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P46995 (SET2_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histone-lysine N-methyltransferase, H3 lysine-36 specific

EC=2.1.1.43
Alternative name(s):
Lysine N-methyltransferase 3
SET domain-containing protein 2
Gene names
Name:SET2
Synonyms:EZL1, KMT3
Ordered Locus Names:YJL168C
ORF Names:J0520
OrganismSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]
Taxonomic identifier559292 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces

Protein attributes

Sequence length733 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Histone methyltransferase that methylates histone H3 to form H3K36me. Involved in transcription elongation as well as in transcription repression. The methyltransferase activity requires the recruitment to the RNA polymerase II, which is CTK1 dependent. Ref.4 Ref.5 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12

Catalytic activity

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].

Subunit structure

Interacts with the RNA polymerase II hyperphosphorylated CTD. Interacts with CYC8. Ref.3 Ref.5 Ref.6 Ref.7 Ref.9 Ref.11 Ref.13

Subcellular location

Nucleus. Chromosome Probable.

Domain

The AWS and SET domains are necessary for transcription repression. Ref.8 Ref.11

Miscellaneous

Present with 217 molecules/cell in log phase SD medium.

Sequence similarities

Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. SET2 subfamily.

Contains 1 AWS domain.

Contains 1 post-SET domain.

Contains 1 SET domain.

Contains 1 WW domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentChromosome
Nucleus
   DomainCoiled coil
   LigandS-adenosyl-L-methionine
   Molecular functionMethyltransferase
Repressor
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA-templated transcription, elongation

Inferred from direct assay Ref.9. Source: SGD

DNA-templated transcription, termination

Inferred from mutant phenotype PubMed 23109428. Source: SGD

ascospore formation

Inferred from mutant phenotype PubMed 17150765. Source: SGD

histone deacetylation

Inferred from mutant phenotype PubMed 16286007. Source: SGD

histone methylation

Inferred from direct assay Ref.4. Source: SGD

negative regulation of antisense RNA transcription

Inferred from mutant phenotype PubMed 21248844. Source: SGD

negative regulation of histone H3-K14 acetylation

Inferred from mutant phenotype PubMed 19948887. Source: SGD

negative regulation of histone H3-K9 acetylation

Inferred from mutant phenotype PubMed 19948887. Source: SGD

negative regulation of reciprocal meiotic recombination

Inferred from mutant phenotype PubMed 18515193. Source: SGD

positive regulation of histone acetylation

Inferred from genetic interaction PubMed 19822662. Source: SGD

regulation of DNA-dependent DNA replication initiation

Inferred from mutant phenotype PubMed 19417103. Source: SGD

regulation of histone exchange

Inferred from mutant phenotype PubMed 22914091. Source: SGD

regulation of transcription, DNA-templated

Inferred from direct assay Ref.4. Source: SGD

   Cellular_componentchromosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Inferred from direct assay PubMed 22932476. Source: SGD

nucleus

Inferred from direct assay PubMed 22932476. Source: SGD

   Molecular_functionhistone methyltransferase activity

Inferred from sequence or structural similarity Ref.4PubMed 12845608. Source: SGD

histone methyltransferase activity (H3-K36 specific)

Inferred from direct assay Ref.4. Source: SGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 733733Histone-lysine N-methyltransferase, H3 lysine-36 specific
PRO_0000186087

Regions

Domain63 – 11856AWS
Domain120 – 237118SET
Domain244 – 26017Post-SET
Domain475 – 50733WW
Region619 – 718100Binding to RNA polymerase II CTD
Coiled coil548 – 63083 Potential

Amino acid modifications

Modified residue101Phosphoserine Ref.15
Modified residue5221Phosphoserine Ref.15

Experimental info

Mutagenesis1951R → G: Reduces dramatically histone methyltransferase activity toward nucleosomes. Ref.4
Mutagenesis2011C → A: Reduces dramatically histone methyltransferase activity toward nucleosomes. Ref.4
Sequence conflict5941A → F in CAA89464. Ref.1
Sequence conflict6051A → S in CAA89464. Ref.1
Sequence conflict7161A → G in CAA89464. Ref.1

Secondary structure

............. 733
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P46995 [UniParc].

