GenomeNet

Database: UniProt
Entry: P42124
LinkDB: P42124
Original site: P42124 
ID   EZ_DROME                Reviewed;         760 AA.
AC   P42124; B7Z0G2; Q9VTA3;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   28-MAR-2003, sequence version 2.
DT   16-JAN-2019, entry version 177.
DE   RecName: Full=Histone-lysine N-methyltransferase E(z);
DE            EC=2.1.1.43;
DE   AltName: Full=Lysine N-methyltransferase 6;
DE   AltName: Full=Protein enhancer of zeste;
GN   Name=E(z); Synonyms=KMT6; ORFNames=CG6502;
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta;
OC   Pterygota; Neoptera; Holometabola; Diptera; Brachycera; Muscomorpha;
OC   Ephydroidea; Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=8413234; DOI=10.1128/MCB.13.10.6357;
RA   Jones R.S., Gelbart W.M.;
RT   "The Drosophila Polycomb-group gene Enhancer of zeste contains a
RT   region with sequence similarity to trithorax.";
RL   Mol. Cell. Biol. 13:6357-6366(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X.,
RA   Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D.,
RA   Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G.,
RA   Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D.,
RA   Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M.,
RA   Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S.,
RA   Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P.,
RA   Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I.,
RA   Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P.,
RA   de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M.,
RA   Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P.,
RA   Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W.,
RA   Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K.,
RA   Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J.,
RA   Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C.,
RA   Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A.,
RA   Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z.,
RA   Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X.,
RA   Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D.,
RA   Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A.,
RA   Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L.,
RA   Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M.,
RA   Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G.,
RA   Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H.,
RA   Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E.,
RA   Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X.,
RA   Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J.,
RA   Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A.,
RA   Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L.,
RA   Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X.,
RA   Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=Berkeley;
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q.,
RA   Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M.,
RA   Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a
RT   systematic review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley; TISSUE=Ovary;
RX   PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA   Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M.,
RA   George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H.,
RA   Rubin G.M., Celniker S.E.;
RT   "A Drosophila full-length cDNA resource.";
RL   Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN   [5]
RP   SUBCELLULAR LOCATION.
RX   PubMed=9012527;
RA   Carrington E.A., Jones R.S.;
RT   "The Drosophila Enhancer of zeste gene encodes a chromosomal protein:
RT   examination of wild-type and mutant protein distribution.";
RL   Development 122:4073-4083(1996).
RN   [6]
RP   INTERACTION WITH ESC.
RX   PubMed=9566901; DOI=10.1128/MCB.18.5.2825;
RA   Jones C.A., Ng J., Peterson A.J., Morgan K., Simon J.A., Jones R.S.;
RT   "The Drosophila esc and E(z) proteins are direct partners in polycomb
RT   group-mediated repression.";
RL   Mol. Cell. Biol. 18:2825-2834(1998).
RN   [7]
RP   IDENTIFICATION IN AN ESC/E(Z) COMPLEX WITH CAF1; ESC AND RPD3.
RX   PubMed=11124122;
RA   Tie F., Furuyama T., Prasad-Sinha J., Jane E., Harte P.J.;
RT   "The Drosophila polycomb group proteins ESC and E(Z) are present in a
RT   complex containing the histone-binding protein p55 and the histone
RT   deacetylase RPD3.";
RL   Development 128:275-286(2001).
RN   [8]
RP   IDENTIFICATION IN A COMPLEX WITH RPD3; PHO AND ESC, AND TRANSIENT
RP   INTERACTION WITH THE PRC1 COMPLEX.
RX   PubMed=11581156; DOI=10.1101/gad.208901;
RA   Poux S., Melfi R., Pirrotta V.;
RT   "Establishment of Polycomb silencing requires a transient interaction
RT   between PC and ESC.";
RL   Genes Dev. 15:2509-2514(2001).
RN   [9]
RP   IDENTIFICATION IN AN ESC/E(Z) COMPLEX WITH CAF1; ESC; RPD3 AND
RP   SU(Z)12, METHYLTRANSFERASE ACTIVITY OF THE COMPLEX, AND MUTAGENESIS OF
RP   702-ASN-HIS-703.
RX   PubMed=12408863; DOI=10.1016/S0092-8674(02)00975-3;
RA   Czermin B., Melfi R., McCabe D., Seitz V., Imhof A., Pirrotta V.;
RT   "Drosophila Enhancer of zeste/ESC complexes have a histone H3
RT   methyltransferase activity that marks chromosomal Polycomb sites.";
RL   Cell 111:185-196(2002).
RN   [10]
RP   IDENTIFICATION IN AN ESC/E(Z) COMPLEX WITH CAF1; ESC AND SU(Z)12,
RP   METHYLTRANSFERASE ACTIVITY OF THE COMPLEX, AND MUTAGENESIS OF ARG-699
RP   AND HIS-703.
