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

Publication

PubMed ID:
9192850 7652577 8528263 14702039 16541075 15489334 2948189 8221695 9003781 9106657 10580009 15107404 15241418 15558030 16782892 18827403 19413330 19124461 19075005 19487459 19369195 21269460 19237565 19237555 9311594 9425228 17344846