Cyclin-dependent kinase 4

Details

Name
Cyclin-dependent kinase 4
Synonyms
  • 2.7.11.22
  • Cell division protein kinase 4
  • PSK-J3
Gene Name
CDK4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0004349|Cyclin-dependent kinase 4
MATSRYEPVAEIGVGAYGTVYKARDPHSGHFVALKSVRVPNGGGGGGGLPISTVREVALL
RRLEAFEHPNVVRLMDVCATSRTDREIKVTLVFEHVDQDLRTYLDKAPPPGLPAETIKDL
MRQFLRGLDFLHANCIVHRDLKPENILVTSGGTVKLADFGLARIYSYQMALTPVVVTLWY
RAPEVLLQSTYATPVDMWSVGCIFAEMFRRKPLFCGNSEADQLGKIFDLIGLPPEDDWPR
DVSLPRGAFPPRGPRPVQSVVPEMEESGAQLLLEMLTFNPHKRISAFRALQHSYLHKDEG
NPE
Number of residues
303
Molecular Weight
33729.55
Theoretical pI
7.01
GO Classification
Functions
ATP binding / cyclin binding / cyclin-dependent protein serine/threonine kinase activity / cyclin-dependent protein serine/threonine kinase regulator activity
Processes
cell division / chromatin organization / circadian rhythm / G1/S transition of mitotic cell cycle / lens development in camera-type eye / mitotic cell cycle / negative regulation of cell cycle arrest / organ regeneration / positive regulation of apoptotic process / positive regulation of cell proliferation / positive regulation of cell size / positive regulation of fibroblast proliferation / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of translation / protein phosphorylation / regulation of gene expression / regulation of protein kinase activity / response to drug / response to hyperoxia / response to lead ion / response to testosterone / response to toxic substance / signal transduction
Components
bicellular tight junction / chromatin / cyclin-dependent protein kinase holoenzyme complex / cytosol / nuclear membrane / nucleolus / nucleoplasm / nucleus / perinuclear region of cytoplasm / transcription factor complex
General Function
Cyclin-dependent protein serine/threonine kinase regulator activity
Specific Function
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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0020596|Cyclin-dependent kinase 4 (CDK4)
ATGGCTACCTCTCGATATGAGCCAGTGGCTGAAATTGGTGTCGGTGCCTATGGGACAGTG
TACAAGGCCCGTGATCCCCACAGTGGCCACTTTGTGGCCCTCAAGAGTGTGAGAGTCCCC
AATGGAGGAGGAGGTGGAGGAGGCCTTCCCATCAGCACAGTTCGTGAGGTGGCTTTACTG
AGGCGACTGGAGGCTTTTGAGCATCCCAATGTTGTCCGGCTGATGGACGTCTGTGCCACA
TCCCGAACTGACCGGGAGATCAAGGTAACCCTGGTGTTTGAGCATGTAGACCAGGACCTA
AGGACATATCTGGACAAGGCACCCCCACCAGGCTTGCCAGCCGAAACGATCAAGGATCTG
ATGCGCCAGTTTCTAAGAGGCCTAGATTTCCTTCATGCCAATTGCATCGTTCACCGAGAT
CTGAAGCCAGAGAACATTCTGGTGACAAGTGGTGGAACAGTCAAGCTGGCTGACTTTGGC
CTGGCCAGAATCTACAGCTACCAGATGGCACTTACACCCGTGGTTGTTACACTCTGGTAC
CGAGCTCCCGAAGTTCTTCTGCAGTCCACATATGCAACACCTGTGGACATGTGGAGTGTT
GGCTGTATCTTTGCAGAGATGTTTCGTCGAAAGCCTCTCTTCTGTGGAAACTCTGAAGCC
GACCAGTTGGGCAAAATCTTTGACCTGATTGGGCTGCCTCCAGAGGATGACTGGCCTCGA
GATGTATCCCTGCCCCGTGGAGCCTTTCCCCCCAGAGGGCCCCGCCCAGTGCAGTCGGTG
GTACCTGAGATGGAGGAGTCGGGAGCACAGCTGCTGCTGGAAATGCTGACTTTTAACCCA
CACAAGCGAATCTCTGCCTTTCGAGCTCTGCAGCACTCTTATCTACATAAGGATGAAGGT
AATCCGGAGTGA
Chromosome Location
12
Locus
12q14
External Identifiers
ResourceLink
UniProtKB IDP11802
UniProtKB Entry NameCDK4_HUMAN
GenBank Protein ID456427
GenBank Gene IDM14505
GenAtlas IDCDK4
HGNC IDHGNC:1773
General References
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  2. Wolfel T, Hauer M, Schneider J, Serrano M, Wolfel C, Klehmann-Hieb E, De Plaen E, Hankeln T, Meyer zum Buschenfelde KH, Beach D: A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science. 1995 Sep 1;269(5228):1281-4. [Article]
  3. Zuo L, Weger J, Yang Q, Goldstein AM, Tucker MA, Walker GJ, Hayward N, Dracopoli NC: Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Nat Genet. 1996 Jan;12(1):97-9. [Article]
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  7. Hanks SK: Homology probing: identification of cDNA clones encoding members of the protein-serine kinase family. Proc Natl Acad Sci U S A. 1987 Jan;84(2):388-92. [Article]
  8. Khatib ZA, Matsushime H, Valentine M, Shapiro DN, Sherr CJ, Look AT: Coamplification of the CDK4 gene with MDM2 and GLI in human sarcomas. Cancer Res. 1993 Nov 15;53(22):5535-41. [Article]
  9. Kitagawa M, Higashi H, Jung HK, Suzuki-Takahashi I, Ikeda M, Tamai K, Kato J, Segawa K, Yoshida E, Nishimura S, Taya Y: The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2. EMBO J. 1996 Dec 16;15(24):7060-9. [Article]
  10. LaBaer J, Garrett MD, Stevenson LF, Slingerland JM, Sandhu C, Chou HS, Fattaey A, Harlow E: New functional activities for the p21 family of CDK inhibitors. Genes Dev. 1997 Apr 1;11(7):847-62. [Article]
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  13. Matsuura I, Denissova NG, Wang G, He D, Long J, Liu F: Cyclin-dependent kinases regulate the antiproliferative function of Smads. Nature. 2004 Jul 8;430(6996):226-31. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB03496Alvocidibexperimental, investigationalunknownDetails
DB02733PurvalanolexperimentalunknownDetails
DB09073Palbociclibapproved, investigationalyesinhibitorDetails
DB11730Ribociclibapproved, investigationalyesantagonistinhibitorDetails
DB12001Abemaciclibapproved, investigationalyesinhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB15442Trilaciclibapproved, investigationalyesinhibitorDetails