RNase A family, or Pancreatic RNases family; includes vertebrate RNase homologs to the bovine pancreatic ribonuclease A (RNase A). Many of these enzymes have special biological activities; for example, some stimulate the development of vascular endothelial cells, dendritic cells, and neurons, are cytotoxic/anti-tumoral and/or anti-pathogenic. RNase A is involved in endonucleolytic cleavage of 3'-phosphomononucleotides and 3'-phosphooligonucleotides ending in C-P or U-P with 2',3'-cyclic phosphate intermediates. The catalytic mechanism is a transphosphorylation of P-O 5' bonds on the 3' side of pyrimidines and subsequent hydrolysis to generate 3' phosphate groups. The RNase A family proteins have a conserved catalytic triad (two histidines and one lysine); recently some family members lacking the catalytic residues have been identified. They also share three or four disulfide bonds. The most conserved disulfide bonds are close to the N and C termini and contribute most significantly to the conformational stability. 8 RNase A homologs had initially been identified in the human genome, pancreatic RNase (RNase 1), Eosinophil Derived Neurotoxin (EDN/RNASE 2), Eosinophil Cationic Protein (ECP/RNase 3), RNase 4, Angiogenin (RNase 5), RNase 6 or k6, the skin derived RNase (RNase 7) and RNase 8. These eight human genes are all located in a cluster on chromosome 14. Recent genomic analysis has extended the family to 13 sequences. However only the first eight identified human RNases, which are refered to as "canonical" RNases, contain the catalytic residues required for RNase A activity. The new genes corresponding to RNases 9-13 are also located in the same chromosome cluster and seem to be related to male-reproductive functions. RNases 9-13 have the characteristic disulfide bridge pattern but are unlikely to share RNase activity. The RNase A family most likely started off in vertebrates as a host-defense protein, and comparative analysis in mammals and birds indicates that the family may have originated from a RNase 5-like gene. This hypothesis is supported by the fact that only RNase 5-like RNases have been reported outside the mammalian class. The RNase 5 group would therefore be the most ancient form of this family, and all other members would have arisen during mammalian evolution.
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