5E6J,5WFI,5W8T,5TL6,4X2Z,6L5T,5BZ0,4OVZ,3MJ5


Conserved Protein Domain Family
CoV_PLPro

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cd21688: CoV_PLPro 
Coronavirus (CoV) papain-like protease (PLPro)
This model represents the papain-like protease (PLPro) found in non-structural protein 3 (Nsp3) of alpha-, beta-, gamma-, and deltacoronavirus, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. 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. PLPro is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. PLPro, which belongs to the MEROPS peptidase C16 family, participates in the proteolytic processing of the N-terminal region of the replicase polyprotein; it can cleave Nsp1|Nsp2, Nsp2|Nsp3, and Nsp3|Nsp4 sites and its activity is dependent on zinc. Besides cleaving the polyproteins, PLPro also possesses a related enzymatic activity to promote virus replication: deubiquitinating (DUB) and de-ISGylating activities. Both, ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15), are involved in preventing viral infection; coronaviruses utilize Ubl-conjugating pathways to counter the pro-inflammatory properties of Ubl-conjugated host proteins via the action of PLPro, which processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. The Nsp3 PLPro domain in many of these CoVs has also been shown to antagonize host innate immune induction of type I interferon by interacting with IRF3 and blocking its activation.
Statistics
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PSSM-Id: 409647
Aligned: 10 rows
Threshold Bit Score: 291.312
Created: 21-Mar-2019
Updated: 25-Oct-2021
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 4 residues -Click on image for an interactive view with Cn3D
Feature 1: Zn binding site [ion binding site], 4 residue positions
Conserved feature residue pattern:C C C CClick to see conserved feature residue pattern help
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                      
5E6J_A       4 KTIKVFTTVDntNLHTQLVDMsmtygqQFGPTYLd-----GADVTKikphvnhegKTFFVLPsd-dtLRSEAFEY----- 72   Severe acute res...
5WFI_A       1 NKVDVLCTVDgvNFRSCCVAEgevfgkTLGSVFCd-----GINVTKvrcsaiykgKVFFQYSdlseaDLVAVKDA----- 70   Murine hepatitis...
5W8T_A       2 LTIEVLVTVDgvNFRTVVLNNkntyrsQLGCVFFn-----GADISDtipdekqngHSLYLADnltadETKALKEL----- 71   Human betacorona...
5TL6_B       7 KTIKVFTTVDntNLHTQLVDMsmtygqQFGPTYLd-----GADVTKikphvnhegKTFFVLPsd-dtLRSEAFEY----- 75   Severe acute res...
4X2Z_A       8 KQKTIYLTEDgvKYRSIVLKPgds-lgQFGQVYA------KNKIVFtadd-vedkEILYVPT-----TDKSILEY----- 69   Avian infectious...
6L5T_A       1 KDVKVKVTADgrNINDVIVTTaetfdaQLGPSAN------GAESLVgvvp--tptDGGKVVNt---vPDVNWSKH----- 64   Swine acute diar...
QDH76194  1090 MNKNHLQVWDa-LNRTIVRTTtd--ydQVTTKALtpqgvlEANLFDg--------EDFVQEPk----PGQIYLEVteevq 1154 Porcine deltacor...
5BZ0_A       6 KQKTIYLTEDgvKYRSIVLKPgds-lgQFGQVYA------KNKIVFtadd-vedkEILYVPT-----TDKSILEY----- 67   Avian infectious...
4OVZ_A       4 KTIKVFTTVDntNLHTQLVDMsmtygqQFGPTYLd-----GADVTKikphvnhegKTFFVLPsd-dtLRSEAFEY----- 72   SARS coronavirus...
3MJ5_A       4 KTIKVFTTVDntNLHTQLVDMsmtygqQFGPTYLd-----GADVTKikphvnhegKTFFVLPsd-dtLRSEAFEY----- 72   Severe acute res...
Feature 1                                                                                      
5E6J_A      73 --YHTLDe--sFLGRYMSALNHTkkwkfpqvgglTSIKWADNNCYLSSVLLALQQl-EVKFNApALQEAYYRARagDAAN 147  Severe acute res...
