P06242 (KIN28_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase KIN28
EC=2.7.11.23

Gene names

Name:	KIN28
Ordered Locus Names:	YDL108W
ORF Names:	D2330

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	306 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalytic component of the TFIIK complex (KIN28-CCL1 dimer) which is the protein kinase component of transcription factor IIH (TFIIH) and phosphorylates the C-terminal domain of RNA polymerase II during transition from transcription to elongation after preinitiation complex (PIC) formation, thereby positively regulating transcription. TFIIH (or factor B) is essential for both basal and activated transcription, and is involved in nucleotide excision repair (NER) of damaged DNA. TFIIH has DNA-dependent ATPase activity and is essential for polymerase II transcription in vitro. Essential for cell proliferation. Ref.10
Catalytic activity	ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.
Subunit structure	CCL1 and KIN28 form the TFIIK complex, a component of the TFIIH holo complex. Component of a complex consisting of KIN28, CCL1 and TFB3. Interacts with TFB3. Also interacts with HNT1 and HOG1. Ref.5 Ref.6 Ref.9 Ref.11 Ref.12
Subcellular location	Nucleus Ref.13.
Post-translational modification	Phosphorylation of Thr-162 regulates the affinity of interaction between CCL1, KIN28 and TFB3. Thr-162 phosphorylation does not vary through the cell cycle and is necessary for full kinase activity.
Miscellaneous	Present with 4400 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	Cell cycle Cell division Transcription Transcription regulation
Cellular component	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	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW phosphorylation of RNA polymerase II C-terminal domain involved in recruitment of 3'-end processing factors to RNA polymerase II holoenzyme complex Inferred from mutant phenotype Ref.10. Source: SGD phosphorylation of RNA polymerase II C-terminal domain serine 5 residues involved in recruitment of mRNA capping enzyme to RNA polymerase II holoenzyme complex Inferred from mutant phenotype Ref.10PubMed 19666497. Source: SGD positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 14749387. Source: SGD transcription from RNA polymerase I promoter Inferred from mutant phenotype PubMed 12015980. Source: SGD transcription from RNA polymerase II promoter Inferred from direct assay PubMed 19818408. Source: SGD
Cellular_component	TFIIK complex Inferred from direct assay Ref.11PubMed 19818408. Source: SGD
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA polymerase II carboxy-terminal domain kinase activity Inferred from direct assay PubMed 7760796PubMed 9702190. Source: SGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CCL1	P37366	6	EBI-9691,EBI-4385

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 306	306	Serine/threonine-protein kinase KIN28		PRO_0000086132
Regions
	Domain	7 – 290	284	Protein kinase
	Nucleotide binding	13 – 21	9	ATP By similarity
Sites
	Active site	129	1	Proton acceptor By similarity
	Binding site	36	1	ATP By similarity
Amino acid modifications
	Modified residue	162	1	Phosphothreonine; by CAK Ref.7 Ref.8 Ref.11 Ref.15 Ref.16 Ref.17
	Modified residue	167	1	Phosphothreonine Ref.17
Experimental info
	Mutagenesis	17 – 18	2	TY → AF: No effect on phosphorylation; no effect on kinase activity. Ref.11
	Mutagenesis	17	1	T → D: Slow growth. Ref.11
	Mutagenesis	17	1	T → E, Q or V: Normal growth. Ref.11
	Mutagenesis	36	1	K → A: Slow growth. Ref.11
	Mutagenesis	54	1	E → Q: Non-viable. Ref.11
	Mutagenesis	147	1	D → N: Abolishes kinase activity. Ref.8 Ref.11
	Mutagenesis	162	1	T → A: Diminishes phosphorylation; 75-80% loss in kinase activity; no effect on survival. Ref.7 Ref.8 Ref.11
	Mutagenesis	162	1	T → S, D or E: No effect on kinase activity. Ref.7 Ref.8 Ref.11
	Mutagenesis	163	1	S → A: Normal growth. Ref.11

