CDK4 - Cyclin-dependent kinase 4 - human protein (Function)
 
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CDK4 »  Cyclin-dependent kinase 4   [ EC 2.7.11.22 ]
 
Protein also known as:  Cell division protein kinase 4.
Gene name:  CDK4
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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.  
3
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Cyclin bindingdefinition[GO:0030332]  
1
  • IPIUniProtKB
Cyclin-dependent protein serine/threonine kinase activitydefinition[GO:0004693]  
1
  • IDABHF-UCL
Protein bindingdefinition[GO:0005515]  
31
  • IPIIntAct
  • IPIUniProtKB
  • IPIBHF-UCL
Protein complex bindingdefinition[GO:0032403] silver  
  • IEAOrtholog Compara
GO biological process 
Cell divisiondefinition[GO:0051301]  
  • IEAUniProtKB KW
Circadian rhythmdefinition[GO:0007623] silver  
  • IEAOrtholog Compara
G1/S transition of mitotic cell cycledefinition[GO:0000082]  
1
  • IMPBHF-UCL
Negative regulation of cell cycle arrestdefinition[GO:0071157]  
1
  • IDAUniProtKB
Organ regenerationdefinition[GO:0031100] silver  
  • IEAOrtholog Compara
Positive regulation of apoptotic processdefinition[GO:0043065] silver  
  • IEAOrtholog Compara
Positive regulation of cell proliferationdefinition[GO:0008284]  
1
  • IMPBHF-UCL
Positive regulation of cell sizedefinition[GO:0045793] silver  
  • IEAOrtholog Compara
Positive regulation of fibroblast proliferationdefinition[GO:0048146]  
1
  • IMPBHF-UCL
Positive regulation of G2/M transition of mitotic cell cycledefinition[GO:0010971]  
1
  • IDAUniProtKB
Positive regulation of translationdefinition[GO:0045727] silver  
  • IEAOrtholog Compara
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDABHF-UCL
Regulation of gene expressiondefinition[GO:0010468]  
1
  • IMPBHF-UCL
Response to drugdefinition[GO:0042493]  
1
  • IGIUniProtKB
Response to hyperoxiadefinition[GO:0055093] silver  
  • IEAOrtholog Compara
Response to lead iondefinition[GO:0010288] silver  
  • IEAOrtholog Compara
Response to testosteronedefinition[GO:0033574] silver  
  • IEAOrtholog Compara
Response to toxic substancedefinition[GO:0009636] silver  
  • IEAOrtholog Compara
Signal transductiondefinition[GO:0007165] silver  
  • IEAOrtholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.22: ATP + a protein ADP + a phosphoprotein.  
3
  • CuratedUniProtKB
It is regulated in the following manner
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.  
1
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Bladder cancer  hsa05219+1019  
Cell cycle  hsa04110+1019  
Chronic myeloid leukemia  hsa05220+1019  
Glioma  hsa05214+1019  
HTLV-I infection  hsa05166+1019  
Measles  hsa05162+1019  
Melanoma  hsa05218+1019  
Non-small cell lung cancer  hsa05223+1019  
p53 signaling pathway  hsa04115+1019  
Pancreatic cancer  hsa05212+1019  
Pathways in cancer  hsa05200+1019  
Small cell lung cancer  hsa05222+1019  
T cell receptor signaling pathway  hsa04660+1019  
Tight junction  hsa04530+1019  
According to Reactome, this protein belongs to the following pathways:
Cell Cycle  REACT_115566  
Cellular responses to stress  REACT_120956  
Meiosis  REACT_111183  
 

Keywords

Biological process 
Cell cycle  definition   [KW-0131]
Cell division  definition   [KW-0132]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Cyclin-dependent_kinase_4
GenomeRNAi: 1019
PRO: PR:P11802
Chemistry
GuidetoPHARMACOLOGY: 1976