Q15910 (EZH2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone-lysine N-methyltransferase EZH2
EC=2.1.1.43

Alternative name(s):
ENX-1
Enhancer of zeste homolog 2
Lysine N-methyltransferase 6

Gene names

Name:	EZH2
Synonyms:	KMT6

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	746 AA.
Sequence status	Complete.
Protein existence	Evidence at protein 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. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1, CDKN2A and retinoic acid target genes. Ref.15 Ref.16 Ref.17 Ref.19 Ref.22 Ref.26 Ref.28 Ref.31 Ref.33 Ref.34 Ref.39 Ref.41 Ref.45
Catalytic activity	S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].
Subunit structure	Binds ATRX via the SET domain Probable. Component of the PRC2/EED-EZH2 complex, which includes EED, EZH2, SUZ12, RBBP4 and RBBP7 and possibly AEBP2. The minimum components required for methyltransferase activity of the PRC2/EED-EZH2 complex are EED, EZH2 and SUZ12. The PRC2 complex may also interact with DNMT1, DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via the SUZ12 subunit. Interacts with HDAC1 and HDAC2. Interacts with PRAME. Ref.8 Ref.9 Ref.10 Ref.11 Ref.16 Ref.22 Ref.24 Ref.28 Ref.41
Subcellular location	Nucleus Ref.9 Ref.13 Ref.15 Ref.17.
Tissue specificity	Expressed in many tissues. Overexpressed in numerous tumor types including carcinomas of the breast, colon, larynx, lymphoma and testis. Ref.15
Developmental stage	Expression decreases during senescence of embryonic fibroblasts (HEFs). Expression peaks at the G1/S phase boundary. Ref.15 Ref.20 Ref.34
Induction	Expression is induced by E2F1, E2F2 and E2F3. Expression is reduced in cells subject to numerous types of stress including UV-, IR- and bleomycin-induced DNA damage and by activation of p53/TP53. Ref.15 Ref.20 Ref.34
Post-translational modification	Phosphorylated by AKT1. Phosphorylation by AKT1 reduces methyltransferase activity. Phosphorylation at Thr-345 by CDK1 and CDK2 promotes maintenance of H3K27me3 levels at EZH2-target loci, thus leading to epigenetic gene silencing. Ref.21 Ref.24 Ref.25 Ref.30 Ref.32 Ref.36 Ref.37 Ref.38 Ref.42 Ref.43 Ref.44 Ref.45
Sequence similarities	Belongs to the histone-lysine methyltransferase family. EZ subfamily. Contains 1 SET domain.
Caution	Two variants of the PRC2 complex have been described, termed PRC3 and PRC4. Each of the three complexes may include a different complement of EED isoforms, although the precise sequences of the isoforms in each complex have not been determined. The PRC2 and PRC4 complexes may also methylate 'Lys-26' of histone H1 in addition to 'Lys-27' of histone H3 (Ref.18 and Ref.23), although other studies have demonstrated no methylation of 'Lys-26' of histone H1 by PRC2 (Ref.27).

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	S-adenosyl-L-methionine
Molecular function	Chromatin regulator Methyltransferase Repressor Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	negative regulation of retinoic acid receptor signaling pathway Inferred from mutant phenotype Ref.22. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from mutant phenotype Ref.22. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	ESC/E(Z) complex Inferred from direct assay. Source: UniProtKB
Molecular function	DNA binding Traceable author statement. Source: ProtInc histone-lysine N-methyltransferase activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction Ref.22. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DNMT1	P26358	4	EBI-530054,EBI-719459
DNMT3A	Q9Y6K1	4	EBI-530054,EBI-923653
DNMT3B	Q9UBC3	4	EBI-530054,EBI-80125
PML-RAR	Q15156	8	EBI-530054,EBI-867256
RARA	P10276	2	EBI-530054,EBI-413374

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q15910-1)

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: Q15910-2)

The sequence of this isoform differs from the canonical sequence as follows:
     297-298: HP → HRKCNYS

Isoform 3 (identifier: Q15910-3)

The sequence of this isoform differs from the canonical sequence as follows:
     83-121: Missing.

Isoform 4 (identifier: Q15910-4)

The sequence of this isoform differs from the canonical sequence as follows:
     74-82: Missing.

Note: No experimental confirmation available.

