The domain within your query sequence starts at position 115 and ends at position 317; the E-value for the DOT1 domain shown below is 9.4e-86.

YNHSVTDPEKLNNYEPFSPEVYGETSFDLVAQMIDEIKMTEDDLFVDLGSGVGQVVLQVA
AATNCKHHYGVEKADIPAKYAETMDREFRKWMKWYGKKHAEYTLERGDFLSEEWRERIAN
TSVIFVNNFAFGPEVDHQLKERFANMKEGGRIVSSKPFAPLNFRINSRNLSDIGTIMRVV
ELSPLKGSVSWTGKPVSYYLHTI

DOT1

DOT1
PFAM accession number:PF08123
Interpro abstract (IPR025789):

This entry represents the DOT1 domain.

The Dot1 protein (Dot1p) is an histone-lysine N-methyltransferase (EC 2.1.1.43) that methylates lysine 79 (Lys-79) of histone H3. It was first identified as a Disruptor Of Telomeric silencing in yeast where Dot1p is implicated in gene silencing and localization of the Silent Information Regulator (SIR) complex; in higher eukaryotes the methylation carried out by this enzyme may be used for differentiating chromatin domains. Unlike other histone-lysine methyltransferases (HKMTs), Dot1p displays a Rossmann-like (Class I) S-adenosyl-L-methyionine (SAM)-dependent MT fold while other HKMTs contain the SET domain and hence belong to a whole different structural class [(PUBMED:15292170), (PUBMED:12628190)].

Whereas most HKMTs, such as Suvar3-9 methylate Lys on the N-terminal tails of histones that stick out from the nucleosome, Dot1p substrate (Lys-79 of histone H3) is located in the conserved histone core, in a short turn connecting the first and second helices, exposed on the nucleosome disk surface [(PUBMED:15292170), (PUBMED:12628190)]. In order for Lys-79 of H3 to be methylated by Dot1p, another lysine, Lys-123 of histone H2B, needs to be ubiquitinated. A possible reason put forward for this requirement is that the ubiquitination may create a space between adjacent nucleosomes, permitting access of Dot1p to its substrate [(PUBMED:15292170), (PUBMED:12628190)]. In yeast, different states of methylation on Lys-79 of histone H3 (unmodified, mono-, di- and trimethylated) co-exist at the same time, but no clear function is associated with these different methylation states [(PUBMED:15292170)].

The strucure of the evolutionary conserved core of Dot1p, the DOT1 domain, has first been described for the yeast Dot1p in complex with S-adenosyl-L-homocysteine (AdoHcy) and then for the human Dot1-like protein (Dot1Lp) in complex with SAM. The DOT1 domain is about 300-350 amino acids long and is usually located at either of the extremities of the protein sequence: it stands at the C terminus of the yeast Dot1p and at the N terminus of the human Dot1Lp [(PUBMED:15292170), (PUBMED:12628190)]. DOT1 displays a rather elongated structure and can be subdivided into two parts: the N- and the C-terminal subdomains [(PUBMED:12628190)]. The N-terminal part is made up of five alpha helices and two pairs of short beta strand hairpins. The C-terminal part displays a Rossmann-like fold: it consists in a seven-stranded beta sheet tucked by five alpha helices (three helices on one side of the sheet and two on the other), the sheet contains a central topological switchpoint resulting in a deep pocket where SAM is bound. The two subdomains are linked covalently by a loop. Altogether the SAM binding pocket is formed by five segments of the DOT1 domain of which four are located in the C-terminal substructure of the DOT1 domain and one in the loop connecting both parts; two of these segments are conserved across different Class I SAM-dependent MTs [(PUBMED:12628190)].

GO function:histone-lysine N-methyltransferase activity (GO:0018024)

This is a PFAM domain. For full annotation and more information, please see the PFAM entry DOT1