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Conserved domains on  [gi|1818222121|gb|QIH31001|]
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ORF1a [Coronavirus HKU15]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
TM_Y_deltaCoV_Nsp3_C cd21711
C-terminus of deltacoronavirus non-structural protein 3, including transmembrane and Y domains; ...
1502-1991 0e+00

C-terminus of deltacoronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from deltacoronavirus, including Magpie-robin coronavirus HKU18 and Bulbul coronavirus HKU11, among others. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In the related betacoronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


:

Pssm-ID: 409659  Cd Length: 490  Bit Score: 976.49  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1502 LYYSAQTLFVSLAPFLMLPAVVSLLNSGYTIGTYLYAKTGWPCNYNATQHFDYNSYCAGDLVCQACFDGQDSLHLYPHLR 1581
Cdd:cd21711      1 LFYSAQTIFVSLAPFLMLPAVASLLSSGYTIGTYLYAKTGLPCYYNATQHYDYNSFCAGDLTCQACFDGQDSLHLYKHLR 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1582 VNQQPIQTTDYTVYALSLILLLANMTLVMGTLIVTFFVNFYGVQIPFYGTLLIDYQSALMMTFSVYYFYKVMKFFRHLTH 1661
Cdd:cd21711     81 VNQQPVQTTDYTVYALSIVLLLANPTLVLGTLLVVFFVNFYGVQIPFYGTLQLDYQNTLVMVFSVYYFYKVMKFFRHLAK 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1662 GCKIPTCMVCAKLRTPPTITVETVVQGRKYPSVIETNGGFTICKEHNFYCKDCSLQTPGTFIPTEAIESLSRATRLSVKP 1741
Cdd:cd21711    161 GCKKPTCSICAKKRIPPTITVETVVQGRKYPSVIETNGGFNICKEHNFYCKNCDSQTPGTFIPTEAVESLSRKTRLSVKP 240
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1742 TAPAFLLARDVECQTDVVVARAMHNQNAHVCISKYSDIRTVDQLLKPTPLFSYTPDVIIAADFDNRGSLKTAKELAVVLS 1821
Cdd:cd21711    241 TAPAYLLARDVECQTDVVVARATHNGNAHVCISKYSDIRTVDQLLKPTPLFSYTPDVIIAADFDNAGSLKTAKELAVVLS 320
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1822 MDLKRTIIIIDQAYSRPIDNYQEVASRIEKYYPVAKITPTGDIFTDIKQATNGQASDSAINAAVLAVQRGLDFTIDNPNN 1901
Cdd:cd21711    321 MDLKRTIIIIDQAYSRPIDNYQEVKSRIEKYYPFQKITPTGDIFADIKQATNGQASDSAINAAILAVQRGLDFTIDNPNN 400
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1902 ILPHYAFDFSTLNAEDQSTILESGCAKGNLKGTNVGVVLSASLVTRLSQQAIRVIANAASRNGVTCAVTPSTLVMRGNIA 1981
Cdd:cd21711    401 ILPHYAFDFSTLSAEDQSTLIESGCAKGNLKGTNVGVVLSANLVTRLSQKAIRVIANAASRNGVTCAVTPSTLVLRGNIA 480
                          490
                   ....*....|
gi 1818222121 1982 TQPLTRIKAG 1991
Cdd:cd21711    481 TQPLTRIKAG 490
deltaCoV_Nsp5_Mpro cd21668
deltacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
2503-2804 0e+00

deltacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in deltacoronaviruses. 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. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


:

Pssm-ID: 394889  Cd Length: 302  Bit Score: 644.56  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2503 QAGIKILLHPSGVVERCMVSVVYNGSALNGIWLKNVVYCPRHVIGKFRGDQWTHMVSIADCRDFIVKCPIQGIQLNVQSV 2582
Cdd:cd21668      1 QAGIKILLHPSGVVERCMVSVTYNGSTLNGIWLHNVVYCPRHVIGKYTGSQWQDMVSIADCRDFVIFCPTQGIQLTVQSV 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2583 KMVGALLQLTVHTNNTATPDYKFERLQPGSSMTIACAYDGIVRHVYHVVLQLNNLIYASFLNGACGSVGYTLKGKTLYLH 2662
Cdd:cd21668     81 KMVGAVLQLTVHTKNLHTPDYEFERATPGSSMTIACAYDGIVRNVYHVVLQTNNLIYASFLNGACGSVGYTLKGKTLLLH 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2663 YMHHIEFNNKTHSGTDLEGNFYGPYVDEEVIQQQTAFQYYTDNVVAQLYAHLLTVDARPKWLAQSQISIEDFNSWAANNS 2742
Cdd:cd21668    161 YMHHLEFNNKTHGGTDLHGHFYGPYVDEEVAQHQTAFQYYTDNVVAQIYAHLLTIDAKPKWLASQEISVEDFNEWAANNS 240
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1818222121 2743 FANFPCEQTNMSYIMGLSQTARVPVERILNTIIQLTTNRDGACIMGSYDFECDWTPEMVYNQ 2804
Cdd:cd21668    241 FANFPCESSNMAYLEGLAQTTKVSVGRVLNTIIQLTLNRGGALIMGKPDFECDWTPEMVYNQ 302
deltaCoV_PLPro cd21734
deltacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
1087-1399 0e+00

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: 628.69  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1087 MNKNHLQVWDALNRTIVRTTTDYDQVTTKALTPQGVLEANLFDGEDFVQEPKPGQIYLEVTEEVQNQAKELDLNLQQYCV 1166
Cdd:cd21734      1 LDKNHLQVWDALNRTVVRTTKDFDQVTTKALTPQGVLDANLFDGEDFVQEPKPGQIYLAVTDEVQQQAKELDLTLSQYCV 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1167 YLKTCHHKWVVSRTNGLMHLKQKDNNCFVSAGVNLFQNTAYQLRPAIDALYREYLNGNPNRFVAWIYASTNRRVGEMGCP 1246
Cdd:cd21734     81 YLKYCHHKWSVSRTNGLMHLKQKDNNCFVSAAINLFQNTHYQLRPAIDALYQEYLNGNPSRFVAWIYASTNQEIGEMGCP 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1247 QQVISLLVSNSDAAFSATTACCNTYFNHTGVISVAREYDPIQPKVYCMKCDVWTPFTPQSGKGAVAIGTSADEPTGPAIK 1326
Cdd:cd21734    161 QQVLSLLVNNSNAKFSGTTACCGTYFTHDGVISVAREYDPLQPKVYCMKCDVWTPFTPQSGKGIVVIGSSAEEPTGPAIK 240
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1818222121 1327 FAAAHCWYTNGKKTVNGYDTKANVVATYHRFDVPKPQLVEDVVALPTKNDFEVLNVEELPQDSVLHLDPPPVQ 1399
Cdd:cd21734    241 FAAAHCWYTNGKKTVNGYDTKANVVAIYHKFDVPKPQPVEDVVTLPTKNDFEVLKVEEIPQDSVLNLDPPEVQ 313
deltaCoV-Nsp6 cd21561
deltacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...
2792-3087 0e+00

deltacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.


:

Pssm-ID: 394847  Cd Length: 296  Bit Score: 573.54  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2792 FECDWTPEMVYNQAPISLQSGVVKKTCTWFFHFVFMAITMLLAAMHVFPVHLYPIVLPCFTVVAFLLTLTIKHTVVFTTT 2871
Cdd:cd21561      1 FECDWTPEMVYNQAPINLQSGVVKKTCMWFFHFLFMAVIFLLAALHVFPVHLYPIVLPVFTILAFLLTLTIKHTVVFTTT 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2872 YLLPSLLMMVVNANTFWIPNTFLRTCYETIFGSPIAQRLYGYTVALYMLIYAGLAINYTLKTLRYRATSFLSFCMQWFQY 2951
Cdd:cd21561     81 YLLPSLLMMVVNANTFWIPNTYLRSIYEYVFGSFISERLYGYTVALYILVYAQLAINYTLRTRRYRATSFISFCMQALQY 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2952 GYVAHIAYKLLNKPWTESLLFTAFTMLTSHPLLAALSWWLAGRVTLPIIMPDLAIRVLAYNVIGYVICVRFGLMWLANRF 3031
Cdd:cd21561    161 GYVAHIVYRLLTTPWTEGLLFTAFSLLTSHPLLAALSWWLAGRIPLPLILPDLAIRVIVYYVIGYVMCMRFGLFWLINKF 240
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1818222121 3032 TTVPMGTYQYMVSVEQLKYMMAVKMSPPRNAFEVLIANIRLLGLGGNRNIAVSTVQ 3087
Cdd:cd21561    241 TTIPMGTYKYMVSIEQLKYMMAVKMSPPRNAFEVLWANIRLLGLGGNRNIAVSTVQ 296
cv_gamma-delta_Nsp2_IBV-like cd21512
gamma- and deltacoronavirus non-structural protein 2 (Nsp2), similar to IBV Nsp2 and related ...
7-379 0e+00

gamma- and deltacoronavirus non-structural protein 2 (Nsp2), similar to IBV Nsp2 and related proteins; Coronavirus non-structural proteins (Nsps) are encoded in ORF1a and ORF1b. Post infection, the genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (pp), pp1a and pp1ab, which are then autoproteolytically cleaved by two viral proteases Nsp3 and Nsp5 into smaller subunits. Nsp2 is one of these cleaved subunits. The functions of Nsp2 remain unclear. This gamma- and deltacoronavirus family includes Avian infectious bronchitis virus (IBV) Nsp2 which has been shown to be a weak protein kinase R (PKR) antagonist, which may suggest that it plays a role in interfering with intracellular immunity. This family may be distantly related to a family of alpha- and betacoronavirus Nsp2, which includes severe acute respiratory syndrome coronavirus (SARS-CoV) Nsp2, and Murine hepatitis virus (MHV) Nsp2 (also known as p65). SARS-CoV Nsp2, rather than playing a role in viral replication, may be involved in altering the host cell environment; deletion of Nsp2 from the SARS-CoV genome results in only a modest reduction in viral titers. It has been shown to interact with two host proteins, prohibitin 1 (PHB1) and PHB2, which have been implicated in cellular functions, including cell-cycle progression, cell migration, cellular differentiation, apoptosis, and mitochondrial biogenesis. MHV Nsp2/p65, different from SARS-CoV Nsp2, may play an important role in the viral life cycle.


:

Pssm-ID: 394837  Cd Length: 365  Bit Score: 561.65  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121    7 KRDAIALPENVPPPLQLFIHVAAAEEGHPKVTTYLGNYNLYATKAPPGVQVLSAKTSLTDFENVFGAQPTLRSIRNLVCE 86
Cdd:cd21512      1 KRHPIVLPPDAPPPLQLFIRVAAAGEGHPFDTVYLGNYNLIGVKAVPGVQVLDANTSLADFENLFGVQPTLRAYRNLLKD 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121   87 ArsAEWTTSKNAFALKATQLDYSDAVLRAMIRFCPPKVSTLAAFALFGRLVKIEDKELAELARDTALELAYTAKIGTSLA 166
Cdd:cd21512     81 A--AQWSLSKEALAAKAKQLTESDDVLRAIILYGAARVSALASLALFGRVVKIDDVELGDLAEDVALELAYTGKIGRALA 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  167 DTRSVSLIHKDAYLTLSNEVVGVTFTAALMAKATTVNGAMQYSNFYLYPRATIKVTDGKAEAIATKPLPAATKGKPITED 246
Cdd:cd21512    159 DAKAIELPQTDAYLTLNFAVCGKVFTSTLLAQATPVNGALQYSDFVLWPLATAKATDGKLQPLAGKPLPASQKGAFFTED 238
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  247 VNLLPDYQQLLVDQVTGTEVKVGALTYVKTTDLPPLYFPKVKGGVvgiALKQQGTAAKKLNVVFHAQPDDVLLAFIQLQQ 326
Cdd:cd21512    239 VNLVPDYQQLAPDQVEGDEVVVGGITYIKTTDVPPLYYPRVKGGV---LLKPQGTADKKVNVVFHAAPSDVLLAFIQLQL 315
                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1818222121  327 FLNRTSDSSVEITDCQSYEVSPTVTVKIGpskPGDVIVATDEEYLKCFETPEV 379
Cdd:cd21512    316 FLVRTSGSCVEVTDDDVYAVPPSVTVSIG---PGDVVVNDDEEYVKCFETPVV 365
cv_Nsp4_TM cd21473
coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in ...
2001-2396 5.13e-134

coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in coronavirus-induced membrane remodeling. In order to assemble the replication-transcription complex (RTC), coronavirus induces the rearrangement of host endoplasmic reticulum (ER) membrane into double membrane vesicles (DMVs), zippered ER, or ER spherules. DMV formation has been observed in SARS-CoV cells overexpressing the three transmembrane-containing non-structural proteins of viral replicase polyprotein 1ab: Nsp3, Nsp4 and Nsp6. Together, Nsp3, Nsp4, and Nsp6 have the ability to induce the formation of DMVs that are similar to those seen in SARS-CoV-infected cells.


:

Pssm-ID: 394836  Cd Length: 376  Bit Score: 425.85  E-value: 5.13e-134
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2001 CVILALAIVYFAAMAFGFLASQITLNTVPTiksdiraSTFYVVRDGVLDTVRSNDKCFANKFLAFDSFIQAPY----TNS 2076
Cdd:cd21473      1 FLWLLLAAILLYAFLPSYSVFTVTVSSFPG-------YDFKVIENGVLRDIRSTDTCFANKFVNFDSWYQAKYgsvpTNS 73
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2077 PDCPVVVGVVEVTTHSIPGIPAGVIHRDGLILNIYEQslyethqrqsmvrdalslktanlfNLGKRVVVGYTQHEVVVGT 2156
Cdd:cd21473     74 KSCPIVVGVIDDVRGSVPGVPAGVLLVGKTLVHFVQT------------------------VFFGDTVVCYTPDGVITYD 129
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2157 SYFNSPALFNAKCTFLQYQDTRQLYCYDTVPTEH-KLYSDVLPHVEYKAIDINgdlvPFKIPEQIM-FYPHIVRYTSNSY 2234
Cdd:cd21473    130 SFYTSACVFNSACTYLTGLGGRQLYCYDTGLVEGaKLYSDLLPHVRYKLVDGN----YIKFPEVILeGGPRIVRTLATTY 205
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2235 CRMGHCFNTNPGICISFTDEFPYSENV-KPGVYCADTSLQLFSNLVLGTVSGIHIFTSTAALLGSTIVIILCVVAVLAVQ 2313
Cdd:cd21473    206 CRVGECEDSKAGVCVSFDGFWVYNNDYyGPGVYCGDGLFDLLTNLLSGFFQPVSVFALSGQLLFNTIVAILAVLACYYVQ 285
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2314 RFFKEY---TTFVMYTCGLAFVNIVGIALMYKCLvFAIFYYAIYLYFVLTFPSFkRNVALFYFAVVIVPHVSNMQLLALI 2390
Cdd:cd21473    286 KFKRAFgdmSVVVVTVVAAALVNNVLYVVTQNPL-LMIVYAVLYFYATLYLTYE-RAWIMHLGWVVAYGPIAPWWLLALY 363

                   ....*.
gi 1818222121 2391 VCSIIY 2396
Cdd:cd21473    364 VVAVLY 369
deltaCoV_Nsp8 cd21833
deltacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...
3184-3372 6.99e-132

deltacoronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) region of deltacoronaviruses that include White-eye coronavirus HKU16 and Quail coronavirus UAE-HKU30, among others. 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. SARS-CoV Nsp8 forms a 8:8 hexadecameric supercomplex with Nsp7 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp8 forms a 1:2 heterotrimer with Nsp7. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.


:

Pssm-ID: 409260  Cd Length: 189  Bit Score: 411.33  E-value: 6.99e-132
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3184 AVADININLDSYRIYKEADAIYKRSVEMNESPQEQKKKLKAVNIAKAEWEREAASQRKLEKLADAAMKSMYLAERAEDRR 3263
Cdd:cd21833      1 AVVDANINLDSYRIYKEADAAYKKSVELNEPPQEQKKKLKAVNIAKAEWEREAASQRKLEKLADAAMKSMYLAERAEDRR 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3264 IKLTSGLTAMLYHMLRRLDSDRVKALFECAKAQILPIHAVVGISNDNLKVIFNDKDSYSHYVEGNTLIHKGVRYTIVKKL 3343
Cdd:cd21833     81 IKLTSGLTAMLYHMLRRLDSDRVKALFECAKQQILPIHAIVGVSNDNLKVIFNDKESYLQYVDGNTLIYKGVRYTIVKKL 160
                          170       180
                   ....*....|....*....|....*....
gi 1818222121 3344 SLDNAPIEGVPEEFPVVVETVREGVPQLQ 3372
Cdd:cd21833    161 SLDNAPIEGIPEEYPVVVETIREGVPQIQ 189
deltaCoV_Nsp10 cd21903
deltacoronavirus non-structural protein 10; This model represents the non-structural protein ...
3483-3610 2.67e-100

deltacoronavirus non-structural protein 10; This model represents the non-structural protein 10 (Nsp10) of deltacoronaviruses, including Thrush coronavirus HKU12-600 and Wigeon coronavirus HKU20. 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Coronaviruses cap their mRNAs; RNA cap methylation may involve at least three proteins: Nsp10, Nsp14, and Nsp16. Nsp10 serves as a cofactor for both Nsp14 and Nsp16. Nsp14 consists of 2 domains with different enzymatic activities: an N-terminal ExoN domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. The association of Nsp10 with Nsp14 enhances Nsp14's exoribonuclease (ExoN) activity, and not its N7-Mtase activity. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The Nsp10/Nsp14 complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end, mimicking an erroneous replication product, and may function in a replicative mismatch repair mechanism. Nsp16 Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) acts sequentially to Nsp14 MTase in RNA capping methylation and methylates the RNA cap at the ribose 2'-O position; it catalyzes the conversion of the cap-0 structure on m7GpppA-RNA to a cap-1 structure. The association of Nsp10 with Nsp16 enhances Nsp16's 2'OMTase activity, possibly through enhanced RNA binding affinity. Additionally, transmissible gastroenteritis virus (TGEV) Nsp10, Nsp16 and their complex can interact with DII4, which normally binds to Notch receptors; this interaction may disturb Notch signaling. Nsp10 also binds 2 zinc ions with high affinity.


:

Pssm-ID: 409328  Cd Length: 128  Bit Score: 317.96  E-value: 2.67e-100
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3483 SGTQIEYQQNASLLTYLAFAVDPKTAYLKHLADGGSPIQGCIQMIATMGPGFAVTTKPQPNEHQYSYGGASICLYCRAHI 3562
Cdd:cd21903      1 NGTQIEYQENASLLTYLAFAVDPKEAYLKHLADGGKPIQGCIQMIAPLGPGFAVTTKPQPNEHQYSYGGASICLYCRAHI 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1818222121 3563 PHPGVDGRCPYKGRFVHIDKDKEPVSFALTHEPCSSCQRWVNYDCTCG 3610
Cdd:cd21903     81 PHPGVDGRCPYKGRFVHIDKDKEPVSFALTHEPCNSCQRWVNYDCTCG 128
deltaCoV_Nsp9 cd21900
deltacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...
3373-3481 4.50e-68

deltacoronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) from deltacoronaviruses such as the Porcine delta coronavirus (PDCoV) Porcine coronavirus HKU15. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for coronavirus replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication.


:

Pssm-ID: 409333  Cd Length: 109  Bit Score: 225.01  E-value: 4.50e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3373 NNELCLRNVFTAQNTAQDFNGNESTVKSFYVTRTGKKILVAITSTKDNLKTVTCLTETGKTVLNLDPPMRFAHTVGGKQS 3452
Cdd:cd21900      1 NNELCLRNVFTAQNTASDGNGNESTAKSFYVSRTGKKILVAVTSTKDNLKTVTCDTDTGKVVLNLDPPMRFSHVVGGKQS 80
                           90       100
                   ....*....|....*....|....*....
gi 1818222121 3453 VVYLYFIQNISSLNRGMVIGHISETTILQ 3481
Cdd:cd21900     81 VVYLYFIQNISSLNRGMVIGHISGTTILQ 109
deltaCoV_Nsp7 cd21829
deltacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...
3088-3183 2.44e-53

deltacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of deltacoronaviruses that include White-eye coronavirus HKU16 and Quail coronavirus UAE-HKU30, among others. 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp7 forms a 2:1 heterotrimer with Nsp8. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.


:

Pssm-ID: 409255  Cd Length: 96  Bit Score: 182.34  E-value: 2.44e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3088 NKILDAKATAVVVANLLEKAGVTNKHAICKKIVKLHNDTLKATTYEEVEVALVKLLSHIIEFLPTDQVDAYLADAANAQH 3167
Cdd:cd21829      1 NKTLDAKATAVVVANLLEKAGVTNKHEVCKKIVKLHNDTLKATTYEEAETSLVKLLAHIIEFLPTDQVDAYLADAVKVQH 80
                           90
                   ....*....|....*.
gi 1818222121 3168 VNTYFDNLLENKAVVQ 3183
Cdd:cd21829     81 LNTYFDSLLENKLVLQ 96
Macro_X_Nsp3-like cd21557
X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The ...
961-1086 4.91e-42

X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The X-domain, also called Mac1, is the macrodomain found in riboviral non-structural protein 3 (Nsp3), including the Nsp3 of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) as well as SARS-CoV-2, and other coronaviruses (alpha-, beta-, gamma-, and deltacoronavirus), among others. The SARS-CoV-2 Nsp3 Mac1 is highly conserved among all CoVs, and binds to and hydrolyzes mono-ADP-ribose (MAR) from target proteins. It appears to counter host-mediated antiviral ADP-ribosylation, a post-translational modification that is part of the host response to viral infections. Mac1 is essential for pathogenesis in multiple animal models of CoV infection, implicating it as a virulence factor and potential therapeutic target. Assays show that the de-MARylating activity leads to a rapid loss of substrate, and that Mac1 could not hydrolyze poly-ADP-ribose; thus, Mac1 is a MAR-hydrolase (mono-ADP ribosylhydrolase). Mac1 was originally named ADP-ribose-1"-phosphatase (ADRP) based on data demonstrating that it could remove the phosphate group from ADP-ribose-1"-phosphate; however, activity was modest and was unclear why this would impact a virus infection. This family also includes the X-domain of Avian infectious bronchitis virus (IBV) strain Beaudette coronavirus that does not bind ADP-ribose; the triple glycine sequence found in the X-domains of SARS-CoV and human coronavirus 229E (HCoV229E), which are involved in ADP-ribose binding, is not conserved in the IBV X-domain. SARS-CoVs have two other macrodomains referred to as the SUD-N (N-terminal subdomain, or Mac2) and SUD-M (middle SUD subdomain, or Mac3) of the SARS-unique domain (SUD), which also do not bind ADP-ribose; these bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). SARS-CoV SUD-N and SUD-M are not included in this group.


:

Pssm-ID: 438957  Cd Length: 127  Bit Score: 151.55  E-value: 4.91e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  961 NSVLVNPANAQLTNGGGAARAIAKLAGPKYQEYCNSVApISGPLTTDSFDAKK--LGVACILHVVPPKGSDPNVQELLYQ 1038
Cdd:cd21557      1 EDVVVNAANENLKHGGGVAGAIYKATGGAFQKESDYIK-KNGPLKVGTAVLLPghGLAKNIIHVVGPRKRKGQDDQLLAA 79
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1818222121 1039 AYKSILTEPAHYVIPILGAGIFGCNPVHSLDAFRKACPSDIGRVTLVT 1086
Cdd:cd21557     80 AYKAVNKEYGSVLTPLLSAGIFGVPPEQSLNALLDAVDTTDADVTVYC 127
CoV_NSP4_C super family cl24800
Coronavirus replicase NSP4, C-terminal; This is the C-terminal domain of the coronavirus ...
2413-2498 2.92e-22

Coronavirus replicase NSP4, C-terminal; This is the C-terminal domain of the coronavirus nonstructural protein 4 (NSP4). NSP4 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. It is a membrane-spanning protein which is thought to anchor the viral replication-transcription complex (RTC) to modified endoplasmic reticulum membranes. This predominantly alpha-helical domain may be involved in protein-protein interactions. It has been shown that in Betacoronavirus, the coexpression of NSP3 and NSP4 results in a membrane rearrangement to induce double-membrane vesicles (DMVs) and convoluted membranes (CMs), playing a critical role in SARS-CoV replication. There are two well conserved amino acid residues (H120 and F121) in NSP4 among Betacoronavirus, essential for membrane rearrangements during interaction with NSP3.


