7BTF


Conserved Protein Domain Family
CoV_RdRp

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cd21530: CoV_RdRp 
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coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: responsible for replication and transcription of the viral RNA genome
This family contains the RNA-dependent RNA polymerase of alpha-, beta-, gamma-, delta-coronaviruses, including three highly pathogenic human coronaviruses (CoVs) such as Middle East respiratory syndrome (MERS)-related CoV, Severe acute respiratory syndrome (SARS) CoV, and SARS-CoV-2, also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which shows potential for the treatment of SARS-CoV-2 viral infections. The structure of SARS-CoV-2 Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides.
Statistics
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PSSM-Id: 394890
View PSSM: cd21530
Aligned: 4 rows
Threshold Bit Score: 1713.13
Threshold Setting Gi: 1405699537
Created: 29-Apr-2020
Updated: 6-Jul-2021
Structure
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Program:
Drawing:
Aligned Rows:
  next features
Conserved site includes 4 residues -Click on image for an interactive view with Cn3D
Feature 1: catalytic residues [active site], 4 residue positions
Conserved feature residue pattern:D [GS] D DClick to see conserved feature residue pattern help
Evidence:
  • Comment:contains the classic divalent-cation-binding residue D618 in the motif A of SARS-CoV-2 structure, which is conserved in most viral polymerases

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                      
7BTF_A       5 QSFLNRVCGVSAarltpcgTGTSTDVVYRAFDIYNDKvAGFAKFLKTNCCRFqekde-----ddnliDSYFVVKRHTFSN 79   Severe acute res...
AHB73997  3936 KNYLNRVRGSSEarliplaNGCDPDVVKRAFDVCNKEsAGMFLNLKRNCARFqevrdte-drnleycDSYFVVKQTTPSN 4014 Infectious bronc...
AVA26872  4042 ISYLNRARGSSAarl-epcNGTDIDKCVRAFDIYNKNvSFLGKCLKMNCVRFkna---------dlkDGYFVIKRCTKSV 4111 Human coronaviru...
AWV67106  3613 SAYLNRVTGSSDarleplqPGTQPDAVKRAFHVHNDTtSGIFLSTKTNCARFktkrsalplpnkgdvDLYFVTKQCSAKV 3692 Sparrow deltacor...
Feature 1                                                                                      
7BTF_A      80 YQHEEtiYNLLKd--------cPAVAKHDFFKFRIdgdmvPHISRQRLTKYTMADLVYALRHFDeGNCDTLKEILvtYNC 151  Severe acute res...
AHB73997  4015 YEHEKacYEDLKs---------AVTADHDFFVFNKn---iYNISRQRLTKYTMMDFCYALRHFDpKDCEVLKEILvtYGC 4082 Infectious bronc...
AVA26872  4112 MEHEQsmYNLLNf--------sGALAEHDFFTWKDgrviyGNVSRHNLTKYTMMDLVYAMRNFDeQNCDVLKEVLvlTGC 4183 Human coronaviru...
AWV67106  3693 FEIEEkcYNALStelyttdesfGVLAKTEFFKFDKi----PNVNRQYLTKYTLLDLAYALRHLS-TSRDVIQEILmtMCG 3767 Sparrow deltacor...
Feature 1                                                                                      
7BTF_A     152 CDDDy----FNKKDWYDFVENPDILRVYanlGERVRQALLKTVqfCDAMRNAGIVGVLTLDNQDLNGNWYDFGDFIqttP 227  Severe acute res...
AHB73997  4083 IDDYhpkwfEENKDWYDPIENPKYYAMLakmGPIVRRALLNAVefGNLMVEKGYVGVVTLDNQDLNGKFYDFGDFQktaP 4162 Infectious bronc...
AVA26872  4184 CDNSy----FDSKGWYDPVENEDIHRVYaslGKIVARAMLKCValCDAMVAKGVVGVLTLDNQDLNGNFYDFGDFVvslP 4259 Human coronaviru...
AWV67106  3768 TPED-----WFGENWFDPIENPSFYKEFhklGDILNLCVLNANkfASACIDAGLVGILTPDNQDLLGQIYDFGDFIitqP 3842 Sparrow deltacor...