Last modified September 21, 2011. Version 2.
Checksum: 05436B181E88EFF5

FASTA73384,461
        10         20         30         40         50         60 
MSKNQSVSAS EDEKEILNNN AEGHKPQRLF DQEPDLTEEA LTKFENLDDC IYANKRIGTF 

        70         80         90        100        110        120 
KNNDFMECDC YEEFSDGVNH ACDEDSDCIN RLTLIECVND LCSSCGNDCQ NQRFQKKQYA 

       130        140        150        160        170        180 
PIAIFKTKHK GYGVRAEQDI EANQFIYEYK GEVIEEMEFR DRLIDYDQRH FKHFYFMMLQ 

       190        200        210        220        230        240 
NGEFIDATIK GSLARFCNHS CSPNAYVNKW VVKDKLRMGI FAQRKILKGE EITFDYNVDR 

       250        260        270        280        290        300 
YGAQAQKCYC EEPNCIGFLG GKTQTDAASL LPQNIADALG VTVSMEKKWL KLKKLSGEPI 

       310        320        330        340        350        360 
IKNENENINI EFLQSLEVQP IDSPVDVTKI MSVLLQQDNK IIASKLLKRL FTIDDDSLRH 

       370        380        390        400        410        420 
QAIKLHGYTC FSKMLKLFIT EQPQVDGKGN ETEEDDIKFI KGILDFLLEL PKTTRNGIES 

       430        440        450        460        470        480 
SQIDNVVKTL PAKFPFLKPN CDELLEKWSK FETYKRITKK DINVAASKMI DLRRVRLPPG 

       490        500        510        520        530        540 
WEIIHENGRP LYYNAEQKTK LHYPPSGSSK VFSSRSNTQV NSPSSSGIPK TPGALDSKKH 

       550        560        570        580        590        600 
KLSDEEYERK KQKRLEYERI ALERAKQEEL ESLKQKLKLE NERKSVLEDI IAEANKQKEL 

       610        620        630        640        650        660 
QKEEAKKLVE AKEAKRLKRK TVSQSQRLEH NWNKFFASFV PNLIKKNPQS KQFDHENIKQ 

       670        680        690        700        710        720 
CAKDIVKILT TKELKKDSSR APPDDLTKGK RHKVKEFINS YMDKIILKKK QKKALALSSA 

