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Literature summary for 2.7.11.23 extracted from

  • Bartkowiak, B.; Liu, P.; Phatnani, H.P.; Fuda, N.J.; Cooper, J.J.; Price, D.H.; Adelman, K.; Lis, J.T.; Greenleaf, A.L.
    CDK12 is a transcription elongation-associated CTD kinase, the metazoan ortholog of yeast Ctk1 (2010), Genes Dev., 24, 2303-2316.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
dCDK12, recombinant expression of the His-tagged chimeric mutant Ctk1/12 kinase in Saccharomyces cerevisiae strain FY23 Drosophila melanogaster
hCDK12, recombinant expression of the His-tagged chimeric mutant Ctk1/12 kinase in Saccharomyces cerevisiae strain FY23 Homo sapiens
hCDK13, recombinant expression of the His-tagged chimeric mutant Ctk1/13 kinase in Saccharomyces cerevisiae strain FY23 Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information RNAi knockdown of dCDK12 in S2 cells. Chimeric yeast/human versions of Ctk1 containing the kinase homology domains of hCDK12/13 (or hCDK9) are functional in yeast cells (and also in vitro) Drosophila melanogaster
additional information RNAi knockdown of hCDK12 in HeLa cells. Chimeric yeast/human versions of Ctk1 containing the kinase homology domains of hCDK12/13 (or hCDK9) are functional in yeast cells (and also in vitro). siRNA knockdown of hCDK12 in HeLa cells results in alterations in the CTD phosphorylation state Homo sapiens
additional information RNAi knockdown of hCDK13 in HeLa cells. chimeric yeast/human versions of Ctk1 containing the kinase homology domains of hCDK12/13 (or hCDK9) are functional in yeast cells (and also in vitro) Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
chromatin
-
Homo sapiens 785
-
chromatin dCDK12 is present on the transcribed regions of active genes. dCDK12 amounts are lower at the 5' end and higher in the middle and at the 3 end of genes (both normalized to RNAPII) Drosophila melanogaster 785
-
chromatin distribution of hCDK12 on chromosomes, overview Homo sapiens 785
-
additional information distribution of dCDK12 and hyperphosphorylated RNAPII (Pol II0) on Dm polytene chromosomes by fluorescence microscopy. The dCDK12 kinase appears to be closely associated with Pol II0, not only at loci expressed normally during development, but also at heat-shock loci Drosophila melanogaster
-
-
nucleus
-
Homo sapiens 5634
-
nucleus
-
Drosophila melanogaster 5634
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens
Mg2+ required Drosophila melanogaster

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + [DNA-directed RNA polymerase] Homo sapiens
-
ADP + phospho-[DNA-directed RNA polymerase]
-
?
ATP + [DNA-directed RNA polymerase] Drosophila melanogaster Ser2 phosphorylation by dCDK12 in the C-terminal repeat domain, CTD ADP + phospho-[DNA-directed RNA polymerase]
-
?

Organism

Organism UniProt Comment Textmining
Drosophila melanogaster Q9VP22
-
-
Homo sapiens Q14004
-
-
Homo sapiens Q9NYV4
-
-

Purification (Commentary)

Purification (Comment) Organism
native hCDK13 from nuclear extracts of HeLa cells by Ion exchange chromatography and affinity chromatography, recombinant His-tagged chimeric mutant Ctk1/13 kinase from Saccharomyces cerevisiae strain FY23 by cation exchange chromatography and nickel affinity chromatography Homo sapiens
recombinant His-tagged chimeric mutant Ctk1/12 kinase from Saccharomyces cerevisiae strain FY23 by cation exchange chromatography and nickel affinity chromatography Drosophila melanogaster
recombinant His-tagged chimeric mutant Ctk1/12 kinase from Saccharomyces cerevisiae strain FY23 by cation exchange chromatographyand nickel affinity chromatography Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
HeLa cell
-
Homo sapiens
-
S2 cell
-
Drosophila melanogaster
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + GST-tagged yCTD fusion protein hCDK13 purified from nuclear extracts displays CTD kinase activity in vitro with recombinant GST-tagged yeast CTD fusion proteins as substrate, hyperphosphorylation of the CTD by hCDK13 kinase Homo sapiens ?
-
?
ATP + [DNA-directed RNA polymerase]
-
Homo sapiens ADP + phospho-[DNA-directed RNA polymerase]
-
?
ATP + [DNA-directed RNA polymerase] Ser2 phosphorylation by dCDK12 in the C-terminal repeat domain, CTD Drosophila melanogaster ADP + phospho-[DNA-directed RNA polymerase]
-
?
ATP + [DNA-directed RNA polymerase] Ser phosphorylation in the C-terminal repeat domain, CTD Homo sapiens ADP + phospho-[DNA-directed RNA polymerase]
-
?
additional information Drosophila CDK12 manifests CTD kinase activity in vitro Drosophila melanogaster ?
-
?

Subunits

Subunits Comment Organism
More cyclin K is associated with purified dCDK12, implicating it as the cyclin subunit of this CTD kinase Drosophila melanogaster

Synonyms

Synonyms Comment Organism
CG7597
-
Drosophila melanogaster
CTD kinase
-
Homo sapiens
CTD kinase
-
Drosophila melanogaster
dCDK12
-
Homo sapiens
dCDK12
-
Drosophila melanogaster
dCDK13
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
Homo sapiens
ATP
-
Drosophila melanogaster
additional information cyclin K is associated with purified dCDK12, implicating it as the cyclin subunit of this CTD kinase Drosophila melanogaster

General Information

General Information Comment Organism
evolution the human orthologue of Saccharomyces cerevisiae Ctk1 is one or both of the isozyme pair, hCDK12-hCDK13 Homo sapiens
evolution the metazoan orthologue of Saccharomyces cerevisiae Ctk1 in Drosophila melanogaster is dCDK12 Drosophila melanogaster
malfunction RNAi knockdown of dCDK12 in S2 cells alters the phosphorylation state of the CTD, reducing its Ser2 phosphorylation levels Drosophila melanogaster
metabolism the majority of Ser2 phosphorylation on productively elongating RNAPII in Saccharomyces cerevisiae appears to be catalyzed by CTDK-I, a three-subunit enzyme consisting of Ctk1 (a CDK homologue), Ctk2 (a cyclin homologue), and Ctk3 Drosophila melanogaster