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 Q08BS4

Entry ID Method Resolution Chain Position Source
AF-Q08BS4-F1 Predicted AlphaFoldDB

No variants for Q08BS4

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q08BS4

No associated diseases with Q08BS4

9 regional properties for Q08BS4

Type Name Position InterPro Accession
domain SANT/Myb domain 160 - 263 IPR001005-1
domain SANT/Myb domain 442 - 490 IPR001005-2
domain SET domain 626 - 747 IPR001214
domain CXC domain 517 - 619 IPR026489
domain Tesmin/TSO1-like CXC domain 569 - 607 IPR033467
domain Polycomb repressive complex 2 subunit EZH1/EZH2, tri-helical domain 159 - 262 IPR041343
domain Pre-SET CXC domain 573 - 604 IPR041355
domain EZH2, SET domain 623 - 742 IPR044439
domain EZH1/2, MCSS domain 270 - 322 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

2 GO annotations of cellular component

Name Definition
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.
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.

6 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.
histone H3K27 methyltransferase activity Catalysis of the reaction
histone H3K27 trimethyltransferase activity Catalysis of the reaction
promoter-specific chromatin binding Binding to a section of chromatin that is associated with gene promoter sequences of DNA.
transcription coactivator activity A transcription coregulator activity that activates or increases the transcription of specific gene sets via binding to a DNA-bound DNA-binding transcription factor, either on its own or as part of a complex. Coactivators often act by altering chromatin structure and modifications. For example, one class of transcription coactivators modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-bound DNA-binding transcription factors with other transcription coregulators. A fourth class of coactivator activity is the bridging of a DNA-binding transcription factor to the general (basal) transcription machinery. The Mediator complex, which bridges sequence-specific DNA binding transcription factors and RNA polymerase, is also a transcription coactivator.
transcription coregulator activity A transcription regulator activity that modulates the transcription of specific gene sets via binding to a DNA-bound DNA-binding transcription factor, either on its own or as part of a complex. Coregulators often act by altering chromatin structure and modifications. For example, one class of transcription coregulators modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-bound DNA-binding transcription factors with other transcription coregulators.

10 GO annotations of biological process

Name Definition
circadian rhythm Any biological process in an organism that recurs with a regularity of approximately 24 hours.
digestive tract development The process whose specific outcome is the progression of the digestive tract over time, from its formation to the mature structure. The digestive tract is the anatomical structure through which food passes and is processed.
fin regeneration The regrowth of fin tissue following its loss or destruction.
heart development The process whose specific outcome is the progression of the heart over time, from its formation to the mature structure. The heart is a hollow, muscular organ, which, by contracting rhythmically, keeps up the circulation of the blood.
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 gene expression, epigenetic An epigenetic process that silences gene expression at specific genomic regions through chromatin remodelling either by modifying higher order chromatin fiber structure, nucleosomal histones, or the DNA.
positive regulation of circadian rhythm Any process that activates or increases the frequency, rate or extent of a circadian rhythm behavior.
positive regulation of hemopoiesis Any process that activates or increases the frequency, rate or extent of hemopoiesis.
tissue homeostasis A homeostatic process involved in the maintenance of an internal steady state within a defined tissue of an organism, including control of cellular proliferation and death and control of metabolic function.

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
P42124 E(z) Histone-lysine N-methyltransferase E Drosophila melanogaster (Fruit fly) 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
10 20 30 40 50 60
MGLTGRKSEK GPVCWRRRVK SEYMRLRQLK RFRRADEVKS MFSSNRQKIL ERTDILNQEW
70 80 90 100 110 120
KLRRIQPVHI MTPVSSLRGT RECTVDSGFS EFSRQVIPLK TLNAVASVPV MYSWSPLQQN
130 140 150 160 170 180
FMVEDETVLH NIPYMGDEIL DQDGTFIEEL IKNYDGKVHG DRECGFINDE IFVELVNALN
190 200 210 220 230 240
QYSDNEEDDE EDDHHDYKFE KMDLCDGKDD AEDHKEQLSS ESHNNDGSKK FPSDKIFEAI
250 260 270 280 290 300
SSMFPDKGST EELKEKYKEL TEQQLPGALP PECTPNIDGP NAKSVQREQS LHSFHTLFCR
310 320 330 340 350 360
RCFKYDCFLH PFQATPNTYK RKNMENLVDS KPCGIYCYMY MVQDGMVREY PAGVVPERAK
370 380 390 400 410 420
TPSKRSTGRR RGRLPNSNSR PSTPTVNSET KDTDSDREGG ADGNDSNDKD DDDKKDETTS
430 440 450 460 470 480
SSEANSRCQT PVKLKLSSEP PENVDWSGAE ASLFRVLIGT YYDNFCAIAR LIGTKTCRQV
490 500 510 520 530 540
YEFRVKESSI IARAPAVDEN TPQRKKKRKH RLWATHCRKI QLKKDGSSNH VYNYQPCDHP
550 560 570 580 590 600
RQPCDSSCPC VTAQNFCEKF CQCSSECQNR FPGCRCKAQC NTKQCPCYLA VRECDPDLCL
610 620 630 640 650 660
TCGAAEHWDS KNVSCKNCSI QRGAKKHLLL APSDVAGWGI FIKEPVQKNE FISEYCGEII
670 680 690 700 710 720
SQDEADRRGK VYDKYMCSFL FNLNNDFVVD ATRKGNKIRF ANHSVNPNCY AKVMMVNGDH
730 740 750
RIGIFAKRAI QTGEELFFDY RYSQADALKY VGIEREMEIP