Q03957 (CTK1_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
CTD kinase subunit alpha
Short name=CTDK-I subunit alpha
EC=2.7.11.23

Alternative name(s):
CTD kinase 58 kDa subunit
CTD kinase subunit 1

Gene names

Name:	CTK1
Ordered Locus Names:	YKL139W

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	528 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.5 Ref.6 Ref.9 Ref.11 Ref.12 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 Ref.21 Ref.22
Catalytic activity	ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.
Subunit structure	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. Ref.4 Ref.8 Ref.16 Ref.18 Ref.21
Subcellular location	Nucleus › nucleolus. Cytoplasm Ref.13 Ref.16.
Post-translational modification	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. Ref.15 Ref.19
Disruption phenotype	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. Ref.4 Ref.6 Ref.7 Ref.11
Miscellaneous	Present with 125 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	DNA damage Protein biosynthesis Stress response Transcription mRNA processing
Cellular component	Cytoplasm Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	mRNA 3'-end processing Inferred from mutant phenotype Ref.9. Source: SGD peptidyl-serine phosphorylation Inferred from direct assay Ref.21. Source: SGD phosphorylation of RNA polymerase II C-terminal domain Inferred from mutant phenotype PubMed 19328068. Source: SGD positive regulation of DNA-dependent transcription, elongation Inferred from direct assay Ref.5. Source: SGD positive regulation of transcription from RNA polymerase I promoter Inferred from mutant phenotype Ref.16. Source: SGD positive regulation of translational fidelity Inferred from mutant phenotype Ref.21. Source: SGD response to DNA damage stimulus Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW translation Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	carboxy-terminal domain protein kinase complex Inferred from physical interaction Ref.4. Source: SGD cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleolus Inferred from direct assay Ref.16. Source: SGD nucleoplasm Inferred from direct assay Ref.16. Source: SGD
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA polymerase II carboxy-terminal domain kinase activity Inferred from electronic annotation. Source: EC cyclin-dependent protein serine/threonine kinase activity Inferred from direct assay Ref.4. Source: SGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CTK2	P46962	10	EBI-5230,EBI-5236
CTK3	P46963	8	EBI-5230,EBI-5241

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 528	528	CTD kinase subunit alpha		PRO_0000085906
Regions
	Domain	183 – 469	287	Protein kinase
	Nucleotide binding	189 – 197	9	ATP By similarity
	Motif	37 – 44	8	Nuclear localization signal Potential
	Compositional bias	506 – 528	23	Asn/Asp-rich
Sites
	Active site	306	1	Proton acceptor By similarity
	Binding site	212	1	ATP By similarity
Amino acid modifications
	Modified residue	14	1	Phosphoserine; by autocatalysis By similarity
	Modified residue	26	1	Phosphoserine Ref.23
	Modified residue	338	1	Phosphothreonine Ref.10 Ref.19 Ref.24
Experimental info
	Mutagenesis	324	1	D → N: Cold-sensitive. Sensitive to hydroxyurea and UV irradiation. Interferes with ATP-binding. Ref.11 Ref.19
	Mutagenesis	338	1	T → A: Cold-sensitive. Abolishes kinase activity. Delayed growth at early stationary phase. Shows no increase in CTD Ser-2 phosphorylation in the transition from rapid growth to stationary phase. Has compromised transcriptional activation of two stationary-phase genes CTT1 and SPI1. Ref.19

