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Conserved domains on  [gi|1258500542|pdb|5W8T|A]
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Chain A, ORF1ab

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
betaCoV_PLPro cd21732
betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
 2-312 2.07e-178

betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) found in non-structural protein 3 (Nsp3) of betacoronavirus, 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. In SARS-CoV and murine hepatitis virus (MHV), the C-terminal non-structural protein 3 region spanning transmembrane regions TM1 and TM2 with 3Ecto domain in between, are important for the PL2pro domain to process Nsp3-Nsp4 cleavage. 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 of 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. Interactions of SARS-CoV and MERS-CoV with antiviral interferon (IFN) responses of human cells are remarkably different; high-dose IFN treatment (type I and type III) shows MERS-CoV was substantially more IFN sensitive than SARS-CoV. This may be due to differences in the architecture of the oxyanion hole and of the S3 as well as the S5 specificity sites, despite the overall structures of SARS-CoV and MERS-CoV PLPro being similar.


:

Pssm-ID: 409649  Cd Length: 304  Bit Score: 495.18  E-value: 2.07e-178
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A        2 LTIEVLVTVDGVNFRTVVLNNKNTYRSQLGCVFFNGADISDTIPDEKQNGHSLYLADNLTADETKALKELYGPVDPTFLH 81
Cdd:cd21732   1 KTIEVLTTVDGVNFRTVLVNNGETFGKQLGNVFCDGVDVTKTKPSAKYEGKVLFQADNLSAEELEAVEYYYGFDDPTFLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A       82 RFYSLKAAVHGWKMVVCDKVRSLKLSDNNCYLNAVIMTLDLLkDIKFVIPALQHAFMKHKGGDSTDFIALIMAYGNCTFG 161
Cdd:cd21732  81 RYYSALAHVKKWKFVVVDGYFSLKQADNNCYLNAACLMLQQL-DLKFNTPALQEAYYEFRAGDPLRFVALVLAYGNFTFG 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A      162 APDDASRLLHTVLAKAELcCSARMVWREWCNVCGIKDVVLQGLKACCYVGVQTVEDLRARMTYVCQCGGERHRQLVEHTT 241
Cdd:cd21732 160 EPDDARDFLRVVLSHADL-VSARRVLEEVCKVCGVKQEQRTGVDAVMYFGTLSLDDLYKGYTIDCSCGRKAIRYLVEQVP 238

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
5W8T_A      242 PWLLLSGTPNEKLVTTStapDFVAFNVFQGIETaVGHYVHARLKgGLILKFDSGTVSKTSDWKCKVTDVLF 312
Cdd:cd21732 239 PFLLMSNTPTEVPLPTG---DFVAANVFTGDES-VGHYTHVKNK-SLLYLYDAGNVKKTSDLKGPVTDVLY 304
 
Name Accession Description Interval E-value
betaCoV_PLPro cd21732
betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
 2-312 2.07e-178

betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) found in non-structural protein 3 (Nsp3) of betacoronavirus, 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. In SARS-CoV and murine hepatitis virus (MHV), the C-terminal non-structural protein 3 region spanning transmembrane regions TM1 and TM2 with 3Ecto domain in between, are important for the PL2pro domain to process Nsp3-Nsp4 cleavage. 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 of 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. Interactions of SARS-CoV and MERS-CoV with antiviral interferon (IFN) responses of human cells are remarkably different; high-dose IFN treatment (type I and type III) shows MERS-CoV was substantially more IFN sensitive than SARS-CoV. This may be due to differences in the architecture of the oxyanion hole and of the S3 as well as the S5 specificity sites, despite the overall structures of SARS-CoV and MERS-CoV PLPro being similar.


Pssm-ID: 409649  Cd Length: 304  Bit Score: 495.18  E-value: 2.07e-178
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A        2 LTIEVLVTVDGVNFRTVVLNNKNTYRSQLGCVFFNGADISDTIPDEKQNGHSLYLADNLTADETKALKELYGPVDPTFLH 81
Cdd:cd21732   1 KTIEVLTTVDGVNFRTVLVNNGETFGKQLGNVFCDGVDVTKTKPSAKYEGKVLFQADNLSAEELEAVEYYYGFDDPTFLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A       82 RFYSLKAAVHGWKMVVCDKVRSLKLSDNNCYLNAVIMTLDLLkDIKFVIPALQHAFMKHKGGDSTDFIALIMAYGNCTFG 161
Cdd:cd21732  81 RYYSALAHVKKWKFVVVDGYFSLKQADNNCYLNAACLMLQQL-DLKFNTPALQEAYYEFRAGDPLRFVALVLAYGNFTFG 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A      162 APDDASRLLHTVLAKAELcCSARMVWREWCNVCGIKDVVLQGLKACCYVGVQTVEDLRARMTYVCQCGGERHRQLVEHTT 241
Cdd:cd21732 160 EPDDARDFLRVVLSHADL-VSARRVLEEVCKVCGVKQEQRTGVDAVMYFGTLSLDDLYKGYTIDCSCGRKAIRYLVEQVP 238

