NCBI Conserved Domain Search

alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...

1498-1784

1.85e-135

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: 426.27 E-value: 1.85e-135

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1498 GTIPIKVTEDTVNQKRVSVALDKTYGEQLkGTVVIKDKDVTNQ-LPSVSDVGEKVvkALDVDWNAYYGFPNAAAFSASSH 1576
Cdd:cd21731      1 KSVVVKVTEDGRNVKDVVVDTDKTFGEQL-GVCSVNDKDVTGVvPPDDSDKVVSV--APDVDWDSHYGFPNAAVFHTLDH 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1577 DAYEFDVVTHNNFIVHKQTDNNCWVNAICLALQRLKPTWKFPGVKSLWDAFLTRKTAGFVHMLYHISGLTKGQPGDAELT 1656
Cdd:cd21731     78 SAYAFESDIVNGKRVLKQSDNNCWVNAVCLQLQFAKPTFKSEGLQALWNKFLTGDVAGFVHWLYWITGANKGDPGDAENT 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1657 LHKLVDLMSSDSAVTVTHTTACDKCAKVETFTGPVV-AAPLLVCGTDEICVHGVHVNVKVTSIRGTVAITSLIGPVVGDV 1735
Cdd:cd21731    158 LNKLSKYLVSSGSVTVERTTGCDSCNSKRTVTTPVVnASVLRSGVDDGVCKHGVKVTTRVVSVKGTVIITSVGKPVVSDA 237

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1983930777 1736 ---IDATGYICYTGLNSRGHYTYYDNRNGLMVDADKAYHFEKNLLQVTTAIA 1784
Cdd:cd21731    238 lllLDGVSYTAFSGDVDNGHYTVYDKATGKVYDGDKTVSFKLDLLSVTSVVV 289

alphaCoV-Nsp6

cd21558

alphacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...

3190-3499

2.32e-135

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: 425.84 E-value: 2.32e-135

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3190 FTPTEVIRQMYGVNLQSGKVKSIFYPMMTAIAILFAFWLEFFMYTPFTWINPTFVSVVLAITTLVSVLLVAGIKHKMLFF 3269
Cdd:cd21558      1 FTTSEVIKQMYGVNLQSGKVKSAFKNVLLVGVFLFMFWSELLMYTSFFWINPGLVTPVFLVLVLVSLLLTLFLKHKMLFL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3270 MSFVMPSVILATAHNVVWDMtYYESLQVLVENVNTTFLPVDMQGVMLALFCVVVFVICTIRFFTCKQSWFSLFATTIFVM 3349
Cdd:cd21558     81 QTFLLPSVIVTAFYNLAWDY-YVTAVLAEYFDYHVSLMSFDIQGVLNIFVCLFVFFLHTYRFVTSGTSWFTYVVSLVFVL 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3350 FNIVKLLGmigepwtddhfllcLVNMLTMLISLTTKDWFVVFASYKVAYYIVVyvMQPAFVQDFGFVKCVSIIYMACGYL 3429
Cdd:cd21558    160 YNYFYGND--------------YLSLLMMVLSSITNNWYVGAIAYKLAYYIVY--VPPSLVADFGTVKAVMLVYVALGYL 223

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3430 FCCYYGILYWVNRFTCMTCGVYQFTVSPAELKYMTANNLSAPKTAYDAMILSFKLMGIGGGRNIKISTVQ 3499
Cdd:cd21558    224 CCVYYGILYWINRFTKLTLGVYDFKVSAAEFKYMVANGLKAPTGVFDALLLSFKLIGIGGERTIKISTVQ 293

alphaCoV_Nsp8

cd21830

alphacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...

3583-3777

1.29e-126

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: 396.72 E-value: 1.29e-126

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3583 SVASAYAALPSWIAYEKARADLEEAKKNDVSPQLLKQLTKACNIAKSEFEREASVQKKLDKMAEQAAASMYKEARAVDRK 3662
Cdd:cd21830      1 SVASTFANMPSFIAYETARQDYEDAVKNGSSPQLIKQLKKAMNIAKSEFDREASVQRKLDRMAEQAAAQMYKEARAVNRK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3663 SKIVSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSIVEVK 3742
Cdd:cd21830     81 SKVISAMHSLLFGMLRRLDMSSVDTILNLAKDGVVPLSIIPAASATRLVVVVPDLESFSKIRRDGCVHYAGVVWTIVDIK 160

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1983930777 3743 DANGAQVHLKEVTAANELNITWPLSITCERTTKLQ 3777
Cdd:cd21830    161 DNDGKVVHLKEVTAANEESLAWPLHLNCERIVKLQ 195

alpha_betaCoV_Nsp10

cd21901

alphacoronavirus and betacoronavirus non-structural protein 10; This model represents the ...

3889-4018

4.99e-93

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: 297.66 E-value: 4.99e-93

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3889 AGKPTEHPSNSGLLTLCAFAPDPAKAYVDAVKRGMQPVTNCVKMLSNGAGNGMAITNGVESNTQQDSYGGASVCIYCRCH 3968
Cdd:cd21901      1 AGKQTEVASNSSLLTLCAFAVDPAKTYLDAVKSGGKPVGNCVKMLTNGTGTGQAITVKPEANTNQDSYGGASVCLYCRAH 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3969 VEHPAIDGLCRFKGKFVQVPTGTQDPIRFCIENEVCVVCGCWLTNGCMCD 4018
Cdd:cd21901     81 VEHPDMDGVCKLKGKYVQVPLGTNDPVRFCLENDVCKVCGCWLGNGCSCD 130

TGEV-like_alphaCoV_Nsp1

cd21687

non-structural protein 1 from transmissible gastroenteritis virus and similar ...

2-105

1.39e-68

non-structural protein 1 from transmissible gastroenteritis virus and similar alphacoronaviruses; This model represents the non-structural protein 1 (Nsp1) from transmissible gastroenteritis virus (TGEV) and similar alphacoronaviruses from the tegacovirus and minacovirus subgenera. 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. Nsp1 is the N-terminal cleavage product released from the ORF1a polyprotein by the action of papain-like protease (PLpro). Though Nsp1s of alphaCoVs and betaCoVs share structural similarity, they show no significant sequence similarity and may be considered as genus-specific markers. Despite low sequence similarity, the Nsp1s of alphaCoVs and betaCoVs exhibit remarkably similar biological functions, and are involved in the regulation of both host and viral gene expression. CoV Nsp1 induces suppression of host gene expression and interferes with host immune response. It inhibits host gene expression in two ways: by targeting the translation and stability of cellular mRNAs, and by inhibiting mRNA translation and inducing an endonucleolytic RNA cleavage in the 5'-UTR of cellular mRNAs through its tight association with the 40S ribosomal subunit, a key component of the cellular translation machinery. Inhibition of host mRNA translation includes that of type I interferons, major components of the host innate immune response. Nsp1 is critical in regulating viral replication and gene expression, as shown by multiple evidences, including: mutations in the Nsp1 coding region of the TGEV and murine hepatitis virus (MHV) genomes cause drastic reduction or elimination of infectious virus; bovine coronavirus (BCoV) Nsp1 is an RNA-binding protein that interacts with cis-acting replication elements in the 5'-UTR of the BCoV genome, implying its potential role in the regulation of viral translation or replication; and SARS-CoV Nsp1 enhances virus replication by binding to a stem-loop structure in the 5'-UTR of its genome.

Pssm-ID: 439284 Cd Length: 104 Bit Score: 226.60 E-value: 1.39e-68

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777    2 SSKQFKILVNEDYQVNVPSLPFRDALQEIKYCYRNGFDGYVFVPEYRRDLVDCNRKDHYVIGVLGNGISDLKPVLLTEPS 81
Cdd:cd21687      1 SSKQFKILVNEDYQVNVPSLPFRDVLQEIKYCYRNGFDGYVFVPEYRRDLVDCDRKDHYVIGVLGNGISDLKPVLLTEPS 80

                           90       100
                   ....*....|....*....|....
gi 1983930777   82 VMLQGFIVRANCNGVLEDFDLKFA 105
Cdd:cd21687     81 VMLQGFIVRANCNGVLEDFDLKIA 104

alphaCoV_Nsp9

cd21897

alphacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...

3778-3888

2.66e-65

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: 217.18 E-value: 2.66e-65

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3778 NNEILPGKLKEKAVKASATIdgdAYGSGKALMASEGGKSFIYAFIASDSNLKYVKWESNNDVIPIELEAPLRFYVDGVNG 3857
Cdd:cd21897      1 NNEIMPGKLKQRAVKAEGDG---FSGDGKALYNNEGGKTFMYAFIADKPDLKYVKWEFDGGCNTIELEPPCKFLVDTPNG 77

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1983930777 3858 PEVKYLYFVKSLNTLRRGAVLGYIGATVRLQ 3888
Cdd:cd21897     78 PQIKYLYFVKNLNTLRRGAVLGYIGATVRLQ 108

CoV_NSP4_C

pfam16348

Coronavirus replicase NSP4, C-terminal; This is the C-terminal domain of the coronavirus ...

2811-2902

1.75e-49

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: 171.56 E-value: 1.75e-49

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2811 GDKFVGSFESAAMGTFVIDMRSYETLVNSTSLDRIKSYANSFNKYKYYTGSMGEADYRMACYAHLGKALMDYSVSRNDML 2890
Cdd:pfam16348    1 GDKFVGTFEEAALGTFVIDKESYEKLKNSISLDKFNRYLSLYNKYKYYSGKMDEADYREACCAHLAKALEDFSNSGNDVL 80

                           90
                   ....*....|..
gi 1983930777 2891 YTPPTVSVNSTL 2902
Cdd:pfam16348   81 YTPPTVSVTSSL 92

Macro_X_Nsp3-like

cd21557

X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The ...

1358-1485

3.18e-47

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: 166.19 E-value: 3.18e-47

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1358 PDVLVNAANGDLRHVGGVARAIDVFTGGKLTKRSKeYLKSSKAIAPGNAVLFENVLEHLSVLNAVGPRNGDSRVEGKLCN 1437
Cdd:cd21557      1 EDVVVNAANENLKHGGGVAGAIYKATGGAFQKESD-YIKKNGPLKVGTAVLLPGHGLAKNIIHVVGPRKRKGQDDQLLAA 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1983930777 1438 VYKAIAKCDGKILTPLISVGIFKVKLEVSLQCLLKTVTDRDLNVFVYT 1485
Cdd:cd21557     80 AYKAVNKEYGSVLTPLLSAGIFGVPPEQSLNALLDAVDTTDADVTVYC 127

alphaCoV_Nsp7

cd21826

alphacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...

3500-3582

2.48e-46

alphacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of alphacoronaviruses that include Feline infectious peritonitis virus (FCoV), Human coronavirus NL63 (HCoV-NL63), and Porcine transmissible gastroenteritis coronavirus (TGEV), 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. FCoV Nsp7 forms a 2:1 heterotrimer with Nsp8; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.

Pssm-ID: 409252 Cd Length: 83 Bit Score: 162.15 E-value: 2.48e-46

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3500 SKLTEMKCTNVVLLGLLSKMHVESNSKEWNYCVGLHNEINLCDDPDAVLEKLLALIAFFLSKHNTCDLSDLIESYFENTT 3579
Cdd:cd21826      1 SKLTDIKCTNVVLLGCLSSMNVAANSKEWAYCVDLHNKINLCDDPEKAQEMLLALLAFFLSKQKDFGLDDLLDSYFDNNS 80


                   ...
gi 1983930777 3580 ILQ 3582
Cdd:cd21826     81 ILQ 83

CoV_NSP2_C

Coronavirus replicase NSP2, C-terminal; This entry corresponds to a presumed domain found at ...

731-879

1.93e-24

Coronavirus replicase NSP2, C-terminal; This entry corresponds to a presumed domain found at the C-terminus of Coronavirus non-structural protein 2 (NSP2). NSP2 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. The function of NSP2 is uncertain. This presumed domain is found in two copies in some viral NSP2 proteins. This domain is found in both alpha and betacoronaviruses.

Pssm-ID: 465996 Cd Length: 156 Bit Score: 102.34 E-value: 1.93e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  731 LGNVKIMLGNGVKV--VCDGCHSFANRLTINYNKLCDTARKDIEIGGIPFSTfktpSSSFIDMKDAIYSVV--------E 800
Cdd:pfam19212    1 LKNAKFTVVNGGIVfvVPKKFKSLVGTLLDLLNKLFDSLVDTVKIAGVKFKA----GGTYYLFSNALVKVVsvklkgkkQ 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  801 YG-----EALSFKTASVPVTNSGIITTDdwsdpILLEPADYVEP-KDNGDVIVIAGYTFYKDEDDHFYPYGSGMVVQKMY 874
Cdd:pfam19212   77 AGlkgakEATVFVGATVPVTPTRVEVVT-----VELEEVDYVPPpVVVGYVVVIDGYAFYKSGDEYYPASTDGVVVPPVF 151


                   ....*
gi 1983930777  875 NKMGG 879
Cdd:pfam19212  152 KLKGG 156

CoV_PLPro super family

cl40457

Coronavirus (CoV) papain-like protease (PLPro); This model represents the papain-like protease ...

1097-1282

1.63e-20

Coronavirus (CoV) papain-like protease (PLPro); This model represents the papain-like protease (PLPro) found in non-structural protein 3 (Nsp3) of alpha-, beta-, gamma-, and deltacoronavirus, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. PLPro is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. PLPro, which belongs to the MEROPS peptidase C16 family, participates in the proteolytic processing of the N-terminal region of the replicase polyprotein; it can cleave Nsp1|Nsp2, Nsp2|Nsp3, and Nsp3|Nsp4 sites and its activity is dependent on zinc. Besides cleaving the polyproteins, PLPro also possesses a related enzymatic activity to promote virus replication: deubiquitinating (DUB) and de-ISGylating activities. Both, ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15), are involved in preventing viral infection; coronaviruses utilize Ubl-conjugating pathways to counter the pro-inflammatory properties of Ubl-conjugated host proteins via the action of PLPro, which processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. The Nsp3 PLPro domain in many of these CoVs has also been shown to antagonize host innate immune induction of type I interferon by interacting with IRF3 and blocking its activation.

The actual alignment was detected with superfamily member cd21731:

Pssm-ID: 424088 Cd Length: 289 Bit Score: 95.00 E-value: 1.63e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1097 TPFKTTN--LNGKIILKQQDNNCWINACCYQLQAFDF-FN----HDLWDGFKKDDVMPFVDFCYAALTLKQGDSGDAEYL 1169
Cdd:cd21731     78 SAYAFESdiVNGKRVLKQSDNNCWVNAVCLQLQFAKPtFKseglQALWNKFLTGDVAGFVHWLYWITGANKGDPGDAENT 157

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1170 LeTMLNDY--STAKVTLS--AKCGCGVKEIVLERTVFKLTPLRNEFKYGVCGDCKQINmCKFASVEGSGVFVHdrIEKQT 1245
Cdd:cd21731    158 L-NKLSKYlvSSGSVTVErtTGCDSCNSKRTVTTPVVNASVLRSGVDDGVCKHGVKVT-TRVVSVKGTVIITS--VGKPV 233

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1983930777 1246 PVSQFI-VTPTMHAVYTGTTQSGHYMIEDCIHDYCVDG 1282
Cdd:cd21731    234 VSDALLlLDGVSYTAFSGDVDNGHYTVYDKATGKVYDG 271

Name

Accession

Description

Interval

E-value

TM_Y_alphaCoV_Nsp3_C

cd21712

C-terminus of alphacoronavirus non-structural protein 3, including transmembrane and Y domains; ...

1907-2407

0e+00

Pssm-ID: 409660 Cd Length: 501 Bit Score: 758.70 E-value: 0e+00

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1907 VRQLNKPALWRYIKLVLLLIALYHFFYLFVSIPVVHKLACSGSVQAYSNSSFVKSEVCGNSILCKACLASYDELADFDHL 1986
Cdd:cd21712      1 VIKLKKKKVWFFAKLLLLLYALYALLFMFVRFPPLNSSLCSGYVDGYANSSFVKSEVCGNSLLCKACLAGYDELSDFPHL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1987 QVSWDYKSDPLWNRVIQLSYFIFLAVFGNNYVRCLLMYFVSQYLNLWLSYFGYVKYSWFLHVVNFESISVEFVIIVVVFK 2066
Cdd:cd21712     81 QVVWDHVSDPLFSNVLPLFYFAFLLIFGNNYVRCFLLYFVAQYINNWGVYFGYQDYSWFLHFVPFDSFSDEIVVIFIVVK 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2067 AVLALKHIFLPCNNPSCKTCSKIARQTRIPIQVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRD 2146
Cdd:cd21712    161 VLLFLKHVIFGCDKPSCKACSKSARLTRIPVQTIVNGSMKSFYVHANGGGKFCKKHNFFCVNCDSYGVGNTFINDEVARE 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2147 LSNSIKQTVYATDRSYQEVTKVECTDGFYRFYVGEEFTAYDYDVKHKKYSSQEVLKTMFLLDDFIVYNPSGSSLASVRNV 2226
Cdd:cd21712    241 LSNVVKTTVQPTGPAYIEVDKVEFSNGFYYLYSGDTFWRYNFDITEKKYSCKEVLKNCNLLDDFIVYNNNGSNVAQVKNA 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2227 CVYFSQLIGRPIKIVNSELLEDLSVDFKGALFNAKKNVIKNSFNVDVSECKNLEECYKLCNLDVTFSTFEMAINNAHRFG 2306
Cdd:cd21712    321 CVYFSQLLCKPIKLVDSALLSSLSVDFNGALHKAFVKVLKNSFNKDLSNCKTLEECKKALGLDVSDDEFESAVSNAHRYD 400

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2307 ILITDRSFNNFWPSKIKPGSSgVSAMDIGKCMTFDAKIVNAKVLTQRGKSVVWLSQDFSTLSSTAQKVLVKTFVEEGVNF 2386
Cdd:cd21712    401 VLLTDRSFNNFVTSYAKPEEK-LSTHDIAVCMRAGAKVVNHNVLTKENVPIVWLAKDFSALSEEARKYIVKTTKAKGVNF 479

                          490       500
                   ....*....|....*....|.
gi 1983930777 2387 SLTFNAVGSDEDLPYERFTES 2407
Cdd:cd21712    480 LLTFNDNRMTTTLPAVSIVSK 500

alphaCoV_Nsp2_HCoV-229E-like

cd21514

alphacoronavirus non-structural protein 2 (Nsp2), similar to HCoV-229E Nsp2 and related ...

