GenomeNet

Database: UniProt
Entry: P46995
LinkDB: P46995
Original site: P46995 
ID   SET2_YEAST              Reviewed;         733 AA.
AC   P46995; D6VW19;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   21-SEP-2011, sequence version 2.
DT   13-FEB-2019, entry version 181.
DE   RecName: Full=Histone-lysine N-methyltransferase, H3 lysine-36 specific;
DE            EC=2.1.1.43;
DE   AltName: Full=Lysine N-methyltransferase 3;
DE   AltName: Full=SET domain-containing protein 2;
GN   Name=SET2; Synonyms=EZL1, KMT3; OrderedLocusNames=YJL168C;
GN   ORFNames=J0520;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina;
OC   Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8641269;
RA   Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N.,
RA   Chuat J.-C., Coster F., Cziepluch C., de Haan M., Domdey H.,
RA   Durand P., Entian K.-D., Gatius M., Goffeau A., Grivell L.A.,
RA   Hennemann A., Herbert C.J., Heumann K., Hilger F., Hollenberg C.P.,
RA   Huang M.-E., Jacq C., Jauniaux J.-C., Katsoulou C., Kirchrath L.,
RA   Kleine K., Kordes E., Koetter P., Liebl S., Louis E.J., Manus V.,
RA   Mewes H.-W., Miosga T., Obermaier B., Perea J., Pohl T.M.,
RA   Portetelle D., Pujol A., Purnelle B., Ramezani Rad M., Rasmussen S.W.,
RA   Rose M., Rossau R., Schaaff-Gerstenschlaeger I., Smits P.H.M.,
RA   Scarcez T., Soriano N., To Van D., Tzermia M., Van Broekhoven A.,
RA   Vandenbol M., Wedler H., von Wettstein D., Wambutt R., Zagulski M.,
RA   Zollner A., Karpfinger-Hartl L.;
RT   "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome
RT   X.";
RL   EMBO J. 15:2031-2049(1996).
RN   [2]
RP   GENOME REANNOTATION, AND SEQUENCE REVISION TO 594; 605 AND 716.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M.,
RA   Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and
RT   now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [3]
RP   INTERACTION WITH RBP1 AND RBP2.
RX   PubMed=12381723; DOI=10.1074/jbc.M209294200;
RA   Li J., Moazed D., Gygi S.P.;
RT   "Association of the histone methyltransferase Set2 with RNA polymerase
RT   II plays a role in transcription elongation.";
RL   J. Biol. Chem. 277:49383-49388(2002).
RN   [4]
RP   FUNCTION, AND MUTAGENESIS OF ARG-195 AND CYS-201.
RX   PubMed=11839797; DOI=10.1128/MCB.22.5.1298-1306.2002;
RA   Strahl B.D., Grant P.A., Briggs S.D., Sun Z.-W., Bone J.R.,
RA   Caldwell J.A., Mollah S., Cook R.G., Shabanowitz J., Hunt D.F.,
RA   Allis C.D.;
RT   "Set2 is a nucleosomal histone H3-selective methyltransferase that
RT   mediates transcriptional repression.";
RL   Mol. Cell. Biol. 22:1298-1306(2002).
RN   [5]
RP   INTERACTION WITH RNA POLYMERASE II, AND FUNCTION.
RX   PubMed=12629047; DOI=10.1101/gad.1055503;
RA   Xiao T., Hall H., Kizer K.O., Shibata Y., Hall M.C., Borchers C.H.,
RA   Strahl B.D.;
RT   "Phosphorylation of RNA polymerase II CTD regulates H3 methylation in
RT   yeast.";
RL   Genes Dev. 17:654-663(2003).
RN   [6]
RP   INTERACTION WITH RNA POLYMERASE II.