Isoform 5 (identifier: Q15910-5)

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

Note: No experimental 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_0000213992
Regions
	Domain	611 – 731	121	SET
	Region	1 – 340	340	Interaction with DNMT1, DNMT3A and DNMT3B
	Region	39 – 68	30	Interaction with EED By similarity
	Compositional bias	523 – 605	83	Cys-rich
Amino acid modifications
	Modified residue	21	1	Phosphoserine; by PKB/AKT1
	Modified residue	339	1	Phosphothreonine Ref.42
	Modified residue	345	1	Phosphothreonine; by CDK1 and CDK2 Ref.45
	Modified residue	363	1	Phosphoserine Ref.44
	Modified residue	366	1	Phosphoserine Ref.42
	Modified residue	367	1	Phosphothreonine Ref.42
	Modified residue	380	1	Phosphoserine Ref.36
	Modified residue	487	1	Phosphothreonine Ref.21 Ref.25 Ref.30 Ref.32 Ref.37 Ref.38 Ref.42 Ref.43 Ref.44
Natural variations
	Alternative sequence	74 – 82	9	Missing in isoform 4 and isoform 5.		VSP_038813
	Alternative sequence	83 – 121	39	Missing in isoform 3.		VSP_038814
	Alternative sequence	297 – 298	2	HP → HRKCNYS in isoform 2.		VSP_038815
	Alternative sequence	511 – 553	43	DGSSN…CSSEC → G in isoform 5.		VSP_038816
	Natural variant	185	1	D → H. Corresponds to variant rs2302427 [ dbSNP | Ensembl ].		VAR_055795
Experimental info
	Mutagenesis	21	1	S → A: Enhances methyltransferase activity towards 'Lys-27' of histone H3 and abrogates phosphorylation by PKB/AKT1. Ref.24
	Mutagenesis	21	1	S → D: Reduces methyltransferase activity towards 'Lys-27' of histone H3 and abrogates phosphorylation by PKB/AKT1. Ref.24
	Mutagenesis	345	1	T → A: Impaired CDK1- and CDK-2 mediated phosphorylation and subsequent gene silencing. Altered EZH2-mediated cell proliferation and migration. Ref.45
	Mutagenesis	588	1	C → Y: Strongly impairs methyltransferase activity towards 'Lys-27' of histone H3. Ref.12
	Mutagenesis	689	1	H → A: Abrogates methyltransferase activity. Ref.12 Ref.41
	Sequence conflict	39	1	K → N in BAG52592. Ref.3
	Sequence conflict	224	1	F → L in CAA64955. Ref.1
	Sequence conflict	724	1	F → V in CAA64955. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 15, 1998. Version 2. Checksum: 1B5029EB9D509BE5	FASTA	746	85,363
	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 ATPNTYKRKN 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 [UniParc]. Checksum: D885CF02E60EF836	FASTA	751	86,018
