ORF1ab polyprotein [Severe acute respiratory syndrome coronavirus 2]
Protein Classification
List of domain hits
| Name | Accession | Description | Interval | E-value | |||||||||||||
| SARS-CoV-like_RdRp | cd21591 | Severe acute respiratory syndrome coronavirus RNA-dependent RNA polymerase, also known as ... |
4394-5321 | 0e+00 | |||||||||||||
Severe acute respiratory syndrome coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the B lineage: responsible for replication and transcription of the viral RNA genome; This group contains the RNA-dependent RNA polymerase (RdRp) of Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 (also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus), and similar proteins from betacoronaviruses in the sarbecovirus subgenera (B lineage). 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. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which shows potential for the treatment of SARS-CoV-2 viral infections. The structure of SARS-CoV-2 Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. Recent studies have shown that the SARS-CoV-2 RdRp requires two iron-sulfur clusters to function optimally. Earlier studies had mistakenly identified these iron-sulfur cluster binding sites for zinc-binding sites, likely because iron-sulfur clusters degrade easily under standard experimental conditions.The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. : Pssm-ID: 394895 Cd Length: 928 Bit Score: 1951.81 E-value: 0e+00
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| betaCoV_Nsp2_SARS-like | cd21516 | betacoronavirus non-structural protein 2 (Nsp2) similar to SARS-CoV Nsp2, and related proteins ... |
182-818 | 0e+00 | |||||||||||||
betacoronavirus non-structural protein 2 (Nsp2) similar to SARS-CoV Nsp2, and related proteins from betacoronaviruses in the B lineage; Non-structural proteins (Nsps) from Severe acute respiratory syndrome coronavirus (SARS-CoV) and betacoronaviruses in the sarbecovirus subgenus (B lineage) are encoded in ORF1a and ORF1b. Post infection, the SARS-CoV genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (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. The function of Nsp2 remains unknown. Deletion of Nsp2 from the SARS-CoV genome results in only a modest reduction in viral titers. Rather than playing a role in viral replication, SARS-CoV Nsp2 may be involved in altering the host cell environment; 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. : Pssm-ID: 439199 Cd Length: 637 Bit Score: 1155.68 E-value: 0e+00
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| TM_Y_SARS-CoV-like_Nsp3_C | cd21717 | C-terminus of non-structural protein 3, including transmembrane and Y domains, from Severe ... |
2232-2762 | 0e+00 | |||||||||||||
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: 1153.97 E-value: 0e+00
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| CoV_Nsp14 super family | cl40464 | nonstructural protein 14 of coronavirus; Nonstructural protein 14 (Nsp14) of coronavirus (CoV) ... |
5927-6337 | 0e+00 | |||||||||||||
nonstructural protein 14 of coronavirus; Nonstructural protein 14 (Nsp14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The association of Nsp14 with Nsp10 stimulates its ExoN activity; the 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. The Nsp10/Nsp14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. Nsp14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or Nsp14 has been found to interfere with protein translation of cellular mRNAs. The actual alignment was detected with superfamily member cd21659: Pssm-ID: 424095 Cd Length: 519 Bit Score: 822.05 E-value: 0e+00
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| betaCoV_Nsp13-helicase | cd21722 | helicase domain of betacoronavirus non-structural protein 13; This model represents the ... |
5572-5911 | 0e+00 | |||||||||||||
helicase domain of betacoronavirus non-structural protein 13; This model represents the helicase domain of non-structural protein 13 (Nsp13) from betacoronavirus, including pathogenic human viruses such as Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. CoV Nsp13 is a member of the helicase superfamily 1 (SF1); SF1 and SF2 helicases do not form toroidal structures, while SF3-6 helicases do. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It is a multidomain protein containing a Cys/His rich zinc-binding domain (CH/ZBD), a stalk domain, a 1B domain involved in nucleic acid substrate binding, and a SF1 helicase core. : Pssm-ID: 409655 [Multi-domain] Cd Length: 340 Bit Score: 702.71 E-value: 0e+00
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| betaCoV_Nsp5_Mpro | cd21666 | betacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ... |
3267-3563 | 0e+00 | |||||||||||||
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: 579.74 E-value: 0e+00
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| cv_Nsp4_TM | cd21473 | coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in ... |
2777-3157 | 9.49e-151 | |||||||||||||
coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in coronavirus-induced membrane remodeling. In order to assemble the replication-transcription complex (RTC), coronavirus induces the rearrangement of host endoplasmic reticulum (ER) membrane into double membrane vesicles (DMVs), zippered ER, or ER spherules. DMV formation has been observed in SARS-CoV cells overexpressing the three transmembrane-containing non-structural proteins of viral replicase polyprotein 1ab: Nsp3, Nsp4 and Nsp6. Together, Nsp3, Nsp4, and Nsp6 have the ability to induce the formation of DMVs that are similar to those seen in SARS-CoV-infected cells. : Pssm-ID: 394836 Cd Length: 376 Bit Score: 474.77 E-value: 9.49e-151
