ID   EZH2_DANRE              Reviewed;         760 AA.
AC   Q08BS4;
DT   22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT   31-OCT-2006, sequence version 1.
DT   02-SEP-2026, entry version 103.
DE   RecName: Full=Histone-lysine N-methyltransferase EZH2;
DE            EC=2.1.1.356 {ECO:0000250|UniProtKB:Q15910};
DE   AltName: Full=Enhancer of zeste homolog 2;
GN   Name=ezh2; Synonyms=zgc:152758;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=AB;
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Catalytic subunit of the PRC2/EED-EZH2 complex, a Polycomb
CC       group (PcG) complex that methylates 'Lys-9' (H3K9me) and 'Lys-27'
CC       (H3K27me) of histone H3, leading to transcriptional repression of the
CC       affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of
CC       histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively.
CC       Displays a preference for substrates with less methylation, loses
CC       activity when progressively more methyl groups are incorporated into
CC       H3K27, H3K27me0 > H3K27me1 > H3K27me2. Compared to EZH1-containing
CC       complexes, it is more abundant in embryonic stem cells and plays a
CC       major role in forming H3K27me3, which is required for embryonic stem
CC       cell identity and proper differentiation. The PRC2/EED-EZH2 complex may
CC       also serve as a recruiting platform for DNA methyltransferases, thereby
CC       linking two epigenetic repression systems.
CC       {ECO:0000250|UniProtKB:Q15910}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl(27)-[histone H3] + 3 S-adenosyl-L-methionine =
CC         N(6),N(6),N(6)-trimethyl-L-lysyl(27)-[histone H3] + 3 S-adenosyl-L-
CC         homocysteine + 3 H(+); Xref=Rhea:RHEA:60292, Rhea:RHEA-COMP:15535,
CC         Rhea:RHEA-COMP:15548, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969,
CC         ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961;
CC         EC=2.1.1.356; Evidence={ECO:0000250|UniProtKB:Q15910};
CC   -!- SUBUNIT: Component of the prc2/eed-ezh2 complex.
CC       {ECO:0000250|UniProtKB:Q15910}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q15910}.
CC   -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC       superfamily. Histone-lysine methyltransferase family. EZ subfamily.
CC       {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR   EMBL; BC124588; AAI24589.1; -; mRNA.
DR   RefSeq; NP_001070747.1; NM_001077279.1.
DR   AlphaFoldDB; Q08BS4; -.
DR   SMR; Q08BS4; -.
DR   FunCoup; Q08BS4; 1320.
DR   STRING; 7955.ENSDARP00000023693; -.
DR   PaxDb; 7955-ENSDARP00000023693; -.
DR   PeptideAtlas; Q08BS4; -.
DR   GeneID; 768133; -.
DR   KEGG; dre:768133; -.
DR   AGR; ZFIN:ZDB-GENE-041111-259; -.
DR   CTD; 2146; -.
DR   ZFIN; ZDB-GENE-041111-259; ezh2.
DR   eggNOG; KOG1079; Eukaryota.
DR   InParanoid; Q08BS4; -.
DR   OrthoDB; 6141102at2759; -.
DR   PhylomeDB; Q08BS4; -.
DR   Reactome; R-DRE-212300; PRC2 methylates histones and DNA.
DR   Reactome; R-DRE-2559580; Oxidative Stress Induced Senescence.
DR   Reactome; R-DRE-3214841; PKMTs methylate histone lysines.
DR   Reactome; R-DRE-8953750; Transcriptional Regulation by E2F6.
DR   Reactome; R-DRE-9764725; Negative Regulation of CDH1 Gene Transcription.
DR   Reactome; R-DRE-9909649; Regulation of PD-L1(CD274) transcription.
DR   PRO; PR:Q08BS4; -.
DR   Proteomes; UP000000437; Chromosome 24.
DR   GO; GO:0035098; C:ESC/E(Z) complex; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0003682; F:chromatin binding; IBA:GO_Central.
DR   GO; GO:0046976; F:histone H3K27 methyltransferase activity; IMP:ZFIN.
DR   GO; GO:0140951; F:histone H3K27 trimethyltransferase activity; ISS:UniProtKB.
DR   GO; GO:1990841; F:promoter-specific chromatin binding; ISS:UniProtKB.
DR   GO; GO:0003713; F:transcription coactivator activity; IDA:ZFIN.
DR   GO; GO:0003712; F:transcription coregulator activity; IDA:ZFIN.
DR   GO; GO:0048565; P:digestive tract development; IMP:ZFIN.
DR   GO; GO:0031101; P:fin regeneration; IMP:ZFIN.
DR   GO; GO:0007507; P:heart development; IMP:ZFIN.
DR   GO; GO:0031507; P:heterochromatin formation; IBA:GO_Central.
DR   GO; GO:0045814; P:negative regulation of gene expression, epigenetic; ISS:UniProtKB.
