P42124 (EZ_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone-lysine N-methyltransferase E(z)
EC=2.1.1.43

Alternative name(s):
Lysine N-methyltransferase 6
Protein enhancer of zeste

Gene names

Name:	E(z)
Synonyms:	KMT6
ORF Names:	CG6502

Organism

Drosophila melanogaster (Fruit fly) [Reference proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Mandibulata › Pancrustacea › Hexapoda › Insecta › Dicondylia › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Eremoneura › Cyclorrhapha › Schizophora › Acalyptratae › Ephydroidea › Drosophilidae › Drosophilinae › Drosophilini › Drosophilina › Drosophiliti › Drosophila › Sophophora › melanogaster group › melanogaster subgroup

Protein attributes

Sequence length	760 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Polycomb group (PcG) protein. Catalytic subunit of the Esc/E(z) complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. While PcG proteins are generally required to maintain the transcriptionally repressive state of homeotic genes throughout development, this protein is specifically required during the first 6 hours of embryogenesis to establish the repressed state. The Esc/E(z) complex is necessary but not sufficient for the repression of homeotic target genes, suggesting that the recruitment of the distinct PRC1 complex is also required.
Catalytic activity	S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].
Subunit structure	Component of the Esc/E(z) complex, composed of Caf1, esc, E(z), Su(z)12, and possibly pho. The Esc/E(z) complex may also associate with Pcl and Rpd3 during early embryogenesis. This complex is distinct from the PRC1 complex, which contains many other PcG proteins like Pc, Ph, Psc, Su(z)2. The two complexes however cooperate and interact together during the first 3 hours of development to establish PcG silencing. Interacts with corto in vitro. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
Subcellular location	Nucleus Ref.5.
Sequence similarities	Belongs to the histone-lysine methyltransferase family. EZ subfamily. Contains 1 CXC domain. Contains 1 SANT domain. Contains 1 SET domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Ligand	S-adenosyl-L-methionine
Molecular function	Chromatin regulator Developmental protein Methyltransferase Repressor Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon guidance Inferred from mutant phenotype PubMed 16495309. Source: FlyBase cuticle hydrocarbon biosynthetic process Inferred from mutant phenotype PubMed 10663138. Source: FlyBase dendrite morphogenesis Inferred from mutant phenotype PubMed 16547170. Source: FlyBase gene silencing Non-traceable author statement Ref.9. Source: UniProtKB muscle organ development Inferred from mutant phenotype PubMed 16547170. Source: FlyBase negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 11571280Ref.12. Source: UniProtKB syncytial blastoderm mitotic cell cycle Inferred from mutant phenotype PubMed 16388795. Source: FlyBase transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	ESC/E(Z) complex Inferred from direct assay Ref.9Ref.10PubMed 18276122PubMed 22354997. Source: FlyBase nuclear chromatin Non-traceable author statement Ref.9. Source: UniProtKB
Molecular_function	DNA binding Non-traceable author statement Ref.9. Source: UniProtKB chromatin binding Inferred from electronic annotation. Source: InterPro histone methyltransferase activity (H3-K27 specific) Inferred from direct assay Ref.9Ref.10. Source: FlyBase histone methyltransferase activity (H3-K9 specific) Inferred from direct assay Ref.9. Source: FlyBase sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 11571280Ref.12. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Bin1	Q9VEX9	7	EBI-112315,EBI-129424
Caf1	Q24572	6	EBI-112315,EBI-75924
corto	P41046	2	EBI-112315,EBI-300379
esc	Q24338	21	EBI-112315,EBI-88911
escl	Q95SW6	2	EBI-112315,EBI-1207935
Pcl	Q24459	11	EBI-112315,EBI-430086
Rpd3	Q94517	9	EBI-112315,EBI-302197