Feature 1                                                                                      
7BTF_A     228 GSGVPVVDSYYSLLMPILTLTRALtaeshv-dtdltkPYIKWDLLKYDFTEERLKLFDRYFKYWDqtYHPNCVNCLDDRC 306  Severe acute res...
AHB73997  4163 GAGVPVFDTYYSYMMPIIAMTDALaperyf-eydvhkGYKSYDLLKYDYTEEKQELFQKYFKYWDqeYHPNCRDCVNDRC 4241 Infectious bronc...
AVA26872  4260 NMGVPCCTSYYSYMMPIMGLTNCLasecfvksdifgsDFKTFDLLKYDFTEHKENLFNKYFKHWSfdYHPNCSDCYDDMC 4339 Human coronaviru...
AWV67106  3843 GNGCVDLASYYSYLMPIMSMTHMLkcecm----dsegKPLEYDGFQYDFTDFKLALFEKYFKYWDrpYHPNTVDCPDDRC 3918 Sparrow deltacor...
Feature 1                                                                                      
7BTF_A     307 ILHCANFNVLFSTVFPPTSFGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLsFKELLVYAADPaMHAASGN 386  Severe acute res...
AHB73997  4242 LIHCANFNVLFSTLIPQTSFGNLCRKVFVDGVPFIATCGYHSKELGVIMNQDNTMSFSKMgLSQLMKFVGDPaLLVGTSN 4321 Infectious bronc...
AVA26872  4340 VIHCANFNTLFATTIPGTAFGPLCRKVFIDGVPLVTTAGYHFKQLGLVWNKDVNTHSVRLtITELLQFVTDPsLIIASSP 4419 Human coronaviru...
AWV67106  3919 VLHCANFNVLFAMCIPNTAFGNLCSRATVDGHLVVQTVGVHLKELGIVLNQDVTTHMANInLNTLLRLVGDPtTIASVSD 3998 Sparrow deltacor...
Feature 1                                                                                      
7BTF_A     387 LLLDKRTTCFSVAALTNNVAFQTVKPGNFNKDFYDFavsKGFFKEGSSvelKHFFFAQDGNAAISDYDYYryNLPTMCDI 466  Severe acute res...
AHB73997  4322 NLVDLRTSCFSVCALASGITHQTVKPGHFNKDFYDFaekAGMFKEGSSiplKHFFYPQTGNAAINDYDYYryNRPTMFDI 4401 Infectious bronc...
AVA26872  4420 ALVDQRTICFSVAALSTGLTNQVVKPGHFNEEFYNFlrlRGFFDEGSEltlKHFFFAQNGDAAVKDFDFYryNKPTILDI 4499 Human coronaviru...
AWV67106  3999 KCLDLRTPCQTLATMSSGIAKQSVKPGHFNQHFYKHlldSNLLDQLGId-iRHFYYMQDGEAAITDYSYYryNTPTMLDI 4077 Sparrow deltacor...
Feature 1                                                                                      
7BTF_A     467 RQLLFVVEVVDKYFDCYDGGCINANQVIVNNLDKSAGFPFNKWGKARLYYDsMSYEDQDALFAYTKRNVIPTITQMNLKY 546  Severe acute res...
AHB73997  4402 RQLLFCLEVTSKYFECYEGGCIPASQVVVTNLDKSAGFPFNKFGKARLYYE-MSLEEQDQLFESTKKNVLPTITQMNLKY 4480 Infectious bronc...
AVA26872  4500 CQARVTYKIVSRYFDIYEGGCIKACEVVVTNLNKSAGWPLNKFGKASLYYEsISYEEQDALFALTKRNVLPTMTQLNLKY 4579 Human coronaviru...
AWV67106  4078 KMFLFCLEVADKYLEPYEGGCINAQSVVVSNLDKSAGYPFNKLGKARNYYD-MTYAEQNQLFEYTKRNVLPTLTQMNLKY 4156 Sparrow deltacor...
Feature 1                                                                             #        
7BTF_A     547 AISAKNRARTVAGVSICSTMTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVENPHLMGWDYPKCDRAM 626  Severe acute res...
AHB73997  4481 AISAKNRARTVAGVSILSTMTNRQFHQKVLKSIVNTRNAPVVIGTTKFYGGWDNMLRNLVQGVEDPMLMGWDYPKCDRAM 4560 Infectious bronc...
