The domain within your query sequence starts at position and ends at position ; the E-value for the PreSET domain shown below is < 1e-12.



N-terminal to some SET domains
SMART accession number:SM00468
Description: A Cys-rich putative Zn2+-binding domain that occurs N-terminal to some SET domains. Function is unknown. Unpublished.
Interpro abstract (IPR003606):

This region is found in a number of histone lysine methyltransferases (HMTase), N-terminal to the SET domain; it is generally described as the pre-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 and stabilising the SET domain.

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)].

GO process:histone lysine methylation (GO:0034968)
GO component:nucleus (GO:0005634)
GO function:zinc ion binding (GO:0008270), histone-lysine N-methyltransferase activity (GO:0018024)
Family alignment:
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There are 139 PreSET domains in 139 proteins in SMART's nrdb database.

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