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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]
CDK4, along with its partner CDK6, are key players in cell cycle progression. The complex has been implicated in a number of cancer types, and is the focus of therapeutic research and development. One targeted therapy for CDK inhibition is palbociclib, which may slow the growth of advanced stage breast cancers. It has also been shown, in mouse, that CDK inhibition may sensitize mutant PIK3CA tumors to PI3K inhibitors.
CDK4 (Cyclin Dependent Kinase 4) is a Protein Coding gene. Diseases associated with CDK4 include Melanoma, Cutaneous Malignant 3 and Myeloma, Multiple. Among its related pathways are Cellular Senescence (REACTOME) and Meiosis. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is CDK6.
Cdks (cyclin-dependent kinases) are heteromeric serine/threonine kinases that control progression through the cell cycle in concert with their regulatory subunits, the cyclins. Although there are 12 different cdk genes, only 5 have been shown to directly drive the cell cycle.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004674 | protein serine/threonine kinase activity | IEA | -- |
GO:0004693 | cyclin-dependent protein serine/threonine kinase activity | IDA,TAS | -- |
GO:0005515 | protein binding | IPI | 7568034 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000307 | cyclin-dependent protein kinase holoenzyme complex | IDA | 17420273 |
GO:0000785 | chromatin | IDA | 18827403 |
GO:0005634 | nucleus | IBA,IDA | 16109376 |
GO:0005654 | nucleoplasm | TAS | -- |
GO:0005667 | transcription factor complex | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | CDK-mediated phosphorylation and removal of Cdc6 |
.78
|
|
2 | Glioma |
.50
.46
|
|
3 | Cyclins and Cell Cycle Regulation |
Cyclins and Cell Cycle Regulation
.67
G1-S Phase Transition
.67
Cell Cycle Control by BTG Proteins
.36
|
.31
|
4 | Cellular Senescence (REACTOME) | ||
5 | Cell cycle Role of SCF complex in cell cycle regulation |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000079 | regulation of cyclin-dependent protein serine/threonine kinase activity | IEA | -- |
GO:0000082 | G1/S transition of mitotic cell cycle | IMP | 7603984 |
GO:0002088 | lens development in camera-type eye | IEA | -- |
GO:0006367 | transcription initiation from RNA polymerase II promoter | TAS | -- |
GO:0006468 | protein phosphorylation | IEA,IDA | 8114739 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Palbociclib | Approved, Investigational | Pharma | Target, inhibitor, Inhibition | 204 | ||
Doxorubicin | Approved, Investigational | Pharma | Topo II inhibitor,immunosuppresive antineoplastic antibiotic | 2016 | ||
Paclitaxel | Approved, Vet_approved | Pharma | Tubulin and Bcl2 inhibitor, Taxanes | 3454 | ||
abemaciclib | Approved, Investigational | Pharma | Target, inhibitor | 0 | ||
fostamatinib | Approved, Investigational | Pharma | Target, inhibitor | Kinase Inhibitors | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor | 58-64-0 |
|
||
(R)-CR8 |
|
294646-77-8 |
|
|
||
Arcyriaflavin A |
|
118458-54-1 |
|
|
Compound | Action | Cas Number |
---|---|---|
(R)-CR8 | Dual cdk1/cdk5 inhibitor; also inhibits CK1 | 294646-77-8 |
Arcyriaflavin A | Potent cdk4/cyclin D1 and CaM Kinase II inhibitor. Antiviral agent (anti-HCMV) | 118458-54-1 |
AZD 5438 | Potent cyclin-dependent kinase (cdk) 1, 2 and 9 inhibitor | 602306-29-6 |
Olomoucine | Cyclin-dependent kinase inhibitor | 101622-51-9 |
SU 9516 | Potent cdk2 inhibitor | 377090-84-1 |
Compound | Action | Cas Number |
---|---|---|
[Ala92]-p16 (84-103) | 189064-08-2 | |
AMG 925 | FLT3/CDK4 inhibitor,potent and selective | 1401033-86-0 |
AT7519 | Multi-CDK inhibitor | 844442-38-2 |
BS-181 HCl | CDK7 inhibitor,highly selective | 1397219-81-6 |
CDK4 inhibitor | CDK4/Cyclin D1 inhibitor | 1256963-02-6 |
Flavopiridol hydrochloride | 131740-09-5 | |
LDC000067 | 1073485-20-7 | |
LEE011 | CDK4/6 inhibitor | 1211441-98-3 |
LEE011 hydrochloride | CDK inhibitor | 1211443-80-9 |
LEE011 succinate | CDK inhibitor | 1374639-75-4 |
LEE011 succinate hydrate | CDK inhibitor | 1374639-79-8 |
LY2835219 | CDK4/6 inhibitor,potent and selective | 1231930-82-7 |
LY2835219 free base | CDK inhibitor | 1231929-97-7 |
NSC 625987 | 141992-47-4 | |
P276-00 | CDK-1/CDK4/CDK9 inhibitor | 920113-03-7 |
Palbociclib (PD0332991) Isethionate | CDK4/6 inhibitor,highly selective | 827022-33-3 |
PD 0332991 (Palbociclib) HCl | CDK4/6 inhibitor,highly selective | 827022-32-2 |
PHA-848125 | CDK inhibitor,potent and ATP-competitive | 802539-81-7 |
Purvalanol A | 212844-53-6 | |
Purvalanol B | CDK1/CDK2/CDK4 inhibitor | 212844-54-7 |
R547 | CDK1/2/4 inhibitor,ATP-competitive | 741713-40-6 |
Ryuvidine | 265312-55-8 |
ExUns: | 1a | · | 1b | · | 1c | · | 1d | · | 1e | ^ | 2a | · | 2b | · | 2c | · | 2d | ^ | 3 | ^ | 4a | · | 4b | ^ | 5 | ^ | 6 | ^ | 7a | · | 7b | ^ | 8a | · | 8b | ^ | 9a | · | 9b |
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SP1: | - | - | - | ||||||||||||||||||||||||||||||||||||
SP2: | - | - | - | ||||||||||||||||||||||||||||||||||||
SP3: | - | - | - | - | - | ||||||||||||||||||||||||||||||||||
SP4: | - | - | - | - | - | - | |||||||||||||||||||||||||||||||||
SP5: | - | - | |||||||||||||||||||||||||||||||||||||
SP6: | - | - | - | - | - | - | - | - | - | - | |||||||||||||||||||||||||||||
SP7: | |||||||||||||||||||||||||||||||||||||||
SP8: | - | - | |||||||||||||||||||||||||||||||||||||
SP9: |