InterPro domain: IPR039383

FHIT (fragile histidine) proteins are related to the HIT family members that carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid) [ 1 ]. On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified into three branches: the Hint branch, which consists of adenosine 5' -monophosphoramide hydrolases, the FHIT branch, that consists of diadenosine polyphosphate hydrolases, and the GalT branch consisting of specific nucloside monophosphate transferases [ 2 , 3 , 4 ]. FHIT plays a very important role in the development of tumours. In fact, FHIT deletions are among the earliest and most frequent genetic alterations in the development of tumours [ 5 , 6 ].

1. Structure-based analysis of catalysis and substrate definition in the HIT protein family. Science 278, 286-90
2. Hint, Fhit, and GalT: function, structure, evolution, and mechanism of three branches of the histidine triad superfamily of nucleotide hydrolases and transferases. Biochemistry 41, 9003-14
3. The HIT protein family: a new family of proteins present in prokaryotes, yeast and mammals. DNA Seq. 3, 177-9
4. Genetic, biochemical, and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit. Proc. Natl. Acad. Sci. U.S.A. 95, 5484-9
5. FHIT: from gene discovery to cancer treatment and prevention. Lancet Oncol. 3, 748-54
6. FHIT as tumor suppressor: mechanisms and therapeutic opportunities. Cancer Biol. Ther. 1, 232-6