110-715

0e+00

Pssm-ID: 394865 Cd Length: 503 Bit Score: 620.43 E-value: 0e+00

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  110 GAIYVDQYMCGADGKPVIEG---EFKDYFGDEDVIIYEGEEYHCAWLTVRDEKPLCQQTLLTIREIQYNLDIPHKLPNCA 186
Cdd:cd21514      1 NTVYVDQYMCGADGKPVLPEdewEFKDYFGDLDEIVINGITYVKAWDVERKDVPYEKQNLLSIESITYLSDIPHTLADGA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  187 IREVAPPVKKNSKVVLSEEYRKLYDIFGSPFMGNGDSLNTCFDSLHFIAATLKCPCGAESSGVGDWTGFKTACCGLHGKV 266
Cdd:cd21514     81 VLRVAKPPKKSKKVVLSEPYKKLYDAFGSPFVTNGSTLLEVVTKPVFIHALVKCKCGKESWTVGDWTGYKSSCCGVPCKP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  267 KGVTLGAVKPGDAIVTSMSAGKGVKFFANSVLQYAGDVENVSVWKVIKTFTVNETVCTTDFEGELsdfirPESTSPVSCS 346
Cdd:cd21514    161 ICVVVGSVKPGDVVVTSLGAGSGVKYYNGMVLKHVCDVDGVSIWRVIKVQSVDGFVASGNFDEEL-----HSELSLDACS 235

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  347 IKRafitgevddavhdciiagkldlstnlfgsanllfkKMPWFVQKCGAIFADAWKVVEELLCSLKLTYKQIYDVVASLC 426
Cdd:cd21514    236 FTN-----------------------------------DKPWFVRKLGDLFESAWDAFVAAVKSLKVTSKQLVDLVKALC 280

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  427 TSAFTIMDYKPVFVVS-SNSVKDLVDKCVKILVKAFDVFTQTITIAGveaKCFVLGSKYLLFNNALVKLVSVKILGKRQK 505
Cdd:cd21514    281 SAALTVVNGVIVFVADvPEKFKSAFEKFVSFVVGLFDLTCDTVKVAG---KKFKRVGDYVLLNNALVKLVSVKVKGVRQA 357

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  506 GLDSAFFATNLIGATVNVTPQRTESAYISLNKVDDAVT-PGGGHIVIIGDMAFYKSEEYYFMMASPDSVLVNNVFKAarv 584
Cdd:cd21514    358 GLKTAQYATVVVGKTTKVTSSRVEVATVNLVLVDEDVPlPGEGYTVVIGGQAFFCSGGYYRLMADPDEVLETPVFKA--- 434

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  585 psynivydvnddtkskmvvkigtsfdfdgdldaaiakvndlliefrqeklcfralkdgenilveaylkkYKMPVCLKNHV 664
Cdd:cd21514    435 ---------------------------------------------------------------------FKAPSYIKDEV 445

                          570       580       590       600       610
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1983930777  665 GLWDIIRQDSGKKGFLDTFNHLNELEDVKDIK-------IQTIKNIICPDLLLELDFG 715
Cdd:cd21514    446 EFVDLCEKYVGEPGFDEFYVAAHEALDLDQFEvalfsfdKVDEKEPECPELLLEIDGG 503

CoV_NSP3_C

pfam19218

Coronavirus replicase NSP3, C-terminal; This family represents the C-terminal region of ...

1943-2391

0e+00

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: 601.25 E-value: 0e+00

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1943 KLACSGSVQAYSNSSFVKSEVCGNSILCKACLASYDELADFDHLQVSWDYKSDPLWNRVIQLSYFIF-----LAVFGNNY 2017
Cdd:pfam19218    1 GYPCDGYVDGYSNSSFNKSDYCNGSILCKACLSGYDSLHDYPHLKVVQQPVKDPLFVDVTPLFYFAIelfvaLALFGGTF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2018 VRCLLMYFVSQYLNLWLSYFGYVKYSWFLHVVNFESISVEFVIIVVVFKAVLALKHIFLPCNNPSCKTCSKIARQTRIPI 2097
Cdd:pfam19218   81 VRVFLLYFLQQYVNFFGVYLGLQDYSWFLTLIPFDSFLREYVVLFYVIKLYRFLKHVVFGCKKPSCLACSKSARLTRVPV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2098 QVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRDLSNSIKQTVYATDRSYQEVTKVECTDGFYRF 2177
Cdd:pfam19218  161 STVVNGSKKSFYVNANGGTKFCKKHNFFCKNCDSYGPGNTFINDEVAEDLSNVTKRSVKPTDPAYYEVDKVEFQNGFYYL 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2178 YVGEEFTAYDYDVKHKKYSSQEVLKTMFL----LDDFIVYNPSGSSLASVRNVCVYFSQLIGRPIKIVNSELLEDL--SV 2251
Cdd:pfam19218  241 YSGREFWRYYFDVTVSKYSDKEVLKNCNIkgypLDDFIVYNSNGSNLAQAKNACVYYSQLLCKPIKLVDSNLLSSLgdSV 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2252 DFKGALFNAKKNVIKNSFNVDVSECKNLEECYKLCNLDVTFSTFEMAINNAHRFGILITDRSFNNFWPSKIKPGSSgVSA 2331
Cdd:pfam19218  321 DVNGALHDAFVEVLLNSFNVDLSKCKTLIECKKDLGSDVDTDSFVNAVLNAHRYDVLLTDDSFNNFVPTYAKPEDS-LST 399

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2332 MDIGKCMTFDAKIVNAKVLTQRGKSVVWLSQDFSTLSSTAQKVLVKTFVEEGVNFSLTFN 2391
Cdd:pfam19218  400 HDLAVCIRFGAKIVNHNVLKKENVPVVWSADDFLKLSEEARKYIVKTAKKKGVTFMLTFN 459

alphaCoV_Nsp5_Mpro

cd21665

alphacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...

2906-3201

0e+00

Pssm-ID: 394886 Cd Length: 296 Bit Score: 590.42 E-value: 0e+00

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2906 LRKMAQPSGVVEPCIVRVAYGNNVLNGLWLGDEVICPRHVIASDTSRVINYENELSSVRLHNFSIAKNNAFLGVVSAKYK 2985
Cdd:cd21665      1 LRKMAQPSGVVEKCVVRVSYGNMVLNGLWLGDTVYCPRHVIASDTTSTIDYDHEYSLMRLHNFSISVGNVFLGVVGVTMR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2986 GVNLVLKVNQVNPNTPEHKFKSVRPGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGTLYFVYMH 3065
Cdd:cd21665     81 GALLVIKVNQNNVNTPKYTFRTLKPGDSFNILACYDGVPSGVYGVNMRTNYTIKGSFINGACGSPGYNLNNGTVEFCYMH 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3066 HLELGNGSHVGSNLEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAALINGERWFVTNTSMTLESYNAWAKTNSFTEIV 3145
Cdd:cd21665    161 QLELGSGCHVGSDLDGVMYGGYEDQPTLQVEGANVLVTENVVAFLYAALLNGCNWWLSSDRVTVEAFNEWAVANGFTTVS 240

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1983930777 3146 STDAFNMLAAKTGYSVEKLLECIVRLNKGFGGRTILSYGSLCDEFTPTEVIRQMYG 3201
Cdd:cd21665    241 STDCFSILAAKTGVDVERLLAAIQRLSKGFGGKTILGYTSLTDEFTLSEVIKQMYG 296

Peptidase_C30

pfam05409

Coronavirus endopeptidase C30; This Coronavirus (CoV) domain, peptidase C30, is also known as ...

2932-3205

1.06e-168

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: 520.85 E-value: 1.06e-168

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2932 GLWLGDEVICPRHVIASDTSRVINYENELSSVRLHNFSIAKNNAFLGVVSAKYKGVNLVLKVNQVNPNTPEHKFKSVRPG 3011
Cdd:pfam05409    1 GLWLGDTVYCPRHVIGSFTGMLPQYEHLLSIARNHDFCVVSGGVQLTVVSAKMQGAILVLKVHTNNPNTPKYKFVRLKPG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3012 ESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGTLYFVYMHHLELGNGSHVGSNLEGEMYGGYEDQP 3091
Cdd:pfam05409   81 ESFTILAAYDGCPQGVYHVTMRSNHTIKGSFLNGACGSVGYNLKGGTVCFVYMHHLELPNGSHTGTDLEGVFYGPYVDEE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3092 SMQLEGTNVMSSDNVVAFLYAALINGERWFVTNTSMTLESYNAWAKTNSFTEIVSTDAFNMLAAKTGYSVEKLLECIVRL 3171
Cdd:pfam05409  161 VAQLEGTDQTYTDNVVAWLYAAIINGPRWFLASTTVSLEDFNAWAMTNGFTPFPCEDAILGLAAKTGVSVERLLAAIKVL 240

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1983930777 3172 NKGFGGRTILSYGSLCDEFTPTEVIRQMYGVNLQ 3205
Cdd:pfam05409  241 NNGFGGRTILGSPSLEDEFTPEDVYNQMAGVTLQ 274

cv_Nsp4_TM

cd21473

coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in ...

2427-2800

1.59e-161

Pssm-ID: 394836 Cd Length: 376 Bit Score: 504.82 E-value: 1.59e-161

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2427 FWCLVLFITLYGLCSVYSVATQSYIdSAEGYDYMVIKNGVVQSFDDSINCVHNTYKGFAVWFKAKHGFVPTFDKSCPIVL 2506
Cdd:cd21473      2 LWLLLAAILLYAFLPSYSVFTVTVS-SFPGYDFKVIENGVLRDIRSTDTCFANKFVNFDSWYQAKYGSVPTNSKSCPIVV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2507 GTVFDLGNMrpIPDVPAYVALVGRSLVFAINAA-FGVTNVCYDHTGAAVSKNSYFDTCVFNSACTTLTGIGGTVVYCAKQ 2585
Cdd:cd21473     81 GVIDDVRGS--VPGVPAGVLLVGKTLVHFVQTVfFGDTVVCYTPDGVITYDSFYTSACVFNSACTYLTGLGGRQLYCYDT 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2586 GLVEGAKLYSELLPDYYYEHASGNMVKIPAIIRSFGLRFVKTQATTYCRVGECTESQAGFCFGGDNWFVYDKEF-GDGYI 2664
Cdd:cd21473    159 GLVEGAKLYSDLLPHVRYKLVDGNYIKFPEVILEGGPRIVRTLATTYCRVGECEDSKAGVCVSFDGFWVYNNDYyGPGVY 238

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2665 CGSSTLGFFKNVFALFNSNMSVVATSGAMLANIVIACLAIAVCYGVLKFKKIFGDCTLLVVMIIVTLVVNNVSYFVTQNT 2744
Cdd:cd21473    239 CGDGLFDLLTNLLSGFFQPVSVFALSGQLLFNTIVAILAVLACYYVQKFKRAFGDMSVVVVTVVAAALVNNVLYVVTQNP 318

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1983930777 2745 FFMIVYAIIYYFTTRKLAY--PGVLDAGFIIAYLNMAPWYVLVLYIMVFLYDSLPSLF 2800
Cdd:cd21473    319 LLMIVYAVLYFYATLYLTYerAWIMHLGWVVAYGPIAPWWLLALYVVAVLYDYLPWFF 376

CoV_NSP4_N

pfam19217

Coronavirus replicase NSP4, N-terminal; This is the N-terminal domain of the coronavirus ...

2438-2785

1.81e-144

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: 454.81 E-value: 1.81e-144

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2438 GLCSVYSVATQSYIDSAEGYDYMVIKNGVVQSFDDSINCVHNTYKGFAVWFKAKHGFvPTFDKSCPIVLGTVF-DLGNMr 2516
Cdd:pfam19217    1 YALSPTFFNTVVYFVSDPVYDFKVIENGVLRDFRSTDTCFHNKFDNFDSWHQAKFGS-PTNSRSCPIVVGVVDeVVGRV- 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2517 pIPDVPAYVALV-GRSLVFAINAAFGVTNVCYDHTGAAVSKNSYFDTCVFNSACTTLTGIGGT-VVYCAKQGLVEGAKLY 2594
Cdd:pfam19217   79 -VPGVPAGVALVgGTILHFVTRVFFGAGNVCYTPSGVVTYESFSASACVFNSACTTLTGLGGTrVLYCYDDGLVEGAKLY 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2595 SELLPDYYYEHASGNMVKIPAIIRSFGLRFVKTQATTYCRVGECTESQAGFCFGGDNWFVYDKEFGDGYICGSSTLGFFK 2674
Cdd:pfam19217  158 SDLVPHVRYKLVDGNYVKLPEVLFRGGFRIVRTLATTYCRVGECEDSKAGVCVGFDRSFVYNNDFGPGVYCGSGFLSLLT 237

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2675 NVFALFNSNMSVVATSGAMLANIVIACLAIAVCYGVLKFKKIFGDCTLLVVMIIVTLVVNNVSYFVTQ-NTFFMIVYAII 2753
Cdd:pfam19217  238 NVFSGFNTPISVFALTGQLMFNCVVALIAVCVCYYVLKFKRAFGDYSTGVLTVVLATLVNNLSYFVTQvNPVLMIVYAVL 317

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1983930777 2754 YYFTTRKLAYP--GVLDAGFIIAYLNMAPWYVLV 2785
Cdd:pfam19217  318 YFYATLYVTPEyaWIWHLGFLVAYVPLAPWWVLL 351

alphaCoV_PLPro

alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...

1498-1784

1.85e-135

Pssm-ID: 409648 Cd Length: 289 Bit Score: 426.27 E-value: 1.85e-135

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1498 GTIPIKVTEDTVNQKRVSVALDKTYGEQLkGTVVIKDKDVTNQ-LPSVSDVGEKVvkALDVDWNAYYGFPNAAAFSASSH 1576
Cdd:cd21731      1 KSVVVKVTEDGRNVKDVVVDTDKTFGEQL-GVCSVNDKDVTGVvPPDDSDKVVSV--APDVDWDSHYGFPNAAVFHTLDH 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1577 DAYEFDVVTHNNFIVHKQTDNNCWVNAICLALQRLKPTWKFPGVKSLWDAFLTRKTAGFVHMLYHISGLTKGQPGDAELT 1656
Cdd:cd21731     78 SAYAFESDIVNGKRVLKQSDNNCWVNAVCLQLQFAKPTFKSEGLQALWNKFLTGDVAGFVHWLYWITGANKGDPGDAENT 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1657 LHKLVDLMSSDSAVTVTHTTACDKCAKVETFTGPVV-AAPLLVCGTDEICVHGVHVNVKVTSIRGTVAITSLIGPVVGDV 1735
Cdd:cd21731    158 LNKLSKYLVSSGSVTVERTTGCDSCNSKRTVTTPVVnASVLRSGVDDGVCKHGVKVTTRVVSVKGTVIITSVGKPVVSDA 237

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1983930777 1736 ---IDATGYICYTGLNSRGHYTYYDNRNGLMVDADKAYHFEKNLLQVTTAIA 1784
Cdd:cd21731    238 lllLDGVSYTAFSGDVDNGHYTVYDKATGKVYDGDKTVSFKLDLLSVTSVVV 289

alphaCoV-Nsp6

cd21558

alphacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...

3190-3499

2.32e-135

Pssm-ID: 394844 Cd Length: 293 Bit Score: 425.84 E-value: 2.32e-135

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3190 FTPTEVIRQMYGVNLQSGKVKSIFYPMMTAIAILFAFWLEFFMYTPFTWINPTFVSVVLAITTLVSVLLVAGIKHKMLFF 3269
Cdd:cd21558      1 FTTSEVIKQMYGVNLQSGKVKSAFKNVLLVGVFLFMFWSELLMYTSFFWINPGLVTPVFLVLVLVSLLLTLFLKHKMLFL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3270 MSFVMPSVILATAHNVVWDMtYYESLQVLVENVNTTFLPVDMQGVMLALFCVVVFVICTIRFFTCKQSWFSLFATTIFVM 3349
Cdd:cd21558     81 QTFLLPSVIVTAFYNLAWDY-YVTAVLAEYFDYHVSLMSFDIQGVLNIFVCLFVFFLHTYRFVTSGTSWFTYVVSLVFVL 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3350 FNIVKLLGmigepwtddhfllcLVNMLTMLISLTTKDWFVVFASYKVAYYIVVyvMQPAFVQDFGFVKCVSIIYMACGYL 3429
Cdd:cd21558    160 YNYFYGND--------------YLSLLMMVLSSITNNWYVGAIAYKLAYYIVY--VPPSLVADFGTVKAVMLVYVALGYL 223

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3430 FCCYYGILYWVNRFTCMTCGVYQFTVSPAELKYMTANNLSAPKTAYDAMILSFKLMGIGGGRNIKISTVQ 3499
Cdd:cd21558    224 CCVYYGILYWINRFTKLTLGVYDFKVSAAEFKYMVANGLKAPTGVFDALLLSFKLIGIGGERTIKISTVQ 293

alphaCoV_Nsp8

cd21830

alphacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...

3583-3777

1.29e-126

Pssm-ID: 409257 Cd Length: 195 Bit Score: 396.72 E-value: 1.29e-126

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3583 SVASAYAALPSWIAYEKARADLEEAKKNDVSPQLLKQLTKACNIAKSEFEREASVQKKLDKMAEQAAASMYKEARAVDRK 3662
Cdd:cd21830      1 SVASTFANMPSFIAYETARQDYEDAVKNGSSPQLIKQLKKAMNIAKSEFDREASVQRKLDRMAEQAAAQMYKEARAVNRK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3663 SKIVSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSIVEVK 3742
Cdd:cd21830     81 SKVISAMHSLLFGMLRRLDMSSVDTILNLAKDGVVPLSIIPAASATRLVVVVPDLESFSKIRRDGCVHYAGVVWTIVDIK 160

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1983930777 3743 DANGAQVHLKEVTAANELNITWPLSITCERTTKLQ 3777
Cdd:cd21830    161 DNDGKVVHLKEVTAANEESLAWPLHLNCERIVKLQ 195

CoV_NSP8

pfam08717

Coronavirus replicase NSP8; Viral NSP8 (non structural protein 8) forms a hexadecameric ...

3583-3773

1.15e-110

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: 351.07 E-value: 1.15e-110

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3583 SVASAYAALPSWIAYEKARADLEEAKKNDVSPQLLKQLTKACNIAKSEFEREASVQKKLDKMAEQAAASMYKEARAVDRK 3662
Cdd:pfam08717    1 SVASEFSSLPSYAAYETAKEAYEEAVANGSSQQVLKQLKKACNIAKSEFDRDAAVQKKLEKMAEQAMTQMYKEARAVDRK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3663 SKIVSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSIVEVK 3742
Cdd:pfam08717   81 SKVVSAMHTLLFSMLRKLDNSALNTIINNARNGVVPLNIIPATTAAKLTVVVPDYETFVKVVDGNTVTYAGAVWEIQEVK 160

                          170       180       190
                   ....*....|....*....|....*....|.
gi 1983930777 3743 DANGAQVHLKEVTAANELNITWPLSITCERT 3773
Cdd:pfam08717  161 DADGKIVHLKEITMDNSPNLAWPLIVTAERA 191

CoV_NSP6

pfam19213

Coronavirus replicase NSP6; This entry represents proteins found in Coronaviruses and includes ...

3230-3499

1.01e-96

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: 313.80 E-value: 1.01e-96

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3230 FFMYTPFTWINPTFVSVVLAITTLVSVLLVAGIKHKMLFFMSFVMPSVILATAHNVVWDMtYYESLQVLVENVNTTFLPV 3309
Cdd:pfam19213    1 LLMYTALYWLPPNLITPVLPVLTCVSAILTLFIKHKVLFLTTFLLPSVVVMAYYNFTWDY-YPNSFLRTVYDYHFSLTSF 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3310 DMQGVMLALFCVVVFVICTIRFFTCKQSWFSLFATTIFVMFNIVKLLGMIGEPWTddhfllclVNMLTMLISLTTKDWFV 3389
Cdd:pfam19213   80 DLQGYFNIASCVFVNVLHTYRFVRSKYSIATYLVSLVVSVYMYVIGYALLTATDV--------LSLLFMVLSLLTSYWYV 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3390 VFASYKVAYYIVVYvMQPAFVQDFGFVKCVSIIYMACGYLFCCYYGILYWVNRFTCMTCGVYQFTVSPAELKYMTANNLS 3469
Cdd:pfam19213  152 GAIAYKLAKYIVVY-VPPSLIAVFGDIKVVLLVYVCIGYVCCVYFGILYWINRFTKLTLGVYDFKVSAAEFKYMVANGLS 230

                          250       260       270
                   ....*....|....*....|....*....|
gi 1983930777 3470 APKTAYDAMILSFKLMGIGGGRNIKISTVQ 3499
Cdd:pfam19213  231 APRNVFEALILNFKLLGIGGNRTIKISTVQ 260

CoV_NSP2_N

pfam19211

Coronavirus replicase NSP2, N-terminal; This entry corresponds to the N-terminal region of ...