DR   GO; GO:0042753; P:positive regulation of circadian rhythm; IDA:ZFIN.
DR   GO; GO:1903708; P:positive regulation of hemopoiesis; IMP:ZFIN.
DR   GO; GO:0039008; P:pronephric nephron tubule morphogenesis; IMP:ZFIN.
DR   GO; GO:0001894; P:tissue homeostasis; IMP:ZFIN.
DR   CDD; cd00167; SANT; 1.
DR   CDD; cd19218; SET_EZH2; 1.
DR   FunFam; 2.170.270.10:FF:000001; Putative histone-lysine N-methyltransferase EZH2; 1.
DR   Gene3D; 2.170.270.10; SET domain; 1.
DR   InterPro; IPR026489; CXC_dom.
DR   InterPro; IPR045318; EZH1/2-like.
DR   InterPro; IPR048358; EZH1/2_MCSS.
DR   InterPro; IPR021654; EZH1/EZH2_N.
DR   InterPro; IPR044439; EZH2_SET.
DR   InterPro; IPR041343; PRC2_HTH_1.
DR   InterPro; IPR041355; Pre-SET_CXC.
DR   InterPro; IPR001005; SANT/Myb.
DR   InterPro; IPR001214; SET_dom.
DR   InterPro; IPR046341; SET_dom_sf.
DR   InterPro; IPR033467; Tesmin/TSO1-like_CXC.
DR   PANTHER; PTHR45747; HISTONE-LYSINE N-METHYLTRANSFERASE E(Z); 1.
DR   PANTHER; PTHR45747:SF18; HISTONE-LYSINE N-METHYLTRANSFERASE EZH2; 1.
DR   Pfam; PF21358; Ezh2_MCSS; 1.
DR   Pfam; PF11616; EZH2_WD-Binding; 1.
DR   Pfam; PF18118; PRC2_HTH_1; 1.
DR   Pfam; PF18264; preSET_CXC; 1.
DR   Pfam; PF00856; SET; 1.
DR   SMART; SM01114; CXC; 1.
DR   SMART; SM00717; SANT; 2.
DR   SMART; SM00317; SET; 1.
DR   SUPFAM; SSF82199; SET domain; 1.
DR   PROSITE; PS51633; CXC; 1.
DR   PROSITE; PS50280; SET; 1.
PE   2: Evidence at transcript level;
KW   Biological rhythms; Chromatin regulator; Methyltransferase; Nucleus;
KW   Reference proteome; Repressor; S-adenosyl-L-methionine; Transcription;
KW   Transcription regulation; Transferase.
FT   CHAIN           1..760
FT                   /note="Histone-lysine N-methyltransferase EZH2"
FT                   /id="PRO_0000345427"
FT   DOMAIN          517..619
FT                   /note="CXC"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00970"
FT   DOMAIN          626..741
FT                   /note="SET"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   REGION          208..231
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          356..444
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        361..373
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        375..388
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        389..400
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   760 AA;  87145 MW;  E04C67897A59905F CRC64;
     MGLTGRKSEK GPVCWRRRVK SEYMRLRQLK RFRRADEVKS MFSSNRQKIL ERTDILNQEW
     KLRRIQPVHI MTPVSSLRGT RECTVDSGFS EFSRQVIPLK TLNAVASVPV MYSWSPLQQN
     FMVEDETVLH NIPYMGDEIL DQDGTFIEEL IKNYDGKVHG DRECGFINDE IFVELVNALN
     QYSDNEEDDE EDDHHDYKFE KMDLCDGKDD AEDHKEQLSS ESHNNDGSKK FPSDKIFEAI
     SSMFPDKGST EELKEKYKEL TEQQLPGALP PECTPNIDGP NAKSVQREQS LHSFHTLFCR
     RCFKYDCFLH PFQATPNTYK RKNMENLVDS KPCGIYCYMY MVQDGMVREY PAGVVPERAK
     TPSKRSTGRR RGRLPNSNSR PSTPTVNSET KDTDSDREGG ADGNDSNDKD DDDKKDETTS
     SSEANSRCQT PVKLKLSSEP PENVDWSGAE ASLFRVLIGT YYDNFCAIAR LIGTKTCRQV
     YEFRVKESSI IARAPAVDEN TPQRKKKRKH RLWATHCRKI QLKKDGSSNH VYNYQPCDHP
     RQPCDSSCPC VTAQNFCEKF CQCSSECQNR FPGCRCKAQC NTKQCPCYLA VRECDPDLCL
     TCGAAEHWDS KNVSCKNCSI QRGAKKHLLL APSDVAGWGI FIKEPVQKNE FISEYCGEII
     SQDEADRRGK VYDKYMCSFL FNLNNDFVVD ATRKGNKIRF ANHSVNPNCY AKVMMVNGDH
     RIGIFAKRAI QTGEELFFDY RYSQADALKY VGIEREMEIP
//