HIT-like domain
IPR011146
Definition
The histidine triad motif (HIT) consists of the conserved sequence HXHXHXX (where X is a hydrophobic amino acid) at the enzymatic catalytic centre, in which the second histidine is strictly conserved and participates in catalysis with the third histidine [[cite:PMID:23373416], [cite:PMID:23659632], [cite:PMID:12119013]]. Proteins containing HIT domains form a superfamily of nucleotide hydrolases and transferases that act on the alpha-phosphate of ribonucleotides [[cite:PMID:12119013], [cite:PMID:23373416]]. They are highly conserved from archaea to humans and are involved in galactose metabolism, DNA repair, and tumor suppression PMID:30622225. HIT-containing proteins can be divided in five families based on catalytic specificities, sequence compositions, and structural similarities of its members: Hint family of protein kinase-interacting proteins, the most ancient class in this superfamily. These include adenosine 5'-monophosphoramide hydrolases (e.g. HIT-nucleotide-binding protein, or HINT) [[cite:PMID:19112177], [cite:PMID:12119013]]. They also have a conserved zinc-binding motif C-X-X-C (where C is a cysteine residue and X is a hydrophobic residue), and a zinc ion is coordinated by these cysteine residues, together with the first histidine residue PMID:30622225. Fragile HIT protein, or FINT, whose name is due to its high rate of mutation at its locus on chromosome 3 in many cancers has been characterised as a tumor suppressor and plays a role in the hydrolysis of dinucleotide polyphosphates [[cite:PMID:23659632], [cite:PMID:30622225]]. HINT and FINT HIT domains have a topology similar to that found in the N-terminal of protein kinases PMID:15904496. GalT family. These include specific nucleoside monophosphate transferases (e.g. galactose-1-phosphate uridylyltransferase, diadenosine tetraphosphate phosphorylase, and adenylyl sulphate:phosphate adenylytransferase). These HIT domains are a duplication consisting of 2 HIT-like motifs. This family binds zinc and iron [[cite:PMID:23659632], [cite:PMID:27005423]]. Aprataxin, which hydrolyses both dinucleotide polyphosphates and phophoramidates, and is involved in DNA repair systems [[cite:PMID:23659632], [cite:PMID:30622225]]. mRNA decapping enzyme family. These include enzymes such as DcpS and Dcp2. The HIT-domain is usually C-terminal in these proteins [[cite:PMID:15273322], [cite:PMID:32723815]].
5 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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