5WFI_A      71 --FGFDEp---QLLKYYTMLGMCkwpvv-vcgnyFAFKQSNNNSYINVACLMLQHl-SLKFPKwQWQEAWNEFRsgKPLR 143  Murine hepatitis...
5W8T_A      72 --YGPVDp--tFLHRFYSLKAAVhgwkmvvcdkvRSLKLSDNNCYLNAVIMTLDLlkDIKFVIpALQHAFMKHKggDSTD 147  Human betacorona...
5TL6_B      76 --YHTLDe--sFLGRYMSALNHTkkwkfpqvgglTSIKWADNNCYLSSVLLALQQl-EVKFNApALQEAYYRARagDAAN 150  Severe acute res...
4X2Z_A      70 --YGLDAq---KYVIYLQTLAQKwnvqy--rdnfLILEWRDGNCWISSAIVLLQAa-KIRFKG-FLTEAWAKLLggDPTD 140  Avian infectious...
6L5T_A      65 --FGFSDa---AAFAVLDHSKFAfdsev--vdgkRALADSDNNCWVNATCLALQFl-KPTFKYvGWEDLWNKFVtgDVAG 136  Swine acute diar...
QDH76194  1155 nqAKELDlnlqQYCVYLKTCHHKwvvsr--tnglMHLKQKDNNCFVSAGVNLFQNt-AYQLRP-AIDALYREYLngNPNR 1230 Porcine deltacor...
5BZ0_A      68 --YGLDAq---KYVIYLQTLAQKwnvqy--rdnfLILEWRDGNSWISSAIVLLQAa-KIRFKG-FLTEAWAKLLggDPTD 138  Avian infectious...
4OVZ_A      73 --YHTLDe--sFLGRYMSALNHTkkwkfpqvgglTSIKWADNNXYLSSVLLALQQl-EVKFNApALQEAYYRARagDAAN 147  SARS coronavirus...
3MJ5_A      73 --YHTLDe--sFLGRYMSALNHTkkwkfpqvgglTSIKWADNNCYLSSVLLALQQl-EVKFNApALQEAYYRARagDAAN 147  Severe acute res...
Feature 1                                                  #  #                                
5E6J_A     148 FCALILAYsNKTVGELGDvRETMTHLLQHan--leSAKRVLNVVCkhCGQKTTTLTGveavmy-mgtlsYDNLKtgVSIP 224  Severe acute res...
5WFI_A     144 FVSLVLAKgSFKFNEPSDsIDFMRVVLREad--lsGATCNLEFVCk-CGVKQEQRKGvdavmh-fgtldKGDLVrgYNIA 219  Murine hepatitis...
5W8T_A     148 FIALIMAYgNCTFGAPDDaSRLLHTVLAKael-ccSARMVWREWCnvCGIKDVVLQGlkaccy-vgvqtVEDLRarMTYV 225  Human betacorona...
5TL6_B     151 FCALILAYsNKTVGELGDvRETMTHLLQHan--leSAKRVLNVVCkhCGQKTTTLTGveavmy-mgtlsYDNLKtgVSIP 227  Severe acute res...
4X2Z_A     141 FVAWCYAScTAKVGDFSDaNWLLANLAEHfdadytNAFLKKRVSCn-CGIKSYELRGleaciqpvratnLLHFKt-QYSN 218  Avian infectious...
6L5T_A     137 FVHLLYYIeGVDKGAKGDvESTLSKLDKYivs-sgSVTVERSTLCdrCNSTVKTVTGaia-------eaSVILNghTDGH 208  Swine acute diar...
QDH76194  1231 FVAWIYAStNRRVGEMGC-PQQVISLLVSn----sDAAFSATTAC--CNTYFNHTGVisv------areYDPIQ--PKVY 1295 Porcine deltacor...
5BZ0_A     139 FVAWCYAScTAKVGDFSDaNWLLANLAEHfdadytNAFLKKRVSCn-CGIKSYELRGleaciqpvratnLLHFKt-QYSN 216  Avian infectious...
