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The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. This kinase is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression and G1/S transition. The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. Altered expression of this gene has been observed in multiple human cancers. A mutation in this gene resulting in reduced cell proliferation, and impaired cell motility and polarity, and has been identified in patients with primary microcephaly. [provided by RefSeq, Aug 2017]
CDK6, along with its partner CDK4, 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.
CDK6 (Cyclin Dependent Kinase 6) is a Protein Coding gene. Diseases associated with CDK6 include Microcephaly 12, Primary, Autosomal Recessive and Primary Autosomal Recessive Microcephaly. Among its related pathways are C-MYB transcription factor network and Small cell lung cancer. 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 CDK4.
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 | 8114739 |
GO:0005515 | protein binding | IPI | 8001816 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000307 | cyclin-dependent protein kinase holoenzyme complex | IDA | 17420273 |
GO:0001726 | ruffle | IDA | 10205165 |
GO:0005634 | nucleus | IBA,IDA | 14985467 |
GO:0005654 | nucleoplasm | TAS | -- |
GO:0005737 | cytoplasm | IEA,IDA | 14985467 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Glioma |
.49
|
.46
|
2 | Cyclins and Cell Cycle Regulation |
Cyclins and Cell Cycle Regulation
.67
G1-S Phase Transition
.67
|
.31
|
3 | Cellular Senescence (REACTOME) | ||
4 | Measles |
.35
|
.33
|
5 | DNA Damage Response |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000082 | G1/S transition of mitotic cell cycle | TAS | 16294322 |
GO:0000122 | negative regulation of transcription by RNA polymerase II | IEA | -- |
GO:0001954 | positive regulation of cell-matrix adhesion | IDA | 10205165 |
GO:0002244 | hematopoietic progenitor cell differentiation | IEA | -- |
GO:0003323 | type B pancreatic cell development | IDA | 20668294 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Palbociclib | Approved, Investigational | Pharma | Target, inhibitor, Inhibition | 229 | ||
Tamoxifen | Approved | Pharma | Agonist, Antagonist | TGF-β modulatory and PKC inhibitory effects, ER antagonist, Anti-Estrogens | 451 | |
abemaciclib | Approved, Investigational | Pharma | Target, inhibitor | 0 | ||
ribociclib | Approved, Investigational | Pharma | Target, antagonist, inhibitor | 0 | ||
Anastrozole | Approved, Investigational | Pharma | Aromatase inhibitor, Potent aromatase (CYP19) inhibitor, Aromatase Inhibitors, Hormone therapy | 337 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 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 |
---|---|---|
AT7519 | Multi-CDK inhibitor | 844442-38-2 |
BS-181 HCl | CDK7 inhibitor,highly selective | 1397219-81-6 |
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 |
LY2835219 | CDK4/6 inhibitor,potent and selective | 1231930-82-7 |
LY2835219 free base | CDK inhibitor | 1231929-97-7 |
Palbociclib (PD0332991) Isethionate | CDK4/6 inhibitor,highly selective | 827022-33-3 |
PD 0332991 (Palbociclib) HCl | CDK4/6 inhibitor,highly selective | 827022-32-2 |
This gene was present in the common ancestor of animals and fungi.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | CDK6 30 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | CDK6 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | CDK6 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | CDK6 30 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | CDK6 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Cdk6 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Cdk6 30 17 |
|
||
E030030I06Rik 31 |
|
OneToOne | |||
Chicken (Gallus gallus) |
Aves | CDK6 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | CDK6 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | cdk6 30 |
|
||
Str.20309 30 |
|
||||
Zebrafish (Danio rerio) |
Actinopterygii | cdk6 30 31 |
|
OneToOne | |
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP005817 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | Cdk4 30 31 32 |
|
OneToMany | |
Worm (Caenorhabditis elegans) |
Secernentea | cdk-4 30 31 32 |
|
ManyToMany | |
F52B5.2 31 |
|
ManyToMany | |||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | CDC28 31 |
|
OneToMany | |
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 07 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
712006 | Likely Benign: not provided | 92,833,258(-) | G/A | SYNONYMOUS_VARIANT | |
712661 | Likely Benign: not provided | 92,615,176(-) | C/T | SYNONYMOUS_VARIANT | |
717291 | Likely Benign: not provided | 92,671,485(-) | G/A | SYNONYMOUS_VARIANT | |
719802 | Likely Benign: not provided | 92,671,527(-) | C/T | SYNONYMOUS_VARIANT | |
723240 | Likely Benign: not provided | 92,774,771(-) | A/G | SYNONYMOUS_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv2762687 | CNV | loss | 21179565 |
esv3576407 | CNV | gain | 25503493 |
esv3614146 | CNV | loss | 21293372 |
esv3614148 | CNV | gain | 21293372 |
esv3614149 | CNV | loss | 21293372 |
nsv1074529 | CNV | deletion | 25765185 |
nsv1133666 | CNV | deletion | 24896259 |
nsv473626 | CNV | novel sequence insertion | 20440878 |
nsv516592 | CNV | gain+loss | 19592680 |
nsv819408 | CNV | gain | 19587683 |
nsv831062 | CNV | gain | 17160897 |
Disorder | Aliases | PubMed IDs |
---|---|---|
microcephaly 12, primary, autosomal recessive |
|
|
primary autosomal recessive microcephaly |
|
|
kaposi sarcoma |
|
|
primary microcephaly |
|
|
stature quantitative trait locus 11 |
|
|