Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Cyclin-dependent kinase 6  

UniProtKB / Swiss-Prot ID :  CDK6_HUMAN

Gene Name (Synonyms) : 
CDK6, CDKN6  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Cytoplasm. Nucleus. Cell projection, ruffle. Note=Localized to the ruffling edge of spreading fibroblasts. Kinase activity only in nucleus. 

Protein 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. 

Protein Sequence MEKDGLCRADQQYECVAEIGEGAYGKVFKARDLKNGGRFVALKRVRVQTGEEGMPLSTIREVAVLRHLET...
Predicted Secondary Structure CCCCCCCCCCCCEEEEEEEECCCCEEEEEEEEECCCCEEEEEEEECCCCCCCCHHHHHHHHHHHHHHHCC...
Protein Variant
LocationDescription
110D -> N (in dbSNP:rs35654944). VAR_041978
199P -> L (in a metastatic melanoma sample;somatic mutation).
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
13PhosphotyrosineADQQYECVA
CCCCEEEEE
12.98HPRD
Link
13PhosphotyrosineADQQYECVA
CCCCEEEEE
12.98PhosphoELM
Link
13PhosphotyrosineADQQYECVA
CCCCEEEEE
12.98Phosphositeplus
Link
13Phosphotyrosine.ADQQYECVA
CCCCEEEEE
12.98UniProtKB
Link
24PhosphotyrosineGEGAYGKVF
ECCCCEEEE
28.47HPRD
Link
24PhosphotyrosineGEGAYGKVF
ECCCCEEEE
28.47PhosphoELM
Link
24PhosphotyrosineGEGAYGKVF
ECCCCEEEE
28.47Phosphositeplus
Link
24Phosphotyrosine.GEGAYGKVF
ECCCCEEEE
28.47UniProtKB
Link
26Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)GAYGKVFKA
CCCEEEEEE
31.64Phosphositeplus
Link
43N6-acetyllysineFVALKRVRV
EEEEEEECC
38.83HPRD
Link
43N6-acetyllysineFVALKRVRV
EEEEEEECC
38.83Phosphositeplus
Link
43N6-acetyllysine.FVALKRVRV
EEEEEEECC
38.83UniProtKB
Link
49PhosphothreonineVRVQTGEEG
ECCCCCCCC
43.64Phosphositeplus
Link-
49Phosphothreonine.VRVQTGEEG
ECCCCCCCC
43.64UniProtKB
Link-
57PhosphoserineGMPLSTIRE
CHHHHHHHH
18.87Phosphositeplus
Link-
57Phosphoserine.GMPLSTIRE
CHHHHHHHH
18.87UniProtKB
Link-
70PhosphothreonineRHLETFEHP
HHHCCCCCC
40.46Phosphositeplus
Link-
70Phosphothreonine.RHLETFEHP
HHHCCCCCC
40.46UniProtKB
Link-
86PhosphoserineVCTVSRTDR
EEECCCCCC
16.00Phosphositeplus
Link
86Phosphoserine.VCTVSRTDR
EEECCCCCC
16.00UniProtKB
Link
147Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)HRDLKPQNI
EEECCCCCE
49.17Phosphositeplus
Link
154Phosphothreonine.NILVTSSGQ
CEEECCCCC
17.46UniProtKB
Link
155PhosphoserineILVTSSGQI
EEECCCCCE
25.62Phosphositeplus
Link
155Phosphoserine.ILVTSSGQI
EEECCCCCE
25.62UniProtKB
Link
177PhosphothreonineQMALTSVVV
CCEEEEEEE
15.22Phosphositeplus
Link
177Phosphothreonine.QMALTSVVV
CCEEEEEEE
15.22UniProtKB
Link
223PhosphoserineFRGSSDVDQ
CCCCCHHHH
44.47Phosphositeplus
Link
223Phosphoserine.FRGSSDVDQ
CCCCCHHHH
44.47UniProtKB
Link
230Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)DQLGKILDV
HHHHHHHHH
49.00Phosphositeplus
Link
257Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)AFHSKSAQP
HCCCCCCCC
41.04Phosphositeplus
Link
264Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)QPIEKFVTD
CCHHHHCCC
45.94Phosphositeplus
Link
264N6-acetyllysineQPIEKFVTD
CCHHHHCCC
45.94HPRD
Link
264N6-acetyllysineQPIEKFVTD
CCHHHHCCC
45.94Phosphositeplus
Link
264N6-acetyllysine.QPIEKFVTD
CCHHHHCCC
45.94UniProtKB
Link
274Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)DELGKDLLL
CHHHHHHHH
58.80Phosphositeplus
Link
290Phosphoserine.AKRISAYSA
CCCCCHHHH
25.78UniProtKB
Link
317Phosphoserine.HLPPSQNTS
CCCCCCCCC
33.84UniProtKB
Link-
325PhosphothreonineSELNTA
CCCCCC
46.50Phosphositeplus
Link-
325Phosphothreonine.SELNTA
CCCCCC
46.50UniProtKB
Link-
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
CCND1_HUMANphysical interactionMINT-50434MINT15232106
