Q64261 · CDK6_MOUSE
- ProteinCyclin-dependent kinase 6
- GeneCdk6
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids326 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and negatively regulates cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans (By similarity).
May play a role in the centrosome organization during the cell cycle phases
May play a role in the centrosome organization during the cell cycle phases
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Activity regulation
Activated by Thr-177 phosphorylation and Tyr-24 dephosphorylation (By similarity).
Rapidly down-regulated prior to cell differentiation (e.g. erythroid and osteoblast) (By similarity).
Rapidly down-regulated prior to cell differentiation (e.g. erythroid and osteoblast) (By similarity).
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCyclin-dependent kinase 6
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ64261
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localized to the ruffling edge of spreading fibroblasts. Kinase activity only in nucleus (By similarity).
Present in the cytosol and in the nucleus in interphase cells and at the centrosome during mitosis from prophase to telophase (By similarity).
Localized to the cytosol of neurons and showed prominent staining around either side of the nucleus
Present in the cytosol and in the nucleus in interphase cells and at the centrosome during mitosis from prophase to telophase (By similarity).
Localized to the cytosol of neurons and showed prominent staining around either side of the nucleus
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Slight anemia and defective proliferation of some hematopoietic cells, thymocytes and progenitor cells. Females are reduced in size and often sterile. Prevents the expansion of neuronally committed precursors by prematurely exiting the cell cycle and lengthening G1 phase duration, reducing concomitantly the production of newborn neurons.
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 31 | Enhanced kinase activity. Over-production of thymocytes and hematopoietic stem cells and progenitor cells. | ||||
Sequence: R → C | ||||||
Mutagenesis | 43 | Loss of kinase activity. Pronounced reduction in thymocytes and hematopoietic stem cells and progenitor cells. | ||||
Sequence: K → M | ||||||
Natural variant | 321 | in strain: SPRET/Ei | ||||
Sequence: S → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 39 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Modified residue | 1 | N-acetylmethionine | ||||
Sequence: M | ||||||
Chain | PRO_0000085790 | 1-326 | Cyclin-dependent kinase 6 | |||
Sequence: MEKDSLSRADQQYECVAEIGEGAYGKVFKARDLKNGGRFVALKRVRVQTSEEGMPLSTIREVAVLRHLETFEHPNVVRLFDVCTVSRTDRETKLTLVFEHVDQDLTTYLDKVPEPGVPTETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARIYSFQMALTSVVVTLWYRAPEVLLQSSYATPVDLWSVGCIFAEMFRRKPLFRGSSDVDQLGKILDIIGLPGEEDWPRDVALPRQAFHSKSAQPIEKFVTDIDELGKDLLLKCLTFNPAKRISAYGALNHPYFQDLERYKDNLNSHLPSNQSTSELNTA | ||||||
Modified residue | 13 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 24 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 49 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 70 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 177 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 264 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 319 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 325 | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
Thr-177 phosphorylation and Tyr-24 dephosphorylation promotes kinase activity.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ) of the lateral ventricles whose neural precursor cells (NPC) give rise to dentate granule neurons and olfactory bulb (OB) interneurons, respectively. Expressed in the neuroepithelium of the cerebral cortex of the developing brain.
Gene expression databases
Interaction
Subunit
Interaction with D-type G1 cyclins. Cyclin binding promotes enzyme activation by phosphorylation at Thr-177 (By similarity).
Binds to RUNX1, CDKN2D, FBXO7 and CDKN2C/p18-INK4c. Forms a cytoplasmic complex with Hsp90/HSP90AB1 and CDC37. FBXO7-binding promotes D-type cyclin binding (By similarity).
Binds to RUNX1, CDKN2D, FBXO7 and CDKN2C/p18-INK4c. Forms a cytoplasmic complex with Hsp90/HSP90AB1 and CDC37. FBXO7-binding promotes D-type cyclin binding (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q64261 | Ccnd3 P30282 | 2 | EBI-847380, EBI-847337 | |
BINARY | Q64261 | Jun P05627 | 2 | EBI-847380, EBI-764369 | |
BINARY | Q64261 | Stat3 P42227 | 3 | EBI-847380, EBI-602878 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 13-300 | Protein kinase | ||||
Sequence: YECVAEIGEGAYGKVFKARDLKNGGRFVALKRVRVQTSEEGMPLSTIREVAVLRHLETFEHPNVVRLFDVCTVSRTDRETKLTLVFEHVDQDLTTYLDKVPEPGVPTETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARIYSFQMALTSVVVTLWYRAPEVLLQSSYATPVDLWSVGCIFAEMFRRKPLFRGSSDVDQLGKILDIIGLPGEEDWPRDVALPRQAFHSKSAQPIEKFVTDIDELGKDLLLKCLTFNPAKRISAYGALNHPYF |
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length326
- Mass (Da)37,028
- Last updated2003-04-30 v2
- Checksum127B7ECFFC54C3AC
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0G2JGA8 | A0A0G2JGA8_MOUSE | Cdk6 | 82 | ||
A0A0G2JGH2 | A0A0G2JGH2_MOUSE | Cdk6 | 29 | ||
A0A0G2JEJ6 | A0A0G2JEJ6_MOUSE | Cdk6 | 23 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF132483 EMBL· GenBank· DDBJ | AAD43504.1 EMBL· GenBank· DDBJ | mRNA | ||
AF132482 EMBL· GenBank· DDBJ | AAD43503.1 EMBL· GenBank· DDBJ | mRNA | ||
AK078973 EMBL· GenBank· DDBJ | BAC37489.1 EMBL· GenBank· DDBJ | mRNA | ||
X65068 EMBL· GenBank· DDBJ | CAA46201.1 EMBL· GenBank· DDBJ | mRNA |