histone-lysine N-methyltransferase EHMT2; euchromatic histone-lysine N-methyltransferase 2; HLA-B-associated transcript 8; histone H3-K9 methyltransferase 3; H3-K9-HMTase 3; lysine N-methyltransferase 1C; protein G9a (EHMT2, BAT8, C6orf30, G9A, KMT1C, NG36)

Function: - histone methyltransferase - specifically mono- & dimethylates Lys-9 of histone H3 (H3K9me1 & H3K9me2, respectively) in euchromatin - H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones - weakly methylates Lys-27 of histone H3 (H3K27me) - 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 &/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 - methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 & itself - phosphorylated upon DNA damage, probably by ATM or ATR - methylated at Lys-185; automethylated - heterodimer; heterodimerizes with EHMT1/GLP - interacts with GFI1B & WIZ - part of the E2F6.com-1 complex in G0 phase S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone] Structure: - the SET domain mediates interaction with WIZ - the ANK repeats bind H3K9me1 & H3K9me2 - belongs to the histone-lysine methyltransferase family, Suvar3-9 subfamily - contains 7 ANK repeats - contains 1 post-SET domain - contains 1 pre-SET domain - contains 1 SET domain Compartment: - nucleus, chromosome - associates with euchromatin - does not associate with heterochromatin Alternative splicing: - named isoforms=3 - additional isoforms seem to exist Expression: - expressed in all tissues examined - expressed in fetal liver, thymus, lymph node, spleen & peripheral blood leukocytes > bone marrow Note: - uncertain whether Met-1 or Met-21 is the initiator methionine

General

ankyrin repeat domain protein (ANKRD) histone N-methyltransferase phosphoprotein

Properties

SIZE: entity length = 1210 aa MW = 132 kD COMPARTMENT: cell nucleus MOTIF: alanine-rich region {2-13} MOTIF: alanine residue (SEVERAL) acetylation site SITE: N-TERMINUS EFFECTOR-BOUND: acetyl Ser phosphorylation site {S140} alanine-rich region {160-163} MOTIF: alanine residue (SEVERAL) Ser phosphorylation site {S173} Ser phosphorylation site {S232} Ser phosphorylation site {S246} glutamate-rich region {300-326} MOTIF: glutamate residue (SEVERAL) Thr phosphorylation site {T555} Ser phosphorylation site {S569} ankyrin repeat NAME: ankyrin repeat SITE: 649-678 ankyrin repeat NAME: ankyrin repeat SITE: 684-713 ankyrin repeat NAME: ankyrin repeat SITE: 717-746 ankyrin repeat NAME: ankyrin repeat SITE: 750-780 ankyrin repeat NAME: ankyrin repeat SITE: 784-813 ankyrin repeat NAME: ankyrin repeat SITE: 817-846 MOTIF: H3K9me binding {817-819} ankyrin repeat NAME: ankyrin repeat SITE: 850-879 pre-SET domain {972-1035} MOTIF: Zn+2-binding site SITE: 974-974 Zn+2-binding site SITE: 976-976 Zn+2-binding site SITE: 980-980 Zn+2-binding site SITE: 985-985 Zn+2-binding site SITE: 987-987 Zn+2-binding site SITE: 1017-1017 Zn+2-binding site SITE: 1021-1021 Zn+2-binding site SITE: 1023-1023 Zn+2-binding site SITE: 1027-1027 SET domain {1037-1159} MOTIF: SAM binding {1048-1050} binding site SITE: 1067-1067 FOR-BINDING-OF: Histone H3K9me H3 interaction {1074-1093} binding site SITE: 1085-1085 FOR-BINDING-OF: S-adenosylmethionine SAM binding {1112-1113} Zn+2-binding site SITE: 1115-1115 H3 interaction {1154-1157} post-SET domain {1164-1180} MOTIF: Zn+2-binding site SITE: 1168-1168 Zn+2-binding site SITE: 1170-1170 Zn+2-binding site SITE: 1175-1175 Thr phosphorylation site {T1210}

Database Correlations

OMIM 604599 UniProt Q96KQ7 PFAM correlations Entrez Gene 10919 Kegg hsa:10919 ENZYME correlations

References

UniProt :accession Q96KQ7