RX   PubMed=12511561; DOI=10.1074/jbc.M212134200;
RA   Li B., Howe L., Anderson S., Yates J.R. III, Workman J.L.;
RT   "The Set2 histone methyltransferase functions through the
RT   phosphorylated carboxyl-terminal domain of RNA polymerase II.";
RL   J. Biol. Chem. 278:8897-8903(2003).
RN   [7]
RP   FUNCTION, AND INTERACTION WITH RNA POLYMERASE II.
RX   PubMed=12773564; DOI=10.1128/MCB.23.12.4207-4218.2003;
RA   Krogan N.J., Kim M., Tong A., Golshani A., Cagney G., Canadien V.,
RA   Richards D.P., Beattie B.K., Emili A., Boone C., Shilatifard A.,
RA   Buratowski S., Greenblatt J.;
RT   "Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is
RT   linked to transcriptional elongation by RNA polymerase II.";
RL   Mol. Cell. Biol. 23:4207-4218(2003).
RN   [8]
RP   FUNCTION, AND DOMAINS.
RX   PubMed=12917322; DOI=10.1128/MCB.23.17.5972-5978.2003;
RA   Landry J., Sutton A., Hesman T., Min J., Xu R.-M., Johnston M.,
RA   Sternglanz R.;
RT   "Set2-catalyzed methylation of histone H3 represses basal expression
RT   of GAL4 in Saccharomyces cerevisiae.";
RL   Mol. Cell. Biol. 23:5972-5978(2003).
RN   [9]
RP   FUNCTION, AND INTERACTION WITH RNA POLYMERASE II.
RX   PubMed=12736296; DOI=10.1093/nar/gkg372;
RA   Schaft D., Roguev A., Kotovic K.M., Shevchenko A., Sarov M.,
RA   Shevchenko A., Neugebauer K.M., Stewart A.F.;
RT   "The histone 3 lysine 36 methyltransferase, SET2, is involved in
RT   transcriptional elongation.";
RL   Nucleic Acids Res. 31:2475-2482(2003).
RN   [10]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A.,
RA   Dephoure N., O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [11]
RP   FUNCTION, DOMAIN, AND INTERACTION WITH RNA POLYMERASE II CTD.
RX   PubMed=15798214; DOI=10.1128/MCB.25.8.3305-3316.2005;
RA   Kizer K.O., Phatnani H.P., Shibata Y., Hall H., Greenleaf A.L.,
RA   Strahl B.D.;
RT   "A novel domain in Set2 mediates RNA polymerase II interaction and
RT   couples histone H3 K36 methylation with transcript elongation.";
RL   Mol. Cell. Biol. 25:3305-3316(2005).
RN   [12]
RP   FUNCTION.
RX   PubMed=16227595; DOI=10.1128/MCB.25.21.9447-9459.2005;
RA   Rao B., Shibata Y., Strahl B.D., Lieb J.D.;
RT   "Dimethylation of histone H3 at lysine 36 demarcates regulatory and
RT   nonregulatory chromatin genome-wide.";
RL   Mol. Cell. Biol. 25:9447-9459(2005).
RN   [13]
RP   INTERACTION WITH CYC8.
RX   PubMed=16329992; DOI=10.1016/j.bbrc.2005.11.103;
RA   Tripic T., Edmondson D.G., Davie J.K., Strahl B.D., Dent S.Y.R.;
RT   "The Set2 methyltransferase associates with Ssn6 yet Tup1-Ssn6
RT   repression is independent of histone methylation.";
RL   Biochem. Biophys. Res. Commun. 339:905-914(2006).
RN   [14]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=18407956; DOI=10.1074/mcp.M700468-MCP200;
RA   Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT   "A multidimensional chromatography technology for in-depth
RT   phosphoproteome analysis.";
RL   Mol. Cell. Proteomics 7:1389-1396(2008).
RN   [15]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10 AND SER-522, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19779198; DOI=10.1126/science.1172867;
RA   Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT   "Global analysis of Cdk1 substrate phosphorylation sites provides
RT   insights into evolution.";
RL   Science 325:1682-1686(2009).