	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 KYDCFLHRKC 310 320 330 340 350 360 NYSFHATPNT YKRKNTETAL DNKPCGPQCY QHLEGAKEFA AALTAERIKT PPKRPGGRRR 370 380 390 400 410 420 GRLPNNSSRP STPTINVLES KDTDSDREAG TETGGENNDK EEEEKKDETS SSSEANSRCQ 430 440 450 460 470 480 TPIKMKPNIE PPENVEWSGA EASMFRVLIG TYYDNFCAIA RLIGTKTCRQ VYEFRVKESS 490 500 510 520 530 540 IIAPAPAEDV DTPPRKKKRK HRLWAAHCRK IQLKKDGSSN HVYNYQPCDH PRQPCDSSCP 550 560 570 580 590 600 CVIAQNFCEK FCQCSSECQN RFPGCRCKAQ CNTKQCPCYL AVRECDPDLC LTCGAADHWD 610 620 630 640 650 660 SKNVSCKNCS IQRGSKKHLL LAPSDVAGWG IFIKDPVQKN EFISEYCGEI ISQDEADRRG 670 680 690 700 710 720 KVYDKYMCSF LFNLNNDFVV DATRKGNKIR FANHSVNPNC YAKVMMVNGD HRIGIFAKRA 730 740 750 IQTGEELFFD YRYSQADALK YVGIEREMEI P
	Isoform 3 [UniParc]. Checksum: 48EAF1393A9EA4F2	FASTA	707	81,038
	10 20 30 40 50 60 MGQTGKKSEK GPVCWRKRVK SEYMRLRQLK RFRRADEVKS MFSSNRQKIL ERTEILNQEW 70 80 90 100 110 120 KQRRIQPVHI LTSVSSLRGT REVEDETVLH NIPYMGDEVL DQDGTFIEEL IKNYDGKVHG 130 140 150 160 170 180 DRECGFINDE IFVELVNALG QYNDDDDDDD GDDPEEREEK QKDLEDHRDD KESRPPRKFP 190 200 210 220 230 240 SDKIFEAISS MFPDKGTAEE LKEKYKELTE QQLPGALPPE CTPNIDGPNA KSVQREQSLH 250 260 270 280 290 300 SFHTLFCRRC FKYDCFLHPF HATPNTYKRK NTETALDNKP CGPQCYQHLE GAKEFAAALT 310 320 330 340 350 360 AERIKTPPKR PGGRRRGRLP NNSSRPSTPT INVLESKDTD SDREAGTETG GENNDKEEEE 370 380 390 400 410 420 KKDETSSSSE ANSRCQTPIK MKPNIEPPEN VEWSGAEASM FRVLIGTYYD NFCAIARLIG 430 440 450 460 470 480 TKTCRQVYEF RVKESSIIAP APAEDVDTPP RKKKRKHRLW AAHCRKIQLK KDGSSNHVYN 490 500 510 520 530 540 YQPCDHPRQP CDSSCPCVIA QNFCEKFCQC SSECQNRFPG CRCKAQCNTK QCPCYLAVRE 550 560 570 580 590 600 CDPDLCLTCG AADHWDSKNV SCKNCSIQRG SKKHLLLAPS DVAGWGIFIK DPVQKNEFIS 610 620 630 640 650 660 EYCGEIISQD EADRRGKVYD KYMCSFLFNL NNDFVVDATR KGNKIRFANH SVNPNCYAKV 670 680 690 700 MMVNGDHRIG IFAKRAIQTG EELFFDYRYS QADALKYVGI EREMEIP
	Isoform 4 [UniParc]. Checksum: 3DC6EA40E093A80B	FASTA	737	84,377
	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 HATPNTYKRK 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 KDGSSNHVYN YQPCDHPRQP CDSSCPCVIA QNFCEKFCQC 550 560 570 580 590 600 SSECQNRFPG CRCKAQCNTK QCPCYLAVRE CDPDLCLTCG AADHWDSKNV SCKNCSIQRG 610 620 630 640 650 660 SKKHLLLAPS DVAGWGIFIK DPVQKNEFIS EYCGEIISQD EADRRGKVYD KYMCSFLFNL 670 680 690 700 710 720 NNDFVVDATR KGNKIRFANH SVNPNCYAKV MMVNGDHRIG IFAKRAIQTG EELFFDYRYS 730 QADALKYVGI EREMEIP
	Isoform 5 [UniParc]. Checksum: 9DEAFE0755468660	FASTA	695	79,621
	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 HATPNTYKRK 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

