Conserved Site

Histidine triad, conserved site (IPR019808)

Short name: Histidine_triad_CS


The Histidine Triad (HIT) motif, His-x-His-x-His-x-x (x, a hydrophobic amino acid) was identified as being highly conserved in a variety of organisms [PMID: 1472710]. Crystal structure of rabbit Hint, purified as an adenosine and AMP-binding protein, showed that proteins in the HIT superfamily are conserved as nucleotide-binding proteins and that Hint homologues, which are found in all forms of life, are structurally related to Fhit homologues and GalT-related enzymes, which have more restricted phylogenetic profiles [PMID: 9164465]. Hint homologues including rabbit Hint and yeast Hnt1 hydrolyse adenosine 5' monophosphoramide substrates such as AMP-NH2 and AMP-lysine to AMP plus the amine product and function as positive regulators of Cdk7/Kin28 in vivo [PMID: 11805111]. Fhit homologues are diadenosine polyphosphate hydrolases [PMID: 8794732] and function as tumour suppressors in human and mouse [PMID: 10758156] though the tumour suppressing function of Fhit does not depend on ApppA hydrolysis [PMID: 9576908]. The third branch of the HIT superfamily, which includes GalT homologues, contains a related His-X-His-X-Gln motif and transfers nucleoside monophosphate moieties to phosphorylated second substrates rather than hydrolysing them [PMID: 12119013].

The bovine protein kinase C inhibitor, PKCI-1, is an inhibitor protein that binds zinc without the use of zinc-finger motifs [PMID: 2307677]. Each protein molecule binds one zinc ion via a novel binding site containing 3 closely-spaced histidine residues [PMID: 1899836]. This region, referred to as the histidine triad (HIT) [PMID: 1899836], has been identified in various prokaryotic and eukaryotic proteins of uncertain function [PMID: 1472710].

The signature pattern used in this entry contains the region of the histidine triad and includes the three conserved histidine residues which are thought to bind the zinc ion.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns