This region is found in a number of histone lysine methyltransferases (HMTase), C-terminal to the SET domain; it is generally described as the post-SET domain.
Histone lysine methylation is part of the histone code that regulated chromatin function and epigenetic control of gene function. Histone lysine methyltransferases (HMTase) differ both in their substrate specificity for the various acceptor lysines as well as in their product specificity for the number of methyl groups (one, two, or three) they transfer. With just one exception [ (PUBMED:12123582) ], the HMTases belong to SET family that can be classified according to the sequences surrounding the SET domain [ (PUBMED:11691919) (PUBMED:11893494) ]. Structural studies on the human SET7/9, a mono-methylase, have revealed the molecular basis for the specificity of the enzyme for the histone-target and the roles of the invariant residues in the SET domain in determining the methylation specificities [ (PUBMED:12540855) ].
The pre-SET domain, as found in the SUV39 SET family, contains nine invariant cysteine residues that are grouped into two segments separated by a region of variable length. These 9 cysteines coordinate 3 zinc ions to form to form a triangular cluster, where each of the zinc ions is coordinated by 4 four cysteines to give a tetrahedral configuration. The function of this domain is structural, holding together 2 long segments of random coils.
The C-terminal region including the post-SET domain is disordered when not interacting with a histone tail and in the absence of zinc. The three conserved cysteines in the post-SET domain form a zinc-binding site when coupled to a fourth conserved cysteine in the knot-like structure close to the SET domain active site [ (PUBMED:12887903) ]. The structured post-SET region brings in the C-terminal residues that participate in S-adenosylmethine-binding and histone tail interactions. The three conserved cysteine residues are essential for HMTase activity, as replacement with serine abolishes HMTase activity [ (PUBMED:12372305) ].
Family alignment:
There are 16430 PostSET domains in 16148 proteins in SMART's nrdb database.
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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing PostSET domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with PostSET domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing PostSET domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31.
EMBO J. 1999; 18: 1923-38
Display abstract
The chromo and SET domains are conserved sequence motifs present in chromosomal proteins that function in epigenetic control of gene expression, presumably by modulating higher order chromatin. Based on sequence information from the SET domain, we have isolated human (SUV39H1) and mouse (Suv39h1) homologues of the dominant Drosophila modifier of position-effect-variegation (PEV) Su(var)3-9. Mammalian homologues contain, in addition to the SET domain, the characteristic chromo domain, a combination that is also preserved in the Schizosaccharyomyces pombe silencing factor clr4. Chromatin-dependent gene regulation is demonstrated by the potential of human SUV39H1 to increase repression of the pericentromeric white marker gene in transgenic flies. Immunodetection of endogenous Suv39h1/SUV39H1 proteins in a variety of mammalian cell lines reveals enriched distribution at heterochromatic foci during interphase and centromere-specific localization during metaphase. In addition, Suv39h1/SUV39H1 proteins associate with M31, currently the only other characterized mammalian SU(VAR) homologue. These data indicate the existence of a mammalian SU(VAR) complex and define Suv39h1/SUV39H1 as novel components of mammalian higher order chromatin.
Metabolism (metabolic pathways involving proteins which contain this domain)
Click the image to view the interactive version of the map in iPath
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with PostSET domain which could be assigned to a KEGG orthologous group, and not all proteins containing PostSET domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
