This entry represents scavenger mRNA decapping enzymes, such as Dcp2 and DcpS. DcpS is a scavenger pyrophosphatase that hydrolyses the residual cap structure following 3' to 5' mRNA degradation. DcpS uses cap dinucleotides or capped oligonucleotides as substrate to release m(7)GMP (N7-methyl GMP), while Dcp2 uses capped mRNA as substrate in order to hydrolyse the cap to release m(7)GDP (N7-methyl GDP) []. The association of DcpS with 3' to 5' exonuclease exosome components suggests that these two activities are linked and there is a coupled exonucleolytic decay-dependent decapping pathway. The family contains a histidine triad (HIT) sequence with three histidines separated by hydrophobic residues []. The central histidine within the DcpS HIT motif is critical for decapping activityand defines the HIT motif as a new mRNA decapping domain, making DcpS the first member of the HIT family of proteins with a defined biological function. This family is related to ().
This superfamily represents the N-terminal domain of scavenger mRNA decapping enzymes, such as Dcp2 and DcpS. DcpS is a scavenger pyrophosphatase that hydrolyses the residual cap structure following 3' to 5' mRNA degradation. DcpS uses cap dinucleotides or capped oligonucleotides as substrate to release m(7)GMP (N7-methyl GMP), while Dcp2 uses capped mRNA as substrate in order to hydrolyse the cap to release m(7)GDP (N7-methyl GDP) []. The association of DcpS with 3' to 5' exonuclease exosome components suggests that these two activities are linked and there is a coupled exonucleolytic decay-dependent decapping pathway. DcpS exists as a dimer and each monomer is comprised of an N-terminal and a C-terminal region. The two N-termini form into a domain-swapped dimer and carry out substrate binding, cap dinucleotide, and hydrolysis [].
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 [, , ]. Proteins containing HIT domains form a superfamily of nucleotide hydrolases and transferases that act on the alpha-phosphate of ribonucleotides [, ]. They are highly conserved from archaea to humans and are involved in galactose metabolism, DNA repair, and tumor suppression []. 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) [, ]. 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 [].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 [, ]. HINT and FINT HIT domains have a topology similar to that found in the N-terminal of protein kinases [].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 [, ].Aprataxin, which hydrolyses both dinucleotide polyphosphates and phophoramidates, and is involved in DNA repair systems [, ].mRNA decapping enzyme family. These include enzymes such as DcpS and Dcp2. The HIT-domain is usually C-terminal in these proteins [, ].
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 [, , ]. Proteins containing HIT domains form a superfamily of nucleotide hydrolases and transferases that act on the alpha-phosphate of ribonucleotides [, ]. They are highly conserved from archaea to humans and are involved in galactose metabolism, DNA repair, and tumor suppression []. 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) [, ]. 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 [].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 [, ]. HINT and FINT HIT domains have a topology similar to that found in the N-terminal of protein kinases [].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 [, ].Aprataxin, which hydrolyses both dinucleotide polyphosphates and phophoramidates, and is involved in DNA repair systems [, ].mRNA decapping enzyme family. These include enzymes such as DcpS and Dcp2. The HIT-domain is usually C-terminal in these proteins [, ].This superfamily also includes CDP-diacylglycerol pyrophosphatases, CDH, which play a role in phospholipid metabolism and regulates phosphatidylinositol levels [], the C-terminal CwfJ domains of CWF19-like protein DRN1 from Saccharomyces cerevisiae () which is involved branched RNA metabolism, modulating the turnover of lariat-intron pre-mRNAs by the lariat-debranching enzyme DBR1 and its homologues. This C-terminal Cwfj domains contain evolutionarily conserved cysteine and histidine residues in an arrangement similar to the CCCH-class of zinc fingers [, ].
