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Conserved domains on  [gi|306440555]
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Chain A, Non-structural protein 3

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
CoV_PLPro super family cl40457
Coronavirus (CoV) papain-like protease (PLPro); This model represents the papain-like protease ...
 5-188 6.81e-26

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.


The actual alignment was detected with superfamily member cd21731:

Pssm-ID: 424088  Cd Length: 289  Bit Score: 101.16  E-value: 6.81e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306440555   5 FKTTNLNGKIILKQGDNNCWINACCYQLQAFDF-FNNE----AWEKFKKGDVMDFVNLCYAATTLARGHSGDAEYLLeLM 79
Cdd:cd21731   82 FESDIVNGKRVLKQSDNNCWVNAVCLQLQFAKPtFKSEglqaLWNKFLTGDVAGFVHWLYWITGANKGDPGDAENTL-NK 160

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306440555  80 LNDY--STAKIVL--AAKCGCGEKEIVLERAVFKLTPLKESFNYGVC--GDCMqvnTCRFLSVEGSGVFVHDILSKQTPE 153
Cdd:cd21731  161 LSKYlvSSGSVTVerTTGCDSCNSKRTVTTPVVNASVLRSGVDDGVCkhGVKV---TTRVVSVKGTVIITSVGKPVVSDA 237

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 306440555 154 AMFvVKPVMHAVYTGTTQNGHYMVDDIEHGYCVDG 188
Cdd:cd21731  238 LLL-LDGVSYTAFSGDVDNGHYTVYDKATGKVYDG 271
 
Name Accession Description Interval E-value
alphaCoV_PLPro cd21731
alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
 5-188 6.81e-26

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: 101.16  E-value: 6.81e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306440555   5 FKTTNLNGKIILKQGDNNCWINACCYQLQAFDF-FNNE----AWEKFKKGDVMDFVNLCYAATTLARGHSGDAEYLLeLM 79
Cdd:cd21731   82 FESDIVNGKRVLKQSDNNCWVNAVCLQLQFAKPtFKSEglqaLWNKFLTGDVAGFVHWLYWITGANKGDPGDAENTL-NK 160

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306440555  80 LNDY--STAKIVL--AAKCGCGEKEIVLERAVFKLTPLKESFNYGVC--GDCMqvnTCRFLSVEGSGVFVHDILSKQTPE 153
Cdd:cd21731  161 LSKYlvSSGSVTVerTTGCDSCNSKRTVTTPVVNASVLRSGVDDGVCkhGVKV---TTRVVSVKGTVIITSVGKPVVSDA 237

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 306440555 154 AMFvVKPVMHAVYTGTTQNGHYMVDDIEHGYCVDG 188
Cdd:cd21731  238 LLL-LDGVSYTAFSGDVDNGHYTVYDKATGKVYDG 271
CoV_peptidase pfam08715
Coronavirus papain-like peptidase; This entry contains coronavirus cysteine endopeptidases ...
 6-178 5.27e-20

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: 85.80  E-value: 5.27e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306440555    6 KTTNLNGKIILKQGDNNCWINACCYQLQAFDF-FN----NEAWEKFKKGDVMDFVNLCYAATTLARGHSGDAEYLLELML 80
Cdd:pfam08715  93 NVQYVDGFLILKWRDNNCWISSVIVALQAAKIrFKgqflTEAWAKLLGGDPTDFVAWCYASCTAKVGDFGDANWTLTNLA 172

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306440555   81 ----NDYSTAKIVLAAKCGCGEK-------EIVLERAVFKLTPLKESfnYGVCGDCMQVNTCRFLSVEGSGVFVHdilSK 149
Cdd:pfam08715 173 ehfdAEYTNAFLKKRVCCNCGIKsyelrglEACIQVRATNLDHFKTG--YSNCCVCGANNTDEVIEASLPYLLLS---AT 247

                         170       180       190
                  ....*....|....*....|....*....|
gi 306440555  150 QTPEAMF-VVKPVMHAVYTGTTQNGHYMVD 178
Cdd:pfam08715 248 DGPAAVDcLEDGVGTVAFVGSTNSGHYTYQ 277
 
Name Accession Description Interval E-value
alphaCoV_PLPro cd21731
alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
 5-188 6.81e-26

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: 101.16  E-value: 6.81e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306440555   5 FKTTNLNGKIILKQGDNNCWINACCYQLQAFDF-FNNE----AWEKFKKGDVMDFVNLCYAATTLARGHSGDAEYLLeLM 79
Cdd:cd21731   82 FESDIVNGKRVLKQSDNNCWVNAVCLQLQFAKPtFKSEglqaLWNKFLTGDVAGFVHWLYWITGANKGDPGDAENTL-NK 160

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306440555  80 LNDY--STAKIVL--AAKCGCGEKEIVLERAVFKLTPLKESFNYGVC--GDCMqvnTCRFLSVEGSGVFVHDILSKQTPE 153
Cdd:cd21731  161 LSKYlvSSGSVTVerTTGCDSCNSKRTVTTPVVNASVLRSGVDDGVCkhGVKV---TTRVVSVKGTVIITSVGKPVVSDA 237

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 306440555 154 AMFvVKPVMHAVYTGTTQNGHYMVDDIEHGYCVDG 188
Cdd:cd21731  238 LLL-LDGVSYTAFSGDVDNGHYTVYDKATGKVYDG 271
CoV_PLPro cd21688
Coronavirus (CoV) papain-like protease (PLPro); This model represents the papain-like protease ...
 11-175 4.95e-21

