Histone-lysine N-methyltransferase EHMT2

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. Also able to mono- and dimethylate histone H1-4 at 'Lys-26' (H1.4K26me1 and H1.4K26me2, respectively). 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.

Classification

Family (Pfam)

PF00023 Ank, PF12796 Ank_2, PF21533 EHMT1-2_CRR, PF05033 Pre-SET, PF00856 SET

InterPro

Ankyrin_rpt, Ankyrin_rpt-contain_sf, EHMT1/EHMT2, EHMT_CRR, Pre-SET_dom, SET_dom, SET_dom_sf, SET_EHMT2

Functional cluster

Homeobox & Zinc-Finger Transcription Factors

Experimental structures · PDB · 32

• 2O8J X-ray 1.80A
• 3DM1 X-ray 2.40A
• 3K5K X-ray 1.70A
• 3RJW X-ray 2.56A
• 4NVQ X-ray 2.03A
• 5JHN X-ray 1.67A
• 5JIN X-ray 1.85A
• 5JIY X-ray 1.48A
• 5JJ0 X-ray 1.72A
• 5T0K X-ray 1.70A
• 5T0M X-ray 1.90A
• 5TTF X-ray 1.72A
• … and 20 more

A predicted model is available from AlphaFold.

Gene Ontology · 23

• GO:0000785 chromatin
• GO:0016607 nuclear speck
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0070742 C2H2 zinc finger domain binding
• GO:0140189 H1-4K26 methyltransferase activity
• GO:0046976 histone H3K27 methyltransferase activity
• GO:0140759 histone H3K56 methyltransferase activity
• GO:0046974 histone H3K9 methyltransferase activity
• GO:0140948 histone H3K9 monomethyltransferase activity
• GO:0002039 p53 binding
• GO:1990841 promoter-specific chromatin binding
• GO:0016279 protein-lysine N-methyltransferase activity
• GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding
• GO:0001222 transcription corepressor binding
• GO:0008270 zinc ion binding
• GO:0009267 cellular response to starvation
• GO:0030261 chromosome condensation
• GO:0006346 DNA methylation-dependent constitutive heterochromatin formation
• GO:0040029 epigenetic regulation of gene expression
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0018027 peptidyl-lysine dimethylation
• GO:0006275 regulation of DNA replication

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Histone-lysine N-methyltransferase EHMT2 0.96
• Histone-lysine N-methyltransferase EHMT1 0.84
• Histone-lysine N-methyltransferase EHMT1 0.80
• Tau-tubulin kinase 1 0.74
• Tau-tubulin kinase 1 0.73
• Zinc finger protein 516 0.73
• Rho GTPase-activating protein 30 0.71
• Ankyrin repeat and SAM domain-containing protein 6 0.70
• Protein capicua homolog 0.69
• Mitogen-activated protein kinase kinase kinase 12 0.69
• Ankyrin repeat domain-containing protein 63 0.69
• Polycomb group protein ASXL1 0.69

Co-cited proteins · studied together in the literature

• Histone-lysine N-methyltransferase EHMT2 5 shared papers
• Histone-lysine N-methyltransferase EHMT1 6 shared papers
• PR domain zinc finger protein 2 1 shared papers
• Zinc finger protein Gfi-1b 1 shared papers
• Protein Wiz 2 shared papers
• Lysine-specific demethylase 4A 1 shared papers
• Protein Wiz 1 shared papers
• Histone-lysine N-methyltransferase SUV39H2 1 shared papers
• Histone H1.4 1 shared papers
• Lethal(3)malignant brain tumor-like protein 2 1 shared papers
• Histone-lysine N-methyltransferase SUV39H1 1 shared papers
• SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 1 shared papers

Literature · 33 cited papers

• The structure of the cysteine-rich region from human histone-lysine N-methyltransferase EHMT2 (G9a). J. Struct. Biol. X · 2021
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• A histone H3K9M mutation traps histone methyltransferase Clr4 to prevent heterochromatin spreading. Elife · 2016
• Discovery and development of potent and selective inhibitors of histone methyltransferase g9a. ACS Med. Chem. Lett. · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
• Histone H3 lysine 56 methylation regulates DNA replication through its interaction with PCNA. Mol. Cell · 2012
• Maintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1. Mol. Cell · 2011
• System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
• G9a and Glp methylate lysine 373 in the tumor suppressor p53. J. Biol. Chem. · 2010
• Structural biology of human H3K9 methyltransferases. PLoS ONE · 2010
• … and 21 more in the literature graph