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Protein

Cyclin-dependent kinase 6

Gene

CDK6

Organism
Homo sapiens (Human)
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. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663).10 Publications

Miscellaneous

Over-expressed in some leukemias and malignancies (including sarcoma, glioma, breast tumors, lymphoma and melanoma) as a consequence of nearby translocations.
Enhances beta-cells engraftment in pancreatic islets of Langerhans of diabetic patients.

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Activity regulationi

Inhibited by INK4 proteins (CDKN2C/p18-INK4c), aminopurvalanol, PD0332991, 4-(Pyrazol-4-yl)-pyrimidines and fisetin, a flavonol inhibitor. Activated by Thr-177 phosphorylation and Tyr-24 dephosphorylation (By similarity). Stimulated by cyclin from herpesvirus saimiri (V-cyclin/ECLF2). Rapidly down-regulated prior to cell differentiation (e.g. erythroid and osteoblast).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei43ATPPROSITE-ProRule annotation1
Active sitei145Proton acceptor1

Regions

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

GO - Molecular functioni

  • ATP binding Source: BHF-UCL
  • cyclin binding Source: BHF-UCL
  • cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
  • FBXO family protein binding Source: ParkinsonsUK-UCL

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

BRENDAi2.7.11.22 2681
ReactomeiR-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2559585 Oncogene Induced Senescence
R-HSA-69231 Cyclin D associated events in G1
R-HSA-8934593 Regulation of RUNX1 Expression and Activity
SignaLinkiQ00534
SIGNORiQ00534

Protein family/group databases

MoonDBiQ00534 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase 6 (EC:2.7.11.22)
Alternative name(s):
Cell division protein kinase 6
Serine/threonine-protein kinase PLSTIRE
Gene namesi
Name:CDK6
Synonyms:CDKN6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000105810.9
HGNCiHGNC:1777 CDK6
MIMi603368 gene
neXtProtiNX_Q00534

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

Involvement in diseasei

Microcephaly 12, primary, autosomal recessive (MCPH12)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small.
See also OMIM:616080
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072638197A → T in MCPH12. 1 PublicationCorresponds to variant dbSNP:rs606231255EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Primary microcephaly

Organism-specific databases

DisGeNETi1021
GeneReviewsiCDK6
MalaCardsiCDK6
MIMi612223 phenotype
616080 phenotype
OpenTargetsiENSG00000105810
Orphaneti2512 Autosomal recessive primary microcephaly
PharmGKBiPA103

Chemistry databases

ChEMBLiCHEMBL2508
DrugBankiDB07379 (2S)-2-({6-[(3-amino-5-chlorophenyl)amino]-9-isopropyl-9H-purin-2-yl}amino)-3-methylbutan-1-ol
DB03496 Flavopiridol
DB09073 Palbociclib
DB11730 Ribociclib
GuidetoPHARMACOLOGYi1978

Polymorphism and mutation databases

BioMutaiCDK6
DMDMi266423

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000857891 – 326Cyclin-dependent kinase 6Add BLAST326

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei13PhosphotyrosineCombined sources1
Modified residuei24PhosphotyrosineCombined sources1
Modified residuei49PhosphothreonineCombined sources1
Modified residuei70PhosphothreonineCombined sources1
Modified residuei177Phosphothreonine1 Publication1
Modified residuei264N6-acetyllysineCombined sources1
Modified residuei325PhosphothreonineCombined sources1

Post-translational modificationi

Thr-177 phosphorylation and Tyr-24 dephosphorylation promotes kinase activity.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ00534
MaxQBiQ00534
PaxDbiQ00534
PeptideAtlasiQ00534
PRIDEiQ00534
ProteomicsDBi57851

PTM databases

iPTMnetiQ00534
PhosphoSitePlusiQ00534

Expressioni

Tissue specificityi

Expressed ubiquitously. Accumulates in squamous cell carcinomas, proliferating hematopoietic progenitor cells, beta-cells of pancreatic islets of Langerhans, and neuroblastomas. Reduced levels in differentiating cells.2 Publications

