CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-010763
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Cyclin-dependent kinase 6 
Protein Synonyms/Alias
 Cell division protein kinase 6; Serine/threonine-protein kinase PLSTIRE 
Gene Name
 CDK6 
Gene Synonyms/Alias
 CDKN6 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
3*****MEKDGLCRADubiquitination[1, 2, 3]
26IGEGAYGKVFKARDLacetylation[3]
26IGEGAYGKVFKARDLubiquitination[1, 2, 3, 4, 5]
29GAYGKVFKARDLKNGubiquitination[2, 3]
43GGRFVALKRVRVQTGacetylation[6]
43GGRFVALKRVRVQTGubiquitination[1, 2]
147RVVHRDLKPQNILVTubiquitination[1, 2, 3, 4, 7, 8]
160VTSSGQIKLADFGLAubiquitination[2, 3]
230SDVDQLGKILDVIGLubiquitination[2, 4, 8]
257PRQAFHSKSAQPIEKubiquitination[1, 2, 3, 4]
264KSAQPIEKFVTDIDEacetylation[6, 9]
264KSAQPIEKFVTDIDEubiquitination[1, 2, 3, 4, 8]
274TDIDELGKDLLLKCLubiquitination[1, 2, 3, 4]
279LGKDLLLKCLTFNPAubiquitination[1, 2, 3]
287CLTFNPAKRISAYSAubiquitination[1, 2, 3]
307FQDLERCKENLDSHLubiquitination[1, 2]
Reference
 [1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [5] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [6] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [7] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [8] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [9] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 13 300 Protein kinase.
 NP_BIND 19 27 ATP (By similarity).
 ACT_SITE 145 145 Proton acceptor.
 BINDING 43 43 ATP (By similarity).
 MOD_RES 13 13 Phosphotyrosine.
 MOD_RES 24 24 Phosphotyrosine.
 MOD_RES 49 49 Phosphothreonine.
 MOD_RES 70 70 Phosphothreonine.
 MOD_RES 177 177 Phosphothreonine.
 MOD_RES 264 264 N6-acetyllysine.
 MOD_RES 325 325 Phosphothreonine.  
Keyword
 3D-structure; Acetylation; ATP-binding; Cell cycle; Cell division; Cell projection; Complete proteome; Cytoplasm; Differentiation; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 326 AA 
Protein Sequence
MEKDGLCRAD QQYECVAEIG EGAYGKVFKA RDLKNGGRFV ALKRVRVQTG EEGMPLSTIR 60
EVAVLRHLET FEHPNVVRLF DVCTVSRTDR ETKLTLVFEH VDQDLTTYLD KVPEPGVPTE 120
TIKDMMFQLL RGLDFLHSHR VVHRDLKPQN ILVTSSGQIK LADFGLARIY SFQMALTSVV 180
VTLWYRAPEV LLQSSYATPV DLWSVGCIFA EMFRRKPLFR GSSDVDQLGK ILDVIGLPGE 240
EDWPRDVALP RQAFHSKSAQ PIEKFVTDID ELGKDLLLKC LTFNPAKRIS AYSALSHPYF 300
QDLERCKENL DSHLPPSQNT SELNTA 326 
Gene Ontology
 GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IDA:BHF-UCL.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005634; C:nucleus; IDA:BHF-UCL.
 GO:0001726; C:ruffle; IDA:BHF-UCL.
 GO:0005524; F:ATP binding; IDA:BHF-UCL.
 GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IDA:BHF-UCL.
 GO:0014002; P:astrocyte development; ISS:UniProtKB.
 GO:0007050; P:cell cycle arrest; TAS:UniProtKB.
 GO:0043697; P:cell dedifferentiation; IMP:BHF-UCL.
 GO:0051301; P:cell division; IEA:UniProtKB-KW.
 GO:0021542; P:dentate gyrus development; ISS:UniProtKB.
 GO:0000080; P:G1 phase of mitotic cell cycle; IEP:BHF-UCL.
 GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:UniProtKB.
 GO:0048699; P:generation of neurons; ISS:UniProtKB.
 GO:0021670; P:lateral ventricle development; ISS:UniProtKB.
 GO:2000773; P:negative regulation of cellular senescence; IDA:UniProtKB.
 GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:BHF-UCL.
 GO:0045638; P:negative regulation of myeloid cell differentiation; IDA:UniProtKB.
 GO:0045668; P:negative regulation of osteoblast differentiation; IDA:BHF-UCL.
 GO:0001954; P:positive regulation of cell-matrix adhesion; IDA:BHF-UCL.
 GO:0048146; P:positive regulation of fibroblast proliferation; IMP:BHF-UCL.
 GO:2000145; P:regulation of cell motility; ISS:UniProtKB.
 GO:0045646; P:regulation of erythrocyte differentiation; IMP:BHF-UCL.
 GO:0010468; P:regulation of gene expression; IDA:BHF-UCL.
 GO:0009615; P:response to virus; IEP:UniProtKB.
 GO:0003323; P:type B pancreatic cell development; IDA:UniProtKB. 
Interpro
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF00069; Pkinase 
SMART
 SM00220; S_TKc 
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS