Q61188

SS
Gene name
Ezh2 (Enx1h)
Protein name
Histone-lysine N-methyltransferase EZH2
Names
EC 2.1.1.356 , ENX-1 , Enhancer of zeste homolog 2
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:14056
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)

737-746 (Disordered C-terminus of SET domain) SS

Target domain

646-731 (Active sites of SET domain)

Relief mechanism

Partner binding, Ligand binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

2 structures for Q61188

Entry ID Method Resolution Chain Position Source
2QXV X-ray 182 A B 39-68 PDB
AF-Q61188-F1 Predicted AlphaFoldDB

45 variants for Q61188

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3388814044 2 G>* No EVA
rs3388810903 3 Q>E No EVA
rs3388831283 4 T>N No EVA
rs3388810826 38 V>I No EVA
rs3388822361 61 K>T No EVA
rs1134749148 66 Q>K No EVA
rs3388822381 80 T>S No EVA
rs3388807417 110 M>I No EVA
rs3388817036 135 G>* No EVA
rs3388817034 137 E>D No EVA
rs3388807349 139 L>M No EVA
rs3388814069 142 D>H No EVA
rs3388810837 176 N>T No EVA
rs3388807436 181 Y>* No EVA
rs3388825885 182 N>I No EVA
rs3388827809 183 D>G No EVA
rs3388828213 189 D>N No EVA
rs3388822411 246 E>Q No EVA
rs3388827930 255 A>T No EVA
rs3395951724 262 P>G No EVA
rs3388827340 265 D>N No EVA
rs3388794506 288 R>Q No EVA
rs3388814086 293 D>Y No EVA
rs3388810885 480 V>I No EVA
rs3388810885 480 V>L No EVA
rs3396709971 483 E>K No EVA
rs3388807418 486 D>V No EVA
rs3388817061 488 P>T No EVA
rs3388814049 525 H>R No EVA
rs3388828146 533 S>L No EVA
rs3396735211 561 R>W No EVA
rs3396784670 563 K>* No EVA
rs3396705758 563 K>I No EVA
rs3396894875 563 K>N No EVA
rs3388831285 594 W>* No EVA
rs3388814017 598 N>I No EVA
rs3388817106 647 S>P No EVA
rs3388831334 672 D>E No EVA
rs3388827844 682 N>I No EVA
rs3388794444 720 E>* No EVA
rs3388825828 721 E>A No EVA
rs3388822355 722 L>W No EVA
rs3396306272 730 Q>* No EVA
rs3395951669 734 L>Q No EVA
rs3396686498 737 V>L No EVA

No associated diseases with Q61188

9 regional properties for Q61188

Type Name Position InterPro Accession
domain Protein kinase domain 134 - 392 IPR000719
domain EF-hand domain 435 - 506 IPR002048-1
domain EF-hand domain 507 - 576 IPR002048-2
active_site Serine/threonine-protein kinase, active site 254 - 266 IPR008271
binding_site Protein kinase, ATP binding site 140 - 167 IPR017441
binding_site EF-Hand 1, calcium-binding site 448 - 460 IPR018247-1
binding_site EF-Hand 1, calcium-binding site 484 - 496 IPR018247-2
binding_site EF-Hand 1, calcium-binding site 520 - 532 IPR018247-3
binding_site EF-Hand 1, calcium-binding site 554 - 566 IPR018247-4

Functions

Description
EC Number 2.1.1.356 Methyltransferases
Subcellular Localization
  • Nucleus
  • Chromosome
  • Localizes to the inactive X chromosome in trophoblast stem cells
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

8 GO annotations of cellular component

Name Definition
chromatin silencing complex Any protein complex that mediates changes in chromatin structure that result in transcriptional silencing.
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.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.
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.
pericentric heterochromatin Heterochromatin that is located adjacent to the CENP-A rich centromere 'central core' and characterized by methylated H3 histone at lysine 9 (H3K9me2/H3K9me3).
pronucleus The nucleus of either the ovum or the spermatozoon following fertilization. Thus, in the fertilized ovum, there are two pronuclei, one originating from the ovum, the other from the spermatozoon that brought about fertilization; they approach each other, but do not fuse until just before the first cleavage, when each pronucleus loses its membrane to release its contents.
synapse The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.

