| Primary Identifier | IPR046341 | Type | Homologous_superfamily |
| Short Name | SET_dom_sf |
| description | 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 eukaryotic organisms, it appears in proteins with an important role in regulating chromatin-mediated gene transcriptional activation and silencing. In viruses,bacteria and archaea, its function is not clear yet []. This superfamily includes eukaryotic proteins with histone methyltransferase activity, which 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 [, ]. Other SET domain-containing proteins function as transcription factors (such as PR domain zinc finger protein 1 from humans []). The structure of the SET domain and the two adjacent regions pre-SET and post-SET have been solved [, , ]. The SET domain structure is all-β, 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 discontinuous segments of the primary sequence forming an approximate L-shape [, , ]. Two of the most conserved motifs in the SET domain are constituted by a stretch at the C-terminal containing a strictly conserved tyrosine residue and 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 [, ]. |