The actual alignment was detected with superfamily member pfam16348:

Pssm-ID: 465099  Cd Length: 92  Bit Score: 93.75  E-value: 2.92e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2413 SSFLDAAKATFVIDNEKYVLLKDLAGAE-FDQYLASYNKYKYFSGTASDKDYDKVCMAFLAKALSSFREGGGSQLYTPPK 2491
Cdd:pfam16348    6 GTFEEAALGTFVIDKESYEKLKNSISLDkFNRYLSLYNKYKYYSGKMDEADYREACCAHLAKALEDFSNSGNDVLYTPPT 85

                   ....*..
gi 1818222121 2492 FAVVQSL 2498
Cdd:pfam16348   86 VSVTSSL 92
MDN1 super family cl34967
Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal ...
492-943 1.77e-05

Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal structure and biogenesis];


The actual alignment was detected with superfamily member COG5271:

Pssm-ID: 444083 [Multi-domain]  Cd Length: 1028  Bit Score: 50.78  E-value: 1.77e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  492 VGNRMLMFTSTGTFLLTKATTKILNKAKYIFDVDPEYPVDVTTSKVVVHEALQQIDTKPARA-----------LEAVDVV 560
Cdd:COG5271     29 AGLDTQSETASEREDKLPDTDKDLLILTDADAASDEGKLLDLKSADGAALSAESDAGASLITaanleegdiagNAADDSA 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  561 VGNTVLQMATDGTAFYPSDGTHASLPGFK------------AGSDELLISFNCDLFDDETNAQINETLAAYELN------ 622
Cdd:COG5271    109 DEESDANAKEDATDDADSSGDAQGDPLATdtlgggdldlatKDGDELLPSLADNDEAAADEGDELAADGDDTLAvadaie 188
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  623 -QLVAPGDSTPRQIATLVVDTLVDAITDHFPEKTIDLPEDYQVFSDHDDLLLAQYHIPD-HLSLYIQAMEGEDDSGDEIC 700
Cdd:COG5271    189 aTPGGTDAVELTATLGATVTTDPGDSVAADDDLAAEEGASAVVEEEDASEDAVAAADETlLADDDDTESAGATAEVGGTP 268
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  701 IEDDD-------YDCPQADENTEGVIPQQWELPDVDKFLLKIQERKTSSDEVLS----VDVYPKPDEVGIDDSASEKKPN 769
Cdd:COG5271    269 DTDDEatddadgLEAAEDDALDAELTAAQAADPESDDDADDSTLAALEGAAEDTeiatADELAAADDEDDDDSAAEDAAE 348
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  770 GDSVLDPEVHPTLESVDVERPTETAN---QAVEDKPSDTTFVVDEV--------QLQESTPEPELRSYEGEFDSDDEIII 838
Cdd:COG5271    349 EAATAEDSAAEDTQDAEDEAAGEAADeseGADTDAAADEADAAADDsaddeeasADGGTSPTSDTDEEEEEADEDASAGE 428
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  839 P------IVPV-----------TPADLKPQTITIKEYFKSEKLETINEgSTESVTQSDDSVDESFVDAESDDPQDPAVYD 901
Cdd:COG5271    429 TedestdVTSAeddiatdeeadSLADEEEEAEAELDTEEDTESAEEDA-DGDEATDEDDASDDGDEEEAEEDAEAEADSD 507
                          490       500       510       520
                   ....*....|....*....|....*....|....*....|..
gi 1818222121  902 DTTIITDSTDVGDEPETTLATIVNTPLTLDNNLPPEAIKQPS 943
Cdd:COG5271    508 ELTAEETSADDGADTDAAADPEDSDEDALEDETEGEENAPGS 549
 
Name Accession Description Interval E-value
TM_Y_deltaCoV_Nsp3_C cd21711
C-terminus of deltacoronavirus non-structural protein 3, including transmembrane and Y domains; ...
1502-1991 0e+00

C-terminus of deltacoronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from deltacoronavirus, including Magpie-robin coronavirus HKU18 and Bulbul coronavirus HKU11, among others. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In the related betacoronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409659  Cd Length: 490  Bit Score: 976.49  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1502 LYYSAQTLFVSLAPFLMLPAVVSLLNSGYTIGTYLYAKTGWPCNYNATQHFDYNSYCAGDLVCQACFDGQDSLHLYPHLR 1581
Cdd:cd21711      1 LFYSAQTIFVSLAPFLMLPAVASLLSSGYTIGTYLYAKTGLPCYYNATQHYDYNSFCAGDLTCQACFDGQDSLHLYKHLR 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1582 VNQQPIQTTDYTVYALSLILLLANMTLVMGTLIVTFFVNFYGVQIPFYGTLLIDYQSALMMTFSVYYFYKVMKFFRHLTH 1661
Cdd:cd21711     81 VNQQPVQTTDYTVYALSIVLLLANPTLVLGTLLVVFFVNFYGVQIPFYGTLQLDYQNTLVMVFSVYYFYKVMKFFRHLAK 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1662 GCKIPTCMVCAKLRTPPTITVETVVQGRKYPSVIETNGGFTICKEHNFYCKDCSLQTPGTFIPTEAIESLSRATRLSVKP 1741
Cdd:cd21711    161 GCKKPTCSICAKKRIPPTITVETVVQGRKYPSVIETNGGFNICKEHNFYCKNCDSQTPGTFIPTEAVESLSRKTRLSVKP 240
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1742 TAPAFLLARDVECQTDVVVARAMHNQNAHVCISKYSDIRTVDQLLKPTPLFSYTPDVIIAADFDNRGSLKTAKELAVVLS 1821
Cdd:cd21711    241 TAPAYLLARDVECQTDVVVARATHNGNAHVCISKYSDIRTVDQLLKPTPLFSYTPDVIIAADFDNAGSLKTAKELAVVLS 320
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1822 MDLKRTIIIIDQAYSRPIDNYQEVASRIEKYYPVAKITPTGDIFTDIKQATNGQASDSAINAAVLAVQRGLDFTIDNPNN 1901
Cdd:cd21711    321 MDLKRTIIIIDQAYSRPIDNYQEVKSRIEKYYPFQKITPTGDIFADIKQATNGQASDSAINAAILAVQRGLDFTIDNPNN 400
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1902 ILPHYAFDFSTLNAEDQSTILESGCAKGNLKGTNVGVVLSASLVTRLSQQAIRVIANAASRNGVTCAVTPSTLVMRGNIA 1981
Cdd:cd21711    401 ILPHYAFDFSTLSAEDQSTLIESGCAKGNLKGTNVGVVLSANLVTRLSQKAIRVIANAASRNGVTCAVTPSTLVLRGNIA 480
                          490
                   ....*....|
gi 1818222121 1982 TQPLTRIKAG 1991
Cdd:cd21711    481 TQPLTRIKAG 490
deltaCoV_Nsp5_Mpro cd21668
deltacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
2503-2804 0e+00

deltacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in deltacoronaviruses. 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. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394889  Cd Length: 302  Bit Score: 644.56  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2503 QAGIKILLHPSGVVERCMVSVVYNGSALNGIWLKNVVYCPRHVIGKFRGDQWTHMVSIADCRDFIVKCPIQGIQLNVQSV 2582
Cdd:cd21668      1 QAGIKILLHPSGVVERCMVSVTYNGSTLNGIWLHNVVYCPRHVIGKYTGSQWQDMVSIADCRDFVIFCPTQGIQLTVQSV 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2583 KMVGALLQLTVHTNNTATPDYKFERLQPGSSMTIACAYDGIVRHVYHVVLQLNNLIYASFLNGACGSVGYTLKGKTLYLH 2662
Cdd:cd21668     81 KMVGAVLQLTVHTKNLHTPDYEFERATPGSSMTIACAYDGIVRNVYHVVLQTNNLIYASFLNGACGSVGYTLKGKTLLLH 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2663 YMHHIEFNNKTHSGTDLEGNFYGPYVDEEVIQQQTAFQYYTDNVVAQLYAHLLTVDARPKWLAQSQISIEDFNSWAANNS 2742
Cdd:cd21668    161 YMHHLEFNNKTHGGTDLHGHFYGPYVDEEVAQHQTAFQYYTDNVVAQIYAHLLTIDAKPKWLASQEISVEDFNEWAANNS 240
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1818222121 2743 FANFPCEQTNMSYIMGLSQTARVPVERILNTIIQLTTNRDGACIMGSYDFECDWTPEMVYNQ 2804
Cdd:cd21668    241 FANFPCESSNMAYLEGLAQTTKVSVGRVLNTIIQLTLNRGGALIMGKPDFECDWTPEMVYNQ 302
deltaCoV_PLPro cd21734
deltacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
1087-1399 0e+00

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: 628.69  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1087 MNKNHLQVWDALNRTIVRTTTDYDQVTTKALTPQGVLEANLFDGEDFVQEPKPGQIYLEVTEEVQNQAKELDLNLQQYCV 1166
Cdd:cd21734      1 LDKNHLQVWDALNRTVVRTTKDFDQVTTKALTPQGVLDANLFDGEDFVQEPKPGQIYLAVTDEVQQQAKELDLTLSQYCV 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1167 YLKTCHHKWVVSRTNGLMHLKQKDNNCFVSAGVNLFQNTAYQLRPAIDALYREYLNGNPNRFVAWIYASTNRRVGEMGCP 1246
Cdd:cd21734     81 YLKYCHHKWSVSRTNGLMHLKQKDNNCFVSAAINLFQNTHYQLRPAIDALYQEYLNGNPSRFVAWIYASTNQEIGEMGCP 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1247 QQVISLLVSNSDAAFSATTACCNTYFNHTGVISVAREYDPIQPKVYCMKCDVWTPFTPQSGKGAVAIGTSADEPTGPAIK 1326
Cdd:cd21734    161 QQVLSLLVNNSNAKFSGTTACCGTYFTHDGVISVAREYDPLQPKVYCMKCDVWTPFTPQSGKGIVVIGSSAEEPTGPAIK 240
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1818222121 1327 FAAAHCWYTNGKKTVNGYDTKANVVATYHRFDVPKPQLVEDVVALPTKNDFEVLNVEELPQDSVLHLDPPPVQ 1399
Cdd:cd21734    241 FAAAHCWYTNGKKTVNGYDTKANVVAIYHKFDVPKPQPVEDVVTLPTKNDFEVLKVEEIPQDSVLNLDPPEVQ 313
deltaCoV-Nsp6 cd21561
deltacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...
2792-3087 0e+00

deltacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.


Pssm-ID: 394847  Cd Length: 296  Bit Score: 573.54  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2792 FECDWTPEMVYNQAPISLQSGVVKKTCTWFFHFVFMAITMLLAAMHVFPVHLYPIVLPCFTVVAFLLTLTIKHTVVFTTT 2871
Cdd:cd21561      1 FECDWTPEMVYNQAPINLQSGVVKKTCMWFFHFLFMAVIFLLAALHVFPVHLYPIVLPVFTILAFLLTLTIKHTVVFTTT 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2872 YLLPSLLMMVVNANTFWIPNTFLRTCYETIFGSPIAQRLYGYTVALYMLIYAGLAINYTLKTLRYRATSFLSFCMQWFQY 2951
Cdd:cd21561     81 YLLPSLLMMVVNANTFWIPNTYLRSIYEYVFGSFISERLYGYTVALYILVYAQLAINYTLRTRRYRATSFISFCMQALQY 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2952 GYVAHIAYKLLNKPWTESLLFTAFTMLTSHPLLAALSWWLAGRVTLPIIMPDLAIRVLAYNVIGYVICVRFGLMWLANRF 3031
Cdd:cd21561    161 GYVAHIVYRLLTTPWTEGLLFTAFSLLTSHPLLAALSWWLAGRIPLPLILPDLAIRVIVYYVIGYVMCMRFGLFWLINKF 240
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1818222121 3032 TTVPMGTYQYMVSVEQLKYMMAVKMSPPRNAFEVLIANIRLLGLGGNRNIAVSTVQ 3087
Cdd:cd21561    241 TTIPMGTYKYMVSIEQLKYMMAVKMSPPRNAFEVLWANIRLLGLGGNRNIAVSTVQ 296
cv_gamma-delta_Nsp2_IBV-like cd21512
gamma- and deltacoronavirus non-structural protein 2 (Nsp2), similar to IBV Nsp2 and related ...
7-379 0e+00

gamma- and deltacoronavirus non-structural protein 2 (Nsp2), similar to IBV Nsp2 and related proteins; Coronavirus non-structural proteins (Nsps) are encoded in ORF1a and ORF1b. Post infection, the genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (pp), pp1a and pp1ab, which are then autoproteolytically cleaved by two viral proteases Nsp3 and Nsp5 into smaller subunits. Nsp2 is one of these cleaved subunits. The functions of Nsp2 remain unclear. This gamma- and deltacoronavirus family includes Avian infectious bronchitis virus (IBV) Nsp2 which has been shown to be a weak protein kinase R (PKR) antagonist, which may suggest that it plays a role in interfering with intracellular immunity. This family may be distantly related to a family of alpha- and betacoronavirus Nsp2, which includes severe acute respiratory syndrome coronavirus (SARS-CoV) Nsp2, and Murine hepatitis virus (MHV) Nsp2 (also known as p65). SARS-CoV Nsp2, rather than playing a role in viral replication, may be involved in altering the host cell environment; deletion of Nsp2 from the SARS-CoV genome results in only a modest reduction in viral titers. It has been shown to interact with two host proteins, prohibitin 1 (PHB1) and PHB2, which have been implicated in cellular functions, including cell-cycle progression, cell migration, cellular differentiation, apoptosis, and mitochondrial biogenesis. MHV Nsp2/p65, different from SARS-CoV Nsp2, may play an important role in the viral life cycle.


Pssm-ID: 394837  Cd Length: 365  Bit Score: 561.65  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121    7 KRDAIALPENVPPPLQLFIHVAAAEEGHPKVTTYLGNYNLYATKAPPGVQVLSAKTSLTDFENVFGAQPTLRSIRNLVCE 86
Cdd:cd21512      1 KRHPIVLPPDAPPPLQLFIRVAAAGEGHPFDTVYLGNYNLIGVKAVPGVQVLDANTSLADFENLFGVQPTLRAYRNLLKD 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121   87 ArsAEWTTSKNAFALKATQLDYSDAVLRAMIRFCPPKVSTLAAFALFGRLVKIEDKELAELARDTALELAYTAKIGTSLA 166
Cdd:cd21512     81 A--AQWSLSKEALAAKAKQLTESDDVLRAIILYGAARVSALASLALFGRVVKIDDVELGDLAEDVALELAYTGKIGRALA 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  167 DTRSVSLIHKDAYLTLSNEVVGVTFTAALMAKATTVNGAMQYSNFYLYPRATIKVTDGKAEAIATKPLPAATKGKPITED 246
Cdd:cd21512    159 DAKAIELPQTDAYLTLNFAVCGKVFTSTLLAQATPVNGALQYSDFVLWPLATAKATDGKLQPLAGKPLPASQKGAFFTED 238
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  247 VNLLPDYQQLLVDQVTGTEVKVGALTYVKTTDLPPLYFPKVKGGVvgiALKQQGTAAKKLNVVFHAQPDDVLLAFIQLQQ 326
Cdd:cd21512    239 VNLVPDYQQLAPDQVEGDEVVVGGITYIKTTDVPPLYYPRVKGGV---LLKPQGTADKKVNVVFHAAPSDVLLAFIQLQL 315
                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1818222121  327 FLNRTSDSSVEITDCQSYEVSPTVTVKIGpskPGDVIVATDEEYLKCFETPEV 379
Cdd:cd21512    316 FLVRTSGSCVEVTDDDVYAVPPSVTVSIG---PGDVVVNDDEEYVKCFETPVV 365
CoV_NSP3_C pfam19218
Coronavirus replicase NSP3, C-terminal; This family represents the C-terminal region of ...
1541-1976 7.03e-156

Coronavirus replicase NSP3, C-terminal; This family represents the C-terminal region of non-structural protein NSP3 (also known as nsp3). NSP3 is the product of ORF1a. It is found in human SARS coronavirus polyprotein 1a and 1ab, and in related coronavirus polyproteins. It is a multifunctional protein comprising up to 16 different domains and regions. NSP3 binds to viral RNA, nucleocapsid protein, as well as other viral proteins and participates in polyprotein processing.


Pssm-ID: 466002  Cd Length: 463  Bit Score: 492.24  E-value: 7.03e-156
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1541 GWPCNYN----ATQHFDYNSYCAGDLVCQACFDGQDSLHLYPHLRVNQQPIQTT---DYTVYALSLILLLANMTLVMGTL 1613
Cdd:pfam19218    1 GYPCDGYvdgySNSSFNKSDYCNGSILCKACLSGYDSLHDYPHLKVVQQPVKDPlfvDVTPLFYFAIELFVALALFGGTF 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1614 IVTFFVNFYGVQIPFYGTLL-----------IDYQSALMMTFSVYYFYKVMKFFRHLTHGCKIPTCMVCAKLRTPPTITV 1682
Cdd:pfam19218   81 VRVFLLYFLQQYVNFFGVYLglqdyswfltlIPFDSFLREYVVLFYVIKLYRFLKHVVFGCKKPSCLACSKSARLTRVPV 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1683 ETVVQGRKYPSVIETNGGFTICKEHNFYCKDCSLQTPG-TFIPTEAIESLSRATRLSVKPTAPAFLLARDVECQTDVV-- 1759
Cdd:pfam19218  161 STVVNGSKKSFYVNANGGTKFCKKHNFFCKNCDSYGPGnTFINDEVAEDLSNVTKRSVKPTDPAYYEVDKVEFQNGFYyl 240
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1760 -VARAMHNQNAHVCISKYSDIRTVDQLLKptplFSYTPDVIIAADfDNRGSLKTAKELAVVLSMDLKRTIIIIDQAYSRP 1838
Cdd:pfam19218  241 ySGREFWRYYFDVTVSKYSDKEVLKNCNI----KGYPLDDFIVYN-SNGSNLAQAKNACVYYSQLLCKPIKLVDSNLLSS 315
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1839 IDNYQEVASRIEKYYP-------------VAKITPTG-DIFTDIKqatngqaSDSAINAAVLAVQRGLDFTIDNPNNILP 1904
Cdd:pfam19218  316 LGDSVDVNGALHDAFVevllnsfnvdlskCKTLIECKkDLGSDVD-------TDSFVNAVLNAHRYDVLLTDDSFNNFVP 388
                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1818222121 1905 HYAFDFSTLNAEDQSTILESGCA---KGNLKGTNVGVVLSASLVTRLSQQAIRVIANAASRNGVTCAVTPSTLVM 1976
Cdd:pfam19218  389 TYAKPEDSLSTHDLAVCIRFGAKivnHNVLKKENVPVVWSADDFLKLSEEARKYIVKTAKKKGVTFMLTFNTNRM 463
Peptidase_C30 pfam05409
Coronavirus endopeptidase C30; This Coronavirus (CoV) domain, peptidase C30, is also known as ...
2532-2810 2.65e-134

Coronavirus endopeptidase C30; This Coronavirus (CoV) domain, peptidase C30, is also known as 3C-like proteinase (3CL-pro), or CoV main protease (M-pro) domain. CoV M-pro is a dimer where each subunit is composed of three domains I, II and III,,. Domains I and II consist of six-stranded antiparallel beta barrels and together resemble the architecture of chymotrypsin, and of picornaviruses 3C proteinases. The substrate-binding site is located in a cleft between these two domains. The catalytic site is situated at the centre of the cleft. A long loop connects domain II to the C-terminal domain (domain III). This latter domain has been implicated in the proteolytic activity of M-pro. In the active site of M-pro, Cys and His form a catalytic dyad,.


Pssm-ID: 398852  Cd Length: 274  Bit Score: 421.85  E-value: 2.65e-134
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2532 GIWLKNVVYCPRHVIGKFRG--DQWTHMVSIADCRDFIVKCpiQGIQLNVQSVKMVGALLQLTVHTNNTATPDYKFERLQ 2609
Cdd:pfam05409    1 GLWLGDTVYCPRHVIGSFTGmlPQYEHLLSIARNHDFCVVS--GGVQLTVVSAKMQGAILVLKVHTNNPNTPKYKFVRLK 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2610 PGSSMTIACAYDGIVRHVYHVVLQLNNLIYASFLNGACGSVGYTLKGKTLYLHYMHHIEFNNKTHSGTDLEGNFYGPYVD 2689
Cdd:pfam05409   79 PGESFTILAAYDGCPQGVYHVTMRSNHTIKGSFLNGACGSVGYNLKGGTVCFVYMHHLELPNGSHTGTDLEGVFYGPYVD 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2690 EEVIQQQTAFQYYTDNVVAQLYAHLLTVdarPKW-LAQSQISIEDFNSWAANNSFANFPCEQTnmsyIMGLSQTARVPVE 2768
Cdd:pfam05409  159 EEVAQLEGTDQTYTDNVVAWLYAAIING---PRWfLASTTVSLEDFNAWAMTNGFTPFPCEDA----ILGLAAKTGVSVE 231
                          250       260       270       280
                   ....*....|....*....|....*....|....*....|...
gi 1818222121 2769 RILNTIIQLTTNRDGACIMGSYDFECDWTPEMVYNQ-APISLQ 2810
Cdd:pfam05409  232 RLLAAIKVLNNGFGGRTILGSPSLEDEFTPEDVYNQmAGVTLQ 274
cv_Nsp4_TM cd21473
coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in ...
2001-2396 5.13e-134

coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in coronavirus-induced membrane remodeling. In order to assemble the replication-transcription complex (RTC), coronavirus induces the rearrangement of host endoplasmic reticulum (ER) membrane into double membrane vesicles (DMVs), zippered ER, or ER spherules. DMV formation has been observed in SARS-CoV cells overexpressing the three transmembrane-containing non-structural proteins of viral replicase polyprotein 1ab: Nsp3, Nsp4 and Nsp6. Together, Nsp3, Nsp4, and Nsp6 have the ability to induce the formation of DMVs that are similar to those seen in SARS-CoV-infected cells.


Pssm-ID: 394836  Cd Length: 376  Bit Score: 425.85  E-value: 5.13e-134
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2001 CVILALAIVYFAAMAFGFLASQITLNTVPTiksdiraSTFYVVRDGVLDTVRSNDKCFANKFLAFDSFIQAPY----TNS 2076
Cdd:cd21473      1 FLWLLLAAILLYAFLPSYSVFTVTVSSFPG-------YDFKVIENGVLRDIRSTDTCFANKFVNFDSWYQAKYgsvpTNS 73
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2077 PDCPVVVGVVEVTTHSIPGIPAGVIHRDGLILNIYEQslyethqrqsmvrdalslktanlfNLGKRVVVGYTQHEVVVGT 2156
Cdd:cd21473     74 KSCPIVVGVIDDVRGSVPGVPAGVLLVGKTLVHFVQT------------------------VFFGDTVVCYTPDGVITYD 129
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2157 SYFNSPALFNAKCTFLQYQDTRQLYCYDTVPTEH-KLYSDVLPHVEYKAIDINgdlvPFKIPEQIM-FYPHIVRYTSNSY 2234
Cdd:cd21473    130 SFYTSACVFNSACTYLTGLGGRQLYCYDTGLVEGaKLYSDLLPHVRYKLVDGN----YIKFPEVILeGGPRIVRTLATTY 205
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2235 CRMGHCFNTNPGICISFTDEFPYSENV-KPGVYCADTSLQLFSNLVLGTVSGIHIFTSTAALLGSTIVIILCVVAVLAVQ 2313
Cdd:cd21473    206 CRVGECEDSKAGVCVSFDGFWVYNNDYyGPGVYCGDGLFDLLTNLLSGFFQPVSVFALSGQLLFNTIVAILAVLACYYVQ 285
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2314 RFFKEY---TTFVMYTCGLAFVNIVGIALMYKCLvFAIFYYAIYLYFVLTFPSFkRNVALFYFAVVIVPHVSNMQLLALI 2390
Cdd:cd21473    286 KFKRAFgdmSVVVVTVVAAALVNNVLYVVTQNPL-LMIVYAVLYFYATLYLTYE-RAWIMHLGWVVAYGPIAPWWLLALY 363

                   ....*.
gi 1818222121 2391 VCSIIY 2396
Cdd:cd21473    364 VVAVLY 369
deltaCoV_Nsp8 cd21833
deltacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...
3184-3372 6.99e-132

deltacoronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) region of deltacoronaviruses that include White-eye coronavirus HKU16 and Quail coronavirus UAE-HKU30, among others. 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. SARS-CoV Nsp8 forms a 8:8 hexadecameric supercomplex with Nsp7 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp8 forms a 1:2 heterotrimer with Nsp7. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.


Pssm-ID: 409260  Cd Length: 189  Bit Score: 411.33  E-value: 6.99e-132
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3184 AVADININLDSYRIYKEADAIYKRSVEMNESPQEQKKKLKAVNIAKAEWEREAASQRKLEKLADAAMKSMYLAERAEDRR 3263
Cdd:cd21833      1 AVVDANINLDSYRIYKEADAAYKKSVELNEPPQEQKKKLKAVNIAKAEWEREAASQRKLEKLADAAMKSMYLAERAEDRR 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3264 IKLTSGLTAMLYHMLRRLDSDRVKALFECAKAQILPIHAVVGISNDNLKVIFNDKDSYSHYVEGNTLIHKGVRYTIVKKL 3343
Cdd:cd21833     81 IKLTSGLTAMLYHMLRRLDSDRVKALFECAKQQILPIHAIVGVSNDNLKVIFNDKESYLQYVDGNTLIYKGVRYTIVKKL 160
                          170       180
                   ....*....|....*....|....*....
gi 1818222121 3344 SLDNAPIEGVPEEFPVVVETVREGVPQLQ 3372
Cdd:cd21833    161 SLDNAPIEGIPEEYPVVVETIREGVPQIQ 189
deltaCoV_Nsp10 cd21903
deltacoronavirus non-structural protein 10; This model represents the non-structural protein ...
3483-3610 2.67e-100

deltacoronavirus non-structural protein 10; This model represents the non-structural protein 10 (Nsp10) of deltacoronaviruses, including Thrush coronavirus HKU12-600 and Wigeon coronavirus HKU20. 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Coronaviruses cap their mRNAs; RNA cap methylation may involve at least three proteins: Nsp10, Nsp14, and Nsp16. Nsp10 serves as a cofactor for both Nsp14 and Nsp16. Nsp14 consists of 2 domains with different enzymatic activities: an N-terminal ExoN domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. The association of Nsp10 with Nsp14 enhances Nsp14's exoribonuclease (ExoN) activity, and not its N7-Mtase activity. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The Nsp10/Nsp14 complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end, mimicking an erroneous replication product, and may function in a replicative mismatch repair mechanism. Nsp16 Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) acts sequentially to Nsp14 MTase in RNA capping methylation and methylates the RNA cap at the ribose 2'-O position; it catalyzes the conversion of the cap-0 structure on m7GpppA-RNA to a cap-1 structure. The association of Nsp10 with Nsp16 enhances Nsp16's 2'OMTase activity, possibly through enhanced RNA binding affinity. Additionally, transmissible gastroenteritis virus (TGEV) Nsp10, Nsp16 and their complex can interact with DII4, which normally binds to Notch receptors; this interaction may disturb Notch signaling. Nsp10 also binds 2 zinc ions with high affinity.