RN   [16]
RP   STRUCTURE BY NMR OF 7-33.
RX   PubMed=10802733; DOI=10.1038/75144;
RA   Macias M.J., Gervais V., Civera C., Oschkinat H.;
RT   "Structural analysis of WW domains and design of a WW prototype.";
RL   Nat. Struct. Biol. 7:375-379(2000).
RN   [17]
RP   STRUCTURE BY NMR OF 619-718.
RX   PubMed=16286474; DOI=10.1074/jbc.C500423200;
RA   Vojnic E., Simon B., Strahl B.D., Sattler M., Cramer P.;
RT   "Structure and carboxyl-terminal domain (CTD) binding of the Set2 SRI
RT   domain that couples histone H3 Lys36 methylation to transcription.";
RL   J. Biol. Chem. 281:13-15(2006).
CC   -!- FUNCTION: Histone methyltransferase that methylates histone H3 to
CC       form H3K36me. Involved in transcription elongation as well as in
CC       transcription repression. The methyltransferase activity requires
CC       the recruitment to the RNA polymerase II, which is CTK1 dependent.
CC       {ECO:0000269|PubMed:11839797, ECO:0000269|PubMed:12629047,
CC       ECO:0000269|PubMed:12736296, ECO:0000269|PubMed:12773564,
CC       ECO:0000269|PubMed:12917322, ECO:0000269|PubMed:15798214,
CC       ECO:0000269|PubMed:16227595}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl-[histone] + S-adenosyl-L-methionine = H(+) +
CC         N(6)-methyl-L-lysyl-[histone] + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:10024, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:9846,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.43;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU00901};
CC   -!- SUBUNIT: Interacts with the RNA polymerase II hyperphosphorylated
CC       CTD. Interacts with CYC8. {ECO:0000269|PubMed:12381723,
CC       ECO:0000269|PubMed:12511561, ECO:0000269|PubMed:12629047,
CC       ECO:0000269|PubMed:12736296, ECO:0000269|PubMed:12773564,
CC       ECO:0000269|PubMed:15798214, ECO:0000269|PubMed:16329992}.
CC   -!- INTERACTION:
CC       P61830:HHT2; NbExp=2; IntAct=EBI-16985, EBI-8098;
CC   -!- SUBCELLULAR LOCATION: Nucleus. Chromosome {ECO:0000305}.
CC   -!- DOMAIN: The AWS and SET domains are necessary for transcription
CC       repression. {ECO:0000269|PubMed:12917322,
CC       ECO:0000269|PubMed:15798214}.
CC   -!- MISCELLANEOUS: Present with 217 molecules/cell in log phase SD
CC       medium. {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the class V-like SAM-binding
CC       methyltransferase superfamily. Histone-lysine methyltransferase
CC       family. SET2 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00901}.
DR   EMBL; Z49444; CAA89464.1; -; Genomic_DNA.
DR   EMBL; BK006943; DAA08635.2; -; Genomic_DNA.
DR   PIR; S56951; S56951.
DR   RefSeq; NP_012367.2; NM_001181601.2.
DR   PDB; 1E0N; NMR; -; A=479-505.
DR   PDB; 2C5Z; NMR; -; A=620-719.
DR   PDBsum; 1E0N; -.
DR   PDBsum; 2C5Z; -.
DR   ProteinModelPortal; P46995; -.
DR   SMR; P46995; -.
DR   BioGrid; 33591; 621.
DR   DIP; DIP-2150N; -.
DR   IntAct; P46995; 62.
DR   MINT; P46995; -.
DR   STRING; 4932.YJL168C; -.
DR   iPTMnet; P46995; -.
DR   MaxQB; P46995; -.
DR   PaxDb; P46995; -.
DR   PRIDE; P46995; -.
DR   EnsemblFungi; YJL168C_mRNA; YJL168C_mRNA; YJL168C.
DR   GeneID; 853271; -.