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 760	760	Histone-lysine N-methyltransferase E(z)		PRO_0000213989
Regions
	Domain	443 – 491	49	SANT
	Domain	518 – 619	102	CXC
	Domain	625 – 745	121	SET
	Motif	505 – 510	6	Nuclear localization signal Potential
	Compositional bias	538 – 619	82	Cys-rich
Amino acid modifications
	Modified residue	493	1	Phosphoserine Ref.14
	Modified residue	502	1	Phosphothreonine Ref.14
Experimental info
	Mutagenesis	699	1	R → A or H: Strongly reduces methytransferase activity of the Esc/E(z) complex. Ref.9 Ref.10
	Mutagenesis	702 – 703	2	NH → AA: Abolishes methytransferase activity of the Esc/E(z) complex. Ref.9 Ref.10
	Mutagenesis	703	1	H → A or K: Strongly reduces methytransferase activity of the Esc/E(z) complex. Ref.9 Ref.10
	Sequence conflict	185 – 187	3	GTA → STS in AAC46462. Ref.1
	Sequence conflict	194	1	T → P in AAC46462. Ref.1
	Sequence conflict	213	1	G → C in AAC46462. Ref.1
	Sequence conflict	223	1	D → E in AAC46462. Ref.1
	Sequence conflict	230	1	E → D in AAC46462. Ref.1
	Sequence conflict	240	1	L → V in AAC46462. Ref.1
	Sequence conflict	250	1	D → A in AAC46462. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P42124 [UniParc]. Last modified March 28, 2003. Version 2. Checksum: 022360ED7772EB60	FASTA	760	86,935
	10 20 30 40 50 60 MNSTKVPPEW KRRVKSEYIK IRQQKRYKRA DEIKEAWIRN WDEHNHNVQD LYCESKVWQA 70 80 90 100 110 120 KPYDPPHVDC VKRAEVTSYN GIPSGPQKVP ICVINAVTPI PTMYTWAPTQ QNFMVEDETV 130 140 150 160 170 180 LHNIPYMGDE VLDKDGKFIE ELIKNYDGKV HGDKDPSFMD DAIFVELVHA LMRSYSKELE 190 200 210 220 230 240 EAAPGTATAI KTETLAKSKQ GEDDGVVDVD ADGESPMKLE KTDSKGDLTE VEKKETEEPL 250 260 270 280 290 300 ETEDADVKPD VEEVKDKLPF PAPIIFQAIS ANFPDKGTAQ ELKEKYIELT EHQDPERPQE 310 320 330 340 350 360 CTPNIDGIKA ESVSRERTMH SFHTLFCRRC FKYDCFLHRL QGHAGPNLQK RRYPELKPFA 370 380 390 400 410 420 EPCSNSCYML IDGMKEKLAA DSKTPPIDSC NEASSEDSND SNSQFSNKDF NHENSKDNGL 430 440 450 460 470 480 TVNSAAVAEI NSIMAGMMNI TSTQCVWTGA DQALYRVLHK VYLKNYCAIA HNMLTKTCRQ 490 500 510 520 530 540 VYEFAQKEDA EFSFEDLRQD FTPPRKKKKK QRLWSLHCRK IQLKKDSSSN HVYNYTPCDH 550 560 570 580 590 600 PGHPCDMNCS CIQTQNFCEK FCNCSSDCQN RFPGCRCKAQ CNTKQCPCYL AVRECDPDLC 610 620 630 640 650 660 QACGADQFKL TKITCKNVCV QRGLHKHLLM APSDIAGWGI FLKEGAQKNE FISEYCGEII 670 680 690 700 710 720 SQDEADRRGK VYDKYMCSFL FNLNNDFVVD ATRKGNKIRF ANHSINPNCY AKVMMVTGDH 730 740 750 760 RIGIFAKRAI QPGEELFFDY RYGPTEQLKF VGIEREMEIV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The Drosophila Polycomb-group gene Enhancer of zeste contains a region with sequence similarity to trithorax." Jones R.S., Gelbart W.M. Mol. Cell. Biol. 13:6357-6366(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[3]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed] [Europe PMC] [Abstract] Cited for: GENOME REANNOTATION. Strain: Berkeley.
[4]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Berkeley. Tissue: Ovary.
[5]	"The Drosophila Enhancer of zeste gene encodes a chromosomal protein: examination of wild-type and mutant protein distribution." Carrington E.A., Jones R.S. Development 122:4073-4083(1996) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[6]	"The Drosophila esc and E(z) proteins are direct partners in polycomb group-mediated repression." Jones C.A., Ng J., Peterson A.J., Morgan K., Simon J.A., Jones R.S. Mol. Cell. Biol. 18:2825-2834(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ESC.
[7]	"The Drosophila polycomb group proteins ESC and E(Z) are present in a complex containing the histone-binding protein p55 and the histone deacetylase RPD3." Tie F., Furuyama T., Prasad-Sinha J., Jane E., Harte P.J. Development 128:275-286(2001) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN AN ESC/E(Z) COMPLEX WITH CAF1; ESC AND RPD3.
