P46995 (SET2_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	733 AA.
Sequence status	Complete.
Protein existence	Evidence 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 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 process	Transcription Transcription regulation
Cellular component	Chromosome Nucleus
Domain	Coiled coil
Molecular function	Methyltransferase Repressor Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA-dependent transcription, elongation Inferred from direct assay Ref.9. Source: SGD ascospore formation Inferred from mutant phenotype PubMed 17150765. Source: SGD histone deacetylation Inferred from mutant phenotype PubMed 16286007. 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
Cellular_component	chromosome Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from physical interaction Ref.4. Source: SGD
Molecular_function	histone methyltransferase activity (H3-K36 specific) Inferred from direct assay Ref.4. Source: SGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 733

733

Histone-lysine N-methyltransferase, H3 lysine-36 specific

PRO_0000186087

Regions

Domain

63 – 118

56

AWS

Domain

119 – 241

123

SET

Domain

244 – 260

17

Post-SET

Domain

475 – 507

33

WW

Region

619 – 718

100

Binding to RNA polymerase II CTD

Coiled coil

548 – 630

83

Potential

Amino acid modifications

Modified residue

522

1

Phosphoserine Ref.14

Experimental info

Mutagenesis

195

1

R → G: Reduces dramatically histone methyltransferase activity toward nucleosomes. Ref.4

Mutagenesis

201

1

C → A: Reduces dramatically histone methyltransferase activity toward nucleosomes. Ref.4

Sequence conflict

594

1

A → F in CAA89464. Ref.1

Sequence conflict

605

1

A → S in CAA89464. Ref.1

Sequence conflict

716

1

A → G in CAA89464. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

733

Helix Strand Turn

Details...

Beta strand

481 – 494

14

Turn

495 – 498

4

Beta strand

499 – 503

5

Helix

624 – 645

22

Turn

648 – 652

5

Helix

655 – 676

22

Helix

688 – 712

25

Sequences

	Sequence		Length	Mass (Da)
	P46995 [UniParc]. Last modified September 21, 2011. Version 2. Checksum: 05436B181E88EFF5	FASTA	733	84,461
	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

References

	« Hide 'large scale' referencesShow '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. , 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 96604 / S288c / FY1679.
[2]	Saccharomyces Genome Database Submitted (MAR-2011) to the EMBL/GenBank/DDBJ databases 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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-522, MASS SPECTROMETRY.
[15]	"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.
[16]	"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.

PIR

S56951.

RefSeq

NP_012367.2. NM_001181601.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1E0N	NMR	-	A	479-505	[»]
2C5Z	NMR	-	A	620-719	[»]

ProteinModelPortal

P46995.

SMR

P46995. Positions 66-261, 479-505, 622-703.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-2150N.

IntAct

P46995. 62 interactions.

MINT

MINT-500810.

STRING

4932.YJL168C.

Proteomic databases

PaxDb

P46995.

PeptideAtlas

P46995.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YJL168C; YJL168C; YJL168C.

GeneID

853271.

KEGG

sce:YJL168C.

Organism-specific databases

CYGD

YJL168c.

SGD

S000003704. SET2.

Phylogenomic databases

eggNOG

COG2940.

GeneTree

ENSGT00700000104009.

HOGENOM

HOG000248214.

KO

K11423.

OMA

ITFDYNV.

OrthoDB

EOG40S3Q4.

Gene expression databases

Genevestigator

P46995.

GermOnline

YJL168C. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR006560. AWS.
IPR025788. Hist-Lys_N-MeTrfase_SET2_fun.
IPR003616. Post-SET_dom.
IPR001214. SET_dom.
IPR013257. SRI.
IPR001202. WW_dom.
[Graphical view]

Pfam

PF00856. SET. 1 hit.
PF08236. SRI. 1 hit.
[Graphical view]

SMART

SM00570. AWS. 1 hit.
SM00508. PostSET. 1 hit.
SM00317. SET. 1 hit.
SM00456. WW. 1 hit.
[Graphical view]

SUPFAM

SSF51045. WW_Rsp5_WWP. 1 hit.

PROSITE

PS51215. AWS. 1 hit.
PS50868. POST_SET. 1 hit.
PS50280. SET. 1 hit.
PS01159. WW_DOMAIN_1. False negative.
PS50020. WW_DOMAIN_2. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P46995.

NextBio

973544.

Entry information

Entry name

SET2_YEAST

Accession

Primary (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:	May 1, 2013
This is version 131 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program