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Protein

Cyclin-dependent kinase 6

Gene

CDK6

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

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei43 – 431ATPPROSITE-ProRule annotation
Active sitei145 – 1451Proton acceptor

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi19 – 279ATPPROSITE-ProRule annotation

GO - Molecular functioni

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

GO - Biological processi

  • astrocyte development Source: UniProtKB
  • cell cycle arrest Source: UniProtKB
  • cell dedifferentiation Source: BHF-UCL
  • cell division Source: UniProtKB-KW
  • dentate gyrus development Source: UniProtKB
  • G1/S transition of mitotic cell cycle Source: UniProtKB
  • generation of neurons Source: UniProtKB
  • gliogenesis Source: BHF-UCL
  • hematopoietic stem cell differentiation Source: Ensembl
  • lateral ventricle development Source: UniProtKB
  • mitotic cell cycle Source: Reactome
  • negative regulation of cell cycle Source: UniProtKB
  • negative regulation of cell differentiation Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of cellular senescence Source: UniProtKB
  • negative regulation of epithelial cell proliferation Source: BHF-UCL
  • negative regulation of myeloid cell differentiation Source: UniProtKB
  • negative regulation of osteoblast differentiation Source: BHF-UCL
  • Notch signaling pathway Source: Ensembl
  • positive regulation of cell-matrix adhesion Source: BHF-UCL
  • positive regulation of fibroblast proliferation Source: BHF-UCL
  • positive regulation of gene expression Source: Ensembl
  • protein phosphorylation Source: BHF-UCL
  • regulation of cell motility Source: UniProtKB
  • regulation of erythrocyte differentiation Source: BHF-UCL
  • regulation of gene expression Source: BHF-UCL
  • response to virus Source: UniProtKB
  • T cell differentiation in thymus Source: Ensembl
  • type B pancreatic cell development Source: UniProtKB
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

BRENDAi2.7.11.22. 2681.
ReactomeiREACT_169168. Senescence-Associated Secretory Phenotype (SASP).
REACT_169325. Oncogene Induced Senescence.
REACT_169436. Oxidative Stress Induced Senescence.
REACT_821. Cyclin D associated events in G1.
SignaLinkiQ00534.

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
ProteomesiUP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:1777. CDK6.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • cyclin-dependent protein kinase holoenzyme complex Source: BHF-UCL
  • cytoplasm Source: BHF-UCL
  • cytosol Source: Reactome
  • nucleoplasm Source: HPA
  • nucleus Source: BHF-UCL
  • ruffle Source: BHF-UCL
Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti197 – 1971A → T in MCPH12. 1 Publication
VAR_072638

Keywords - Diseasei

Disease mutation, Primary microcephaly

Organism-specific databases

MIMi612223. phenotype.
616080. phenotype.
Orphaneti2512. Autosomal recessive primary microcephaly.
PharmGKBiPA103.

Polymorphism and mutation databases

BioMutaiCDK6.
DMDMi266423.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 326326Cyclin-dependent kinase 6PRO_0000085789Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine1 Publication
Modified residuei13 – 131Phosphotyrosine1 Publication
Modified residuei24 – 241Phosphotyrosine2 Publications
Modified residuei49 – 491Phosphothreonine1 Publication
Modified residuei70 – 701Phosphothreonine1 Publication
Modified residuei177 – 1771Phosphothreonine1 Publication
Modified residuei264 – 2641N6-acetyllysine1 Publication
Modified residuei325 – 3251Phosphothreonine1 Publication

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ00534.
PaxDbiQ00534.
PeptideAtlasiQ00534.
PRIDEiQ00534.

PTM databases

PhosphoSiteiQ00534.