[8]	"Establishment of Polycomb silencing requires a transient interaction between PC and ESC." Poux S., Melfi R., Pirrotta V. Genes Dev. 15:2509-2514(2001) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH RPD3; PHO AND ESC, TRANSIENT INTERACTION WITH THE PRC1 COMPLEX.
[9]	"Drosophila Enhancer of zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites." Czermin B., Melfi R., McCabe D., Seitz V., Imhof A., Pirrotta V. Cell 111:185-196(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN AN ESC/E(Z) COMPLEX WITH CAF1; ESC; RPD3 AND SU(Z)12, METHYLTRANSFERASE ACTIVITY OF THE COMPLEX, MUTAGENESIS OF 702-ASN-HIS-703.
[10]	"Histone methyltransferase activity of a Drosophila Polycomb group repressor complex." Mueller J., Hart C.M., Francis N.J., Vargas M.L., Sengupta A., Wild B., Miller E.L., O'Connor M.B., Kingston R.E., Simon J.A. Cell 111:197-208(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN AN ESC/E(Z) COMPLEX WITH CAF1; ESC AND SU(Z)12, METHYLTRANSFERASE ACTIVITY OF THE COMPLEX, MUTAGENESIS OF ARG-699 AND HIS-703.
[11]	"Polycomb group proteins ESC and E(Z) are present in multiple distinct complexes that undergo dynamic changes during development." Furuyama T., Tie F., Harte P.J. Genesis 35:114-124(2003) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN AN ESC/E(Z) COMPLEX WITH CAF1; ESC AND RPD3.
[12]	"A 1-megadalton ESC/E(Z) complex from Drosophila that contains polycomblike and RPD3." Tie F., Prasad-Sinha J., Birve A., Rasmuson-Lestander A., Harte P.J. Mol. Cell. Biol. 23:3352-3362(2003) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN AN ESC/E(Z) COMPLEX WITH CAF1; ESC; PCL; RPD3 AND SU(Z)12.
[13]	"The Drosophila Corto protein interacts with Polycomb-group proteins and the GAGA factor." Salvaing J., Lopez A., Boivin A., Deutsch J.S., Peronnet F. Nucleic Acids Res. 31:2873-2882(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CORTO.
[14]	"Phosphoproteome analysis of Drosophila melanogaster embryos." Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P. J. Proteome Res. 7:1675-1682(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-493 AND THR-502, MASS SPECTROMETRY. Tissue: Embryo.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U00180 mRNA. Translation: AAC46462.1. AE014296 Genomic DNA. Translation: AAF50149.1. AE014296 Genomic DNA. Translation: ACL83287.1. AY051785 mRNA. Translation: AAK93209.1.
RefSeq	NP_001137932.1. NM_001144460.3. NP_524021.2. NM_079297.3.
UniGene	Dm.2823.
3D structure databases
ProteinModelPortal	P42124.
SMR	P42124. Positions 592-751.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-20386N.
IntAct	P42124. 10 interactions.
MINT	MINT-266852.
STRING	7227.FBpp0076008.
Proteomic databases
PaxDb	P42124.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0076279; FBpp0076008; FBgn0000629. FBtr0273338; FBpp0271846; FBgn0000629.
GeneID	39203.
KEGG	dme:Dmel_CG6502.
Organism-specific databases
CTD	39203.
FlyBase	FBgn0000629. E(z).
Phylogenomic databases
eggNOG	COG2940.
GeneTree	ENSGT00700000104213.
InParanoid	P42124.
KO	K11430.
OMA	NRDDKES.
OrthoDB	EOG4JM64M.
Enzyme and pathway databases
SignaLink	P42124.
Gene expression databases
Bgee	P42124.
GermOnline	CG6502. Drosophila melanogaster.
Family and domain databases
InterPro	IPR026489. CXC_dom. IPR001005. SANT/Myb. IPR001214. SET_dom. [Graphical view]
Pfam	PF00856. SET. 1 hit. [Graphical view]
SMART	SM00717. SANT. 2 hits. SM00317. SET. 1 hit. [Graphical view]
PROSITE	PS51633. CXC. 1 hit. PS51293. SANT. False negative. PS50280. SET. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	39203.
NextBio	812462.

Entry information

Entry name

EZ_DROME

Accession

Primary (citable) accession number: P42124
Secondary accession number(s): B7Z0G2, Q9VTA3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	March 28, 2003
Last modified:	May 29, 2013
This is version 126 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project