Activating Compound | Comment | Organism | Structure |
---|---|---|---|
cyclin A | required for CDK2 activity | Homo sapiens | |
cyclin B | - |
Homo sapiens | |
cyclin D1 | - |
Homo sapiens | |
cyclin D2 | - |
Homo sapiens | |
cyclin D3 | - |
Homo sapiens | |
additional information | substrate phosphorylation by CDK6 with K-cyclin from Kaposi sarcoma herpesvirus, K-cyclin expression in U2OS cells leads to fragmentation of actin stress fibers. CDK-cyclin and CDK-inhibitor-cyclin interaction mutational analysis, overview. Analysis of the inhibitor p27KIP1 docking site on cyclins, overview | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
p27KIP1-cyclin A-CDK2 complex, X-ray diffraction structure determination and analysis | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | generation of single mutations in K-cyclin cluster A and of several truncation mutants of the K-cyclin, overview. Inability to overcome a p16INK4a-dependent cell cycle inhibition in cells expressing each of the K-cyclin mutants resembling cyclin A | Human gammaherpesvirus 8 |
additional information | loss of p27KIP1 (or p21CIP) binding to the mutant cyclin D2-CDK complex. Mutagenesis of the isostructural residues in clusters A and B of the cellular cyclinD2 to resemble those of wild-type Kaposi sarcoma herpesvirus K-cyclin and investigated the impact of these alterations on the activity of the cellular cyclin | Homo sapiens |
T177A | site-directed mutagenesis of CDK6 | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
E2F1 peptide | 81PALGRPPVKRRLDLE95 | Homo sapiens | |
KSLNRPFPDKIPELK | - |
Homo sapiens | |
additional information | CDK-inhibitor-cyclin interaction mutational analysis, overview. Analysis of the inhibitor p27KIP1 docking site on cyclins, overview. Loss of p27KIP1 (or p21CIP) binding to the mutant cyclin D2-CDK complex, but not of p16INK4a | Homo sapiens | |
additional information | docking of CIP/KIP inhibitors and surface region involved, overview | Human gammaherpesvirus 8 | |
p16Ink4a | as recombinant His-tagged protein | Homo sapiens | |
p21CIP | as recombinant GST-tagged protein | Homo sapiens | |
p27Kip1 | as recombinant GST-tagged protein, formation of p27KIP1-cyclin A-CDK2 complex, the inhibitor interacts with both the cyclin and the CDK, analysis of the p27KIP1 docking site on cyclins, overview. p27KIP1 binds to the cyclin in a shallow groove where the hydrophobic amino acids of the MRAIL helix make multiple van der Waals contacts with p27KIP1 | Homo sapiens | |
pRb peptide | 866SNPPKPLKKLRFDIE880 | Homo sapiens | |
RXL motif-containing peptide | addition of this peptide significantly reduces substrate phosphorylation by cyclin E-CDK2 and cyclin D2-CDK6 | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Human gammaherpesvirus 8 | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
U2-OS cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + CALD1 protein | reccombinant human GST-tagged substrate, with CDK6 | Homo sapiens | ADP + CALD1 phosphoprotein | - |
? | |
ATP + RNA polymerase II C-terminal domain | reccombinant GST-tagged substrate | Homo sapiens | ADP + phosphorylated RNA polymerase II C-terminal domain | - |
? | |
ATP + RXL motif-containing peptide | peptide sequence corresponding to amino acids 866-880 of RNA polymerase II C-terminal domain. Substrate phosphorylation by CDK6 with K-cyclin from Kaposi sarcoma herpesvirus, but addition of this peptide significantly reduces substrate phosphorylation by cyclin E-CDK2 and cyclin D2-CDK6 | Homo sapiens | ADP + RXL motif-containing phosphopeptide | - |
? |
Synonyms | Comment | Organism |
---|---|---|
CDK2 | - |
Homo sapiens |
cdk6 | - |
Homo sapiens |
KSHV cyclin | - |
Human gammaherpesvirus 8 |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
evolution | primate herpesviruses, including the oncogenic Kaposi sarcoma herpesvirus, encode cyclinDhomologues. Viral cyclins have diverged from their cellular progenitor in that they elicit holoenzyme activity independent of activating phosphorylation by the CDK-activating kinase and resistant to inhibition by CDK inhibitors | Human gammaherpesvirus 8 |
additional information | amino acids in cluster A and B modulate substrate recognition and specificity. Substrate phosphorylation by CDK6 with K-cyclin from Kaposi sarcoma herpesvirus, K-cyclin expression in U2OS cells leads to fragmentation of actin stress fibers | Homo sapiens |
physiological function | cyclin/cyclin-dependent kinase (CDK) complexes are critical regulators of cellular proliferation. A complex network of regulatory mechanisms has evolved to control their activity, including activating and inactivating phosphorylation of the catalytic CDK subunit and inhibition through specific regulatory proteins, molecular mechanism, overview | Homo sapiens |
physiological function | primate herpesviruses, including the oncogenic Kaposi sarcoma herpesvirus, encode cyclinDhomologues. Viral cyclins have diverged from their cellular progenitor in that they elicit holoenzyme activity independent of activating phosphorylation by the CDK-activating kinase and resistant to inhibition by CDK inhibitors, molecular mechanism, overview | Human gammaherpesvirus 8 |