111-310

4.51e-94

Coronavirus replicase NSP2, N-terminal; This entry corresponds to the N-terminal region of coronavirus non-structural protein 2. NSP2 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. The function of this protein is uncertain. This region contains numerous conserved and semi-conserved cysteine residues.

Pssm-ID: 465995 [Multi-domain] Cd Length: 204 Bit Score: 303.88 E-value: 4.51e-94

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  111 AIYVDQYMCGADGKPVIEG---EFKDYFGDEDVIIYEGEEYHCAWLTVRDEKPLCQQTLLTIREIQYNLDIPHKLPNCAI 187
Cdd:pfam19211    2 VIPVDQYMCGADGKPVLPEdtwCFKDYFGDDGEIVLNGGTYRKAWKVVRKNVPYPKQSLFTINSITYLGDIPHVLPNGAV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  188 REVAPPVKKNSKVVLSEEYRKLYDIFGSPFMGNGDSLNTCFDSLHFIAATLKCPCGAESSGVGDWTGFKTACCGLHGKVK 267
Cdd:pfam19211   82 LHVAPRVKKSKKVVLSEKYKSLYDTYGSPFVTNGSTLLEIVPKPVFHHALVKCSCGRESWTVGDWSGFKCLCCGVYGKPI 161

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1983930777  268 GVTLGAVKPGDAIVTSMSAGKGVKFFANSVLQYAGDVENVSVW 310
Cdd:pfam19211  162 CVSAGDVKPGDVLITKAPVGRGKKFFGGAVLKYVGCVEGVSVW 204

alpha_betaCoV_Nsp10

cd21901

alphacoronavirus and betacoronavirus non-structural protein 10; This model represents the ...

3889-4018

4.99e-93

Pssm-ID: 409326 Cd Length: 130 Bit Score: 297.66 E-value: 4.99e-93

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3889 AGKPTEHPSNSGLLTLCAFAPDPAKAYVDAVKRGMQPVTNCVKMLSNGAGNGMAITNGVESNTQQDSYGGASVCIYCRCH 3968
Cdd:cd21901      1 AGKQTEVASNSSLLTLCAFAVDPAKTYLDAVKSGGKPVGNCVKMLTNGTGTGQAITVKPEANTNQDSYGGASVCLYCRAH 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3969 VEHPAIDGLCRFKGKFVQVPTGTQDPIRFCIENEVCVVCGCWLTNGCMCD 4018
Cdd:cd21901     81 VEHPDMDGVCKLKGKYVQVPLGTNDPVRFCLENDVCKVCGCWLGNGCSCD 130

CoV_NSP10

pfam09401

Coronavirus RNA synthesis protein NSP10; Non-structural protein 10 (NSP10) is involved in RNA ...

3900-4018

2.51e-75

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: 246.58 E-value: 2.51e-75

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3900 GLLTLCAFAPDPAKAYVDAVKRGMQPVTNCVKMLSNGAGNGMAITNGVESNTQQDSYGGASVCIYCRCHVEHPAIDGLCR 3979
Cdd:pfam09401    1 SLLSLCAFAVDPAKAYLDYLAQGGQPITNCVKMLCNHAGTGMAITVKPEANTDQDSYGGASVCLYCRAHIEHPNVDGLCQ 80

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1983930777 3980 FKGKFVQVPTGTQDPIRFCIENEVCVVCGCWLTNGCMCD 4018
Cdd:pfam09401   81 LKGKFVQIPTGTKDPVSFCLTNTVCTVCGCWLGYGCSCD 119

TGEV-like_alphaCoV_Nsp1

cd21687

non-structural protein 1 from transmissible gastroenteritis virus and similar ...

2-105

1.39e-68

Pssm-ID: 439284 Cd Length: 104 Bit Score: 226.60 E-value: 1.39e-68

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777    2 SSKQFKILVNEDYQVNVPSLPFRDALQEIKYCYRNGFDGYVFVPEYRRDLVDCNRKDHYVIGVLGNGISDLKPVLLTEPS 81
Cdd:cd21687      1 SSKQFKILVNEDYQVNVPSLPFRDVLQEIKYCYRNGFDGYVFVPEYRRDLVDCDRKDHYVIGVLGNGISDLKPVLLTEPS 80

                           90       100
                   ....*....|....*....|....
gi 1983930777   82 VMLQGFIVRANCNGVLEDFDLKFA 105
Cdd:cd21687     81 VMLQGFIVRANCNGVLEDFDLKIA 104

CNV-Replicase_N

pfam16688

Replicase polyprotein N-term from Coronavirus nsp1; CNV-Replicase_N is the N-terminal domain ...

1-108

2.62e-68

Replicase polyprotein N-term from Coronavirus nsp1; CNV-Replicase_N is the N-terminal domain of a family of ssRNA positive-stranded porcine transmissible gastroenteritis coronaviruses. the domain folds into a six-stranded beta-barrel fold with a long alpha helix on the rim of the barrel. This fold is shared with SARS-CoV nsp1.

Pssm-ID: 465234 Cd Length: 108 Bit Score: 226.03 E-value: 2.62e-68

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777    1 MSSKQFKILVNEDYQVNVPSLPFRDALQEIKYCYRNGFDGYVFVPEYRRDLVDCNRKDHYVIGVLGNGISDLKPVLLTEP 80
Cdd:pfam16688    1 MSSKQFKILVNEDYQVNVPSLPFRDVLQDIKYCYRNGFDGYVFVPEYRRDLVDCNRKDHYVIGVLGNGISDLKPVLLTEP 80

                           90       100
                   ....*....|....*....|....*...
gi 1983930777   81 SVMLQGFIVRANCNGVLEDFDLKFARTG 108
Cdd:pfam16688   81 SVMLQGFIVRADCNGVLEDFDLKIARTG 108

alphaCoV_Nsp9

cd21897

alphacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...

3778-3888

2.66e-65

Pssm-ID: 409330 Cd Length: 108 Bit Score: 217.18 E-value: 2.66e-65

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3778 NNEILPGKLKEKAVKASATIdgdAYGSGKALMASEGGKSFIYAFIASDSNLKYVKWESNNDVIPIELEAPLRFYVDGVNG 3857
Cdd:cd21897      1 NNEIMPGKLKQRAVKAEGDG---FSGDGKALYNNEGGKTFMYAFIADKPDLKYVKWEFDGGCNTIELEPPCKFLVDTPNG 77

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1983930777 3858 PEVKYLYFVKSLNTLRRGAVLGYIGATVRLQ 3888
Cdd:cd21897     78 PQIKYLYFVKNLNTLRRGAVLGYIGATVRLQ 108

CoV_NSP9

pfam08710

Coronavirus replicase NSP9; Nsp9 is a single-stranded RNA-binding viral protein involved in ...

3778-3888

4.91e-53

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: 182.29 E-value: 4.91e-53

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3778 NNEILPGKLKEKAVKASATiDGDAYGSGKALMASEGGKSFIYAFIASDSNLKYVKWESNND-VIPIELEAPLRFYVDGVN 3856
Cdd:pfam08710    1 NNELMPGKLKTKACKAGVT-DAHCSVEGKAYYNNEGGGSFVYAILSSNPNLKYAKFEKEDGnVIYVELEPPCRFVVDTPK 79

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1983930777 3857 GPEVKYLYFVKSLNTLRRGAVLGYIGATVRLQ 3888
Cdd:pfam08710   80 GPEVKYLYFVKNLNNLRRGMVLGYISATVRLQ 111

CoV_NSP4_C

pfam16348

Coronavirus replicase NSP4, C-terminal; This is the C-terminal domain of the coronavirus ...

2811-2902

1.75e-49

Pssm-ID: 465099 Cd Length: 92 Bit Score: 171.56 E-value: 1.75e-49

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2811 GDKFVGSFESAAMGTFVIDMRSYETLVNSTSLDRIKSYANSFNKYKYYTGSMGEADYRMACYAHLGKALMDYSVSRNDML 2890
Cdd:pfam16348    1 GDKFVGTFEEAALGTFVIDKESYEKLKNSISLDKFNRYLSLYNKYKYYSGKMDEADYREACCAHLAKALEDFSNSGNDVL 80

                           90
                   ....*....|..
gi 1983930777 2891 YTPPTVSVNSTL 2902
Cdd:pfam16348   81 YTPPTVSVTSSL 92

Macro_X_Nsp3-like

cd21557

X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The ...

1358-1485

3.18e-47

Pssm-ID: 438957 Cd Length: 127 Bit Score: 166.19 E-value: 3.18e-47

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1358 PDVLVNAANGDLRHVGGVARAIDVFTGGKLTKRSKeYLKSSKAIAPGNAVLFENVLEHLSVLNAVGPRNGDSRVEGKLCN 1437
Cdd:cd21557      1 EDVVVNAANENLKHGGGVAGAIYKATGGAFQKESD-YIKKNGPLKVGTAVLLPGHGLAKNIIHVVGPRKRKGQDDQLLAA 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1983930777 1438 VYKAIAKCDGKILTPLISVGIFKVKLEVSLQCLLKTVTDRDLNVFVYT 1485
Cdd:cd21557     80 AYKAVNKEYGSVLTPLLSAGIFGVPPEQSLNALLDAVDTTDADVTVYC 127

alphaCoV_Nsp7

cd21826

alphacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...

3500-3582

2.48e-46

Pssm-ID: 409252 Cd Length: 83 Bit Score: 162.15 E-value: 2.48e-46

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3500 SKLTEMKCTNVVLLGLLSKMHVESNSKEWNYCVGLHNEINLCDDPDAVLEKLLALIAFFLSKHNTCDLSDLIESYFENTT 3579
Cdd:cd21826      1 SKLTDIKCTNVVLLGCLSSMNVAANSKEWAYCVDLHNKINLCDDPEKAQEMLLALLAFFLSKQKDFGLDDLLDSYFDNNS 80


                   ...
gi 1983930777 3580 ILQ 3582
Cdd:cd21826     81 ILQ 83

CoV_NSP7

pfam08716

Coronavirus replicase NSP7; NSP7 (non structural protein 7) has been implicated in viral RNA ...

3500-3582

5.66e-43

Coronavirus replicase NSP7; NSP7 (non structural protein 7) has been implicated in viral RNA replication and is predominantly alpha helical in structure. It forms a hexadecameric supercomplex with NSP8 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.

Pssm-ID: 285878 Cd Length: 83 Bit Score: 152.61 E-value: 5.66e-43

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3500 SKLTEMKCTNVVLLGLLSKMHVESNSKEWNYCVGLHNEINLCDDPDAVLEKLLALIAFFLSKHNTCDLSDLIESYFENTT 3579
Cdd:pfam08716    1 SKLTDVKCTNVVLLGLLQKLHVESNSKLWAYCVELHNEILLCDDPTEAFEKLLALLAVLLSKHSAVDLSDLCDSYLENRT 80


                   ...
gi 1983930777 3580 ILQ 3582
Cdd:pfam08716   81 ILQ 83

CoV_peptidase

Coronavirus papain-like peptidase; This entry contains coronavirus cysteine endopeptidases ...

1499-1780

2.25e-40

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

Pssm-ID: 430171 Cd Length: 318 Bit Score: 153.98 E-value: 2.25e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1499 TIPIKVTEDTVNQKRVSVALDKTYGEQLkGTVVIKDKDVTNQLPSVSDVGEKVVKALDVDWNAYYGFPNAAAFSASSHDA 1578
Cdd:pfam08715    4 QITIYLTEDGVNYHSIVVKPGDSLGQQF-GQVYAKNKDLSGVFPADDVEDKEILYVPTTDWVEFYGFKSILEYYTLDASK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1579 Y-------EFDVVTHNNFIVHKQTDNNCWVNAICLALQRLKPTWKFPGVKSLWDAFLTRKTAGFVHMLYHISGLTKGQPG 1651
Cdd:pfam08715   83 YviylsalTKNVQYVDGFLILKWRDNNCWISSVIVALQAAKIRFKGQFLTEAWAKLLGGDPTDFVAWCYASCTAKVGDFG 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1652 DAELTLHKLVDLMSSDSAVTVTHTTACDKC-AKVETFTGpVVAAplLVCGT----------DEICVHGVHVNVKVTSIRG 1720
Cdd:pfam08715  163 DANWTLTNLAEHFDAEYTNAFLKKRVCCNCgIKSYELRG-LEAC--IQVRAtnldhfktgySNCCVCGANNTDEVIEASL 239

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1983930777 1721 TVAITSLIG--PVVGDVIDATGYICYTGLNSRGHYtYYDNRNGLMVDADKAYHFEKNLLQVT 1780
Cdd:pfam08715  240 PYLLLSATDgpAAVDCLEDGVGTVAFVGSTNSGHY-TYQTAKQAFYDGAKDRKFGKKSPYVT 300

CoV_NSP2_C

Coronavirus replicase NSP2, C-terminal; This entry corresponds to a presumed domain found at ...

731-879

1.93e-24

Pssm-ID: 465996 Cd Length: 156 Bit Score: 102.34 E-value: 1.93e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  731 LGNVKIMLGNGVKV--VCDGCHSFANRLTINYNKLCDTARKDIEIGGIPFSTfktpSSSFIDMKDAIYSVV--------E 800
Cdd:pfam19212    1 LKNAKFTVVNGGIVfvVPKKFKSLVGTLLDLLNKLFDSLVDTVKIAGVKFKA----GGTYYLFSNALVKVVsvklkgkkQ 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  801 YG-----EALSFKTASVPVTNSGIITTDdwsdpILLEPADYVEP-KDNGDVIVIAGYTFYKDEDDHFYPYGSGMVVQKMY 874
Cdd:pfam19212   77 AGlkgakEATVFVGATVPVTPTRVEVVT-----VELEEVDYVPPpVVVGYVVVIDGYAFYKSGDEYYPASTDGVVVPPVF 151


                   ....*
gi 1983930777  875 NKMGG 879
Cdd:pfam19212  152 KLKGG 156

A1pp

smart00506

Appr-1"-p processing enzyme; Function determined by Martzen et al. Extended family detected by ...

1341-1470

9.02e-22

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: 93.91 E-value: 9.02e-22

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  1341 KVSFYQGDLDVLinflEPDVLVNAANGDLRHVGGVARAIDVFTGGKLTKrsKEYLKS-SKAIAPGNAVLFEN-VLEHLSV 1418
Cdd:smart00506    1 ILKVVKGDITKP----RADAIVNAANSDGAHGGGVAGAIARAAGKALSK--EEVRKLaGGECPVGTAVVTEGgNLPAKYV 74

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 1983930777  1419 LNAVGPRNGDSRVEG--KLCNVYK-----AIAKCDGKILTPLISVGIFKVKLEVSLQCL 1470
Cdd:smart00506   75 IHAVGPRASGHSKEGfeLLENAYRnclelAIELGITSVALPLIGTGIYGVPKDRSAQAL 133

alphaCoV_PLPro

alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...

1097-1282

1.63e-20

Pssm-ID: 409648 Cd Length: 289 Bit Score: 95.00 E-value: 1.63e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1097 TPFKTTN--LNGKIILKQQDNNCWINACCYQLQAFDF-FN----HDLWDGFKKDDVMPFVDFCYAALTLKQGDSGDAEYL 1169
Cdd:cd21731     78 SAYAFESdiVNGKRVLKQSDNNCWVNAVCLQLQFAKPtFKseglQALWNKFLTGDVAGFVHWLYWITGANKGDPGDAENT 157

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1170 LeTMLNDY--STAKVTLS--AKCGCGVKEIVLERTVFKLTPLRNEFKYGVCGDCKQINmCKFASVEGSGVFVHdrIEKQT 1245
Cdd:cd21731    158 L-NKLSKYlvSSGSVTVErtTGCDSCNSKRTVTTPVVNASVLRSGVDDGVCKHGVKVT-TRVVSVKGTVIITS--VGKPV 233

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1983930777 1246 PVSQFI-VTPTMHAVYTGTTQSGHYMIEDCIHDYCVDG 1282
Cdd:cd21731    234 VSDALLlLDGVSYTAFSGDVDNGHYTVYDKATGKVYDG 271

CoV_peptidase

Coronavirus papain-like peptidase; This entry contains coronavirus cysteine endopeptidases ...

1082-1316

1.70e-15

Pssm-ID: 430171 Cd Length: 318 Bit Score: 80.80 E-value: 1.70e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1082 AAVDEQEAEQPKPSLTpFKTTNLNGKIILKQQDNNCWINACCYQLQAFDF-----FNHDLWDGFKKDDVMPFVDFCYAAL 1156
Cdd:pfam08715   76 YTLDASKYVIYLSALT-KNVQYVDGFLILKWRDNNCWISSVIVALQAAKIrfkgqFLTEAWAKLLGGDPTDFVAWCYASC 154

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1157 TLKQGDSGDAEYLLETML----NDYSTAKVTLSAKCGCGVKEIVL---ERTVFKLTPLRNEFK--YGVCGDCKQINMCKF 1227
Cdd:pfam08715  155 TAKVGDFGDANWTLTNLAehfdAEYTNAFLKKRVCCNCGIKSYELrglEACIQVRATNLDHFKtgYSNCCVCGANNTDEV 234

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1228 ASVEGSGVFVHdrIEKQTPVSQFIVTPTMHAVYTGTTQSGHYMiedciHDYCVDGMGIKPRKHKFYTSTLFLNANVMTAK 1307
Cdd:pfam08715  235 IEASLPYLLLS--ATDGPAAVDCLEDGVGTVAFVGSTNSGHYT-----YQTAKQAFYDGAKDRKFGKKSPYVTAVYTRFA 307


                   ....*....
gi 1983930777 1308 SKTMVEPPV 1316
Cdd:pfam08715  308 FKNETSLPV 316

Macro

pfam01661

Macro domain; The Macro or A1pp domain is a module of about 180 amino acids which can bind ...

1362-1470

7.04e-09

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: 56.42 E-value: 7.04e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1362 VNAANGDLRHVGGVARAIDVFTGGKLTKRSKEYLKSSkaIAPGNAVLFEN-VLEHLSVLNAVGPR----NGDSRVEgKLC 1436
Cdd:pfam01661    1 VNAANSRLLGGGGVAGAIHRAAGPELLEECRELKKGG--CPTGEAVVTPGgNLPAKYVIHTVGPTwrhgGSHGEEE-LLE 77

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1983930777 1437 NVYK-AIAKCDGK----ILTPLISVGIFKVKLEVSLQCL 1470
Cdd:pfam01661   78 SCYRnALALAEELgiksIAFPAISTGIYGFPWEEAARIA 116

YmdB

COG2110

O-acetyl-ADP-ribose deacetylase (regulator of RNase III), contains Macro domain [Translation, ...