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: 88.31  E-value: 4.95e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306440555  11 NGKIILKQGDNNCWINACCYQLQAFDF-FN----NEAWEKFKKGDVMDFVNLCYAATTLARGHSGDAEYLLELML--NDY 83
Cdd:cd21688   92 DGLRSLKWSDNNCYVSAVILALQQLKIkFKapalQEAWNKFLGGDPARFVALIYASGNKTVGEPGDVRETLTHLLqhADL 171

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306440555  84 STAKIVLAAKC-GCGEKEIVL---ERAVFKLTPLKESFNYGVCGDCMQVNTCRFLSVEGSGVFVhdILSKQTPEAMFVVK 159
Cdd:cd21688  172 SSATRVLRVVCkHCGIKTTTLtgvEAVMYVGALSYDDLKTGVSIPCPCGGEWTVQVIQQESPFL--LLSAAPPAEYKLQQ 249

                        170
                 ....*....|....*...
gi 306440555 160 PVMHA--VYTGTTQNGHY 175
Cdd:cd21688  250 DTFVAanVFTGNTNVGHY 267
CoV_peptidase pfam08715
Coronavirus papain-like peptidase; This entry contains coronavirus cysteine endopeptidases ...
 6-178 5.27e-20

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: 85.80  E-value: 5.27e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306440555    6 KTTNLNGKIILKQGDNNCWINACCYQLQAFDF-FN----NEAWEKFKKGDVMDFVNLCYAATTLARGHSGDAEYLLELML 80
Cdd:pfam08715  93 NVQYVDGFLILKWRDNNCWISSVIVALQAAKIrFKgqflTEAWAKLLGGDPTDFVAWCYASCTAKVGDFGDANWTLTNLA 172

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306440555   81 ----NDYSTAKIVLAAKCGCGEK-------EIVLERAVFKLTPLKESfnYGVCGDCMQVNTCRFLSVEGSGVFVHdilSK 149
Cdd:pfam08715 173 ehfdAEYTNAFLKKRVCCNCGIKsyelrglEACIQVRATNLDHFKTG--YSNCCVCGANNTDEVIEASLPYLLLS---AT 247

                         170       180       190
                  ....*....|....*....|....*....|
gi 306440555  150 QTPEAMF-VVKPVMHAVYTGTTQNGHYMVD 178
Cdd:pfam08715 248 DGPAAVDcLEDGVGTVAFVGSTNSGHYTYQ 277
gammaCoV_PLPro cd21733
gammacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
 11-103 9.68e-18

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: 79.40  E-value: 9.68e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306440555  11 NGKIILKQGDNNCWINACCYQLQA----FDFFNNEAWEKFKKGDVMDFVNLCYAATTLARGHSGDAEYLL----ELMLND 82
Cdd:cd21733   89 DNFLILEWRDGNCWISSAIVLLQAakirFKGFLAEAWAKFLGGDPTEFVAWCYASCNAKVGDFSDANWLLanlaEYFDAD 168

                         90       100
                 ....*....|....*....|.
gi 306440555  83 YSTAKIVLAAKCGCGEKEIVL 103
Cdd:cd21733  169 YTNAFLKRRVSCNCGVKNYEL 189
betaCoV_PLPro cd21732
betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
 6-176 1.33e-13

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: 68.00  E-value: 1.33e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306440555   6 KTTNLNGKIILKQGDNNCWINACCYQLQAFDF-FN----NEAWEKFKKGDVMDFVNLCYAATTLARGHSGDAEYLLELML 80
Cdd:cd21732   93 KFVVVDGYFSLKQADNNCYLNAACLMLQQLDLkFNtpalQEAYYEFRAGDPLRFVALVLAYGNFTFGEPDDARDFLRVVL 172

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306440555  81 N--DYSTAKIVLAAKC-GCGEKEIVLE--RAVF-----KLTPLKESFNYG-VCGD----CMQVNTCRFLsvegsgvfvhd 145
Cdd:cd21732  173 ShaDLVSARRVLEEVCkVCGVKQEQRTgvDAVMyfgtlSLDDLYKGYTIDcSCGRkairYLVEQVPPFL----------- 241

                        170       180       190
                 ....*....|....*....|....*....|...
gi 306440555 146 ILSkQTPEAMFVVKPVMHA--VYTGTTQNGHYM 176
Cdd:cd21732  242 LMS-NTPTEVPLPTGDFVAanVFTGDESVGHYT 273
deltaCoV_PLPro cd21734
deltacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
 6-97 4.20e-07

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: 49.35  E-value: 4.20e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306440555   6 KTTNLNGKIILKQGDNNCWINAccyqlqAFDFFNN----------EAWEKFKKGDVMDFVNLCYAATTLARGHSGDAEYL 75
Cdd:cd21734   90 SVSRTNGLMHLKQKDNNCFVSA------AINLFQNthyqlrpaidALYQEYLNGNPSRFVAWIYASTNQEIGEMGCPQQV 163

                         90       100
                 ....*....|....*....|..
gi 306440555  76 LELMLNdYSTAKIVLAAKCgCG 97
Cdd:cd21734  164 LSLLVN-NSNAKFSGTTAC-CG 183
 
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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