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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672077623  25 TSMEHLHVDYPQSAVPLRYCNYMILQRVIREpDYTCRKVHVFIHERPQKINRICtSSKKMTCPNYSEiFCFQSDTKFRMT 104
Cdd:cd00163    4 RTFRRQHIDYPKSNGDPRYCNSMMRRKKVTE-NGSCKKQHTFIHESLEEVQAVC-NNPSVFCKNGGE-NCHRSKRPLDLT 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 672077623 105 VCQLTGGSKYPACRYQISPTEGFVLVTCDDLGPVNFQ 141
Cdd:cd00163   81 VCKLTGGSRIPNCRYNTTYTEKFILVTCDDKPIVPVH 117

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672077623  25 TSMEHLHVDYPQSAVPLRYCNYMILQRVIREpDYTCRKVHVFIHERPQKINRICtSSKKMTCPNYSEiFCFQSDTKFRMT 104
Cdd:cd00163    4 RTFRRQHIDYPKSNGDPRYCNSMMRRKKVTE-NGSCKKQHTFIHESLEEVQAVC-NNPSVFCKNGGE-NCHRSKRPLDLT 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 672077623 105 VCQLTGGSKYPACRYQISPTEGFVLVTCDDLGPVNFQ 141
Cdd:cd00163   81 VCKLTGGSRIPNCRYNTTYTEKFILVTCDDKPIVPVH 117

Pancreatic ribonuclease;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672077623    31 HVDYPQSAVPLRYCNYMiLQRVIREPDYtCRKVHVFIHERPQKINRICtSSKKMTCPNYSEIfCFQSDTKFRMTVCQLTG 110
Cdd:smart00092  12 HIDSTPSSSSSNYCNQM-MKRRNMTQGR-CKPVNTFVHESLADVKAVC-SQKNVTCKNGQTN-CYQSNSRFHITDCRLTG 87

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 672077623   111 GSKYPACRYQISPTEGFVLVTCDD--LGPVNFQGYV 144
Cdd:smart00092  88 SSKYPNCRYKTTQANKHIIVACEGnpYVPVHFDASV 123

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672077623  25 TSMEHLHVDYPQSAVPLRYCNYMILQRVIREpDYTCRKVHVFIHERPQKINRICtSSKKMTCPNYSEiFCFQSDTKFRMT 104
Cdd:cd00163    4 RTFRRQHIDYPKSNGDPRYCNSMMRRKKVTE-NGSCKKQHTFIHESLEEVQAVC-NNPSVFCKNGGE-NCHRSKRPLDLT 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 672077623 105 VCQLTGGSKYPACRYQISPTEGFVLVTCDDLGPVNFQ 141
Cdd:cd00163   81 VCKLTGGSRIPNCRYNTTYTEKFILVTCDDKPIVPVH 117

Canonical RNase A family includes all vertebrate homologues to the bovine pancreatic ribonuclease A (RNase A) that contain the catalytic site, necessary for RNase activity. In the human genome 8 RNases , refered to as "canonical" RNases, have been identified, pancreatic RNase (RNase 1), Eosinophil Derived Neurotoxin (SEDN/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. The eight human genes are all located in a cluster on chromosome 14. Canonical RNase A 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 canonical RNase A family proteins have a conserved catalytic triad (two histidines and one lysine). They also share 6 to 8 cysteines that form three to four disulfide bonds. Two disulfide bonds that are close to the N and C termini contribute most significantly to conformational stability. Angiogenin or RNAse 5 has been implicated in tumor-associated angiogenesis. Comparative analysis in mammals and birds indicates that the whole 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672077623  31 HVDYPQSAVplRYCNYMILQRVIREPDytCRKVHVFIHERPQKINRICTSsKKMTCPNYSEIfCFQSDTKFRMTVCQLTG 110
Cdd:cd06265   10 HVDPPRTGI--RYCNVMMRRRNMTKGR--CKPVNTFIHESFADVRAVCTN-PNVTCKNGRNN-CHKSNSPFPVTDCNLTG 83

                         90       100       110
                 ....*....|....*....|....*....|
gi 672077623 111 GSKYPACRYQISPTEGFVLVTCDDLGPVNF 140
Cdd:cd06265   84 GSRYPNCRYRGTPSTRKIVVACENGVPVHL 113