1342-1497

7.70e-09

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: 57.88 E-value: 7.70e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1342 VSFYQGDldvlINFLEPDVLVNAANGDLRHVGGVARAIDVFTGGKLTKRSKEYLKsSKAIAPGNAVLFEnvLEHLS---V 1418
Cdd:COG2110      1 IEIVQGD----ITELDVDAIVNAANSSLLGGGGVAGAIHRAAGPELLEECRRLCK-QGGCPTGEAVITP--AGNLPakyV 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1419 LNAVGP--RNGDSRVEGKLCNVYK-AIAKCDGKILT----PLISVGIFKVKLEVSLQCLLKTVTD--------RDLNVFV 1483
Cdd:COG2110     74 IHTVGPvwRGGGPSEEELLASCYRnSLELAEELGIRsiafPAIGTGVGGFPWEEAAPIAVETLRDfleehpslEEVRFVL 153

                          170
                   ....*....|....
gi 1983930777 1484 YTDQERVTIENFFN 1497
Cdd:COG2110    154 FDEEDYEAYRRALA 167

PRK00431

ADP-ribose-binding protein;

1346-1476

1.95e-05

ADP-ribose-binding protein;

Pssm-ID: 234759 Cd Length: 177 Bit Score: 47.91 E-value: 1.95e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1346 QGDldvlINFLEPDVLVNAANGDLRHVGGVARAIDVFTGGKLTKRSKEYLKSSKAIAPGNAVLFE-NVLEHLSVLNAVGP 1424
Cdd:PRK00431     9 QGD----ITELEVDAIVNAANSSLLGGGGVDGAIHRAAGPEILEECRELRQQQGPCPTGEAVITSaGRLPAKYVIHTVGP 84

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1983930777 1425 --RNGDSRVEGKLCNVYK-AIAKCDGKILT----PLISVGIFKVKLEVSLQCLLKTVTD 1476
Cdd:PRK00431    85 vwRGGEDNEAELLASAYRnSLRLAAELGLRsiafPAISTGVYGYPLEDAARIAVKTVRE 143

Name

Accession

Description

Interval

E-value

TM_Y_alphaCoV_Nsp3_C

cd21712

C-terminus of alphacoronavirus non-structural protein 3, including transmembrane and Y domains; ...

1907-2407

0e+00

Pssm-ID: 409660 Cd Length: 501 Bit Score: 758.70 E-value: 0e+00

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1907 VRQLNKPALWRYIKLVLLLIALYHFFYLFVSIPVVHKLACSGSVQAYSNSSFVKSEVCGNSILCKACLASYDELADFDHL 1986
Cdd:cd21712      1 VIKLKKKKVWFFAKLLLLLYALYALLFMFVRFPPLNSSLCSGYVDGYANSSFVKSEVCGNSLLCKACLAGYDELSDFPHL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1987 QVSWDYKSDPLWNRVIQLSYFIFLAVFGNNYVRCLLMYFVSQYLNLWLSYFGYVKYSWFLHVVNFESISVEFVIIVVVFK 2066
Cdd:cd21712     81 QVVWDHVSDPLFSNVLPLFYFAFLLIFGNNYVRCFLLYFVAQYINNWGVYFGYQDYSWFLHFVPFDSFSDEIVVIFIVVK 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2067 AVLALKHIFLPCNNPSCKTCSKIARQTRIPIQVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRD 2146
Cdd:cd21712    161 VLLFLKHVIFGCDKPSCKACSKSARLTRIPVQTIVNGSMKSFYVHANGGGKFCKKHNFFCVNCDSYGVGNTFINDEVARE 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2147 LSNSIKQTVYATDRSYQEVTKVECTDGFYRFYVGEEFTAYDYDVKHKKYSSQEVLKTMFLLDDFIVYNPSGSSLASVRNV 2226
Cdd:cd21712    241 LSNVVKTTVQPTGPAYIEVDKVEFSNGFYYLYSGDTFWRYNFDITEKKYSCKEVLKNCNLLDDFIVYNNNGSNVAQVKNA 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2227 CVYFSQLIGRPIKIVNSELLEDLSVDFKGALFNAKKNVIKNSFNVDVSECKNLEECYKLCNLDVTFSTFEMAINNAHRFG 2306
Cdd:cd21712    321 CVYFSQLLCKPIKLVDSALLSSLSVDFNGALHKAFVKVLKNSFNKDLSNCKTLEECKKALGLDVSDDEFESAVSNAHRYD 400

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2307 ILITDRSFNNFWPSKIKPGSSgVSAMDIGKCMTFDAKIVNAKVLTQRGKSVVWLSQDFSTLSSTAQKVLVKTFVEEGVNF 2386
Cdd:cd21712    401 VLLTDRSFNNFVTSYAKPEEK-LSTHDIAVCMRAGAKVVNHNVLTKENVPIVWLAKDFSALSEEARKYIVKTTKAKGVNF 479

                          490       500
                   ....*....|....*....|.
gi 1983930777 2387 SLTFNAVGSDEDLPYERFTES 2407
Cdd:cd21712    480 LLTFNDNRMTTTLPAVSIVSK 500

alphaCoV_Nsp2_HCoV-229E-like

cd21514

alphacoronavirus non-structural protein 2 (Nsp2), similar to HCoV-229E Nsp2 and related ...

110-715

0e+00

Pssm-ID: 394865 Cd Length: 503 Bit Score: 620.43 E-value: 0e+00

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  110 GAIYVDQYMCGADGKPVIEG---EFKDYFGDEDVIIYEGEEYHCAWLTVRDEKPLCQQTLLTIREIQYNLDIPHKLPNCA 186
Cdd:cd21514      1 NTVYVDQYMCGADGKPVLPEdewEFKDYFGDLDEIVINGITYVKAWDVERKDVPYEKQNLLSIESITYLSDIPHTLADGA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  187 IREVAPPVKKNSKVVLSEEYRKLYDIFGSPFMGNGDSLNTCFDSLHFIAATLKCPCGAESSGVGDWTGFKTACCGLHGKV 266
Cdd:cd21514     81 VLRVAKPPKKSKKVVLSEPYKKLYDAFGSPFVTNGSTLLEVVTKPVFIHALVKCKCGKESWTVGDWTGYKSSCCGVPCKP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  267 KGVTLGAVKPGDAIVTSMSAGKGVKFFANSVLQYAGDVENVSVWKVIKTFTVNETVCTTDFEGELsdfirPESTSPVSCS 346
Cdd:cd21514    161 ICVVVGSVKPGDVVVTSLGAGSGVKYYNGMVLKHVCDVDGVSIWRVIKVQSVDGFVASGNFDEEL-----HSELSLDACS 235

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  347 IKRafitgevddavhdciiagkldlstnlfgsanllfkKMPWFVQKCGAIFADAWKVVEELLCSLKLTYKQIYDVVASLC 426
Cdd:cd21514    236 FTN-----------------------------------DKPWFVRKLGDLFESAWDAFVAAVKSLKVTSKQLVDLVKALC 280

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  427 TSAFTIMDYKPVFVVS-SNSVKDLVDKCVKILVKAFDVFTQTITIAGveaKCFVLGSKYLLFNNALVKLVSVKILGKRQK 505
Cdd:cd21514    281 SAALTVVNGVIVFVADvPEKFKSAFEKFVSFVVGLFDLTCDTVKVAG---KKFKRVGDYVLLNNALVKLVSVKVKGVRQA 357

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  506 GLDSAFFATNLIGATVNVTPQRTESAYISLNKVDDAVT-PGGGHIVIIGDMAFYKSEEYYFMMASPDSVLVNNVFKAarv 584
Cdd:cd21514    358 GLKTAQYATVVVGKTTKVTSSRVEVATVNLVLVDEDVPlPGEGYTVVIGGQAFFCSGGYYRLMADPDEVLETPVFKA--- 434

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  585 psynivydvnddtkskmvvkigtsfdfdgdldaaiakvndlliefrqeklcfralkdgenilveaylkkYKMPVCLKNHV 664
Cdd:cd21514    435 ---------------------------------------------------------------------FKAPSYIKDEV 445

                          570       580       590       600       610
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1983930777  665 GLWDIIRQDSGKKGFLDTFNHLNELEDVKDIK-------IQTIKNIICPDLLLELDFG 715
Cdd:cd21514    446 EFVDLCEKYVGEPGFDEFYVAAHEALDLDQFEvalfsfdKVDEKEPECPELLLEIDGG 503

CoV_NSP3_C

pfam19218

Coronavirus replicase NSP3, C-terminal; This family represents the C-terminal region of ...

1943-2391

0e+00

Pssm-ID: 466002 Cd Length: 463 Bit Score: 601.25 E-value: 0e+00

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1943 KLACSGSVQAYSNSSFVKSEVCGNSILCKACLASYDELADFDHLQVSWDYKSDPLWNRVIQLSYFIF-----LAVFGNNY 2017
Cdd:pfam19218    1 GYPCDGYVDGYSNSSFNKSDYCNGSILCKACLSGYDSLHDYPHLKVVQQPVKDPLFVDVTPLFYFAIelfvaLALFGGTF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2018 VRCLLMYFVSQYLNLWLSYFGYVKYSWFLHVVNFESISVEFVIIVVVFKAVLALKHIFLPCNNPSCKTCSKIARQTRIPI 2097
Cdd:pfam19218   81 VRVFLLYFLQQYVNFFGVYLGLQDYSWFLTLIPFDSFLREYVVLFYVIKLYRFLKHVVFGCKKPSCLACSKSARLTRVPV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2098 QVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRDLSNSIKQTVYATDRSYQEVTKVECTDGFYRF 2177
Cdd:pfam19218  161 STVVNGSKKSFYVNANGGTKFCKKHNFFCKNCDSYGPGNTFINDEVAEDLSNVTKRSVKPTDPAYYEVDKVEFQNGFYYL 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2178 YVGEEFTAYDYDVKHKKYSSQEVLKTMFL----LDDFIVYNPSGSSLASVRNVCVYFSQLIGRPIKIVNSELLEDL--SV 2251
Cdd:pfam19218  241 YSGREFWRYYFDVTVSKYSDKEVLKNCNIkgypLDDFIVYNSNGSNLAQAKNACVYYSQLLCKPIKLVDSNLLSSLgdSV 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2252 DFKGALFNAKKNVIKNSFNVDVSECKNLEECYKLCNLDVTFSTFEMAINNAHRFGILITDRSFNNFWPSKIKPGSSgVSA 2331
Cdd:pfam19218  321 DVNGALHDAFVEVLLNSFNVDLSKCKTLIECKKDLGSDVDTDSFVNAVLNAHRYDVLLTDDSFNNFVPTYAKPEDS-LST 399

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2332 MDIGKCMTFDAKIVNAKVLTQRGKSVVWLSQDFSTLSSTAQKVLVKTFVEEGVNFSLTFN 2391
Cdd:pfam19218  400 HDLAVCIRFGAKIVNHNVLKKENVPVVWSADDFLKLSEEARKYIVKTAKKKGVTFMLTFN 459

alphaCoV_Nsp5_Mpro

cd21665

alphacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...

2906-3201

0e+00

Pssm-ID: 394886 Cd Length: 296 Bit Score: 590.42 E-value: 0e+00

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2906 LRKMAQPSGVVEPCIVRVAYGNNVLNGLWLGDEVICPRHVIASDTSRVINYENELSSVRLHNFSIAKNNAFLGVVSAKYK 2985
Cdd:cd21665      1 LRKMAQPSGVVEKCVVRVSYGNMVLNGLWLGDTVYCPRHVIASDTTSTIDYDHEYSLMRLHNFSISVGNVFLGVVGVTMR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2986 GVNLVLKVNQVNPNTPEHKFKSVRPGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGTLYFVYMH 3065
Cdd:cd21665     81 GALLVIKVNQNNVNTPKYTFRTLKPGDSFNILACYDGVPSGVYGVNMRTNYTIKGSFINGACGSPGYNLNNGTVEFCYMH 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3066 HLELGNGSHVGSNLEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAALINGERWFVTNTSMTLESYNAWAKTNSFTEIV 3145
Cdd:cd21665    161 QLELGSGCHVGSDLDGVMYGGYEDQPTLQVEGANVLVTENVVAFLYAALLNGCNWWLSSDRVTVEAFNEWAVANGFTTVS 240

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1983930777 3146 STDAFNMLAAKTGYSVEKLLECIVRLNKGFGGRTILSYGSLCDEFTPTEVIRQMYG 3201
Cdd:cd21665    241 STDCFSILAAKTGVDVERLLAAIQRLSKGFGGKTILGYTSLTDEFTLSEVIKQMYG 296

Peptidase_C30

pfam05409

Coronavirus endopeptidase C30; This Coronavirus (CoV) domain, peptidase C30, is also known as ...

2932-3205

1.06e-168

Pssm-ID: 398852 Cd Length: 274 Bit Score: 520.85 E-value: 1.06e-168

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2932 GLWLGDEVICPRHVIASDTSRVINYENELSSVRLHNFSIAKNNAFLGVVSAKYKGVNLVLKVNQVNPNTPEHKFKSVRPG 3011
Cdd:pfam05409    1 GLWLGDTVYCPRHVIGSFTGMLPQYEHLLSIARNHDFCVVSGGVQLTVVSAKMQGAILVLKVHTNNPNTPKYKFVRLKPG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3012 ESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGTLYFVYMHHLELGNGSHVGSNLEGEMYGGYEDQP 3091
Cdd:pfam05409   81 ESFTILAAYDGCPQGVYHVTMRSNHTIKGSFLNGACGSVGYNLKGGTVCFVYMHHLELPNGSHTGTDLEGVFYGPYVDEE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3092 SMQLEGTNVMSSDNVVAFLYAALINGERWFVTNTSMTLESYNAWAKTNSFTEIVSTDAFNMLAAKTGYSVEKLLECIVRL 3171
Cdd:pfam05409  161 VAQLEGTDQTYTDNVVAWLYAAIINGPRWFLASTTVSLEDFNAWAMTNGFTPFPCEDAILGLAAKTGVSVERLLAAIKVL 240

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1983930777 3172 NKGFGGRTILSYGSLCDEFTPTEVIRQMYGVNLQ 3205
Cdd:pfam05409  241 NNGFGGRTILGSPSLEDEFTPEDVYNQMAGVTLQ 274

cv_Nsp4_TM

cd21473

coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in ...

2427-2800

1.59e-161

Pssm-ID: 394836 Cd Length: 376 Bit Score: 504.82 E-value: 1.59e-161

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2427 FWCLVLFITLYGLCSVYSVATQSYIdSAEGYDYMVIKNGVVQSFDDSINCVHNTYKGFAVWFKAKHGFVPTFDKSCPIVL 2506
Cdd:cd21473      2 LWLLLAAILLYAFLPSYSVFTVTVS-SFPGYDFKVIENGVLRDIRSTDTCFANKFVNFDSWYQAKYGSVPTNSKSCPIVV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2507 GTVFDLGNMrpIPDVPAYVALVGRSLVFAINAA-FGVTNVCYDHTGAAVSKNSYFDTCVFNSACTTLTGIGGTVVYCAKQ 2585
Cdd:cd21473     81 GVIDDVRGS--VPGVPAGVLLVGKTLVHFVQTVfFGDTVVCYTPDGVITYDSFYTSACVFNSACTYLTGLGGRQLYCYDT 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2586 GLVEGAKLYSELLPDYYYEHASGNMVKIPAIIRSFGLRFVKTQATTYCRVGECTESQAGFCFGGDNWFVYDKEF-GDGYI 2664
Cdd:cd21473    159 GLVEGAKLYSDLLPHVRYKLVDGNYIKFPEVILEGGPRIVRTLATTYCRVGECEDSKAGVCVSFDGFWVYNNDYyGPGVY 238

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2665 CGSSTLGFFKNVFALFNSNMSVVATSGAMLANIVIACLAIAVCYGVLKFKKIFGDCTLLVVMIIVTLVVNNVSYFVTQNT 2744
Cdd:cd21473    239 CGDGLFDLLTNLLSGFFQPVSVFALSGQLLFNTIVAILAVLACYYVQKFKRAFGDMSVVVVTVVAAALVNNVLYVVTQNP 318

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1983930777 2745 FFMIVYAIIYYFTTRKLAY--PGVLDAGFIIAYLNMAPWYVLVLYIMVFLYDSLPSLF 2800
Cdd:cd21473    319 LLMIVYAVLYFYATLYLTYerAWIMHLGWVVAYGPIAPWWLLALYVVAVLYDYLPWFF 376

CoV_NSP4_N

pfam19217

Coronavirus replicase NSP4, N-terminal; This is the N-terminal domain of the coronavirus ...

2438-2785

1.81e-144

Pssm-ID: 466001 Cd Length: 351 Bit Score: 454.81 E-value: 1.81e-144

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2438 GLCSVYSVATQSYIDSAEGYDYMVIKNGVVQSFDDSINCVHNTYKGFAVWFKAKHGFvPTFDKSCPIVLGTVF-DLGNMr 2516
Cdd:pfam19217    1 YALSPTFFNTVVYFVSDPVYDFKVIENGVLRDFRSTDTCFHNKFDNFDSWHQAKFGS-PTNSRSCPIVVGVVDeVVGRV- 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2517 pIPDVPAYVALV-GRSLVFAINAAFGVTNVCYDHTGAAVSKNSYFDTCVFNSACTTLTGIGGT-VVYCAKQGLVEGAKLY 2594
Cdd:pfam19217   79 -VPGVPAGVALVgGTILHFVTRVFFGAGNVCYTPSGVVTYESFSASACVFNSACTTLTGLGGTrVLYCYDDGLVEGAKLY 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2595 SELLPDYYYEHASGNMVKIPAIIRSFGLRFVKTQATTYCRVGECTESQAGFCFGGDNWFVYDKEFGDGYICGSSTLGFFK 2674
Cdd:pfam19217  158 SDLVPHVRYKLVDGNYVKLPEVLFRGGFRIVRTLATTYCRVGECEDSKAGVCVGFDRSFVYNNDFGPGVYCGSGFLSLLT 237

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2675 NVFALFNSNMSVVATSGAMLANIVIACLAIAVCYGVLKFKKIFGDCTLLVVMIIVTLVVNNVSYFVTQ-NTFFMIVYAII 2753
Cdd:pfam19217  238 NVFSGFNTPISVFALTGQLMFNCVVALIAVCVCYYVLKFKRAFGDYSTGVLTVVLATLVNNLSYFVTQvNPVLMIVYAVL 317

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1983930777 2754 YYFTTRKLAYP--GVLDAGFIIAYLNMAPWYVLV 2785
Cdd:pfam19217  318 YFYATLYVTPEyaWIWHLGFLVAYVPLAPWWVLL 351

CoV_Nsp5_Mpro

cd21646

coronavirus non-structural protein 5, also called Main protease (Mpro); This family contains ...

2907-3198

9.98e-142

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: 444.17 E-value: 9.98e-142

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2907 RKMAQPSGVVEPCIVRVAYGNNVLNGLWLGDEVICPRHVIASDTSRVINYENELSSVRLHNFSIAKNNAFLGVVSAKYKG 2986
Cdd:cd21646      1 KKMAQPSGKVERCMVSVTYGSTTLNGLWLDDTVYCPRHVICKSTTSGPDYDDLLSRARNHNFSVQSGGVQLRVVGVTMQG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2987 VNLVLKVNQVNPNTPEHKFKSVRPGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGTLYFVYMHH 3066
Cdd:cd21646     81 ALLRLKVDTSNPHTPKYKFVTVKPGDSFTILACYNGSPSGVYGVNMRSNYTIKGSFLNGACGSVGYNIDGGTVEFCYMHH 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3067 LELGNGSHVGSNLEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAALINGERWFVTNTSMTLESYNAWAKTNSFTEIVS 3146
Cdd:cd21646    161 LELPNGCHTGTDLTGKFYGPYVDQQVAQVEGADTLITDNVVAWLYAAIINGDRWWLNSSRTTVNDFNEWAMANGFTPVSQ 240

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1983930777 3147 TDAFNMLAAKTGYSVEKLLECIVRLNKGFGGRTILSYGSLCDEFTPTEVIRQ 3198
Cdd:cd21646    241 VDCLSILAAKTGVSVERLLAAIQQLHQNFGGKQILGSTSLEDEFTPEDVVRQ 292

alphaCoV_PLPro

alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...

1498-1784

1.85e-135

Pssm-ID: 409648 Cd Length: 289 Bit Score: 426.27 E-value: 1.85e-135

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1498 GTIPIKVTEDTVNQKRVSVALDKTYGEQLkGTVVIKDKDVTNQ-LPSVSDVGEKVvkALDVDWNAYYGFPNAAAFSASSH 1576
Cdd:cd21731      1 KSVVVKVTEDGRNVKDVVVDTDKTFGEQL-GVCSVNDKDVTGVvPPDDSDKVVSV--APDVDWDSHYGFPNAAVFHTLDH 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1577 DAYEFDVVTHNNFIVHKQTDNNCWVNAICLALQRLKPTWKFPGVKSLWDAFLTRKTAGFVHMLYHISGLTKGQPGDAELT 1656
Cdd:cd21731     78 SAYAFESDIVNGKRVLKQSDNNCWVNAVCLQLQFAKPTFKSEGLQALWNKFLTGDVAGFVHWLYWITGANKGDPGDAENT 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1657 LHKLVDLMSSDSAVTVTHTTACDKCAKVETFTGPVV-AAPLLVCGTDEICVHGVHVNVKVTSIRGTVAITSLIGPVVGDV 1735
Cdd:cd21731    158 LNKLSKYLVSSGSVTVERTTGCDSCNSKRTVTTPVVnASVLRSGVDDGVCKHGVKVTTRVVSVKGTVIITSVGKPVVSDA 237

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1983930777 1736 ---IDATGYICYTGLNSRGHYTYYDNRNGLMVDADKAYHFEKNLLQVTTAIA 1784
Cdd:cd21731    238 lllLDGVSYTAFSGDVDNGHYTVYDKATGKVYDGDKTVSFKLDLLSVTSVVV 289

alphaCoV-Nsp6

cd21558

alphacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...

3190-3499

2.32e-135

Pssm-ID: 394844 Cd Length: 293 Bit Score: 425.84 E-value: 2.32e-135

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3190 FTPTEVIRQMYGVNLQSGKVKSIFYPMMTAIAILFAFWLEFFMYTPFTWINPTFVSVVLAITTLVSVLLVAGIKHKMLFF 3269
Cdd:cd21558      1 FTTSEVIKQMYGVNLQSGKVKSAFKNVLLVGVFLFMFWSELLMYTSFFWINPGLVTPVFLVLVLVSLLLTLFLKHKMLFL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3270 MSFVMPSVILATAHNVVWDMtYYESLQVLVENVNTTFLPVDMQGVMLALFCVVVFVICTIRFFTCKQSWFSLFATTIFVM 3349
Cdd:cd21558     81 QTFLLPSVIVTAFYNLAWDY-YVTAVLAEYFDYHVSLMSFDIQGVLNIFVCLFVFFLHTYRFVTSGTSWFTYVVSLVFVL 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3350 FNIVKLLGmigepwtddhfllcLVNMLTMLISLTTKDWFVVFASYKVAYYIVVyvMQPAFVQDFGFVKCVSIIYMACGYL 3429
Cdd:cd21558    160 YNYFYGND--------------YLSLLMMVLSSITNNWYVGAIAYKLAYYIVY--VPPSLVADFGTVKAVMLVYVALGYL 223

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3430 FCCYYGILYWVNRFTCMTCGVYQFTVSPAELKYMTANNLSAPKTAYDAMILSFKLMGIGGGRNIKISTVQ 3499
Cdd:cd21558    224 CCVYYGILYWINRFTKLTLGVYDFKVSAAEFKYMVANGLKAPTGVFDALLLSFKLIGIGGERTIKISTVQ 293

alphaCoV_Nsp8

cd21830

alphacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...

3583-3777

1.29e-126

Pssm-ID: 409257 Cd Length: 195 Bit Score: 396.72 E-value: 1.29e-126

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3583 SVASAYAALPSWIAYEKARADLEEAKKNDVSPQLLKQLTKACNIAKSEFEREASVQKKLDKMAEQAAASMYKEARAVDRK 3662
Cdd:cd21830      1 SVASTFANMPSFIAYETARQDYEDAVKNGSSPQLIKQLKKAMNIAKSEFDREASVQRKLDRMAEQAAAQMYKEARAVNRK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3663 SKIVSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSIVEVK 3742
Cdd:cd21830     81 SKVISAMHSLLFGMLRRLDMSSVDTILNLAKDGVVPLSIIPAASATRLVVVVPDLESFSKIRRDGCVHYAGVVWTIVDIK 160

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1983930777 3743 DANGAQVHLKEVTAANELNITWPLSITCERTTKLQ 3777
Cdd:cd21830    161 DNDGKVVHLKEVTAANEESLAWPLHLNCERIVKLQ 195

betaCoV_Nsp5_Mpro

cd21666

betacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...

2907-3199

3.47e-114

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: 365.57 E-value: 3.47e-114

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2907 RKMAQPSGVVEPCIVRVAYGNNVLNGLWLGDEVICPRHVIASDTSRVI-NYENELSSVRLHNFSIAKNNAFLGVVSAKYK 2985
Cdd:cd21666      1 RKMAFPSGKVEGCMVQVTCGTMTLNGLWLDDTVYCPRHVICTAEDMLNpNYEDLLIRKTNHSFLVQAGNVQLRVIGHSMQ 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2986 GVNLVLKVNQVNPNTPEHKFKSVRPGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGTLYFVYMH 3065
Cdd:cd21666     81 GCLLRLTVDTSNPKTPKYKFVRVKPGQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLCGSCGSVGYNIDGDCVSFCYMH 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3066 HLELGNGSHVGSNLEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAALINGERWFVTNTSMTLESYNAWAKTNSFTEIV 3145
Cdd:cd21666    161 QMELPTGVHTGTDLEGKFYGPFVDRQTAQAAGTDTTITLNVLAWLYAAVLNGDRWFVNRFTTTLNDFNLWAMKYNYEPLT 240

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1983930777 3146 --STDAFNMLAAKTGYSVEKLLECIVRLNKGFG-GRTILSYGSLCDEFTPTEVIRQM 3199
Cdd:cd21666    241 qdHVDILDPLAAQTGIAVEDMLAALKELLQGGMqGRTILGSTILEDEFTPFDVVRQC 297

CoV_NSP8

pfam08717

Coronavirus replicase NSP8; Viral NSP8 (non structural protein 8) forms a hexadecameric ...

3583-3773

1.15e-110

Pssm-ID: 400866 Cd Length: 197 Bit Score: 351.07 E-value: 1.15e-110

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3583 SVASAYAALPSWIAYEKARADLEEAKKNDVSPQLLKQLTKACNIAKSEFEREASVQKKLDKMAEQAAASMYKEARAVDRK 3662
Cdd:pfam08717    1 SVASEFSSLPSYAAYETAKEAYEEAVANGSSQQVLKQLKKACNIAKSEFDRDAAVQKKLEKMAEQAMTQMYKEARAVDRK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3663 SKIVSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSIVEVK 3742
Cdd:pfam08717   81 SKVVSAMHTLLFSMLRKLDNSALNTIINNARNGVVPLNIIPATTAAKLTVVVPDYETFVKVVDGNTVTYAGAVWEIQEVK 160

                          170       180       190
                   ....*....|....*....|....*....|.
gi 1983930777 3743 DANGAQVHLKEVTAANELNITWPLSITCERT 3773
Cdd:pfam08717  161 DADGKIVHLKEITMDNSPNLAWPLIVTAERA 191

CoV_Nsp8

cd21816

Coronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) ...

3586-3777

1.25e-99

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: 319.08 E-value: 1.25e-99

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3586 SAYAALPSWIAYEKARADLEEAKKNDVSPQLLKQLTKACNIAKSEFEREASVQKKLDKMAEQAAASMYKEARAVDRKSKI 3665
Cdd:cd21816      1 SEFSHLPSYAAYATAQAAYEQAVKNGDSPQELKKLTKALNIAKSEFDRDAAVQKKLEKMADQAMTSMYKEARAEDRRAKI 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3666 VSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSIVEVKDAN 3745
Cdd:cd21816     81 TSAMHALLFSMLKKLDSDAVNNIFEQARDGVVPLNIIPLTTANKLMVVIPDYETYKKTVDGNTFTYAGALWSIVTVVDAD 160

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1983930777 3746 GAQVHLKEVTAANELNITWPLSITCERT--TKLQ 3777
Cdd:cd21816    161 GKIVHLSEINMDNSPNIAWPLIVTCLRAgaVKLQ 194

CoV_NSP6

pfam19213

Coronavirus replicase NSP6; This entry represents proteins found in Coronaviruses and includes ...

3230-3499

1.01e-96

Pssm-ID: 465997 Cd Length: 260 Bit Score: 313.80 E-value: 1.01e-96

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3230 FFMYTPFTWINPTFVSVVLAITTLVSVLLVAGIKHKMLFFMSFVMPSVILATAHNVVWDMtYYESLQVLVENVNTTFLPV 3309
Cdd:pfam19213    1 LLMYTALYWLPPNLITPVLPVLTCVSAILTLFIKHKVLFLTTFLLPSVVVMAYYNFTWDY-YPNSFLRTVYDYHFSLTSF 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3310 DMQGVMLALFCVVVFVICTIRFFTCKQSWFSLFATTIFVMFNIVKLLGMIGEPWTddhfllclVNMLTMLISLTTKDWFV 3389
Cdd:pfam19213   80 DLQGYFNIASCVFVNVLHTYRFVRSKYSIATYLVSLVVSVYMYVIGYALLTATDV--------LSLLFMVLSLLTSYWYV 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3390 VFASYKVAYYIVVYvMQPAFVQDFGFVKCVSIIYMACGYLFCCYYGILYWVNRFTCMTCGVYQFTVSPAELKYMTANNLS 3469
Cdd:pfam19213  152 GAIAYKLAKYIVVY-VPPSLIAVFGDIKVVLLVYVCIGYVCCVYFGILYWINRFTKLTLGVYDFKVSAAEFKYMVANGLS 230

                          250       260       270
                   ....*....|....*....|....*....|
gi 1983930777 3470 APKTAYDAMILSFKLMGIGGGRNIKISTVQ 3499
Cdd:pfam19213  231 APRNVFEALILNFKLLGIGGNRTIKISTVQ 260

CoV_NSP2_N

pfam19211

Coronavirus replicase NSP2, N-terminal; This entry corresponds to the N-terminal region of ...

111-310

4.51e-94

Pssm-ID: 465995 [Multi-domain] Cd Length: 204 Bit Score: 303.88 E-value: 4.51e-94

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  111 AIYVDQYMCGADGKPVIEG---EFKDYFGDEDVIIYEGEEYHCAWLTVRDEKPLCQQTLLTIREIQYNLDIPHKLPNCAI 187
Cdd:pfam19211    2 VIPVDQYMCGADGKPVLPEdtwCFKDYFGDDGEIVLNGGTYRKAWKVVRKNVPYPKQSLFTINSITYLGDIPHVLPNGAV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  188 REVAPPVKKNSKVVLSEEYRKLYDIFGSPFMGNGDSLNTCFDSLHFIAATLKCPCGAESSGVGDWTGFKTACCGLHGKVK 267
Cdd:pfam19211   82 LHVAPRVKKSKKVVLSEKYKSLYDTYGSPFVTNGSTLLEIVPKPVFHHALVKCSCGRESWTVGDWSGFKCLCCGVYGKPI 161

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1983930777  268 GVTLGAVKPGDAIVTSMSAGKGVKFFANSVLQYAGDVENVSVW 310
Cdd:pfam19211  162 CVSAGDVKPGDVLITKAPVGRGKKFFGGAVLKYVGCVEGVSVW 204

alpha_betaCoV_Nsp10

cd21901

alphacoronavirus and betacoronavirus non-structural protein 10; This model represents the ...

3889-4018

4.99e-93

Pssm-ID: 409326 Cd Length: 130 Bit Score: 297.66 E-value: 4.99e-93

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3889 AGKPTEHPSNSGLLTLCAFAPDPAKAYVDAVKRGMQPVTNCVKMLSNGAGNGMAITNGVESNTQQDSYGGASVCIYCRCH 3968
Cdd:cd21901      1 AGKQTEVASNSSLLTLCAFAVDPAKTYLDAVKSGGKPVGNCVKMLTNGTGTGQAITVKPEANTNQDSYGGASVCLYCRAH 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3969 VEHPAIDGLCRFKGKFVQVPTGTQDPIRFCIENEVCVVCGCWLTNGCMCD 4018
Cdd:cd21901     81 VEHPDMDGVCKLKGKYVQVPLGTNDPVRFCLENDVCKVCGCWLGNGCSCD 130

gammaCoV_Nsp5_Mpro

cd21667

gammacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...

2905-3205

2.24e-82

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: 274.36 E-value: 2.24e-82

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2905 GLRKMAQPSGVVEPCIVRVAYGNNVLNGLWLGDEVICPRHVIASDTSRviNYENELSSVRLHNFSIAKNN-AFLGVVSAK 2983
Cdd:cd21667      1 GFKKLVSPSSAVEKCIVSVSYRGNNLNGLWLGDSIYCPRHVLGKFSGD--QWQDVLNLANNHEFEVVTQNgVTLNVVSRR 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2984 YKGVNLVLKVNQVNPNTPEHKFKSVRPGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGTLYFVY 3063
Cdd:cd21667     79 LKGAVLILQTAVANANTPKYKFVKANCGDSFTIACSYGGTVVGLYPVTMRSNGTIRASFLAGACGSVGFNIEKGVVNFFY 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3064 MHHLELGNGSHVGSNLEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAALINGE-------RWfVTNTSMTLESYNAWA 3136
Cdd:cd21667    159 MHHLELPNALHTGTDLMGEFYGGYVDEEVAQRVPPDNLVTNNIVAWLYAAIISVKessfslpKW-LESTTVSVEDYNKWA 237

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1983930777 3137 KTNSFTEIVSTDAFNMLAAKTGYSVEKLLECIVRLNKGFGGRTILSYGSLCDEFTPTEVIRQMYGVNLQ 3205
Cdd:cd21667    238 SDNGFTPFSTSTAITKLSAITGVDVCKLLRTIMVKSAQWGSDPILGQYNFEDELTPESVFNQVGGVRLQ 306

CoV_NSP10

pfam09401

Coronavirus RNA synthesis protein NSP10; Non-structural protein 10 (NSP10) is involved in RNA ...

3900-4018

2.51e-75

Pssm-ID: 462788 Cd Length: 119 Bit Score: 246.58 E-value: 2.51e-75

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3900 GLLTLCAFAPDPAKAYVDAVKRGMQPVTNCVKMLSNGAGNGMAITNGVESNTQQDSYGGASVCIYCRCHVEHPAIDGLCR 3979
Cdd:pfam09401    1 SLLSLCAFAVDPAKAYLDYLAQGGQPITNCVKMLCNHAGTGMAITVKPEANTDQDSYGGASVCLYCRAHIEHPNVDGLCQ 80

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1983930777 3980 FKGKFVQVPTGTQDPIRFCIENEVCVVCGCWLTNGCMCD 4018
Cdd:pfam09401   81 LKGKFVQIPTGTKDPVSFCLTNTVCTVCGCWLGYGCSCD 119

TM_Y_CoV_Nsp3_C

cd21686

C-terminus of coronavirus non-structural protein 3, including transmembrane and Y domains; ...

1916-2391

2.65e-75

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: 260.59 E-value: 2.65e-75

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1916 WRYIKLVLL------LIALYHFFYLFVSIPVVHKLACSGSVQAYSNSSFV-KSEVCGNSILCKACLASYDELADFDHLQV 1988
Cdd:cd21686      1 LFYLASVLFkslapfLLLPAVLYLLNSGYTLGTGSYCKTYWPGYYNSTQHdYNSYCAGDLVCQVCLDGQDSLHLYPHLRV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1989 SWDYKSDplWNRVIQLSYFIFLAVFGNNYVRCLLMYFVSQYLNLWLSYFGyvkysWFLHVVNFESIsVEFVIIVVVFKAV 2068
Cdd:cd21686     81 VQQPLQT--TDYTVYALSLILYLANMTLFMGTFIVTFFVNFYGVGIPFYG-----WLLIDVPQSAF-MMTFSVFFFYYVL 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2069 LALKHIFLPCNNPSCKTCSKIARQTRIPIQVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRDLS 2148
Cdd:cd21686    153 KFFVHVTHGCKIPTCMVCAKLARPPRVEVETVVQGRKYSFYVYTNGGFTFCKEHNFYCKNCDLYGPGCTFISDEVAEELS 232

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2149 NSIKQTVYATDRSYQEVTKVECTDgfyrfyvgeeftaYDYDVKHK-KYSSQEVLKTMFLLDDFIVYNPSGS---SLASVR 2224
Cdd:cd21686    233 RATKLSVKPTAPAFLLVDDVEVQN-------------DVVFARAKyNQNAHVSLSKFSDIPDFIIAANFGSnceQLSTAK 299

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2225 NVCVYFSQLIGRPIKIVNSELLEDLSVDFkgalfnakKNVIKNSFNVDVSECKNLEEC---YKLCNLDVTFSTFEMAINN 2301
Cdd:cd21686    300 NAAVYYSQDLCKPILILDQALSRPIDNYQ--------EVASRIEKYYPVAKIKPTGDIftdIKQGTDGEASDSAINAAVL 371

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2302 AHRFGILITDRSFNNFWPSKIKPgSSGVSAMDIGkcMTFDAKIVNAKVLTQRGKSVVWLSQDFSTLSSTAQKVLVKTFVE 2381
Cdd:cd21686    372 AHQRDVEFTGDSFNNILPSYAKD-ESKLTAEDQA--MSVIAESGNANVNVKGTIPVVWLVADFIRLSEQARKYIISAAKK 448

                          490
                   ....*....|
gi 1983930777 2382 EGVNFSLTFN 2391
Cdd:cd21686    449 NGVTFALTPS 458

TGEV-like_alphaCoV_Nsp1

cd21687

non-structural protein 1 from transmissible gastroenteritis virus and similar ...

2-105

1.39e-68

Pssm-ID: 439284 Cd Length: 104 Bit Score: 226.60 E-value: 1.39e-68

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777    2 SSKQFKILVNEDYQVNVPSLPFRDALQEIKYCYRNGFDGYVFVPEYRRDLVDCNRKDHYVIGVLGNGISDLKPVLLTEPS 81
Cdd:cd21687      1 SSKQFKILVNEDYQVNVPSLPFRDVLQEIKYCYRNGFDGYVFVPEYRRDLVDCDRKDHYVIGVLGNGISDLKPVLLTEPS 80

                           90       100
                   ....*....|....*....|....
gi 1983930777   82 VMLQGFIVRANCNGVLEDFDLKFA 105
Cdd:cd21687     81 VMLQGFIVRANCNGVLEDFDLKIA 104

CNV-Replicase_N

pfam16688

Replicase polyprotein N-term from Coronavirus nsp1; CNV-Replicase_N is the N-terminal domain ...