AVA26872  4580 AISGKERARTVGGVSLLSTMTTRQYHQKHLKSIVNTRNATVVIGTTKFYGGWNNMLRTLIDGVENPMLMGWDYPKCDRAL 4659 Human coronaviru...
AWV67106  4157 AISAKDRARTVAGVSIISTMTNRQYHQKMLKSISLARNQTIVIGTTKFYGGWDNMLRRLMCNINNPILVGWDYPKCDRSM 4236 Sparrow deltacor...
Feature 1                                                                                      
7BTF_A     627 PNMLRIMASLVLARKHttCCs-lSHRFYRLANECAQVLSEMVmcgGSLYVKPGGTSSGDATTAYANSVFNIcQAVTANVN 705  Severe acute res...
AHB73997  4561 PNLLRIAASLVLARKHtnCCt-wSERIYRLYNECAQVLSETVlatGGIYVKPGGTSSGDATTAYANSVFNIiQATSANVA 4639 Infectious bronc...
AVA26872  4660 PNMIRMISAMVLGSKHvnCCt-vTDRFYRLGNELAQVLTEVVysnGGFYFKPGGTTSGDASTAYANSIFNIfQAVSSNIN 4738 Human coronaviru...
AWV67106  4237 PNMLRIAASCLLARKHt-CCnqsQRFYRLANECCQVLSEVVVs-gNNLYVKPGGTSSGDATTAYANSVFNIlQVVSANVA 4314 Sparrow deltacor...
Feature 1                                                           ###                        
7BTF_A     706 ALLSTDGNKIadKYVRNLQHRLYECLYRNRdvDTDFVNEFYAYLRKHFSMMILSDDAVVCFNs-tYASQGLVAsIKNFKS 784  Severe acute res...
AHB73997  4640 RLLSVITRDIvyDDIKSLQYELYQQVYRRSnfDPAFVEKFYSYLCKNFSLMILSDDGVVCYNn-tLAKQGLVAdISGFRE 4718 Infectious bronc...
AVA26872  4739 RLLSVPSDSCnnVNVRDLQRRLYDNCYRLTsvEESFIDDYYGYLRKHFSMMILSDDGVVCYNk-dYAELGYIAdISAFKA 4817 Human coronaviru...
AWV67106  4315 TFLSTSTTSHinKEIADLHRSLYEDIYRGDsnDITVINRFYQHLQNYFGLMILSDDGVACIDsdvAKSGAVAD-LDGFRD 4393 Sparrow deltacor...
Feature 1                                                                                      
7BTF_A     785 VLYYQNNVFMSEAKCWTETDLTKGPHEFCSQHTMLVKqGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFvsLAI 864  Severe acute res...
AHB73997  4719 ILYYQNNVYMADSKCWVEPDLEKGPHEFCSQHTMLVEvDGEPRYLPYPDPSRILGACVFVDEVDKTEPVAVMERYiaLAI 4798 Infectious bronc...
AVA26872  4818 TLYYQNNVFMSTSKCWVEEDLTKGPHEFCSQHTMQIVdKDGTYYLPYPDPSRILSAGVFVDDVVKTDAVVLLERYvsLAI 4897 Human coronaviru...
AWV67106  4394 ILFYQNNVYMADSKCWTETDMTVGPHEFCSQHTVLAEhDGKPYYLPYPDVSRILGACIFVDDVNKADPVQNLERYisLAI 4473 Sparrow deltacor...
Feature 1                                                                          
7BTF_A     865 DAYPLTKHPNQEYaDVFHlyLQYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQ 932  Severe acute respiratory syn...
AHB73997  4799 DAYPLVHHENEEYkKVFFvlLSYIRKLYQELSQNMLMDYSFVMDIDKGSKFWEQEFYENMYRAPTTLQ 4866 Infectious bronchitis virus
AVA26872  4898 DAYPLSKHPNSEYrKVFYvlLDWVKHLNKNLNEGVLESFSVTLLDNQEDKFWCEDFYASMYENSTILQ 4965 Human coronavirus NL63
AWV67106  4474 DAYPLTKVDPIKG-KVFYllLDYIRVLAQELQDGILDAFQSLTDMSYINNFLNEAFYAQMYEQSPTLQ 4540 Sparrow deltacoronavirus

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