18 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.
chromatin DNA binding Binding to DNA that is assembled into chromatin.
DNA binding Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid).
histone H3K27 methyltransferase activity Catalysis of the reaction
histone H3K27 trimethyltransferase activity Catalysis of the reaction
histone methyltransferase activity Catalysis of the reaction
lncRNA binding Binding to a long noncoding RNA (lncRNA).
primary miRNA binding Binding to a primary microRNA (pri-miRNA) transcript, an RNA molecule that is processed into a short hairpin-shaped structure called a pre-miRNA and finally into a functional miRNA. Both double-stranded and single-stranded regions of a pri-miRNA are required for binding.
promoter-specific chromatin binding Binding to a section of chromatin that is associated with gene promoter sequences of DNA.
protein-lysine N-methyltransferase activity Catalysis of the transfer of a methyl group from S-adenosyl-L-methionine to the epsilon-amino group of a lysine residue in a protein substrate.
ribonucleoprotein complex binding Binding to a complex of RNA and protein.
RNA binding Binding to an RNA molecule or a portion thereof.
RNA polymerase II cis-regulatory region sequence-specific DNA binding Binding to a specific upstream regulatory DNA sequence (transcription factor recognition sequence or binding site) located in cis relative to the transcription start site (i.e., on the same strand of DNA) of a gene transcribed by RNA polymerase II.
RNA polymerase II core promoter sequence-specific DNA binding Binding to a DNA sequence that is part of the core promoter of a RNA polymerase II-transcribed gene.
sequence-specific DNA binding Binding to DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA e.g. promotor binding or rDNA binding.
transcription cis-regulatory region binding Binding to a specific sequence of DNA that is part of a regulatory region that controls transcription of that section of the DNA. The transcribed region might be described as a gene, cistron, or operon.
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.
transcription corepressor binding Binding to a transcription corepressor, a protein involved in negative regulation of transcription via protein-protein interactions with transcription factors and other proteins that negatively regulate transcription. Transcription corepressors do not bind DNA directly, but rather mediate protein-protein interactions between repressing transcription factors and the basal transcription machinery.

