AiPD: Autoinhibited Protein Database

Q28D84

Gene name	ezh2 (TGas092f05.1)
Protein name	Histone-lysine N-methyltransferase EZH2
Names	EC 2.1.1.356 , Enhancer of zeste homolog 2
Species	Xenopus tropicalis (Western clawed frog) (Silurana tropicalis)
KEGG Pathway	xtr:550047
EC number	2.1.1.356: Methyltransferases
Protein Class

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)

739-748 (Disordered C-terminus of SET domain) SS

Target domain	648-733 (Active sites of SET domain)
Relief mechanism	Partner binding, Ligand binding
Assay

AID

739-748 (Disordered C-terminus of SET domain)

Target domain

648-733 (Active sites of SET domain)

Relief mechanism

Partner binding (Interactions with EED or SUZ12), Ligand binding (Interactions with ligands)

Assay

Accessory elements

No accessory elements

References

Antonysamy S et al. (2013) "Structural context of disease-associated mutations and putative mechanism of autoinhibition revealed by X-ray crystallographic analysis of the EZH2-SET domain", PloS one, 8, e84147

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

4 regional properties for Q28D84

Type	Name	Position	InterPro Accession
domain	Dbl homology (DH) domain	376 - 560	IPR000219
domain	SH3 domain	715 - 776	IPR001452
domain	Pleckstrin homology domain	592 - 706	IPR001849
domain	Ephexin-like, PH domain	580 - 706	IPR047270

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