1-108

2.62e-68

Pssm-ID: 465234 Cd Length: 108 Bit Score: 226.03 E-value: 2.62e-68

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777    1 MSSKQFKILVNEDYQVNVPSLPFRDALQEIKYCYRNGFDGYVFVPEYRRDLVDCNRKDHYVIGVLGNGISDLKPVLLTEP 80
Cdd:pfam16688    1 MSSKQFKILVNEDYQVNVPSLPFRDVLQDIKYCYRNGFDGYVFVPEYRRDLVDCNRKDHYVIGVLGNGISDLKPVLLTEP 80

                           90       100
                   ....*....|....*....|....*...
gi 1983930777   81 SVMLQGFIVRANCNGVLEDFDLKFARTG 108
Cdd:pfam16688   81 SVMLQGFIVRADCNGVLEDFDLKIARTG 108

betaCoV_Nsp8

cd21831

betacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...

3586-3777

1.27e-67

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: 227.75 E-value: 1.27e-67

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3586 SAYAALPSWIAYEKARADLEEAKKN-DVSPQLLKQLTKACNIAKSEFEREASVQKKLDKMAEQAAASMYKEARAVDRKSK 3664
Cdd:cd21831      1 SEFSNLASYAEYETAQKAYDEAVASgDASPQVLKALKKAVNVAKSAYEKDKAVARKLERMADQAMTSMYKQARAEDKKSK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3665 IVSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSIVEVKDA 3744
Cdd:cd21831     81 VVSAMQTMLFGMIRKLDNDALNNIINNARNGCVPLSIIPLTAANKLRVVVPDYSVYKQVVDGPTLTYAGALWDIQQINDA 160

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1983930777 3745 NGAQVHLKEVTAANElNITWPLSITCER----TTKLQ 3777
Cdd:cd21831    161 DGKIVQLSDITEDSE-NLAWPLVVTATRanssAVKLQ 196

alphaCoV_Nsp9

cd21897

alphacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...

3778-3888

2.66e-65

Pssm-ID: 409330 Cd Length: 108 Bit Score: 217.18 E-value: 2.66e-65

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3778 NNEILPGKLKEKAVKASATIdgdAYGSGKALMASEGGKSFIYAFIASDSNLKYVKWESNNDVIPIELEAPLRFYVDGVNG 3857
Cdd:cd21897      1 NNEIMPGKLKQRAVKAEGDG---FSGDGKALYNNEGGKTFMYAFIADKPDLKYVKWEFDGGCNTIELEPPCKFLVDTPNG 77

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1983930777 3858 PEVKYLYFVKSLNTLRRGAVLGYIGATVRLQ 3888
Cdd:cd21897     78 PQIKYLYFVKNLNTLRRGAVLGYIGATVRLQ 108

deltaCoV_Nsp5_Mpro

cd21668

deltacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...

2903-3198

2.70e-63

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: 219.68 E-value: 2.70e-63

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2903 QSGLRKMAQPSGVVEPCIVRVAYGNNVLNGLWLGDEVICPRHVIASDTSrvinyenelsSVRLHNFSIAKNNAF------ 2976
Cdd:cd21668      1 QAGIKILLHPSGVVERCMVSVTYNGSTLNGIWLHNVVYCPRHVIGKYTG----------SQWQDMVSIADCRDFvifcpt 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2977 ----LGVVSAKYKGVNLVLKVNQVNPNTPEHKFKSVRPGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGY 3052
Cdd:cd21668     71 qgiqLTVQSVKMVGAVLQLTVHTKNLHTPDYEFERATPGSSMTIACAYDGIVRNVYHVVLQTNNLIYASFLNGACGSVGY 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3053 VLENGTLYFVYMHHLELGNGSHVGSNLEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAAL--INGERWFVTNTSMTLE 3130
Cdd:cd21668    151 TLKGKTLLLHYMHHLEFNNKTHGGTDLHGHFYGPYVDEEVAQHQTAFQYYTDNVVAQIYAHLltIDAKPKWLASQEISVE 230

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1983930777 3131 SYNAWAKTNSFTEIVSTDAfNM-----LAAKTGYSVEKLLECIVRLNKGFGGRTILSYGSLCDEFTPTEVIRQ 3198
Cdd:cd21668    231 DFNEWAANNSFANFPCESS-NMaylegLAQTTKVSVGRVLNTIIQLTLNRGGALIMGKPDFECDWTPEMVYNQ 302

CoV_Nsp10

cd21872

coronavirus non-structural protein 10; This model represents the non-structural protein 10 ...

3889-4018

6.37e-55

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: 188.45 E-value: 6.37e-55

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3889 AGKPTEHPSNSGLLTLCAFAPDPAKAYVDAVKRGMQPVTNCVKMLSNGAGNGMAITNGVESNTQQDSYGGASVCIYCRCH 3968
Cdd:cd21872      1 AGNATEVPANSTVLSFCAFAVDPAKAYKDYLASGGQPITNCVKMLCTHTGTGQAITVKPEANMDQESFGGASVCLYCRAH 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1983930777 3969 VEHPAIDGLCRFKGKFVQVPTGTQ-DPIRFCIENEVCVVCGCWLTNGCMCD 4018
Cdd:cd21872     81 IDHPNPDGFCDYKGKFVQIPTTCAnDPVGFTLRNTVCTVCQMWKGYGCSCD 131

CoV_NSP9

pfam08710

Coronavirus replicase NSP9; Nsp9 is a single-stranded RNA-binding viral protein involved in ...

3778-3888

4.91e-53

Pssm-ID: 285872 Cd Length: 111 Bit Score: 182.29 E-value: 4.91e-53

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3778 NNEILPGKLKEKAVKASATiDGDAYGSGKALMASEGGKSFIYAFIASDSNLKYVKWESNND-VIPIELEAPLRFYVDGVN 3856
Cdd:pfam08710    1 NNELMPGKLKTKACKAGVT-DAHCSVEGKAYYNNEGGGSFVYAILSSNPNLKYAKFEKEDGnVIYVELEPPCRFVVDTPK 79

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1983930777 3857 GPEVKYLYFVKSLNTLRRGAVLGYIGATVRLQ 3888
Cdd:pfam08710   80 GPEVKYLYFVKNLNNLRRGMVLGYISATVRLQ 111

TM_Y_betaCoV_Nsp3_C

cd21713

C-terminus of betacoronavirus non-structural protein 3, including transmembrane and Y domains; ...

1921-2391

5.58e-53

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: 197.33 E-value: 5.58e-53

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1921 LVLLLIALYHFFYLFVSIPVVHKL-----ACSGSVQAYSNSS----FVKSEVCGNSILCKACLASYDELADFDHLQVSWD 1991
Cdd:cd21713     12 LLLWFNFLYANFILSDSPTFVGSIvawfkYTLGISTICDFYQvtylGDISEFCTGSMLCSLCLSGMDSLDNYDALNMVQH 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1992 YKSDPLWNRVIQ-------LSYFIFLAVFGNNYVRCLLMYFVSQY-LNLWLSYFGYVKYSWFLHVVNFESISVEFVIIVV 2063
Cdd:cd21713     92 TVSSRLSDDYIFklvlelfFAYLLYTVAFYVLGLLAILQLFFSYLpLFFMLNSWLVVLFVYVINMVPASTLVRMYIVVAS 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2064 VFKAVLALKHIFLPCNNPSCKTCSKIARQTRIPIQVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEI 2143
Cdd:cd21713    172 LYFVYKLYVHVVYGCNDTACLMCYKRNRATRVECSTVVNGSKRSFYVMANGGTGFCTKHNWNCVNCDTYGPGNTFICDEV 251

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2144 VRDLSNSIKQTVYATDRSYQEVTKVECTDGFYRFY-------VGEEFTA-YDYDVKHKKYSSqevLKTMfLLDDFIVYNP 2215
Cdd:cd21713    252 AADLSTQFKRPINPTDSSYYSVTSVEVKNGSVHLYyerdgqrVYERFSLsLFVNLDKLKHSE---VKGS-PPFNVIVFDA 327

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2216 SG-SSLASVRNVCVYFSQLIGRPIKIVNSELLEDL--SVDFKGALFNAKKNVIKNSFNVDVSECKNL-----EECYKLCN 2287
Cdd:cd21713    328 SNrAEENGAKSAAVYYSQLLCKPILLVDKKLVTTVgdSAEVARKMFDAYVNSFLSTYNVTMDKLKTLvstahNSLKEGVQ 407

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2288 LDVTFSTF-------------------EMAINNAHRFGILITDRSFNNFWPSKIKPGSsgVSAMDIGKCMTFDAKIVNAK 2348
Cdd:cd21713    408 LEQVLKTFigaarqkaavesdvetkdiVKCVQLAHQADVDFTTDSCNNLVPTYVKVDT--ITTADLGVLIDNNAKHVNAN 485

                          490       500       510       520
                   ....*....|....*....|....*....|....*....|...
gi 1983930777 2349 VLTQRGKSVVWLSQDFSTLSSTAQKVLVKTFVEEGVNFSLTFN 2391
Cdd:cd21713    486 VAKAANVALIWNVAAFLKLSESLRRQLRSAARKTGLNFKLTTS 528

gammaCoV_Nsp8

cd21832

gammacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...

3583-3774

6.06e-51

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: 180.54 E-value: 6.06e-51

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3583 SVASAYAALPSWIAYEKARADLEE----AKKNDVSPQLLKQLTKACNIAKSEFEREASVQKKLDKMAEQAAASMYKEARA 3658
Cdd:cd21832      1 SVTQEFSHIPSYAEYERAKDLYEKvladSKNGGVTQQELAAYRKAANIAKSVFDRDLAVQKKLDSMAERAMTTMYKEARV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3659 VDRKSKIVSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSI 3738
Cdd:cd21832     81 TDRRAKLVSSLHALLFSMLKKIDSEKLNVLFDQASSGVVPLATVPIVCSNKLTLVIPDPETWVKCVEGMHVTYSTVVWNI 160

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1983930777 3739 VEVKDANGAQVHlkEVTAANEL-------NITWPLSITCERTT 3774
Cdd:cd21832    161 DTVIDADGTELH--PTSTGSGLtycisgdNIAWPLKVNLTRNG 201

CoV_NSP4_C

pfam16348

Coronavirus replicase NSP4, C-terminal; This is the C-terminal domain of the coronavirus ...

2811-2902

1.75e-49

Pssm-ID: 465099 Cd Length: 92 Bit Score: 171.56 E-value: 1.75e-49

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2811 GDKFVGSFESAAMGTFVIDMRSYETLVNSTSLDRIKSYANSFNKYKYYTGSMGEADYRMACYAHLGKALMDYSVSRNDML 2890
Cdd:pfam16348    1 GDKFVGTFEEAALGTFVIDKESYEKLKNSISLDKFNRYLSLYNKYKYYSGKMDEADYREACCAHLAKALEDFSNSGNDVL 80

                           90
                   ....*....|..
gi 1983930777 2891 YTPPTVSVNSTL 2902
Cdd:pfam16348   81 YTPPTVSVTSSL 92

Macro_X_Nsp3-like

cd21557

X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The ...

1358-1485

3.18e-47

Pssm-ID: 438957 Cd Length: 127 Bit Score: 166.19 E-value: 3.18e-47

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1358 PDVLVNAANGDLRHVGGVARAIDVFTGGKLTKRSKeYLKSSKAIAPGNAVLFENVLEHLSVLNAVGPRNGDSRVEGKLCN 1437
Cdd:cd21557      1 EDVVVNAANENLKHGGGVAGAIYKATGGAFQKESD-YIKKNGPLKVGTAVLLPGHGLAKNIIHVVGPRKRKGQDDQLLAA 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1983930777 1438 VYKAIAKCDGKILTPLISVGIFKVKLEVSLQCLLKTVTDRDLNVFVYT 1485
Cdd:cd21557     80 AYKAVNKEYGSVLTPLLSAGIFGVPPEQSLNALLDAVDTTDADVTVYC 127

gammaCoV_Nsp10

cd21902

gammacoronavirus non-structural protein 10; This model represents the non-structural protein ...

3890-4018

4.71e-47

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: 166.23 E-value: 4.71e-47

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3890 GKPTEHPSNSGLLTLCAFAPDPAKAYVDAVKRGMQPVTNCVKMLSNGAGNGMAITNGVESNTQQDSYGGASVCIYCRCHV 3969
Cdd:cd21902      2 GHETEEVDAVGILSLCSFAVDPADTYCKYVAAGNQPLGNCVKMLTVHNGSGFAITSKPSPTPDQDSYGGASVCLYCRAHI 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1983930777 3970 EHPA----IDGLCRFKGKFVQVPTGTQDPIRFCIENEVCVVCGCWLTNGCMCD 4018
Cdd:cd21902     82 AHPGgagnLDGRCQFKGSFVQIPTTEKDPVGFCLRNKVCTVCQCWIGYGCQCD 134

alphaCoV_Nsp7

cd21826

alphacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...

3500-3582

2.48e-46

Pssm-ID: 409252 Cd Length: 83 Bit Score: 162.15 E-value: 2.48e-46

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3500 SKLTEMKCTNVVLLGLLSKMHVESNSKEWNYCVGLHNEINLCDDPDAVLEKLLALIAFFLSKHNTCDLSDLIESYFENTT 3579
Cdd:cd21826      1 SKLTDIKCTNVVLLGCLSSMNVAANSKEWAYCVDLHNKINLCDDPEKAQEMLLALLAFFLSKQKDFGLDDLLDSYFDNNS 80


                   ...
gi 1983930777 3580 ILQ 3582
Cdd:cd21826     81 ILQ 83

CoV_Nsp6

cd21526

coronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell ...

3195-3499

1.33e-44

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: 165.01 E-value: 1.33e-44

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3195 VIRQMYGVNLQS---GKVKSIFYPMMTAIAILFAFWLeffMYTPFTWINPTFVSVVLAITTLVsvllvagiKHKMLFFMS 3271
Cdd:cd21526      1 VYNQAPGVLLQSvfvVKKTSTFWSHFLFAAFTMLLAA---PLVFPVHAYVILLMCFTVVTFTV--------KHKVAFLTT 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3272 FVMPSVILATA-HNVVWD------MTYYESlqvlvenVNTTFLPVDMQGVMLALFCVVVFVICTIRFFTCKQSWFSLFAT 3344
Cdd:cd21526     70 FLLPSLITMVAiANTFWIqvvtflRTWYDT-------VFVSPIAQDLYGYTVALYMLIYAGLATNYTLKTLRYRATSFLS 142

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3345 TIFVMFNI--VKLLGMIGEPWTddhfllclVNMLTMLISLTTKDWFVVFASYKVAYYIVVYVMQPAFVQdfgfVKCVSII 3422
Cdd:cd21526    143 FLMQNFLTlyTAHYAYKLLPWT--------ESLLFTALTMLSSHSLIGAIVFWLARWMLRVEYPIIFPD----LAIRVLA 210

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1983930777 3423 YMACGYLFCCYYGILYWVNRFTCMTCGVYQFTVSPAELKYMTANNLSAPKTAYDAMILSFKLMGIGGGRNIKISTVQ 3499
Cdd:cd21526    211 YNVIGYVCTCYFGLMWLANRFFTLTLGVYDYMVSVEQFRYMMAVKLNPPKNAFEVFILNIKLLGIGGNRNIKVATVQ 287

CoV_NSP7

pfam08716

Coronavirus replicase NSP7; NSP7 (non structural protein 7) has been implicated in viral RNA ...

3500-3582

5.66e-43

Pssm-ID: 285878 Cd Length: 83 Bit Score: 152.61 E-value: 5.66e-43

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3500 SKLTEMKCTNVVLLGLLSKMHVESNSKEWNYCVGLHNEINLCDDPDAVLEKLLALIAFFLSKHNTCDLSDLIESYFENTT 3579
Cdd:pfam08716    1 SKLTDVKCTNVVLLGLLQKLHVESNSKLWAYCVELHNEILLCDDPTEAFEKLLALLAVLLSKHSAVDLSDLCDSYLENRT 80


                   ...
gi 1983930777 3580 ILQ 3582
Cdd:pfam08716   81 ILQ 83

CoV_NSP2_C

Coronavirus replicase NSP2, C-terminal; This entry corresponds to a presumed domain found at ...

425-582

4.88e-42

Pssm-ID: 465996 Cd Length: 156 Bit Score: 152.80 E-value: 4.88e-42

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  425 LCTSAFTIMDYKPVFVVSSNsVKDLVDKCVKILVKAFDVFTQTITIAGVEAKCfvlGSKYLLFNNALVKLVSVKILGKRQ 504
Cdd:pfam19212    1 LKNAKFTVVNGGIVFVVPKK-FKSLVGTLLDLLNKLFDSLVDTVKIAGVKFKA---GGTYYLFSNALVKVVSVKLKGKKQ 76

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1983930777  505 KGLDSAFFATNLIGATVNVTPQRTESAYISLNKVDDAV-TPGGGHIVIIGDMAFYKSEEYYFmMASPDSVLVNNVFKAA 582
Cdd:pfam19212   77 AGLKGAKEATVFVGATVPVTPTRVEVVTVELEEVDYVPpPVVVGYVVVIDGYAFYKSGDEYY-PASTDGVVVPPVFKLK 154

TM_Y_MERS-CoV-like_Nsp3_C

cd21716

C-terminus of non-structural protein 3, including transmembrane and Y domains, from Middle ...

1945-2405

2.74e-41

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: 163.06 E-value: 2.74e-41

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1945 ACSGSVQAYSNSSFVKSEVCGN-SILCKACLASYDELADFDHLQVSWDYKS------DPLWNRV-IQLSYFIFLAVFGNN 2016
Cdd:cd21716     55 ACDGLASAYRANSFDVPDFCANrSALCNWCLIGQDSITHYSALKMVQTHLShyvlniDWLWFALeLLLAYVLYTSAFNWL 134

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2017 YVRCLLMYFVSQ---YLNlWLSYfGYVKYSWFLHvvnFESISVEFVIIVVVFKAVLAL-----KHIFLPCNNPSCKTCSK 2088
Cdd:cd21716    135 LLACTLQYFFAQtsaFVD-WRSY-NYVVSGIFLL---FTHIPLDGLVRIYNVLACLWFlrkfyNHVINGCKDTACLLCYK 209

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2089 IARQTRIPIQVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRDLSNSIKQTVYATDRSYQEVTKV 2168
Cdd:cd21716    210 RNRLTRVEASTVVCGGKRTFYITANGGTSFCRRHNWNCVDCDTAGVGNTFICEEVANDLTTSLRRLVKPTDRSHYYVDSV 289

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2169 ECTDGFYRF-YVGEEFTAYD-----YDVKHKKYSSQEVLKTMFLLDD--FIVYNPSG---SSLAsvRNVCVYFSQLIGRP 2237
Cdd:cd21716    290 EVKDTVVQLnYRRDGQSCYErfplcYFTNLDKLKFKEVCKTTTGIPEhnFIIYDSSDrgqENLA--RSACVYYSQVLCKP 367

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2238 IKIVNSELLEDL--SVDFKGALFNAKKNVIKNSFNVDVSECKNLEECYKLC-----NLDVTFSTFEMA------------ 2298
Cdd:cd21716    368 ILLVDSNLVTSVgdSSEIAIKMFDSFVNSFVSLYNVTRDKLEKLISTARDGvkrgdNFQSVLKTFIDAargpagvesdve 447

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2299 -------INNAHRFGILITDRSFNNFWPSKIKPGSsgVSAMDIGKCMTFDAKIVNAKVLTQRGKSVVWLSQDFSTLSSTA 2371
Cdd:cd21716    448 tneivdaVQYAHKHDIQLTTESYNNYVPSYVKPDS--VATSDLGSLIDCNAASVNQTSMRNANGACIWNAAAYMKLSDSL 525

                          490       500       510
                   ....*....|....*....|....*....|....
gi 1983930777 2372 QKVLVKTFVEEGVNFSLTFNAVGSDEDLPYERFT 2405
Cdd:cd21716    526 KRQIRIACRKCNLNFRLTTSKLRANDNILSVKFS 559

alpha_betaCoV_Nsp1

cd21874

non-structural protein 1 from alpha- and betacoronavirus; This model represents the ...

