Tclin CDK4 Cyclin-dependent kinase 4

Protein Summary

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. The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. Multiple polyadenylation sites of this gene have been reported. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P11802
• B2R9A0
• B4DNF9
• O00576
• Q6FG61

Gene Name

• CDK4

Ensembl ID

• ENST00000257904
• ENSP00000257904
• ENSG00000135446

Symbol

• CMM3
• PSK-J3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
chemical	1
kinase perturbation	1
interacting protein	0.99
molecular function	0.99
drug perturbation	0.96

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Tyrosine Protein Kinase / Cyclin-dependent Kinase 4

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Cyclin-dependent Kinase 4

DTO Classes

Protein / Kinase / Protein Kinase / Cmgc Group / Cdk Family / Cdk4 Subfamily / Cyclin-dependent Kinase 4

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2941.76   (req: < 5)

Gene RIFs: 356   (req: <= 3)

Antibodies: 995   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2941.76   (req: >= 5)

Gene RIFs: 356   (req: > 3)

Antibodies: 995   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 37

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 526

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 4