Pssm-ID: 409328  Cd Length: 128  Bit Score: 317.96  E-value: 2.67e-100
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3483 SGTQIEYQQNASLLTYLAFAVDPKTAYLKHLADGGSPIQGCIQMIATMGPGFAVTTKPQPNEHQYSYGGASICLYCRAHI 3562
Cdd:cd21903      1 NGTQIEYQENASLLTYLAFAVDPKEAYLKHLADGGKPIQGCIQMIAPLGPGFAVTTKPQPNEHQYSYGGASICLYCRAHI 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1818222121 3563 PHPGVDGRCPYKGRFVHIDKDKEPVSFALTHEPCSSCQRWVNYDCTCG 3610
Cdd:cd21903     81 PHPGVDGRCPYKGRFVHIDKDKEPVSFALTHEPCNSCQRWVNYDCTCG 128
CoV_NSP4_N pfam19217
Coronavirus replicase NSP4, N-terminal; This is the N-terminal domain of the coronavirus ...
2018-2387 3.02e-97

Coronavirus replicase NSP4, N-terminal; This is the N-terminal domain of the coronavirus nonstructural protein 4 (NSP4). NSP4 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. NSP4 is a membrane-spanning protein which is thought to anchor the viral replication-transcription complex to modified endoplasmic reticulum membranes. This N-terminal region represents the membrane spanning region, covering four transmembrane regions.


Pssm-ID: 466001  Cd Length: 351  Bit Score: 318.83  E-value: 3.02e-97
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2018 FLASQITLNTVPTIKSDiRASTFYVVRDGVLDTVRSNDKCFANKFLAFDSFIQA---PYTNSPDCPVVV-GVVEVTTHSI 2093
Cdd:pfam19217    1 YALSPTFFNTVVYFVSD-PVYDFKVIENGVLRDFRSTDTCFHNKFDNFDSWHQAkfgSPTNSRSCPIVVgVVDEVVGRVV 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2094 PGIPAGVIHRDGLILNIyeqslyethqrqsmvrdalslKTANLFNLGKrvvVGYTQHEVVVGTSYFNSPALFNAKCTFLQ 2173
Cdd:pfam19217   80 PGVPAGVALVGGTILHF---------------------VTRVFFGAGN---VCYTPSGVVTYESFSASACVFNSACTTLT 135
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2174 -YQDTRQLYCYD-TVPTEHKLYSDVLPHVEYKAIDinGDLVPFkiPEQIM-FYPHIVRYTSNSYCRMGHCFNTNPGICIS 2250
Cdd:pfam19217  136 gLGGTRVLYCYDdGLVEGAKLYSDLVPHVRYKLVD--GNYVKL--PEVLFrGGFRIVRTLATTYCRVGECEDSKAGVCVG 211
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2251 FTDEFPYSENVKPGVYCADTSLQLFSNLVLGTVSGIHIFTSTAALLGSTIV--IILCV-VAVLAVQRFFKEYTTFVMYTC 2327
Cdd:pfam19217  212 FDRSFVYNNDFGPGVYCGSGFLSLLTNVFSGFNTPISVFALTGQLMFNCVValIAVCVcYYVLKFKRAFGDYSTGVLTVV 291
                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2328 GLAFVNIVGIALMYKCLVFAIFYYAIYLYFVLTFPSFKRNVALFYFAVVIVPHVSNMQLL 2387
Cdd:pfam19217  292 LATLVNNLSYFVTQVNPVLMIVYAVLYFYATLYVTPEYAWIWHLGFLVAYVPLAPWWVLL 351
CoV_NSP6 pfam19213
Coronavirus replicase NSP6; This entry represents proteins found in Coronaviruses and includes ...
2831-3087 4.67e-91

Coronavirus replicase NSP6; This entry represents proteins found in Coronaviruses and includes the Non-structural Protein 6 (NSP6). Coronaviruses encode large replicase polyproteins which are proteolytically processed by viral proteases to generate mature Nonstructural Proteins (NSPs). NSP6 is a membrane protein containing 6 transmembrane domains with a large C-terminal tail. NSP6 from the avian coronavirus, infectious bronchitis virus (IBV) and the mouse hepatitis virus (MHV) have been shown to localize to the ER and to generate autophagosomes. Coronavirus NSP6 proteins have also been shown to limit autophagosome expansion. This may favour coronavirus infection by reducing the ability of autophagosomes to deliver viral components to lysosomes for degradation. NSP6 from IBV, MHV and severe acute respiratory syndrome coronavirus (SARS-CoV) have also been found to activate autophagy.


Pssm-ID: 465997  Cd Length: 260  Bit Score: 297.24  E-value: 4.67e-91
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2831 MLLAAMHVFPVHLYPIVLPCFTVVAFLLTLTIKHTVVFTTTYLLPSLLMMVVNANTFW-IPNTFLRTCYETifgspiAQR 2909
Cdd:pfam19213    2 LMYTALYWLPPNLITPVLPVLTCVSAILTLFIKHKVLFLTTFLLPSVVVMAYYNFTWDyYPNSFLRTVYDY------HFS 75
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2910 LYGYTVALYMLIYAGLAINYT-----LKTLRYRATSFLSFCMQWfqYGYVahIAYKLLNKPWTESLLFTAFTMLTSHPLL 2984
Cdd:pfam19213   76 LTSFDLQGYFNIASCVFVNVLhtyrfVRSKYSIATYLVSLVVSV--YMYV--IGYALLTATDVLSLLFMVLSLLTSYWYV 151
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2985 AALSWWLAGRVTLPI------IMPDLAIRVLAYNVIGYVICVRFGLMWLANRFTTVPMGTYQYMVSVEQLKYMMAVKMSP 3058
Cdd:pfam19213  152 GAIAYKLAKYIVVYVppsliaVFGDIKVVLLVYVCIGYVCCVYFGILYWINRFTKLTLGVYDFKVSAAEFKYMVANGLSA 231
                          250       260
                   ....*....|....*....|....*....
gi 1818222121 3059 PRNAFEVLIANIRLLGLGGNRNIAVSTVQ 3087
Cdd:pfam19213  232 PRNVFEALILNFKLLGIGGNRTIKISTVQ 260
deltaCoV_Nsp9 cd21900
deltacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...
3373-3481 4.50e-68

deltacoronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) from deltacoronaviruses such as the Porcine delta coronavirus (PDCoV) Porcine coronavirus HKU15. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for coronavirus replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication.


Pssm-ID: 409333  Cd Length: 109  Bit Score: 225.01  E-value: 4.50e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3373 NNELCLRNVFTAQNTAQDFNGNESTVKSFYVTRTGKKILVAITSTKDNLKTVTCLTETGKTVLNLDPPMRFAHTVGGKQS 3452
Cdd:cd21900      1 NNELCLRNVFTAQNTASDGNGNESTAKSFYVSRTGKKILVAVTSTKDNLKTVTCDTDTGKVVLNLDPPMRFSHVVGGKQS 80
                           90       100
                   ....*....|....*....|....*....
gi 1818222121 3453 VVYLYFIQNISSLNRGMVIGHISETTILQ 3481
Cdd:cd21900     81 VVYLYFIQNISSLNRGMVIGHISGTTILQ 109
CoV_NSP10 pfam09401
Coronavirus RNA synthesis protein NSP10; Non-structural protein 10 (NSP10) is involved in RNA ...
3494-3610 1.01e-62

Coronavirus RNA synthesis protein NSP10; Non-structural protein 10 (NSP10) is involved in RNA synthesis. It is synthesized as a polyprotein whose cleavage generates many non-structural proteins. NSP10 contains two zinc binding motifs and forms two anti-parallel helices which are stacked against an irregular beta sheet. A cluster of basic residues on the protein surface suggests a nucleic acid-binding function. NSP10 interacts with NSP14 and NSP16 and regulates their respective ExoN and 2-O-MTase activities. When binding to the N-terminal of NSP14, nsp10 allows the ExoN active site to adopt a stably closed conformation and is an allosteric regulator that stabilizes NSP16. The residue Tyr-96 plays a crucial role in the NSP10-NSP16/NSP14 interaction. This residue is specific for SARS-CoV NSP10 and is a phenylalanine in most other Coronavirus homologs.


Pssm-ID: 462788  Cd Length: 119  Bit Score: 210.37  E-value: 1.01e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3494 SLLTYLAFAVDPKTAYLKHLADGGSPIQGCIQMIAT-MGPGFAVTTKPQPNEHQYSYGGASICLYCRAHIPHPGVDGRCP 3572
Cdd:pfam09401    1 SLLSLCAFAVDPAKAYLDYLAQGGQPITNCVKMLCNhAGTGMAITVKPEANTDQDSYGGASVCLYCRAHIEHPNVDGLCQ 80
                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1818222121 3573 YKGRFVHIDKD-KEPVSFALTHEPCSSCQRWVNYDCTCG 3610
Cdd:pfam09401   81 LKGKFVQIPTGtKDPVSFCLTNTVCTVCGCWLGYGCSCD 119
deltaCoV_Nsp7 cd21829
deltacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...
3088-3183 2.44e-53

deltacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of deltacoronaviruses that include White-eye coronavirus HKU16 and Quail coronavirus UAE-HKU30, among others. 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp7 forms a 2:1 heterotrimer with Nsp8. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.


Pssm-ID: 409255  Cd Length: 96  Bit Score: 182.34  E-value: 2.44e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3088 NKILDAKATAVVVANLLEKAGVTNKHAICKKIVKLHNDTLKATTYEEVEVALVKLLSHIIEFLPTDQVDAYLADAANAQH 3167
Cdd:cd21829      1 NKTLDAKATAVVVANLLEKAGVTNKHEVCKKIVKLHNDTLKATTYEEAETSLVKLLAHIIEFLPTDQVDAYLADAVKVQH 80
                           90
                   ....*....|....*.
gi 1818222121 3168 VNTYFDNLLENKAVVQ 3183
Cdd:cd21829     81 LNTYFDSLLENKLVLQ 96
Macro_X_Nsp3-like cd21557
X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The ...
961-1086 4.91e-42

X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The X-domain, also called Mac1, is the macrodomain found in riboviral non-structural protein 3 (Nsp3), including the Nsp3 of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) as well as SARS-CoV-2, and other coronaviruses (alpha-, beta-, gamma-, and deltacoronavirus), among others. The SARS-CoV-2 Nsp3 Mac1 is highly conserved among all CoVs, and binds to and hydrolyzes mono-ADP-ribose (MAR) from target proteins. It appears to counter host-mediated antiviral ADP-ribosylation, a post-translational modification that is part of the host response to viral infections. Mac1 is essential for pathogenesis in multiple animal models of CoV infection, implicating it as a virulence factor and potential therapeutic target. Assays show that the de-MARylating activity leads to a rapid loss of substrate, and that Mac1 could not hydrolyze poly-ADP-ribose; thus, Mac1 is a MAR-hydrolase (mono-ADP ribosylhydrolase). Mac1 was originally named ADP-ribose-1"-phosphatase (ADRP) based on data demonstrating that it could remove the phosphate group from ADP-ribose-1"-phosphate; however, activity was modest and was unclear why this would impact a virus infection. This family also includes the X-domain of Avian infectious bronchitis virus (IBV) strain Beaudette coronavirus that does not bind ADP-ribose; the triple glycine sequence found in the X-domains of SARS-CoV and human coronavirus 229E (HCoV229E), which are involved in ADP-ribose binding, is not conserved in the IBV X-domain. SARS-CoVs have two other macrodomains referred to as the SUD-N (N-terminal subdomain, or Mac2) and SUD-M (middle SUD subdomain, or Mac3) of the SARS-unique domain (SUD), which also do not bind ADP-ribose; these bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). SARS-CoV SUD-N and SUD-M are not included in this group.


Pssm-ID: 438957  Cd Length: 127  Bit Score: 151.55  E-value: 4.91e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  961 NSVLVNPANAQLTNGGGAARAIAKLAGPKYQEYCNSVApISGPLTTDSFDAKK--LGVACILHVVPPKGSDPNVQELLYQ 1038
Cdd:cd21557      1 EDVVVNAANENLKHGGGVAGAIYKATGGAFQKESDYIK-KNGPLKVGTAVLLPghGLAKNIIHVVGPRKRKGQDDQLLAA 79
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1818222121 1039 AYKSILTEPAHYVIPILGAGIFGCNPVHSLDAFRKACPSDIGRVTLVT 1086
Cdd:cd21557     80 AYKAVNKEYGSVLTPLLSAGIFGVPPEQSLNALLDAVDTTDADVTVYC 127
CoV_NSP8 pfam08717
Coronavirus replicase NSP8; Viral NSP8 (non structural protein 8) forms a hexadecameric ...
3184-3340 2.87e-35

Coronavirus replicase NSP8; Viral NSP8 (non structural protein 8) forms a hexadecameric supercomplex with NSP7 that adopts a hollow cylinder-like structure. The dimensions of the central channel and positive electrostatic properties of the cylinder imply that it confers processivity on RNA-dependent RNA polymerase. NSP7 and NSP8 heterodimers play a role in the stabilization of NSP12 regions involved in RNA binding and are essential for a highly active NSP12 polymerase complex. It has been demonstrated that NSP8 acts as an oligo(U)-templated polyadenylyltransferase but also has robust (mono/oligo) adenylate transferase activities. NSP8 has N- and C-terminal D/ExD/E conserved motifs, being the N-terminal motif critical for RNA polymerase activity as these residues are part of the Mg2-binding active site.


Pssm-ID: 400866  Cd Length: 197  Bit Score: 134.59  E-value: 2.87e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3184 AVADININLDSYRIYKEADAIYKRSVEMNESPQEQKKKLKAVNIAKAEWEREAASQRKLEKLADAAMKSMYLAERAEDRR 3263
Cdd:pfam08717    1 SVASEFSSLPSYAAYETAKEAYEEAVANGSSQQVLKQLKKACNIAKSEFDRDAAVQKKLEKMAEQAMTQMYKEARAVDRK 80
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1818222121 3264 IKLTSGLTAMLYHMLRRLDSDRVKALFECAKAQILPIHAVVGISNDNLKVIFNDKDSYSHYVEGNTLIHKGVRYTIV 3340
Cdd:pfam08717   81 SKVVSAMHTLLFSMLRKLDNSALNTIINNARNGVVPLNIIPATTAAKLTVVVPDYETFVKVVDGNTVTYAGAVWEIQ 157
CoV_NSP4_C pfam16348
Coronavirus replicase NSP4, C-terminal; This is the C-terminal domain of the coronavirus ...
2413-2498 2.92e-22

Coronavirus replicase NSP4, C-terminal; This is the C-terminal domain of the coronavirus nonstructural protein 4 (NSP4). NSP4 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. It is a membrane-spanning protein which is thought to anchor the viral replication-transcription complex (RTC) to modified endoplasmic reticulum membranes. This predominantly alpha-helical domain may be involved in protein-protein interactions. It has been shown that in Betacoronavirus, the coexpression of NSP3 and NSP4 results in a membrane rearrangement to induce double-membrane vesicles (DMVs) and convoluted membranes (CMs), playing a critical role in SARS-CoV replication. There are two well conserved amino acid residues (H120 and F121) in NSP4 among Betacoronavirus, essential for membrane rearrangements during interaction with NSP3.


Pssm-ID: 465099  Cd Length: 92  Bit Score: 93.75  E-value: 2.92e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2413 SSFLDAAKATFVIDNEKYVLLKDLAGAE-FDQYLASYNKYKYFSGTASDKDYDKVCMAFLAKALSSFREGGGSQLYTPPK 2491
Cdd:pfam16348    6 GTFEEAALGTFVIDKESYEKLKNSISLDkFNRYLSLYNKYKYYSGKMDEADYREACCAHLAKALEDFSNSGNDVLYTPPT 85

                   ....*..
gi 1818222121 2492 FAVVQSL 2498
Cdd:pfam16348   86 VSVTSSL 92
CoV_NSP9 pfam08710
Coronavirus replicase NSP9; Nsp9 is a single-stranded RNA-binding viral protein involved in ...
3373-3481 1.94e-19

Coronavirus replicase NSP9; Nsp9 is a single-stranded RNA-binding viral protein involved in RNA synthesis. Several crystallographic structures of nsp9 have shown that it is composed of seven beta strands and a single alpha helix. Nsp9 proteins have N-finger motifs and highly conserved GXXXG motifs that both play critical roles in dimerization. The conserved helix-helix dimer interface containing a GXXXG protein-protein interaction motif is biologically relevant to SARS-CoV replication.


Pssm-ID: 285872  Cd Length: 111  Bit Score: 86.38  E-value: 1.94e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3373 NNELCLRNVFTAQNTAQDFNGNEST-VKSFYVTRTGKKILVAITSTKDNLKTVTCLTETGKTV-LNLDPPMRFAHTVGGK 3450
Cdd:pfam08710    1 NNELMPGKLKTKACKAGVTDAHCSVeGKAYYNNEGGGSFVYAILSSNPNLKYAKFEKEDGNVIyVELEPPCRFVVDTPKG 80
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1818222121 3451 QSVVYLYFIQNISSLNRGMVIGHISETTILQ 3481
Cdd:pfam08710   81 PEVKYLYFVKNLNNLRRGMVLGYISATVRLQ 111
Macro pfam01661
Macro domain; The Macro or A1pp domain is a module of about 180 amino acids which can bind ...
965-1062 4.74e-13

Macro domain; The Macro or A1pp domain is a module of about 180 amino acids which can bind ADP-ribose (an NAD metabolite) or related ligands. Binding to ADP-ribose could be either covalent or non-covalent: in certain cases it is believed to bind non-covalently; while in other cases (such as Aprataxin) it appears to bind both non-covalently through a zinc finger motif, and covalently through a separate region of the protein. This domain is found in a number of otherwise unrelated proteins. It is found at the C-terminus of the macro-H2A histone protein 4 and also in the non-structural proteins of several types of ssRNA viruses such as NSP3 from alpha-viruses and coronaviruses. This domain is also found on its own in a family of proteins from bacteria, archaebacteria and eukaryotes. The 3D structure of the SARS-CoV Macro domain has a mixed alpha/beta fold consisting of a central seven-stranded twisted mixed beta sheet sandwiched between two alpha helices on one face, and three on the other. The final alpha-helix, located on the edge of the central beta-sheet, forms the C terminus of the protein. The crystal structure of AF1521 (a Macro domain-only protein from Archaeoglobus fulgidus) has also been reported and compared with other Macro domain containing proteins. Several Macro domain only proteins are shorter than AF1521, and appear to lack either the first strand of the beta-sheet or the C-terminal helix 5. Well conserved residues form a hydrophobic cleft and cluster around the AF1521-ADP-ribose binding site.


Pssm-ID: 460286  Cd Length: 116  Bit Score: 67.98  E-value: 4.74e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  965 VNPANAQLTNGGGAARAIAKLAGPKYQEYCNSVapISGPLTT-DSF--DAKKLGVACILHVVPPK---GSDPNVQELLYQ 1038
Cdd:pfam01661    1 VNAANSRLLGGGGVAGAIHRAAGPELLEECREL--KKGGCPTgEAVvtPGGNLPAKYVIHTVGPTwrhGGSHGEEELLES 78
                           90       100
                   ....*....|....*....|....*....
gi 1818222121 1039 AYKSILTEPA-----HYVIPILGAGIFGC 1062
Cdd:pfam01661   79 CYRNALALAEelgikSIAFPAISTGIYGF 107
A1pp smart00506
Appr-1"-p processing enzyme; Function determined by Martzen et al. Extended family detected by ...
946-1064 7.86e-12

Appr-1"-p processing enzyme; Function determined by Martzen et al. Extended family detected by reciprocal PSI-BLAST searches (unpublished results, and Pehrson _ Fuji).


Pssm-ID: 214701  Cd Length: 133  Bit Score: 65.40  E-value: 7.86e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121   946 KVELVVGELASIKFDnsVLVNPANAQLTNGGGAARAIAKLAGPKY-QEYCNSVAPISGPL-TTDSFDAKKLGVACILHVV 1023
Cdd:smart00506    1 ILKVVKGDITKPRAD--AIVNAANSDGAHGGGVAGAIARAAGKALsKEEVRKLAGGECPVgTAVVTEGGNLPAKYVIHAV 78
                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*....
gi 1818222121  1024 PPKGSDPNVQ--ELLYQAYKSILTEpAH------YVIPILGAGIFGCNP 1064
Cdd:smart00506   79 GPRASGHSKEgfELLENAYRNCLEL-AIelgitsVALPLIGTGIYGVPK 126
YmdB COG2110
O-acetyl-ADP-ribose deacetylase (regulator of RNase III), contains Macro domain [Translation, ...
947-1085 8.27e-11

O-acetyl-ADP-ribose deacetylase (regulator of RNase III), contains Macro domain [Translation, ribosomal structure and biogenesis];


Pssm-ID: 441713  Cd Length: 168  Bit Score: 63.27  E-value: 8.27e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  947 VELVVGELASIKFDnsVLVNPANAQLTNGGGAARAIAKLAGPKYQEYCNSVAPISGPLT-----TDSFDakkLGVACILH 1021
Cdd:COG2110      1 IEIVQGDITELDVD--AIVNAANSSLLGGGGVAGAIHRAAGPELLEECRRLCKQGGCPTgeaviTPAGN---LPAKYVIH 75
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1818222121 1022 VVPP--KGSDPNVQELLYQAYKSILTEPAHY-----VIPILGAGIFGCNP-------VHSLDAFRKACPSdIGRVTLV 1085
Cdd:COG2110     76 TVGPvwRGGGPSEEELLASCYRNSLELAEELgirsiAFPAIGTGVGGFPWeeaapiaVETLRDFLEEHPS-LEEVRFV 152
CoV_peptidase pfam08715
Coronavirus papain-like peptidase; This entry contains coronavirus cysteine endopeptidases ...
1100-1269 1.66e-10

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: 65.39  E-value: 1.66e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1100 RTIVRTTTD-----YDQVTTKALTPQGVLEANLFDGEDFVQEPKPGQIYLEVTEEVQNQAKeldLNLQQYCVYLKTChhK 1174
Cdd:pfam08715   17 HSIVVKPGDslgqqFGQVYAKNKDLSGVFPADDVEDKEILYVPTTDWVEFYGFKSILEYYT---LDASKYVIYLSAL--T 91
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1175 WVVSRTNGLMHLKQKDNNCFVSAGVNLFQNTAYQLR-PAIDALYREYLNGNPNRFVAWIYASTNRRVGEMGCPQQVISLL 1253
Cdd:pfam08715   92 KNVQYVDGFLILKWRDNNCWISSVIVALQAAKIRFKgQFLTEAWAKLLGGDPTDFVAWCYASCTAKVGDFGDANWTLTNL 171
                          170       180
                   ....*....|....*....|
gi 1818222121 1254 VSNSDA----AFSATTACCN 1269
Cdd:pfam08715  172 AEHFDAeytnAFLKKRVCCN 191
PRK00431 PRK00431
ADP-ribose-binding protein;
945-1098 7.53e-09

ADP-ribose-binding protein;


Pssm-ID: 234759  Cd Length: 177  Bit Score: 57.93  E-value: 7.53e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  945 TKVELVVGELASIKFDnsVLVNPANAQLTNGGGAARAIAKLAGPKYQEYCNSVAPISGPL-------TTdsfdAKKLGVA 1017
Cdd:PRK00431     3 MRIEVVQGDITELEVD--AIVNAANSSLLGGGGVDGAIHRAAGPEILEECRELRQQQGPCptgeaviTS----AGRLPAK 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1018 CILHVVPP--KGSDPNVQELLYQAYKSILT--EPAHYV---IPILGAGIFGCnPVHslDAFRKAC---------PSDIGR 1081
Cdd:PRK00431    77 YVIHTVGPvwRGGEDNEAELLASAYRNSLRlaAELGLRsiaFPAISTGVYGY-PLE--DAARIAVktvrefltrHKSPEE 153
                          170
                   ....*....|....*..
gi 1818222121 1082 VTLVTMNKNHLQVWDAL 1098
Cdd:PRK00431   154 VYFVCYDEEAYRLYERL 170
MDN1 COG5271
Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal ...
492-943 1.77e-05

Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal structure and biogenesis];


Pssm-ID: 444083 [Multi-domain]  Cd Length: 1028  Bit Score: 50.78  E-value: 1.77e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  492 VGNRMLMFTSTGTFLLTKATTKILNKAKYIFDVDPEYPVDVTTSKVVVHEALQQIDTKPARA-----------LEAVDVV 560
Cdd:COG5271     29 AGLDTQSETASEREDKLPDTDKDLLILTDADAASDEGKLLDLKSADGAALSAESDAGASLITaanleegdiagNAADDSA 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  561 VGNTVLQMATDGTAFYPSDGTHASLPGFK------------AGSDELLISFNCDLFDDETNAQINETLAAYELN------ 622
Cdd:COG5271    109 DEESDANAKEDATDDADSSGDAQGDPLATdtlgggdldlatKDGDELLPSLADNDEAAADEGDELAADGDDTLAvadaie 188
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  623 -QLVAPGDSTPRQIATLVVDTLVDAITDHFPEKTIDLPEDYQVFSDHDDLLLAQYHIPD-HLSLYIQAMEGEDDSGDEIC 700
Cdd:COG5271    189 aTPGGTDAVELTATLGATVTTDPGDSVAADDDLAAEEGASAVVEEEDASEDAVAAADETlLADDDDTESAGATAEVGGTP 268
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  701 IEDDD-------YDCPQADENTEGVIPQQWELPDVDKFLLKIQERKTSSDEVLS----VDVYPKPDEVGIDDSASEKKPN 769
Cdd:COG5271    269 DTDDEatddadgLEAAEDDALDAELTAAQAADPESDDDADDSTLAALEGAAEDTeiatADELAAADDEDDDDSAAEDAAE 348
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  770 GDSVLDPEVHPTLESVDVERPTETAN---QAVEDKPSDTTFVVDEV--------QLQESTPEPELRSYEGEFDSDDEIII 838
Cdd:COG5271    349 EAATAEDSAAEDTQDAEDEAAGEAADeseGADTDAAADEADAAADDsaddeeasADGGTSPTSDTDEEEEEADEDASAGE 428
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  839 P------IVPV-----------TPADLKPQTITIKEYFKSEKLETINEgSTESVTQSDDSVDESFVDAESDDPQDPAVYD 901
Cdd:COG5271    429 TedestdVTSAeddiatdeeadSLADEEEEAEAELDTEEDTESAEEDA-DGDEATDEDDASDDGDEEEAEEDAEAEADSD 507
                          490       500       510       520
                   ....*....|....*....|....*....|....*....|..
gi 1818222121  902 DTTIITDSTDVGDEPETTLATIVNTPLTLDNNLPPEAIKQPS 943
Cdd:COG5271    508 ELTAEETSADDGADTDAAADPEDSDEDALEDETEGEENAPGS 549
 
Name Accession Description Interval E-value
TM_Y_deltaCoV_Nsp3_C cd21711
C-terminus of deltacoronavirus non-structural protein 3, including transmembrane and Y domains; ...
1502-1991 0e+00

C-terminus of deltacoronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from deltacoronavirus, including Magpie-robin coronavirus HKU18 and Bulbul coronavirus HKU11, among others. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In the related betacoronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409659  Cd Length: 490  Bit Score: 976.49  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1502 LYYSAQTLFVSLAPFLMLPAVVSLLNSGYTIGTYLYAKTGWPCNYNATQHFDYNSYCAGDLVCQACFDGQDSLHLYPHLR 1581
Cdd:cd21711      1 LFYSAQTIFVSLAPFLMLPAVASLLSSGYTIGTYLYAKTGLPCYYNATQHYDYNSFCAGDLTCQACFDGQDSLHLYKHLR 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1582 VNQQPIQTTDYTVYALSLILLLANMTLVMGTLIVTFFVNFYGVQIPFYGTLLIDYQSALMMTFSVYYFYKVMKFFRHLTH 1661
Cdd:cd21711     81 VNQQPVQTTDYTVYALSIVLLLANPTLVLGTLLVVFFVNFYGVQIPFYGTLQLDYQNTLVMVFSVYYFYKVMKFFRHLAK 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1662 GCKIPTCMVCAKLRTPPTITVETVVQGRKYPSVIETNGGFTICKEHNFYCKDCSLQTPGTFIPTEAIESLSRATRLSVKP 1741
Cdd:cd21711    161 GCKKPTCSICAKKRIPPTITVETVVQGRKYPSVIETNGGFNICKEHNFYCKNCDSQTPGTFIPTEAVESLSRKTRLSVKP 240
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1742 TAPAFLLARDVECQTDVVVARAMHNQNAHVCISKYSDIRTVDQLLKPTPLFSYTPDVIIAADFDNRGSLKTAKELAVVLS 1821
Cdd:cd21711    241 TAPAYLLARDVECQTDVVVARATHNGNAHVCISKYSDIRTVDQLLKPTPLFSYTPDVIIAADFDNAGSLKTAKELAVVLS 320
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1822 MDLKRTIIIIDQAYSRPIDNYQEVASRIEKYYPVAKITPTGDIFTDIKQATNGQASDSAINAAVLAVQRGLDFTIDNPNN 1901
Cdd:cd21711    321 MDLKRTIIIIDQAYSRPIDNYQEVKSRIEKYYPFQKITPTGDIFADIKQATNGQASDSAINAAILAVQRGLDFTIDNPNN 400
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1902 ILPHYAFDFSTLNAEDQSTILESGCAKGNLKGTNVGVVLSASLVTRLSQQAIRVIANAASRNGVTCAVTPSTLVMRGNIA 1981
Cdd:cd21711    401 ILPHYAFDFSTLSAEDQSTLIESGCAKGNLKGTNVGVVLSANLVTRLSQKAIRVIANAASRNGVTCAVTPSTLVLRGNIA 480
                          490
                   ....*....|
gi 1818222121 1982 TQPLTRIKAG 1991
Cdd:cd21711    481 TQPLTRIKAG 490
TM_Y_CoV_Nsp3_C cd21686
C-terminus of coronavirus non-structural protein 3, including transmembrane and Y domains; ...
1502-1990 0e+00

C-terminus of coronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from 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. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In SARS-CoV and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409657  Cd Length: 476  Bit Score: 666.97  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1502 LYYSAQTLFVSLAPFLMLPAVVSLLNSGYTIGTYLYAKTGWPCNYNATQHfDYNSYCAGDLVCQACFDGQDSLHLYPHLR 1581
Cdd:cd21686      1 LFYLASVLFKSLAPFLLLPAVLYLLNSGYTLGTGSYCKTYWPGYYNSTQH-DYNSYCAGDLVCQVCLDGQDSLHLYPHLR 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1582 VNQQPIQTTDYTVYALSLILLLANMTLVMGTLIVTFFVNFYGVQIPFYGTLLIDY-QSALMMTFSVYYFYKVMKFFRHLT 1660
Cdd:cd21686     80 VVQQPLQTTDYTVYALSLILYLANMTLFMGTFIVTFFVNFYGVGIPFYGWLLIDVpQSAFMMTFSVFFFYYVLKFFVHVT 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1661 HGCKIPTCMVCAKLRTPPTITVETVVQGRKYPSVIETNGGFTICKEHNFYCKDCSLQTPG-TFIPTEAIESLSRATRLSV 1739
Cdd:cd21686    160 HGCKIPTCMVCAKLARPPRVEVETVVQGRKYSFYVYTNGGFTFCKEHNFYCKNCDLYGPGcTFISDEVAEELSRATKLSV 239
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1740 KPTAPAFLLARDVECQTDVVVARAMHNQNAHVCISKYSDIrtvdqllkptplfsytPDVIIAADF-DNRGSLKTAKELAV 1818
Cdd:cd21686    240 KPTAPAFLLVDDVEVQNDVVFARAKYNQNAHVSLSKFSDI----------------PDFIIAANFgSNCEQLSTAKNAAV 303
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1819 VLSMDLKRTIIIIDQAYSRPIDNYQEVASRIEKYYPVAKITPTGDIFTDIKQATNGQASDSAINAAVLAVQRGLDFTIDN 1898
Cdd:cd21686    304 YYSQDLCKPILILDQALSRPIDNYQEVASRIEKYYPVAKIKPTGDIFTDIKQGTDGEASDSAINAAVLAHQRDVEFTGDS 383
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1899 PNNILPHYAFDFSTLNAEDQ--STILESGCAKGNLKGTNVGVVLSASlVTRLSQQAIRVIANAASRNGVTCAVTPSTLVM 1976
Cdd:cd21686    384 FNNILPSYAKDESKLTAEDQamSVIAESGNANVNVKGTIPVVWLVAD-FIRLSEQARKYIISAAKKNGVTFALTPSTLRM 462
                          490
                   ....*....|....
gi 1818222121 1977 RGNIATQPLTRIKA 1990
Cdd:cd21686    463 RGNIATQPLIAIKK 476
deltaCoV_Nsp5_Mpro cd21668
deltacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
2503-2804 0e+00

deltacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in deltacoronaviruses. 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. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394889  Cd Length: 302  Bit Score: 644.56  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2503 QAGIKILLHPSGVVERCMVSVVYNGSALNGIWLKNVVYCPRHVIGKFRGDQWTHMVSIADCRDFIVKCPIQGIQLNVQSV 2582
Cdd:cd21668      1 QAGIKILLHPSGVVERCMVSVTYNGSTLNGIWLHNVVYCPRHVIGKYTGSQWQDMVSIADCRDFVIFCPTQGIQLTVQSV 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2583 KMVGALLQLTVHTNNTATPDYKFERLQPGSSMTIACAYDGIVRHVYHVVLQLNNLIYASFLNGACGSVGYTLKGKTLYLH 2662
Cdd:cd21668     81 KMVGAVLQLTVHTKNLHTPDYEFERATPGSSMTIACAYDGIVRNVYHVVLQTNNLIYASFLNGACGSVGYTLKGKTLLLH 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2663 YMHHIEFNNKTHSGTDLEGNFYGPYVDEEVIQQQTAFQYYTDNVVAQLYAHLLTVDARPKWLAQSQISIEDFNSWAANNS 2742
Cdd:cd21668    161 YMHHLEFNNKTHGGTDLHGHFYGPYVDEEVAQHQTAFQYYTDNVVAQIYAHLLTIDAKPKWLASQEISVEDFNEWAANNS 240
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1818222121 2743 FANFPCEQTNMSYIMGLSQTARVPVERILNTIIQLTTNRDGACIMGSYDFECDWTPEMVYNQ 2804
Cdd:cd21668    241 FANFPCESSNMAYLEGLAQTTKVSVGRVLNTIIQLTLNRGGALIMGKPDFECDWTPEMVYNQ 302
deltaCoV_PLPro cd21734
deltacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
1087-1399 0e+00

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: 628.69  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1087 MNKNHLQVWDALNRTIVRTTTDYDQVTTKALTPQGVLEANLFDGEDFVQEPKPGQIYLEVTEEVQNQAKELDLNLQQYCV 1166
Cdd:cd21734      1 LDKNHLQVWDALNRTVVRTTKDFDQVTTKALTPQGVLDANLFDGEDFVQEPKPGQIYLAVTDEVQQQAKELDLTLSQYCV 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1167 YLKTCHHKWVVSRTNGLMHLKQKDNNCFVSAGVNLFQNTAYQLRPAIDALYREYLNGNPNRFVAWIYASTNRRVGEMGCP 1246
Cdd:cd21734     81 YLKYCHHKWSVSRTNGLMHLKQKDNNCFVSAAINLFQNTHYQLRPAIDALYQEYLNGNPSRFVAWIYASTNQEIGEMGCP 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1247 QQVISLLVSNSDAAFSATTACCNTYFNHTGVISVAREYDPIQPKVYCMKCDVWTPFTPQSGKGAVAIGTSADEPTGPAIK 1326
Cdd:cd21734    161 QQVLSLLVNNSNAKFSGTTACCGTYFTHDGVISVAREYDPLQPKVYCMKCDVWTPFTPQSGKGIVVIGSSAEEPTGPAIK 240
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1818222121 1327 FAAAHCWYTNGKKTVNGYDTKANVVATYHRFDVPKPQLVEDVVALPTKNDFEVLNVEELPQDSVLHLDPPPVQ 1399
Cdd:cd21734    241 FAAAHCWYTNGKKTVNGYDTKANVVAIYHKFDVPKPQPVEDVVTLPTKNDFEVLKVEEIPQDSVLNLDPPEVQ 313
deltaCoV-Nsp6 cd21561
deltacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...
2792-3087 0e+00

deltacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.


Pssm-ID: 394847  Cd Length: 296  Bit Score: 573.54  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2792 FECDWTPEMVYNQAPISLQSGVVKKTCTWFFHFVFMAITMLLAAMHVFPVHLYPIVLPCFTVVAFLLTLTIKHTVVFTTT 2871
Cdd:cd21561      1 FECDWTPEMVYNQAPINLQSGVVKKTCMWFFHFLFMAVIFLLAALHVFPVHLYPIVLPVFTILAFLLTLTIKHTVVFTTT 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2872 YLLPSLLMMVVNANTFWIPNTFLRTCYETIFGSPIAQRLYGYTVALYMLIYAGLAINYTLKTLRYRATSFLSFCMQWFQY 2951
Cdd:cd21561     81 YLLPSLLMMVVNANTFWIPNTYLRSIYEYVFGSFISERLYGYTVALYILVYAQLAINYTLRTRRYRATSFISFCMQALQY 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2952 GYVAHIAYKLLNKPWTESLLFTAFTMLTSHPLLAALSWWLAGRVTLPIIMPDLAIRVLAYNVIGYVICVRFGLMWLANRF 3031
Cdd:cd21561    161 GYVAHIVYRLLTTPWTEGLLFTAFSLLTSHPLLAALSWWLAGRIPLPLILPDLAIRVIVYYVIGYVMCMRFGLFWLINKF 240
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1818222121 3032 TTVPMGTYQYMVSVEQLKYMMAVKMSPPRNAFEVLIANIRLLGLGGNRNIAVSTVQ 3087
Cdd:cd21561    241 TTIPMGTYKYMVSIEQLKYMMAVKMSPPRNAFEVLWANIRLLGLGGNRNIAVSTVQ 296
cv_gamma-delta_Nsp2_IBV-like cd21512
gamma- and deltacoronavirus non-structural protein 2 (Nsp2), similar to IBV Nsp2 and related ...
7-379 0e+00

gamma- and deltacoronavirus non-structural protein 2 (Nsp2), similar to IBV Nsp2 and related proteins; Coronavirus non-structural proteins (Nsps) are encoded in ORF1a and ORF1b. Post infection, the genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (pp), pp1a and pp1ab, which are then autoproteolytically cleaved by two viral proteases Nsp3 and Nsp5 into smaller subunits. Nsp2 is one of these cleaved subunits. The functions of Nsp2 remain unclear. This gamma- and deltacoronavirus family includes Avian infectious bronchitis virus (IBV) Nsp2 which has been shown to be a weak protein kinase R (PKR) antagonist, which may suggest that it plays a role in interfering with intracellular immunity. This family may be distantly related to a family of alpha- and betacoronavirus Nsp2, which includes severe acute respiratory syndrome coronavirus (SARS-CoV) Nsp2, and Murine hepatitis virus (MHV) Nsp2 (also known as p65). SARS-CoV Nsp2, rather than playing a role in viral replication, may be involved in altering the host cell environment; deletion of Nsp2 from the SARS-CoV genome results in only a modest reduction in viral titers. It has been shown to interact with two host proteins, prohibitin 1 (PHB1) and PHB2, which have been implicated in cellular functions, including cell-cycle progression, cell migration, cellular differentiation, apoptosis, and mitochondrial biogenesis. MHV Nsp2/p65, different from SARS-CoV Nsp2, may play an important role in the viral life cycle.


Pssm-ID: 394837  Cd Length: 365  Bit Score: 561.65  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121    7 KRDAIALPENVPPPLQLFIHVAAAEEGHPKVTTYLGNYNLYATKAPPGVQVLSAKTSLTDFENVFGAQPTLRSIRNLVCE 86
Cdd:cd21512      1 KRHPIVLPPDAPPPLQLFIRVAAAGEGHPFDTVYLGNYNLIGVKAVPGVQVLDANTSLADFENLFGVQPTLRAYRNLLKD 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121   87 ArsAEWTTSKNAFALKATQLDYSDAVLRAMIRFCPPKVSTLAAFALFGRLVKIEDKELAELARDTALELAYTAKIGTSLA 166
Cdd:cd21512     81 A--AQWSLSKEALAAKAKQLTESDDVLRAIILYGAARVSALASLALFGRVVKIDDVELGDLAEDVALELAYTGKIGRALA 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  167 DTRSVSLIHKDAYLTLSNEVVGVTFTAALMAKATTVNGAMQYSNFYLYPRATIKVTDGKAEAIATKPLPAATKGKPITED 246
Cdd:cd21512    159 DAKAIELPQTDAYLTLNFAVCGKVFTSTLLAQATPVNGALQYSDFVLWPLATAKATDGKLQPLAGKPLPASQKGAFFTED 238
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  247 VNLLPDYQQLLVDQVTGTEVKVGALTYVKTTDLPPLYFPKVKGGVvgiALKQQGTAAKKLNVVFHAQPDDVLLAFIQLQQ 326
Cdd:cd21512    239 VNLVPDYQQLAPDQVEGDEVVVGGITYIKTTDVPPLYYPRVKGGV---LLKPQGTADKKVNVVFHAAPSDVLLAFIQLQL 315
                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1818222121  327 FLNRTSDSSVEITDCQSYEVSPTVTVKIGpskPGDVIVATDEEYLKCFETPEV 379
Cdd:cd21512    316 FLVRTSGSCVEVTDDDVYAVPPSVTVSIG---PGDVVVNDDEEYVKCFETPVV 365
CoV_NSP3_C pfam19218
Coronavirus replicase NSP3, C-terminal; This family represents the C-terminal region of ...
1541-1976 7.03e-156

Coronavirus replicase NSP3, C-terminal; This family represents the C-terminal region of non-structural protein NSP3 (also known as nsp3). NSP3 is the product of ORF1a. It is found in human SARS coronavirus polyprotein 1a and 1ab, and in related coronavirus polyproteins. It is a multifunctional protein comprising up to 16 different domains and regions. NSP3 binds to viral RNA, nucleocapsid protein, as well as other viral proteins and participates in polyprotein processing.


Pssm-ID: 466002  Cd Length: 463  Bit Score: 492.24  E-value: 7.03e-156
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1541 GWPCNYN----ATQHFDYNSYCAGDLVCQACFDGQDSLHLYPHLRVNQQPIQTT---DYTVYALSLILLLANMTLVMGTL 1613
Cdd:pfam19218    1 GYPCDGYvdgySNSSFNKSDYCNGSILCKACLSGYDSLHDYPHLKVVQQPVKDPlfvDVTPLFYFAIELFVALALFGGTF 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1614 IVTFFVNFYGVQIPFYGTLL-----------IDYQSALMMTFSVYYFYKVMKFFRHLTHGCKIPTCMVCAKLRTPPTITV 1682
Cdd:pfam19218   81 VRVFLLYFLQQYVNFFGVYLglqdyswfltlIPFDSFLREYVVLFYVIKLYRFLKHVVFGCKKPSCLACSKSARLTRVPV 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1683 ETVVQGRKYPSVIETNGGFTICKEHNFYCKDCSLQTPG-TFIPTEAIESLSRATRLSVKPTAPAFLLARDVECQTDVV-- 1759
Cdd:pfam19218  161 STVVNGSKKSFYVNANGGTKFCKKHNFFCKNCDSYGPGnTFINDEVAEDLSNVTKRSVKPTDPAYYEVDKVEFQNGFYyl 240
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1760 -VARAMHNQNAHVCISKYSDIRTVDQLLKptplFSYTPDVIIAADfDNRGSLKTAKELAVVLSMDLKRTIIIIDQAYSRP 1838
Cdd:pfam19218  241 ySGREFWRYYFDVTVSKYSDKEVLKNCNI----KGYPLDDFIVYN-SNGSNLAQAKNACVYYSQLLCKPIKLVDSNLLSS 315
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1839 IDNYQEVASRIEKYYP-------------VAKITPTG-DIFTDIKqatngqaSDSAINAAVLAVQRGLDFTIDNPNNILP 1904
Cdd:pfam19218  316 LGDSVDVNGALHDAFVevllnsfnvdlskCKTLIECKkDLGSDVD-------TDSFVNAVLNAHRYDVLLTDDSFNNFVP 388
                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1818222121 1905 HYAFDFSTLNAEDQSTILESGCA---KGNLKGTNVGVVLSASLVTRLSQQAIRVIANAASRNGVTCAVTPSTLVM 1976
Cdd:pfam19218  389 TYAKPEDSLSTHDLAVCIRFGAKivnHNVLKKENVPVVWSADDFLKLSEEARKYIVKTAKKKGVTFMLTFNTNRM 463
CoV_Nsp5_Mpro cd21646
coronavirus non-structural protein 5, also called Main protease (Mpro); This family contains ...
2507-2804 1.26e-141

coronavirus non-structural protein 5, also called Main protease (Mpro); This family contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro). 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. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394885  Cd Length: 292  Bit Score: 443.79  E-value: 1.26e-141
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2507 KILLHPSGVVERCMVSVVYNGSALNGIWLKNVVYCPRHVIGKFR--GDQWTHMVSIADCRDFIVKCPiqGIQLNVQSVKM 2584
Cdd:cd21646      1 KKMAQPSGKVERCMVSVTYGSTTLNGLWLDDTVYCPRHVICKSTtsGPDYDDLLSRARNHNFSVQSG--GVQLRVVGVTM 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2585 VGALLQLTVHTNNTATPDYKFERLQPGSSMTIACAYDGIVRHVYHVVLQLNNLIYASFLNGACGSVGYTLKGKTLYLHYM 2664
Cdd:cd21646     79 QGALLRLKVDTSNPHTPKYKFVTVKPGDSFTILACYNGSPSGVYGVNMRSNYTIKGSFLNGACGSVGYNIDGGTVEFCYM 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2665 HHIEFNNKTHSGTDLEGNFYGPYVDEEVIQQQTAFQYYTDNVVAQLYAHLLTVDarPKWLAQSQISIEDFNSWAANNSFA 2744
Cdd:cd21646    159 HHLELPNGCHTGTDLTGKFYGPYVDQQVAQVEGADTLITDNVVAWLYAAIINGD--RWWLNSSRTTVNDFNEWAMANGFT 236
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1818222121 2745 NFPCeqtnMSYIMGLSQTARVPVERILNTIIQLTTNRDGACIMGsYDFECDW-TPEMVYNQ 2804
Cdd:cd21646    237 PVSQ----VDCLSILAAKTGVSVERLLAAIQQLHQNFGGKQILG-STSLEDEfTPEDVVRQ 292
Peptidase_C30 pfam05409
Coronavirus endopeptidase C30; This Coronavirus (CoV) domain, peptidase C30, is also known as ...
2532-2810 2.65e-134

Coronavirus endopeptidase C30; This Coronavirus (CoV) domain, peptidase C30, is also known as 3C-like proteinase (3CL-pro), or CoV main protease (M-pro) domain. CoV M-pro is a dimer where each subunit is composed of three domains I, II and III,,. Domains I and II consist of six-stranded antiparallel beta barrels and together resemble the architecture of chymotrypsin, and of picornaviruses 3C proteinases. The substrate-binding site is located in a cleft between these two domains. The catalytic site is situated at the centre of the cleft. A long loop connects domain II to the C-terminal domain (domain III). This latter domain has been implicated in the proteolytic activity of M-pro. In the active site of M-pro, Cys and His form a catalytic dyad,.


Pssm-ID: 398852  Cd Length: 274  Bit Score: 421.85  E-value: 2.65e-134
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2532 GIWLKNVVYCPRHVIGKFRG--DQWTHMVSIADCRDFIVKCpiQGIQLNVQSVKMVGALLQLTVHTNNTATPDYKFERLQ 2609
Cdd:pfam05409    1 GLWLGDTVYCPRHVIGSFTGmlPQYEHLLSIARNHDFCVVS--GGVQLTVVSAKMQGAILVLKVHTNNPNTPKYKFVRLK 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2610 PGSSMTIACAYDGIVRHVYHVVLQLNNLIYASFLNGACGSVGYTLKGKTLYLHYMHHIEFNNKTHSGTDLEGNFYGPYVD 2689
Cdd:pfam05409   79 PGESFTILAAYDGCPQGVYHVTMRSNHTIKGSFLNGACGSVGYNLKGGTVCFVYMHHLELPNGSHTGTDLEGVFYGPYVD 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2690 EEVIQQQTAFQYYTDNVVAQLYAHLLTVdarPKW-LAQSQISIEDFNSWAANNSFANFPCEQTnmsyIMGLSQTARVPVE 2768
Cdd:pfam05409  159 EEVAQLEGTDQTYTDNVVAWLYAAIING---PRWfLASTTVSLEDFNAWAMTNGFTPFPCEDA----ILGLAAKTGVSVE 231
                          250       260       270       280
                   ....*....|....*....|....*....|....*....|...
gi 1818222121 2769 RILNTIIQLTTNRDGACIMGSYDFECDWTPEMVYNQ-APISLQ 2810
Cdd:pfam05409  232 RLLAAIKVLNNGFGGRTILGSPSLEDEFTPEDVYNQmAGVTLQ 274
cv_Nsp4_TM cd21473
coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in ...
2001-2396 5.13e-134

coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in coronavirus-induced membrane remodeling. In order to assemble the replication-transcription complex (RTC), coronavirus induces the rearrangement of host endoplasmic reticulum (ER) membrane into double membrane vesicles (DMVs), zippered ER, or ER spherules. DMV formation has been observed in SARS-CoV cells overexpressing the three transmembrane-containing non-structural proteins of viral replicase polyprotein 1ab: Nsp3, Nsp4 and Nsp6. Together, Nsp3, Nsp4, and Nsp6 have the ability to induce the formation of DMVs that are similar to those seen in SARS-CoV-infected cells.


