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MGP005920

UniProt Annotations

Entry Information
Gene Nameeuchromatic histone-lysine N-methyltransferase 1
Protein EntryEHMT1_HUMAN
UniProt IDQ9H9B1
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Comment=Experimental confirmation may be lacking for some isoforms.; Name=1; IsoId=Q9H9B1-1; Sequence=Displayed; Name=2; IsoId=Q9H9B1-2; Sequence=VSP_002222, VSP_002223; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.; Name=3; IsoId=Q9H9B1-3; Sequence=VSP_002224, VSP_002225; Name=4; IsoId=Q9H9B1-4; Sequence=VSP_040717, VSP_040718;
Catalytic ActivityS-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. {ECO:0000269|PubMed:12004135}.
DiseaseKleefstra syndrome (KLESTS) [MIM:610253]: A syndrome characterized by severe mental retardation, hypotonia, brachy(micro)cephaly, and facial dysmorphisms. Additionally, congenital heart defects, urogenital defects, epilepsy and behavioral problems are frequently observed. {ECO:0000269|PubMed:16826528, ECO:0000269|PubMed:19264732}. Note=The disease is caused by mutations affecting the gene represented in this entry (PubMed:16826528). The syndrome can be either caused by intragenic EHMT1 mutations leading to haploinsufficiency of the EHMT1 gene or by a submicroscopic 9q34.3 deletion. Although it is not known if and to what extent other genes in the 9q34.3 region contribute to the syndrome observed in deletion cases, EHMT1 seems to be the major determinant of the core disease phenotype (PubMed:19264732). {ECO:0000269|PubMed:16826528, ECO:0000269|PubMed:19264732}.
DomainIn the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster. {ECO:0000269|PubMed:18264113}.
DomainThe 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. {ECO:0000250, ECO:0000269|PubMed:18264113}.
DomainThe SET domain mediates interaction with WIZ. {ECO:0000269|PubMed:18264113}.
Enzyme RegulationMethyltransferase 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. {ECO:0000269|PubMed:20434463}.
FunctionHistone 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. {ECO:0000269|PubMed:12004135, ECO:0000269|PubMed:20118233}.
InteractionQ99549:MPHOSPH8; NbExp=2; IntAct=EBI-766087, EBI-2653928; Q04206:RELA; NbExp=3; IntAct=EBI-766087, EBI-73886; Q04207:Rela (xeno); NbExp=5; IntAct=EBI-766087, EBI-644400;
Sequence CautionSequence=BAB14321.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305}; Sequence=CAD28534.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; Sequence=CAH71077.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAI17354.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
SimilarityBelongs to the class V-like SAM-binding methyltransferase superfamily. {ECO:0000255|PROSITE- ProRule:PRU00190}.
SimilarityContains 1 pre-SET domain. {ECO:0000255|PROSITE- ProRule:PRU00157}.
SimilarityContains 1 SET domain. {ECO:0000255|PROSITE- ProRule:PRU00190}.
SimilarityContains 8 ANK repeats. {ECO:0000255|PROSITE- ProRule:PRU00023}.
Subcellular LocationNucleus. Chromosome. Note=Associates with euchromatic regions.
SubunitHeterodimer; heterodimerizes with EHMT2. Interacts with WIZ and EHMT2. 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. Interacts (via ANK repeats) with RELA (when monomethylated at 'Lys-310'). Interacts with MPHOSPH8. Interacts with CDYL. Interacts with REST only in the presence of CDYL. Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2. {ECO:0000269|PubMed:12004135, ECO:0000269|PubMed:16702210, ECO:0000269|PubMed:18264113, ECO:0000269|PubMed:19061646, ECO:0000269|PubMed:20084102, ECO:0000269|PubMed:20118233, ECO:0000269|PubMed:20434463, ECO:0000269|PubMed:20871592}.
Tissue SpecificityWidely expressed. {ECO:0000269|PubMed:11347906}.
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