Conserved Protein Domain Family

cd00163: RNase_A 
Click on image for an interactive view with Cn3D
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.
PSSM-Id: 119386
View PSSM: cd00163
Aligned: 17 rows
Threshold Bit Score: 109.001
Threshold Setting Gi: 7245973
Created: 1-Nov-2000
Updated: 17-Jan-2013
Aligned Rows:
catalytic sitedimerization
Conserved site includes 7 residues -Click on image for an interactive view with Cn3D
Feature 1:catalytic site [active site]
  • 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:
                         10        20        30        40        50        60        70        80
Feature 1                 #                                   #   #                           #  
1QMT_A         7 TRAQWFAIQHISln-----------ppRCTIAMRAINnyr--wrCKNQNTFLRTtFANVVNVCGnqsircphnrtlnNCH 73
11BG_A         3 SAAAKFERQHMDsgnsp-----ssssnYCNLMMCCRKmtq--gkCKPVNTFVHEsLADVKAVCSqkkvtc--kngqtNCY 73
gi 38605200   60 TKEKVKRRILVNpgmpl------gdsgYCNYQIMRKNvyy-kysCVTEHYFLLMqYDELQKTCYnrfvpc--kngirKCN 130
gi 67459908   22 AVMSTLEHLHVDypqndv----pvparYCNHMIIQRVirepdhtCKKEHVFIHErPRKINGICIspkkvacqnlsaiFCF 97
gi 55741813   88 VGGNKMLRAQAFsqsypnylrsdlmdrECNTLMAKKMkpy-nhtCISQYIFIHEePDEIKAVCKsppvac--elkggKCH 164
gi 61175227  105 SNKDYLRLDQTDr--------------ECNDMMAHKMkep-sqsCIAQYAFIHEdLNTVKAVCNspviac--elkggKCH 167
gi 81905284   92 RAEPRFQSKQDYlkfd-------lsvrDCNTMMAHKIkep-nqsCINQYTFIHEdPNTVKAVCNgslvdc--dlqggKCY 161
gi 149568755  34 SKARTFRLMHIDfprsef---apgfrgYCNGLMAYVRaqreswqCPEKHFVLHApAATVRAICAhtdsfc--edfgeFCT 108
gi 59276062   27 IGSRNFYTLSIDyprvny---pkgfrgYCNGLMSYMRgkmqnsdCPKIHYVIHApWKAIQKFCKysdsfc--enyneYCT 101
gi 73978107  103 SNKAYLRSDLLAr--------------ECNTLMAPKVkgh-nrtCISQYTFIHEdLDTVQAVCNspvvac--qlkggKCH 165
                         90       100       110       120       130       140
Feature 1                 #                                               ## 
1QMT_A        74 RSrfRVPLLHCDLinpgaqnisNCRYADRp--GRRFYVVACDnrdprdsprypvvPVHLD 131
11BG_A        74 QSksTMRITDCREtgss--kypNCAYKTTq--VEKHIIVACGgkp--------svPVHFD 121
gi 38605200  131 MSkkLVEGVYCNLtkas--nipLCQYNSFy--RRGYVLITCTwqnemqklipypiNDLVE 186
gi 67459908   98 QSetKFKMTVCQLiegt--rypACRYHYSp--TEGFVLVTCDdl----------rPDSFL 143
gi 55741813  165 KSarPFDLTFCKLskpg-qvtpHCNYVTFl--LEKHILISCNd-----------mKVQVM 210
gi 61175227  168 KSsrPFDLTLCELsqpd-qvtpNCNYLTSv--IKKHIIITCNd-----------mKRQLP 213
gi 81905284  162 KSprPFDLTLCKLakpg-qvtpNCHYLTYi--TEKSIFMTCNd------------KRQLE 206
gi 149568755 109 RShkPLPVTTCARtpgl--ppsVCRYNATvhvQSHRVWLLCSskf-------egfPMDVI 159
gi 59276062  102 LTqdSLPITVCSLshqq--pptSCYYNSTl--TNQKLYLLCSrky-------eadPIGIA 150
gi 73978107  166 RSsrPFDLTFCRLskpg-qvtpHCHYVTFi--FEKYIIISCNd-----------mKVQVV 211

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