Descriptions

The histone-lysine N-methyltransferase EZH2 (EZH2) is a catalytic subunit of the polycomb repressive complex 2 (PRC2) and is involved in histone methylation and transcriptional repression. Autoinhibition of EZH2 is achieved through the C-terminus folding back into the active site, effectively blocking substrate engagement. This conformational state is inactive, preventing enzymatic activity and ensuring EZH2 only functions when properly complexed, preventing aberrant methylation activity. The inhibited activity of EZH2 could be alleviated by interactions with its binding partners EED and SUZ12, which could induce a conformational change in EZH2

Autoinhibitory domains (AIDs)

Target domain

660-745 (Active sites of SET domain)

Relief mechanism

Partner binding, Ligand binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for P42124

Entry ID Method Resolution Chain Position Source
AF-P42124-F1 Predicted AlphaFoldDB

No variants for P42124

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for P42124

No associated diseases with P42124

9 regional properties for P42124

Type Name Position InterPro Accession
domain SANT/Myb domain 152 - 292 IPR001005-1
domain SANT/Myb domain 443 - 491 IPR001005-2
domain SET domain 626 - 747 IPR001214
domain CXC domain 518 - 619 IPR026489
domain Tesmin/TSO1-like CXC domain 570 - 607 IPR033467
domain Polycomb repressive complex 2 subunit EZH1/EZH2, tri-helical domain 151 - 291 IPR041343
domain Pre-SET CXC domain 574 - 605 IPR041355
domain EZH2, SET domain 623 - 742 IPR044439
domain EZH1/2, MCSS domain 298 - 352 IPR048358

Functions

Description
EC Number 2.1.1.356 Methyltransferases
Subcellular Localization
  • Nucleus
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

4 GO annotations of cellular component

Name Definition
chromatin The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome.
ESC/E(Z) complex A multimeric protein complex that can methylate lysine-27 and lysine-9 residues of histone H3. In Drosophila the core subunits of the complex include ESC, E(Z), CAF1 (NURF-55) and SU(Z)12. In mammals the core subunits of the complex include EED, EZH2, SUZ12 and RBBP4.
histone methyltransferase complex A multimeric complex that is able to catalyze the addition of methyl groups to histone proteins.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.

7 GO annotations of molecular function

Name Definition
chromatin binding Binding to chromatin, the network of fibers of DNA, protein, and sometimes RNA, that make up the chromosomes of the eukaryotic nucleus during interphase.
DNA binding Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid).
histone H3K27 methyltransferase activity Catalysis of the reaction
histone H3K27 trimethyltransferase activity Catalysis of the reaction
histone H3K9 methyltransferase activity Catalysis of the reaction
histone methyltransferase activity Catalysis of the reaction
sequence-specific DNA binding Binding to DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA e.g. promotor binding or rDNA binding.

10 GO annotations of biological process

Name Definition
anterior/posterior axis specification The establishment, maintenance and elaboration of the anterior/posterior axis. The anterior-posterior axis is defined by a line that runs from the head or mouth of an organism to the tail or opposite end of the organism.
axon guidance The chemotaxis process that directs the migration of an axon growth cone to a specific target site in response to a combination of attractive and repulsive cues.
facultative heterochromatin formation The compaction of chromatin into a conformation that is refactory to transcription but that be converted to euchromatin and allow transcription in specific contexts. These can be temporal (e.g., developmental states or specific cell-cycle stages), spatial (e.g., nuclear localization changes from the center to the periphery or vice versa due to exogenous factors/signals), or parental/heritable (e.g., monoallelic gene expression).
heterochromatin formation An epigenetic gene silencing mechanism in which chromatin is compacted into heterochromatin, resulting in a chromatin conformation refractory to transcription. This process starts with heterochromatin nucleation, its spreading, and ends with heterochromatin boundary formation.
methylation The process in which a methyl group is covalently attached to a molecule.
negative regulation of DNA-templated transcription Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription.
neurogenesis Generation of cells within the nervous system.
regulation of neuroblast proliferation Any process that modulates the frequency, rate or extent of neuroblast proliferation.
regulation of transcription by RNA polymerase II Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II.
syncytial blastoderm mitotic cell cycle Mitotic division cycles 10 to 13 of the insect embryo. This is the second phase of the syncytial period where nuclei divide in a common cytoplasm without cytokinesis. The majority of migrating nuclei reach the embryo surface during cycle 10, after which they divide less synchronously than before, and the syncytial blastoderm cycles lengthen progressively.

8 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
A7E2Z2 EZH1 Histone-lysine N-methyltransferase EZH1 Bos taurus (Bovine) SS
Q92800 EZH1 Histone-lysine N-methyltransferase EZH1 Homo sapiens (Human) SS
Q15910 EZH2 Histone-lysine N-methyltransferase EZH2 Homo sapiens (Human) EV
P70351 Ezh1 Histone-lysine N-methyltransferase EZH1 Mus musculus (Mouse) SS
Q61188 Ezh2 Histone-lysine N-methyltransferase EZH2 Mus musculus (Mouse) SS
O65312 MEA Histone-lysine N-methyltransferase MEDEA Arabidopsis thaliana (Mouse-ear cress) PR
Q28D84 ezh2 Histone-lysine N-methyltransferase EZH2 Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) SS
Q08BS4 ezh2 Histone-lysine N-methyltransferase EZH2 Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MNSTKVPPEW KRRVKSEYIK IRQQKRYKRA DEIKEAWIRN WDEHNHNVQD LYCESKVWQA
70 80 90 100 110 120
KPYDPPHVDC VKRAEVTSYN GIPSGPQKVP ICVINAVTPI PTMYTWAPTQ QNFMVEDETV
130 140 150 160 170 180
LHNIPYMGDE VLDKDGKFIE ELIKNYDGKV HGDKDPSFMD DAIFVELVHA LMRSYSKELE
190 200 210 220 230 240
EAAPGTATAI KTETLAKSKQ GEDDGVVDVD ADGESPMKLE KTDSKGDLTE VEKKETEEPL
250 260 270 280 290 300
ETEDADVKPD VEEVKDKLPF PAPIIFQAIS ANFPDKGTAQ ELKEKYIELT EHQDPERPQE
310 320 330 340 350 360
CTPNIDGIKA ESVSRERTMH SFHTLFCRRC FKYDCFLHRL QGHAGPNLQK RRYPELKPFA
370 380 390 400 410 420
EPCSNSCYML IDGMKEKLAA DSKTPPIDSC NEASSEDSND SNSQFSNKDF NHENSKDNGL
430 440 450 460 470 480
TVNSAAVAEI NSIMAGMMNI TSTQCVWTGA DQALYRVLHK VYLKNYCAIA HNMLTKTCRQ
490 500 510 520 530 540
VYEFAQKEDA EFSFEDLRQD FTPPRKKKKK QRLWSLHCRK IQLKKDSSSN HVYNYTPCDH
550 560 570 580 590 600
PGHPCDMNCS CIQTQNFCEK FCNCSSDCQN RFPGCRCKAQ CNTKQCPCYL AVRECDPDLC
610 620 630 640 650 660
QACGADQFKL TKITCKNVCV QRGLHKHLLM APSDIAGWGI FLKEGAQKNE FISEYCGEII
670 680 690 700 710 720
SQDEADRRGK VYDKYMCSFL FNLNNDFVVD ATRKGNKIRF ANHSINPNCY AKVMMVTGDH
730 740 750
RIGIFAKRAI QPGEELFFDY RYGPTEQLKF VGIEREMEIV