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
5W8T_A      242 PWLLLSGTPNEKLVTTStapDFVAFNVFQGIETaVGHYVHARLKgGLILKFDSGTVSKTSDWKCKVTDVLF 312
Cdd:cd21732 239 PFLLMSNTPTEVPLPTG---DFVAANVFTGDES-VGHYTHVKNK-SLLYLYDAGNVKKTSDLKGPVTDVLY 304
CoV_peptidase pfam08715
Coronavirus papain-like peptidase; This entry contains coronavirus cysteine endopeptidases ...
 3-319 6.31e-40

Coronavirus papain-like peptidase; This entry contains coronavirus cysteine endopeptidases that belong to MEROPS peptidase family C16 and are required for proteolytic processing of the replicase polyprotein. All coronaviruses encode between one and two accessory cysteine proteinases that recognize and process one or two sites in the amino-terminal half of the replicase polyprotein during assembly of the viral replication complex. HCoV and TGEV encode two accessory proteinases, called coronavirus papain-like proteinase 1 and 2 (PL1-PRO and PL2-PRO). IBV and SARS encodes only one called PL-PRO. The structure of this protein has shown it adopts a fold similar that of de-ubiquitinating enzymes. The peptidase family C16 domain is about 260 amino acids in length. This domain is predicted to have an alpha-beta structural organization known as the papain-like fold. It consists of three alpha-helices and three strands of antiparallel beta-sheet.


Pssm-ID: 430171  Cd Length: 318  Bit Score: 142.43  E-value: 6.31e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A          3 TIEVLVTVDGVNFRTVVLNNKNTYRSQLGCVFFNGADISDTIPDEKQNGHSLYLADNLTADETKALKEL--YGPVDPTFL 80
Cdd:pfam08715   4 QITIYLTEDGVNYHSIVVKPGDSLGQQFGQVYAKNKDLSGVFPADDVEDKEILYVPTTDWVEFYGFKSIleYYTLDASKY 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A         81 HRFYSlkaAVHgWKMVVCDKVRSLKLSDNNCYLNAVIMTLDLLKdIKFVIPALQHAFMKHKGGDSTDFIALIMAYGNCTF 160
Cdd:pfam08715  84 VIYLS---ALT-KNVQYVDGFLILKWRDNNCWISSVIVALQAAK-IRFKGQFLTEAWAKLLGGDPTDFVAWCYASCTAKV 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A        161 GAPDDASRLLHTVLAKAELCCSARMVWREWCNVCGIKDVVLQGLKACCYVGVQTVEDLRARMTYVCQCGGERHRQLVEHT 240
Cdd:pfam08715 159 GDFGDANWTLTNLAEHFDAEYTNAFLKKRVCCNCGIKSYELRGLEACIQVRATNLDHFKTGYSNCCVCGANNTDEVIEAS 238

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
5W8T_A        241 TPWLLLSGTpnEKLVTTSTAPDFVAFNVFQGiETAVGHYVHARLKGGLilkFDSGTVSKTSDWKCKVTDVLFPGQKYSS 319
Cdd:pfam08715 239 LPYLLLSAT--DGPAAVDCLEDGVGTVAFVG-STNSGHYTYQTAKQAF---YDGAKDRKFGKKSPYVTAVYTRFAFKNE 311
 
Name Accession Description Interval E-value
betaCoV_PLPro cd21732
betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
 2-312 2.07e-178

betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) found in non-structural protein 3 (Nsp3) of betacoronavirus, 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. In SARS-CoV and murine hepatitis virus (MHV), the C-terminal non-structural protein 3 region spanning transmembrane regions TM1 and TM2 with 3Ecto domain in between, are important for the PL2pro domain to process Nsp3-Nsp4 cleavage. 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 of 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. Interactions of SARS-CoV and MERS-CoV with antiviral interferon (IFN) responses of human cells are remarkably different; high-dose IFN treatment (type I and type III) shows MERS-CoV was substantially more IFN sensitive than SARS-CoV. This may be due to differences in the architecture of the oxyanion hole and of the S3 as well as the S5 specificity sites, despite the overall structures of SARS-CoV and MERS-CoV PLPro being similar.


