EZH2
entrez
2146
canonical
uniprot
Q15910
canonical
ensembl
ENSG00000106462
resolver
ensp
ENSP00000223193
resolver
ensp
ENSP00000320147
resolver
ensp
ENSP00000419050
resolver
ensp
ENSP00000419711
resolver
ensp
ENSP00000419856
resolver
ensp
ENSP00000563423
resolver
ensp
ENSP00000563425
resolver
ensp
ENSP00000602009
resolver
ensp
ENSP00000602011
resolver
ensp
ENSP00000602013
resolver
ensp
ENSP00000602016
resolver
ensp
ENSP00000602018
resolver
ensp
ENSP00000679344
resolver
genesymbol
EZH2
resolver
genesymbol_syn
KMT6
resolver
hgnc
HGNC:3527
resolver
uniprot
B2RAQ1
resolver
uniprot
B3KS30
resolver
uniprot
B7Z1D6
resolver
uniprot
B7Z7L6
resolver
uniprot
F2YMM1
resolver
uniprot
Q15755
resolver
uniprot
Q75MG3
resolver
uniprot
Q92857
resolver
uniprot
Q96FI6
resolver
uniprot_entry
EZH2_HUMAN
resolver
uniprot_entry
F2YMM1_HUMAN
resolver
uniprot_sec
B2RAQ1
resolver
uniprot_sec
B3KS30
resolver
uniprot_sec
B7Z1D6
resolver
uniprot_sec
B7Z7L6
resolver
uniprot_sec
Q15755
resolver
uniprot_sec
Q75MG3
resolver
uniprot_sec
Q92857
resolver
uniprot_sec
Q96FI6
resolver
amino_acid_sequence
MGQTGKKSEKGPVCWRKRVKSEYMRLRQLKRFRRADEVKSMFSSNRQKILERTEILNQEWKQRRIQPVHILTSVSSLRGTRECSVTSDLDFPTQVIPLKTLNAVASVPIMYSWSPLQQNFMVEDETVLHNIPYMGDEVLDQDGTFIEELIKNYDGKVHGDRECGFINDEIFVELVNALGQYNDDDDDDDGDDPEEREEKQKDLEDHRDDKESRPPRKFPSDKIFEAISSMFPDKGTAEELKEKYKELTEQQLPGALPPECTPNIDGPNAKSVQREQSLHSFHTLFCRRCFKYDCFLHPFHATPNTYKRKNTETALDNKPCGPQCYQHLEGAKEFAAALTAERIKTPPKRPGGRRRGRLPNNSSRPSTPTINVLESKDTDSDREAGTETGGENNDKEEEEKKDETSSSSEANSRCQTPIKMKPNIEPPENVEWSGAEASMFRVLIGTYYDNFCAIARLIGTKTCRQVYEFRVKESSIIAPAPAEDVDTPPRKKKRKHRLWAAHCRKIQLKKDGSSNHVYNYQPCDHPRQPCDSSCPCVIAQNFCEKFCQCSSECQNRFPGCRCKAQCNTKQCPCYLAVRECDPDLCLTCGAADHWDSKNVSCKNCSIQRGSKKHLLLAPSDVAGWGIFIKDPVQKNEFISEYCGEIISQDEADRRGKVYDKYMCSFLFNLNNDFVVDATRKGNKIRFANHSVNPNCYAKVMMVNGDHRIGIFAKRAIQTGEELFFDYRYSQADALKYVGIEREMEIP
uniprot
proteins
disease_involvement
DISEASE: Weaver syndrome (WVS) [MIM:277590]: A syndrome of accelerated growth and osseous maturation, unusual craniofacial appearance, hoarse and low-pitched cry, and hypertonia with camptodactyly. Distinguishing features of Weaver syndrome include broad forehead and face, ocular hypertelorism, prominent wide philtrum, micrognathia, deep horizontal chin groove, and deep-set nails. In addition, carpal bone development is advanced over the rest of the hand. {ECO:0000269|PubMed:22177091, ECO:0000269|PubMed:22190405, ECO:0000269|PubMed:23239504, ECO:0000269|PubMed:26694085, ECO:0000269|PubMed:28229514}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.1.1.356
uniprot
proteins
function
FUNCTION: Catalytic subunit of the PRC2/EED-EZH2 complex, a Polycomb group (PcG) complex that methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene (PubMed:14532106, PubMed:15225548, PubMed:15385962, PubMed:16618801, PubMed:16936726, PubMed:17344414, PubMed:22323599, PubMed:24474760, PubMed:26581166, PubMed:30026490, PubMed:30923826). Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively (PubMed:15231737, PubMed:17210787, PubMed:18285464, PubMed:22323599, PubMed:30923826). Displays a preference for substrates with less methylation, loses activity when progressively more methyl groups are incorporated into H3K27, H3K27me0 > H3K27me1 > H3K27me2 (PubMed:22323599, PubMed:30923826). Compared to EZH1-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 (PubMed:19026781). The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (PubMed:16357870, PubMed:17200670). Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1, CDKN2A and retinoic acid target genes (PubMed:16179254, PubMed:18086877, PubMed:20935635). EZH2 can also methylate non-histone proteins such as the transcription factor GATA4 and the nuclear receptor RORA (PubMed:23063525). Regulates the circadian clock via histone methylation at the promoter of the circadian genes (PubMed:16717091). Essential for the CRY1/2-mediated repression of the transcriptional activation of PER1/2 by the CLOCK-BMAL1 heterodimer; involved in the di and trimethylation of 'Lys-27' of histone H3 on PER1/2 promoters which is necessary for the CRY1/2 proteins to inhibit transcription (By similarity). {ECO:0000250|UniProtKB:Q61188, ECO:0000269|PubMed:14532106, ECO:0000269|PubMed:15225548, ECO:0000269|PubMed:15231737, ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:16179254, ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:16618801, ECO:0000269|PubMed:16717091, ECO:0000269|PubMed:16936726, ECO:0000269|PubMed:17200670, ECO:0000269|PubMed:17210787, ECO:0000269|PubMed:17344414, ECO:0000269|PubMed:18086877, ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:19026781, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:22323599, ECO:0000269|PubMed:23063525, ECO:0000269|PubMed:24474760, ECO:0000269|PubMed:26581166, ECO:0000269|PubMed:30026490, ECO:0000269|PubMed:30923826}.
