Post Translational Modifications | Phosphorylation at Thr-172 is required for enzymatic activity. Phosphorylated, in vitro, at this site by CCNH-CDK7, but, in vivo, appears to be phosphorylated by a proline-directed kinase. In the cyclin D-CDK4-CDKN1B complex, this phosphorylation and consequent CDK4 enzyme activity, is dependent on the tyrosine phosphorylation state of CDKN1B. Thus, in proliferating cells, CDK4 within the complex is phosphorylated on Thr-172 in the T-loop. In resting cells, phosphorylation on Thr-172 is prevented by the non-tyrosine-phosphorylated form of CDKN1B. |
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. |
Protein Name | Cyclin-Dependent Kinase 4Cell Division Protein Kinase 4Psk-J3 |
Database Links | Reactome: R-HSA-187577Reactome: R-HSA-2559580Reactome: R-HSA-2559582Reactome: R-HSA-2559585Reactome: R-HSA-3214858Reactome: R-HSA-381340Reactome: R-HSA-69231Reactome: R-HSA-75815Reactome: R-HSA-8849470Reactome: R-HSA-8878166Reactome: R-HSA-912446Reactome: R-HSA-9616222Reactome: R-HSA-9630791Reactome: R-HSA-9630794Reactome: R-HSA-9632697Reactome: R-HSA-9632700Reactome: R-HSA-9661069Reactome: R-HSA-9754119 |
Cellular Localisation | CytoplasmNucleusNucleus MembraneCytoplasmic When Non-ComplexedForms A Cyclin D-Cdk4 Complex In The Cytoplasm As Cells Progress Through G(1) PhaseThe Complex Accumulates On The Nuclear Membrane And Enters The Nucleus On Transition From G(1) To S PhaseAlso Present In Nucleoli And Heterochromatin LumpsColocalizes With Rb1 After Release Into The Nucleus |
Alternative Antibody Names | Anti-Cyclin-Dependent Kinase 4 antibodyAnti-Cell Division Protein Kinase 4 antibodyAnti-Psk-J3 antibodyAnti-CDK4 antibody |
Information sourced from Uniprot.org