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

BgeeiQ00534.
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

WithEntry#Exp.IntActNotes
CCND1P243852EBI-295663,EBI-375001
CCND3P302818EBI-295663,EBI-375013
CDC37Q165433EBI-295663,EBI-295634
CDKN2AP4277110EBI-295663,EBI-375053
CDKN2BP427726EBI-295663,EBI-711280
CDKN2CP427739EBI-295663,EBI-711290
CDKN2DP552735EBI-295663,EBI-745859
FOXM1Q08050-12EBI-295663,EBI-866499
HSP90AB1P082382EBI-295663,EBI-352572
RUNX1Q011965EBI-295663,EBI-925904

Protein-protein interaction databases

BioGridi107456. 111 interactions.
DIPiDIP-687N.
IntActiQ00534. 95 interactions.
MINTiMINT-232049.
STRINGi9606.ENSP00000265734.

Structurei

Secondary structure

1
326
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi9 – 113Combined sources
Beta strandi13 – 2210Combined sources
Beta strandi25 – 328Combined sources
Turni33 – 375Combined sources
Beta strandi39 – 4911Combined sources
Helixi58 – 7013Combined sources
Beta strandi79 – 879Combined sources
Beta strandi89 – 9911Combined sources
Beta strandi102 – 1043Combined sources
Helixi105 – 1117Combined sources
Turni113 – 1153Combined sources
Helixi119 – 13820Combined sources
Helixi148 – 1503Combined sources
Beta strandi151 – 1533Combined sources
Beta strandi159 – 1613Combined sources
Helixi172 – 1765Combined sources
Beta strandi180 – 1823Combined sources
Helixi183 – 1853Combined sources
Helixi188 – 1914Combined sources
Helixi199 – 21416Combined sources
Helixi224 – 23512Combined sources
Helixi240 – 2423Combined sources
Beta strandi245 – 2495Combined sources
Helixi251 – 2533Combined sources
Helixi262 – 2643Combined sources
Beta strandi266 – 2683Combined sources
Helixi271 – 28010Combined sources
Turni285 – 2873Combined sources
Helixi291 – 2955Combined sources
Helixi298 – 3003Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliQ00534.
SMRiQ00534. Positions 5-309.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ00534.

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.
GeneTreeiENSGT00790000122973.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ00534.
KOiK02091.
OMAiEDWPQEV.
OrthoDBiEOG73JKVV.
PhylomeDBiQ00534.
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.

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti110 – 1101D → N.1 Publication
Corresponds to variant rs35654944 [ dbSNP | Ensembl ].
VAR_041978
Natural varianti197 – 1971A → T in MCPH12. 1 Publication
VAR_072638
Natural varianti199 – 1991P → L in a metastatic melanoma sample; somatic mutation. 1 Publication
VAR_041979

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_006715835.1.
XP_011514033.1. XM_011515731.1.
UniGeneiHs.119882.

Genome annotation databases

EnsembliENST00000265734; ENSP00000265734; ENSG00000105810.
ENST00000424848; ENSP00000397087; ENSG00000105810.
GeneIDi1021.
KEGGihsa:1021.
UCSCiuc010lez.3. human.

Keywords - Coding sequence diversityi

Polymorphism

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_006715835.1.
XP_011514033.1. XM_011515731.1.
UniGeneiHs.119882.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliQ00534.
SMRiQ00534. Positions 5-309.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107456. 111 interactions.
DIPiDIP-687N.
IntActiQ00534. 95 interactions.
MINTiMINT-232049.
STRINGi9606.ENSP00000265734.

Chemistry

BindingDBiQ00534.
ChEMBLiCHEMBL3301386.
GuidetoPHARMACOLOGYi1978.

PTM databases

PhosphoSiteiQ00534.

Polymorphism and mutation databases

BioMutaiCDK6.
DMDMi266423.

Proteomic databases

MaxQBiQ00534.
PaxDbiQ00534.
PeptideAtlasiQ00534.
PRIDEiQ00534.

Protocols and materials databases

DNASUi1021.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265734; ENSP00000265734; ENSG00000105810.
ENST00000424848; ENSP00000397087; ENSG00000105810.
GeneIDi1021.
KEGGihsa:1021.
UCSCiuc010lez.3. human.

