxidative Stress Induced Senescence
R-MMU-2559582 Senescence-Associated Secretory Phenotype (SASP)
R-MMU-2559585 Oncogene Induced Senescence
R-MMU-69231 Cyclin D associated events in G1
R-MMU-8934593 Regulation of RUNX1 Expression and Activity

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1277162 Cdk6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoskeleton, 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)DescriptionActionsGraphical viewLength
Mutagenesisi31R → C: Enhanced kinase activity. Over-production of thymocytes and hematopoietic stem cells and progenitor cells. 1 Publication1
Mutagenesisi43K → M: Loss of kinase activity. Pronounced reduction in thymocytes and hematopoietic stem cells and progenitor cells. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000857901 – 326Cyclin-dependent kinase 6Add BLAST326

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei13PhosphotyrosineBy similarity1
Modified residuei24PhosphotyrosineBy similarity1
Modified residuei49PhosphothreonineBy similarity1
Modified residuei70PhosphothreonineBy similarity1
Modified residuei177PhosphothreonineBy similarity1
Modified residuei264N6-acetyllysineBy similarity1
Modified residuei319PhosphoserineCombined sources1
Modified residuei325PhosphothreonineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ64261
MaxQBiQ64261
PaxDbiQ64261
PRIDEiQ64261

PTM databases

iPTMnetiQ64261
PhosphoSitePlusiQ64261

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. Expressed in the neuroepithelium of the cerebral cortex of the developing brain.2 Publications

Gene expression databases

BgeeiENSMUSG00000040274
CleanExiMM_CDK6
ExpressionAtlasiQ64261 baseline and differential
GenevisibleiQ64261 MM

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

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198649, 9 interactors
CORUMiQ64261
DIPiDIP-24175N
IntActiQ64261, 7 interactors
MINTiQ64261
STRINGi10090.ENSMUSP00000037925

Structurei

3D structure databases

ProteinModelPortaliQ64261
SMRiQ64261
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 300Protein kinasePROSITE-ProRule annotationAdd BLAST288

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0594 Eukaryota
ENOG410XPP3 LUCA
GeneTreeiENSGT00910000144030
HOGENOMiHOG000233024
HOVERGENiHBG014652
InParanoidiQ64261
KOiK02091
OMAiCIIFEMF
OrthoDBiEOG091G0I1Q
PhylomeDBiQ64261
TreeFamiTF101022

Family and domain databases

CDDicd07862 STKc_CDK6, 1 hit
InterProiView protein in InterPro
IPR028788 CDK6
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequencei

Sequence statusi: Complete.

Q64261-1 [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)DescriptionActionsGraphical viewLength
Natural varianti321S → A in strain: SPRET/Ei. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_009873.3
UniGeneiMm.31672
Mm.389058
Mm.399714

Genome annotation databases

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

Similar proteinsi

Entry informationi

Entry nameiCDK6_MOUSE
AccessioniPrimary (citable) accession number: Q64261
Secondary accession number(s): Q9R1D2, Q9R1D3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: April 30, 2003
Last modified: May 23, 2018
This is version 169 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health