P70351
SS
Gene name |
Ezh1 (Enx2) |
Protein name |
Histone-lysine N-methyltransferase EZH1 |
Names |
EC 2.1.1.356 , ENX-2 , Enhancer of zeste homolog 1 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:14055 |
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)
Target domain |
647-732 (Active sites of SET domain) |
Relief mechanism |
Partner binding, Ligand binding |
Assay |
|
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
1 structures for P70351
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P70351-F1 | Predicted | AlphaFoldDB |
44 variants for P70351
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3389207391 | 17 | R>G | No | EVA | |
| rs864289240 | 20 | K>R | No | EVA | |
| rs3389204810 | 26 | L>I | No | EVA | |
| rs3389204459 | 44 | A>G | No | EVA | |
| rs3389214061 | 44 | A>S | No | EVA | |
| rs3402796886 | 69 | Q>H | No | EVA | |
| rs233057293 | 70 | P>Q | No | EVA | |
| rs3389167018 | 72 | K>R | No | EVA | |
| rs3389167015 | 76 | G>R | No | EVA | |
| rs3412794619 | 78 | P>L | No | EVA | |
| rs3402697677 | 80 | L>Q | No | EVA | |
| rs3389197099 | 86 | E>* | No | EVA | |
| rs3411775326 | 112 | Y>H | No | EVA | |
| rs3411897523 | 115 | S>F | No | EVA | |
| rs3389200546 | 119 | Q>E | No | EVA | |
| rs3389204819 | 147 | I>F | No | EVA | |
| rs3389175312 | 164 | M>I | No | EVA | |
| rs3389207152 | 168 | S>T | No | EVA | |
| rs3389207135 | 175 | V>M | No | EVA | |
| rs3389197064 | 223 | N>K | No | EVA | |
| rs3389214042 | 247 | N>D | No | EVA | |
| rs3389200537 | 314 | A>T | No | EVA | |
| rs3389203551 | 339 | L>F | No | EVA | |
| rs3389204865 | 339 | L>P | No | EVA | |
| rs3389204432 | 379 | A>P | No | EVA | |
| rs3549198595 | 380 | M>V | No | EVA | |
| rs3389207160 | 383 | T>I | No | EVA | |
| rs3389178974 | 392 | T>I | No | EVA | |
| rs3389200503 | 424 | V>A | No | EVA | |
| rs3389140972 | 439 | E>G | No | EVA | |
| rs3412877936 | 464 | T>S | No | EVA | |
| rs3389178231 | 504 | C>S | No | EVA | |
| rs3389218264 | 514 | N>I | No | EVA | |
| rs3389175280 | 541 | Q>* | No | EVA | |
| rs3389200494 | 556 | N>K | No | EVA | |
| rs3389207140 | 558 | F>C | No | EVA | |
| rs864265510 | 575 | Y>H | No | EVA | |
| rs3389178200 | 580 | E>D | No | EVA | |
| rs3389141026 | 608 | Q>R | No | EVA | |
| rs3389167045 | 609 | R>G | No | EVA | |
| rs235053911 | 631 | E>D | No | EVA | |
| rs3389197091 | 673 | D>E | No | EVA | |
| rs3389205755 | 724 | F>L | No | EVA | |
| rs3402073537 | 741 | E>K | No | EVA |
No associated diseases with P70351
9 regional properties for P70351
| 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 |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
4 GO annotations of cellular component
| Name | Definition |
|---|---|
| chromosome, telomeric region | The end of a linear chromosome, required for the integrity and maintenance of the end. A chromosome telomere usually includes a region of telomerase-encoded repeats the length of which rarely exceeds 20 bp each and that permits the formation of a telomeric loop (T-loop). The telomeric repeat region is usually preceded by a sub-telomeric region that is gene-poor but rich in repetitive elements. Some telomeres only consist of the latter part (for eg. D. melanogaster telomeres). |
| 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. |
| heterochromatin | A compact and highly condensed form of chromatin that is refractory to transcription. |
| 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. |
4 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 |
| transcription corepressor activity | A transcription coregulator activity that represses or decreases 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. Corepressors often act by altering chromatin structure and modifications. For example, one class of transcription corepressors 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 |
|---|---|
| chromatin remodeling | A dynamic process of chromatin reorganization resulting in changes to chromatin structure. These changes allow DNA metabolic processes such as transcriptional regulation, DNA recombination, DNA repair, and DNA replication. |
| 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). |
| hepatocyte homeostasis | Any biological process involved in the maintenance of the steady-state number of hepatocytes within a population of cells. Hepatocytes are specialized epithelial cells of the liver that are organized into interconnected plates called lobules. |
| 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. |
| liver regeneration | The regrowth of lost or destroyed liver. |
| methylation | The process in which a methyl group is covalently attached to a molecule. |
| negative regulation of transcription by RNA polymerase II | Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II. |
| positive regulation of transcription by RNA polymerase II | Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. |
| response to tetrachloromethane | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a tetrachloromethane stimulus. |
| subtelomeric heterochromatin formation | The compaction of chromatin into heterochromatin at the subtelomeric region. |
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 |
| 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 |
| MDIASPPTSK | CITYWKRKVK | SEYMRLRQLK | RLQANMGAKA | LYVANFAKVQ | EKTQILNEEW |
| 70 | 80 | 90 | 100 | 110 | 120 |
| KKLRVQPVQP | MKPVSGHPFL | KKCTIESIFP | GFDSQDMLMR | SLNTVALVPI | MYSWSPLQQN |
| 130 | 140 | 150 | 160 | 170 | 180 |
| FMVEDETVLC | NIPYMGDEVK | EEDETFIEEL | INNYDGKVHG | EEEMIPGSVL | ISDAVFLELV |
| 190 | 200 | 210 | 220 | 230 | 240 |
| DALNQYSDEE | EDGHNDPSDG | KQDDSKEDLP | VTRKRKRHAI | EGNKKSSKKQ | 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 |
| RRRRHPVVSA | SCSNASASAM | AETKEGDSDR | DTGNDWASSS | SEANSRCQTP | TKQKASPAPA |
| 430 | 440 | 450 | 460 | 470 | 480 |
| QLCVVEAPSE | PVEWTGAEES | LFRVFHGTYF | NNFCSIARLL | GTKTCKQVFQ | FAVKESLILK |
| 490 | 500 | 510 | 520 | 530 | 540 |
| LPTDELMNPA | QKKKRKHRLW | AAHCRKIQLK | KDNNSTQVYN | YQPCDHPDRP | CDSTCPCIMT |
| 550 | 560 | 570 | 580 | 590 | 600 |
| QNFCEKFCQC | SPDCQNRFPG | 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 | ERETDVF |