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Catalytic Activity
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ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.
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Disruption Phenotype
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Null mutants are viable, but grow more slowly than wild-type cells at 30 degrees Celsius. They are cold- sensitive, failing to grow at 12 degrees Celsius. They display flocculent growth in liquid media and they show abnormal cell morphologies, for example, a significant fraction of the cells are greatly enlarged. Deletion mutant has increased phosphorylation of 'Ser-5' of the CTD repeat during logarithmic growth. Deletion eliminates transient increase in CTD 'Ser-2' phosphorylation observed during diauxic shift. Deletion mutant is synthetically lethal when combined with deletion of DST1 or ELP genes. Deletion mutants are modestly sensitive to the uracil analog 6-azauracil (6AU), which inhibits elongation by depleting nucleotide pools. Deletion mutant is sensitive to the DNA synthesis inhibitor hydroxyurea (HU) and UV irradiation. 'Ser-2' phosphorylation within the CTD repeats is not increased in deletion mutants upon treatment with DNA-damaging agents. {ECO:0000269|PubMed:10488128, ECO:0000269|PubMed:11311553, ECO:0000269|PubMed:12684377, ECO:0000269|PubMed:7565723}.
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Function
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Catalytic subunit of the CTDK-I complex, which hyperphosphorylates the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit. CTDK-I phosphorylates 'Ser-5' if the CTD substrate is not phosphorylated at 'Ser-5', but will phosphorylate 'Ser-2' of a CTD substrate if 'Ser-5' is already phosphorylated. CTDK-I is also more reactive toward substrates that are prephosphorylated at 'Ser-2' or 'Ser-5' compared with an unphosphorylated CTD substrate, therefore efficiently creating doubly phosphorylated CTD repeats. Involved in RNA polymerase II transcriptional elongation, and through PTI1, pre-mRNA 3'-end processing. Participates in both positive and negative regulation of CTD phosphorylation. Required for DNA damage induced transcription, including the expression of the RNR genes, and reprogramming of gene expression upon amino acid starvation. Required for SET2 mediated H3K36 methylation. Also regulates H3K4 methylation. Controls the maintenance of suppressive chromatin in the coding regions of genes by both promoting H3K36 methylation, which leads to histone deacetylation, and catalyzing phosphorylation of the CTD required to localize H3K4 chromatin modification specifically to the 5' ends of genes, thereby creating a boundary for H3K4 methylation that prevents a mark associated with transcriptional initiation from spreading into the bodies of genes. Involved in RNA polymerase I transcription. Involved in telomere maintenance. Acts together with SNF1 to induce GSY2 transcription in response to glucose limitation. Involved in the adaptation to alternative carbon sources, including galactose, glycerol and ethanol, but not raffinose. Required for the integrity of the rDNA locus. Functions in translation elongation by enhancing decoding fidelity. Needed for translational accuracy by phosphorylating RPS2. {ECO:0000269|PubMed:10488128, ECO:0000269|PubMed:12504017, ECO:0000269|PubMed:12629047, ECO:0000269|PubMed:12684377, ECO:0000269|PubMed:15047695, ECO:0000269|PubMed:15161972, ECO:0000269|PubMed:15520468, ECO:0000269|PubMed:16182287, ECO:0000269|PubMed:16984969, ECO:0000269|PubMed:17088384, ECO:0000269|PubMed:17545469, ECO:0000269|PubMed:9110987}.
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Interaction
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P46962:CTK2; NbExp=10; IntAct=EBI-5230, EBI-5236; P46963:CTK3; NbExp=8; IntAct=EBI-5230, EBI-5241;
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Miscellaneous
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Present with 125 molecules/cell in log phase SD medium. {ECO:0000269|PubMed:14562106}.
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Ptm
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Phosphorylated on Thr-338 by CAK1. Phosphorylation is essential for the elevated CTD Ser-2 phosphorylation and required to activate transcription of stationary-phase genes during the diauxic shift. {ECO:0000269|PubMed:15870265}.
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Similarity
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Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
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Similarity
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Contains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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Subcellular Location
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Nucleus, nucleolus. Cytoplasm.
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Subunit
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CTDK-I consists of three subunits, CTK1, CTK2 and CTK3 (also called alpha, beta and gamma). Interacts directly with the CTK2 and CTK3 subunits, this interaction is required for kinase activity. Interacts with RNA polymerase I. Interacts with SNF1, but only at low glucose concentrations. Interacts with translating ribosomes. {ECO:0000269|PubMed:11118453, ECO:0000269|PubMed:15520468, ECO:0000269|PubMed:16182287, ECO:0000269|PubMed:17545469, ECO:0000269|PubMed:7565723}.
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