CD2A1_HUMANphysical interactionMINT-25084MINT9751050
MCM2_HUMANphysical interactionMINT-50420MINT15232106
RUNX1_HUMANphysical interactionMINT-4791064MINT17431401
RUNX1_HUMANphysical interactionMINT-4791100MINT17431401
MCM10_HUMANphysical interactionMINT-50419MINT15232106
Q96TE0_HUMANphysical interactionDIP:553EDIP8822197
RB_HUMANphysical interactionDIP:554EDIP8822197
CCND1_HUMANphysical interaction
direct interaction
direct interaction
EBI-1255333
EBI-768466
EBI-37
intact17517622
14681455
15232106
CCND3_HUMANphysical interaction
direct interaction
direct interaction
EBI-1255333
EBI-768433
EBI-37
intact17517622
14681455
15232106
CD2A1_HUMANphysical interaction
physical interaction
physical interaction
physical interaction
physical interaction
direct interaction
direct interac
EBI-1542776
EBI-1542753
EBI-1
intact17909018
17909018
17909018
17909018
17909018
9751050
15232106
ATX1_HUMANphysical interactionEBI-955438
intact16713569
CDC37_HUMANphysical interaction
physical interaction
EBI-295662
EBI-295678
intact9150368
9150368
MCM2_HUMANin vitroHPRD:04533HPRD15232106
CCND2_HUMANin vitroHPRD:04533HPRD11358847
CCND3_HUMANin vitro
in vivo
HPRD:04533HPRD8114739
11360184
15232106
PCNA_HUMANin vivoHPRD:04533HPRD9667749
CCND1_HUMANin vitro
in vivo
HPRD:04533HPRD11739795
15232106
CDN2D_HUMANin vitroHPRD:04533HPRD9751050
9751051
CD2A2_HUMANin vitroHPRD:04533HPRD9751050
CDK6_HUMANin vitroHPRD:04533HPRD11124804
CDN1A_HUMANin vitroHPRD:04533HPRD15232106
TGFR1_HUMANin vivoHPRD:04533HPRD15761153
ATX1_HUMANyeast 2-hybridHPRD:04533HPRD16713569
CDC37_HUMANENSP00000265734STRING
CCND1_HUMANENSP00000265734STRING
CDN1B_HUMANENSP00000265734STRING
CDN1A_HUMANENSP00000265734STRING
CDK4_HUMANENSP00000265734STRING
CCND2_HUMANENSP00000265734STRING
RBL2_HUMANENSP00000265734STRING
CDN2C_HUMANENSP00000265734STRING
MCM2_HUMANENSP00000265734STRING
RB_HUMANENSP00000265734STRING
CDN2B_HUMANENSP00000265734STRING
MPIP1_HUMANENSP00000265734STRING
MCM10_HUMANENSP00000265734STRING
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Disease Reference
Kegg disease
OMIM disease
616080Microcephaly 12, primary, autosomal recessive (MCPH12)
Drug Reference
There are no disease associations of PTM sites.
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Related Literatures of Post-Translational Modification
Acetylation
ReferencePubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions.";
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.;
Science 325:834-840(2009).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-43 AND LYS-264, AND MASSSPECTROMETRY.
Phosphorylation
ReferencePubMed
"Immunoaffinity profiling of tyrosine phosphorylation in cancercells.";
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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-13 AND TYR-24, AND MASSSPECTROMETRY.
"Large-scale proteomics analysis of the human kinome.";
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.;
Mol. Cell. Proteomics 8:1751-1764(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-24; THR-49; SER-57;THR-70; SER-86; THR-154; SER-155; SER-223; SER-290; SER-317 ANDTHR-325, AND MASS SPECTROMETRY.
"Structural basis for CDK6 activation by a virus-encoded cyclin.";
Schulze-Gahmen U., Kim S.-H.;
Nat. Struct. Biol. 9:177-181(2002).
Cited for: X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 1-308 IN COMPLEX WITHHERPESVIRUS SAIMIRI VCYCLIN/ECLF2, AND PHOSPHORYLATION AT THR-177.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures