Conserved Protein Domain Family

cd06265: RNase_A_canonical 
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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.
PSSM-Id: 119387
View PSSM: cd06265
Aligned: 33 rows
Threshold Bit Score: 97.0376
Threshold Setting Gi: 28373596
Created: 18-Jun-2008
Updated: 2-Oct-2020
Aligned Rows:
Conserved site includes 7 residues -Click on image for an interactive view with Cn3D
Feature 1:catalytic site [active site]
  • Structure:1M07; bullfrog cytotoxic ribonuclease with bound ds nucleotide (ACGA)
    View structure with Cn3D
  • Structure:11BG_A, Bovine seminal RNase A binds uridylyl-2'-5'-phospho-guanosine and sulfate
    View structure with Cn3D
  • Comment:catalytic site of RNase A consists of pyrimidine binding ( B1) and catalytic ( P1) subsites.
  • Structure:11BG_A, Bovine seminal RNAse A binds uridylyl-2'-5'-phospho-guanosine and sulfate at P1 subsite.
    View structure with Cn3D
  • Comment:P1 subsites accommodate the phosphate where phosphodiester bond cleavage occurs.
  • Structure:11BG_A, Bovine seminal RNAse A binds uridylyl-2'-5'-phospho-guanosine and sulfate at B1 subsite
    View structure with Cn3D
  • Comment:B1 subsites accommodate the nucleotide bases on the 3' sides of the scissile bond.
  • Citation:PMID 7492594
  • Citation:PMID 9918722
  • Citation:PMID 8120892

Sequence Alignment
Format: Row Display: Color Bits: Type Selection:
Feature 1                 #                            #   #                                     
1RRA_A         3 SSADKFKRQHMDTEGPskssptYCNQMMKRQGmtkgsCKPVNTFVHEPLEDVQAICSqgqvtc----------------- 65  Norway rat
11BG_A         3 SAAAKFERQHMDSGNSpssssnYCNLMMCCRKmtqgkCKPVNTFVHESLADVKAVCSqkkvtc----------------- 65  Bos taurus
1DZA_A         4 SAAAKFERQHMDSGNSpsssstYCNQMMRRRNmtqgrCKPVNTFVHESLVDVQNVCFqekvtc----------------- 66  human
XP_001379395  13 SQEDKFKRQHLDSGTKgnpgkkYCDQMMAKRGmtkrkCKPVNTFLHESYQNIENICHepnvpc----------------- 75  gray short-tail...
2HKY_A         7 TSSQWFKIQHMQPSPQ------ACNSAMKNINkhtkrCKDLNTFLHEPFSSVAATCQtpkiac----------------- 63  human
AAD48540       6 TLTQWFQIQHVNMTNP------RCTIAMRVVNgyksqCKRRNTFLHTTYPDIVKVCGtpnipcp---------------- 63  South African g...
O35291        29 ILSQKFYTQHIYNSTYp-----RCDAVMRVVNryrprCKDINTFLHTSFADVVAVCGhpnitc----------------- 86  house mouse
NP_001098981  33 TRALWFEIQHINMAHP------QCNAAMRVVNryrmvCKNKNTFLHRTFAYVAGICNtpnvtc----------------- 89  cattle
1QMT_A         7 TRAQWFAIQHISLNPP------RCTIAMRAINnyrwrCKNQNTFLRTTFANVVNVCGnqsircp---------------- 64  human
EDL42279      29 TASQWFATQHITYKANl-----QCNVEMQAINmhrprCKGLNTFLHTSFINVVGVCGnpsglpapsqkfytepihnstyp 103 house mouse
Feature 1                                                      #           #                     
1RRA_A        66 -----------------------------------------kngrnNCHKSssTLRITDCRLkgss--kypNCDYTTTDS 102 Norway rat
11BG_A        66 -----------------------------------------kngqtNCYQSksTMRITDCREtgss--kypNCAYKTTQV 102 Bos taurus
1DZA_A        67 -----------------------------------------kngqgNCYKSnsSMHITDCRLtngs--rypNCAYRTSPK 103 human
XP_001379395  76 ----------------------------------------anknmhNCHKSnhPMKITECHLsggs--kpgKCRYRMNNV 113 gray short-tail...
2HKY_A        64 -----------------------------------------kngdkNCHQShgPVSLTMCKLtsg---kypNCRYKEKRQ 99  human
AAD48540      64 ----------------------------------------tnatrkNCHKSlvQVPLTDCNLtsrp-tpvrDCKYSDKPE 102 South African g...
O35291        87 ----------------------------------------nnltrkNCHASsfQVFITFCNLtmpt-rictQCRYQTTGS 125 house mouse
NP_001098981  90 ----------------------------------------skpgrmNCHNSsvQVPITFCNLtrpa-lnytNCQYQQTRA 128 cattle
1QMT_A        65 ----------------------------------------hnrtlnNCHRSrfRVPLLHCDLinpgaqnisNCRYADRPG 104 human
EDL42279     104 rcddamlvvnryrprckdvdtfrhtsfanvcvcghpsgfckehksaNCHNSssQVPIIVCNLttpg-rtytQCRYQMKGS 182 house mouse
Feature 1                                ##  
1RRA_A       103 QKHIIIACDgnp--------yvPVHFDA 122 Norway rat
11BG_A       103 EKHIIVACGgkp--------svPVHFDA 122 Bos taurus
1DZA_A       104 ERHIIVACEgsp--------yvPVHFDA 123 human
XP_001379395 114 KKNVTVACVgkt--------lkPVHLDP 133 gray short-tailed opossum
2HKY_A       100 NKSYVVACKppqkkdsqqfhlvPVHLDR 127 human
AAD48540     103 EKFYVVACNkrdprdsplypvvPVHLDR 130 South African galago
O35291       126 VKYYRVACEnrtpqdtpmypvvPVHLDG 153 house mouse
NP_001098981 129 WRIFIVACDnrsprdsprypvvPVHLDN 156 cattle
1QMT_A       105 RRFYVVACDnrdprdsprypvvPVHLDT 132 human
EDL42279     183 VKYYRVACEnrtpwdspiypvvPVHLHG 210 house mouse

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