54 GO annotations of biological process

Name Definition
B cell differentiation The process in which a precursor cell type acquires the specialized features of a B cell. A B cell is a lymphocyte of B lineage with the phenotype CD19-positive and capable of B cell mediated immunity.
cardiac muscle hypertrophy in response to stress The physiological enlargement or overgrowth of all or part of the heart muscle due to an increase in size (not length) of individual cardiac muscle fibers, without cell division, as a result of a disturbance in organismal or cellular homeostasis.
cellular response to hydrogen peroxide Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hydrogen peroxide (H2O2) stimulus.
cellular response to trichostatin A Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a trichostatin A stimulus.
cerebellar cortex development The process whose specific outcome is the progression of the cerebellar cortex over time, from its formation to the mature structure. The cerebellar cortex is a thin mantle of gray matter that covers the surface of each cerebral hemisphere. It has a characteristic morphology with convolutions (gyri) and crevices (sulci) that have specific functions. Six layers of nerve cells and the nerve pathways that connect them comprise the cerebellar cortex. Together, these regions are responsible for the processes of conscious thought, perception, emotion and memory as well as advanced motor function.
DNA methylation-dependent heterochromatin formation Repression of transcription by methylation of DNA, leading to the formation of heterochromatin.
epidermal cell differentiation The process in which a relatively unspecialized cell acquires specialized features of an epidermal cell, any of the cells making up the epidermis.
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).
G1 to G0 transition A cell cycle arrest process that results in arrest during G1 phase, whereupon the cell enters a specialized resting state known as G0 or quiescence.
G1/S transition of mitotic cell cycle The mitotic cell cycle transition by which a cell in G1 commits to S phase. The process begins with the build up of G1 cyclin-dependent kinase (G1 CDK), resulting in the activation of transcription of G1 cyclins. The process ends with the positive feedback of the G1 cyclins on the G1 CDK which commits the cell to S phase, in which DNA replication is initiated.
hemopoiesis The process whose specific outcome is the progression of the myeloid and lymphoid derived organ/tissue systems of the blood and other parts of the body over time, from formation to the mature structure. The site of hemopoiesis is variable during development, but occurs primarily in bone marrow or kidney in many adult vertebrates.
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.
hippocampus development The progression of the hippocampus over time from its initial formation until its mature state.
immunoglobulin heavy chain V-D-J recombination The process in which immunoglobulin heavy chain V, D, and J gene segments are recombined within a single locus utilizing the conserved heptamer and nonomer recombination signal sequences (RSS).
keratinocyte differentiation The process in which a relatively unspecialized cell acquires specialized features of a keratinocyte.
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 cytokine production involved in inflammatory response Any process that stops, prevents or reduces the frequency, rate or extent of cytokine production involved in inflammatory response.
negative regulation of DNA-templated transcription Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription.
negative regulation of epidermal cell differentiation Any process that stops, prevents, or reduces the frequency, rate or extent of epidermal cell differentiation.
negative regulation of G1/S transition of mitotic cell cycle Any signalling pathway that decreases or inhibits the activity of a cell cycle cyclin-dependent protein kinase to modulate the switch from G1 phase to S phase of the mitotic cell cycle.
negative regulation of gene expression Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
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.
negative regulation of keratinocyte differentiation Any process that stops, prevents, or reduces the frequency, rate or extent of keratinocyte differentiation.
negative regulation of retinoic acid receptor signaling pathway Any process that stops, prevents, or reduces the frequency, rate or extent of retinoic acid receptor signaling pathway activity.
negative regulation of stem cell differentiation Any process that stops, prevents or reduces the frequency, rate or extent of stem cell differentiation.
negative regulation of striated muscle cell differentiation Any process that stops, prevents, or reduces the frequency, rate or extent of striated muscle cell differentiation.
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.
negative regulation of transcription elongation by RNA polymerase II Any process that stops, prevents, or reduces the frequency, rate or extent of transcription elongation, the extension of an RNA molecule after transcription initiation and promoter clearance by the addition of ribonucleotides, catalyzed by RNA polymerase II.
positive regulation of cell cycle G1/S phase transition Any signalling pathway that activates or increases the activity of a cell cycle cyclin-dependent protein kinase to modulate the switch from G1 phase to S phase of the cell cycle.
positive regulation of cell population proliferation Any process that activates or increases the rate or extent of cell proliferation.
positive regulation of dendrite development Any process that activates or increases the frequency, rate or extent of dendrite development.
positive regulation of epithelial to mesenchymal transition Any process that increases the rate, frequency, or extent of epithelial to mesenchymal transition. Epithelial to mesenchymal transition is where an epithelial cell loses apical/basolateral polarity, severs intercellular adhesive junctions, degrades basement membrane components and becomes a migratory mesenchymal cell.
positive regulation of GTPase activity Any process that activates or increases the activity of a GTPase.
positive regulation of MAP kinase activity Any process that activates or increases the frequency, rate or extent of MAP kinase activity.
positive regulation of protein serine/threonine kinase activity Any process that increases the rate, frequency, or extent of protein serine/threonine kinase activity.
protein localization to chromatin Any process in which a protein is transported to, or maintained at, a part of a chromosome that is organized into chromatin.
protein modification process The covalent alteration of one or more amino acids occurring in proteins, peptides and nascent polypeptides (co-translational, post-translational modifications). Includes the modification of charged tRNAs that are destined to occur in a protein (pre-translation modification).
regulation of cell population proliferation Any process that modulates the frequency, rate or extent of cell proliferation.
regulation of circadian rhythm Any process that modulates the frequency, rate or extent of a circadian rhythm. A circadian rhythm is a biological process in an organism that recurs with a regularity of approximately 24 hours.
regulation of gene expression Any process that modulates the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
regulation of gliogenesis Any process that modulates the frequency, rate or extent of gliogenesis, the formation of mature glia.
regulation of kidney development Any process that modulates the rate, frequency or extent of kidney development. Kidney development is the process whose specific outcome is the progression of the kidney over time, from its formation to the mature structure. The kidney is an organ that filters the blood and excretes the end products of body metabolism in the form of urine.
regulation of neurogenesis Any process that modulates the frequency, rate or extent of neurogenesis, the generation of cells in the nervous system.
regulation of protein phosphorylation Any process that modulates the frequency, rate or extent of addition of phosphate groups into an amino acid in a protein.
regulation of transcription by RNA polymerase II Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II.
response to estradiol 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 stimulus by estradiol, a C18 steroid hormone hydroxylated at C3 and C17 that acts as a potent estrogen.
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.
rhythmic process Any process pertinent to the generation and maintenance of rhythms in the physiology of an organism.
skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration Any process by which the number of skeletal muscle satellite cells in a skeletal muscle is maintained during muscle regeneration. There are at least three mechanisms by which this is achieved. Skeletal muscle satellite stem cell asymmetric division ensures satellite stem cell numbers are kept constant. Symmetric division of these cells amplifies the number of skeletal muscle satellite stem cells. Some adult skeletal muscle myoblasts (descendants of activated satellite cells) can develop back into quiescent satellite cells, replenishing the overall pool of satellite cells.
stem cell differentiation The process in which a relatively unspecialized cell acquires specialized features of a stem cell. A stem cell is a cell that retains the ability to divide and proliferate throughout life to provide progenitor cells that can differentiate into specialized cells.
subtelomeric heterochromatin formation The compaction of chromatin into heterochromatin at the subtelomeric region.
synaptic transmission, GABAergic The vesicular release of gamma-aminobutyric acid (GABA). from a presynapse, across a chemical synapse, the subsequent activation of GABA receptors at the postsynapse of a target cell (neuron, muscle, or secretory cell) and the effects of this activation on the postsynaptic membrane potential and ionic composition of the postsynaptic cytosol. This process encompasses both spontaneous and evoked release of neurotransmitter and all parts of synaptic vesicle exocytosis. Evoked transmission starts with the arrival of an action potential at the presynapse.