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[1]	"Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2." Chen H., Rossier C., Antonarakis S.E. Genomics 38:30-37(1996) [PubMed: 8954776] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Mammalian homologues of the Polycomb-group gene Enhancer of zeste mediate gene silencing in Drosophila heterochromatin and at S. cerevisiae telomeres." Laible G., Wolf A., Dorn R., Reuter G., Nislow C., Lebersorger A., Popkin D., Pillus L., Jenuwein T. EMBO J. 16:3219-3232(1997) [PubMed: 9214638] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 4 AND 5). Tissue: Brain and Testis.
[4]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Pancreas.
[7]	"Interaction of Vav with ENX-1, a putative transcriptional regulator of homeobox gene expression." Hobert O., Jallal B., Ullrich A. Mol. Cell. Biol. 16:3066-3073(1996) [PubMed: 8649418] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 134-746.
[8]	"Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein." Cardoso C., Timsit S., Villard L., Khrestchatisky M., Fontes M., Colleaux L. Hum. Mol. Genet. 7:679-684(1998) [PubMed: 9499421] [Abstract] Cited for: INTERACTION WITH ATRX.
[9]	"Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes." Sewalt R.G.A.B., van der Vlag J., Gunster M.J., Hamer K.M., den Blaauwen J.L., Satijn D.P.E., Hendrix T., van Driel R., Otte A.P. Mol. Cell. Biol. 18:3586-3595(1998) [PubMed: 9584199] [Abstract] Cited for: INTERACTION WITH EED, SUBCELLULAR LOCATION.
[10]	"Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation." van der Vlag J., Otte A.P. Nat. Genet. 23:474-478(1999) [PubMed: 10581039] [Abstract] Cited for: INTERACTION WITH EED; HDAC1 AND HDAC2.
[11]	"The polycomb group protein EED interacts with YY1, and both proteins induce neural tissue in Xenopus embryos." Satijn D.P.E., Hamer K.M., den Blaauwen J., Otte A.P. Mol. Cell. Biol. 21:1360-1369(2001) [PubMed: 11158321] [Abstract] Cited for: INTERACTION WITH EED.
[12]	"Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein." Kuzmichev A., Nishioka K., Erdjument-Bromage H., Tempst P., Reinberg D. Genes Dev. 16:2893-2905(2002) [PubMed: 12435631] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE PRC2 COMPLEX WITH EED; RBBP4; RBBP7 AND SUZ12, METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX, MUTAGENESIS OF CYS-588 AND HIS-689.
[13]	"Selective interactions between vertebrate polycomb homologs and the SUV39H1 histone lysine methyltransferase suggest that histone H3-K9 methylation contributes to chromosomal targeting of Polycomb group proteins." Sewalt R.G.A.B., Lachner M., Vargas M., Hamer K.M., den Blaauwen J.L., Hendrix T., Melcher M., Schweizer D., Jenuwein T., Otte A.P. Mol. Cell. Biol. 22:5539-5553(2002) [PubMed: 12101246] [Abstract] Cited for: SUBCELLULAR LOCATION.
[14]	"Role of histone H3 lysine 27 methylation in Polycomb-group silencing." Cao R., Wang L., Wang H., Xia L., Erdjument-Bromage H., Tempst P., Jones R.S., Zhang Y. Science 298:1039-1043(2002) [PubMed: 12351676] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE PRC2 COMPLEX WITH EED; RBBP4; RBBP7 AND SUZ12, METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX.
[15]	"EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer." Bracken A.P., Pasini D., Capra M., Prosperini E., Colli E., Helin K. EMBO J. 22:5323-5335(2003) [PubMed: 14532106] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, INDUCTION, TISSUE SPECIFICITY.
[16]	"Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity." Pasini D., Bracken A.P., Jensen M.R., Lazzerini Denchi E., Helin K. EMBO J. 23:4061-4071(2004) [PubMed: 15385962] [Abstract] Cited for: FUNCTION, INTERACTION WITH EED AND SUZ12, METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX.
[17]	"Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27." Kirmizis A., Bartley S.M., Kuzmichev A., Margueron R., Reinberg D., Green R., Farnham P.J. Genes Dev. 18:1592-1605(2004) [PubMed: 15231737] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[18]	"Different EZH2-containing complexes target methylation of histone H1 or nucleosomal histone H3." Kuzmichev A., Jenuwein T., Tempst P., Reinberg D. Mol. Cell 14:183-193(2004) [PubMed: 15099518] [Abstract] Cited for: CHARACTERIZATION OF THE PRC2 AND PRC3 COMPLEXES INCLUDING EED; EZH2; RBBP4; RBBP7 AND SUZ12, METHYLTRANSFERASE ACTIVITY OF THE PRC2 AND PRC3 COMPLEXES.
[19]	"SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex." Cao R., Zhang Y. Mol. Cell 15:57-67(2004) [PubMed: 15225548] [Abstract] Cited for: FUNCTION, CHARACTERIZATION OF THE PRC2 COMPLEX INCLUDING AEBP2; EED; EZH2; RBBP4 AND SUZ12, METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX.
[20]	"Activated p53 suppresses the histone methyltransferase EZH2 gene." Tang X., Milyavsky M., Shats I., Erez N., Goldfinger N., Rotter V. Oncogene 23:5759-5769(2004) [PubMed: 15208672] [Abstract] Cited for: DEVELOPMENTAL STAGE, INDUCTION.
[21]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-487, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling." Epping M.T., Wang L., Edel M.J., Carlee L., Hernandez M., Bernards R. Cell 122:835-847(2005) [PubMed: 16179254] [Abstract] Cited for: FUNCTION IN RETINOIC ACID SIGNALING, INTERACTION WITH PRAME.
[23]	"Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation." Kuzmichev A., Margueron R., Vaquero A., Preissner T.S., Scher M., Kirmizis A., Ouyang X., Brockdorff N., Abate-Shen C., Farnham P.J., Reinberg D. Proc. Natl. Acad. Sci. U.S.A. 102:1859-1864(2005) [PubMed: 15684044] [Abstract] Cited for: CHARACTERIZATION OF THE PRC4 COMPLEX INCLUDING EED; EZH2; RBBP4; RBBP7; SUZ12 AND SIRT1, METHYLTRANSFERASE ACTIVITY OF THE PRC4 COMPLEX.
