SET

SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain
SET
SMART accession number:SM00317
Description: Putative methyl transferase, based on outlier plant homologues
Interpro abstract (IPR001214):

The SET domain is a 130 to 140 amino acid, evolutionary well conserved sequence motif that was initially characterised in the Drosophila proteins Su(var)3-9, Enhancer-of-zeste and Trithorax. In addition to these chromosomal proteins modulating gene activities and/or chromatin structure, the SET domain is found in proteins of diverse functions ranging from yeast to mammals, but also including some bacteria and viruses [(PUBMED:9487389), (PUBMED:10949293)].

The SET domains of mammalian SUV39H1 and 2 and fission yeast clr4 have been shown to be necessary for the methylation of lysine-9 in the histone H3 N terminus [(PUBMED:10949293)]. However, this histone methyltransferase (HMTase) activity is probably restricted to a subset of SET domain proteins as it requires the combination of the SET domain with the adjacent cysteine-rich regions, one located N-terminally (pre-SET) and the other posterior to the SET domain (post-SET). Post- and pre- SET regions seem then to play a crucial role when it comes to substrate recognition and enzymatic activity [(PUBMED:12826405), (PUBMED:12372294)].

The structure of the SET domain and the two adjacent regions pre-SET and post-SET have been solved [(PUBMED:12372305), (PUBMED:12372304), (PUBMED:12372303)]. The SET structure is all beta, but consists only in sets of few short strands composing no more than a couple of small sheets. Consequently the SET structure is mostly defined by turns and loops. An unusual feature is that the SET core is made up of two discontinual segments of the primary sequence forming an approximate L shape [(PUBMED:9632640), (PUBMED:12826405), (PUBMED:12372294)]. Two of the most conserved motifs in the SET domain are constituted by (1) a stretch at the C-terminal containing a strictly conserved tyrosine residue and (2) a preceding loop inside which the C-terminal segment passes forming a knot-like structure, but not quite a true knot. These two regions have been proven to be essential for SAM binding and catalysis, particularly the invariant tyrosine where in all likelihood catalysis takes place [(PUBMED:12826405), (PUBMED:12372294)].

GO function:protein binding (GO:0005515)
Family alignment:
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There are 4609 SET domains in 4580 proteins in SMART's nrdb database.

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