|PROSITE documentation PDOC00694 [for PROSITE entry PS00892]|
HIT (histidine triad) proteins, named for a short motif related to the sequence (His-x-His-x-His-x-x, where x is a hydrophobic residue) [1,2] are a superfamily of nucleotide hydrolases which acts on the α-phosphate of ribonucleotides [3,4]. This superfamily can be divided in two branches: the Hint branch that is the most widely conserved and has representatives in all cellular life and the Fhit (for “fragile histidine triad”) branch which is only found in animals and fungi. The two branches share a conserved core region of about 1oo amino acids, the HIT domain.
Crystal structures of the HINT-nucleotide complexe revealed that the HIT domain is related to GalT nucleotide-binding proteins (see <PDOC00108>) (see <PDB:3RHN>) . The GalT monomer can be seen as consisting of two repeated HIT domains. Their nucleotide binding sites also retain some of the same residues for binding a nucleoside monophosphate. The histidine triad is located outside the nucleotide binding pocket and stabilize it.
Some proteins known to contain a HIT domain are listed below:
As a signature pattern, we selected the region of the histidine triad. We also developed a profile that covers the whole HIT domain.Expert(s) to contact by email:
April 2006 / Pattern revised.
PROSITE methods (with tools and information) covered by this documentation:
|Title||The HIT protein family: a new family of proteins present in prokaryotes, yeast and mammals.|
|Source||DNA Seq. 3:177-179(1992).|
|2||Authors||Brenner C. Bieganowski P. Pace H.C. Huebner K.|
|Title||The histidine triad superfamily of nucleotide-binding proteins.|
|Source||J. Cell. Physiol. 181:179-187(1999).|
|3||Authors||Huang Y. Garrison P.N. Barnes L.D.|
|Title||Cloning of the Schizosaccharomyces pombe gene encoding diadenosine 5',5''-P1,P4-tetraphosphate (Ap4A) asymmetrical hydrolase: sequence similarity with the histidine triad (HIT) protein family.|
|Source||Biochem. J. 312:925-932(1995).|
|Title||Hint, Fhit, and GalT: function, structure, evolution, and mechanism of three branches of the histidine triad superfamily of nucleotide hydrolases and transferases.|
|5||Authors||Brenner C. Garrison P. Gilmour J. Peisach D. Ringe D. Petsko G.A. Lowenstein J.M.|
|Title||Crystal structures of HINT demonstrate that histidine triad proteins are GalT-related nucleotide-binding proteins.|
|Source||Nat. Struct. Biol. 4:231-238(1997).|