histone-lysine N-methyltransferase SUV39H1; histone H3-K9 methyltransferase 1; H3-K9-HMTase 1; lysine N-methyltransferase 1A; position-effect variegation 3-9 homolog; suppressor of variegation 3-9 homolog 1; Su(var)3-9 homolog 1 (SUV39H1, KMT1A, SUV39H)

Function: - histone methyltransferase - specifically trimethylates Lys-9 of histone H3 using monomethylated H3 Lys-9 as substrate - also weakly methylates histone H1 (in vitro) - H3 Lys-9 trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 &/or CBX5) proteins to methylated histones - functions in heterochromatin regions, thus playing a role in establishment of constitutive heterochromatin at pericentric & telomere regions - H3 Lys-9 trimethylation is also required to direct DNA methylation at pericentric repeats - SUV39H1 is targeted to histone H3 via its interaction with RB1 & is involved in many processes, including a) repression of MYOD1-stimulated differentiation b) regulating exiting of the cell cycle & entering differentiation c) repression by the PML-RARA fusion protein d) BMP-induced repression e) repression of switch recombination to IgA f) regulation of telomere length - component of the eNoSC complex - negatively regulated by KIAA1967/DBC1 - phosphorylated on Ser, & to a lesser degree, on Thr - the phosphorylated form is stabilized by SBF1 & is less active in its transcriptional repressor function - acetylated at Lys-266, leading to inhibition of enzyme activity - SIRT1-mediated deacetylation relieves this inhibition - interacts with H3 & H4 histones - interacts with GFI1B, DNMT3B, CBX1, CBX4, KIAA1967/DBC1, MBD1, RUNX1, RUNX3, MYOD1, SMAD5 & RB1 - interacts with SBF1 through the SET domain - interacts with HDAC1 & HDAC2 through the N-terminus & associates with the core histone deacetylase complex composed of HDAC1, HDAC2, RBBP4 & RBBP7 - in case of infection, interacts with HTLV-1 Tax protein, leading to abrogate Tax transactivation of HTLV-1 LTR - interacts (via SET domain) with MECOM; e nhances MECOM transcriptional repression activity , S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone] Inhibition: - inhibited by S-adenosyl-L-homocysteine Structure: - although the SET domain contains the active site of enzymatic activity, both pre-SET & post-SET domains are required for methyltransferase activity - the SET domain also participates in stable binding to heterochromatin - belongs to the histone-lysine methyltransferase family, Suvar3-9 subfamily - contains 1 chromo domain - contains 1 post-SET domain - contains 1 pre-SET domain - contains 1 SET domain Compartment: - nucleus, chromosome, centromere - associates with centromeric constitutive heterochromatin Expression: - accumulates during mitosis at centromeres during prometaphase, but dissociates from the centromere at the metaphase to anaphase transition

General

histone N-methyltransferase phosphoprotein

Properties

SIZE: entity length = 412 aa MW = 48 kD COMPARTMENT: cell nucleus MOTIF: SIRT1 interaction {1-89} chromodomain NAME: chromodomain SITE: 43-101 FOR-BINDING-OF: heterochromatin pre-SET domain {179-240} SET domain {242-370} Mediates interaction with MECOM {255-377} Ser phosphorylation site {S391} post-SET domain {396-412}

Database Correlations

OMIM 300254 UniProt O43463 PFAM correlations Entrez Gene 6839 Kegg hsa:6839 ENZYME 2.1.1.43

References

UniProt :accession O43463