InterPro domain: IPR002646

This group includes nucleic acid independent RNA polymerases, such as polynucleotide adenylyltransferase ( 2.7.7.19 ), which adds the poly (A) tail to mRNA. This group also includes the tRNA nucleotidyltransferase that adds the CCA to the 3' of the tRNA ( 2.7.7.25 ).

CCA-adding enzymes add the sequence [cytidine(C)-cytidine-adenosine (A)]., one nucleotide at a time, onto the 3' end of tRNA, in a template-independent reaction [ 1 , 2 ]. This Class II group is comprised mainly of eubacterial and eukaryotic enzymes and includes Bacillus stearothermophilus CCAase [ 3 ], Escherichia coli poly(A) polymerase I [ 4 , 5 ], human mitochondrial CCAase [ 6 , 7 ], and Saccharomyces cerevisiae CCAase (CCA1) [ 8 , 9 , 10 ]. CCA-adding enzymes have a single catalytic pocket, which recognizes both ATP and CTP substrates [ 11 , 12 ]. This family belongs to the Pol beta-like NT superfamily [ 13 , 14 ].

Escherichia coli CCAase is related to this group but has not been included in this alignment as this enzyme lacks the N-terminal helix conserved in the remainder of the NT superfamily.

In the Pol beta-like NT superfamily [ 15 , 15 ], the majority of enzymes have two carboxylates, Dx[D/E], together with a third more distal carboxylate, which coordinate two divalent metal cations involved in a two-metal ion mechanism of nucleotide addition. These carboxylate residues are fairly well conserved in this family.

1. Metal-ion-dependent catalysis and specificity of CCA-adding enzymes: a comparison of two classes. Biochemistry 44, 12849-59
2. A story with a good ending: tRNA 3'-end maturation by CCA-adding enzymes. Curr. Opin. Struct. Biol. 16, 12-7
3. Crystal structures of the Bacillus stearothermophilus CCA-adding enzyme and its complexes with ATP or CTP. Cell 111, 815-24
4. Localization of Escherichia coli poly(A) polymerase I in cellular membrane. Biochem. Biophys. Res. Commun. 329, 598-602
5. Analysis of the function of Escherichia coli poly(A) polymerase I in RNA metabolism. Mol. Microbiol. 34, 1094-108
6. Crystal structure of the human CCA-adding enzyme: insights into template-independent polymerization. J. Mol. Biol. 328, 985-94
7. Identification and characterization of mammalian mitochondrial tRNA nucleotidyltransferases. J. Biol. Chem. 276, 40041-9
8. Isolation of a temperature-sensitive mutant with an altered tRNA nucleotidyltransferase and cloning of the gene encoding tRNA nucleotidyltransferase in the yeast Saccharomyces cerevisiae. J. Biol. Chem. 265, 16216-20
9. A mutation in the tRNA nucleotidyltransferase gene promotes stabilization of mRNAs in Saccharomyces cerevisiae. Mol. Cell. Biol. 12, 5778-84
10. Cytoplasmic and mitochondrial tRNA nucleotidyltransferase activities are derived from the same gene in the yeast Saccharomyces cerevisiae. J. Biol. Chem. 267, 14879-83
11. Poly(A) polymerase I of Escherichia coli: characterization of the catalytic domain, an RNA binding site and regions for the interaction with proteins involved in mRNA degradation. Mol. Microbiol. 32, 765-75
12. Characterization of the E.coli poly(A) polymerase: nucleotide specificity, RNA-binding affinities and RNA structure dependence. Nucleic Acids Res. 28, 1139-44
13. DNA polymerase beta-like nucleotidyltransferase superfamily: identification of three new families, classification and evolutionary history. Nucleic Acids Res. 27, 1609-18
14. DNA polymerase beta belongs to an ancient nucleotidyltransferase superfamily. Trends Biochem. Sci. 20, 345-7