Human Gene EHMT2 (uc003nxz.1)
  Description: Homo sapiens euchromatic histone-lysine N-methyltransferase 2 (EHMT2), transcript variant NG36/G9a, mRNA.
RefSeq Summary (NM_006709): This gene encodes a methyltransferase that methylates lysine residues of histone H3. Methylation of H3 at lysine 9 by this protein results in recruitment of additional epigenetic regulators and repression of transcription. This gene was initially thought to be two different genes, NG36 and G9a, adjacent to each other in the HLA locus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016].
Transcript (Including UTRs)
   Position: hg19 chr6:31,847,537-31,865,464 Size: 17,928 Total Exon Count: 28 Strand: -
Coding Region
   Position: hg19 chr6:31,847,861-31,865,454 Size: 17,594 Coding Exon Count: 28 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr6:31,847,537-31,865,464)mRNA (may differ from genome)Protein (1210 aa)
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MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: EHMT2_HUMAN
DESCRIPTION: RecName: Full=Histone-lysine N-methyltransferase EHMT2; EC=2.1.1.-; EC=2.1.1.43; AltName: Full=Euchromatic histone-lysine N-methyltransferase 2; AltName: Full=HLA-B-associated transcript 8; AltName: Full=Histone H3-K9 methyltransferase 3; Short=H3-K9-HMTase 3; AltName: Full=Lysine N-methyltransferase 1C; AltName: Full=Protein G9a;
FUNCTION: Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys- 373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself.
CATALYTIC ACTIVITY: S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].
SUBUNIT: Heterodimer; heterodimerizes with EHMT1/GLP. Interacts with GFI1B and WIZ. Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EHMT1, RING1, RNF2, MBLR, L3MBTL2 and YAF2. Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2. Interacts with UHRF1.
INTERACTION: Q99684:GFI1; NbExp=2; IntAct=EBI-744366, EBI-949368; Q07120:Gfi1 (xeno); NbExp=3; IntAct=EBI-744366, EBI-4289236; Q13547:HDAC1; NbExp=2; IntAct=EBI-744366, EBI-301834; Q9NQX1:PRDM5; NbExp=3; IntAct=EBI-744366, EBI-4292031; Q5JSZ5:PRRC2B; NbExp=2; IntAct=EBI-744366, EBI-744891;
SUBCELLULAR LOCATION: Nucleus. Chromosome. Note=Associates with euchromatic regions. Does not associate with heterochromatin.
TISSUE SPECIFICITY: Expressed in all tissues examined, with high levels in fetal liver, thymus, lymph node, spleen and peripheral blood leukocytes and lower level in bone marrow.
DOMAIN: The SET domain mediates interaction with WIZ.
DOMAIN: The ANK repeats bind H3K9me1 and H3K9me2.
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
PTM: Methylated at Lys-185; automethylated.
SIMILARITY: Belongs to the histone-lysine methyltransferase family. Suvar3-9 subfamily.
SIMILARITY: Contains 7 ANK repeats.
SIMILARITY: Contains 1 post-SET domain.
SIMILARITY: Contains 1 pre-SET domain.
SIMILARITY: Contains 1 SET domain.
CAUTION: While NG36 and G9a were originally thought to derive from 2 separate genes, all G9A transcripts also contain the in frame coding sequence of NG36 (PubMed:11707778).
CAUTION: It is uncertain whether Met-1 or Met-21 is the initiator methionine.
SEQUENCE CAUTION: Sequence=AAD21811.1; Type=Erroneous gene model prediction; Sequence=AAD21812.1; Type=Erroneous gene model prediction; Sequence=AAH02686.2; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=AAH09351.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=AAH18718.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAH20970.2; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=BAB63294.1; Type=Erroneous gene model prediction; Sequence=BAB63295.1; Type=Erroneous gene model prediction; Sequence=CAA49491.1; Type=Erroneous initiation; Note=Translation N-terminally extended;