Pssm-ID: 409649  Cd Length: 304  Bit Score: 495.18  E-value: 2.07e-178
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A        2 LTIEVLVTVDGVNFRTVVLNNKNTYRSQLGCVFFNGADISDTIPDEKQNGHSLYLADNLTADETKALKELYGPVDPTFLH 81
Cdd:cd21732   1 KTIEVLTTVDGVNFRTVLVNNGETFGKQLGNVFCDGVDVTKTKPSAKYEGKVLFQADNLSAEELEAVEYYYGFDDPTFLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A       82 RFYSLKAAVHGWKMVVCDKVRSLKLSDNNCYLNAVIMTLDLLkDIKFVIPALQHAFMKHKGGDSTDFIALIMAYGNCTFG 161
Cdd:cd21732  81 RYYSALAHVKKWKFVVVDGYFSLKQADNNCYLNAACLMLQQL-DLKFNTPALQEAYYEFRAGDPLRFVALVLAYGNFTFG 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A      162 APDDASRLLHTVLAKAELcCSARMVWREWCNVCGIKDVVLQGLKACCYVGVQTVEDLRARMTYVCQCGGERHRQLVEHTT 241
Cdd:cd21732 160 EPDDARDFLRVVLSHADL-VSARRVLEEVCKVCGVKQEQRTGVDAVMYFGTLSLDDLYKGYTIDCSCGRKAIRYLVEQVP 238

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
5W8T_A      242 PWLLLSGTPNEKLVTTStapDFVAFNVFQGIETaVGHYVHARLKgGLILKFDSGTVSKTSDWKCKVTDVLF 312
Cdd:cd21732 239 PFLLMSNTPTEVPLPTG---DFVAANVFTGDES-VGHYTHVKNK-SLLYLYDAGNVKKTSDLKGPVTDVLY 304
CoV_PLPro cd21688
Coronavirus (CoV) papain-like protease (PLPro); This model represents the papain-like protease ...
 2-312 2.07e-137

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.


Pssm-ID: 409647  Cd Length: 299  Bit Score: 391.08  E-value: 2.07e-137
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A        2 LTIEVLVTVDGVNFRTVVLNNKNTYRSQLGCVFFNGADISDTIPDeKQNGHSLYLADNltaDETKALKELYGPVDPTFLH 81
Cdd:cd21688   1 KTKKVLVTVDGVNFRTIVVTTGDTYGQQLGPVYLDGADVTKGKPD-NHEGETFFVLPS---TPDKAALEYYGFLDPSFLG 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A       82 RFYSLKAAVHGWKMvvCDKVRSLKLSDNNCYLNAVIMTLDLLKdIKFVIPALQHAFMKHKGGDSTDFIALIMAYGNCTFG 161
Cdd:cd21688  77 RYLSTLAHKWKVKV--VDGLRSLKWSDNNCYVSAVILALQQLK-IKFKAPALQEAWNKFLGGDPARFVALIYASGNKTVG 153

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A      162 APDDASRLLHTVLAKAElCCSARMVWREWCNVCGIKDVVLQGLKACCYVGVQTVEDLRARMTYVCQCGGERHRQLVEHTT 241
Cdd:cd21688 154 EPGDVRETLTHLLQHAD-LSSATRVLRVVCKHCGIKTTTLTGVEAVMYVGALSYDDLKTGVSIPCPCGGEWTVQVIQQES 232

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
5W8T_A      242 PWLLLS-GTPNEKLVTTStapDFVAFNVFQGIETaVGHYVHARLKgGLILKFDSGTVSKTSDWKCKVTDVLF 312
Cdd:cd21688 233 PFLLLSaAPPAEYKLQQD---TFVAANVFTGNTN-VGHYTHVTAK-ELLQKFDGAKVTKTSEDKGPVTDVLY 299
CoV_peptidase pfam08715
Coronavirus papain-like peptidase; This entry contains coronavirus cysteine endopeptidases ...
 3-319 6.31e-40

Coronavirus papain-like peptidase; This entry contains coronavirus cysteine endopeptidases that belong to MEROPS peptidase family C16 and are required for proteolytic processing of the replicase polyprotein. All coronaviruses encode between one and two accessory cysteine proteinases that recognize and process one or two sites in the amino-terminal half of the replicase polyprotein during assembly of the viral replication complex. HCoV and TGEV encode two accessory proteinases, called coronavirus papain-like proteinase 1 and 2 (PL1-PRO and PL2-PRO). IBV and SARS encodes only one called PL-PRO. The structure of this protein has shown it adopts a fold similar that of de-ubiquitinating enzymes. The peptidase family C16 domain is about 260 amino acids in length. This domain is predicted to have an alpha-beta structural organization known as the papain-like fold. It consists of three alpha-helices and three strands of antiparallel beta-sheet.


