CDK4

Protein CDK4 map

Identifiers
cyclin-dependent kinase 4
HUGO:CDK4 HGNC:1773 ENTREZ:1019 UNIPROT:P11802 GENECARDS:CDK4 REACTOME:68329 KEGG:1019 ATLASONC:CDK4ID238ch12q14 WIKI:CDK4

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 Cell cycle  map  / CYCLIND  map

References
The native protein is first correctly folded by HSP90 and CDC37 before being able to bind to the D-type cyclins.
PMID:10385618, PMID:10498883

CDK4@Cytoplasm

References
e_re1276( EMT  map ):
PMID:10197981
PMID:12193595
PMID:16156666
Erk kinases phosphorylate Smad2 and Smad3 at specific sites in the region linking the DNA-binding domain and the transcriptional activation domain.
These sites are separate from the TGFB receptor phosphorylation sites that activate Smad nuclear translocation.
Feedback loop: TGFB activates Ras/Raf/Mek/Erk signaling (PMID:17673906) and Erk reduces TGFB/Smads transcriptional activity.
PMID:15241418
Feedback loop
CDK phosphorylation of Smad3 on Thr8/Thr179/Ser213 inhibits its transcriptional activity and antiproliferative function.
Because cancer cells often contain high levels of CDK activity, diminishing Smad3 activity by CDK phosphorylation may contribute to tumorigenesis and TGFB- resistance in
cancers.

CDK4|​NF_don@Cytoplasm

References
c_re165( Cell cycle  map ):
sequestration of CDK4 to prevent its association with Cyclins D and RB phosphorylation.
PMID:11960696, PMID:8078588, PMID:8741839, PMID:8001816, PMID:8259215
c_re191:( Cell cycle  map ) PMID:10385618, PMID:10498883


Modifications:
In compartment: Cytoplasm
  1. CDK4@Cytoplasm map

  2. CDK4|​NF_don@Cytoplasm map

Participates in complexes:
In compartment: Cytoplasm

  1. CDC37:​CDK4|​NF_don@Cytoplasm map

  2. CDK4:​CyclinD1*:​p21CIP1*@Cytoplasm map

In compartment: Nucleus

  1. CDK4:​CyclinD*@Nucleus map

  2. CDK4:​CyclinD*|​Thr286_pho@Nucleus map
  3. CDK4:​CyclinD*:​p21CIP1*@Nucleus map
  4. CDK4:​CyclinD*:​p27KIP1*@Nucleus map
  5. CDK4|​Thr172_pho:​CyclinD*:​p27KIP1*@Nucleus map

Participates in reactions:
As Reactant or Product:

  1. CDK4|​NF_don@Cytoplasm map + p16INK4A*@Cytoplasm map map c_s763

  2. CDK4|​NF_don@Cytoplasm map + p15INK4B*@Cytoplasm map map c_s762
  3. CDK4:​CyclinD*:​p27KIP1*@Nucleus map map CDK4|​Thr172_pho:​CyclinD*:​p27KIP1*@Nucleus map
  4. c_s761 map CDK4:​CyclinD*@Nucleus map
  5. p27KIP1*@Nucleus map + CDK4:​CyclinD*@Nucleus map map CDK4:​CyclinD*:​p27KIP1*@Nucleus map
  6. CDK4:​CyclinD*@Nucleus map map CDK4:​CyclinD*|​Thr286_pho@Nucleus map
  7. CDK4:​CyclinD*|​Thr286_pho@Nucleus map map c_s757
  8. CDK4|​NF_don@Cytoplasm map + CDC37@Cytoplasm map map CDC37:​CDK4|​NF_don@Cytoplasm map
  9. HSP90*|​hm2@Cytoplasm map + CDC37:​CDK4|​NF_don@Cytoplasm map map CDC37:​HSP90*|​hm2@Cytoplasm map
  10. CDK4@Cytoplasm map + CyclinD*@Cytoplasm map map c_s761
  11. CDC37:​HSP90*|​hm2@Cytoplasm map map CDK4@Cytoplasm map + CDC37:​HSP90*|​hm2@Cytoplasm map
  12. c_s757 map CyclinD*|​Thr286_pho@Cytoplasm map + CDK4@Cytoplasm map
  13. CDK4@Cytoplasm map + p16INK4A*@Cytoplasm map map c_s763
  14. p21CIP1*@Nucleus map + CDK4:​CyclinD*@Nucleus map map CDK4:​CyclinD*:​p21CIP1*@Nucleus map
  15. CDK4_6*@Cytoplasm map map CDK4@Cytoplasm map
  16. CDK2_4*@Cytoplasm map map CDK4@Cytoplasm map
  17. p21CIP1*@Cytoplasm map + CDK4_6*:​CyclinD1*@Cytoplasm map map CDK4:​CyclinD1*:​p21CIP1*@Cytoplasm map

As Catalyser:

  1. DP2*:​E2F4:​SIN3B:​SUV39H1:​p130*@Nucleus map map DP2*:​E2F4:​SIN3B:​SUV39H1:​p130*|​pho@Nucleus map

  2. BAF250*:​DP1*:​E2F1:​RB1|​pho@Nucleus map map HDAC1@Nucleus map + BAF250*:​DP1*:​E2F1:​RB1|​pho|​pho@Nucleus map
  3. DP2*:​E2F4:​p107*@Nucleus map map DP2*:​E2F4:​p107*|​pho@Nucleus map
  4. SMAD3|​S423_pho|​S425_pho@Cytoplasm map map SMAD3|​T179_pho|​S204_pho|​S208_pho|​S213_pho|​S423_pho|​S425_pho@Cytoplasm map

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