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): EHMT2
CDC HuGE Published Literature: EHMT2
Positive Disease Associations: Lupus Erythematosus, Systemic , Macular Degeneration , Multiple Sclerosis , overall effect
Related Studies:
  1. Lupus Erythematosus, Systemic
    , , . [PubMed 0]
  2. Lupus Erythematosus, Systemic
    Geoffrey Hom et al. The New England journal of medicine 2008, Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX., The New England journal of medicine. [PubMed 18204098]
    We identified and then confirmed through replication two new genetic loci for SLE: a promoter-region allele associated with reduced expression of BLK and increased expression of C8orf13 and variants in the ITGAM-ITGAX region.
  3. Macular Degeneration
    , , . [PubMed 0]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: EHMT2
Diseases sorted by gene-association score: kleefstra syndrome (7)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 35.48 RPKM in Brain - Cerebellum
Total median expression: 899.99 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
3' UTR -105.60324-0.326 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR002110 - Ankyrin_rpt
IPR020683 - Ankyrin_rpt-contain_dom
IPR003616 - Post-SET_dom
IPR007728 - Pre-SET_dom
IPR003606 - Pre-SET_Zn-bd_sub
IPR001214 - SET_dom

Pfam Domains:
PF00023 - Ankyrin repeat
PF00856 - SET domain
PF05033 - Pre-SET motif
PF12796 - Ankyrin repeats (3 copies)
PF13606 - Ankyrin repeat
PF13637 - Ankyrin repeats (many copies)
PF13857 - Ankyrin repeats (many copies)

SCOP Domains:
82199 - SET domain
48403 - Ankyrin repeat

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2O8J - X-ray MuPIT 3DM1 - X-ray MuPIT 3K5K - X-ray MuPIT 3RJW - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q96KQ7
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
 Gene Details    
 Gene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0002039 p53 binding
GO:0005515 protein binding
GO:0008168 methyltransferase activity
GO:0008270 zinc ion binding
GO:0016279 protein-lysine N-methyltransferase activity
GO:0016740 transferase activity
GO:0018024 histone-lysine N-methyltransferase activity
GO:0046872 metal ion binding
GO:0046974 histone methyltransferase activity (H3-K9 specific)
GO:0046976 histone methyltransferase activity (H3-K27 specific)
GO:0070742 C2H2 zinc finger domain binding
GO:1990841 promoter-specific chromatin binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0006275 regulation of DNA replication
GO:0006306 DNA methylation
GO:0006325 chromatin organization
GO:0009267 cellular response to starvation
GO:0016571 histone methylation
GO:0018027 peptidyl-lysine dimethylation
GO:0032259 methylation
GO:0034968 histone lysine methylation
GO:0051567 histone H3-K9 methylation
GO:0070317 negative regulation of G0 to G1 transition
GO:0070734 histone H3-K27 methylation

Cellular Component:
GO:0000790 nuclear chromatin
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0016607 nuclear speck


-  Descriptions from all associated GenBank mRNAs
  X69838 - H.sapiens mRNA for G9a.
AB209433 - Homo sapiens mRNA for HLA-B associated transcript 8 BAT8 isoform a variant, partial cds.
BC002686 - Homo sapiens euchromatic histone-lysine N-methyltransferase 2, mRNA (cDNA clone IMAGE:3607648), partial cds.
BC020970 - Homo sapiens euchromatic histone-lysine N-methyltransferase 2, mRNA (cDNA clone IMAGE:3912870), partial cds.
BC009351 - Homo sapiens euchromatic histone-lysine N-methyltransferase 2, mRNA (cDNA clone IMAGE:4138717), partial cds.
BC018718 - Homo sapiens euchromatic histone-lysine N-methyltransferase 2, mRNA (cDNA clone MGC:31802 IMAGE:4123580), complete cds.
AK092866 - Homo sapiens cDNA FLJ35547 fis, clone SPLEN2004124, highly similar to H.sapiens mRNA for G9a.
AK302904 - Homo sapiens cDNA FLJ61730 complete cds, highly similar to Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 (EC 2.1.1.43).
AJ315532 - Homo sapiens mRNA for NG36/G9a protein.
KJ902177 - Synthetic construct Homo sapiens clone ccsbBroadEn_11571 EHMT2 gene, encodes complete protein.
JD298940 - Sequence 279964 from Patent EP1572962.
JD193232 - Sequence 174256 from Patent EP1572962.
JD368665 - Sequence 349689 from Patent EP1572962.
JD446594 - Sequence 427618 from Patent EP1572962.
JD473187 - Sequence 454211 from Patent EP1572962.
JD242349 - Sequence 223373 from Patent EP1572962.
JD157052 - Sequence 138076 from Patent EP1572962.
JD272495 - Sequence 253519 from Patent EP1572962.
JD222367 - Sequence 203391 from Patent EP1572962.
JD189330 - Sequence 170354 from Patent EP1572962.
JD260810 - Sequence 241834 from Patent EP1572962.
JD419289 - Sequence 400313 from Patent EP1572962.
JD098391 - Sequence 79415 from Patent EP1572962.
JD209078 - Sequence 190102 from Patent EP1572962.
JD463437 - Sequence 444461 from Patent EP1572962.
JD387281 - Sequence 368305 from Patent EP1572962.
JD468206 - Sequence 449230 from Patent EP1572962.
JD114777 - Sequence 95801 from Patent EP1572962.
JD246088 - Sequence 227112 from Patent EP1572962.
CU676794 - Synthetic construct Homo sapiens gateway clone IMAGE:100017876 5' read EHMT2 mRNA.
AK056936 - Homo sapiens cDNA FLJ32374 fis, clone SALGL1000047, highly similar to NG36.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00310 - Lysine degradation