3-104

1.81e-40

non-structural protein 1 from alpha- and betacoronavirus; This model represents the non-structural protein 1 (Nsp1) from 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), and Middle East respiratory syndrome-related (MERS) CoV. Gamma- and deltaCoVs do not have Nsp1. 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. Nsp1 is the N-terminal cleavage product released from the ORF1a polyprotein by the action of papain-like protease (PLpro). Though Nsp1s of alphaCoVs and betaCoVs share structural similarity, they show no significant sequence similarity and may be considered as genus-specific markers. Despite low sequence similarity, the Nsp1s of alphaCoVs and betaCoVs exhibit remarkably similar biological functions, and are involved in the regulation of both host and viral gene expression. CoV Nsp1 induces suppression of host gene expression and interferes with host immune response. It inhibits host gene expression in two ways: by targeting the translation and stability of cellular mRNAs, and by inhibiting mRNA translation and inducing an endonucleolytic RNA cleavage in the 5'-UTR of cellular mRNAs through its tight association with the 40S ribosomal subunit, a key component of the cellular translation machinery. Inhibition of host mRNA translation includes that of type I interferons, major components of the host innate immune response. Nsp1 is critical in regulating viral replication and gene expression, as shown by multiple evidences, including: mutations in the Nsp1 coding region of the transmissible gastroenteritis virus (TGEV) and murine hepatitis virus (MHV) genomes cause drastic reduction or elimination of infectious virus; bovine coronavirus (BCoV) Nsp1 is an RNA-binding protein that interacts with cis-acting replication elements in the 5'-UTR of the BCoV genome, implying its potential role in the regulation of viral translation or replication; and SARS-CoV Nsp1 enhances virus replication by binding to a stem-loop structure in the 5'-UTR of its genome.

Pssm-ID: 409336 Cd Length: 103 Bit Score: 146.20 E-value: 1.81e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777    3 SKQFKILVNE-DYQVNVPSLPFRDALQEIKYCYRNGFDGYVFVPEYRRDLVDCNRKDHYVIGVLGNGISDLKPVLLTEPS 81
Cdd:cd21874      1 SVQLSLPVLQvDVLVRGFGDSVEEALSEAREHLKNGFGTCGFVELEKGDLVDCPQLEQYVVFVKGSKVVELVAEMDGIRS 80

                           90       100
                   ....*....|....*....|...
gi 1983930777   82 VMLQGFIVRANCNGVLEDFDLKF 104
Cdd:cd21874     81 GITLGVLVPHNCNIALENVLLRK 103

CoV_peptidase

Coronavirus papain-like peptidase; This entry contains coronavirus cysteine endopeptidases ...

1499-1780

2.25e-40

Pssm-ID: 430171 Cd Length: 318 Bit Score: 153.98 E-value: 2.25e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1499 TIPIKVTEDTVNQKRVSVALDKTYGEQLkGTVVIKDKDVTNQLPSVSDVGEKVVKALDVDWNAYYGFPNAAAFSASSHDA 1578
Cdd:pfam08715    4 QITIYLTEDGVNYHSIVVKPGDSLGQQF-GQVYAKNKDLSGVFPADDVEDKEILYVPTTDWVEFYGFKSILEYYTLDASK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1579 Y-------EFDVVTHNNFIVHKQTDNNCWVNAICLALQRLKPTWKFPGVKSLWDAFLTRKTAGFVHMLYHISGLTKGQPG 1651
Cdd:pfam08715   83 YviylsalTKNVQYVDGFLILKWRDNNCWISSVIVALQAAKIRFKGQFLTEAWAKLLGGDPTDFVAWCYASCTAKVGDFG 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1652 DAELTLHKLVDLMSSDSAVTVTHTTACDKC-AKVETFTGpVVAAplLVCGT----------DEICVHGVHVNVKVTSIRG 1720
Cdd:pfam08715  163 DANWTLTNLAEHFDAEYTNAFLKKRVCCNCgIKSYELRG-LEAC--IQVRAtnldhfktgySNCCVCGANNTDEVIEASL 239

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1983930777 1721 TVAITSLIG--PVVGDVIDATGYICYTGLNSRGHYtYYDNRNGLMVDADKAYHFEKNLLQVT 1780
Cdd:pfam08715  240 PYLLLSATDgpAAVDCLEDGVGTVAFVGSTNSGHY-TYQTAKQAFYDGAKDRKFGKKSPYVT 300

TM_Y_SARS-CoV-like_Nsp3_C

cd21717

C-terminus of non-structural protein 3, including transmembrane and Y domains, from Severe ...

1921-2389

1.35e-39

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: 157.46 E-value: 1.35e-39

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1921 LVLLLIALYHFFYLFVSIPVVHK-----LACSGSVQAYSNSSFVK-SEVCGNSILCKACLASYDELADFDHL---QVSWD 1991
Cdd:cd21717      2 LLLLSICLGSLIYVTAALGVLLSnlgapSYCDGVRESYLNSSNVTtMDFCEGSFPCSVCLSGLDSLDSYPALetiQVTIS 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1992 -YKSDPLWNRVIQ---LSYFIFLAVFgnnYVRCLlmyfvSQYLNLWLSYFG--YVKYSWFL----HVVNFESISVEFVII 2061
Cdd:cd21717     82 sYKLDLTILGLAAewfLAYMLFTKFF---YLLGL-----SAIMQVFFGYFAshFISNSWLMwfiiSIVQMAPVSAMVRMY 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2062 VVVFKAVLALK---HIFLPCNNPSCKTCSKIARQTRIPIQVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTF 2138
Cdd:cd21717    154 IFFASFYYIWKsyvHIMDGCTSSTCMMCYKRNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCAGSTF 233

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2139 ICDEIVRDLSNSIKQTVYATDRSYQEVTKVECTDGFYRFYvgeeftaydYDVKHKKYSSQEVLKTMFLLDDFIVYNPSGS 2218
Cdd:cd21717    234 ISDEVARDLSLQFKRPINPTDQSSYVVDSVAVKNGALHLY---------FDKAGQKTYERHPLSHFVNLDNLRANNTKGS 304

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2219 --------------SLASVRNVCVYFSQLIGRPIKIVNSELLEDL--SVDFKGALFNAKKNVIKNSFNVDVSECKNL--- 2279
Cdd:cd21717    305 lpinvivfdgkskcDESAAKSASVYYSQLMCQPILLLDQALVSDVgdSTEVSVKMFDAYVDTFSATFSVPMEKLKALvat 384

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2280 --EECYKLCNLDVTFSTFEMAINN------------------AHRFGILITDRSFNNFWPSKIKpgSSGVSAMDIGKCMT 2339
Cdd:cd21717    385 ahSELAKGVALDGVLSTFVSAARQgvvdtdvdtkdvieclklSHHSDLEVTGDSCNNFMLTYNK--VENMTPRDLGACID 462

                          490       500       510       520       530
                   ....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2340 FDAKIVNAKVLTQRGKSVVWLSQDFSTLSSTAQKVLVKTFVEEGVNFSLT 2389
Cdd:cd21717    463 CNARHINAQVAKSHNVSLIWNVKDYMSLSEQLRKQIRSAAKKNNIPFRLT 512

betaCoV-Nsp6

cd21560

betacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell ...

3207-3499

7.06e-39

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: 148.54 E-value: 7.06e-39

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3207 GKVKSIFYPMMTAIAILFA----FWLEFFMYTPFTWINPTFVSVVLAITTLVSVLLVAGIKHKMLFFMSFVMPSVILATA 3282
Cdd:cd21560      1 SKVKRVVKGTLHWLLATFVlfylIILQLTKWTMFMYLTETMLLPLTPALCCVSACVMLLVKHKHTFLTLFLLPVLLTLAY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3283 HNVVWdmTYYESLQVLVENVNTTFLP-VDMQGVMLALFCVVVFVICTIRFFTCKQSWFSLfattIFVMFNIVKLLGMIGE 3361
Cdd:cd21560     81 YNYVY--VPKSSFLGYVYNWLNYVNPyVDYTYTDEVTYGSLLLVLMLVTMRLVNHDAFSR----VWAVCRVITWVYMWYT 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3362 PWTDDHFLLclvnMLTMLISLTTKDWFVVFASYKVAYYIVVYVMQ--PAFVQDFGFVKCVSIIYMACGYLFCCYYGILYW 3439
Cdd:cd21560    155 GSLEESALS----YLTFLFSVTTNYTGVVTVSLALAKFITALWLAynPLLFLDIPEVKCVLLVYLFIGYICTCYFGVFSL 230

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3440 VNRFTCMTCGVYQFTVSPAELKYMTANNLSAPKTAYDAMILSFKLMGIGGGRNIKISTVQ 3499
Cdd:cd21560    231 LNRLFRCPLGVYDYKVSTQEFRYMNANGLRPPRNSWEALMLNFKLLGIGGVPCIKVSTVQ 290

CoV_Nsp7

cd21811

coronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) ...

3500-3582

1.42e-38

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: 139.93 E-value: 1.42e-38

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3500 SKLTEMKCTNVVLLGLLSKMHVESNSKEWNYCVGLHNEINLCDDPDAVLEKLLALIAFFLSKHNTCDLSDLIESYFENTT 3579
Cdd:cd21811      1 SKLTDVKCTAVVLLSLLQKLRVESNSKLWKQCVQLHNDILLAKDTTEVFEKLVSLLSVLLSMQGAVDLNRLCEEMLENRA 80


                   ...
gi 1983930777 3580 ILQ 3582
Cdd:cd21811     81 VLQ 83

CoV_PLPro

cd21688

Coronavirus (CoV) papain-like protease (PLPro); This model represents the papain-like protease ...

1499-1768

3.09e-36

Pssm-ID: 409647 Cd Length: 299 Bit Score: 141.08 E-value: 3.09e-36

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1499 TIPIKVTEDTVNQKRVSVALDKTYGEQLkGTVVIKDKDVTNQLPSV--SDVGEKVVKALDVDWNAYYGFPNA-AAFSASS 1575
Cdd:cd21688      2 TKKVLVTVDGVNFRTIVVTTGDTYGQQL-GPVYLDGADVTKGKPDNheGETFFVLPSTPDKAALEYYGFLDPsFLGRYLS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1576 HDAYEFDVVTHNNFIVHKQTDNNCWVNAICLALQRLKPTWKFPGVKSLWDAFLTRKTAGFVHMLYHISGLTKGQPGDAEL 1655
Cdd:cd21688     81 TLAHKWKVKVVDGLRSLKWSDNNCYVSAVILALQQLKIKFKAPALQEAWNKFLGGDPARFVALIYASGNKTVGEPGDVRE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1656 TLHKLVDLMSSDSAvTVTHTTACDKC-AKVETFTGPVVAAPL-------LVCGTDEICVHGVHVNVKVTSIRGTVAITSL 1727
Cdd:cd21688    161 TLTHLLQHADLSSA-TRVLRVVCKHCgIKTTTLTGVEAVMYVgalsyddLKTGVSIPCPCGGEWTVQVIQQESPFLLLSA 239

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....
gi 1983930777 1728 IGPVVGDVIDAT--GYICYTGLNSRGHYTYYDNRN-GLMVDADK 1768
Cdd:cd21688    240 APPAEYKLQQDTfvAANVFTGNTNVGHYTHVTAKElLQKFDGAK 283

deltaCoV_Nsp10

cd21903

deltacoronavirus non-structural protein 10; This model represents the non-structural protein ...

3890-4017

3.57e-35

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: 131.91 E-value: 3.57e-35

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3890 GKPTEHPSNSGLLTLCAFAPDPAKAYVDAVKRGMQPVTNCVKMLSNgAGNGMAITNGVESNTQQDSYGGASVCIYCRCHV 3969
Cdd:cd21903      2 GTQIEYQENASLLTYLAFAVDPKEAYLKHLADGGKPIQGCIQMIAP-LGPGFAVTTKPQPNEHQYSYGGASICLYCRAHI 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1983930777 3970 EHPAIDGLCRFKGKFVQVPTgTQDPIRFCIENEVCVVCGCWLTNGCMC 4017
Cdd:cd21903     81 PHPGVDGRCPYKGRFVHIDK-DKEPVSFALTHEPCNSCQRWVNYDCTC 127

CoV_Nsp9

cd21881

coronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) ...

3778-3888

2.01e-33

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: 126.48 E-value: 2.01e-33

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3778 NNEILPGKLKEKAVKASATiDGDAYGSGKALMASEGGKSFIYAFIASDSNLKYVKWE-SNNDVIPIELEAPLRFYVDGVN 3856
Cdd:cd21881      1 NNELSPVALKQMSCAAGTD-QTCTDDEAKAYYNNSKGGRFVLAITSDKPDLKVARFLkEDGGTIYTELEPPCRFVTDVPK 79

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1983930777 3857 GPEVKYLYFVKSLNTLRRGAVLGYIGATVRLQ 3888
Cdd:cd21881     80 GPKVKYLYFIKNLNSLNRGMVLGSISATVRLQ 111

deltaCoV-Nsp6

cd21561

deltacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...

3187-3499

7.94e-33

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: 131.33 E-value: 7.94e-33

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3187 CDeFTPTEVIRQMyGVNLQSGKVKS----IFYPMMTAIAILFAFW--LEFFMYTpftwinptfvsVVLAITTLVSVLLVA 3260
Cdd:cd21561      3 CD-WTPEMVYNQA-PINLQSGVVKKtcmwFFHFLFMAVIFLLAALhvFPVHLYP-----------IVLPVFTILAFLLTL 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3261 GIKHKMLFFMSFVMPSVILATAH-NVVWDMTYYesLQVLVENVNTTFLPVDMQGVMLALFcVVVFVICTI-------RFF 3332
Cdd:cd21561     70 TIKHTVVFTTTYLLPSLLMMVVNaNTFWIPNTY--LRSIYEYVFGSFISERLYGYTVALY-ILVYAQLAInytlrtrRYR 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3333 TCKQSWFSLFATTIFVMFNIVKLLgmIGEPWTDDHfLLCLVNMLTMLISLTTkdwfvvfasykVAYYIVVYVMQPAFVQD 3412
Cdd:cd21561    147 ATSFISFCMQALQYGYVAHIVYRL--LTTPWTEGL-LFTAFSLLTSHPLLAA-----------LSWWLAGRIPLPLILPD 212

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3413 FGFVKCVsiiYMACGYLFCCYYGILYWVNRFTCMTCGVYQFTVSPAELKYMTANNLSAPKTAYDAMILSFKLMGIGGGRN 3492
Cdd:cd21561    213 LAIRVIV---YYVIGYVMCMRFGLFWLINKFTTIPMGTYKYMVSIEQLKYMMAVKMSPPRNAFEVLWANIRLLGLGGNRN 289


                   ....*..
gi 1983930777 3493 IKISTVQ 3499
Cdd:cd21561    290 IAVSTVQ 296

TM_Y_HKU9-like_Nsp3_C

cd21715

C-terminus of non-structural protein 3, including transmembrane and Y domains, from Rousettus ...

2021-2396

2.08e-29

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: 126.51 E-value: 2.08e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2021 LLMYFVSQYLNLWLSYFGYvkysWFLHVVNFESISVEFVIIVVVFKAVLALKHIFLPCNNPSCKTCSKIARQTRIPIQVV 2100
Cdd:cd21715    112 LVLYLPIPLGNSWLVVFLY----YIIRLVPFTSMLRMYIVIAFLWLCYKGFVHVRYGCNNVACLMCYKKNVAKRIECSTV 187

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2101 VNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRDLSNSIKQTVYATDRSYQEVTKVECTDGFYRFYVG 2180
Cdd:cd21715    188 VNGVKRMFYVNANGGTYFCTKHNWNCVSCDTYTVDSTFISRQVALDLSAQFKRPINHTDEAYYEVTSVEVRNGYVYCYFD 267

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2181 -------EEFTAYDYDVKHKKYSSQevLKTMFLLDDFIVYNPSGS-SLASVRNVCVYFSQLIGRPIKIVNSELLEDLSVD 2252
Cdd:cd21715    268 sdgqrsyERFPMDAFTNVSKLHYSE--LKGAAPAFNVLVFDATNRiEENAVKTAAIYYAQLACKPILLVDKRMVGVVGDD 345

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2253 --FKGALFN--AKKNVIKNSFNVDV------------------------------SECKNLEEcyklcnlDVTFSTFEMA 2298
Cdd:cd21715    346 atIAKAMFEayAQNYLLKYSIAMDKvkhlystalqqiasgmtvesvlkvfvgstrAEAKDLES-------DVDTNDLVSC 418

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2299 INNAHRFGILITDRSFNNFWPSKIKPGSsgVSAMDIGKCMTFDAKIVNAKVLTQRGKSVVWLSQDFSTLSSTAQKVLVKT 2378
Cdd:cd21715    419 IRLCHQEGWDWTTDSWNNLVPTYIKQDT--LSTLEVGQFMTANARYVNANVAKGAAVNLVWRYADFIKLSESMRRQLRVA 496

                          410
                   ....*....|....*...
gi 1983930777 2379 FVEEGVNFSLTFNAVGSD 2396
Cdd:cd21715    497 ARKTGLNLLVTTSSLKAD 514

TM_Y_gammaCoV_Nsp3_C

cd21710

C-terminus of gammacoronavirus non-structural protein 3, including transmembrane and Y domains; ...

1948-2389

2.59e-28

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: 122.94 E-value: 2.59e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1948 GSVQAYSNSSFVKSEVCGNSILCKACLASYDELADFDH-LQVSWDYKSDPL-----WNRViqlsYFIFLAVFGNNYVRCL 2021
Cdd:cd21710     46 GPYNDYGKDSFDVLRYCGDDFTCRVCLHDKDSLHLYKHaYSVEQFYKDAVSgisfnWNWL----YLVFLILFVKPVAGFV 121

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2022 LMYFVSQYLNLWLSYF--GYVKYSWFLHVV----NFESISVEFVIIVvvfKAVLALKHIfLPCNNPSCKTCSKIARQTRI 2095
Cdd:cd21710    122 IICYCVKYLVLSSTVLqtGVGFLDWFIQTVfthfNFMGAGFYFWLFY---KIYIQVHHI-LYCKDITCEVCKRVARSNRH 197

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2096 PIQVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRDLSNSIKQTVYATDRSYQEVTKVECTDGFy 2175
Cdd:cd21710    198 EVSVVVGGRKQLVHVYTNSGYNFCKRHNWYCRNCDKYGHQNTFMSPEVAGELSEKLKRHVKPTAHAYHVVDDACLVDDF- 276

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2176 rfyVGEEFTAY-----DYDVKHKKYSSQEVLKTMFLL-----------DDFIVYNP-SGSSLASVRNVCVYFSQLIGRPI 2238
Cdd:cd21710    277 ---VNLKYKAAtpgkdGAHSAVKCFSVSDFLKKAVFLkdalkceqisnDSFIVCNTqSAHALEEAKNAAIYYAQYLCKPI 353

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2239 KIVNSELLEDLSVD-FKGALFNAKKNVIKNSFNVDVSECKNLEECYKLCNLDVTF--STFEMAInNAHRFGILITDRSFN 2315
Cdd:cd21710    354 LILDQALYEQLVVEpVSKSVVDKVCSILSNIISVDTAALNYKAGTLRDALLSVTKdeEAVDMAI-FCHNNDVEYTSDGFT 432

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2316 NFWPS------KIKPgssgvsaMDIGKCMTFDAKIVNAKVltQRGKSVVWLSQDFSTLSSTAQKVLVKTFVEEGVNFSLT 2389
Cdd:cd21710    433 NVVPSygidtdKLTP-------RDRGFLINADASIANLRV--KNAPPVVWKFSDLIKLSDSCLKYLISATVKSGGRFFIT 503

betaCoV_Nsp9

cd21898

betacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ...

