Reviewed, UniProtKB/Swiss-Prot Q15910 (EZH2_HUMAN)

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
    ENX-1
    Lysine N-methyltransferase 6

Gene names

Name:	EZH2
Synonyms:	KMT6

Organism

Homo sapiens (Human) [Complete proteome]

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.12 Ref.13 Ref.14 Ref.16 Ref.19 Ref.23 Ref.25 Ref.28 Ref.30 Ref.31 Ref.36 Ref.38
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.13 Ref.19 Ref.25 Ref.38 Ref.5 Ref.6 Ref.7 Ref.8 Ref.21
Subcellular location	Nucleus Ref.12 Ref.14 Ref.6 Ref.10.
Tissue specificity	Expressed in many tissues. Overexpressed in numerous tumor types including carcinomas of the breast, colon, larynx, lymphoma and testis. Ref.12
Developmental stage	Expression decreases during senescence of embryonic fibroblasts (HEFs). Expression peaks at the G1/S phase boundary. Ref.12 Ref.31 Ref.17
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 TP53/p53. Ref.12 Ref.31 Ref.17
Post-translational modification	Phosphorylated by AKT1. Phosphorylation by AKT1 reduces methyltransferase activity. Ref.21 Ref.18 Ref.22 Ref.27 Ref.29 Ref.33 Ref.34 Ref.35 Ref.39 Ref.40 Ref.41
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.15 and Ref.20), although other studies have demonstrated no methylation of 'Lys-26' of histone H1 by PRC2 (Ref.24).

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	S-adenosyl-L-methionine
Molecular function	Chromatin regulator Methyltransferase Repressor Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of retinoic acid receptor signaling pathway Ref.19 Inferred from mutant phenotype. Source: UniProtKB regulation of transcription, DNA-dependent Traceable author statement. Source: ProtInc transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	ESC/E(Z) complex Ref.13 Inferred from direct assay. Source: MGI
Molecular function	DNA binding Ref.1 Traceable author statement. Source: ProtInc histone-lysine N-methyltransferase activity Inferred from electronic annotation. Source: EC protein binding Ref.19 Ref.25 Inferred from physical interaction. Source: UniProtKB transcription repressor activity Ref.19 Inferred from mutant phenotype. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DNMT1	P26358	3	EBI-530054,EBI-719459
DNMT3A	Q9Y6K1	3	EBI-530054,EBI-923653
DNMT3B	Q9UBC3	3	EBI-530054,EBI-80125
RARA	P10276	2	EBI-530054,EBI-413374

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.39
	Modified residue	363	1	Phosphoserine Ref.41
	Modified residue	366	1	Phosphoserine Ref.39
	Modified residue	367	1	Phosphothreonine Ref.39
	Modified residue	380	1	Phosphoserine Ref.33
	Modified residue	487	1	Phosphothreonine Ref.18 Ref.22 Ref.27 Ref.29 Ref.34 Ref.35 Ref.39 Ref.40 Ref.41
Natural variations
	Natural variant	185	1	D → H: dbSNP rs2302427.		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.21
	Mutagenesis	21	1	S → D: Reduces methyltransferase activity towards 'Lys-27' of histone H3 and abrogates phosphorylation by PKB/AKT1. Ref.21
	Mutagenesis	588	1	C → Y: Strongly impairs methyltransferase activity towards 'Lys-27' of histone H3. Ref.9
	Mutagenesis	689	1	H → A: Abrogates methyltransferase activity. Ref.38 Ref.9
	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)
	Q15910-1 [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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]. 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].
[3]	"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].
[4]	"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.
[5]	"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.
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	"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.
[18]	"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: Epithelium.
[19]	"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.
[20]	"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.
[21]	"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.
[22]	"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: Epithelium.
[23]	"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.
[24]	"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.
[25]	"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.
[26]	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)
[27]	"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: Epithelium.
[28]	"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.
[29]	"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: Epithelium.
[30]	"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.
[31]	"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.
[32]	"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.
[33]	"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.
[34]	"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.
[35]	"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.
[36]	"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.
[37]	"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.
[38]	"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.
[39]	"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.
[40]	"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.
[41]	"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: T-cell.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X95653 mRNA. Translation: CAA64955.1.
U61145 mRNA. Translation: AAC51520.1.
AC006323 Genomic DNA. No translation available.
AC073140 Genomic DNA. No translation available.
U52965 Genomic DNA. Translation: AAC50591.1.

IPI

IPI00947357.

PIR

G02838.

UniGene

Hs.444082

3D structure databases

PDBe
RCSB PDB
PDBj

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

SMR

Q15910. Positions 40-68, 503-731, 553-732.

ModBase

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Protein-protein interaction databases

IntAct

Q15910. 20 interactions.

STRING

Q15910.

PTM databases

PhosphoSite

Q15910.

Proteomic databases

PRIDE

Q15910.

Genome annotation databases

Ensembl

ENST00000460911; ENSP00000419711; ENSG00000106462; Homo sapiens. [Genome view]

UCSC

uc003wfd.1. human.

Organism-specific databases

GeneCards

GC07M148135.

HGNC

HGNC:3527. EZH2.

HPA

CAB009589.

MIM

601573. gene.

PharmGKB

PA27939.

GenAtlas

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Phylogenomic databases

eggNOG

prNOG17111.

HOVERGEN

Q15910.

InParanoid

Q15910.

Gene expression databases

ArrayExpress

Q15910.

Bgee

Q15910.

CleanEx

HS_EZH2.

Genevestigator

Q15910.

GermOnline

ENSG00000106462. Homo sapiens.

Family and domain databases

InterPro

IPR001005. SANT_DNA-bd.
IPR001214. SET_dom.
[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

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Other Resources

SOURCE

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Entry information

Entry name

EZH2_HUMAN

Accession

Primary (citable) accession number: Q15910
Secondary accession number(s): Q15755, Q92857

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 15, 1998
Last modified:	February 9, 2010
This is version 91 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.