Protein Domain : IPR025789

Type:  Domain Name:  Histone-lysine N-methyltransferase DOT1 domain
Description:  This entry represents the DOT 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 firstidentified as a Disruptor Of Telomeric silencing in yeast where Dot1p is implicated in gene silencing and localization of the Silent InformationRegulator (SIR) complex; in higher eukaryotes the methylation carried out by this enzyme may be used for differentiating chromatin domains. Unlike otherhistone-lysine methyltransferases (HKMTs), Dot1p displays a Rossmann-like (Class I) S-adenosyl-L-methyionine (SAM)-dependent MT foldwhile other HKMTs contain the SET domain and hence belong to a whole different structural class [, ].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 ofhistone H3) is located in the conserved histone core, in a short turn connecting the first and second helices, exposed on the nucleosome disksurface [, ]. In order for Lys-79 of H3 to be methylated by Dot1p, anotherlysine, Lys-123 of histone H2B, needs to be ubiquitinated. A possible reason put forward for this requirement is that the ubiquitination may create a spacebetween adjacent nucleosomes, permitting access of Dot1p to its substrate [, ]. 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 [].The strucure of the evolutionary conserved core of Dot1p, the DOT1 domain, has first been described for the yeast Dot1p in complex withS-adenosyl-L-homocysteine (AdoHcy) and then for the human Dot1-like protein (Dot1Lp) in complex with SAM. The DOT1domain 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 theyeast Dot1p and at the N terminus of the human Dot1Lp [, ]. DOT1 displays arather elongated structure and can be subdivided into two parts: the N- and the C-terminal subdomains []. The N-terminal part is made up of five alphahelices and two pairs of short beta strand hairpins. The C-terminal part displays a Rossmann-like fold: it consists in aseven-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 centraltopological switchpoint resulting in a deep pocket where SAM is bound. The two subdomains are linked covalently by a loop. Altogether the SAM binding pocketis 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 bothparts; two of these segments are conserved across different Class I SAM-dependent MTs []. Short Name:  DOT1_dom
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0 Child Features

0 Contains

1 Cross References

Identifier
PS51569

0 Found In

1 GO Annotation

GO Term Gene Name
GO:0018024 IPR025789

1 Ontology Annotations

GO Term Gene Name
GO:0018024 IPR025789

1 Parent Features

DB identifier Type Name
IPR029063 Domain S-adenosyl-L-methionine-dependent methyltransferase

3 Proteins

DB identifier UniProt Accession Secondary Identifier Organism Name Length
160928 C1N1A3 PAC:27340505 Micromonas pusilla CCMP1545 225  
62902 C1FJQ6 PAC:27399992 Micromonas sp RCC299 272  
Bobra.0183s0009.1.p PAC:40716320 Botryococcus braunii 186  

2 Publications

First Author Title Year Journal Volume Pages PubMed ID
            15292170
            12628190