DR   KEGG; sce:YJL168C; -.
DR   EuPathDB; FungiDB:YJL168C; -.
DR   SGD; S000003704; SET2.
DR   HOGENOM; HOG000248214; -.
DR   InParanoid; P46995; -.
DR   KO; K11423; -.
DR   OMA; NHACGED; -.
DR   BioCyc; YEAST:G3O-31606-MONOMER; -.
DR   Reactome; R-SCE-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR   Reactome; R-SCE-3214841; PKMTs methylate histone lysines.
DR   Reactome; R-SCE-427359; SIRT1 negatively regulates rRNA expression.
DR   Reactome; R-SCE-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR   EvolutionaryTrace; P46995; -.
DR   PRO; PR:P46995; -.
DR   Proteomes; UP000002311; Chromosome X.
DR   GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IDA:SGD.
DR   GO; GO:0005634; C:nucleus; IDA:SGD.
DR   GO; GO:0042054; F:histone methyltransferase activity; ISS:SGD.
DR   GO; GO:0046975; F:histone methyltransferase activity (H3-K36 specific); IDA:SGD.
DR   GO; GO:0030437; P:ascospore formation; IMP:SGD.
DR   GO; GO:0006354; P:DNA-templated transcription, elongation; IDA:SGD.
DR   GO; GO:0006353; P:DNA-templated transcription, termination; IMP:SGD.
DR   GO; GO:0016575; P:histone deacetylation; IMP:SGD.
DR   GO; GO:0016571; P:histone methylation; IDA:SGD.
DR   GO; GO:0060195; P:negative regulation of antisense RNA transcription; IMP:SGD.
DR   GO; GO:0071441; P:negative regulation of histone H3-K14 acetylation; IMP:SGD.
DR   GO; GO:2000616; P:negative regulation of histone H3-K9 acetylation; IMP:SGD.
DR   GO; GO:0045128; P:negative regulation of reciprocal meiotic recombination; IMP:SGD.
DR   GO; GO:0035066; P:positive regulation of histone acetylation; IGI:SGD.
DR   GO; GO:0030174; P:regulation of DNA-dependent DNA replication initiation; IMP:SGD.
DR   GO; GO:1900049; P:regulation of histone exchange; IMP:SGD.
DR   GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:SGD.
DR   Gene3D; 1.10.1740.100; -; 1.
DR   InterPro; IPR006560; AWS_dom.
DR   InterPro; IPR025788; Hist-Lys_N-MeTrfase_SET2_fun.
DR   InterPro; IPR003616; Post-SET_dom.
DR   InterPro; IPR001214; SET_dom.
DR   InterPro; IPR013257; SRI.
DR   InterPro; IPR038190; SRI_sf.
DR   InterPro; IPR001202; WW_dom.
DR   InterPro; IPR036020; WW_dom_sf.
DR   Pfam; PF17907; AWS; 1.
DR   Pfam; PF00856; SET; 1.
DR   Pfam; PF08236; SRI; 1.
DR   Pfam; PF18507; WW_1; 1.
DR   SMART; SM00570; AWS; 1.
DR   SMART; SM00508; PostSET; 1.
DR   SMART; SM00317; SET; 1.
DR   SMART; SM00456; WW; 1.
DR   SUPFAM; SSF51045; SSF51045; 1.
DR   PROSITE; PS51215; AWS; 1.
DR   PROSITE; PS50868; POST_SET; 1.
DR   PROSITE; PS51568; SAM_MT43_SET2_1; 1.
DR   PROSITE; PS50280; SET; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Chromosome; Coiled coil; Complete proteome;
KW   Methyltransferase; Nucleus; Phosphoprotein; Reference proteome;
KW   Repressor; S-adenosyl-L-methionine; Transcription;
KW   Transcription regulation; Transferase.
FT   CHAIN         1    733       Histone-lysine N-methyltransferase, H3
FT                                lysine-36 specific.
FT                                /FTId=PRO_0000186087.