Sequences

	Sequence		Length	Mass (Da)
	Q03957 [UniParc]. Last modified October 1, 1993. Version 1. Checksum: 9862EB10FD476F6B	FASTA	528	60,501
	10 20 30 40 50 60 MSYNNGNTYS KSYSRNNKRP LFGKRSPNPQ SLARPPPPKR IRTDSGYQSN MDNISSHRVN 70 80 90 100 110 120 SNDQPGHTKS RGNNNLSRYN DTSFQTSSRY QGSRYNNNNT SYENRPKSIK RDETKAEFLS 130 140 150 160 170 180 HLPKGPKSVE KSRYNNSSNT SNDIKNGYHA SKYYNHKGQE GRSVIAKKVP VSVLTQQRST 190 200 210 220 230 240 SVYLRIMQVG EGTYGKVYKA KNTNTEKLVA LKKLRLQGER EGFPITSIRE IKLLQSFDHP 250 260 270 280 290 300 NVSTIKEIMV ESQKTVYMIF EYADNDLSGL LLNKEVQISH SQCKHLFKQL LLGMEYLHDN 310 320 330 340 350 360 KILHRDVKGS NILIDNQGNL KITDFGLARK MNSRADYTNR VITLWYRPPE LLLGTTNYGT 370 380 390 400 410 420 EVDMWGCGCL LVELFNKTAI FQGSNELEQI ESIFKIMGTP TINSWPTLYD MPWFFMIMPQ 430 440 450 460 470 480 QTTKYVNNFS EKFKSVLPSS KCLQLAINLL CYDQTKRFSA TEALQSDYFK EEPKPEPLVL 490 500 510 520 DGLVSCHEYE VKLARKQKRP NILSTNTNNK GNGNSNNNNN NNNDDDDK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"CTD kinase large subunit is encoded by CTK1, a gene required for normal growth of Saccharomyces cerevisiae." Lee J.M., Greenleaf A.L. Gene Expr. 1:149-167(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Complete DNA sequence of yeast chromosome XI." Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V., Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P., Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L., Daignan-Fornier B., del Rey F., Dion C. , Domdey H., Duesterhoeft A., Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H., Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L., Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M., Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H., Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J., Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H., Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J., Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S., Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F., Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R., Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W., Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M., Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C., Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H., Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L., van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S., von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M., Becker I., Mewes H.-W. Nature 369:371-378(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[3]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[4]	"The yeast carboxyl-terminal repeat domain kinase CTDK-I is a divergent cyclin-cyclin-dependent kinase complex." Sterner D.E., Lee J.M., Hardin S.E., Greenleaf A.L. Mol. Cell. Biol. 15:5716-5724(1995) [PubMed] [Europe PMC] [Abstract] Cited for: CTD KINASE ACTIVITY, SUBUNIT, DISRUPTION PHENOTYPE.
[5]	"Modulation of RNA polymerase II elongation efficiency by C-terminal heptapeptide repeat domain kinase I." Lee J.M., Greenleaf A.L. J. Biol. Chem. 272:10990-10993(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN RNA POLYMERASE II TRANSCRIPTION.
[6]	"Yeast carboxyl-terminal domain kinase I positively and negatively regulates RNA polymerase II carboxyl-terminal domain phosphorylation." Patturajan M., Conrad N.K., Bregman D.B., Corden J.L. J. Biol. Chem. 274:27823-27828(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION REGULATION, DISRUPTION PHENOTYPE.
[7]	"Involvement of yeast carboxy-terminal domain kinase I (CTDK-I) in transcription elongation in vivo." Jona G., Wittschieben B.O., Svejstrup J.Q., Gileadi O. Gene 267:31-36(2001) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[8]	"Activation of the cyclin-dependent kinase CTDK-I requires the heterodimerization of two unstable subunits." Hautbergue G., Goguel V. J. Biol. Chem. 276:8005-8013(2001) [PubMed] [Europe PMC] [Abstract] Cited for: ACTIVATION, INTERACTION WITH CTK2 AND CTK3.
[9]	"The RNA polymerase II CTD kinase CTDK-I affects pre-mRNA 3' cleavage/polyadenylation through the processing component Pti1p." Skaar D.A., Greenleaf A.L. Mol. Cell 10:1429-1439(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PRE-MRNA END PROCESSING.
[10]	"Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae." Ficarro S.B., McCleland M.L., Stukenberg P.T., Burke D.J., Ross M.M., Shabanowitz J., Hunt D.F., White F.M. Nat. Biotechnol. 20:301-305(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-338, MASS SPECTROMETRY. Strain: 2124.
