Names & Taxonomy
- Uniprot ID:
- P11802
- Entry Name:
- CDK4_HUMAN
- Status:
- reviewed
- Protein Names:
- Cyclin-dependent kinase 4 (EC 2.7.11.22) (Cell division protein kinase 4) (PSK-J3)
- Gene Names:
- CDK4
- Gene Names Primary:
- CDK4
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 303
- Sequence:
- MATSRYEPVAEIGVGAYGTVYKARDPHSGHFVALKSVRVPNGGGGGGGLPISTVREVALLRRLEAFEHPNVVRLMDVCATSRTDREIKVTLVFEHVDQDLRTYLDKAPPPGLPAETIKDLMRQFLRGLDFLHANCIVHRDLKPENILVTSGGTVKLADFGLARIYSYQMALTPVVVTLWYRAPEVLLQSTYATPVDMWSVGCIFAEMFRRKPLFCGNSEADQLGKIFDLIGLPPEDDWPRDVSLPRGAFPPRGPRPVQSVVPEMEESGAQLLLEMLTFNPHKRISAFRALQHSYLHKDEGNPE
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cytoplasm. Nucleus. Membrane. Note=Cytoplasmic when non-complexed. Forms a cyclin D-CDK4 complex in the cytoplasm as cells progress through G(1) phase. The complex accumulates on the nuclear membrane and enters the nucleus on transition from G(1) to S phase. Also present in nucleoli and heterochromatin lumps. Colocalizes with RB1 after release into the nucleus.
Function
- 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.
- Catalytic Activity:
- ATP + a protein = ADP + a phosphoprotein.
- Enzyme Regulation:
- ENZYME REGULATION: Both phosphorylation at Thr-172 and binding of a D-type cyclin are necessary for enzymatic activity. Full activation of the cyclin-D-CDK4 complex appears to require other factors such as recruitment of the substrate via a substrate recruitment motif, and/or formation of the CDKN1B ternary complex. Inhibited by INK4 family members. In resting cells, the non-tyrosine-phosphorylated form of CDKN1B prevents phosphorylation at Thr-172 and inactivation, while, in proliferating cells, tyrosine phosphorylation of CDKN1B allows phosphorylation of Thr-172 of CDK4 and subsequennt activation.
- Active Site:
- ACT_SITE 140 140 Proton acceptor.
- Cross Reference Drug Bank:
- DB09073
- Gene Ontology Go:
- bicellular tight junction
chromatin
cyclin-dependent protein kinase holoenzyme complex
cytosol
nuclear membrane
nucleolus
nucleoplasm
nucleus
perinuclear region of cytoplasm
transcription factor complex
ATP binding
cyclin binding
cyclin-dependent protein serine/threonine kinase activity
cyclin-dependent protein serine/threonine kinase regulator activity
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 - Gene Ontology Biological Process:
- 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 - Gene Ontology Molecular Function:
- ATP binding
cyclin binding
cyclin-dependent protein serine/threonine kinase activity
cyclin-dependent protein serine/threonine kinase regulator activity - Gene Ontology Cellular Component:
- bicellular tight junction
chromatin
cyclin-dependent protein kinase holoenzyme complex
cytosol
nuclear membrane
nucleolus
nucleoplasm
nucleus
perinuclear region of cytoplasm
transcription factor complex - Keywords:
- 3D-structure
ATP-binding
Acetylation
Alternative splicing
Cell cycle
Cell division
Complete proteome
Cytoplasm
Disease mutation
Kinase
Membrane
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Transferase - Interacts With:
- P24385; P30281; Q16543; P38936; P46527; P42771; P42772; P42773; P55273; Q9UJC3; P08238; P01106; P28749; Q8N720