Pssm-ID: 394836  Cd Length: 376  Bit Score: 425.85  E-value: 5.13e-134
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2001 CVILALAIVYFAAMAFGFLASQITLNTVPTiksdiraSTFYVVRDGVLDTVRSNDKCFANKFLAFDSFIQAPY----TNS 2076
Cdd:cd21473      1 FLWLLLAAILLYAFLPSYSVFTVTVSSFPG-------YDFKVIENGVLRDIRSTDTCFANKFVNFDSWYQAKYgsvpTNS 73
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2077 PDCPVVVGVVEVTTHSIPGIPAGVIHRDGLILNIYEQslyethqrqsmvrdalslktanlfNLGKRVVVGYTQHEVVVGT 2156
Cdd:cd21473     74 KSCPIVVGVIDDVRGSVPGVPAGVLLVGKTLVHFVQT------------------------VFFGDTVVCYTPDGVITYD 129
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2157 SYFNSPALFNAKCTFLQYQDTRQLYCYDTVPTEH-KLYSDVLPHVEYKAIDINgdlvPFKIPEQIM-FYPHIVRYTSNSY 2234
Cdd:cd21473    130 SFYTSACVFNSACTYLTGLGGRQLYCYDTGLVEGaKLYSDLLPHVRYKLVDGN----YIKFPEVILeGGPRIVRTLATTY 205
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2235 CRMGHCFNTNPGICISFTDEFPYSENV-KPGVYCADTSLQLFSNLVLGTVSGIHIFTSTAALLGSTIVIILCVVAVLAVQ 2313
Cdd:cd21473    206 CRVGECEDSKAGVCVSFDGFWVYNNDYyGPGVYCGDGLFDLLTNLLSGFFQPVSVFALSGQLLFNTIVAILAVLACYYVQ 285
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2314 RFFKEY---TTFVMYTCGLAFVNIVGIALMYKCLvFAIFYYAIYLYFVLTFPSFkRNVALFYFAVVIVPHVSNMQLLALI 2390
Cdd:cd21473    286 KFKRAFgdmSVVVVTVVAAALVNNVLYVVTQNPL-LMIVYAVLYFYATLYLTYE-RAWIMHLGWVVAYGPIAPWWLLALY 363

                   ....*.
gi 1818222121 2391 VCSIIY 2396
Cdd:cd21473    364 VVAVLY 369
deltaCoV_Nsp8 cd21833
deltacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...
3184-3372 6.99e-132

deltacoronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) region of deltacoronaviruses that include White-eye coronavirus HKU16 and Quail coronavirus UAE-HKU30, among others. 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. SARS-CoV Nsp8 forms a 8:8 hexadecameric supercomplex with Nsp7 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp8 forms a 1:2 heterotrimer with Nsp7. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.


Pssm-ID: 409260  Cd Length: 189  Bit Score: 411.33  E-value: 6.99e-132
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3184 AVADININLDSYRIYKEADAIYKRSVEMNESPQEQKKKLKAVNIAKAEWEREAASQRKLEKLADAAMKSMYLAERAEDRR 3263
Cdd:cd21833      1 AVVDANINLDSYRIYKEADAAYKKSVELNEPPQEQKKKLKAVNIAKAEWEREAASQRKLEKLADAAMKSMYLAERAEDRR 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3264 IKLTSGLTAMLYHMLRRLDSDRVKALFECAKAQILPIHAVVGISNDNLKVIFNDKDSYSHYVEGNTLIHKGVRYTIVKKL 3343
Cdd:cd21833     81 IKLTSGLTAMLYHMLRRLDSDRVKALFECAKQQILPIHAIVGVSNDNLKVIFNDKESYLQYVDGNTLIYKGVRYTIVKKL 160
                          170       180
                   ....*....|....*....|....*....
gi 1818222121 3344 SLDNAPIEGVPEEFPVVVETVREGVPQLQ 3372
Cdd:cd21833    161 SLDNAPIEGIPEEYPVVVETIREGVPQIQ 189
CoV_Nsp6 cd21526
coronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell ...
2801-3087 2.22e-129

coronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.


Pssm-ID: 394843  Cd Length: 287  Bit Score: 408.46  E-value: 2.22e-129
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2801 VYNQAPISLQSGV--VKKTCTWFFHFVFMAITMLLAAMHVFPVHLYPIVLPCFTVVAFlltlTIKHTVVFTTTYLLPSLL 2878
Cdd:cd21526      1 VYNQAPGVLLQSVfvVKKTSTFWSHFLFAAFTMLLAAPLVFPVHAYVILLMCFTVVTF----TVKHKVAFLTTFLLPSLI 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2879 MMVVNANTFWIP-NTFLRTCYETIFGSPIAQRLYGYTVALYMLIYAGLAINYTLKTLRYRATSFLSFCMQWFQYGYVAHI 2957
Cdd:cd21526     77 TMVAIANTFWIQvVTFLRTWYDTVFVSPIAQDLYGYTVALYMLIYAGLATNYTLKTLRYRATSFLSFLMQNFLTLYTAHY 156
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2958 AYKLLnkPWTESLLFTAFTMLTSHPLLAALSWWLAG---RVTLPIIMPDLAIRVLAYNVIGYVICVRFGLMWLANRFTTV 3034
Cdd:cd21526    157 AYKLL--PWTESLLFTALTMLSSHSLIGAIVFWLARwmlRVEYPIIFPDLAIRVLAYNVIGYVCTCYFGLMWLANRFFTL 234
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1818222121 3035 PMGTYQYMVSVEQLKYMMAVKMSPPRNAFEVLIANIRLLGLGGNRNIAVSTVQ 3087
Cdd:cd21526    235 TLGVYDYMVSVEQFRYMMAVKLNPPKNAFEVFILNIKLLGIGGNRNIKVATVQ 287
deltaCoV_Nsp10 cd21903
deltacoronavirus non-structural protein 10; This model represents the non-structural protein ...
3483-3610 2.67e-100

deltacoronavirus non-structural protein 10; This model represents the non-structural protein 10 (Nsp10) of deltacoronaviruses, including Thrush coronavirus HKU12-600 and Wigeon coronavirus HKU20. 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Coronaviruses cap their mRNAs; RNA cap methylation may involve at least three proteins: Nsp10, Nsp14, and Nsp16. Nsp10 serves as a cofactor for both Nsp14 and Nsp16. Nsp14 consists of 2 domains with different enzymatic activities: an N-terminal ExoN domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. The association of Nsp10 with Nsp14 enhances Nsp14's exoribonuclease (ExoN) activity, and not its N7-Mtase activity. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The Nsp10/Nsp14 complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end, mimicking an erroneous replication product, and may function in a replicative mismatch repair mechanism. Nsp16 Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) acts sequentially to Nsp14 MTase in RNA capping methylation and methylates the RNA cap at the ribose 2'-O position; it catalyzes the conversion of the cap-0 structure on m7GpppA-RNA to a cap-1 structure. The association of Nsp10 with Nsp16 enhances Nsp16's 2'OMTase activity, possibly through enhanced RNA binding affinity. Additionally, transmissible gastroenteritis virus (TGEV) Nsp10, Nsp16 and their complex can interact with DII4, which normally binds to Notch receptors; this interaction may disturb Notch signaling. Nsp10 also binds 2 zinc ions with high affinity.


Pssm-ID: 409328  Cd Length: 128  Bit Score: 317.96  E-value: 2.67e-100
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3483 SGTQIEYQQNASLLTYLAFAVDPKTAYLKHLADGGSPIQGCIQMIATMGPGFAVTTKPQPNEHQYSYGGASICLYCRAHI 3562
Cdd:cd21903      1 NGTQIEYQENASLLTYLAFAVDPKEAYLKHLADGGKPIQGCIQMIAPLGPGFAVTTKPQPNEHQYSYGGASICLYCRAHI 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1818222121 3563 PHPGVDGRCPYKGRFVHIDKDKEPVSFALTHEPCSSCQRWVNYDCTCG 3610
Cdd:cd21903     81 PHPGVDGRCPYKGRFVHIDKDKEPVSFALTHEPCNSCQRWVNYDCTCG 128
CoV_NSP4_N pfam19217
Coronavirus replicase NSP4, N-terminal; This is the N-terminal domain of the coronavirus ...
2018-2387 3.02e-97

Coronavirus replicase NSP4, N-terminal; This is the N-terminal domain of the coronavirus nonstructural protein 4 (NSP4). NSP4 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. NSP4 is a membrane-spanning protein which is thought to anchor the viral replication-transcription complex to modified endoplasmic reticulum membranes. This N-terminal region represents the membrane spanning region, covering four transmembrane regions.


Pssm-ID: 466001  Cd Length: 351  Bit Score: 318.83  E-value: 3.02e-97
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2018 FLASQITLNTVPTIKSDiRASTFYVVRDGVLDTVRSNDKCFANKFLAFDSFIQA---PYTNSPDCPVVV-GVVEVTTHSI 2093
Cdd:pfam19217    1 YALSPTFFNTVVYFVSD-PVYDFKVIENGVLRDFRSTDTCFHNKFDNFDSWHQAkfgSPTNSRSCPIVVgVVDEVVGRVV 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2094 PGIPAGVIHRDGLILNIyeqslyethqrqsmvrdalslKTANLFNLGKrvvVGYTQHEVVVGTSYFNSPALFNAKCTFLQ 2173
Cdd:pfam19217   80 PGVPAGVALVGGTILHF---------------------VTRVFFGAGN---VCYTPSGVVTYESFSASACVFNSACTTLT 135
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2174 -YQDTRQLYCYD-TVPTEHKLYSDVLPHVEYKAIDinGDLVPFkiPEQIM-FYPHIVRYTSNSYCRMGHCFNTNPGICIS 2250
Cdd:pfam19217  136 gLGGTRVLYCYDdGLVEGAKLYSDLVPHVRYKLVD--GNYVKL--PEVLFrGGFRIVRTLATTYCRVGECEDSKAGVCVG 211
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2251 FTDEFPYSENVKPGVYCADTSLQLFSNLVLGTVSGIHIFTSTAALLGSTIV--IILCV-VAVLAVQRFFKEYTTFVMYTC 2327
Cdd:pfam19217  212 FDRSFVYNNDFGPGVYCGSGFLSLLTNVFSGFNTPISVFALTGQLMFNCVValIAVCVcYYVLKFKRAFGDYSTGVLTVV 291
                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2328 GLAFVNIVGIALMYKCLVFAIFYYAIYLYFVLTFPSFKRNVALFYFAVVIVPHVSNMQLL 2387
Cdd:pfam19217  292 LATLVNNLSYFVTQVNPVLMIVYAVLYFYATLYVTPEYAWIWHLGFLVAYVPLAPWWVLL 351
gammaCoV_Nsp5_Mpro cd21667
gammacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
2505-2804 4.39e-92

gammacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in gammacoronaviruses. 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. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394888  Cd Length: 306  Bit Score: 302.09  E-value: 4.39e-92
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2505 GIKILLHPSGVVERCMVSVVYNGSALNGIWLKNVVYCPRHVIGKFRGDQWTHMVSIADCRDFIVKCPiQGIQLNVQSVKM 2584
Cdd:cd21667      1 GFKKLVSPSSAVEKCIVSVSYRGNNLNGLWLGDSIYCPRHVLGKFSGDQWQDVLNLANNHEFEVVTQ-NGVTLNVVSRRL 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2585 VGALLQLTVHTNNTATPDYKFERLQPGSSMTIACAYDGIVRHVYHVVLQLNNLIYASFLNGACGSVGYTLKGKTLYLHYM 2664
Cdd:cd21667     80 KGAVLILQTAVANANTPKYKFVKANCGDSFTIACSYGGTVVGLYPVTMRSNGTIRASFLAGACGSVGFNIEKGVVNFFYM 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2665 HHIEFNNKTHSGTDLEGNFYGPYVDEEVIQQQTAFQYYTDNVVAQLYAHLLTVD----ARPKWLAQSQISIEDFNSWAAN 2740
Cdd:cd21667    160 HHLELPNALHTGTDLMGEFYGGYVDEEVAQRVPPDNLVTNNIVAWLYAAIISVKessfSLPKWLESTTVSVEDYNKWASD 239
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1818222121 2741 NSFANFpceqTNMSYIMGLSQTARVPVERILNTIIQLTTNRDGACIMGSYDFECDWTPEMVYNQ 2804
Cdd:cd21667    240 NGFTPF----STSTAITKLSAITGVDVCKLLRTIMVKSAQWGSDPILGQYNFEDELTPESVFNQ 299
CoV_NSP6 pfam19213
Coronavirus replicase NSP6; This entry represents proteins found in Coronaviruses and includes ...
2831-3087 4.67e-91

Coronavirus replicase NSP6; This entry represents proteins found in Coronaviruses and includes the Non-structural Protein 6 (NSP6). Coronaviruses encode large replicase polyproteins which are proteolytically processed by viral proteases to generate mature Nonstructural Proteins (NSPs). NSP6 is a membrane protein containing 6 transmembrane domains with a large C-terminal tail. NSP6 from the avian coronavirus, infectious bronchitis virus (IBV) and the mouse hepatitis virus (MHV) have been shown to localize to the ER and to generate autophagosomes. Coronavirus NSP6 proteins have also been shown to limit autophagosome expansion. This may favour coronavirus infection by reducing the ability of autophagosomes to deliver viral components to lysosomes for degradation. NSP6 from IBV, MHV and severe acute respiratory syndrome coronavirus (SARS-CoV) have also been found to activate autophagy.


Pssm-ID: 465997  Cd Length: 260  Bit Score: 297.24  E-value: 4.67e-91
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2831 MLLAAMHVFPVHLYPIVLPCFTVVAFLLTLTIKHTVVFTTTYLLPSLLMMVVNANTFW-IPNTFLRTCYETifgspiAQR 2909
Cdd:pfam19213    2 LMYTALYWLPPNLITPVLPVLTCVSAILTLFIKHKVLFLTTFLLPSVVVMAYYNFTWDyYPNSFLRTVYDY------HFS 75
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2910 LYGYTVALYMLIYAGLAINYT-----LKTLRYRATSFLSFCMQWfqYGYVahIAYKLLNKPWTESLLFTAFTMLTSHPLL 2984
Cdd:pfam19213   76 LTSFDLQGYFNIASCVFVNVLhtyrfVRSKYSIATYLVSLVVSV--YMYV--IGYALLTATDVLSLLFMVLSLLTSYWYV 151
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2985 AALSWWLAGRVTLPI------IMPDLAIRVLAYNVIGYVICVRFGLMWLANRFTTVPMGTYQYMVSVEQLKYMMAVKMSP 3058
Cdd:pfam19213  152 GAIAYKLAKYIVVYVppsliaVFGDIKVVLLVYVCIGYVCCVYFGILYWINRFTKLTLGVYDFKVSAAEFKYMVANGLSA 231
                          250       260
                   ....*....|....*....|....*....
gi 1818222121 3059 PRNAFEVLIANIRLLGLGGNRNIAVSTVQ 3087
Cdd:pfam19213  232 PRNVFEALILNFKLLGIGGNRTIKISTVQ 260
CoV_PLPro cd21688
Coronavirus (CoV) papain-like protease (PLPro); This model represents the papain-like protease ...
1087-1397 4.76e-89

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: 293.24  E-value: 4.76e-89
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1087 MNKNHLQVWDALN-RTIVRTTTD--YDQVTTKALTpqgvlEANLFD-------GEDFVQEPK-PGQIYLEVteevqnqAK 1155
Cdd:cd21688      1 KTKKVLVTVDGVNfRTIVVTTGDtyGQQLGPVYLD-----GADVTKgkpdnheGETFFVLPStPDKAALEY-------YG 68
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1156 ELDLnlQQYCVYLKTCHHKWVVSRTNGLMHLKQKDNNCFVSAGVNLFQNTAYQLR-PAIDALYREYLNGNPNRFVAWIYA 1234
Cdd:cd21688     69 FLDP--SFLGRYLSTLAHKWKVKVVDGLRSLKWSDNNCYVSAVILALQQLKIKFKaPALQEAWNKFLGGDPARFVALIYA 146
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1235 STNRRVGEMGC-PQQVISLLVSN--SDAAFSATTAC--CNTYFNHTGVISV-----AREYDPIQ--PKVYCMKCDVWTPF 1302
Cdd:cd21688    147 SGNKTVGEPGDvRETLTHLLQHAdlSSATRVLRVVCkhCGIKTTTLTGVEAvmyvgALSYDDLKtgVSIPCPCGGEWTVQ 226
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1303 TPQSGKgAVAIGTSadeptGPAIKFAAAHCwytnGKKTVNGYDTKANVvatYHRFDVPKPqlvedvvALPTKNDFEvlNV 1382
Cdd:cd21688    227 VIQQES-PFLLLSA-----APPAEYKLQQD----TFVAANVFTGNTNV---GHYTHVTAK-------ELLQKFDGA--KV 284
                          330
                   ....*....|....*
gi 1818222121 1383 EELPQDSVLHLDPPP 1397
Cdd:cd21688    285 TKTSEDKGPVTDVLY 299
CoV_Nsp8 cd21816
Coronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) ...
3189-3372 4.32e-85

Coronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) of alpha-, beta-, gamma- and deltacoronaviruses, 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. SARS-CoV Nsp8 forms a 8:8 hexadecameric supercomplex with Nsp7 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp8 forms a 1:2 heterotrimer with Nsp7. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.


Pssm-ID: 409256  Cd Length: 194  Bit Score: 277.48  E-value: 4.32e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3189 NINLDSYRIYKEADAIYKRSVEMNESPQEQKKKLKAVNIAKAEWEREAASQRKLEKLADAAMKSMYLAERAEDRRIKLTS 3268
Cdd:cd21816      3 FSHLPSYAAYATAQAAYEQAVKNGDSPQELKKLTKALNIAKSEFDRDAAVQKKLEKMADQAMTSMYKEARAEDRRAKITS 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3269 GLTAMLYHMLRRLDSDRVKALFECAKAQILPIHAVVGISNDNLKVIFNDKDSYSHYVEGNTLIHKGVRYTIVKKLSLDNA 3348
Cdd:cd21816     83 AMHALLFSMLKKLDSDAVNNIFEQARDGVVPLNIIPLTTANKLMVVIPDYETYKKTVDGNTFTYAGALWSIVTVVDADGK 162
                          170       180       190
                   ....*....|....*....|....*....|..
gi 1818222121 3349 PIE--------GVPEEFPVVVETVREGVPQLQ 3372
Cdd:cd21816    163 IVHlseinmdnSPNIAWPLIVTCLRAGAVKLQ 194
betaCoV_Nsp5_Mpro cd21666
betacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
2511-2804 4.17e-80

betacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in betacoronaviruses. 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. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394887  Cd Length: 297  Bit Score: 267.35  E-value: 4.17e-80
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2511 HPSGVVERCMVSVVYNGSALNGIWLKNVVYCPRHVIGKfrGDQWTH------MVSIADcRDFIVKCpiQGIQLNVQSVKM 2584
Cdd:cd21666      5 FPSGKVEGCMVQVTCGTMTLNGLWLDDTVYCPRHVICT--AEDMLNpnyedlLIRKTN-HSFLVQA--GNVQLRVIGHSM 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2585 VGALLQLTVHTNNTATPDYKFERLQPGSSMTIACAYDGIVRHVYHVVLQLNNLIYASFLNGACGSVGYTLKGKTLYLHYM 2664
Cdd:cd21666     80 QGCLLRLTVDTSNPKTPKYKFVRVKPGQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLCGSCGSVGYNIDGDCVSFCYM 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2665 HHIEFNNKTHSGTDLEGNFYGPYVDEEVIQQQTAFQYYTDNVVAQLYAHLLTVDarpKWLAQSQ-ISIEDFNSWAANNSF 2743
Cdd:cd21666    160 HQMELPTGVHTGTDLEGKFYGPFVDRQTAQAAGTDTTITLNVLAWLYAAVLNGD---RWFVNRFtTTLNDFNLWAMKYNY 236
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1818222121 2744 ANFPCEQTnmSYIMGLSQTARVPVERILNTIIQLTTN-RDGACIMGSYDFECDWTPEMVYNQ 2804
Cdd:cd21666    237 EPLTQDHV--DILDPLAAQTGIAVEDMLAALKELLQGgMQGRTILGSTILEDEFTPFDVVRQ 296
alphaCoV_Nsp5_Mpro cd21665
alphacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
2512-2804 2.44e-72

alphacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in alphacoronaviruses. 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. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394886  Cd Length: 296  Bit Score: 245.28  E-value: 2.44e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2512 PSGVVERCMVSVVYNGSALNGIWLKNVVYCPRHVIGK--------------FRgdqwTHMVSIADCRDFivkcpiqgiqL 2577
Cdd:cd21665      7 PSGVVEKCVVRVSYGNMVLNGLWLGDTVYCPRHVIASdttstidydheyslMR----LHNFSISVGNVF----------L 72
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2578 NVQSVKMVGALLQLTVHTNNTATPDYKFERLQPGSSMTIACAYDGIVRHVYHVVLQLNNLIYASFLNGACGSVGYTLKGK 2657
Cdd:cd21665     73 GVVGVTMRGALLVIKVNQNNVNTPKYTFRTLKPGDSFNILACYDGVPSGVYGVNMRTNYTIKGSFINGACGSPGYNLNNG 152
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2658 TLYLHYMHHIEFNNKTHSGTDLEGNFYGPYVDEEVIQQQTAFQYYTDNVVAQLYAHLLTVDARpkWLAQSQISIEDFNSW 2737
Cdd:cd21665    153 TVEFCYMHQLELGSGCHVGSDLDGVMYGGYEDQPTLQVEGANVLVTENVVAFLYAALLNGCNW--WLSSDRVTVEAFNEW 230
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1818222121 2738 AANNSFANFpceQTNMSYIMGLSQTArVPVERILNTIIQLTTNRDGACIMGSYDFECDWTPEMVYNQ 2804
Cdd:cd21665    231 AVANGFTTV---SSTDCFSILAAKTG-VDVERLLAAIQRLSKGFGGKTILGYTSLTDEFTLSEVIKQ 293
CoV_Nsp10 cd21872
coronavirus non-structural protein 10; This model represents the non-structural protein 10 ...
3483-3610 9.11e-70

coronavirus non-structural protein 10; This model represents the non-structural protein 10 (Nsp10) of alpha-, beta-, gamma- and deltacoronaviruses, 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Coronaviruses cap their mRNAs; RNA cap methylation may involve at least three proteins: Nsp10, Nsp14, and Nsp16. Nsp10 serves as a cofactor for both Nsp14 and Nsp16. Nsp14 consists of 2 domains with different enzymatic activities: an N-terminal ExoN domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. The association of Nsp10 with Nsp14 enhances Nsp14's exoribonuclease (ExoN) activity, and not its N7-Mtase activity. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The Nsp10/Nsp14 complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end, mimicking an erroneous replication product, and may function in a replicative mismatch repair mechanism. Nsp16 Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) acts sequentially to Nsp14 MTase in RNA capping methylation, and methylates the RNA cap at the ribose 2'-O position; it catalyzes the conversion of the cap-0 structure on m7GpppA-RNA to a cap-1 structure. The association of Nsp10 with Nsp16 enhances Nsp16's 2'OMTase activity, possibly through enhanced RNA binding affinity. Additionally, transmissible gastroenteritis virus (TGEV) Nsp10, Nsp16, and their complex can interact with DII4, which normally binds to Notch receptors; this interaction may disturb Notch signaling. Nsp10 also binds 2 zinc ions with high affinity.


Pssm-ID: 409325  Cd Length: 131  Bit Score: 230.82  E-value: 9.11e-70
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3483 SGTQIEYQQNASLLTYLAFAVDPKTAYLKHLADGGSPIQGCIQMIA-TMGPGFAVTTKPQPNEHQYSYGGASICLYCRAH 3561
Cdd:cd21872      1 AGNATEVPANSTVLSFCAFAVDPAKAYKDYLASGGQPITNCVKMLCtHTGTGQAITVKPEANMDQESFGGASVCLYCRAH 80
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1818222121 3562 IPHPGVDGRCPYKGRFVHIDKD--KEPVSFALTHEPCSSCQRWVNYDCTCG 3610
Cdd:cd21872     81 IDHPNPDGFCDYKGKFVQIPTTcaNDPVGFTLRNTVCTVCQMWKGYGCSCD 131
deltaCoV_Nsp9 cd21900
deltacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...
3373-3481 4.50e-68

deltacoronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) from deltacoronaviruses such as the Porcine delta coronavirus (PDCoV) Porcine coronavirus HKU15. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for coronavirus replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication.


