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

648-733 (Active sites of SET domain)

Relief mechanism

Partner binding, Ligand binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q28D84

Entry ID Method Resolution Chain Position Source
AF-Q28D84-F1 Predicted AlphaFoldDB

No variants for Q28D84

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q28D84

No associated diseases with Q28D84

5 regional properties for Q28D84

Type Name Position InterPro Accession
domain Helicase, C-terminal domain-like 377 - 542 IPR001650
domain DEAD/DEAH box helicase domain 175 - 354 IPR011545
domain Helicase superfamily 1/2, ATP-binding domain 170 - 381 IPR014001
domain RNA helicase, DEAD-box type, Q motif 151 - 179 IPR014014
domain Ded1/Dbp1, DEAD-box helicase domain 152 - 372 IPR044763

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

1 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.

2 GO annotations of molecular function

Name Definition
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.

4 GO annotations of biological process

Name Definition
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.
rhythmic process Any process pertinent to the generation and maintenance of rhythms in the physiology of an organism.

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
Q15910 EZH2 Histone-lysine N-methyltransferase EZH2 Homo sapiens (Human) EV
Q92800 EZH1 Histone-lysine N-methyltransferase EZH1 Homo sapiens (Human) SS
Q61188 Ezh2 Histone-lysine N-methyltransferase EZH2 Mus musculus (Mouse) SS
P70351 Ezh1 Histone-lysine N-methyltransferase EZH1 Mus musculus (Mouse) SS
O65312 MEA Histone-lysine N-methyltransferase MEDEA Arabidopsis thaliana (Mouse-ear cress) PR
Q08BS4 ezh2 Histone-lysine N-methyltransferase EZH2 Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MGQTGKKSEK GPVCWRKRVK SEYMRLRQLK RFRRADEVKS MFNTNRQKIM ERTEILNQEW
70 80 90 100 110 120
KQRRIQPVHI MTTVSSLRGT RECSVTSDLD FPKQVIPLKT LTAVASVPIM YSWSPLQQNF
130 140 150 160 170 180
MVEDETVLHN IPYMGDEVLD QDGTFIEELI KNYDGKVHGD RECGFINDEI FVELVNALAQ
190 200 210 220 230 240
YSDYEDDEDG DDNQDDERDD TAKDQDDNME DQETQPLRKF PSDKIFEAIS SMFPDKGTLE
250 260 270 280 290 300
ELKEKYKELT EQQLPGALPP ECTPNIDGPN AKSVQREQSL HSFHTLFCRR CFKYDCFLHP
310 320 330 340 350 360
FHATPNTYKR KNNEAANDGK PCGPHCYQLL EGAREFAAAL TAERIKTPPK RPSGRRRGRL
370 380 390 400 410 420
PNNTSRPSTP TVNVLEAKDT DSDREAGTET GGESNDKEEE EKKDETSSSS EANSRCQTPI
430 440 450 460 470 480
KMKPNIEPPE NVEWSGAEAS LFRVLIGTYY DNFCAIARLI GTKTCRQVYE FRVKESSIIA
490 500 510 520 530 540
PVIAEDVDTP PRKKKRKHRL WAAHCRKIQL KKDGSSNHVY NYQPCDHPRQ PCDSSCPCVI
550 560 570 580 590 600
AQNFCEKFCQ CSSECQNRFP GCRCKAQCNT KQCPCYLAVR ECDPDLCLTC GAADHWDSKN
610 620 630 640 650 660
VSCKNCSIQR GSKKHLLLAP SDVAGWGIFI KDPVQKNEFI SEYCGEIISQ DEADRRGKVY
670 680 690 700 710 720
DKYMCSFLFN LNNDFVVDAT RKGNKIRFAN HSVNPNCYAK VMMVNGDHRI GIFAKRAIQT
730 740
GEELFFDYRY SQADALKYVG IEREMEIP