Reviewed, UniProtKB/Swiss-Prot Q4R381 (EZH2_MACFA)

Names and origin

Protein names

Recommended name:
    Histone-lysine N-methyltransferase EZH2
    EC=2.1.1.43
Alternative name(s):
    Enhancer of zeste homolog 2

Gene names

Name:	EZH2
ORF Names:	QtsA-15957, QtsA-18821

Organism

Macaca fascicularis (Crab eating macaque) (Cynomolgus monkey)

Taxonomic identifier

9541 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Cercopithecidae › Cercopithecinae › Macaca

Protein attributes

Sequence length	746 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Compared to EZH2-containing complexes, it is more abundant in embryonic stem cells and plays a major role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems By similarity.
Catalytic activity	S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N(6)-methyl-L-lysine.
Subunit structure	Component of the PRC2/EED-EZH2 complex, which includes EED, EZH2, SUZ12, RBBP4 and RBBP7 and possibly AEBP2 By similarity. The minimum components required for methyltransferase activity of the PRC2/EED-EZH2 complex are EED, EZH2 and SUZ12 By similarity. The PRC2 complex may also interact with DNMT1, DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via the SUZ12 subunit By similarity. Interacts with HDAC1 and HDAC2 By similarity. Binds ATRX via the SET domain Probable.
Subcellular location	Nucleus By similarity.
Post-translational modification	Phosphorylated by AKT1 By similarity. Phosphorylation by AKT1 reduces methyltransferase activity By similarity.
Sequence similarities	Belongs to the histone-lysine methyltransferase family. EZ subfamily. Contains 1 SET domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	S-adenosyl-L-methionine
Molecular function	Chromatin regulator Methyltransferase Repressor Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	DNA binding Inferred from electronic annotation. Source: InterPro histone-lysine N-methyltransferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q4R381-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q4R381-2)

The sequence of this isoform differs from the canonical sequence as follows:
     74-82: Missing.
     511-553: DGSSNHVYNYQPCDHPRQPCDSSCPCVIAQNFCEKFCQCSSEC → G

