Human Gene EHMT1 (uc011mfc.2) Description and Page Index
  Description: Homo sapiens euchromatic histone-lysine N-methyltransferase 1 (EHMT1), transcript variant 1, mRNA.
RefSeq Summary (NM_024757): The protein encoded by this gene is a histone methyltransferase that methylates the lysine-9 position of histone H3. This action marks the genomic region packaged with these methylated histones for transcriptional repression. This protein may be involved in the silencing of MYC- and E2F-responsive genes and therefore could play a role in the G0/G1 cell cycle transition. Defects in this gene are a cause of chromosome 9q subtelomeric deletion syndrome (9q-syndrome, also known as Kleefstra syndrome). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017].
Transcript (Including UTRs)
   Position: hg19 chr9:140,513,444-140,730,578 Size: 217,135 Total Exon Count: 27 Strand: +
Coding Region
   Position: hg19 chr9:140,513,481-140,729,405 Size: 215,925 Coding Exon Count: 27 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr9:140,513,444-140,730,578)mRNA (may differ from genome)Protein (1298 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCEUniProtKB

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Histone-lysine N-methyltransferase EHMT1; EC=2.1.1.-; EC=; AltName: Full=Euchromatic histone-lysine N-methyltransferase 1; Short=Eu-HMTase1; AltName: Full=G9a-like protein 1; Short=GLP; Short=GLP1; AltName: Full=Histone H3-K9 methyltransferase 5; Short=H3-K9-HMTase 5; AltName: Full=Lysine N-methyltransferase 1D;
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 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. During G0 phase, it probably contributes to silencing of MYC- and E2F-responsive genes, suggesting a role in G0/G1 transition in cell cycle. In addition to the histone methyltransferase activity, also methylates non- histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53.
CATALYTIC ACTIVITY: S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].
ENZYME REGULATION: Methyltransferase activity is inhibited by BIX- 01294. Efficiently inhibited by compound E72, a BIX-01294 derivative in which the diazepane ring and the benzyl are replaced with a 3-dimethylaminopropyl and a 5-aminopentyl group at sites B and C, respectively.
SUBUNIT: Heterodimer; heterodimerizes with EHMT2/G9a. Interacts with WIZ and EHMT2. Part of the complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EHMT1, RING1, RNF2, MBLR, L3MBTL2 and YAF2. Interacts (via ANK repeats) with RELA (when monomethylated at 'Lys-310'). Interacts with MPHOSPH8.
INTERACTION: Q04206:RELA; NbExp=3; IntAct=EBI-766087, EBI-73886; Q04207:Rela (xeno); NbExp=5; IntAct=EBI-766087, EBI-644400;
SUBCELLULAR LOCATION: Nucleus. Chromosome. Note=Associates with euchromatic regions.
TISSUE SPECIFICITY: Widely expressed.
DOMAIN: The ANK repeats recognize and bind RELA subunit of NF- kappa-B, when RELA is monomethylated at 'Lys-310' (By similarity). They also specifically recognize and bind H3K9me1 and H3K9me2.
DOMAIN: The SET domain mediates interaction with WIZ.
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
DISEASE: Defects in EHMT1 are the cause of chromosome 9q subtelomeric deletion syndrome (9q- syndrome) [MIM:610253]. Common features seen in these patients are severe mental retardation, hypotonia, brachy(micro)cephaly, epileptic seizures, flat face with hypertelorism, synophrys, anteverted nares, cupid bow or tented upper lip, everted lower lip, prognathism, macroglossia, conotruncal heart defects, and behavioral problems.
SIMILARITY: Belongs to the histone-lysine methyltransferase family.
SIMILARITY: Contains 8 ANK repeats.
SIMILARITY: Contains 1 pre-SET domain.
SIMILARITY: Contains 1 SET domain.
SEQUENCE CAUTION: Sequence=CAD28534.1; Type=Miscellaneous discrepancy; Note=Intron retention; Sequence=CAH71077.1; Type=Erroneous gene model prediction; Sequence=CAI17354.1; Type=Erroneous gene model prediction;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): EHMT1
CDC HuGE Published Literature: EHMT1
Positive Disease Associations: Macular Degeneration , overall effect
Related Studies:
  1. Macular Degeneration
    , , . [PubMed 0]
  2. overall effect
    Nasim Mavaddat , et al. Cancer epidemiology, biomarkers & prevention 2009 18(1):255-9, Common genetic variation in candidate genes and susceptibility to subtypes of breast cancer., Cancer epidemiology, biomarkers & prevention 2009 18(1):255-9. [PubMed 19124506]

