HIT family: 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, which act on the alpha-phosphate of ribonucleotides. On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified in the literacture into three major 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. Further sequence analysis reveals several new closely related, yet uncharacterized subgroups.

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                  ....*....|....*....|....*....|....*....|....*....
gi 1039010794  75 PTIFDKIIAKEIPSDIVYEDENVLAFRDINPQAPVHVLVIPKLRDGLTS 123
Cdd:cd01276     1 DCIFCKIIRGEIPAKKVYEDDEVLAFHDINPQAPVHILVIPKKHIASLS 49

Protein Kinase C Interacting protein related (PKCI): PKCI and related proteins belong to the ubiquitous HIT family of hydrolases that act on alpha-phosphates of ribonucleotides. The members of this subgroup have a conserved HxHxHxx motif (x is a hydrophobic residue) that is a signature for this family. No enzymatic activity has been reported however, for PKCI and its related members.

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                  ....*....|....*....|....*....|....*....|....*....
gi 1039010794  75 PTIFDKIIAKEIPSDIVYEDENVLAFRDINPQAPVHVLVIPKLRDGLTS 123
Cdd:cd01276     1 DCIFCKIIRGEIPAKKVYEDDEVLAFHDINPQAPVHILVIPKKHIASLS 49

purine nucleoside phosphoramidase; Provisional

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                  ....*....|....*....|....*....|....*....|..
gi 1039010794  76 TIFDKIIAKEIPSDIVYEDENVLAFRDINPQAPVHVLVIPKL 117
Cdd:PRK10687    5 TIFSKIIRREIPSDIVYQDELVTAFRDISPQAPTHILIIPNI 46

Protein Kinase C Interacting protein related (PKCI): PKCI and related proteins belong to the ubiquitous HIT family of hydrolases that act on alpha-phosphates of ribonucleotides. The members of this subgroup have a conserved HxHxHxx motif (x is a hydrophobic residue) that is a signature for this family. No enzymatic activity has been reported however, for PKCI and its related members.

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                  ....*....|....*....|....*....|....*....|....*....
gi 1039010794  75 PTIFDKIIAKEIPSDIVYEDENVLAFRDINPQAPVHVLVIPKLRDGLTS 123
Cdd:cd01276     1 DCIFCKIIRGEIPAKKVYEDDEVLAFHDINPQAPVHILVIPKKHIASLS 49

HINT (histidine triad nucleotide-binding protein) subgroup: Members of this CD belong to the superfamily of histidine triad hydrolases that act on alpha-phosphate of ribonucleotides. This subgroup includes members from all three forms of cellular life. Although the biochemical function has not been characterised for many of the members of this subgroup, the proteins from Yeast have been shown to be involved in secretion, peroxisome formation and gene expression.

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                  ....*....|....*....|....*....|....*....|
gi 1039010794  77 IFDKIIAKEIPSDIVYEDENVLAFRDINPQAPVHVLVIPK 116
Cdd:cd01277     3 IFCKIIAGEIPSYKVYEDDHVLAFLDINPASKGHTLVIPK 42

Scavenger mRNA decapping enzyme C-term binding; This family consists of several scavenger mRNA decapping enzymes (DcpS) and is the C-terminal region. DcpS is a scavenger pyrophosphatase that hydrolyses the residual cap structure following 3' to 5' decay of an mRNA. 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 C-terminal domain 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 activity and 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.

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                  ....*....|....*....|....*....|....*....|....*....
gi 1039010794  76 TIFDKIIAKEIPSDIVYEDENVLAFRDINPQAPVHVLVIPKlrDGLTSL 124
Cdd:pfam11969   2 WVFCIIAKGEEPERVVYEDEGFVVFKDIKPKAPLHLLVIPK--RHIKSL 48

aprataxin related: Aprataxin, a HINT family hydrolase is mutated in ataxia oculomotor apraxia syndrome. All the members of this subgroup have the conserved HxHxHxx (where x is a hydrophobic residue) signature motif. Members of this subgroup are predominantly eukaryotic in origin.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 1039010794  87 PSDIVYEDENVLAFRDINPQAPVHVLVIPKlrdglTSLGKIKILPETYLPL 137
Cdd:cd01278    15 PEDQVYEDDRVVVFKDIYPKARHHYLVIPK-----EHIASLKALTKEDVPL 60