AiPD: Autoinhibited Protein Database

A7E2Z2

Gene name	EZH1
Protein name	Histone-lysine N-methyltransferase EZH1
Names	EC 2.1.1.356 , Enhancer of zeste homolog 1
Species	Bos taurus (Bovine)
KEGG Pathway	bta:533087
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)

738-747 (Disordered C-terminus of SET domain) SS

Target domain	647-732 (Active sites of SET domain)
Relief mechanism	Partner binding, Ligand binding
Assay

AID

738-747 (Disordered C-terminus of SET domain)

Target domain

647-732 (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 A7E2Z2

Entry ID	Method	Resolution	Chain	Position	Source
AF-A7E2Z2-F1	Predicted				AlphaFoldDB

No variants for A7E2Z2

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
No variants for A7E2Z2

No associated diseases with A7E2Z2

9 regional properties for A7E2Z2

Type	Name	Position	InterPro Accession
domain	SANT/Myb domain	135 - 263	IPR001005-1
domain	SANT/Myb domain	430 - 478	IPR001005-2
domain	SET domain	613 - 734	IPR001214
domain	CXC domain	504 - 606	IPR026489
domain	Tesmin/TSO1-like CXC domain	556 - 593	IPR033467
domain	Polycomb repressive complex 2 subunit EZH1/EZH2, tri-helical domain	159 - 262	IPR041343
domain	Pre-SET CXC domain	560 - 591	IPR041355
domain	EZH1, SET domain	608 - 743	IPR044438
domain	EZH1/2, MCSS domain	270 - 322	IPR048358

Functions

		Description
EC Number	2.1.1.356	Methyltransferases
Subcellular Localization	Nucleus	Colocalizes with trimethylated 'Lys-27' of histone H3
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.

3 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

2 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.

8 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
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
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
MDIPNPPTSK	CITYWKRKVK	SEYMRLRQLK	RLQANMGAKA	LYVANFAKVQ	EKTQILNEEW
70	80	90	100	110	120
KKLRVQPVQL	MKPVSGHPFL	KKCTIESIFP	GFASQHMLMR	SLNTVALVPI	MYSWSPLQQN
130	140	150	160	170	180
FMVEDETVLC	NIPYMGDEVK	EEDETFIEEL	INNYDGKVHG	EEEMIPGSVL	ISDAVFLELV
190	200	210	220	230	240
DALNQYSDED	EEGHNDTSDG	KQDDSKEDLP	VTRKRKRHAI	EGSKKSSKKQ	FPNDMIFSAI
250	260	270	280	290	300
ASMFPENGVP	DDMKERYREL	TEMSDPNALP	PQCTPNIDGP	NAKSVQREQS	LHSFHTLFCR
310	320	330	340	350	360
RCFKYDCFLH	PFHATPNVYK	RKNKEIKIEP	EPCGTDCFLL	LEGAKEYAML	HNPRSKCSGR
370	380	390	400	410	420
RRRRHHVVNA	SCSNTSASAV	AETKEGDSDR	DTGNDWASSS	SEANSRCQTP	TKQKASPAPP
430	440	450	460	470	480
QLCVVEAPSE	PVEWTGAEES	LFRVFHGTYF	NNFCSIARLL	GTKTCKQVFQ	FAVKESLILK
490	500	510	520	530	540
LPTDELMNPS	QKKKRKHRLW	AAHCRKIQLK	KDNSSTQVYN	YQPCDHPDRP	CDSTCPCIMT
550	560	570	580	590	600
QNFCEKFCQC	NPDCQNRFPG	CRCKTQCNTK	QCPCYLAVRE	CDPDLCLTCG	ASEHWDCKVV
610	620	630	640	650	660
SCKNCSIQRG	LKKHLLLAPS	DVAGWGTFIK	ESVQKNEFIS	EYCGELISQD	EADRRGKVYD
670	680	690	700	710	720
KYMSSFLFNL	NNDFVVDATR	KGNKIRFANH	SVNPNCYAKV	VMVNGDHRIG	IFAKRAIQAG
730	740
EELFFDYRYS	QADALKYVGI	ERETDVL