FHIT (fragile histidine) proteins are related to the HIT family members that carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid) []. 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 [, , ]. 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 [, ].
The Histidine Triad (HIT) motif, His-x-His-x-His-x-x (x, ahydrophobic amino acid) was identified as being highly conserved in a variety of organisms [, ]. 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 [, ]. In budding yeast Hnt1 has been shown to have adenosine monophosphoramidase activity and function as positive regulators of Cdk7/Kin28 in vivo [, ]. 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 [, ]. 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 ratherthan hydrolysing them [].
The Histidine Triad (HIT) motif, His-x-His-x-His-x-x (x, ahydrophobic amino acid) was identified as being highly conserved in a variety of organisms []. Crystal structure of rabbit Hint, purified as an adenosine and AMP-binding protein, showed that proteins in the HITsuperfamily 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 []. Hint homologues including rabbit Hint and yeastHnt1 hydrolyse adenosine 5' monophosphoramide substrates such as AMP-NH2 andAMP-lysineto AMP plus the amine product and function as positive regulatorsof Cdk7/Kin28 in vivo []. Fhit homologues are diadenosine polyphosphate hydrolases []and function as tumour suppressors in human and mouse []though the tumour suppressing function of Fhit does not depend on ApppA hydrolysis []. The third branch of the HIT superfamily, which includesGalT homologues, contains a related His-X-His-X-Gln motif and transfersnucleoside monophosphate moieties to phosphorylated second substrates ratherthan hydrolysing them [].The bovine protein kinase C inhibitor, PKCI-1, is an inhibitor protein that binds zinc without the use of zinc-finger motifs []. Each protein molecule binds one zinc ion via a novel binding site containing 3 closely-spaced histidine residues []. This region, referred to as the histidine triad (HIT) [], has been identified in various prokaryotic and eukaryotic proteins of uncertain function [].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.
HIT (Histidine triad) proteins, named for a motif related to the sequence HxHxH/Qxx (x, a hydrophobic amino acid), are a superfamily of nucleotide hydrolases and transferases that act on the alpha-phosphate of ribonucleotides. On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified in the literature into three major branches: the Hint branch, which consists of adenosine 5' -monophosphoramide hydrolases, the Fhit branch, which consists of diadenosine polyphosphate hydrolases, and the GalT branch, consisting of specific nucleoside monophosphate transferases. Further sequence analysis reveals several new, closely related, yet uncharacterised subgroups. This group includes bacterial proteins which are members from the Hint branch of hydrolases. For additional information please see [, , , , , ].
Proteins containing this domain include mammalian Nit1 and Nit2, the Nit1-like domain of the invertebrate NitFhit, yeast Nit3 and various uncharacterized bacterial and archaeal Nit-like proteins. In general, they are amidases involved in various metabolic processes. Nit1 is a deaminated glutathione amidase [], while Nit2 is an omega-amidase []. They are candidate tumour suppressor proteins []. In NitFhit, the Nit1-like domain is encoded as a fusion protein with the non-homologous tumour suppressor, fragile histidine triad (Fhit) []. Mammalian Nit1 and Fhit may affect distinct signal pathways, and both may participate in DNA damage-induced apoptosis []. Nit1 is a negative regulator in T cells []. Overexpression of Nit2 in HeLa cells leads to a suppression of cell growth through cell cycle arrest in G2 [].
HINT (histidine triad nucleotide-binding protein) are related to the HIT family members that carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid) []. 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 []. HINT family includes members from all three forms of cellular life. In budding yeast Hnt1 has been shown to have adenosine monophosphoramidase activity []. It is involved in secretion, peroxisome formation and gene expression [, ]. The bacterial and archaeal members of this family are mostly uncharacterised.