Inductioni

Down-regulated in response to enterovirus 71 (EV71) infection. Induced by NANOG during S-phase entry.2 Publications

Gene expression databases

BgeeiENSG00000105810 Expressed in 208 organ(s), highest expression level in adrenal tissue
CleanExiHS_CDK6
GenevisibleiQ00534 HS

Organism-specific databases

HPAiCAB004363
HPA002637

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. Interacts with Kaposi's sarcoma herpesvirus (KSHV) V-cyclin and herpesvirus saimiri (V-cyclin/ECLF2); the CDK6/V-cyclin complex phosphorylates NPM1 and thus lead to viral reactivation by reducing viral LANA levels.By similarity10 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107456, 126 interactors
ComplexPortaliCPX-2013 Cyclin D3-CDK6 complex
CPX-2014 Cyclin D1-CDK6 complex
CORUMiQ00534
DIPiDIP-687N
IntActiQ00534, 101 interactors
MINTiQ00534
STRINGi9606.ENSP00000265734

Chemistry databases

BindingDBiQ00534

Structurei

Secondary structure

1326
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ00534
SMRiQ00534
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ00534

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
InParanoidiQ00534
KOiK02091
OMAiKRISAYG
OrthoDBiEOG091G0I1Q
PhylomeDBiQ00534
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.

Q00534-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MEKDGLCRAD QQYECVAEIG EGAYGKVFKA RDLKNGGRFV ALKRVRVQTG
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 ILDVIGLPGE EDWPRDVALP
260 270 280 290 300
RQAFHSKSAQ PIEKFVTDID ELGKDLLLKC LTFNPAKRIS AYSALSHPYF
310 320
QDLERCKENL DSHLPPSQNT SELNTA
Length:326
Mass (Da):36,938
Last modified:April 1, 1993 - v1
Checksum:i571733EE6BE7FD4A
GO

Polymorphismi

Genetic variations in CDK6 may influence stature as a quantitative trait, contributing to the stature quantitative trait locus 11 (STQTL11) [MIMi:612223]. Adult height is an easily observable and highly heritable complex continuous trait. Because of this, it is a model trait for studying genetic influence on quantitative traits.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041978110D → N1 PublicationCorresponds to variant dbSNP:rs35654944EnsemblClinVar.1
Natural variantiVAR_072638197A → T in MCPH12. 1 PublicationCorresponds to variant dbSNP:rs606231255EnsemblClinVar.1
Natural variantiVAR_041979199P → L in a metastatic melanoma sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X66365 mRNA Translation: CAA47008.1
AY128534 Genomic DNA Translation: AAM76970.1
AK313491 mRNA Translation: BAG36273.1
AC000065 Genomic DNA No translation available.
AC004128 Genomic DNA No translation available.
AC004011 Genomic DNA No translation available.
CH236949 Genomic DNA Translation: EAL24146.1
CH471091 Genomic DNA Translation: EAW76827.1
BC052264 mRNA Translation: AAH52264.1
CCDSiCCDS5628.1
PIRiS23387
RefSeqiNP_001138778.1, NM_001145306.1
NP_001250.1, NM_001259.6
XP_006715898.1, XM_006715835.2
UniGeneiHs.119882

Genome annotation databases

EnsembliENST00000265734; ENSP00000265734; ENSG00000105810
ENST00000424848; ENSP00000397087; ENSG00000105810
GeneIDi1021
KEGGihsa:1021
UCSCiuc010lez.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X66365 mRNA Translation: CAA47008.1
AY128534 Genomic DNA Translation: AAM76970.1
AK313491 mRNA Translation: BAG36273.1
AC000065 Genomic DNA No translation available.
AC004128 Genomic DNA No translation available.
AC004011 Genomic DNA No translation available.
CH236949 Genomic DNA Translation: EAL24146.1
CH471091 Genomic DNA Translation: EAW76827.1
BC052264 mRNA Translation: AAH52264.1
CCDSiCCDS5628.1
PIRiS23387
RefSeqiNP_001138778.1, NM_001145306.1
NP_001250.1, NM_001259.6
XP_006715898.1, XM_006715835.2
UniGeneiHs.119882