Pssm-ID: 430171  Cd Length: 318  Bit Score: 142.43  E-value: 6.31e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A          3 TIEVLVTVDGVNFRTVVLNNKNTYRSQLGCVFFNGADISDTIPDEKQNGHSLYLADNLTADETKALKEL--YGPVDPTFL 80
Cdd:pfam08715   4 QITIYLTEDGVNYHSIVVKPGDSLGQQFGQVYAKNKDLSGVFPADDVEDKEILYVPTTDWVEFYGFKSIleYYTLDASKY 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A         81 HRFYSlkaAVHgWKMVVCDKVRSLKLSDNNCYLNAVIMTLDLLKdIKFVIPALQHAFMKHKGGDSTDFIALIMAYGNCTF 160
Cdd:pfam08715  84 VIYLS---ALT-KNVQYVDGFLILKWRDNNCWISSVIVALQAAK-IRFKGQFLTEAWAKLLGGDPTDFVAWCYASCTAKV 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A        161 GAPDDASRLLHTVLAKAELCCSARMVWREWCNVCGIKDVVLQGLKACCYVGVQTVEDLRARMTYVCQCGGERHRQLVEHT 240
Cdd:pfam08715 159 GDFGDANWTLTNLAEHFDAEYTNAFLKKRVCCNCGIKSYELRGLEACIQVRATNLDHFKTGYSNCCVCGANNTDEVIEAS 238

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
5W8T_A        241 TPWLLLSGTpnEKLVTTSTAPDFVAFNVFQGiETAVGHYVHARLKGGLilkFDSGTVSKTSDWKCKVTDVLFPGQKYSS 319
Cdd:pfam08715 239 LPYLLLSAT--DGPAAVDCLEDGVGTVAFVG-STNSGHYTYQTAKQAF---YDGAKDRKFGKKSPYVTAVYTRFAFKNE 311
gammaCoV_PLPro cd21733
gammacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
 6-279 1.32e-21

gammacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) found in non-structural protein 3 (Nsp3) of gammacoronavirus, including Avian coronavirus, Canada goose coronavirus, and Beluga whale coronavirus SW1. 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 several CoVs has also been shown to antagonize host innate immune induction of type I interferon by interacting with IRF3 and blocking its activation.


Pssm-ID: 409650  Cd Length: 304  Bit Score: 92.88  E-value: 1.32e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A        6 VLVTVDGVNFRTVVLNNKNTYrSQLGCVFfngadisdtipdekQNGHSLYLADNLTADETkalkeLYGP-VDPTFLhRFY 84
Cdd:cd21733   7 IYLTEDGVKYRSVVVKPGDSL-SQFGQVF--------------ARNKTVFTADDVEDKEI-----LFIPtTDKAVL-EYY 65

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A       85 SLKAA---------VHGWKMVVCDKVRSLKLSDNNCYLNAVIMTLDLLKdIKFViPALQHAFMKHKGGDSTDFIALIMAY 155
Cdd:cd21733  66 GLDAQkyviylqtlAQKWNVQYRDNFLILEWRDGNCWISSAIVLLQAAK-IRFK-GFLAEAWAKFLGGDPTEFVAWCYAS 143

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A      156 GNCTFGAPDDASRLLHTvLAK---AELCCsARMVWREWCNvCGIKDVVLQGLKACcyvgVQTVE--DLRARMTY--VC-Q 227
Cdd:cd21733 144 CNAKVGDFSDANWLLAN-LAEyfdADYTN-AFLKRRVSCN-CGVKNYELRGLEAC----IQPVRapNLLHFKTQysNCpT 216

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|..
5W8T_A      228 CGGERHRQLVEHTTPWLLLSGTPNEKLVTTSTapDFVAFNVFQGiETAVGHY 279
Cdd:cd21733 217 CGANSVDEVVEASLPYLLLLATDGPATVDCDE--NAVGNVVFIG-STNSGHC 265
Ubl2_PLpro_N_CoV_Nsp3-like cd21466
second ubiquitin-like (Ubl) domain located N-terminal to the papain-like protease (PLpro) ...
 3-56 1.41e-19

second ubiquitin-like (Ubl) domain located N-terminal to the papain-like protease (PLpro) domain in coronavirus non-structural protein 3 (Nsp3) and related proteins; This model represents the second ubiquitin-like (Ubl) domain located N-terminal to the papain-like protease (PLpro) domain of non-structural protein 3 (Nsp3) from coronavirus (CoV), including highly pathogenic human CoVs such as Severe acute respiratory syndrome (SARS)-CoV and SARS-CoV-2 (also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus). SARS-CoV non-structural proteins (Nsps) are encoded in ORF1a and ORF1b. Post infection, the SARS-CoV genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (pps), pp1a and pp1ab. Papain-like protease (PLpro) is one of two SARS-CoV proteases which process these polyproteins; it cleaves pp1a at three sites, releasing Nsp1, Nsp2, and Nsp3. Nsp3 is a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). This ubiquitin-like (Ubl) domain (sometimes referred to as Ubl2, the second Ubl domain of Nsp3) is located N-terminal to the PLpro domain of Nsp3. In addition to being a protease, SARS-CoV PLpro is a deubiquitinating enzyme (DUB), and may be involved in subverting cellular ubiquitination machinery to facilitate viral replication. A number of cellular DUBs have a Ubl domain, where it may serve a regulatory function. The exact functional role of this Ubl domain is unclear.


Pssm-ID: 439190  Cd Length: 54  Bit Score: 80.72  E-value: 1.41e-19
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
5W8T_A        3 TIEVLVTVDGVNFRTVVLNNKNTYRSQLGCVFFNGADISDTIPDEKQNGHSLYL 56
Cdd:cd21466   1 TVKVLVTEDGVNFRTVVVDTSKTFGEQLGTVFVDGVDVTDTKPTVKDEGKVVFV 54
alphaCoV_PLPro cd21731
alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
 3-183 6.88e-09

alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) found in non-structural protein 3 (Nsp3) of alphacoronavirus, including Swine acute diarrhea syndrome coronavirus (SADS-CoV) which causes severe diarrhea in piglets, and Human coronavirus 229E which infects humans and bats and causes the common cold. 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 SADS-CoV and many others has also been shown to antagonize host innate immune induction of type I interferon by interacting with IRF3 and blocking its activation.


Pssm-ID: 409648  Cd Length: 289  Bit Score: 56.09  E-value: 6.88e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A        3 TIEVLVTVDGVNFRTVVLNNKNTYRSQLGCVFFNGADISDTIPDekqnghslylaDNLTADETKAL----KELYGPVDP- 77
Cdd:cd21731   2 SVVVKVTEDGRNVKDVVVDTDKTFGEQLGVCSVNDKDVTGVVPP-----------DDSDKVVSVAPdvdwDSHYGFPNAa 70

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A       78 ---TFLHRFYSLKAAVHgwkmvvcDKVRSLKLSDNNCYLNAVIMTLDLLKdIKFVIPALQHAFMKHKGGDSTDFIALIMA 154
Cdd:cd21731  71 vfhTLDHSAYAFESDIV-------NGKRVLKQSDNNCWVNAVCLQLQFAK-PTFKSEGLQALWNKFLTGDVAGFVHWLYW 142

                       170       180
                ....*....|....*....|....*....
5W8T_A      155 YGNCTFGAPDDASRLLHtVLAKAeLCCSA 183
Cdd:cd21731 143 ITGANKGDPGDAENTLN-KLSKY-LVSSG 169
deltaCoV_PLPro cd21734
deltacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
 35-161 7.60e-03

deltacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) found in the non-structural protein 3 (Nsp3) region of deltacoronavirus, including Porcine deltacoronavirus, Bulbul coronavirus HKU11, and Common moorhen coronavirus HKU21. 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.


Pssm-ID: 409651  Cd Length: 313  Bit Score: 37.41  E-value: 7.60e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5W8T_A       35 FNGAD-ISDTIPDekqnghSLYLAdnLTADETKALKELygpvDPTFLHRFYSLKAAVHGWKMVVCDKVRSLKLSDNNCYL 113
Cdd:cd21734  42 FDGEDfVQEPKPG------QIYLA--VTDEVQQQAKEL----DLTLSQYCVYLKYCHHKWSVSRTNGLMHLKQKDNNCFV 109

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
5W8T_A      114 NAVImtlDLLKDIKFVI-PALQHAFMKHKGGDSTDFIALIMAYGNCTFG 161
Cdd:cd21734 110 SAAI---NLFQNTHYQLrPAIDALYQEYLNGNPSRFVAWIYASTNQEIG 155
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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