[24]	"Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3." Cha T.-L., Zhou B.P., Xia W., Wu Y., Yang C.-C., Chen C.-T., Ping B., Otte A.P., Hung M.-C. Science 310:306-310(2005) [PubMed: 16224021] [Abstract] Cited for: INTERACTION WITH EED AND SUZ12, PHOSPHORYLATION BY AKT1, MUTAGENESIS OF SER-21.
[25]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-487, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[26]	"Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions." Bracken A.P., Dietrich N., Pasini D., Hansen K.H., Helin K. Genes Dev. 20:1123-1136(2006) [PubMed: 16618801] [Abstract] Cited for: FUNCTION.
[27]	"Substrate preferences of the EZH2 histone methyltransferase complex." Martin C., Cao R., Zhang Y. J. Biol. Chem. 281:8365-8370(2006) [PubMed: 16431907] [Abstract] Cited for: METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX.
[28]	"The Polycomb group protein EZH2 directly controls DNA methylation." Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C., Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M., Esteller M., Di Croce L., de Launoit Y., Fuks F. Nature 439:871-874(2006) [PubMed: 16357870] [Abstract] Cited for: FUNCTION, INTERACTION OF THE PRC2 COMPLEX WITH DNMT1; DNMT3A AND DNMT3B.
[29]	Erratum Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C., Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M., Esteller M., Di Croce L., de Launoit Y., Fuks F. Nature 446:824-824(2006)
[30]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-487, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[31]	"Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells." Kim D.H., Villeneuve L.M., Morris K.V., Rossi J.J. Nat. Struct. Mol. Biol. 13:793-797(2006) [PubMed: 16936726] [Abstract] Cited for: FUNCTION.
[32]	"Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-487, MASS SPECTROMETRY. Tissue: Cervix adenocarcinoma.
[33]	"pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene." Kotake Y., Cao R., Viatour P., Sage J., Zhang Y., Xiong Y. Genes Dev. 21:49-54(2007) [PubMed: 17210787] [Abstract] Cited for: FUNCTION.
[34]	"The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells." Bracken A.P., Kleine-Kohlbrecher D., Dietrich N., Pasini D., Gargiulo G., Beekman C., Theilgaard-Moench K., Minucci S., Porse B.T., Marine J.-C., Hansen K.H., Helin K. Genes Dev. 21:525-530(2007) [PubMed: 17344414] [Abstract] Cited for: FUNCTION, DEVELOPMENTAL STAGE, INDUCTION.
[35]	"Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer." Schlesinger Y., Straussman R., Keshet I., Farkash S., Hecht M., Zimmerman J., Eden E., Yakhini Z., Ben-Shushan E., Reubinoff B.E., Bergman Y., Simon I., Cedar H. Nat. Genet. 39:232-236(2007) [PubMed: 17200670] [Abstract] Cited for: DE NOVO DNA METHYLATION OF PRC2 TARGET GENES.
[36]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-380, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[37]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-487, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[38]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-487, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[39]	"Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms." Margueron R., Li G., Sarma K., Blais A., Zavadil J., Woodcock C.L., Dynlacht B.D., Reinberg D. Mol. Cell 32:503-518(2008) [PubMed: 19026781] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN THE PRC2/EED-EZH1 COMPLEX.
[40]	"Role of hPHF1 in H3K27 methylation and Hox gene silencing." Cao R., Wang H., He J., Erdjument-Bromage H., Tempst P., Zhang Y. Mol. Cell. Biol. 28:1862-1872(2008) [PubMed: 18086877] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE PRC2 COMPLEX, METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX.
[41]	"Ezh2 requires PHF1 to efficiently catalyze H3 lysine 27 trimethylation in vivo." Sarma K., Margueron R., Ivanov A., Pirrotta V., Reinberg D. Mol. Cell. Biol. 28:2718-2731(2008) [PubMed: 18285464] [Abstract] Cited for: FUNCTION, INTERACTION WITH EED; SUZ12 AND PHF1, METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX, MUTAGENESIS OF HIS-689.
[42]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-339; SER-366; THR-367 AND THR-487, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[43]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-487, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[44]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363 AND THR-487, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[45]	"Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2." Chen S., Bohrer L.R., Rai A.N., Pan Y., Gan L., Zhou X., Bagchi A., Simon J.A., Huang H. Nat. Cell Biol. 12:1108-1114(2010) [PubMed: 20935635] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT THR-345 BY CDK1 AND CDK2, MUTAGENESIS OF THR-345.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X95653 mRNA. Translation: CAA64955.1.
U61145 mRNA. Translation: AAC51520.1.
AK302216 mRNA. Translation: BAH13652.1.
AK092676 mRNA. Translation: BAG52592.1.
AK293239 mRNA. Translation: BAH11472.1.
AK314291 mRNA. Translation: BAG36948.1.
AC006323 Genomic DNA. No translation available.
AC073140 Genomic DNA. No translation available.
CH471146 Genomic DNA. Translation: EAW80067.1.
CH471146 Genomic DNA. Translation: EAW80070.1.
BC010858 mRNA. Translation: AAH10858.1.
U52965 Genomic DNA. Translation: AAC50591.1.