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BI7X-ray3.40A1-326[»]
1BI8X-ray2.80A/C1-326[»]
1BLXX-ray1.90A1-326[»]
1G3NX-ray2.90A/E1-326[»]
1JOWX-ray3.10B1-308[»]
1XO2X-ray2.90B1-308[»]
2EUFX-ray3.00B1-308[»]
2F2CX-ray2.80B1-308[»]
3NUPX-ray2.60A1-301[»]
3NUXX-ray2.70A1-301[»]
4AUAX-ray2.31A1-301[»]
4EZ5X-ray2.70A1-301[»]
4TTHX-ray2.90B1-326[»]
5L2IX-ray2.75A1-301[»]
5L2SX-ray2.27A1-301[»]
5L2TX-ray2.37A1-301[»]
ProteinModelPortaliQ00534
SMRiQ00534
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107456, 126 interactors
ComplexPortaliCPX-2013 Cyclin D3-CDK6 complex
CPX-2014 Cyclin D1-CDK6 complex
CORUMiQ00534
DIPiDIP-687N
IntActiQ00534, 101 interactors
MINTiQ00534
STRINGi9606.ENSP00000265734

Chemistry databases

BindingDBiQ00534
ChEMBLiCHEMBL2508
DrugBankiDB07379 (2S)-2-({6-[(3-amino-5-chlorophenyl)amino]-9-isopropyl-9H-purin-2-yl}amino)-3-methylbutan-1-ol
DB03496 Flavopiridol
DB09073 Palbociclib
DB11730 Ribociclib
GuidetoPHARMACOLOGYi1978

Protein family/group databases

MoonDBiQ00534 Predicted

PTM databases

iPTMnetiQ00534
PhosphoSitePlusiQ00534

Polymorphism and mutation databases

BioMutaiCDK6
DMDMi266423

Proteomic databases

EPDiQ00534
MaxQBiQ00534
PaxDbiQ00534
PeptideAtlasiQ00534
PRIDEiQ00534
ProteomicsDBi57851

Protocols and materials databases

DNASUi1021
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265734; ENSP00000265734; ENSG00000105810
ENST00000424848; ENSP00000397087; ENSG00000105810
GeneIDi1021
KEGGihsa:1021
UCSCiuc010lez.4 human

Organism-specific databases

CTDi1021
DisGeNETi1021
EuPathDBiHostDB:ENSG00000105810.9
GeneCardsiCDK6
GeneReviewsiCDK6
HGNCiHGNC:1777 CDK6
HPAiCAB004363
HPA002637
MalaCardsiCDK6
MIMi603368 gene
612223 phenotype
616080 phenotype
neXtProtiNX_Q00534
OpenTargetsiENSG00000105810
Orphaneti2512 Autosomal recessive primary microcephaly
PharmGKBiPA103
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0594 Eukaryota
ENOG410XPP3 LUCA
GeneTreeiENSGT00910000144030
HOGENOMiHOG000233024
HOVERGENiHBG014652
InParanoidiQ00534
KOiK02091
OMAiKRISAYG
OrthoDBiEOG091G0I1Q
PhylomeDBiQ00534
TreeFamiTF101022

Enzyme and pathway databases

BRENDAi2.7.11.22 2681
ReactomeiR-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2559585 Oncogene Induced Senescence
R-HSA-69231 Cyclin D associated events in G1
R-HSA-8934593 Regulation of RUNX1 Expression and Activity
SignaLinkiQ00534
SIGNORiQ00534

Miscellaneous databases

ChiTaRSiCDK6 human
EvolutionaryTraceiQ00534
GeneWikiiCyclin-dependent_kinase_6
GenomeRNAii1021
PROiPR:Q00534
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105810 Expressed in 208 organ(s), highest expression level in adrenal tissue
CleanExiHS_CDK6
GenevisibleiQ00534 HS

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
ProtoNetiSearch...

Entry informationi

Entry nameiCDK6_HUMAN
AccessioniPrimary (citable) accession number: Q00534
Secondary accession number(s): A4D1G0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: November 7, 2018
This is version 206 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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Main funding by: National Institutes of Health

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