3778-3888

2.81e-27

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: 108.64 E-value: 2.81e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3778 NNEILPGKLKEKAVKA-----SATIDGDAYGSgkalmASEGGKsFIYAFIASDSNLKYVKWE-SNNDVIPIELEAPLRFY 3851
Cdd:cd21898      1 NNELMPQGLKTMVVTAgpdqtACNTPALAYYN-----NVQGGR-MVMAILSDVDGLKYAKVEkSDGGFVVLELDPPCKFL 74

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1983930777 3852 VDGVNGPEVKYLYFVKSLNTLRRGAVLGYIGATVRLQ 3888
Cdd:cd21898     75 VQTPKGPKVKYLYFVKGLNNLHRGQVLGTIAATVRLQ 111

TM_Y_MHV-like_Nsp3_C

cd21714

C-terminus of non-structural protein 3, including transmembrane and Y domains, from murine ...

1959-2391

5.46e-27

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: 119.48 E-value: 5.46e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1959 VKSEVCGNSILCKACLASYDELADFDHLQV---------SWDYKSdpLWNRVIQL--SYFIFLAVFgnnY-VRCLLmyfV 2026
Cdd:cd21714     67 FKSQFCNGSMACQLCLSGFDMLDNYKAIDVvqyevdrrvFFDYTS--VLKLVVELvvSYALYTVWF---YpLFCLI---G 138

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2027 SQYLNLWL-SYFGYVKYSWFLHVVNFES-------ISVEFVIIVVVFKAVLALKHIFLPCNNPSCKTCSKIARQTRIPIQ 2098
Cdd:cd21714    139 LQLLTTWLpEFFMLETLHWSVRLFVFLAnmlpahvFLRFYIVVTAMYKIFCLFRHVVYGCSKPGCLFCYKRNRSVRVKCS 218

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2099 VVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVRDLSNSIKQTVYATDRSYQEVTKVECTDGFYR-F 2177
Cdd:cd21714    219 TIVGGMLRYYDVMANGGTGFCSKHQWNCINCDSYKPGNTFITVEAAAELSKELKRPVNPTDVAYYTVTDVKQVGCSMRlF 298

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2178 YVGEEFTAYDyDVKHKKYSSQEVL---KTMFLLDDFIVYNPSGSSLASVRNVCVYFSQLIGRPIKIVNSELLE------- 2247
Cdd:cd21714    299 YERDGQRVYD-DVNASLFVDMNGLlhsKVKGVPNTHVVVVENDADKANFLNAAVFYAQSLFRPMLMVDKKLITtantgts 377

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2248 ------DLSVDFKGALFNAKKNVIKNSFNV---DVSECKNLEECY--------KLCNLDVTFSTFEMA--INNAHRFGIL 2308
Cdd:cd21714    378 vsqtmfDVYVDTFLSMFDVDRKSLNSFINTahsSLKEGVQLEKVLdtfigcarKSCSIDSDVDTKCIAksVMSAVAAGLE 457

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2309 ITDRSFNNFWPSKIKpgSSGVSAMDIGKCMTFDAKIVNAKVLTQRGKSVVWLSQDFSTLSSTAQKVLVKTFVEEGVNFSL 2388
Cdd:cd21714    458 FTDESCNNLVPTYIK--SDNIVAADLGVLIQNSAKHVQGNVAKAANVACIWSVDAFNQLSSDFQHKLKKACVKTGLKLKL 535


                   ...
gi 1983930777 2389 TFN 2391
Cdd:cd21714    536 TYN 538

deltaCoV_Nsp8

cd21833

deltacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ...

3583-3749

2.75e-25

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: 105.86 E-value: 2.75e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3583 SVASAYAALPSWIAYEKARADLEEAKKNDVSPQLLKQLTKACNIAKSEFEREASVQKKLDKMAEQAAASMYKEARAVDRK 3662
Cdd:cd21833      1 AVVDANINLDSYRIYKEADAAYKKSVELNEPPQEQKKKLKAVNIAKAEWEREAASQRKLEKLADAAMKSMYLAERAEDRR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3663 SKIVSAMHSLLFGMLKKLDMSSVNTIIEQARNGVLPLSIIPAASATRLIVVTPNLEVLSKVRQENNVHYAGAIWSIVEVK 3742
Cdd:cd21833     81 IKLTSGLTAMLYHMLRRLDSDRVKALFECAKQQILPIHAIVGVSNDNLKVIFNDKESYLQYVDGNTLIYKGVRYTIVKKL 160


                   ....*..
gi 1983930777 3743 DANGAQV 3749
Cdd:cd21833    161 SLDNAPI 167

CoV_NSP2_C

Coronavirus replicase NSP2, C-terminal; This entry corresponds to a presumed domain found at ...

731-879

1.93e-24

Pssm-ID: 465996 Cd Length: 156 Bit Score: 102.34 E-value: 1.93e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  731 LGNVKIMLGNGVKV--VCDGCHSFANRLTINYNKLCDTARKDIEIGGIPFSTfktpSSSFIDMKDAIYSVV--------E 800
Cdd:pfam19212    1 LKNAKFTVVNGGIVfvVPKKFKSLVGTLLDLLNKLFDSLVDTVKIAGVKFKA----GGTYYLFSNALVKVVsvklkgkkQ 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  801 YG-----EALSFKTASVPVTNSGIITTDdwsdpILLEPADYVEP-KDNGDVIVIAGYTFYKDEDDHFYPYGSGMVVQKMY 874
Cdd:pfam19212   77 AGlkgakEATVFVGATVPVTPTRVEVVT-----VELEEVDYVPPpVVVGYVVVIDGYAFYKSGDEYYPASTDGVVVPPVF 151


                   ....*
gi 1983930777  875 NKMGG 879
Cdd:pfam19212  152 KLKGG 156

betaCoV_Nsp7

cd21827

betacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...

3500-3582

1.85e-22

betacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of betacoronaviruses including the 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. 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; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.

Pssm-ID: 409253 Cd Length: 83 Bit Score: 94.05 E-value: 1.85e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3500 SKLTEMKCTNVVLLGLLSKMHVESNSKEWNYCVGLHNEINLCDDPDAVLEKLLALIAFFLSKHNTCDLSDLIESYFENTT 3579
Cdd:cd21827      1 SKLTDVKCTSVVLLSVLQQLHVESNSKLWAYCVKLHNDILAAKDPTEAFEKFVSLLSVLLSFPGAVDLDALCSELLDNPT 80


                   ...
gi 1983930777 3580 ILQ 3582
Cdd:cd21827     81 VLQ 83

alpha_betaCoV_Nsp2

cd21511

alpha- and betacoronavirus non-structural protein 2; Coronavirus Nsps are encoded in ORF1a and ...

113-463

2.02e-22

alpha- and betacoronavirus non-structural protein 2; Coronavirus 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 subunits. This alpha- and betacoronavirus family includes alphacoronavirus human coronavirus 229E (HCoV-229E) Nsp2, betacoronavirus Severe acute respiratory syndrome coronavirus (SARS-CoV) Nsp2, SARS-CoV-2 Nsp2, and Murine hepatitis virus (MHV) Nsp2 (also known as p65). The function of Nsp2 remains unclear. 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. This family may be distantly related to the gammacoronavirus Avian infectious bronchitis virus (IBV) Nsp2; IBV Nsp2 is a weak protein kinase R (PKR) antagonist, which may suggest that it plays a role in interfering with intracellular immunity.

Pssm-ID: 439197 Cd Length: 399 Bit Score: 103.01 E-value: 2.02e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  113 YVDQYMCGADGKPV---------------IEGEFKDYFGDE-DVIIYEGEEYHCAWLTVRDEKPLCQQTLLTIREI---Q 173
Cdd:cd21511      4 YVDQYGCGPDGKPVecikdlldvakkgscTLSEQLDGIELKnGVYDLRDHEVVIAWYVERKDVPYEKQTIFTIKSAkfgT 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  174 YNLDIP-HKLPNCAI-REVAPPVKKNSKVVLSEEYRKLYDIFGspfmgngdslnTCFDSLHFIAATLKC-PCGAESSGVG 250
Cdd:cd21511     84 FVGEVPaHVFPLNSIvKEIQPRVKKKKKVTLSGVIRSFYSKAS-----------PNECNPITLSALVKCtHCDEKSWQTG 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  251 DWT-GFKTACCGLHGKVK-GVTLGAVKPGDAIVTSMSA-----------GKGVKFFANSVLQYAGDVENVSVWkviktft 317
Cdd:cd21511    153 DFVdGFTCECGAEYLNWKlDAQSSGVLPPGAVVKTQCPacvnretflrgGGRIVYFGGAVYSYVGCINGVAYW------- 225

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  318 vnetvcttdfegelsdfiRPESTSPVSCsikraFITGEVDDAVHdciiagkldlstnlfGSANLLFKkmpwfVQKCGAIF 397
Cdd:cd21511    226 ------------------VPRASSSVGC-----FHTGVVGKIVP---------------GAWGLGAS-----AQKLTPLT 262

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1983930777  398 ADAWKVVEELLC-SLKLTYKQIYDVVASLCTSAFTIMDYKPVFVVSSNSVKDLVDKCVKILVKAFDV 463
Cdd:cd21511    263 TGAAVVFVLIFArTLFAAVGSVPQLQASAPTILDGIVNASDRLVDAMQFSADLVVATTTSAGAAGYV 329

A1pp

smart00506

Appr-1"-p processing enzyme; Function determined by Martzen et al. Extended family detected by ...

1341-1470

9.02e-22

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: 93.91 E-value: 9.02e-22

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777  1341 KVSFYQGDLDVLinflEPDVLVNAANGDLRHVGGVARAIDVFTGGKLTKrsKEYLKS-SKAIAPGNAVLFEN-VLEHLSV 1418
Cdd:smart00506    1 ILKVVKGDITKP----RADAIVNAANSDGAHGGGVAGAIARAAGKALSK--EEVRKLaGGECPVGTAVVTEGgNLPAKYV 74

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 1983930777  1419 LNAVGPRNGDSRVEG--KLCNVYK-----AIAKCDGKILTPLISVGIFKVKLEVSLQCL 1470
Cdd:smart00506   75 IHAVGPRASGHSKEGfeLLENAYRnclelAIELGITSVALPLIGTGIYGVPKDRSAQAL 133

TM_Y_deltaCoV_Nsp3_C

cd21711

C-terminus of deltacoronavirus non-structural protein 3, including transmembrane and Y domains; ...

1913-2175

2.48e-21

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: 100.93 E-value: 2.48e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1913 PALWRYiKLVLLLIALYhffYLFVSIPVVHKLACSG-SVQAYSNSSFvksevCGNSILCKACLASYDELADFDHLQVSwd 1991
Cdd:cd21711     14 PFLMLP-AVASLLSSGY---TIGTYLYAKTGLPCYYnATQHYDYNSF-----CAGDLTCQACFDGQDSLHLYKHLRVN-- 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1992 ykSDPLWNRVIQLSYFIFLAVFGNNYVRC--LLMYFVSQYLNLWLSYFGYVKYSWFLHVVNFESISVEFviivvvfKAVL 2069
Cdd:cd21711     83 --QQPVQTTDYTVYALSIVLLLANPTLVLgtLLVVFFVNFYGVQIPFYGTLQLDYQNTLVMVFSVYYFY-------KVMK 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 2070 ALKHIFLPCNNPSCKTCSKIARQTRIPIQVVVNGSMKTVYVHANGTGKLCKKHNFYCKNCDSYGFDHTFICDEIVrDLSN 2149
Cdd:cd21711    154 FFRHLAKGCKKPTCSICAKKRIPPTITVETVVQGRKYPSVIETNGGFNICKEHNFYCKNCDSQTPGTFIPTEAVE-SLSR 232

                          250       260
                   ....*....|....*....|....*.
gi 1983930777 2150 SIKQTVYATDRSYQEVTKVECTDGFY 2175
Cdd:cd21711    233 KTRLSVKPTAPAYLLARDVECQTDVV 258

alphaCoV_PLPro

alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...

1097-1282

1.63e-20

Pssm-ID: 409648 Cd Length: 289 Bit Score: 95.00 E-value: 1.63e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1097 TPFKTTN--LNGKIILKQQDNNCWINACCYQLQAFDF-FN----HDLWDGFKKDDVMPFVDFCYAALTLKQGDSGDAEYL 1169
Cdd:cd21731     78 SAYAFESdiVNGKRVLKQSDNNCWVNAVCLQLQFAKPtFKseglQALWNKFLTGDVAGFVHWLYWITGANKGDPGDAENT 157

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1170 LeTMLNDY--STAKVTLS--AKCGCGVKEIVLERTVFKLTPLRNEFKYGVCGDCKQINmCKFASVEGSGVFVHdrIEKQT 1245
Cdd:cd21731    158 L-NKLSKYlvSSGSVTVErtTGCDSCNSKRTVTTPVVNASVLRSGVDDGVCKHGVKVT-TRVVSVKGTVIITS--VGKPV 233

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1983930777 1246 PVSQFI-VTPTMHAVYTGTTQSGHYMIEDCIHDYCVDG 1282
Cdd:cd21731    234 VSDALLlLDGVSYTAFSGDVDNGHYTVYDKATGKVYDG 271

betaCoV_PLPro

cd21732

betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...

1499-1759

2.60e-20

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: 94.96 E-value: 2.60e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1499 TIPIKVTEDTVNQKRVSVALDKTYGEQLkGTVVIKDKDVTNQLPSVSDVGeKVVKALDVDWNA-------YYGFPN---- 1567
Cdd:cd21732      2 TIEVLTTVDGVNFRTVLVNNGETFGKQL-GNVFCDGVDVTKTKPSAKYEG-KVLFQADNLSAEeleaveyYYGFDDptfl 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1568 AAAFSASSHDAYEfDVVTHNNFIVHKQTDNNCWVNAICLALQRLKPTWKFPGVKSLWDAFLTRKTAGFVHMLYHISGLTK 1647
Cdd:cd21732     80 LRYYSALAHVKKW-KFVVVDGYFSLKQADNNCYLNAACLMLQQLDLKFNTPALQEAYYEFRAGDPLRFVALVLAYGNFTF 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1648 GQPGDAELTLHKLVDLMSSDSAVTVThTTACDKC-AKVETFTGpvVAAPL---------LVCGTDEICVHGVHVNVKVTS 1717
Cdd:cd21732    159 GEPDDARDFLRVVLSHADLVSARRVL-EEVCKVCgVKQEQRTG--VDAVMyfgtlslddLYKGYTIDCSCGRKAIRYLVE 235

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*
gi 1983930777 1718 IRGTVAITSliGPVVGDVIDATGYIC---YTGLNSRGHYTYYDNR 1759
Cdd:cd21732    236 QVPPFLLMS--NTPTEVPLPTGDFVAanvFTGDESVGHYTHVKNK 278

gammaCoV-Nsp6

cd21559

gammacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...

3195-3499

1.92e-19

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: 92.14 E-value: 1.92e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3195 VIRQMYGVNLQSGKVK------------SIFYPMMTAIAILFAFWLEFFMYtpftwinptfvsvvLAITTLVSVLLVA-G 3261
Cdd:cd21559      3 VFNQVGGVRLQSSFVKkatswfwsrcvlACFLFVLCAIVLFTAVPLKYYVH--------------AAVILLVAVLFISfT 68

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3262 IKHKMLFFMSFVMP---SVILATAHNV--VWDMTYYESLQVLVE----NVNTTFLPVdmqgvMLALFCVVVFvictirfF 3332
Cdd:cd21559     69 VKHVMAFMDTFLLPtlcTVIIGVCAEVpfIYNTLISQVVIFFSQwydpVVFDTVVPW-----MFLPLVLYTA-------F 136

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3333 TCKQSWFSL--FATTIFVMFNIVKL------LGMIGEPWTDDHFLLCLVNMLTMLISLTTKDWFVVFASYKVAYYiVVYV 3404
Cdd:cd21559    137 KCVQGCYSInsFSTSLLVLYQFMKLgfviytSSNTLTAYTEGNWELFFELVHTTVLANFSSNSLIGLIVFKIAKW-MLYY 215

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3405 MQPAFVQDFgfvkcVSIIYMAC--GYLFCCYYGILYWVNRFTCMTCGVYQFTVSPAELKYMTANNLSAPKTAYDAMILSF 3482
Cdd:cd21559    216 CNATYFNSY-----VLMAVMVNviGWLFTCYFGLYWWLNKVFGLTLGKYNYKVSVEQYKYMCLHKIRPPKSVWDVFSTNM 290

                          330
                   ....*....|....*..
gi 1983930777 3483 KLMGIGGGRNIKISTVQ 3499
Cdd:cd21559    291 LIQGIGGERVLPIATVQ 307

Macro_Af1521_BAL-like

cd02907

macrodomain, Af1521-like family; Macrodomains are found in a variety of proteins with diverse ...

1341-1476

3.44e-18

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: 84.46 E-value: 3.44e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1341 KVSFYQGDL---DVlinflepDVLVNAANGDLRHVGGVARAIDVFTGGKLTKRSKEYLKSSKAIAPGNAVlfenvleHLS 1417
Cdd:cd02907      3 KVSVYKGDItkeKV-------DAIVNAANERLKHGGGVAGAISKAGGPEIQEECDKYIKKNGKLRVGEVV-------VTS 68

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1983930777 1418 --------VLNAVGPR---NGDSRVEGKLCN-VYKAIAKCDGKILT----PLISVGIFKVKLEVSLQCLLKTVTD 1476
Cdd:cd02907     69 agklpckyVIHAVGPRwsgGSKEECEDLLYKaVLNSLEEAEELKATsiaiPAISSGIFGFPLDLCAEAIVEAIKD 143

gammaCoV_Nsp7

cd21828

gammacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ...

3500-3582

3.62e-16

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: 75.98 E-value: 3.62e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 3500 SKLTEMKCTNVVLLGLLSKMHVESNSKEWNYCVGLHNEINLCDDPDAVLEKLLALIAFFLSKHNTCDLSDLIESYFENTT 3579
Cdd:cd21828      1 SKLTDVKCTTVVLMQLLTKLNVEANSKMHKYLVELHNKILASDDVVECMDNLLGMLVTLLCIDSTIDLSEYCDDILKRST 80


                   ...
gi 1983930777 3580 ILQ 3582
Cdd:cd21828     81 VLQ 83

gammaCoV_PLPro

cd21733

gammacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ...

1105-1219

1.40e-15

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: 80.55 E-value: 1.40e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1983930777 1105 NGKIILKQQDNNCWINACCYQLQA----FDFFNHDLWDGFKKDDVMPFVDFCYAALTLKQGDSGDAEYLL----ETMLND 1176
Cdd:cd21733     89 DNFLILEWRDGNCWISSAIVLLQAakirFKGFLAEAWAKFLGGDPTEFVAWCYASCNAKVGDFSDANWLLanlaEYFDAD 168

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1983930777 1177 YSTAKVTLSAKCGCGVKEIVLERTVFKLTPLRN----EFK--YGVCGDC 1219
Cdd:cd21733    169 YTNAFLKRRVSCNCGVKNYELRGLEACIQPVRApnllHFKtqYSNCPTC 217

CoV_peptidase