-  MalaCards Disease Associations
  MalaCards Gene Search: EHMT1
Diseases sorted by gene-association score: kleefstra syndrome* (1360), autism spectrum disorder* (406), polymicrogyria* (400), chromosome 9q deletion* (400), kleefstra syndrome due to a point mutation* (350), polymicrogyria, bilateral temporooccipital* (283), kleefstra syndrome due to 9q34 microdeletion* (25), deafness, autosomal recessive 79 (9), deafness, autosomal recessive 33 (9), hypoplastic left heart syndrome (8)
* = Manually curated disease association

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

+  Common Gene Haplotype Alleles
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-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 14.04 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 268.56 RPKM

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

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -20.3037-0.549 Picture PostScript Text
3' UTR -414.451173-0.353 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
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

- X-ray MuPIT

- X-ray MuPIT

- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
3B95 - X-ray MuPIT 3FPD - X-ray MuPIT 3HNA - X-ray MuPIT
3MO0 - X-ray MuPIT 3MO2 - X-ray MuPIT 3MO5 - X-ray MuPIT
3SW9 - X-ray MuPIT 3SWC - X-ray MuPIT

ModBase Predicted Comparative 3D Structure on Q9H9B1
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 orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
  Protein Sequence   

-  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

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0006306 DNA methylation
GO:0006325 chromatin organization
GO:0009790 embryo development
GO:0016571 histone methylation
GO:0018026 peptidyl-lysine monomethylation
GO:0018027 peptidyl-lysine dimethylation
GO:0032259 methylation
GO:0034968 histone lysine methylation
GO:0045892 negative regulation of transcription, DNA-templated
GO:0051567 histone H3-K9 methylation
GO:0060992 response to fungicide
GO:0070317 negative regulation of G0 to G1 transition
GO:0070734 histone H3-K27 methylation

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0016604 nuclear body

-  Descriptions from all associated GenBank mRNAs
  BC047504 - Homo sapiens euchromatic histone-lysine N-methyltransferase 1, mRNA (cDNA clone MGC:50973 IMAGE:5298029), complete cds.
AK022941 - Homo sapiens cDNA FLJ12879 fis, clone NT2RP2003857, weakly similar to MYOTROPHIN.
AY083210 - Homo sapiens euchromatic histone methyltransferase 1 mRNA, complete cds.
AK309602 - Homo sapiens cDNA, FLJ99643.
AB028932 - Homo sapiens mRNA for GLP1, complete cds.
AB058779 - Homo sapiens mRNA for KIAA1876 protein, partial cds.
BC025772 - Homo sapiens euchromatic histone-lysine N-methyltransferase 1, mRNA (cDNA clone IMAGE:5209740), partial cds.
BC011608 - Homo sapiens euchromatic histone-lysine N-methyltransferase 1, mRNA (cDNA clone IMAGE:3161748), partial cds.
AL713772 - Homo sapiens mRNA; cDNA DKFZp667G072 (from clone DKFZp667G072).
AL832865 - Homo sapiens mRNA; cDNA DKFZp667M072 (from clone DKFZp667M072).
AF461894 - Homo sapiens FP13812 mRNA, complete cds.

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

Reactome (by CSHL, EBI, and GO)

Protein Q9H9B1 (Reactome details) participates in the following event(s):

R-HSA-3788725 Cdh1:APC/C complex binds EHMT1:EHMT2
R-HSA-8953418 EHMT1:EHMT2 complex binds core
R-HSA-3788724 Cdh1:APC/C ubiquitinates EHMT1 and EHMT2
R-HSA-9007283 CBX3 and PRC1.6 associate with
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 complex binds the E2F1 gene promoter
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP)
R-HSA-8953750 Transcriptional Regulation by E2F6
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-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-8953897 Cellular responses to external stimuli
R-HSA-74160 Gene expression (Transcription)
R-HSA-4839726 Chromatin organization
R-HSA-3700989 Transcriptional Regulation by TP53

-  Other Names for This Gene
  Alternate Gene Symbols: B1AQ58, B1AQ59, EHMT1_HUMAN, EUHMTASE1, GLP, KIAA1876, KMT1D, NM_024757, NP_079033, Q86X08, Q8TCN7, Q96F53, Q96JF1, Q96KH4, Q9H9B1
UCSC ID: uc011mfc.2
RefSeq Accession: NM_024757
Protein: Q9H9B1 (aka EHMT1_HUMAN or HMT1_HUMAN)
CCDS: CCDS7050.2

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene EHMT1:
kleefstra (Kleefstra Syndrome)

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_024757.4
exon count: 27CDS single in 3' UTR: no RNA size: 5123
ORF size: 3897CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 7282.00frame shift in genome: no % Coverage: 99.69
has start codon: yes stop codon in genome: no # of Alignments: 1
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.