4OVZ_A     148 FCALILAYsNKTVGELGDvRETMTHLLQHan--leSAKRVLNVVCkhCGQKTTTLTGveavmy-mgtlsYDNLKtgVSIP 224  SARS coronavirus...
3MJ5_A     148 FCALILAYsNKTVGELGDvRETMTHLLQHan--leSAKRVLNVVCkhCGQKTTTLTGveavmy-mgtlsYDNLKtgVSIP 224  Severe acute res...
Feature 1      #  #                                                                            
5E6J_A     225 CV-CgRDATQYLVQQEs-sFVMMSA------PPAEYKLQqg----tfLCANEYTGNyq---cGHYTHITak-------et 282  Severe acute res...
5WFI_A     220 CT-C-GSKLVHCTQFNv-pFLICSN------TPEGRKLPdd-----vVAANIFTGGs----vGHYTHVKck-------pk 274  Murine hepatitis...
5W8T_A     226 CQ-CgGERHRQLVEHTt-pWLLLSG------TPNEKLVTtsta-pdfVAFNVFQGIet--avGHYVHARlkg------gl 288  Human betacorona...
5TL6_B     228 CV-CgRDATQYLVQQEs-sFVMMSA------PPAEYKLQqg----tfLCANEYTGNyq---cGHYTHITak-------et 285  Severe acute res...
4X2Z_A     219 CPtCgANNTDEVIEASl-pYLLLFAt----dGPATVDCDed-----aVGTVVFVGStn---sGHCYTQAa---------- 275  Avian infectious...
6L5T_A     209 CP-HnFEWRVQVIGVKg-dIILLHSg-----SLLNGPYVy------gDAYVAFSGNtd---nGHYTVFDnk--------l 264  Swine acute diar...
QDH76194  1296 CMkC-DVWTPFTPQSGkgaVAIGTSadeptgPAIKFAAAhcwytngkKTVNGYDTKanvvatYHRFDVPkpqlvedvval 1374 Porcine deltacor...
5BZ0_A     217 CPtCgANNTDEVIEASl-pYLLLFAt----dGPATVDCDed-----aVGTVVFVGStn---sGHCYTQAa---------- 273  Avian infectious...
4OVZ_A     225 CV-CgRDATQYLVQQEs-sFVMMSA------PPAEYKLQqg----tfLCANEYTGNyq---xGHYTHITak-------et 282  SARS coronavirus...
3MJ5_A     225 CV-CgRDATQYLVQQEs-sFVMMSA------PPAEYKLQqg----tfLCANEYTGNyq---cGHYTHITak-------et 282  Severe acute res...
Feature 1                                
5E6J_A     283 LYRIDGa--HLTKMsEYKGpvTDVFY 306  Severe acute respiratory syndrome-related coronavirus
5WFI_A     275 YQLYDAc--NVNKVsEAKGnfTDCLY 298  Murine hepatitis virus strain A59
5W8T_A     289 ILKFDSg--TVSKTsDWKCkvTDVLF 312  Human betacoronavirus 2c EMC/2012
5TL6_B     286 LYRIDGa--HLTKMsEYKGpvTDVFY 309  Severe acute respiratory syndrome-related coronavirus
4X2Z_A     276 GQAFDNl-aKDRKF-GKKSpyITAXY 299  Avian infectious bronchitis virus (strain Beaudette)
6L5T_A     265 SKMYDGi--KCVKTtLDTLvaSSVVI 288  Swine acute diarrhea syndrome coronavirus
QDH76194  1375 PTKNDFevlNVEELpQDSVlhLDPPP 1400 Porcine deltacoronavirus
5BZ0_A     274 GQAFDNl-aKDRKF-GKKSpyITAXY 297  Avian infectious bronchitis virus (strain Beaudette)
4OVZ_A     283 LYRIDGa--HLTKMsEYKGpvTDVFY 306  SARS coronavirus Urbani
3MJ5_A     283 LYRIDGa--HLTKMsEYKGpvTDVFY 306  Severe acute respiratory syndrome-related coronavirus

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