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Protein

Cyclin-dependent kinase 6

Gene

Cdk6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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 (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

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

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.

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
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1277162. Cdk6.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198649. 9 interactors.
DIPiDIP-24175N.
IntActiQ64261. 7 interactors.
MINTiMINT-4090464.
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

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0594. Eukaryota.
ENOG410XPP3. LUCA.
GeneTreeiENSGT00830000128256.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ64261.
KOiK02091.
OMAiEDWPQEV.
OrthoDBiEOG091G0I1Q.
PhylomeDBiQ64261.
TreeFamiTF101022.

Family and domain databases

InterProiIPR028788. CDK6.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
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

        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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ64261.
SMRiQ64261.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198649. 9 interactors.
DIPiDIP-24175N.
IntActiQ64261. 7 interactors.
MINTiMINT-4090464.
STRINGi10090.ENSMUSP00000037925.

PTM databases

iPTMnetiQ64261.
PhosphoSitePlusiQ64261.

Proteomic databases

EPDiQ64261.
MaxQBiQ64261.
PaxDbiQ64261.
PRIDEiQ64261.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi1021.
MGIiMGI:1277162. Cdk6.

Phylogenomic databases

eggNOGiKOG0594. Eukaryota.
ENOG410XPP3. LUCA.
GeneTreeiENSGT00830000128256.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ64261.
KOiK02091.
OMAiEDWPQEV.
OrthoDBiEOG091G0I1Q.
PhylomeDBiQ64261.
TreeFamiTF101022.

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.

Miscellaneous databases

PROiQ64261.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000040274.
CleanExiMM_CDK6.
ExpressionAtlasiQ64261. baseline and differential.
GenevisibleiQ64261. MM.

Family and domain databases

InterProiIPR028788. CDK6.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
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]
ProtoNetiSearch...

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: November 30, 2016
This is version 154 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.