[11]	"Budding yeast CTDK-I is required for DNA damage-induced transcription." Ostapenko D., Solomon M.J. Eukaryot. Cell 2:274-283(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASP-324, DISRUPTION PHENOTYPE.
[12]	"Phosphorylation of RNA polymerase II CTD regulates H3 methylation in yeast." Xiao T., Hall H., Kizer K.O., Shibata Y., Hall M.C., Borchers C.H., Strahl B.D. Genes Dev. 17:654-663(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN H3K36 METHYLATION.
[13]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[14]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[15]	"C-terminal repeat domain kinase I phosphorylates Ser2 and Ser5 of RNA polymerase II C-terminal domain repeats." Jones J.C., Phatnani H.P., Haystead T.A., MacDonald J.A., Alam S.M., Greenleaf A.L. J. Biol. Chem. 279:24957-24964(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE CTDK-I COMPLEX IN PHOSPHORYLATION.
[16]	"CTD kinase I is involved in RNA polymerase I transcription." Bouchoux C., Hautbergue G., Grenetier S., Carles C., Riva M., Goguel V. Nucleic Acids Res. 32:5851-5860(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN RNA POLYMERASE I TRANSCRIPTION, INTERACTION WITH RNA POLYMERASE I, SUBCELLULAR LOCATION.
[17]	"A genome-wide screen for Saccharomyces cerevisiae deletion mutants that affect telomere length." Askree S.H., Yehuda T., Smolikov S., Gurevich R., Hawk J., Coker C., Krauskopf A., Kupiec M., McEachern M.J. Proc. Natl. Acad. Sci. U.S.A. 101:8658-8663(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN TELOMERE MAINTENANCE.
[18]	"Glucose deprivation mediates interaction between CTDK-I and Snf1 in Saccharomyces cerevisiae." Van Driessche B., Coddens S., Van Mullem V., Vandenhaute J. FEBS Lett. 579:5318-5324(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN RESPONSE TO GLUCOSE LIMITATION, INTERACTION WITH SNF1.
[19]	"Phosphorylation by Cak1 regulates the C-terminal domain kinase Ctk1 in Saccharomyces cerevisiae." Ostapenko D., Solomon M.J. Mol. Cell. Biol. 25:3906-3913(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-338 BY CAK1, MUTAGENESIS OF ASP-324 AND THR-338.
[20]	"CTD kinase I is required for the integrity of the rDNA tandem array." Grenetier S., Bouchoux C., Goguel V. Nucleic Acids Res. 34:4996-5006(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[21]	"The RNA polymerase II CTD kinase Ctk1 functions in translation elongation." Roether S., Straesser K. Genes Dev. 21:1409-1421(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN TRANSLATION, INTERACTION WITH RIBOSOMES.
[22]	"The RNA polymerase II kinase Ctk1 regulates positioning of a 5' histone methylation boundary along genes." Xiao T., Shibata Y., Rao B., Laribee R.N., O'Rourke R., Buck M.J., Greenblatt J.F., Krogan N.J., Lieb J.D., Strahl B.D. Mol. Cell. Biol. 27:721-731(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN H3K4 METHYLATION.
[23]	"Analysis of phosphorylation sites on proteins from Saccharomyces cerevisiae by electron transfer dissociation (ETD) mass spectrometry." Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L., Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F. Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26, MASS SPECTROMETRY.
[24]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-338, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M69024 Genomic DNA. Translation: AAC41642.1. Z28139 Genomic DNA. Translation: CAA81980.1. BK006944 Genomic DNA. Translation: DAA09023.1.
PIR	S32593.
RefSeq	NP_012783.1. NM_001179705.1.
3D structure databases
ProteinModelPortal	Q03957.
SMR	Q03957. Positions 181-478.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-6631N.
IntAct	Q03957. 31 interactions.
MINT	MINT-636105.
STRING	4932.YKL139W.
Proteomic databases
PaxDb	Q03957.
PeptideAtlas	Q03957.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YKL139W; YKL139W; YKL139W.
GeneID	853718.
KEGG	sce:YKL139W.
Organism-specific databases
CYGD	YKL139w.
SGD	S000001622. CTK1.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00690000102025.
HOGENOM	HOG000233024.
KO	K00916.
OMA	HTDQHNN.
OrthoDB	EOG4TF3V4.
Enzyme and pathway databases
BRENDA	2.7.11.22. 984.
Gene expression databases
Genevestigator	Q03957.
GermOnline	YKL139W. Saccharomyces cerevisiae.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	974737.

Entry information

Entry name

CTK1_YEAST

Accession

Primary (citable) accession number: Q03957
Secondary accession number(s): D6VX57

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	October 1, 1993
Last modified:	May 1, 2013
This is version 130 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program