RX   PubMed=12408864; DOI=10.1016/S0092-8674(02)00976-5;
RA   Mueller J., Hart C.M., Francis N.J., Vargas M.L., Sengupta A.,
RA   Wild B., Miller E.L., O'Connor M.B., Kingston R.E., Simon J.A.;
RT   "Histone methyltransferase activity of a Drosophila Polycomb group
RT   repressor complex.";
RL   Cell 111:197-208(2002).
RN   [11]
RP   IDENTIFICATION IN AN ESC/E(Z) COMPLEX WITH CAF1; ESC AND RPD3.
RX   PubMed=12533794; DOI=10.1002/gene.10173;
RA   Furuyama T., Tie F., Harte P.J.;
RT   "Polycomb group proteins ESC and E(Z) are present in multiple distinct
RT   complexes that undergo dynamic changes during development.";
RL   Genesis 35:114-124(2003).
RN   [12]
RP   IDENTIFICATION IN AN ESC/E(Z) COMPLEX WITH CAF1; ESC; PCL; RPD3 AND
RP   SU(Z)12.
RX   PubMed=12697833; DOI=10.1128/MCB.23.9.3352-3362.2003;
RA   Tie F., Prasad-Sinha J., Birve A., Rasmuson-Lestander A., Harte P.J.;
RT   "A 1-megadalton ESC/E(Z) complex from Drosophila that contains
RT   polycomblike and RPD3.";
RL   Mol. Cell. Biol. 23:3352-3362(2003).
RN   [13]
RP   INTERACTION WITH CORTO.
RX   PubMed=12771214; DOI=10.1093/nar/gkg381;
RA   Salvaing J., Lopez A., Boivin A., Deutsch J.S., Peronnet F.;
RT   "The Drosophila Corto protein interacts with Polycomb-group proteins
RT   and the GAGA factor.";
RL   Nucleic Acids Res. 31:2873-2882(2003).
RN   [14]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-493 AND THR-502, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Embryo;
RX   PubMed=18327897; DOI=10.1021/pr700696a;
RA   Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT   "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL   J. Proteome Res. 7:1675-1682(2008).
CC   -!- FUNCTION: Polycomb group (PcG) protein. Catalytic subunit of the
CC       Esc/E(z) complex, which methylates 'Lys-9' and 'Lys-27' of histone
CC       H3, leading to transcriptional repression of the affected target
CC       gene. While PcG proteins are generally required to maintain the
CC       transcriptionally repressive state of homeotic genes throughout
CC       development, this protein is specifically required during the
CC       first 6 hours of embryogenesis to establish the repressed state.
CC       The Esc/E(z) complex is necessary but not sufficient for the
CC       repression of homeotic target genes, suggesting that the
CC       recruitment of the distinct PRC1 complex is also required.
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   -!- SUBUNIT: Component of the Esc/E(z) complex, composed of Caf1, esc,
CC       E(z), Su(z)12, and possibly pho. The Esc/E(z) complex may also
CC       associate with Pcl and Rpd3 during early embryogenesis. This
CC       complex is distinct from the PRC1 complex, which contains many
CC       other PcG proteins like Pc, Ph, Psc, Su(z)2. The two complexes
CC       however cooperate and interact together during the first 3 hours
CC       of development to establish PcG silencing. Interacts with corto in
CC       vitro. {ECO:0000269|PubMed:11124122, ECO:0000269|PubMed:11581156,
CC       ECO:0000269|PubMed:12408863, ECO:0000269|PubMed:12408864,
CC       ECO:0000269|PubMed:12533794, ECO:0000269|PubMed:12697833,
CC       ECO:0000269|PubMed:12771214, ECO:0000269|PubMed:9566901}.
CC   -!- INTERACTION:
CC       Q9VEX9:Bin1; NbExp=7; IntAct=EBI-112315, EBI-129424;
CC       Q24572:Caf1; NbExp=7; IntAct=EBI-112315, EBI-75924;
CC       P41046:corto; NbExp=2; IntAct=EBI-112315, EBI-300379;
CC       Q24338:esc; NbExp=21; IntAct=EBI-112315, EBI-88911;
CC       Q95SW6:escl; NbExp=2; IntAct=EBI-112315, EBI-1207935;
CC       Q24459:Pcl; NbExp=14; IntAct=EBI-112315, EBI-430086;
CC       Q94517:Rpd3; NbExp=9; IntAct=EBI-112315, EBI-302197;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9012527}.
