Histidine triad (HIT) protein (IPR001310)

Short name: Histidine_triad_HIT

Overlapping homologous superfamilies

Family relationships


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].

Contributing signatures

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