Pssm-ID: 409333  Cd Length: 109  Bit Score: 225.01  E-value: 4.50e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3373 NNELCLRNVFTAQNTAQDFNGNESTVKSFYVTRTGKKILVAITSTKDNLKTVTCLTETGKTVLNLDPPMRFAHTVGGKQS 3452
Cdd:cd21900      1 NNELCLRNVFTAQNTASDGNGNESTAKSFYVSRTGKKILVAVTSTKDNLKTVTCDTDTGKVVLNLDPPMRFSHVVGGKQS 80
                           90       100
                   ....*....|....*....|....*....
gi 1818222121 3453 VVYLYFIQNISSLNRGMVIGHISETTILQ 3481
Cdd:cd21900     81 VVYLYFIQNISSLNRGMVIGHISGTTILQ 109
CoV_NSP10 pfam09401
Coronavirus RNA synthesis protein NSP10; Non-structural protein 10 (NSP10) is involved in RNA ...
3494-3610 1.01e-62

Coronavirus RNA synthesis protein NSP10; Non-structural protein 10 (NSP10) is involved in RNA synthesis. It is synthesized as a polyprotein whose cleavage generates many non-structural proteins. NSP10 contains two zinc binding motifs and forms two anti-parallel helices which are stacked against an irregular beta sheet. A cluster of basic residues on the protein surface suggests a nucleic acid-binding function. NSP10 interacts with NSP14 and NSP16 and regulates their respective ExoN and 2-O-MTase activities. When binding to the N-terminal of NSP14, nsp10 allows the ExoN active site to adopt a stably closed conformation and is an allosteric regulator that stabilizes NSP16. The residue Tyr-96 plays a crucial role in the NSP10-NSP16/NSP14 interaction. This residue is specific for SARS-CoV NSP10 and is a phenylalanine in most other Coronavirus homologs.


Pssm-ID: 462788  Cd Length: 119  Bit Score: 210.37  E-value: 1.01e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3494 SLLTYLAFAVDPKTAYLKHLADGGSPIQGCIQMIAT-MGPGFAVTTKPQPNEHQYSYGGASICLYCRAHIPHPGVDGRCP 3572
Cdd:pfam09401    1 SLLSLCAFAVDPAKAYLDYLAQGGQPITNCVKMLCNhAGTGMAITVKPEANTDQDSYGGASVCLYCRAHIEHPNVDGLCQ 80
                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1818222121 3573 YKGRFVHIDKD-KEPVSFALTHEPCSSCQRWVNYDCTCG 3610
Cdd:pfam09401   81 LKGKFVQIPTGtKDPVSFCLTNTVCTVCGCWLGYGCSCD 119
deltaCoV_Nsp7 cd21829
deltacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...
3088-3183 2.44e-53

deltacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of deltacoronaviruses that include White-eye coronavirus HKU16 and Quail coronavirus UAE-HKU30, among others. 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp7 forms a 2:1 heterotrimer with Nsp8. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.


Pssm-ID: 409255  Cd Length: 96  Bit Score: 182.34  E-value: 2.44e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3088 NKILDAKATAVVVANLLEKAGVTNKHAICKKIVKLHNDTLKATTYEEVEVALVKLLSHIIEFLPTDQVDAYLADAANAQH 3167
Cdd:cd21829      1 NKTLDAKATAVVVANLLEKAGVTNKHEVCKKIVKLHNDTLKATTYEEAETSLVKLLAHIIEFLPTDQVDAYLADAVKVQH 80
                           90
                   ....*....|....*.
gi 1818222121 3168 VNTYFDNLLENKAVVQ 3183
Cdd:cd21829     81 LNTYFDSLLENKLVLQ 96
CoV_Nsp9 cd21881
coronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) ...
3373-3481 5.31e-53

coronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) from coronaviruses, 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 assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for CoV replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG at the C-terminus; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication.


Pssm-ID: 409329  Cd Length: 111  Bit Score: 181.94  E-value: 5.31e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3373 NNELCLRNVFTAQNTAQDFNG-NESTVKSFYVTRTGKKILVAITSTKDNLKTVTCLTET-GKTVLNLDPPMRFAHTVGGK 3450
Cdd:cd21881      1 NNELSPVALKQMSCAAGTDQTcTDDEAKAYYNNSKGGRFVLAITSDKPDLKVARFLKEDgGTIYTELEPPCRFVTDVPKG 80
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1818222121 3451 QSVVYLYFIQNISSLNRGMVIGHISETTILQ 3481
Cdd:cd21881     81 PKVKYLYFIKNLNSLNRGMVLGSISATVRLQ 111
alpha_betaCoV_Nsp10 cd21901
alphacoronavirus and betacoronavirus non-structural protein 10; This model represents the ...
3484-3609 3.24e-50

alphacoronavirus and betacoronavirus non-structural protein 10; This model represents the non-structural protein 10 (Nsp10) of alpha- and betacoronaviruses, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), Middle East respiratory syndrome-related (MERS) CoV, and alphacoronaviruses such as Human coronavirus 229E. 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Coronaviruses cap their mRNAs; RNA cap methylation may involve at least three proteins: Nsp10, Nsp14, and Nsp16. Nsp10 serves as a cofactor for both Nsp14 and Nsp16. Nsp14 consists of 2 domains with different enzymatic activities: an N-terminal ExoN domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. The association of Nsp10 with Nsp14 enhances Nsp14's exoribonuclease (ExoN) activity, and not its N7-Mtase activity. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The Nsp10/Nsp14 complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end, mimicking an erroneous replication product, and may function in a replicative mismatch repair mechanism. Nsp16 Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) acts sequentially to Nsp14 MTase in RNA capping methylation, and methylates the RNA cap at the ribose 2'-O position; it catalyzes the conversion of the cap-0 structure on m7GpppA-RNA to a cap-1 structure. The association of Nsp10 with Nsp16 enhances Nsp16's 2'OMTase activity, possibly through enhanced RNA binding affinity. Additionally, transmissible gastroenteritis virus (TGEV) Nsp10, Nsp16 and their complex can interact with DII4, which normally binds to Notch receptors; this interaction may disturb Notch signaling. Nsp10 also binds 2 zinc ions with high affinity.


Pssm-ID: 409326  Cd Length: 130  Bit Score: 174.78  E-value: 3.24e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3484 GTQIEYQQNASLLTYLAFAVDPKTAYLKHLADGGSPIQGCIQMIAT-MGPGFAVTTKPQPNEHQYSYGGASICLYCRAHI 3562
Cdd:cd21901      2 GKQTEVASNSSLLTLCAFAVDPAKTYLDAVKSGGKPVGNCVKMLTNgTGTGQAITVKPEANTNQDSYGGASVCLYCRAHV 81
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1818222121 3563 PHPGVDGRCPYKGRFVHIDKD-KEPVSFALTHEPCSSCQRWVNYDCTC 3609
Cdd:cd21901     82 EHPDMDGVCKLKGKYVQVPLGtNDPVRFCLENDVCKVCGCWLGNGCSC 129
Macro_X_Nsp3-like cd21557
X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The ...
961-1086 4.91e-42

X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The X-domain, also called Mac1, is the macrodomain found in riboviral non-structural protein 3 (Nsp3), including the Nsp3 of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) as well as SARS-CoV-2, and other coronaviruses (alpha-, beta-, gamma-, and deltacoronavirus), among others. The SARS-CoV-2 Nsp3 Mac1 is highly conserved among all CoVs, and binds to and hydrolyzes mono-ADP-ribose (MAR) from target proteins. It appears to counter host-mediated antiviral ADP-ribosylation, a post-translational modification that is part of the host response to viral infections. Mac1 is essential for pathogenesis in multiple animal models of CoV infection, implicating it as a virulence factor and potential therapeutic target. Assays show that the de-MARylating activity leads to a rapid loss of substrate, and that Mac1 could not hydrolyze poly-ADP-ribose; thus, Mac1 is a MAR-hydrolase (mono-ADP ribosylhydrolase). Mac1 was originally named ADP-ribose-1"-phosphatase (ADRP) based on data demonstrating that it could remove the phosphate group from ADP-ribose-1"-phosphate; however, activity was modest and was unclear why this would impact a virus infection. This family also includes the X-domain of Avian infectious bronchitis virus (IBV) strain Beaudette coronavirus that does not bind ADP-ribose; the triple glycine sequence found in the X-domains of SARS-CoV and human coronavirus 229E (HCoV229E), which are involved in ADP-ribose binding, is not conserved in the IBV X-domain. SARS-CoVs have two other macrodomains referred to as the SUD-N (N-terminal subdomain, or Mac2) and SUD-M (middle SUD subdomain, or Mac3) of the SARS-unique domain (SUD), which also do not bind ADP-ribose; these bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). SARS-CoV SUD-N and SUD-M are not included in this group.


Pssm-ID: 438957  Cd Length: 127  Bit Score: 151.55  E-value: 4.91e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  961 NSVLVNPANAQLTNGGGAARAIAKLAGPKYQEYCNSVApISGPLTTDSFDAKK--LGVACILHVVPPKGSDPNVQELLYQ 1038
Cdd:cd21557      1 EDVVVNAANENLKHGGGVAGAIYKATGGAFQKESDYIK-KNGPLKVGTAVLLPghGLAKNIIHVVGPRKRKGQDDQLLAA 79
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1818222121 1039 AYKSILTEPAHYVIPILGAGIFGCNPVHSLDAFRKACPSDIGRVTLVT 1086
Cdd:cd21557     80 AYKAVNKEYGSVLTPLLSAGIFGVPPEQSLNALLDAVDTTDADVTVYC 127
gammaCoV_Nsp10 cd21902
gammacoronavirus non-structural protein 10; This model represents the non-structural protein ...
3484-3609 2.09e-41

gammacoronavirus non-structural protein 10; This model represents the non-structural protein 10 (Nsp10) of gammacoronaviruses, including Infectious bronchitis virus (IBV)and Bottlenose dolphin coronavirus HKU22(BdCoV HKU22). 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Coronaviruses cap their mRNAs; RNA cap methylation may involve at least three proteins: Nsp10, Nsp14, and Nsp16. Nsp10 serves as a cofactor for both Nsp14 and Nsp16. Nsp14 consists of 2 domains with different enzymatic activities: an N-terminal ExoN domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. The association of Nsp10 with Nsp14 enhances Nsp14's exoribonuclease (ExoN) activity, and not its N7-Mtase activity. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The Nsp10/Nsp14 complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end, mimicking an erroneous replication product, and may function in a replicative mismatch repair mechanism. Nsp16 Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) acts sequentially to Nsp14 MTase in RNA capping methylation and methylates the RNA cap at the ribose 2'-O position; it catalyzes the conversion of the cap-0 structure on m7GpppA-RNA to a cap-1 structure. The association of Nsp10 with Nsp16 enhances Nsp16's 2'OMTase activity, possibly through enhanced RNA binding affinity. Additionally, transmissible gastroenteritis virus (TGEV) Nsp10, Nsp16 and their complex can interact with DII4, which normally binds to Notch receptors; this interaction may disturb Notch signaling. Nsp10 also binds 2 zinc ions with high affinity.


Pssm-ID: 409327  Cd Length: 134  Bit Score: 150.05  E-value: 2.09e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3484 GTQIEYQQNASLLTYLAFAVDPKTAYLKHLADGGSPIQGCIQMIATM-GPGFAVTTKPQPNEHQYSYGGASICLYCRAHI 3562
Cdd:cd21902      2 GHETEEVDAVGILSLCSFAVDPADTYCKYVAAGNQPLGNCVKMLTVHnGSGFAITSKPSPTPDQDSYGGASVCLYCRAHI 81
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1818222121 3563 PHPGV----DGRCPYKGRFVHI-DKDKEPVSFALTHEPCSSCQRWVNYDCTC 3609
Cdd:cd21902     82 AHPGGagnlDGRCQFKGSFVQIpTTEKDPVGFCLRNKVCTVCQCWIGYGCQC 133
alphaCoV-Nsp6 cd21558
alphacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...
2797-3087 2.90e-37

alphacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.


Pssm-ID: 394844  Cd Length: 293  Bit Score: 143.88  E-value: 2.90e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2797 TPEMVYNQAPISLQSGVVKKTC---TWFFHFVFMAITMLLAAMHVFPVHLYPI--VLPCFTVVAFLLTLTIKHTVVFTTT 2871
Cdd:cd21558      3 TSEVIKQMYGVNLQSGKVKSAFknvLLVGVFLFMFWSELLMYTSFFWINPGLVtpVFLVLVLVSLLLTLFLKHKMLFLQT 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2872 YLLPSLLMMVVNaNTFWipNTFLRTCYETIFGSPIAqrLYGYTVALYMLIYAGLAINYtLKTLRY--RATSFLSFCMQWF 2949
Cdd:cd21558     83 FLLPSVIVTAFY-NLAW--DYYVTAVLAEYFDYHVS--LMSFDIQGVLNIFVCLFVFF-LHTYRFvtSGTSWFTYVVSLV 156
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2950 QYGYVAHIAYKLLnkpwteSLLFTAFTMLTSHPLLAALSWWLAGRVT-----LPIIMPDLAIRVLAYNVIGYVICVRFGL 3024
Cdd:cd21558    157 FVLYNYFYGNDYL------SLLMMVLSSITNNWYVGAIAYKLAYYIVyvppsLVADFGTVKAVMLVYVALGYLCCVYYGI 230
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1818222121 3025 MWLANRFTTVPMGTYQYMVSVEQLKYMMAVKMSPPRNAFEVLIANIRLLGLGGNRNIAVSTVQ 3087
Cdd:cd21558    231 LYWINRFTKLTLGVYDFKVSAAEFKYMVANGLKAPTGVFDALLLSFKLIGIGGERTIKISTVQ 293
CoV_NSP8 pfam08717
Coronavirus replicase NSP8; Viral NSP8 (non structural protein 8) forms a hexadecameric ...
3184-3340 2.87e-35

Coronavirus replicase NSP8; Viral NSP8 (non structural protein 8) forms a hexadecameric supercomplex with NSP7 that adopts a hollow cylinder-like structure. The dimensions of the central channel and positive electrostatic properties of the cylinder imply that it confers processivity on RNA-dependent RNA polymerase. NSP7 and NSP8 heterodimers play a role in the stabilization of NSP12 regions involved in RNA binding and are essential for a highly active NSP12 polymerase complex. It has been demonstrated that NSP8 acts as an oligo(U)-templated polyadenylyltransferase but also has robust (mono/oligo) adenylate transferase activities. NSP8 has N- and C-terminal D/ExD/E conserved motifs, being the N-terminal motif critical for RNA polymerase activity as these residues are part of the Mg2-binding active site.


Pssm-ID: 400866  Cd Length: 197  Bit Score: 134.59  E-value: 2.87e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3184 AVADININLDSYRIYKEADAIYKRSVEMNESPQEQKKKLKAVNIAKAEWEREAASQRKLEKLADAAMKSMYLAERAEDRR 3263
Cdd:pfam08717    1 SVASEFSSLPSYAAYETAKEAYEEAVANGSSQQVLKQLKKACNIAKSEFDRDAAVQKKLEKMAEQAMTQMYKEARAVDRK 80
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1818222121 3264 IKLTSGLTAMLYHMLRRLDSDRVKALFECAKAQILPIHAVVGISNDNLKVIFNDKDSYSHYVEGNTLIHKGVRYTIV 3340
Cdd:pfam08717   81 SKVVSAMHTLLFSMLRKLDNSALNTIINNARNGVVPLNIIPATTAAKLTVVVPDYETFVKVVDGNTVTYAGAVWEIQ 157
TM_Y_betaCoV_Nsp3_C cd21713
C-terminus of betacoronavirus non-structural protein 3, including transmembrane and Y domains; ...
1498-1989 1.20e-34

C-terminus of betacoronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from 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. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In SARS-CoV and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409661  Cd Length: 545  Bit Score: 142.63  E-value: 1.20e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1498 TCL-GLYYSAQTLFVSLAPFLMLPAVVSLLNsgyTIGTYLYAKTgwPC-NYNATQHFDYNSYCAGDLVCQACFDGQDSLH 1575
Cdd:cd21713      7 LCLtVLLLWFNFLYANFILSDSPTFVGSIVA---WFKYTLGIST--ICdFYQVTYLGDISEFCTGSMLCSLCLSGMDSLD 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1576 LYPHLRVNQQPIQTTDYTVYALSL-----------------ILLLANMTLVMGTLIVTFFVNFYGVQIPFYGTLLIDYQS 1638
Cdd:cd21713     82 NYDALNMVQHTVSSRLSDDYIFKLvlelffayllytvafyvLGLLAILQLFFSYLPLFFMLNSWLVVLFVYVINMVPAST 161
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1639 ALMMTFSVYYFYKVMKFFRHLTHGCKIPTCMVCAKLRTPPTITVETVVQGRKYPSVIETNGGFTICKEHNFYCKDCSLQT 1718
Cdd:cd21713    162 LVRMYIVVASLYFVYKLYVHVVYGCNDTACLMCYKRNRATRVECSTVVNGSKRSFYVMANGGTGFCTKHNWNCVNCDTYG 241
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1719 PG-TFIPTEAIESLSRATRLSVKPTAPAFLLARDVECQTDVVvaRAMHNQNAHVCISKYSDIRTVD-QLLKPTPLFSYTP 1796
Cdd:cd21713    242 PGnTFICDEVAADLSTQFKRPINPTDSSYYSVTSVEVKNGSV--HLYYERDGQRVYERFSLSLFVNlDKLKHSEVKGSPP 319
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1797 DVIIAADFDNRGSLKTAKELAVVLSMDLKRTIIIIDQAYSRPIDNYQEVAS-------------------RIEKYYPVAK 1857
Cdd:cd21713    320 FNVIVFDASNRAEENGAKSAAVYYSQLLCKPILLVDKKLVTTVGDSAEVARkmfdayvnsflstynvtmdKLKTLVSTAH 399
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1858 --------ITPTGDIFTDIKQATNGQASD----SAINAAVLAVQRGLDFTIDNPNNILPHYAfDFSTLNAEDQSTILESG 1925
Cdd:cd21713    400 nslkegvqLEQVLKTFIGAARQKAAVESDvetkDIVKCVQLAHQADVDFTTDSCNNLVPTYV-KVDTITTADLGVLIDNN 478
                          490       500       510       520       530       540
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1818222121 1926 CAKGN---LKGTNVGVVLSASLVTRLSQQAIRVIANAASRNGVTCAVTPSTLVMRGNIATQPLTRIK 1989
Cdd:cd21713    479 AKHVNanvAKAANVALIWNVAAFLKLSESLRRQLRSAARKTGLNFKLTTSKLRAVVPILTTPFSLKG 545
TM_Y_alphaCoV_Nsp3_C cd21712
C-terminus of alphacoronavirus non-structural protein 3, including transmembrane and Y domains; ...
1497-1992 1.15e-32

C-terminus of alphacoronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from alphacoronavirus, including Porcine epidemic diarrhea virus and Human coronavirus 229E, among others. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In the related betacoronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409660  Cd Length: 501  Bit Score: 135.83  E-value: 1.15e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1497 KTCLGLY--YSAQTLFVSLAPFlmlpavVSLLNSGYTIGtylYAktgwpcnyNATqhFDYNSYCAGDLVCQACFDGQDSL 1574
Cdd:cd21712     14 KLLLLLYalYALLFMFVRFPPL------NSSLCSGYVDG---YA--------NSS--FVKSEVCGNSLLCKACLAGYDEL 74
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1575 HLYPHLRVNQQ----PIQTTDYTVYALSLILLLANMTLVMGTL-IVTFFVN----FYGVQIPFYGTLLIDYQSALMMTFS 1645
Cdd:cd21712     75 SDFPHLQVVWDhvsdPLFSNVLPLFYFAFLLIFGNNYVRCFLLyFVAQYINnwgvYFGYQDYSWFLHFVPFDSFSDEIVV 154
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1646 VYYFYKVMKFFRHLTHGCKIPTCMVCAKLRTPPTITVETVVQGRKYPSVIETNGGFTICKEHNFYCKDCSLQTPG-TFIP 1724
Cdd:cd21712    155 IFIVVKVLLFLKHVIFGCDKPSCKACSKSARLTRIPVQTIVNGSMKSFYVHANGGGKFCKKHNFFCVNCDSYGVGnTFIN 234
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1725 TEAIESLSRATRLSVKPTAPAFLLARDVECQTD---VVVARAMHNQNAHVCISKYSdirtVDQLLKPTPLFSytpDVIIa 1801
Cdd:cd21712    235 DEVARELSNVVKTTVQPTGPAYIEVDKVEFSNGfyyLYSGDTFWRYNFDITEKKYS----CKEVLKNCNLLD---DFIV- 306
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1802 adFDNRGS-LKTAKELAVVLSMDLKRTIIIIDQAY--SRPIDNYQEVASriekyypvAKITPTGDIF----------TDI 1868
Cdd:cd21712    307 --YNNNGSnVAQVKNACVYFSQLLCKPIKLVDSALlsSLSVDFNGALHK--------AFVKVLKNSFnkdlsncktlEEC 376
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1869 KQATNGQASDSA-INAAVLAVQRGLDFTIDNPNNILPHYAFDFSTLNAEDQSTILESGCAKGN---LKGTNVGVVLSASL 1944
Cdd:cd21712    377 KKALGLDVSDDEfESAVSNAHRYDVLLTDRSFNNFVTSYAKPEEKLSTHDIAVCMRAGAKVVNhnvLTKENVPIVWLAKD 456
                          490       500       510       520
                   ....*....|....*....|....*....|....*....|....*...
gi 1818222121 1945 VTRLSQQAIRVIANAASRNGVTCAVTPSTLVMRGNIatqPLTRIKAGA 1992
Cdd:cd21712    457 FSALSEEARKYIVKTTKAKGVNFLLTFNDNRMTTTL---PAVSIVSKK 501
CoV_Nsp7 cd21811
coronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) ...
3088-3183 3.19e-32

coronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of alpha-, beta-, gamma- and deltacoronaviruses, 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp7 forms a 2:1 heterotrimer with Nsp8. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.


Pssm-ID: 409251  Cd Length: 83  Bit Score: 121.82  E-value: 3.19e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3088 NKILDAKATAVVVANLLEKAGVTNKHAICKKIVKLHNDTLKATTYEEVEVALVKLLSHIIEFLPTdqvdayladaanaQH 3167
Cdd:cd21811      1 SKLTDVKCTAVVLLSLLQKLRVESNSKLWKQCVQLHNDILLAKDTTEVFEKLVSLLSVLLSMQGA-------------VD 67
                           90
                   ....*....|....*.
gi 1818222121 3168 VNTYFDNLLENKAVVQ 3183
Cdd:cd21811     68 LNRLCEEMLENRAVLQ 83
gammaCoV-Nsp6 cd21559
gammacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...
2799-3087 4.79e-32

gammacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.


Pssm-ID: 394845  Cd Length: 307  Bit Score: 129.12  E-value: 4.79e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2799 EMVYNQ-APISLQSGVVKKTCTWFFHFV----FMAITMLLAAMHVFPVHLYP-IVLPCFTVVAFLlTLTIKHTVVFTTTY 2872
Cdd:cd21559      1 ESVFNQvGGVRLQSSFVKKATSWFWSRCvlacFLFVLCAIVLFTAVPLKYYVhAAVILLVAVLFI-SFTVKHVMAFMDTF 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2873 LLPSLLMMV--VNANTFWIPNTFLRTCYetIFGSPIAQRLYGYTVALYMLIYAGLAINYTLKTLRYRATSF---LSFCMQ 2947
Cdd:cd21559     80 LLPTLCTVIigVCAEVPFIYNTLISQVV--IFFSQWYDPVVFDTVVPWMFLPLVLYTAFKCVQGCYSINSFstsLLVLYQ 157
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2948 WFQYGYVAHIAYKLLNK----PWTESLLFTAFTML---TSHPLLAALSWWLAG---RVTLPIIMPDLAIRVLAYNVIGYV 3017
Cdd:cd21559    158 FMKLGFVIYTSSNTLTAytegNWELFFELVHTTVLanfSSNSLIGLIVFKIAKwmlYYCNATYFNSYVLMAVMVNVIGWL 237
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3018 ICVRFGLMWLANRFTTVPMGTYQYMVSVEQLKYMMAVKMSPPRNAFEVLIANIRLLGLGGNRNIAVSTVQ 3087
Cdd:cd21559    238 FTCYFGLYWWLNKVFGLTLGKYNYKVSVEQYKYMCLHKIRPPKSVWDVFSTNMLIQGIGGERVLPIATVQ 307
alphaCoV_Nsp8 cd21830
alphacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...
3184-3350 7.87e-32

alphacoronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) region of alphacoronaviruses that include Feline infectious peritonitis virus (FCoV), Human coronavirus NL63 (HCoV-NL63), and Porcine epidemic diarrhea coronavirus (PEDV), among others. 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. FCoV Nsp8 forms a 1:2 heterotrimer with Nsp7; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.