FT   DOMAIN       63    118       AWS. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00562}.
FT   DOMAIN      120    237       SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00190}.
FT   DOMAIN      244    260       Post-SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00155}.
FT   DOMAIN      475    507       WW.
FT   REGION      619    718       Binding to RNA polymerase II CTD.
FT   COILED      548    630       {ECO:0000255}.
FT   MOD_RES      10     10       Phosphoserine.
FT                                {ECO:0000244|PubMed:19779198}.
FT   MOD_RES     522    522       Phosphoserine.
FT                                {ECO:0000244|PubMed:19779198}.
FT   MUTAGEN     195    195       R->G: Reduces dramatically histone
FT                                methyltransferase activity toward
FT                                nucleosomes.
FT                                {ECO:0000269|PubMed:11839797}.
FT   MUTAGEN     201    201       C->A: Reduces dramatically histone
FT                                methyltransferase activity toward
FT                                nucleosomes.
FT                                {ECO:0000269|PubMed:11839797}.
FT   CONFLICT    594    594       A -> F (in Ref. 1; CAA89464).
FT                                {ECO:0000305}.
FT   CONFLICT    605    605       A -> S (in Ref. 1; CAA89464).
FT                                {ECO:0000305}.
FT   CONFLICT    716    716       A -> G (in Ref. 1; CAA89464).
FT                                {ECO:0000305}.
FT   STRAND      481    494       {ECO:0000244|PDB:1E0N}.
FT   TURN        495    498       {ECO:0000244|PDB:1E0N}.
FT   STRAND      499    503       {ECO:0000244|PDB:1E0N}.
FT   HELIX       624    645       {ECO:0000244|PDB:2C5Z}.
FT   TURN        648    652       {ECO:0000244|PDB:2C5Z}.
FT   HELIX       655    676       {ECO:0000244|PDB:2C5Z}.
FT   HELIX       688    712       {ECO:0000244|PDB:2C5Z}.
SQ   SEQUENCE   733 AA;  84461 MW;  05436B181E88EFF5 CRC64;
     MSKNQSVSAS EDEKEILNNN AEGHKPQRLF DQEPDLTEEA LTKFENLDDC IYANKRIGTF
     KNNDFMECDC YEEFSDGVNH ACDEDSDCIN RLTLIECVND LCSSCGNDCQ NQRFQKKQYA
     PIAIFKTKHK GYGVRAEQDI EANQFIYEYK GEVIEEMEFR DRLIDYDQRH FKHFYFMMLQ
     NGEFIDATIK GSLARFCNHS CSPNAYVNKW VVKDKLRMGI FAQRKILKGE EITFDYNVDR
     YGAQAQKCYC EEPNCIGFLG GKTQTDAASL LPQNIADALG VTVSMEKKWL KLKKLSGEPI
     IKNENENINI EFLQSLEVQP IDSPVDVTKI MSVLLQQDNK IIASKLLKRL FTIDDDSLRH
     QAIKLHGYTC FSKMLKLFIT EQPQVDGKGN ETEEDDIKFI KGILDFLLEL PKTTRNGIES
     SQIDNVVKTL PAKFPFLKPN CDELLEKWSK FETYKRITKK DINVAASKMI DLRRVRLPPG
     WEIIHENGRP LYYNAEQKTK LHYPPSGSSK VFSSRSNTQV NSPSSSGIPK TPGALDSKKH
     KLSDEEYERK KQKRLEYERI ALERAKQEEL ESLKQKLKLE NERKSVLEDI IAEANKQKEL
     QKEEAKKLVE AKEAKRLKRK TVSQSQRLEH NWNKFFASFV PNLIKKNPQS KQFDHENIKQ
     CAKDIVKILT TKELKKDSSR APPDDLTKGK RHKVKEFINS YMDKIILKKK QKKALALSSA
     STRMSSPPPS TSS
//
DBGET integrated database retrieval system