CC   -!- SIMILARITY: Belongs to the class V-like SAM-binding
CC       methyltransferase superfamily. Histone-lysine methyltransferase
CC       family. EZ subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
DR   EMBL; U00180; AAC46462.1; -; mRNA.
DR   EMBL; AE014296; AAF50149.1; -; Genomic_DNA.
DR   EMBL; AE014296; ACL83287.1; -; Genomic_DNA.
DR   EMBL; AY051785; AAK93209.1; -; mRNA.
DR   RefSeq; NP_001137932.1; NM_001144460.3.
DR   RefSeq; NP_524021.2; NM_079297.3.
DR   UniGene; Dm.2823; -.
DR   ProteinModelPortal; P42124; -.
DR   BioGrid; 64582; 42.
DR   DIP; DIP-20386N; -.
DR   IntAct; P42124; 23.
DR   MINT; P42124; -.
DR   STRING; 7227.FBpp0306192; -.
DR   BindingDB; P42124; -.
DR   ChEMBL; CHEMBL2169719; -.
DR   iPTMnet; P42124; -.
DR   PaxDb; P42124; -.
DR   PRIDE; P42124; -.
DR   EnsemblMetazoa; FBtr0076279; FBpp0076008; FBgn0000629.
DR   EnsemblMetazoa; FBtr0273338; FBpp0271846; FBgn0000629.
DR   GeneID; 39203; -.
DR   KEGG; dme:Dmel_CG6502; -.
DR   CTD; 39203; -.
DR   FlyBase; FBgn0000629; E(z).
DR   eggNOG; KOG1079; Eukaryota.
DR   eggNOG; COG2940; LUCA.
DR   InParanoid; P42124; -.
DR   KO; K11430; -.
DR   OrthoDB; 875190at2759; -.
DR   PhylomeDB; P42124; -.
DR   Reactome; R-DME-212300; PRC2 methylates histones and DNA.
DR   Reactome; R-DME-2559580; Oxidative Stress Induced Senescence.
DR   Reactome; R-DME-8943724; Regulation of PTEN gene transcription.
DR   Reactome; R-DME-8953750; Transcriptional Regulation by E2F6.
DR   SignaLink; P42124; -.
DR   GenomeRNAi; 39203; -.
DR   PRO; PR:P42124; -.
DR   Proteomes; UP000000803; Chromosome 3L.
DR   Bgee; FBgn0000629; Expressed in 41 organ(s), highest expression level in embryo.
DR   ExpressionAtlas; P42124; baseline and differential.
DR   Genevisible; P42124; DM.
DR   GO; GO:0035098; C:ESC/E(Z) complex; IDA:FlyBase.
DR   GO; GO:0035097; C:histone methyltransferase complex; IDA:FlyBase.
DR   GO; GO:0000790; C:nuclear chromatin; NAS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR   GO; GO:0003677; F:DNA binding; NAS:UniProtKB.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR   GO; GO:0042054; F:histone methyltransferase activity; IDA:FlyBase.
DR   GO; GO:0046976; F:histone methyltransferase activity (H3-K27 specific); IDA:FlyBase.
DR   GO; GO:0046974; F:histone methyltransferase activity (H3-K9 specific); IDA:FlyBase.
DR   GO; GO:0007411; P:axon guidance; IMP:FlyBase.
DR   GO; GO:0006723; P:cuticle hydrocarbon biosynthetic process; IMP:FlyBase.
DR   GO; GO:0016458; P:gene silencing; NAS:UniProtKB.
DR   GO; GO:0070734; P:histone H3-K27 methylation; IDA:FlyBase.
DR   GO; GO:0051567; P:histone H3-K9 methylation; IDA:FlyBase.
DR   GO; GO:0016571; P:histone methylation; IDA:FlyBase.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR   GO; GO:0022008; P:neurogenesis; IMP:FlyBase.
DR   GO; GO:0031062; P:positive regulation of histone methylation; IMP:UniProtKB.
DR   GO; GO:1902692; P:regulation of neuroblast proliferation; IGI:UniProtKB.
DR   GO; GO:0035186; P:syncytial blastoderm mitotic cell cycle; IMP:FlyBase.
DR   CDD; cd00167; SANT; 1.
DR   InterPro; IPR026489; CXC_dom.
DR   InterPro; IPR001005; SANT/Myb.
DR   InterPro; IPR001214; SET_dom.
DR   InterPro; IPR033467; Tesmin/TSO1-like_CXC.
DR   Pfam; PF00856; SET; 1.
DR   SMART; SM01114; CXC; 1.
DR   SMART; SM00717; SANT; 2.
DR   SMART; SM00317; SET; 1.