Organism-specific databases

CTDi1021.
GeneCardsiGC07M092234.
GeneReviewsiCDK6.
HGNCiHGNC:1777. CDK6.
HPAiCAB004363.
HPA002637.
MIMi603368. gene.
612223. phenotype.
616080. phenotype.
neXtProtiNX_Q00534.
Orphaneti2512. Autosomal recessive primary microcephaly.
PharmGKBiPA103.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00790000122973.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ00534.
KOiK02091.
OMAiEDWPQEV.
OrthoDBiEOG73JKVV.
PhylomeDBiQ00534.
TreeFamiTF101022.

Enzyme and pathway databases

BRENDAi2.7.11.22. 2681.
ReactomeiREACT_169168. Senescence-Associated Secretory Phenotype (SASP).
REACT_169325. Oncogene Induced Senescence.
REACT_169436. Oxidative Stress Induced Senescence.
REACT_821. Cyclin D associated events in G1.
SignaLinkiQ00534.

Miscellaneous databases

ChiTaRSiCDK6. human.
EvolutionaryTraceiQ00534.
GeneWikiiCyclin-dependent_kinase_6.
GenomeRNAii1021.
NextBioi4291.
PROiQ00534.
SOURCEiSearch...

Gene expression databases

BgeeiQ00534.
CleanExiHS_CDK6.
GenevisibleiQ00534. HS.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A family of human cdc2-related protein kinases."
    Meyerson M., Enders G.H., Wu C.-L., Su L.-K., Gorka C., Nelson C., Harlow E., Tsai L.-H.
    EMBO J. 11:2909-2917(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. NIEHS SNPs program
    Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Tongue.
  4. "The DNA sequence of human chromosome 7."
    Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L.
    , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
    Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "Human chromosome 7: DNA sequence and biology."
    Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S.
    , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
    Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  8. "Identification of G1 kinase activity for cdk6, a novel cyclin D partner."
    Meyerson M., Harlow E.
    Mol. Cell. Biol. 14:2077-2086(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS PRB/RB1 KINASE, TISSUE SPECIFICITY, INTERACTION WITH D-TYPE CYCLINS.
  9. "Active cdk6 complexes are predominantly nuclear and represent only a minority of the cdk6 in T cells."
    Mahony D., Parry D.A., Lees E.
    Oncogene 16:603-611(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH D-TYPE CYCLINS; CDKN2D; HSP90AB1 AND CDC37.
  10. "CDK6 blocks differentiation: coupling cell proliferation to the block to differentiation in leukemic cells."
    Matushansky I., Radparvar F., Skoultchi A.I.
    Oncogene 22:4143-4149(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN DIFFERENTIATION, ENZYME REGULATION.
  11. "Cyclin-dependent kinase 6 inhibits proliferation of human mammary epithelial cells."
    Lucas J.J., Domenico J., Gelfand E.W.
    Mol. Cancer Res. 2:105-114(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CELL PROLIFERATION.
  12. "Bone morphogenetic protein 2-induced osteoblast differentiation requires Smad-mediated down-regulation of Cdk6."
    Ogasawara T., Kawaguchi H., Jinno S., Hoshi K., Itaka K., Takato T., Nakamura K., Okayama H.
    Mol. Cell. Biol. 24:6560-6568(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN DIFFERENTIATION.
  13. "Transforming activity of Fbxo7 is mediated specifically through regulation of cyclin D/cdk6."
    Laman H., Funes J.M., Ye H., Henderson S., Galinanes-Garcia L., Hara E., Knowles P., McDonald N., Boshoff C.
    EMBO J. 24:3104-3116(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FBXO7, SUBCELLULAR LOCATION.
  14. "Preferences for phosphorylation sites in the retinoblastoma protein of D-type cyclin-dependent kinases, Cdk4 and Cdk6, in vitro."
    Takaki T., Fukasawa K., Suzuki-Takahashi I., Semba K., Kitagawa M., Taya Y., Hirai H.
    J. Biochem. 137:381-386(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS PRB/RB1 KINASE.
  15. "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
    Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
    Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-13 AND TYR-24, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  16. "Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection."
    Leong W.F., Chow V.T.
    Cell. Microbiol. 8:565-580(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION, IDENTIFICATION BY MASS SPECTROMETRY.
  17. "Cdk6 blocks myeloid differentiation by interfering with Runx1 DNA binding and Runx1-C/EBPalpha interaction."