Sequences

	Sequence		Length	Mass (Da)
	P06242 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: 763A5720A1D9ACF3	FASTA	306	35,247
	10 20 30 40 50 60 MKVNMEYTKE KKVGEGTYAV VYLGCQHSTG RKIAIKEIKT SEFKDGLDMS AIREVKYLQE 70 80 90 100 110 120 MQHPNVIELI DIFMAYDNLN LVLEFLPTDL EVVIKDKSIL FTPADIKAWM LMTLRGVYHC 130 140 150 160 170 180 HRNFILHRDL KPNNLLFSPD GQIKVADFGL ARAIPAPHEI LTSNVVTRWY RAPELLFGAK 190 200 210 220 230 240 HYTSAIDIWS VGVIFAELML RIPYLPGQND VDQMEVTFRA LGTPTDRDWP EVSSFMTYNK 250 260 270 280 290 300 LQIYPPPSRD ELRKRFIAAS EYALDFMCGM LTMNPQKRWT AVQCLESDYF KELPPPSDPS SIKIRN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"KIN28, a yeast split gene coding for a putative protein kinase homologous to CDC28." Simon M., Seraphin B., Faye G. EMBO J. 5:2697-2701(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The sequence of a 20.3 kb DNA fragment from the left arm of Saccharomyces cerevisiae chromosome IV contains the KIN28, MSS2, PHO2, POL3 and DUN1 genes, and six new open reading frames." Saiz J.E., Buitrago M.J., Garcia R., Revuelta J.L., del Rey F. Yeast 12:1077-1084(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[3]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome IV." Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G., Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C., Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F., Delaveau T. , del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M., Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T., Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C., Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S., Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L., Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H., Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M., Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M., Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A., Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G., Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E., Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S., Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D., Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V., Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E., Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M., Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D., Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X., Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A., Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T., Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L., Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E., Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L., Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M., Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K., Mewes H.-W., Zollner A., Zaccaria P. Nature 387:75-78(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[4]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[5]	"The kin28 protein kinase is associated with a cyclin in Saccharomyces cerevisiae." Valay J.G., Simon M., Faye G. J. Mol. Biol. 234:307-310(1993) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CCL1.
[6]	"Genes for Tfb2, Tfb3, and Tfb4 subunits of yeast transcription/repair factor IIH. Homology to human cyclin-dependent kinase activating kinase and IIH subunits." Feaver W.J., Henry N.L., Wang Z., Wu X., Svejstrup J.Q., Bushnell D.A., Friedberg E.C., Kornberg R.D. J. Biol. Chem. 272:19319-19327(1997) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, INTERACTION WITH TFB3. Strain: DBY2019.
[7]	"Cak1 is required for Kin28 phosphorylation and activation in vivo." Espinoza F.H., Farrell A., Nourse J.L., Chamberlin H.M., Gileadi O., Morgan D.O. Mol. Cell. Biol. 18:6365-6373(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-162, MUTAGENESIS OF THR-162.
[8]	"Activating phosphorylation of the Kin28p subunit of yeast TFIIH by Cak1p." Kimmelman J., Kaldis P., Hengartner C.J., Laff G.M., Koh S.S., Young R.A., Solomon M.J. Mol. Cell. Biol. 19:4774-4787(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-162, MUTAGENESIS OF ASP-147; 17-THR-TYR-18 AND THR-162.
[9]	"Interactions of Cdk7 and Kin28 with Hint/PKCI-1 and Hnt1 histidine triad proteins." Korsisaari N., Makela T.P. J. Biol. Chem. 275:34837-34840(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HNT1.
[10]	"Kin28, the TFIIH-associated carboxy-terminal domain kinase, facilitates the recruitment of mRNA processing machinery to RNA polymerase II." Rodriguez C.R., Cho E.-J., Keogh M.-C., Moore C.L., Greenleaf A.L., Buratowski S. Mol. Cell. Biol. 20:104-112(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"Kin28 is found within TFIIH and a Kin28-Ccl1-Tfb3 trimer complex with differential sensitivities to T-loop phosphorylation." Keogh M.-C., Cho E.-J., Podolny V., Buratowski S. Mol. Cell. Biol. 22:1288-1297(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH CCL1 AND TFB3, PHOSPHORYLATION AT THR-162, MUTAGENESIS OF THR-17; LYS-36; GLU-54; ASP-147; THR-162 AND SER-163.
[12]	"Osmostress-induced transcription by Hot1 depends on a Hog1-mediated recruitment of the RNA Pol II." Alepuz P.M., de Nadal E., Zapater M., Ammerer G., Posas F. EMBO J. 22:2433-2442(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HOG1.
[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]	"Quantitative phosphoproteomics applied to the yeast pheromone signaling pathway." Gruhler A., Olsen J.V., Mohammed S., Mortensen P., Faergeman N.J., Mann M., Jensen O.N. Mol. Cell. Proteomics 4:310-327(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-162, MASS SPECTROMETRY. Strain: YAL6B.
[16]	"Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases." Smolka M.B., Albuquerque C.P., Chen S.H., Zhou H. Proc. Natl. Acad. Sci. U.S.A. 104:10364-10369(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-162, MASS SPECTROMETRY.
[17]	"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-162 AND THR-167, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X04423 Genomic DNA. Translation: CAA28019.1. X95644 Genomic DNA. Translation: CAA64904.1. Z74156 Genomic DNA. Translation: CAA98675.1. BK006938 Genomic DNA. Translation: DAA11752.1.
PIR	A25698.
RefSeq	NP_010175.1. NM_001180167.1.
3D structure databases
ProteinModelPortal	P06242.
SMR	P06242. Positions 13-297.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-2259N.
IntAct	P06242. 9 interactions.
MINT	MINT-526112.
STRING	4932.YDL108W.
Proteomic databases
PaxDb	P06242.
PeptideAtlas	P06242.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YDL108W; YDL108W; YDL108W.
GeneID	851450.
KEGG	sce:YDL108W.
Organism-specific databases
CYGD	YDL108w.
SGD	S000002266. KIN28.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00680000099989.
HOGENOM	HOG000233024.
KO	K02202.
OMA	THWILHR.
OrthoDB	EOG4DV8W4.
Enzyme and pathway databases
BRENDA	2.7.11.22. 984.
Gene expression databases
Genevestigator	P06242.
GermOnline	YDL108W. 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
BindingDB	P06242.
ChEMBL	CHEMBL5370.
NextBio	968708.

Entry information

Entry name

KIN28_YEAST

Accession

Primary (citable) accession number: P06242
Secondary accession number(s): D6VRP2

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	January 1, 1988
Last modified:	May 1, 2013
This is version 147 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program