DR   PROSITE; PS51633; CXC; 1.
DR   PROSITE; PS50280; SET; 1.
PE   1: Evidence at protein level;
KW   Chromatin regulator; Complete proteome; Developmental protein;
KW   Methyltransferase; Nucleus; Phosphoprotein; Reference proteome;
KW   Repressor; S-adenosyl-L-methionine; Transcription;
KW   Transcription regulation; Transferase.
FT   CHAIN         1    760       Histone-lysine N-methyltransferase E(z).
FT                                /FTId=PRO_0000213989.
FT   DOMAIN      443    491       SANT.
FT   DOMAIN      518    619       CXC. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00970}.
FT   DOMAIN      626    741       SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00190}.
FT   MOTIF       505    510       Nuclear localization signal.
FT                                {ECO:0000255}.
FT   COMPBIAS    538    619       Cys-rich.
FT   MOD_RES     493    493       Phosphoserine.
FT                                {ECO:0000269|PubMed:18327897}.
FT   MOD_RES     502    502       Phosphothreonine.
FT                                {ECO:0000269|PubMed:18327897}.
FT   MUTAGEN     699    699       R->A,H: Strongly reduces
FT                                methyltransferase activity of the
FT                                Esc/E(z) complex.
FT                                {ECO:0000269|PubMed:12408864}.
FT   MUTAGEN     702    703       NH->AA: Abolishes methyltransferase
FT                                activity of the Esc/E(z) complex.
FT                                {ECO:0000269|PubMed:12408863}.
FT   MUTAGEN     703    703       H->A,K: Strongly reduces
FT                                methyltransferase activity of the
FT                                Esc/E(z) complex.
FT                                {ECO:0000269|PubMed:12408864}.
FT   CONFLICT    185    187       GTA -> STS (in Ref. 1; AAC46462).
FT                                {ECO:0000305}.
FT   CONFLICT    194    194       T -> P (in Ref. 1; AAC46462).
FT                                {ECO:0000305}.
FT   CONFLICT    213    213       G -> C (in Ref. 1; AAC46462).
FT                                {ECO:0000305}.
FT   CONFLICT    223    223       D -> E (in Ref. 1; AAC46462).
FT                                {ECO:0000305}.
FT   CONFLICT    230    230       E -> D (in Ref. 1; AAC46462).
FT                                {ECO:0000305}.
FT   CONFLICT    240    240       L -> V (in Ref. 1; AAC46462).
FT                                {ECO:0000305}.
FT   CONFLICT    250    250       D -> A (in Ref. 1; AAC46462).
FT                                {ECO:0000305}.
SQ   SEQUENCE   760 AA;  86935 MW;  022360ED7772EB60 CRC64;
     MNSTKVPPEW KRRVKSEYIK IRQQKRYKRA DEIKEAWIRN WDEHNHNVQD LYCESKVWQA
     KPYDPPHVDC VKRAEVTSYN GIPSGPQKVP ICVINAVTPI PTMYTWAPTQ QNFMVEDETV
     LHNIPYMGDE VLDKDGKFIE ELIKNYDGKV HGDKDPSFMD DAIFVELVHA LMRSYSKELE
     EAAPGTATAI KTETLAKSKQ GEDDGVVDVD ADGESPMKLE KTDSKGDLTE VEKKETEEPL
     ETEDADVKPD VEEVKDKLPF PAPIIFQAIS ANFPDKGTAQ ELKEKYIELT EHQDPERPQE
     CTPNIDGIKA ESVSRERTMH SFHTLFCRRC FKYDCFLHRL QGHAGPNLQK RRYPELKPFA
     EPCSNSCYML IDGMKEKLAA DSKTPPIDSC NEASSEDSND SNSQFSNKDF NHENSKDNGL
     TVNSAAVAEI NSIMAGMMNI TSTQCVWTGA DQALYRVLHK VYLKNYCAIA HNMLTKTCRQ
     VYEFAQKEDA EFSFEDLRQD FTPPRKKKKK QRLWSLHCRK IQLKKDSSSN HVYNYTPCDH
     PGHPCDMNCS CIQTQNFCEK FCNCSSDCQN RFPGCRCKAQ CNTKQCPCYL AVRECDPDLC
     QACGADQFKL TKITCKNVCV QRGLHKHLLM APSDIAGWGI FLKEGAQKNE FISEYCGEII
     SQDEADRRGK VYDKYMCSFL FNLNNDFVVD ATRKGNKIRF ANHSINPNCY AKVMMVTGDH
     RIGIFAKRAI QPGEELFFDY RYGPTEQLKF VGIEREMEIV
//
DBGET integrated database retrieval system