DOT1 Like, Histone H3 Methyltransferase (DOT1L)

DOT1; KMT4; Histone-lysine N-methyltransferase, H3 lysine-79 specific; Histone H3-K79 methyltransferase; Lysine N-methyltransferase 4

SPN	M942
HGNC	24948
MGI	2143886
PubMed	23861670
RGD	1306644
UniProt	Q8TEK3
Wiki	DOT1L

DOT1L is inactive against free core histones, but shows significant histone methyltransferase activity against nucleosomes. DOT1L is a nucleosomal histone-3 (H3)-specific methyltransferase that requires the SAM and sequences between amino acids 351 and 472 for activity. Overexpression of DOT1L in human embryonic kidney cells significantly increased methylation of lys79 of H3, but had no effect on lys4 or lys9. Methylation of lys79, attributed to DOT1L, was regulated during the cell cycle in synchronized HeLa cells. The deduced 1,537-amino acid protein has a calculated molecular mass of 165 kD and contains a SAM (sterile alpha motif) domain for protein-protein interaction. DOT1L does not, however, have the SET domain found in most histone lysine methyltransferases.

Reference

"Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain."
Curr. Biol. 12:1052-1058(2002) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and biology of human chromosome 19."
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]

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DNA Res. 8:85-95(2001) [PubMed] [Europe PMC] [Abstract]

"Characterization of long cDNA clones from human adult spleen. II. The complete sequences of 81 cDNA clones."
DNA Res. 10:49-57(2003) [PubMed] [Europe PMC] [Abstract]

"hDOT1L links histone methylation to leukemogenesis."
Cell 121:167-178(2005) [PubMed] [Europe PMC] [Abstract]

"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]

"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]

"Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase."
Cell 112:711-723(2003) [PubMed] [Europe PMC] [Abstract]