       730 
STRMSSPPPS TSS 

« Hide

References

« Hide 'large scale' references
[1]"Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X."
Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C., Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D., Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J., Heumann K. expand/collapse author list , Hilger F., Hollenberg C.P., Huang M.-E., Jacq C., Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E., Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T., Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B., Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R., Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N., To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H., von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.
EMBO J. 15:2031-2049(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 204508 / S288c.
[2]"The reference genome sequence of Saccharomyces cerevisiae: Then and now."
Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.
G3 (Bethesda) 4:389-398(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: GENOME REANNOTATION, SEQUENCE REVISION TO 594; 605 AND 716.
Strain: ATCC 204508 / S288c.
[3]"Association of the histone methyltransferase Set2 with RNA polymerase II plays a role in transcription elongation."
Li J., Moazed D., Gygi S.P.
J. Biol. Chem. 277:49383-49388(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RBP1 AND RBP2.
[4]"Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression."
Strahl B.D., Grant P.A., Briggs S.D., Sun Z.-W., Bone J.R., Caldwell J.A., Mollah S., Cook R.G., Shabanowitz J., Hunt D.F., Allis C.D.
Mol. Cell. Biol. 22:1298-1306(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ARG-195 AND CYS-201.
[5]"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: INTERACTION WITH RNA POLYMERASE II, FUNCTION.
[6]"The Set2 histone methyltransferase functions through the phosphorylated carboxyl-terminal domain of RNA polymerase II."
Li B., Howe L., Anderson S., Yates J.R. III, Workman J.L.
J. Biol. Chem. 278:8897-8903(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RNA POLYMERASE II.
[7]"Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II."
Krogan N.J., Kim M., Tong A., Golshani A., Cagney G., Canadien V., Richards D.P., Beattie B.K., Emili A., Boone C., Shilatifard A., Buratowski S., Greenblatt J.
Mol. Cell. Biol. 23:4207-4218(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RNA POLYMERASE II.
[8]"Set2-catalyzed methylation of histone H3 represses basal expression of GAL4 in Saccharomyces cerevisiae."
Landry J., Sutton A., Hesman T., Min J., Xu R.-M., Johnston M., Sternglanz R.
Mol. Cell. Biol. 23:5972-5978(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DOMAINS.
[9]"The histone 3 lysine 36 methyltransferase, SET2, is involved in transcriptional elongation."
Schaft D., Roguev A., Kotovic K.M., Shevchenko A., Sarov M., Shevchenko A., Neugebauer K.M., Stewart A.F.
Nucleic Acids Res. 31:2475-2482(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RNA POLYMERASE II.
[10]"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].
[11]"A novel domain in Set2 mediates RNA polymerase II interaction and couples histone H3 K36 methylation with transcript elongation."
Kizer K.O., Phatnani H.P., Shibata Y., Hall H., Greenleaf A.L., Strahl B.D.
Mol. Cell. Biol. 25:3305-3316(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DOMAIN, INTERACTION WITH RNA POLYMERASE II CTD.
[12]"Dimethylation of histone H3 at lysine 36 demarcates regulatory and nonregulatory chromatin genome-wide."
Rao B., Shibata Y., Strahl B.D., Lieb J.D.
Mol. Cell. Biol. 25:9447-9459(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"The Set2 methyltransferase associates with Ssn6 yet Tup1-Ssn6 repression is independent of histone methylation."
Tripic T., Edmondson D.G., Davie J.K., Strahl B.D., Dent S.Y.R.
Biochem. Biophys. Res. Commun. 339:905-914(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CYC8.
[14]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Global analysis of Cdk1 substrate phosphorylation sites provides insights into evolution."
Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.
Science 325:1682-1686(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10 AND SER-522, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Structural analysis of WW domains and design of a WW prototype."
Macias M.J., Gervais V., Civera C., Oschkinat H.
Nat. Struct. Biol. 7:375-379(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 7-33.
[17]"Structure and carboxyl-terminal domain (CTD) binding of the Set2 SRI domain that couples histone H3 Lys36 methylation to transcription."
Vojnic E., Simon B., Strahl B.D., Sattler M., Cramer P.
J. Biol. Chem. 281:13-15(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 619-718.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z49444 Genomic DNA. Translation: CAA89464.1.
BK006943 Genomic DNA. Translation: DAA08635.2.
PIRS56951.
RefSeqNP_012367.2. NM_001181601.2.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1E0NNMR-A479-505[»]
2C5ZNMR-A620-719[»]
ProteinModelPortalP46995.
SMRP46995. Positions 66-261, 479-505, 622-703.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid33591. 392 interactions.
DIPDIP-2150N.
IntActP46995. 62 interactions.
MINTMINT-500810.
STRING4932.YJL168C.

Proteomic databases

MaxQBP46995.
PaxDbP46995.
PeptideAtlasP46995.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblFungiYJL168C; YJL168C; YJL168C.
GeneID853271.
KEGGsce:YJL168C.

Organism-specific databases

CYGDYJL168c.
SGDS000003704. SET2.

Phylogenomic databases

eggNOGCOG2940.
GeneTreeENSGT00750000117355.
HOGENOMHOG000248214.
KOK11423.
OMASCNPNAY.
OrthoDBEOG7P8PH3.

Enzyme and pathway databases

BioCycYEAST:G3O-31606-MONOMER.

Gene expression databases

GenevestigatorP46995.

Family and domain databases

InterProIPR006560. AWS.
IPR025788. Hist-Lys_N-MeTrfase_SET2_fun.
IPR003616. Post-SET_dom.
IPR001214. SET_dom.
IPR013257. SRI.
IPR001202. WW_dom.
[Graphical view]
PfamPF00856. SET. 1 hit.
PF08236. SRI. 1 hit.
[Graphical view]
SMARTSM00570. AWS. 1 hit.
SM00508. PostSET. 1 hit.
SM00317. SET. 1 hit.
SM00456. WW. 1 hit.
[Graphical view]
SUPFAMSSF51045. SSF51045. 1 hit.
PROSITEPS51215. AWS. 1 hit.
PS50868. POST_SET. 1 hit.
PS51568. SAM_MT43_SET2_1. 1 hit.
PS50280. SET. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP46995.
NextBio973544.

Entry information

Entry nameSET2_YEAST
AccessionPrimary (citable) accession number: P46995
Secondary accession number(s): D6VW19
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: September 21, 2011
Last modified: June 11, 2014
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

Yeast chromosome X

Yeast (Saccharomyces cerevisiae) chromosome X: entries and gene names

Yeast

Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references