Pssm-ID: 409257  Cd Length: 195  Bit Score: 124.77  E-value: 7.87e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3184 AVADININLDSYRIYKEADAIYKRSVEMNESPQEQKKKLKAVNIAKAEWEREAASQRKLEKLADAAMKSMYLAERAEDRR 3263
Cdd:cd21830      1 SVASTFANMPSFIAYETARQDYEDAVKNGSSPQLIKQLKKAMNIAKSEFDREASVQRKLDRMAEQAAAQMYKEARAVNRK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3264 IKLTSGLTAMLYHMLRRLDSDRVKALFECAKAQILPIHAVVGISNDNLKVIFNDKDSYSHYVEGNTLIHKGVRYTIVKKL 3343
Cdd:cd21830     81 SKVISAMHSLLFGMLRRLDMSSVDTILNLAKDGVVPLSIIPAASATRLVVVVPDLESFSKIRRDGCVHYAGVVWTIVDIK 160

                   ....*..
gi 1818222121 3344 SLDNAPI 3350
Cdd:cd21830    161 DNDGKVV 167
betaCoV_Nsp8 cd21831
betacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...
3191-3365 2.29e-30

betacoronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) the highly pathogenic betacoronaviruses that include 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. SARS-CoV Nsp8 forms a 8:8 hexadecameric supercomplex with Nsp7 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.


Pssm-ID: 409258  Cd Length: 196  Bit Score: 120.66  E-value: 2.29e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3191 NLDSYRIYKEADAIYKRSVEMNESPQEQKKKL-KAVNIAKAEWEREAASQRKLEKLADAAMKSMYLAERAEDRRIKLTSG 3269
Cdd:cd21831      5 NLASYAEYETAQKAYDEAVASGDASPQVLKALkKAVNVAKSAYEKDKAVARKLERMADQAMTSMYKQARAEDKKSKVVSA 84
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3270 LTAMLYHMLRRLDSDRVKALFECAKAQILPIHAVVGISNDNLKVIFNDKDSYSHYVEGNTLIHKGVRYTIVKKLSLDNAP 3349
Cdd:cd21831     85 MQTMLFGMIRKLDNDALNNIINNARNGCVPLSIIPLTAANKLRVVVPDYSVYKQVVDGPTLTYAGALWDIQQINDADGKI 164
                          170       180
                   ....*....|....*....|...
gi 1818222121 3350 I-------EGVPEEFPVVVETVR 3365
Cdd:cd21831    165 VqlsditeDSENLAWPLVVTATR 187
betaCoV-Nsp6 cd21560
betacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell ...
2814-3087 2.10e-28

betacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.


Pssm-ID: 394846  Cd Length: 290  Bit Score: 118.11  E-value: 2.10e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2814 VKKTCTWFFHFVFM-AITMLLAAMHV--------FPVHLYPIVLPCFTVVAFLLTLTIKHTVVFTTTYLLPSLlMMVVNA 2884
Cdd:cd21560      3 VKRVVKGTLHWLLAtFVLFYLIILQLtkwtmfmyLTETMLLPLTPALCCVSACVMLLVKHKHTFLTLFLLPVL-LTLAYY 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2885 NTFWIPNTFLRTCYETIFGSPIAQRLYGYTVALYMLIYAGLAINYTLKTLRYRATS---FLSFCMQWFQ---YGYVAHIA 2958
Cdd:cd21560     82 NYVYVPKSSFLGYVYNWLNYVNPYVDYTYTDEVTYGSLLLVLMLVTMRLVNHDAFSrvwAVCRVITWVYmwyTGSLEESA 161
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2959 YKLLnkpwteSLLFTAFTMLTSHPLLA------ALSWWLAGRVTLPIIMPDLAIRVLAYNVIGYVICVRFGLMWLANRFT 3032
Cdd:cd21560    162 LSYL------TFLFSVTTNYTGVVTVSlalakfITALWLAYNPLLFLDIPEVKCVLLVYLFIGYICTCYFGVFSLLNRLF 235
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1818222121 3033 TVPMGTYQYMVSVEQLKYMMAVKMSPPRNAFEVLIANIRLLGLGGNRNIAVSTVQ 3087
Cdd:cd21560    236 RCPLGVYDYKVSTQEFRYMNANGLRPPRNSWEALMLNFKLLGIGGVPCIKVSTVQ 290
gammaCoV_Nsp8 cd21832
gammacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...
3194-3339 6.55e-25

gammacoronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) region of gammacoronaviruses that include Avian infectious bronchitis virus (IBV) and Canada goose coronavirus (CGCoV), among others. 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9, and Nsp10 form functional complexes with CoV core enzymes and thereby stimulate replication. Most importantly, a complex of Nsp8 with Nsp7 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the genes encoding Nsp8 and Nsp7 have been shown to delay virus growth. Nsp8 and Nsp7 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp8 with Nsp7 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp8 has a novel 'golf-club' fold composed of an N-terminal 'shaft' domain and a C-terminal 'head' domain. The shaft domain contains three helices, one of which is very long, while the head domain contains another three helices and seven beta-strands, forming an alpha/beta fold. SARS-CoV Nsp8 forms a 8:8 hexadecameric supercomplex with Nsp7 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp8 forms a 1:2 heterotrimer with Nsp7. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to the template length.


Pssm-ID: 409259  Cd Length: 210  Bit Score: 105.42  E-value: 6.55e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3194 SYRIYKEADAIYKR----SVEMNESPQEQKKKLKAVNIAKAEWEREAASQRKLEKLADAAMKSMYLAERAEDRRIKLTSG 3269
Cdd:cd21832     11 SYAEYERAKDLYEKvladSKNGGVTQQELAAYRKAANIAKSVFDRDLAVQKKLDSMAERAMTTMYKEARVTDRRAKLVSS 90
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3270 LTAMLYHMLRRLDSDRVKALFECAKAQILPIHAVVGISNDNLKVIFNDKDSYSHYVEGNTLIHKGVRYTI 3339
Cdd:cd21832     91 LHALLFSMLKKIDSEKLNVLFDQASSGVVPLATVPIVCSNKLTLVIPDPETWVKCVEGMHVTYSTVVWNI 160
TM_Y_gammaCoV_Nsp3_C cd21710
C-terminus of gammacoronavirus non-structural protein 3, including transmembrane and Y domains; ...
1552-1972 1.91e-24

C-terminus of gammacoronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from gammacoronavirus, including Infectious bronchitis virus. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In the related betacoronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409658  Cd Length: 525  Bit Score: 111.00  E-value: 1.91e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1552 FDYNSYCAGDLVCQACFDGQDSLHLYPHL----RVNQQPIQTTDYTVYALSLILLLANMTLVMGTLIVTFFVNFY--GVQ 1625
Cdd:cd21710     56 FDVLRYCGDDFTCRVCLHDKDSLHLYKHAysveQFYKDAVSGISFNWNWLYLVFLILFVKPVAGFVIICYCVKYLvlSST 135
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1626 IPFYGTLLIDYQSALMMT--------FSVYYFYKVMKFFRHLTHgCKIPTCMVCAKLRTPPTITVETVVQGRKYPSVIET 1697
Cdd:cd21710    136 VLQTGVGFLDWFIQTVFThfnfmgagFYFWLFYKIYIQVHHILY-CKDITCEVCKRVARSNRHEVSVVVGGRKQLVHVYT 214
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1698 NGGFTICKEHNFYCKDCSLQTP-GTFIPTEAIESLSRATRLSVKPTAPAFLLArDVECQTDVVV-----ARAMHNQNAHV 1771
Cdd:cd21710    215 NSGYNFCKRHNWYCRNCDKYGHqNTFMSPEVAGELSEKLKRHVKPTAHAYHVV-DDACLVDDFVnlkykAATPGKDGAHS 293
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1772 CISKYSdirtVDQLLKPTPLF-------SYTPDVIIAADFDNRGSLKTAKELAVVLSMDLKRTIIIIDQAYsrpidnYQE 1844
Cdd:cd21710    294 AVKCFS----VSDFLKKAVFLkdalkceQISNDSFIVCNTQSAHALEEAKNAAIYYAQYLCKPILILDQAL------YEQ 363
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1845 VASRiekyyPVAK--ITPTGDIFTDI----KQATNGQA------------SDSAINAAVLAVQRGLDFTIDNPNNILPHY 1906
Cdd:cd21710    364 LVVE-----PVSKsvVDKVCSILSNIisvdTAALNYKAgtlrdallsvtkDEEAVDMAIFCHNNDVEYTSDGFTNVVPSY 438
                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1818222121 1907 AFDFSTLNAEDQSTILESGCAKGNLKGTNV-GVVLSASLVTRLSQQAIRVIANAASRNGVTCAVTPS 1972
Cdd:cd21710    439 GIDTDKLTPRDRGFLINADASIANLRVKNApPVVWKFSDLIKLSDSCLKYLISATVKSGGRFFITRS 505
CoV_NSP4_C pfam16348
Coronavirus replicase NSP4, C-terminal; This is the C-terminal domain of the coronavirus ...
2413-2498 2.92e-22

Coronavirus replicase NSP4, C-terminal; This is the C-terminal domain of the coronavirus nonstructural protein 4 (NSP4). NSP4 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. It is a membrane-spanning protein which is thought to anchor the viral replication-transcription complex (RTC) to modified endoplasmic reticulum membranes. This predominantly alpha-helical domain may be involved in protein-protein interactions. It has been shown that in Betacoronavirus, the coexpression of NSP3 and NSP4 results in a membrane rearrangement to induce double-membrane vesicles (DMVs) and convoluted membranes (CMs), playing a critical role in SARS-CoV replication. There are two well conserved amino acid residues (H120 and F121) in NSP4 among Betacoronavirus, essential for membrane rearrangements during interaction with NSP3.


Pssm-ID: 465099  Cd Length: 92  Bit Score: 93.75  E-value: 2.92e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 2413 SSFLDAAKATFVIDNEKYVLLKDLAGAE-FDQYLASYNKYKYFSGTASDKDYDKVCMAFLAKALSSFREGGGSQLYTPPK 2491
Cdd:pfam16348    6 GTFEEAALGTFVIDKESYEKLKNSISLDkFNRYLSLYNKYKYYSGKMDEADYREACCAHLAKALEDFSNSGNDVLYTPPT 85

                   ....*..
gi 1818222121 2492 FAVVQSL 2498
Cdd:pfam16348   86 VSVTSSL 92
TM_Y_MERS-CoV-like_Nsp3_C cd21716
C-terminus of non-structural protein 3, including transmembrane and Y domains, from Middle ...
1541-1980 4.89e-20

C-terminus of non-structural protein 3, including transmembrane and Y domains, from Middle East respiratory syndrome-related coronavirus and betacoronavirus in the C lineage; This model represents the C-terminus of non-structural protein 3 (Nsp3) from betacoronavirus in the merbecovirus subgenus (C lineage), including Middle East respiratory syndrome-related coronavirus (MERS-CoV) and Tylonycteris bat coronavirus HKU4. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In the related betacoronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409664  Cd Length: 566  Bit Score: 97.57  E-value: 4.89e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1541 GWPCNYNATQhFDYNSYCAG-DLVCQACFDGQDSLHLYPHLRVNQQPIQ----TTDYTVYALSLILLLA------NMTLV 1609
Cdd:cd21716     58 GLASAYRANS-FDVPDFCANrSALCNWCLIGQDSITHYSALKMVQTHLShyvlNIDWLWFALELLLAYVlytsafNWLLL 136
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1610 MGTLiVTFFVnfygvqipfYGTLLIDYQSALMMTFSVYYF------------YKVM-------KFFRHLTHGCKIPTCMV 1670
Cdd:cd21716    137 ACTL-QYFFA---------QTSAFVDWRSYNYVVSGIFLLfthipldglvriYNVLaclwflrKFYNHVINGCKDTACLL 206
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1671 CAKLRTPPTITVETVVQGRKYPSVIETNGGFTICKEHNFYCKDCSLQTPG-TFIPTEAIESLSRATRLSVKPTAPAFLLA 1749
Cdd:cd21716    207 CYKRNRLTRVEASTVVCGGKRTFYITANGGTSFCRRHNWNCVDCDTAGVGnTFICEEVANDLTTSLRRLVKPTDRSHYYV 286
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1750 RDVECQTDVVvaRAMHNQNAHVCISKYS-------DIRTVDQLLKPT---PLFSYtpdviIAADFDNRGSLKTAKELAVV 1819
Cdd:cd21716    287 DSVEVKDTVV--QLNYRRDGQSCYERFPlcyftnlDKLKFKEVCKTTtgiPEHNF-----IIYDSSDRGQENLARSACVY 359
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1820 LSMDLKRTIIIIDQAYSRPIDNYQEVAS-------------------RIEKYYPVAK--------ITPTGDIFTDIKQAT 1872
Cdd:cd21716    360 YSQVLCKPILLVDSNLVTSVGDSSEIAIkmfdsfvnsfvslynvtrdKLEKLISTARdgvkrgdnFQSVLKTFIDAARGP 439
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1873 NGQASDSAINAAVLAVQRG----LDFTIDNPNNILPHYaFDFSTLNAEDQSTILESGCA---KGNLKGTNVGVVLSASLV 1945
Cdd:cd21716    440 AGVESDVETNEIVDAVQYAhkhdIQLTTESYNNYVPSY-VKPDSVATSDLGSLIDCNAAsvnQTSMRNANGACIWNAAAY 518
                          490       500       510
                   ....*....|....*....|....*....|....*
gi 1818222121 1946 TRLSQQAIRVIANAASRNGVTCAVTPSTLVMRGNI 1980
Cdd:cd21716    519 MKLSDSLKRQIRIACRKCNLNFRLTTSKLRANDNI 553
gammaCoV_Nsp9 cd21899
gammacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...
3371-3481 1.91e-19

gammacoronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) from gammacoronaviruses such as Avian infectious bronchitis virus (IBV). CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for coronavirus replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication.


Pssm-ID: 409332  Cd Length: 113  Bit Score: 86.45  E-value: 1.91e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3371 LQNNELCLRNVFTAQNTAQDFNGNEST-VKSFYVTRTGKKILVAITSTKDNLKTVTCLTETGKTV-LNLDPPMRFAHTVG 3448
Cdd:cd21899      1 LQNNELMPHGVKTKACVAGVDQAHCSVeSKCYYTNISGNSVVAAITSSNPNLKVASFLNEAGNQIyVDLDPPCKFGMKVG 80
                           90       100       110
                   ....*....|....*....|....*....|...
gi 1818222121 3449 GKQSVVYLYFIQNISSLNRGMVIGHISETTILQ 3481
Cdd:cd21899     81 DKVEVVYLYFIKNTRSIVRGMVLGAISNVVVLQ 113
CoV_NSP9 pfam08710
Coronavirus replicase NSP9; Nsp9 is a single-stranded RNA-binding viral protein involved in ...
3373-3481 1.94e-19

Coronavirus replicase NSP9; Nsp9 is a single-stranded RNA-binding viral protein involved in RNA synthesis. Several crystallographic structures of nsp9 have shown that it is composed of seven beta strands and a single alpha helix. Nsp9 proteins have N-finger motifs and highly conserved GXXXG motifs that both play critical roles in dimerization. The conserved helix-helix dimer interface containing a GXXXG protein-protein interaction motif is biologically relevant to SARS-CoV replication.


Pssm-ID: 285872  Cd Length: 111  Bit Score: 86.38  E-value: 1.94e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3373 NNELCLRNVFTAQNTAQDFNGNEST-VKSFYVTRTGKKILVAITSTKDNLKTVTCLTETGKTV-LNLDPPMRFAHTVGGK 3450
Cdd:pfam08710    1 NNELMPGKLKTKACKAGVTDAHCSVeGKAYYNNEGGGSFVYAILSSNPNLKYAKFEKEDGNVIyVELEPPCRFVVDTPKG 80
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1818222121 3451 QSVVYLYFIQNISSLNRGMVIGHISETTILQ 3481
Cdd:pfam08710   81 PEVKYLYFVKNLNNLRRGMVLGYISATVRLQ 111
TM_Y_SARS-CoV-like_Nsp3_C cd21717
C-terminus of non-structural protein 3, including transmembrane and Y domains, from Severe ...
1509-1970 2.25e-19

C-terminus of non-structural protein 3, including transmembrane and Y domains, from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the C-terminus of non-structural protein 3 (Nsp3) from betacoronavirus in the sarbecovirus subgenus (B lineage), including highly pathogenic human coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In SARS-CoV and the related murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409665  Cd Length: 531  Bit Score: 95.06  E-value: 2.25e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1509 LFVSLAPFLMLPAVVSLLNSGYTIGTYLyakTGWPCNYNATQHFDYNSYCAGDLVCQACFDGQDSLHLYPHLRVNQQPIQ 1588
Cdd:cd21717      5 LSICLGSLIYVTAALGVLLSNLGAPSYC---DGVRESYLNSSNVTTMDFCEGSFPCSVCLSGLDSLDSYPALETIQVTIS 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1589 T--TDYTVYALSLILLLANM-------TLVMGTLIVTFFVNF--YGVQIPFYGTLLID-YQSA---LMMTFSVYY--FYK 1651
Cdd:cd21717     82 SykLDLTILGLAAEWFLAYMlftkffyLLGLSAIMQVFFGYFasHFISNSWLMWFIISiVQMApvsAMVRMYIFFasFYY 161
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1652 VMKFFRHLTHGCKIPTCMVCAKLRTPPTITVETVVQGRKYPSVIETNGGFTICKEHNFYCKDCSLQTPG-TFIPTEAIES 1730
Cdd:cd21717    162 IWKSYVHIMDGCTSSTCMMCYKRNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCAGsTFISDEVARD 241
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1731 LSRATRLSVKPTapafllardvECQTDVVVARAMHNQNAHVCISK----------YSDIRTVDQLLKPTPLFSYTPDVII 1800
Cdd:cd21717    242 LSLQFKRPINPT----------DQSSYVVDSVAVKNGALHLYFDKagqktyerhpLSHFVNLDNLRANNTKGSLPINVIV 311
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1801 aadFDNRGSLK--TAKELAVVLSMDLKRTIIIIDQAYSRPIDNYQEVASRIEKYY----------PVAKITPTgdIFTDI 1868
Cdd:cd21717    312 ---FDGKSKCDesAAKSASVYYSQLMCQPILLLDQALVSDVGDSTEVSVKMFDAYvdtfsatfsvPMEKLKAL--VATAH 386
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1869 KQATNGQASDSAINAAVLAVQRG----------------------LDFTIDNPNNILPHYAfDFSTLNAEDQSTILESGC 1926
Cdd:cd21717    387 SELAKGVALDGVLSTFVSAARQGvvdtdvdtkdvieclklshhsdLEVTGDSCNNFMLTYN-KVENMTPRDLGACIDCNA 465
                          490       500       510       520       530
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1818222121 1927 AKGN---LKGTNVGVVLSASLVTRLSQQAIRVIANAASRNGV----TCAVT 1970
Cdd:cd21717    466 RHINaqvAKSHNVSLIWNVKDYMSLSEQLRKQIRSAAKKNNIpfrlTCATT 516
gammaCoV_PLPro cd21733
gammacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
1158-1244 7.01e-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: 87.49  E-value: 7.01e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1158 DLNLQQYCVYLKTCHHKWVVSRTNGLMHLKQKDNNCFVSAGVNLFQNTAYQLRPAIDALYREYLNGNPNRFVAWIYASTN 1237
Cdd:cd21733     66 GLDAQKYVIYLQTLAQKWNVQYRDNFLILEWRDGNCWISSAIVLLQAAKIRFKGFLAEAWAKFLGGDPTEFVAWCYASCN 145

                   ....*..
gi 1818222121 1238 RRVGEMG 1244
Cdd:cd21733    146 AKVGDFS 152
TM_Y_MHV-like_Nsp3_C cd21714
C-terminus of non-structural protein 3, including transmembrane and Y domains, from murine ...
1544-1753 1.12e-16

C-terminus of non-structural protein 3, including transmembrane and Y domains, from murine hepatitis virus and betacoronavirus in the A lineage; This model represents the C-terminus of non-structural protein 3 (Nsp3) from betacoronavirus in the embecovirus subgenus (A lineage), including murine hepatitis virus (MHV) and Human coronavirus HKU1. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In MHV and the related Severe acute respiratory syndrome-related coronavirus (SARS-CoV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409662  Cd Length: 555  Bit Score: 86.73  E-value: 1.12e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1544 CNYNATQHFDY-NSYCAGDLVCQACFDGQDSLHLYPHLRVNQQPIQTT---DYTV-----------YALSLILLLANMTL 1608
Cdd:cd21714     57 CDLYSVSDVGFkSQFCNGSMACQLCLSGFDMLDNYKAIDVVQYEVDRRvffDYTSvlklvvelvvsYALYTVWFYPLFCL 136
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1609 VMGTLIVTFFVNFYGVQIPFYGTLLIDYQSALMMTFS-------VYYFYKVMKFFRHLTHGCKIPTCMVCAKLRTPPTIT 1681
Cdd:cd21714    137 IGLQLLTTWLPEFFMLETLHWSVRLFVFLANMLPAHVflrfyivVTAMYKIFCLFRHVVYGCSKPGCLFCYKRNRSVRVK 216
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1818222121 1682 VETVVQGR-KYPSVIeTNGGFTICKEHNFYCKDCSLQTPG-TFIPTEAIESLSRATRLSVKPTAPAFLLARDVE 1753
Cdd:cd21714    217 CSTIVGGMlRYYDVM-ANGGTGFCSKHQWNCINCDSYKPGnTFITVEAAAELSKELKRPVNPTDVAYYTVTDVK 289
Macro_Af1521_BAL-like cd02907
macrodomain, Af1521-like family; Macrodomains are found in a variety of proteins with diverse ...
946-1062 1.74e-15

macrodomain, Af1521-like family; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. The macrodomains in this family show similarity to Af1521, a protein from Archaeoglobus fulgidus containing a stand-alone macrodomain. Af1521 binds ADP-ribose and exhibits phosphatase activity toward ADP-ribose-1"-monophosphate (Appr-1"-p). Also included in this family are the N-terminal (or first) macrodomains of BAL (B-aggressive lymphoma) proteins which contain multiple macrodomains, such as the first macrodomain of mono-ADP-ribosyltransferase PARP14 (PARP-14, also known as ADP-ribosyltransferase diphtheria toxin-like 8, ATRD8, B aggressive lymphoma protein 2, or BAL2). Most BAL proteins also contain a C-terminal PARP active site and are also named as PARPs. Human BAL1 (or PARP-9) was originally identified as a risk-related gene in diffuse large B-cell lymphoma that promotes malignant B-cell migration. Some BAL family proteins exhibit PARP activity. Poly (ADP-ribosyl)ation is an immediate DNA-damage-dependent post-translational modification of histones and other nuclear proteins. BAL proteins may also function as transcriptional repressors.


Pssm-ID: 394877 [Multi-domain]  Cd Length: 158  Bit Score: 76.37  E-value: 1.74e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  946 KVELVVGELASIKFDnsVLVNPANAQLTNGGGAARAIAKLAGPKYQEYCNSVAPISGPLTTD---SFDAKKLGVACILHV 1022
Cdd:cd02907      3 KVSVYKGDITKEKVD--AIVNAANERLKHGGGVAGAISKAGGPEIQEECDKYIKKNGKLRVGevvVTSAGKLPCKYVIHA 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1818222121 1023 VPPK---GSDPNVQELLYQAYKSILTEpAHYV------IPILGAGIFGC 1062
Cdd:cd02907     81 VGPRwsgGSKEECEDLLYKAVLNSLEE-AEELkatsiaIPAISSGIFGF 128
alphaCoV_Nsp9 cd21897
alphacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...
3399-3481 2.53e-13

alphacoronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) of alphacoronaviruses, including Porcine epidemic diarrhea virus (PEDV), Porcine transmissible gastroenteritis coronavirus (TGEV), and Human coronavirus 229E. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for coronavirus replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication.


Pssm-ID: 409330  Cd Length: 108  Bit Score: 68.50  E-value: 2.53e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3399 KSFYVTRTGKKILVAITSTKDNLKTVTCLTETGKTVLNLDPPMRFA-HTVGGKQsVVYLYFIQNISSLNRGMVIGHISET 3477
Cdd:cd21897     26 KALYNNEGGKTFMYAFIADKPDLKYVKWEFDGGCNTIELEPPCKFLvDTPNGPQ-IKYLYFVKNLNTLRRGAVLGYIGAT 104

                   ....
gi 1818222121 3478 TILQ 3481
Cdd:cd21897    105 VRLQ 108
betaCoV_Nsp9 cd21898
betacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...
3373-3481 2.76e-13

betacoronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) from betacoronaviruses including highly pathogenic 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 assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for coronavirus replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication.


