Reviewed, UniProtKB/Swiss-Prot P42124 (EZ_DROME)

Names and origin

Protein names

Recommended name:
    Histone-lysine N-methyltransferase E(z)
    EC=2.1.1.43
Alternative name(s):
    Protein enhancer of zeste
    Lysine N-methyltransferase 6

Gene names

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

Organism

Drosophila melanogaster (Fruit fly) [Complete proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	760 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 + histone L-lysine = S-adenosyl-L-homocysteine + histone N(6)-methyl-L-lysine.
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.8 Ref.13
Subcellular location	Nucleus. Ref.5
Sequence similarities	Belongs to the histone-lysine methyltransferase family. EZ subfamily. 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
Gene Ontology (GO)
Biological process	axon guidance Inferred from mutant phenotype. Source: FlyBase dendrite morphogenesis Inferred from mutant phenotype. Source: FlyBase gene silencing Ref.9 Non-traceable author statement. Source: UniProtKB histone H3-K27 methylation Inferred from mutant phenotype. Source: FlyBase muscle organ development Inferred from mutant phenotype. Source: FlyBase negative regulation of transcription, DNA-dependent Ref.12 Inferred from direct assay. Source: UniProtKB syncytial blastoderm mitotic cell cycle Inferred from mutant phenotype. Source: FlyBase transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	ESC/E(Z) complex Ref.10 Inferred from direct assay. Source: FlyBase nuclear chromatin Ref.9 Non-traceable author statement. Source: UniProtKB
Molecular function	histone methyltransferase activity (H3-K27 specific) Ref.10 Inferred from direct assay. Source: FlyBase protein binding Ref.7 Ref.12 Ref.13 Inferred from physical interaction. Source: UniProtKB transcription factor activity Ref.12 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	Q9W3D5	1	EBI-112315,EBI-93497
Bin1	Q9VEX9	5	EBI-112315,EBI-129424
Caf1	Q24572	1	EBI-112315,EBI-75924
corto	P41046	1	EBI-112315,EBI-300379
esc	Q24338	3	EBI-112315,EBI-88911
escl	Q95SW6	1	EBI-112315,EBI-1207935
Pcl	Q24459	3	EBI-112315,EBI-430086
Rpd3	Q94517	2	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	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)
	P42124-1 [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: 8413234] [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: 10731132] [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: 12537572] [Abstract] Cited for: GENOME REANNOTATION.
[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: 12537569] [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: 9012527] [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: 9566901] [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: 11124122] [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: 11581156] [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: 12408863] [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: 12408864] [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: 12533794] [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: 12697833] [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: 12771214] [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: 18327897] [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
EMBLGenBankDDBJ	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. NP_524021.2.
UniGene	Dm.2823
3D structure databases
HSSP	HSSP built from PDB template 1ML9 based on UniProtKB Q8X225.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:20386N.
IntAct	P42124. 10 interactions.
STRING	P42124.
Genome annotation databases
Ensembl	FBtr0076279; FBpp0076008; FBgn0000629; Drosophila melanogaster. [Genome view]
GeneID	39203.
KEGG	dme:Dmel_CG6502.
NMPDR	fig|7227.3.peg.9237.
Organism-specific databases
CTD	39203.
FlyBase	FBgn0000629. E(z).
Phylogenomic databases
HOGENOM	P42124.
OMA	ITCKNVC.
Enzyme and pathway databases
BioCyc	DMEL-XXX-02:DMEL-XXX-02-016127-MON.
Gene expression databases
ArrayExpress	P42124.
Bgee	P42124.
GermOnline	CG6502. Drosophila melanogaster.
Family and domain databases
InterPro	IPR001005. SANT_DNA-bd. IPR001214. SET. [Graphical view]
Pfam	PF00856. SET. 1 hit. [Graphical view]
SMART	SM00717. SANT. 2 hits. SM00317. SET. 1 hit. [Graphical view]
PROSITE	PS51293. SANT. False negative. PS50280. SET. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
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:	November 3, 2009
This is version 92 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project