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
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
MGQTGKKSEK GPVCWRKRVK SEYMRLRQLK RFRRADEVKT MFSSNRQKIL ERTETLNQEW
70 80 90 100 110 120
KQRRIQPVHI MTSVSSLRGT RECSVTSDLD FPAQVIPLKT LNAVASVPIM YSWSPLQQNF
130 140 150 160 170 180
MVEDETVLHN IPYMGDEVLD QDGTFIEELI KNYDGKVHGD RECGFINDEI FVELVNALGQ
190 200 210 220 230 240
YNDDDDDDDG DDPDEREEKQ KDLEDNRDDK ETCPPRKFPA DKIFEAISSM FPDKGTAEEL
250 260 270 280 290 300
KEKYKELTEQ QLPGALPPEC TPNIDGPNAK SVQREQSLHS FHTLFCRRCF KYDCFLHPFH
310 320 330 340 350 360
ATPNTYKRKN TETALDNKPC GPQCYQHLEG AKEFAAALTA ERIKTPPKRP GGRRRGRLPN
370 380 390 400 410 420
NSSRPSTPTI SVLESKDTDS DREAGTETGG ENNDKEEEEK KDETSSSSEA NSRCQTPIKM
430 440 450 460 470 480
KPNIEPPENV EWSGAEASMF RVLIGTYYDN FCAIARLIGT KTCRQVYEFR VKESSIIAPV
490 500 510 520 530 540
PTEDVDTPPR KKKRKHRLWA AHCRKIQLKK DGSSNHVYNY QPCDHPRQPC DSSCPCVIAQ
550 560 570 580 590 600
NFCEKFCQCS SECQNRFPGC RCKAQCNTKQ CPCYLAVREC DPDLCLTCGA ADHWDSKNVS
610 620 630 640 650 660
CKNCSIQRGS KKHLLLAPSD VAGWGIFIKD PVQKNEFISE YCGEIISQDE ADRRGKVYDK
670 680 690 700 710 720
YMCSFLFNLN NDFVVDATRK GNKIRFANHS VNPNCYAKVM MVNGDHRIGI FAKRAIQTGE
730 740
ELFFDYRYSQ ADALKYVGIE REMEIP