Cdk4
entrez
94201
canonical
uniprot
P35426
canonical
genesymbol
Cdk4
resolver
uniprot_entry
CDK4_RAT
resolver
activity_regulation
ACTIVITY 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 subsequent activation. {ECO:0000250|UniProtKB:P11802}.
uniprot
proteins
amino_acid_sequence
MATTRYEPVAEIGVGAYGTVYKARDPHSGHFVALKSVRVPNGGAAGGGLPVSTVREVALLRRLEAFEHPNVVRLMDVCATSRTDRDIKVTLVFEHIDQDLRTYLDKAPPPGLPVETIKDLMRQFLSGLDFLHANCIVHRDLKPENILVTSNGTVKLADFGLARIYSYQMALTPVVVTLWYRAPEVLLQSTYATPVDMWSVGCIFAEMFRRKPLFCGNSEADQLGKIFDLIGLPPEDDWPREVSLPRGAFSPRGPRPVQSVVPEMEESGAQLLLEMLTFNPLKRISAFRALQHSYLHKEESDPE
uniprot
proteins
ec_number
2.7.11.22
uniprot
proteins
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 (By similarity). {ECO:0000250|UniProtKB:P11802}.
uniprot
proteins
mass_dalton
33799
uniprot
proteins
protein_family
CDC2/CDKX subfamily
uniprot
proteins
protein_family
CMGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
22673903
uniprot
proteins
pubmed
8466525
uniprot
proteins
sequence_length
303
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P11802}. Nucleus {ECO:0000250|UniProtKB:P11802}. Nucleus membrane {ECO:0000250|UniProtKB:P11802}. 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 (By similarity). {ECO:0000250|UniProtKB:P11802}.
uniprot
proteins