uniprot
proteins
mass_dalton
85363
uniprot
proteins
mutagenesis
MUTAGEN 21; /note="S->A: Enhances methyltransferase activity towards 'Lys-27' of histone H3 and abrogates phosphorylation by PKB/AKT1."; /evidence="ECO:0000269|PubMed:16224021"; MUTAGEN 21; /note="S->D: Reduces methyltransferase activity towards 'Lys-27' of histone H3 and abrogates phosphorylation by PKB/AKT1."; /evidence="ECO:0000269|PubMed:16224021"; MUTAGEN 75; /note="S->A: Reduced protein stability."; /evidence="ECO:0000269|PubMed:24474760"; MUTAGEN 345; /note="T->A: Impaired CDK1- and CDK-2 mediated phosphorylation and subsequent gene silencing. Altered EZH2-mediated cell proliferation and migration."; /evidence="ECO:0000269|PubMed:20935635"; MUTAGEN 588; /note="C->Y: Strongly impairs methyltransferase activity towards 'Lys-27' of histone H3."; /evidence="ECO:0000269|PubMed:12435631"; MUTAGEN 667; /note="F->I: Strongly decreases histone methyltransferase activity."; /evidence="ECO:0000269|PubMed:26694085"; MUTAGEN 689; /note="H->A: Abrogates methyltransferase activity."; /evidence="ECO:0000269|PubMed:12435631, ECO:0000269|PubMed:18285464
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000269|PubMed:16224021, ECO:0000269|PubMed:20935635}.; PTM: Sumoylated. {ECO:0000269|PubMed:18628979}.; PTM: Glycosylated: O-GlcNAcylation at Ser-75 by OGT increases stability of EZH2 and facilitates the formation of H3K27me3 by the PRC2/EED-EZH2 complex. {ECO:0000269|PubMed:24474760}.
uniprot
proteins
protein_family
Class V-like SAM-binding methyltransferase superfamily
uniprot
proteins
protein_family
EZ subfamily
uniprot
proteins
protein_family
Histone-lysine methyltransferase family
uniprot
proteins
pubmed
10581039
uniprot
proteins
pubmed
11158321
uniprot
proteins
pubmed
12101246
uniprot
proteins
pubmed
12351676
uniprot
proteins
pubmed
12435631
uniprot
proteins
pubmed
12853948
uniprot
proteins
pubmed
14532106
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15099518
uniprot
proteins
pubmed
15208672
uniprot
proteins
pubmed
15225548
uniprot
proteins
pubmed
15231737
uniprot
proteins
pubmed
15385962
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15684044
uniprot
proteins
pubmed
16179254
uniprot
proteins
pubmed
16224021
uniprot
proteins
pubmed
16357870
uniprot
proteins
pubmed
16431907
uniprot
proteins
pubmed
16618801
uniprot
proteins
pubmed
16717091
uniprot
proteins
pubmed
16936726
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17200670
uniprot
proteins
pubmed
17210787
uniprot
proteins
pubmed
17344414
uniprot
proteins
pubmed
18086877
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18285464
uniprot
proteins
pubmed
18628979
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19026781
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20081860
uniprot
proteins
pubmed
20601953
uniprot
proteins
pubmed
20935635
uniprot
proteins
pubmed
21190999
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21828135
uniprot
proteins
pubmed
22009739
uniprot
proteins
pubmed
22177091
uniprot
proteins
pubmed
22190405
uniprot
proteins
pubmed
22323599
uniprot
proteins
pubmed
23063525
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23239504
uniprot
proteins
pubmed
24474760
uniprot
proteins
pubmed
26581166
uniprot
proteins
pubmed
26694085
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
28229514
uniprot
proteins
pubmed
30026490
uniprot
proteins
pubmed
30923826
uniprot
proteins
pubmed
31086175
uniprot
proteins
pubmed
31451685
uniprot
proteins
pubmed
32051553
uniprot
proteins
pubmed
33323928
uniprot
proteins
pubmed
36064715
uniprot
proteins
pubmed
8649418
uniprot
proteins
pubmed
8954776
uniprot
proteins
pubmed
9214638
uniprot
proteins
pubmed
9499421
uniprot
proteins
pubmed
9584199
uniprot
proteins
sequence_length
746
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12101246, ECO:0000269|PubMed:14532106, ECO:0000269|PubMed:15231737, ECO:0000269|PubMed:9584199}. Note=Localizes to the inactive X chromosome in trophoblast stem cells. {ECO:0000250|UniProtKB:Q61188}.
uniprot
proteins