Reactome (by CSHL, EBI, and GO)

Protein Q96KQ7 (Reactome details) participates in the following event(s):

R-HSA-427404 Recruitment of ERCC6 (CSB), EHMT2 (G9a), and NuRD to the promoter of rRNA gene
R-HSA-3788725 Cdh1:APC/C complex binds EHMT1:EHMT2
R-HSA-8953418 EHMT1:EHMT2 complex binds E2F6.com-1 core
R-HSA-427336 TTF1:rRNA promoter:ERCC6:EHMT2 complex dimethylates histone H3 at lysine-9.
R-HSA-3788724 Cdh1:APC/C ubiquitinates EHMT1 and EHMT2
R-HSA-9007283 CBX3 and PRC1.6 associate with E2F6.com-1
R-HSA-3788745 EHMT1:EHMT2 methylates IL8 promoter
R-HSA-3788748 EHMT1:EHMT2 methylates IL6 promoter
R-HSA-5634729 EHMT1:EHMT2 (KMT1D:KMT1C) methylates methyl-lysine-10 of histone H3 (H3K9)
R-HSA-5634750 EHMT1:EHMT2 (KMT1D:KMT1C) methylates lysine-10 of histone H3 (H3K9)
R-HSA-6805755 EHMT1:EHMT2 dimethylates TP53
R-HSA-8953452 E2F6.com-1 complex binds the E2F1 gene promoter
R-HSA-427389 ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP)
R-HSA-8953750 Transcriptional Regulation by E2F6
R-HSA-5250913 Positive epigenetic regulation of rRNA expression
R-HSA-2559583 Cellular Senescence
R-HSA-212436 Generic Transcription Pathway
R-HSA-3214841 PKMTs methylate histone lysines
R-HSA-6804760 Regulation of TP53 Activity through Methylation
R-HSA-212165 Epigenetic regulation of gene expression
R-HSA-2262752 Cellular responses to stress
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-3247509 Chromatin modifying enzymes
R-HSA-5633007 Regulation of TP53 Activity
R-HSA-74160 Gene expression (Transcription)
R-HSA-8953897 Cellular responses to external stimuli
R-HSA-4839726 Chromatin organization
R-HSA-3700989 Transcriptional Regulation by TP53

-  Other Names for This Gene
  Alternate Gene Symbols: B0UZY2, BAT8, C6orf30, EHMT2_HUMAN, G9A, KMT1C, NG36, NM_006709, NP_006700, Q14349, Q5JP83, Q5JQ92, Q5JQA1, Q5JQG3, Q6PK06, Q96KQ7, Q96MH5, Q96QD0, Q9UQL8, Q9Y331
UCSC ID: uc003nxz.1
RefSeq Accession: NM_006709
Protein: Q96KQ7 (aka EHMT2_HUMAN)
CCDS: CCDS4725.1, CCDS4726.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_006709.3
exon count: 28CDS single in 3' UTR: no RNA size: 3982
ORF size: 3633CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 7322.00frame shift in genome: no % Coverage: 99.62
has start codon: yes stop codon in genome: no # of Alignments: 7
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.