Note: No expeirmental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 746	746	Histone-lysine N-methyltransferase EZH2		PRO_0000345426
Regions
	Domain	611 – 731	121	SET
	Region	1 – 340	340	Interaction with DNMT1, DNMT3A and DNMT3B By similarity
	Region	39 – 68	30	Interaction with EED By similarity
	Compositional bias	183 – 209	27	Asp-rich
	Compositional bias	523 – 588	66	Cys-rich
Amino acid modifications
	Modified residue	21	1	Phosphoserine; by PKB/AKT1 By similarity
	Modified residue	339	1	Phosphothreonine By similarity
	Modified residue	366	1	Phosphoserine By similarity
	Modified residue	367	1	Phosphothreonine By similarity
	Modified residue	380	1	Phosphoserine By similarity
	Modified residue	487	1	Phosphothreonine By similarity
Natural variations
	Alternative sequence	74 – 82	9	Missing in isoform 2.		VSP_034951
	Alternative sequence	511 – 553	43	DGSSN…CSSEC → G in isoform 2.		VSP_034952
Experimental info
	Sequence conflict	305	1	A → T in BAE01042. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 19, 2005. Version 1. Checksum: 16942199E6E75621	FASTA	746	85,333
	10 20 30 40 50 60 MGQTGKKSEK GPVCWRKRVK SEYMRLRQLK RFRRADEVKS MFSSNRQKIL ERTEILNQEW 70 80 90 100 110 120 KQRRIQPVHI LTSVSSLRGT RECSVTSDLD FPTQVIPLKT LNAVASVPIM YSWSPLQQNF 130 140 150 160 170 180 MVEDETVLHN IPYMGDEVLD QDGTFIEELI KNYDGKVHGD RECGFINDEI FVELVNALGQ 190 200 210 220 230 240 YNDDDDDDDG DDPEEREEKQ KDLEDHRDDK ESRPPRKFPS DKIFEAISSM FPDKGTAEEL 250 260 270 280 290 300 KEKYKELTEQ QLPGALPPEC TPNIDGPNAK SVQREQSLHS FHTLFCRRCF KYDCFLHPFH 310 320 330 340 350 360 ATPNAYKRKN TETALDNKPC GPQCYQHLEG AKEFAAALTA ERIKTPPKRP GGRRRGRLPN 370 380 390 400 410 420 NSSRPSTPTI NVLESKDTDS DREAGTETGG ENNDKEEEEK KDETSSSSEA NSRCQTPIKM 430 440 450 460 470 480 KPNIEPPENV EWSGAEASMF RVLIGTYYDN FCAIARLIGT KTCRQVYEFR VKESSIIAPA 490 500 510 520 530 540 PAEDVDTPPR KKKRKHRLWA AHCRKIQLKK DGSSNHVYNY QPCDHPRQPC DSSCPCVIAQ 550 560 570 580 590 600 NFCEKFCQCS SECQNRFPGC RCKAQCNTKQ CPCYLAVREC DPDLCLTCGA ADHWDSKNVS 610 620 630 640 650 660 CKNCSIQRGS KKHLLLAPSD VAGWGIFIKD PVQKNEFISE YCGEIISQDE ADRRGKVYDK 670 680 690 700 710 720 YMCSFLFNLN NDFVVDATRK GNKIRFANHS VNPNCYAKVM MVNGDHRIGI FAKRAIQTGE 730 740 ELFFDYRYSQ ADALKYVGIE REMEIP
	Isoform 2. Checksum: 5ACBCFF4E22411FC	FASTA	695	79,591
	10 20 30 40 50 60 MGQTGKKSEK GPVCWRKRVK SEYMRLRQLK RFRRADEVKS MFSSNRQKIL ERTEILNQEW 70 80 90 100 110 120 KQRRIQPVHI LTSCSVTSDL DFPTQVIPLK TLNAVASVPI MYSWSPLQQN FMVEDETVLH 130 140 150 160 170 180 NIPYMGDEVL DQDGTFIEEL IKNYDGKVHG DRECGFINDE IFVELVNALG QYNDDDDDDD 190 200 210 220 230 240 GDDPEEREEK QKDLEDHRDD KESRPPRKFP SDKIFEAISS MFPDKGTAEE LKEKYKELTE 250 260 270 280 290 300 QQLPGALPPE CTPNIDGPNA KSVQREQSLH SFHTLFCRRC FKYDCFLHPF HATPNAYKRK 310 320 330 340 350 360 NTETALDNKP CGPQCYQHLE GAKEFAAALT AERIKTPPKR PGGRRRGRLP NNSSRPSTPT 370 380 390 400 410 420 INVLESKDTD SDREAGTETG GENNDKEEEE KKDETSSSSE ANSRCQTPIK MKPNIEPPEN 430 440 450 460 470 480 VEWSGAEASM FRVLIGTYYD NFCAIARLIG TKTCRQVYEF RVKESSIIAP APAEDVDTPP 490 500 510 520 530 540 RKKKRKHRLW AAHCRKIQLK KGQNRFPGCR CKAQCNTKQC PCYLAVRECD PDLCLTCGAA 550 560 570 580 590 600 DHWDSKNVSC KNCSIQRGSK KHLLLAPSDV AGWGIFIKDP VQKNEFISEY CGEIISQDEA 610 620 630 640 650 660 DRRGKVYDKY MCSFLFNLNN DFVVDATRKG NKIRFANHSV NPNCYAKVMM VNGDHRIGIF 670 680 690 AKRAIQTGEE LFFDYRYSQA DALKYVGIER EMEIP

References

[1]

"DNA sequences of macaque genes expressed in brain or testis and its evolutionary implications." International consortium for macaque cDNA sequencing and analysis Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Testis.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB168941 mRNA. Translation: BAE01042.1. AB179385 mRNA. Translation: BAE02436.1.
3D structure databases
ModBase	Search...
Phylogenomic databases
HOVERGEN	Q4R381.
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	PS50280. SET. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

EZH2_MACFA

Accession

Primary (citable) accession number: Q4R381
Secondary accession number(s): Q4R780

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 22, 2008
Last sequence update:	July 19, 2005
Last modified:	June 16, 2009
This is version 20 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)