Pssm-ID: 409331  Cd Length: 111  Bit Score: 68.58  E-value: 2.76e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3373 NNELCLRNVFT-AQNTAQDFNGNESTVKSFYVTRTGKKILVAITSTKDNLKTVTCLTETGKTV-LNLDPPMRFA-HTVGG 3449
Cdd:cd21898      1 NNELMPQGLKTmVVTAGPDQTACNTPALAYYNNVQGGRMVMAILSDVDGLKYAKVEKSDGGFVvLELDPPCKFLvQTPKG 80
                           90       100       110
                   ....*....|....*....|....*....|..
gi 1818222121 3450 KQsVVYLYFIQNISSLNRGMVIGHISETTILQ 3481
Cdd:cd21898     81 PK-VKYLYFVKGLNNLHRGQVLGTIAATVRLQ 111
Macro pfam01661
Macro domain; The Macro or A1pp domain is a module of about 180 amino acids which can bind ...
965-1062 4.74e-13

Macro domain; The Macro or A1pp domain is a module of about 180 amino acids which can bind ADP-ribose (an NAD metabolite) or related ligands. Binding to ADP-ribose could be either covalent or non-covalent: in certain cases it is believed to bind non-covalently; while in other cases (such as Aprataxin) it appears to bind both non-covalently through a zinc finger motif, and covalently through a separate region of the protein. This domain is found in a number of otherwise unrelated proteins. It is found at the C-terminus of the macro-H2A histone protein 4 and also in the non-structural proteins of several types of ssRNA viruses such as NSP3 from alpha-viruses and coronaviruses. This domain is also found on its own in a family of proteins from bacteria, archaebacteria and eukaryotes. The 3D structure of the SARS-CoV Macro domain has a mixed alpha/beta fold consisting of a central seven-stranded twisted mixed beta sheet sandwiched between two alpha helices on one face, and three on the other. The final alpha-helix, located on the edge of the central beta-sheet, forms the C terminus of the protein. The crystal structure of AF1521 (a Macro domain-only protein from Archaeoglobus fulgidus) has also been reported and compared with other Macro domain containing proteins. Several Macro domain only proteins are shorter than AF1521, and appear to lack either the first strand of the beta-sheet or the C-terminal helix 5. Well conserved residues form a hydrophobic cleft and cluster around the AF1521-ADP-ribose binding site.


Pssm-ID: 460286  Cd Length: 116  Bit Score: 67.98  E-value: 4.74e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  965 VNPANAQLTNGGGAARAIAKLAGPKYQEYCNSVapISGPLTT-DSF--DAKKLGVACILHVVPPK---GSDPNVQELLYQ 1038
Cdd:pfam01661    1 VNAANSRLLGGGGVAGAIHRAAGPELLEECREL--KKGGCPTgEAVvtPGGNLPAKYVIHTVGPTwrhGGSHGEEELLES 78
                           90       100
                   ....*....|....*....|....*....
gi 1818222121 1039 AYKSILTEPA-----HYVIPILGAGIFGC 1062
Cdd:pfam01661   79 CYRNALALAEelgikSIAFPAISTGIYGF 107
A1pp smart00506
Appr-1"-p processing enzyme; Function determined by Martzen et al. Extended family detected by ...
946-1064 7.86e-12

Appr-1"-p processing enzyme; Function determined by Martzen et al. Extended family detected by reciprocal PSI-BLAST searches (unpublished results, and Pehrson _ Fuji).


Pssm-ID: 214701  Cd Length: 133  Bit Score: 65.40  E-value: 7.86e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121   946 KVELVVGELASIKFDnsVLVNPANAQLTNGGGAARAIAKLAGPKY-QEYCNSVAPISGPL-TTDSFDAKKLGVACILHVV 1023
Cdd:smart00506    1 ILKVVKGDITKPRAD--AIVNAANSDGAHGGGVAGAIARAAGKALsKEEVRKLAGGECPVgTAVVTEGGNLPAKYVIHAV 78
                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*....
gi 1818222121  1024 PPKGSDPNVQ--ELLYQAYKSILTEpAH------YVIPILGAGIFGCNP 1064
Cdd:smart00506   79 GPRASGHSKEgfELLENAYRNCLEL-AIelgitsVALPLIGTGIYGVPK 126
Macro_SF cd02749
macrodomain superfamily; Macrodomains are found in a variety of proteins with diverse cellular ...
962-1064 5.21e-11

macrodomain superfamily; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. Macrodomains include the yeast macrodomain Poa1 which is a phosphatase of ADP-ribose-1"-phosphate, a by-product of tRNA splicing. Some macrodomains have ADPr-unrelated binding partners such as the coronavirus SUD-N (N-terminal subdomain) and SUD-M (middle subdomain) of the SARS-unique domain (SUD) which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). Macrodomains regulate a wide variety of cellular and organismal processes, including DNA damage repair, signal transduction, and immune response.


Pssm-ID: 394871  Cd Length: 121  Bit Score: 62.42  E-value: 5.21e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  962 SVLVNPANAQLTNGGGAARAIAKLAGPKYQEYCNSVAPIsGPLTTDS---FDAKKLGVACILHVVPPKG-SDPNVQELLY 1037
Cdd:cd02749      1 DAIVNPANNDLYLGGGVAKAISKKAGGDLQEECEERKKN-GYLKVGEvavTKGGNLPARYIIHVVGPVAsSKKKTYEPLK 79
                           90       100       110
                   ....*....|....*....|....*....|..
gi 1818222121 1038 QAYKSIL--TEPAHY---VIPILGAGIFGCNP 1064
Cdd:cd02749     80 KCVKNCLslADEKGLksvAFPAIGTGIAGFPP 111
YmdB COG2110
O-acetyl-ADP-ribose deacetylase (regulator of RNase III), contains Macro domain [Translation, ...
947-1085 8.27e-11

O-acetyl-ADP-ribose deacetylase (regulator of RNase III), contains Macro domain [Translation, ribosomal structure and biogenesis];


Pssm-ID: 441713  Cd Length: 168  Bit Score: 63.27  E-value: 8.27e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  947 VELVVGELASIKFDnsVLVNPANAQLTNGGGAARAIAKLAGPKYQEYCNSVAPISGPLT-----TDSFDakkLGVACILH 1021
Cdd:COG2110      1 IEIVQGDITELDVD--AIVNAANSSLLGGGGVAGAIHRAAGPELLEECRRLCKQGGCPTgeaviTPAGN---LPAKYVIH 75
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1818222121 1022 VVPP--KGSDPNVQELLYQAYKSILTEPAHY-----VIPILGAGIFGCNP-------VHSLDAFRKACPSdIGRVTLV 1085
Cdd:COG2110     76 TVGPvwRGGGPSEEELLASCYRNSLELAEELgirsiAFPAIGTGVGGFPWeeaapiaVETLRDFLEEHPS-LEEVRFV 152
CoV_peptidase pfam08715
Coronavirus papain-like peptidase; This entry contains coronavirus cysteine endopeptidases ...
1100-1269 1.66e-10

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: 65.39  E-value: 1.66e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1100 RTIVRTTTD-----YDQVTTKALTPQGVLEANLFDGEDFVQEPKPGQIYLEVTEEVQNQAKeldLNLQQYCVYLKTChhK 1174
Cdd:pfam08715   17 HSIVVKPGDslgqqFGQVYAKNKDLSGVFPADDVEDKEILYVPTTDWVEFYGFKSILEYYT---LDASKYVIYLSAL--T 91
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1175 WVVSRTNGLMHLKQKDNNCFVSAGVNLFQNTAYQLR-PAIDALYREYLNGNPNRFVAWIYASTNRRVGEMGCPQQVISLL 1253
Cdd:pfam08715   92 KNVQYVDGFLILKWRDNNCWISSVIVALQAAKIRFKgQFLTEAWAKLLGGDPTDFVAWCYASCTAKVGDFGDANWTLTNL 171
                          170       180
                   ....*....|....*....|
gi 1818222121 1254 VSNSDA----AFSATTACCN 1269
Cdd:pfam08715  172 AEHFDAeytnAFLKKRVCCN 191
TM_Y_HKU9-like_Nsp3_C cd21715
C-terminus of non-structural protein 3, including transmembrane and Y domains, from Rousettus ...
1567-1974 2.14e-10

C-terminus of non-structural protein 3, including transmembrane and Y domains, from Rousettus bat coronavirus HKU9 and betacoronavirus in the D lineage; This model represents the C-terminus of non-structural protein 3 (Nsp3) from betacoronavirus in the nobecovirus subgenus (D lineage), including Rousettus bat coronavirus HKU9. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In the related betacoronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain.


Pssm-ID: 409663  Cd Length: 526  Bit Score: 66.42  E-value: 2.14e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1567 CFDGQDSLHlYPHLRVNQQPIQTT-DYTVYALSLILLLANMTL-----VMGTLIVTFFVNFYgVQIP----------FYG 1630
Cdd:cd21715     55 CMAGMDGLD-YPALRMQQHRYGSPyDYTYILMLLEAFCAYLLYtpalpIVGILAVLHLLVLY-LPIPlgnswlvvflYYI 132
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1631 TLLIDYQSALMMTFSVYYFYKVMKFFRHLTHGCKIPTCMVCAKLRTPPTITVETVVQGRKYPSVIETNGGFTICKEHNFY 1710
Cdd:cd21715    133 IRLVPFTSMLRMYIVIAFLWLCYKGFVHVRYGCNNVACLMCYKKNVAKRIECSTVVNGVKRMFYVNANGGTYFCTKHNWN 212
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1711 CKDCSLQT-PGTFIPTEAIESLSRATRLSVKPTAPAFLLARDVE-------CQTDVVVARAMHN--QNAHVCISK--YSD 1778
Cdd:cd21715    213 CVSCDTYTvDSTFISRQVALDLSAQFKRPINHTDEAYYEVTSVEvrngyvyCYFDSDGQRSYERfpMDAFTNVSKlhYSE 292
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1779 IRTVdqllkpTPLFSytpdvIIAADFDNRGSLKTAKELAVVLSMDLKRTIIIID------------------QAYSRP-I 1839
Cdd:cd21715    293 LKGA------APAFN-----VLVFDATNRIEENAVKTAAIYYAQLACKPILLVDkrmvgvvgddatiakamfEAYAQNyL 361
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1840 DNYQEVASRIEKYYPVA--KITPTGDIFTDIK---QATNGQA----SDSAINAAV----LAVQRGLDFTIDNPNNILPHY 1906
Cdd:cd21715    362 LKYSIAMDKVKHLYSTAlqQIASGMTVESVLKvfvGSTRAEAkdleSDVDTNDLVscirLCHQEGWDWTTDSWNNLVPTY 441
                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1818222121 1907 AfdfstlnAEDQSTILESG--------CAKGNL-KGTNVGVVLSASLVTRLSQQAIRVIANAASRNGVTCAVTPSTL 1974
Cdd:cd21715    442 I-------KQDTLSTLEVGqfmtanarYVNANVaKGAAVNLVWRYADFIKLSESMRRQLRVAARKTGLNLLVTTSSL 511
PRK00431 PRK00431
ADP-ribose-binding protein;
945-1098 7.53e-09

ADP-ribose-binding protein;


Pssm-ID: 234759  Cd Length: 177  Bit Score: 57.93  E-value: 7.53e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  945 TKVELVVGELASIKFDnsVLVNPANAQLTNGGGAARAIAKLAGPKYQEYCNSVAPISGPL-------TTdsfdAKKLGVA 1017
Cdd:PRK00431     3 MRIEVVQGDITELEVD--AIVNAANSSLLGGGGVDGAIHRAAGPEILEECRELRQQQGPCptgeaviTS----AGRLPAK 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1018 CILHVVPP--KGSDPNVQELLYQAYKSILT--EPAHYV---IPILGAGIFGCnPVHslDAFRKAC---------PSDIGR 1081
Cdd:PRK00431    77 YVIHTVGPvwRGGEDNEAELLASAYRNSLRlaAELGLRsiaFPAISTGVYGY-PLE--DAARIAVktvrefltrHKSPEE 153
                          170
                   ....*....|....*..
gi 1818222121 1082 VTLVTMNKNHLQVWDAL 1098
Cdd:PRK00431   154 VYFVCYDEEAYRLYERL 170
Macro_Ttha0132-like cd03330
Macrodomain, uncharacterized family similar to Thermus thermophilus hypothetical protein ...
946-1086 6.87e-08

Macrodomain, uncharacterized family similar to Thermus thermophilus hypothetical protein Ttha0132; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. Macrodomains include the yeast macrodomain Poa1 which is a phosphatase of ADP-ribose-1"-phosphate, a by-product of tRNA splicing. Some macrodomains have ADPr-unrelated binding partners such as the coronavirus SUD-N (N-terminal subdomain) and SUD-M (middle subdomain) of the SARS-unique domain (SUD) which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). Macrodomains regulate a wide variety of cellular and organismal processes, including DNA damage repair, signal transduction, and immune response. This family is composed of uncharacterized proteins containing a stand-alone macrodomain, similar to Thermus thermophilus hypothetical protein Ttha0132.


Pssm-ID: 394879  Cd Length: 147  Bit Score: 54.36  E-value: 6.87e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  946 KVELVVGELASikFDNSVLVNPANAQLTNGGGAARAIAKLAGPKYQEYCNSVAPIS--GPLTTdsfDAKKLGVACILHVV 1023
Cdd:cd03330      1 RLIVVQGDITE--QDADAIVNAANRRLLMGSGVAGAIKRKGGEEIEREAMRKGPIRvgEAVET---GAGKLPAKYVIHAA 75
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1818222121 1024 ----PPKGSDPNVQEllyqAYKSILTEPAHY-----VIPILGAGIFGCnPVHS-----LDAFRKACPSDIGRVTLVT 1086
Cdd:cd03330     76 vmgmPGRSSEESIRD----ATRNALAKAEELglesvAFPAIGTGVGGF-PVEEvarimLEEIKKCDPPLLEEVRLYR 147
Macro_OAADPr_deacetylase cd02908
macrodomain, O-acetyl-ADP-ribose (OAADPr) family; Macrodomains are found in a variety of ...
946-1044 1.33e-06

macrodomain, O-acetyl-ADP-ribose (OAADPr) family; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. This family includes eukaryotic macrodomain proteins such as human MacroD1 and MacroD2, and bacterial proteins such as Escherichia coli YmdB; these have been shown to be O-acetyl-ADP-ribose (OAADPr) deacetylases that efficiently catalyze the hydrolysis of OAADPr to produce ADP-ribose and free acetate. OAADPr is a sirtuin reaction product generated from the NAD+-dependent protein deacetylation reactions and has been implicated as a signaling molecule. By acting on mono-ADP-ribosylated substrates, OAADPr deacetylases may reverse cellular ADP-ribosylation.


Pssm-ID: 438955  Cd Length: 166  Bit Score: 50.97  E-value: 1.33e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  946 KVELVVGELASIKFDnsVLVNPANAQLTNGGGAARAIAKLAGPKYQEYCnsvAPISGPLTTDsfDAK-----KLGVACIL 1020
Cdd:cd02908      1 KISLWRGDITKLEVD--AIVNAANSSLLGGGGVDGAIHRAAGPELLEEC---RKLGGVCPTG--EAKitpgyNLPAKYVI 73
                           90       100
                   ....*....|....*....|....*.
gi 1818222121 1021 HVVPPKGSD--PNVQELLYQAYKSIL 1044
Cdd:cd02908     74 HTVGPIGEGgvEEEPELLASCYRSSL 99
Macro_H2A-like cd02904
macrodomain, macroH2A-like family; Macrodomains are found in a variety of proteins with ...
946-1045 1.33e-06

macrodomain, macroH2A-like family; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. Members of this family are similar to macroH2A, a variant of the major-type core histone H2A, which contains an N-terminal H2A domain and a C-terminal nonhistone macrodomain. Histone macroH2A is enriched on the inactive X chromosome of mammalian female cells. It does not bind poly ADP-ribose, but does bind the monomeric SirT1 metabolite O-acetyl-ADP-ribose (OAADPR) with high affinity through its macrodomain. This family also includes the ADP-ribose binding macrodomain of the macroH2A variant, macroH2A1.1. The macroH2A1.1 isoform inhibits PARP1-dependent DNA-damage induced chromatin dynamics. The putative ADP-ribose binding pocket of the human macroH2A2 macrodomain exhibits marked structural differences compared with the macroH2A1.1 variant.


Pssm-ID: 394875  Cd Length: 188  Bit Score: 51.55  E-value: 1.33e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  946 KVELVVGELASIKFDnsVLVNPANAQLTNGGGAARAIAKLAGPKYQEYCNSVAPISGPLTTDSF---DAKKLGVACILHV 1022
Cdd:cd02904     19 KLTVVQGDIASIKAD--AIVHPTNATFYLGGEVGSALEKAGGKEFVEEVKELRKSNGPLEVAGAaisPGHNLPAKFVIHC 96
                           90       100
                   ....*....|....*....|...
gi 1818222121 1023 VPPKGSDPNVQELLYQAYKSILT 1045
Cdd:cd02904     97 NSPSWGSDKCEELLEKTVKNCLA 119
betaCoV_PLPro cd21732
betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
1161-1242 6.01e-06

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: 51.05  E-value: 6.01e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1161 LQQYCVYLKTCHhKWVVSRTNGLMHLKQKDNNCFVSAGVNLFQN-----TAYQLRPAidalYREYLNGNPNRFVAWIYAS 1235
Cdd:cd21732     79 LLRYYSALAHVK-KWKFVVVDGYFSLKQADNNCYLNAACLMLQQldlkfNTPALQEA----YYEFRAGDPLRFVALVLAY 153

                   ....*..
gi 1818222121 1236 TNRRVGE 1242
Cdd:cd21732    154 GNFTFGE 160
Macro_BAL-like cd02903
macrodomain, B-aggressive lymphoma (BAL)-like family; Macrodomains are found in a variety of ...
946-1058 1.09e-05

macrodomain, B-aggressive lymphoma (BAL)-like family; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. Members of this family show similarity to BAL (B-aggressive lymphoma) proteins, which contain one to three macrodomains. Most BAL family macrodomains belong to this family except for the most N-terminal domain in multiple-domain containing proteins. This family includes the second and third macrodomains of mono-ADP-ribosyltransferase PARP14 (PARP-14, also known as ADP-ribosyltransferase diphtheria toxin-like 8, ATRD8, B aggressive lymphoma protein 2, or BAL2). Most BAL proteins also contain a C-terminal PARP active site and are also named as PARPs. Human BAL1 (or PARP-9) was originally identified as a risk-related gene in diffuse large B-cell lymphoma that promotes malignant B-cell migration. Some BAL family proteins exhibit PARP activity. Poly (ADP-ribosyl)ation is an immediate DNA-damage-dependent post-translational modification of histones and other nuclear proteins. BAL proteins may also function as transcriptional repressors.


Pssm-ID: 394874  Cd Length: 175  Bit Score: 48.79  E-value: 1.09e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  946 KVELVVGELASIKFDnsVLVNPANAQLTNGGGAARAIAKLAGPKYQEYCNSVAPisGPLTTDSFDAKKLGVAC--ILHVV 1023
Cdd:cd02903      9 TVQLVKGDITKEKTD--VIVNSVSSDLLLKGGVSKAILKAAGPELQDECANQGK--QPASGDVIVTSGGNLPCkyVYHVV 84
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1818222121 1024 PPKGSDPN-------VQELLYQA----YKSIltepahyVIPILGAG 1058
Cdd:cd02903     85 LPHYNPGNektlkdiVRKCLEKAenykMSSI-------SFPAIGTG 123
MDN1 COG5271
Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal ...
492-943 1.77e-05

Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal structure and biogenesis];


Pssm-ID: 444083 [Multi-domain]  Cd Length: 1028  Bit Score: 50.78  E-value: 1.77e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  492 VGNRMLMFTSTGTFLLTKATTKILNKAKYIFDVDPEYPVDVTTSKVVVHEALQQIDTKPARA-----------LEAVDVV 560
Cdd:COG5271     29 AGLDTQSETASEREDKLPDTDKDLLILTDADAASDEGKLLDLKSADGAALSAESDAGASLITaanleegdiagNAADDSA 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  561 VGNTVLQMATDGTAFYPSDGTHASLPGFK------------AGSDELLISFNCDLFDDETNAQINETLAAYELN------ 622
Cdd:COG5271    109 DEESDANAKEDATDDADSSGDAQGDPLATdtlgggdldlatKDGDELLPSLADNDEAAADEGDELAADGDDTLAvadaie 188
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  623 -QLVAPGDSTPRQIATLVVDTLVDAITDHFPEKTIDLPEDYQVFSDHDDLLLAQYHIPD-HLSLYIQAMEGEDDSGDEIC 700
Cdd:COG5271    189 aTPGGTDAVELTATLGATVTTDPGDSVAADDDLAAEEGASAVVEEEDASEDAVAAADETlLADDDDTESAGATAEVGGTP 268
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  701 IEDDD-------YDCPQADENTEGVIPQQWELPDVDKFLLKIQERKTSSDEVLS----VDVYPKPDEVGIDDSASEKKPN 769
Cdd:COG5271    269 DTDDEatddadgLEAAEDDALDAELTAAQAADPESDDDADDSTLAALEGAAEDTeiatADELAAADDEDDDDSAAEDAAE 348
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  770 GDSVLDPEVHPTLESVDVERPTETAN---QAVEDKPSDTTFVVDEV--------QLQESTPEPELRSYEGEFDSDDEIII 838
Cdd:COG5271    349 EAATAEDSAAEDTQDAEDEAAGEAADeseGADTDAAADEADAAADDsaddeeasADGGTSPTSDTDEEEEEADEDASAGE 428
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  839 P------IVPV-----------TPADLKPQTITIKEYFKSEKLETINEgSTESVTQSDDSVDESFVDAESDDPQDPAVYD 901
Cdd:COG5271    429 TedestdVTSAeddiatdeeadSLADEEEEAEAELDTEEDTESAEEDA-DGDEATDEDDASDDGDEEEAEEDAEAEADSD 507
                          490       500       510       520
                   ....*....|....*....|....*....|....*....|..
gi 1818222121  902 DTTIITDSTDVGDEPETTLATIVNTPLTLDNNLPPEAIKQPS 943
Cdd:COG5271    508 ELTAEETSADDGADTDAAADPEDSDEDALEDETEGEENAPGS 549
MDN1 COG5271
Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal ...
602-919 3.30e-05

Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal structure and biogenesis];


Pssm-ID: 444083 [Multi-domain]  Cd Length: 1028  Bit Score: 50.01  E-value: 3.30e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  602 DLFDDETNAQINETLAAYELNQLVAPGDSTPRQIATLVVDTLVDAITDHFPEKTIDLPEDyqVFSDHDDLLLAQYHIPDH 681
Cdd:COG5271    339 DDSAAEDAAEEAATAEDSAAEDTQDAEDEAAGEAADESEGADTDAAADEADAAADDSADD--EEASADGGTSPTSDTDEE 416
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  682 LS---LYIQAMEGEDDSGDEICIEDDDydcpQADENTEGVipqqweLPDVDKFLLKIQERKTSSDEVLSVDvypkPDEVG 758
Cdd:COG5271    417 EEeadEDASAGETEDESTDVTSAEDDI----ATDEEADSL------ADEEEEAEAELDTEEDTESAEEDAD----GDEAT 482
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  759 IDDSASEKKPNGDSVLDPEVHPTLESVDVE--------------RPTETANQAVEDKPSDTTFVVDEVQLQESTPEPELR 824
Cdd:COG5271    483 DEDDASDDGDEEEAEEDAEAEADSDELTAEetsaddgadtdaaaDPEDSDEDALEDETEGEENAPGSDQDADETDEPEAT 562
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121  825 SYEGEFDSDDEIIIPIVPVTPAD---LKPQTITIKEYFKSEKLETINEGSTESVTQSDDSVDESFV-DAESDDPQDPAVY 900
Cdd:COG5271    563 AEEDEPDEAEAETEDATENADADeteESADESEEAEASEDEAAEEEEADDDEADADADGAADEEETeEEAAEDEAAEPET 642
                          330
                   ....*....|....*....
gi 1818222121  901 DDTTIITDSTDVGDEPETT 919
Cdd:COG5271    643 DASEAADEDADAETEAEAS 661
alphaCoV_PLPro cd21731
alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...
1181-1281 5.09e-04

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: 44.92  E-value: 5.09e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 1181 NGLMHLKQKDNNCFVSAgvnlfqnTAYQLR--------PAIDALYREYLNGNPNRFVAWIYASTNRRVGEMGCPQQVIS- 1251
Cdd:cd21731     88 NGKRVLKQSDNNCWVNA-------VCLQLQfakptfksEGLQALWNKFLTGDVAGFVHWLYWITGANKGDPGDAENTLNk 160
                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1818222121 1252 ---LLVSNSDAAFSATTACC---NTYFNHTGVISVA 1281
Cdd:cd21731    161 lskYLVSSGSVTVERTTGCDscnSKRTVTTPVVNAS 196
gammaCoV_Nsp7 cd21828
gammacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...
3089-3183 2.14e-03

gammacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of gammacoronaviruses that include Avian infectious bronchitis virus (IBV) and Canada goose coronavirus (CGCoV), among others. 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. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp7 forms a 2:1 heterotrimer with Nsp8. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.


Pssm-ID: 409254  Cd Length: 83  Bit Score: 39.77  E-value: 2.14e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1818222121 3089 KILDAKATAVVVANLLEKAGVTNKHAICKKIVKLHNDTLKATTYEEvevALVKLLSHIIEFLPTDQvDAYLADaanaqhv 3168
Cdd:cd21828      2 KLTDVKCTTVVLMQLLTKLNVEANSKMHKYLVELHNKILASDDVVE---CMDNLLGMLVTLLCIDS-TIDLSE------- 70
                           90
                   ....*....|....*
gi 1818222121 3169 ntYFDNLLENKAVVQ 3183
Cdd:cd21828     71 --YCDDILKRSTVLQ 83
 
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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