UniProt Accession

 CDK4_HUMAN; P11802; O00576; Q6FG61 

Genbank Protein ID

 M14505; U81031; Z48970; U37022; AF507942; CR407668; CR542247; AC025165; CH471054; BC003644; BC005864; BC010153; S67448 

Genbank Nucleotide ID

 AAA35673.1; AAC39521.2; CAA88834.1; AAC50506.1; AAM23014.1; CAG28596.1; CAG47043.1; EAW97058.1; AAH03644.1; AAH05864.1; AAH10153.1; AAD13991.1 

Protein Name

 Cyclin-dependent kinase 4 

Protein Synonyms/Alias

 Cell division protein kinase 4; PSK-J3 

Gene Name

 CDK4 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
22	GAYGTVYKARDPHSG	ubiquitination	[1, 2, 3]
35	SGHFVALKSVRVPNG	ubiquitination	[3, 4]
106	DLRTYLDKAPPPGLP	ubiquitination	[1, 3, 5]
118	GLPAETIKDLMRQFL	ubiquitination	[1, 3, 5]
142	CIVHRDLKPENILVT	ubiquitination	[1, 2, 3, 5]
155	VTSGGTVKLADFGLA	ubiquitination	[1, 3]
211	FAEMFRRKPLFCGNS	ubiquitination	[2, 3, 6]
297	LQHSYLHKDEGNPE*	ubiquitination	[3]

Reference

 [1] 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]
 [2] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] 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] 

Functional Description

 Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. 

Sequence Annotation

 DOMAIN 6 295 Protein kinase.
 NP_BIND 12 20 ATP (By similarity).
 REGION 50 56 Required for binding D-type cyclins.
 ACT_SITE 140 140 Proton acceptor (By similarity).
 BINDING 35 35 ATP (By similarity).
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 172 172 Phosphothreonine.  

Keyword

 3D-structure; Acetylation; ATP-binding; Cell cycle; Cell division; Complete proteome; Cytoplasm; Disease mutation; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 303 AA 

Protein Sequence

Gene Ontology

 GO:0000785; C:chromatin; IDA:UniProtKB.
 GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IDA:UniProtKB.
 GO:0005829; C:cytosol; IDA:UniProtKB.
 GO:0031965; C:nuclear membrane; IDA:UniProtKB.
 GO:0005730; C:nucleolus; IDA:UniProtKB.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:Compara.
 GO:0005923; C:tight junction; IEA:Compara.
 GO:0005667; C:transcription factor complex; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IDA:BHF-UCL.
 GO:0051301; P:cell division; IEA:UniProtKB-KW.
 GO:0007623; P:circadian rhythm; IEA:Compara.
 GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:BHF-UCL.
 GO:0031100; P:organ regeneration; IEA:Compara.
 GO:0043065; P:positive regulation of apoptotic process; IEA:Compara.
 GO:0045793; P:positive regulation of cell size; IEA:Compara.
 GO:0048146; P:positive regulation of fibroblast proliferation; IMP:BHF-UCL.
 GO:0045727; P:positive regulation of translation; IEA:Compara.
 GO:0051726; P:regulation of cell cycle; IEA:Compara.
 GO:0010468; P:regulation of gene expression; IMP:BHF-UCL.
 GO:0042493; P:response to drug; IGI:UniProtKB.
 GO:0055093; P:response to hyperoxia; IEA:Compara.
 GO:0010288; P:response to lead ion; IEA:Compara.
 GO:0033574; P:response to testosterone stimulus; IEA:Compara.
 GO:0009636; P:response to toxic substance; IEA:Compara.
 GO:0007165; P:signal transduction; IEA:Compara. 

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