    Fujimoto T., Anderson K., Jacobsen S.E., Nishikawa S.I., Nerlov C.
    EMBO J. 26:2361-2370(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN MYELOID DIFFERENTIATION, INTERACTION WITH RUNX1.
  18. "CDK4 and CDK6 delay senescence by kinase-dependent and p16INK4a-independent mechanisms."
    Ruas M., Gregory F., Jones R., Poolman R., Starborg M., Rowe J., Brookes S., Peters G.
    Mol. Cell. Biol. 27:4273-4282(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN SENESCENCE.
  19. "A role for NANOG in G1 to S transition in human embryonic stem cells through direct binding of CDK6 and CDC25A."
    Zhang X., Neganova I., Przyborski S., Yang C., Cooke M., Atkinson S.P., Anyfantis G., Fenyk S., Keith W.N., Hoare S.F., Hughes O., Strachan T., Stojkovic M., Hinds P.W., Armstrong L., Lako M.
    J. Cell Biol. 184:67-82(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY NANOG.
  20. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-24; THR-49; THR-70 AND THR-325, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  21. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  22. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-264, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  23. "Induction of human beta-cell proliferation and engraftment using a single G1/S regulatory molecule, cdk6."
    Fiaschi-Taesch N.M., Salim F., Kleinberger J., Troxell R., Cozar-Castellano I., Selk K., Cherok E., Takane K.K., Scott D.K., Stewart A.F.
    Diabetes 59:1926-1936(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN BETA-CELL PROLIFERATION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  24. Cited for: FUNCTION AS NPM1 KINASE, INTERACTION WITH KSHV V-CYCLIN.
  25. "Beyond the cell cycle: a new role for Cdk6 in differentiation."
    Grossel M.J., Hinds P.W.
    J. Cell. Biochem. 97:485-493(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON CELL DIFFERENTIATION.
  26. "Cell cycle, CDKs and cancer: a changing paradigm."
    Malumbres M., Barbacid M.
    Nat. Rev. Cancer 9:153-166(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON CELL CYCLE CONTROL, INHIBITORS, GENE FAMILY.
  27. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  28. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  29. Cited for: FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN MCPH12, VARIANT MCPH12 THR-197.
  30. "Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a."
    Russo A.A., Tong L., Lee J.O., Jeffrey P.D., Pavletich N.P.
    Nature 395:237-243(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF COMPLEXES WITH INK4A AND INK4D.
  31. "Structural basis of inhibition of CDK-cyclin complexes by INK4 inhibitors."
    Jeffrey P.D., Tong L., Pavletich N.P.
    Genes Dev. 14:3115-3125(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) IN COMPLEX WITH INHIBITOR CDKN2C/P18-INK4C.
  32. "Structural basis for CDK6 activation by a virus-encoded cyclin."
    Schulze-Gahmen U., Kim S.-H.
    Nat. Struct. Biol. 9:177-181(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 1-308 IN COMPLEX WITH HERPESVIRUS SAIMIRI V-CYCLIN/ECLF2, PHOSPHORYLATION AT THR-177.
  33. "Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin."
    Lu H., Chang D.J., Baratte B., Meijer L., Schulze-Gahmen U.
    J. Med. Chem. 48:737-743(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 1-308 IN COMPLEX WITH INHIBITOR.
  34. "Toward understanding the structural basis of cyclin-dependent kinase 6 specific inhibition."
    Lu H., Schulze-Gahmen U.
    J. Med. Chem. 49:3826-3831(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 1-308 IN COMPLEX WITH INHIBITORS AND V-CYCLIN.
  35. Cited for: X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 1-301 IN COMPLEX WITH INHIBITORS.
  36. "Patterns of somatic mutation in human cancer genomes."
    Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASN-110 AND LEU-199.

Entry informationi

Entry nameiCDK6_HUMAN
AccessioniPrimary (citable) accession number: Q00534
Secondary accession number(s): A4D1G0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: July 22, 2015
This is version 172 of the entry and version 1 of the sequence. [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

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.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  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 and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.