IPI

IPI00171252.
IPI00376787.
IPI00945286.
IPI00947348.
IPI00947357.

PIR

G02838.

RefSeq

NP_001190176.1. NM_001203247.1.
NP_001190177.1. NM_001203248.1.
NP_001190178.1. NM_001203249.1.
NP_004447.2. NM_004456.4.
NP_694543.1. NM_152998.2.

UniGene

Hs.444082.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2C6V	model	-	A	508-734	[»]

ProteinModelPortal

Q15910.

SMR

Q15910. Positions 40-68, 533-733.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-34002N.

IntAct

Q15910. 19 interactions.

MINT

MINT-1371596.

STRING

Q15910.

PTM databases

PhosphoSite

Q15910.

Polymorphism databases

DMDM

3334180.

Proteomic databases

PRIDE

Q15910.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000350995; ENSP00000223193; ENSG00000106462.
ENST00000460911; ENSP00000419711; ENSG00000106462.
ENST00000476773; ENSP00000419050; ENSG00000106462.
ENST00000478654; ENSP00000417062; ENSG00000106462.
ENST00000483967; ENSP00000419856; ENSG00000106462.

GeneID

2146.

KEGG

hsa:2146.

UCSC

uc003wfd.1. human.

Organism-specific databases

CTD

2146.

GeneCards

GC07M148504.

HGNC

HGNC:3527. EZH2.

HPA

CAB009589.

MIM

601573. gene.

neXtProt

NX_Q15910.

PharmGKB

PA27939.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17111.

GeneTree

ENSGT00560000076698.

HOVERGEN

HBG002453.

InParanoid

Q15910.

OMA

PDEREEK.

OrthoDB

EOG4WWRJ0.

Gene expression databases

ArrayExpress

Q15910.

Bgee

Q15910.

CleanEx

HS_EZH2.

Genevestigator

Q15910.

GermOnline

ENSG00000106462. Homo sapiens.

Family and domain databases

InterPro

IPR021654. EZH2_WD-Binding.
IPR001005. SANT_DNA-bd.
IPR001214. SET_dom.
[Graphical view]

KO

K11430.

Pfam

PF11616. EZH2_WD-Binding. 1 hit.
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...

Other

SOURCE

Search...

Entry information

Entry name

EZH2_HUMAN

Accession

Primary (citable) accession number: Q15910
Secondary accession number(s): B2RAQ1 , B3KS30, B7Z1D6, B7Z7L6, Q15755, Q92857, Q96FI6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 15, 1998
Last modified:	January 25, 2012
This is version 111 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.