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| betaCoV_PLPro | cd21732 | betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ... |
1566-1868 | 2.08e-149 | |||||||||||||
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: 467.45 E-value: 2.08e-149
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| betaCoV-Nsp6 | cd21560 | betacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell ... |
3570-3856 | 1.26e-137 | |||||||||||||
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: 433.21 E-value: 1.26e-137
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| CoV_Methyltr_2 super family | cl20156 | Coronavirus 2'-O-methyltransferase; This domain covers the NSP16 region of the coronavirus ... |
6797-7092 | 5.21e-119 | |||||||||||||
Coronavirus 2'-O-methyltransferase; This domain covers the NSP16 region of the coronavirus polyprotein. The SARS-CoV RNA cap SAM-dependent (nucleoside-2'-O-)-methyltransferase (2'-O-MTase) is a heterodimer comprising SARS-CoV nsp10 and nsp16. When bound to nsp10, nsp16 is active as a type-0 RNA cap-dependent 2'-O-MTase, ie., active only when the cap guanine is methylated at its N7 position. Nsp10 binds to nsp16 through an activation surface area in nsp10, and the resulting complex exhibits RNA cap (nucleoside-2'-O)-methyltransferase activity. Nsp10 is a double zinc finger protein together with nsp4, nsp5, nsp12, nsp14, and nsp16, nsp10 has been found to be essential in the assembly of a functional replication/transcription complex. Nsp16 adopts a typical fold of the S-adenosylmethionine-dependent methyltransferase (SAM) family as defined initially for the catechol O-MTase but it lacks several elements of the canonical MTase fold, such as helices B and C. The nsp16 topology matches those of dengue virus NS5 N-terminal domain and of vaccinia virus VP39 MTases. The actual alignment was detected with superfamily member pfam06460: Pssm-ID: 461919 Cd Length: 296 Bit Score: 379.90 E-value: 5.21e-119
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| CoV_NSP8 | pfam08717 | Coronavirus replicase NSP8; Viral NSP8 (non structural protein 8) forms a hexadecameric ... |
3940-4136 | 4.24e-111 | |||||||||||||
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: 353.00 E-value: 4.24e-111
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| alpha_betaCoV_Nsp10 | cd21901 | alphacoronavirus and betacoronavirus non-structural protein 10; This model represents the ... |
4251-4381 | 8.40e-81 | |||||||||||||
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: 263.37 E-value: 8.40e-81
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| SARS-CoV-like_Nsp1_N | cd21796 | N-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related ... |
13-127 | 1.29e-77 | |||||||||||||
N-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the N-terminal domain of non-structural protein 1 (Nsp1) from betacoronaviruses in the sarbecovirus subgenus (B lineage), including highly pathogenic coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). 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: 439285 Cd Length: 115 Bit Score: 253.66 E-value: 1.29e-77
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| SARS-CoV-like_Nsp3_NAB | cd21822 | nucleic acid binding domain of non-structural protein 3 from Severe acute respiratory ... |
1913-2019 | 1.03e-69 | |||||||||||||
nucleic acid binding domain of non-structural protein 3 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the nucleic acid binding (NAB) domain of non-structural protein 3 (Nsp3) from betacoronavirus in the sarbecovirus subgenus (B lineage) and hibecovirus subgenus, including highly pathogenic human coronaviruses (CoVs) such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). The NAB domain represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. NAB is a cytoplasmic domain located between the papain-like protease (PLPro) and betacoronavirus-specific marker (betaSM) domains of CoV Nsp3. 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. The NAB domain both binds ssRNA and unwinds dsDNA. It prefers to bind ssRNA containing repeats of three consecutive guanines. A group of residues that form a positively charged patch on the protein surface of SARS-CoV Nsp3 NAB serves as the binding site of nucleic acids. This site is conserved in the NAB of Nsp3 from betacoronavirus in the B lineage. : Pssm-ID: 409348 Cd Length: 107 Bit Score: 230.50 E-value: 1.03e-69
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| SARS-CoV-like_Nsp3_betaSM | cd21814 | betacoronavirus-specific marker of non-structural protein 3 from Severe acute respiratory ... |
2044-2159 | 4.77e-69 | |||||||||||||
betacoronavirus-specific marker of non-structural protein 3 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the betacoronavirus-specific marker (betaSM), also called group 2-specific marker (G2M), 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). The betaSM/G2M is located C-terminal to the nucleic acid-binding (NAB) domain. This region is absent in alpha- and deltacoronavirus Nsp3; there is a gammacoronavirus-specific marker (gammaSM) at this position in gammacoronavirus Nsp3. 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. Little is known about the betaSM/G2M domain; it is predicted to be non-enzymatic and may be an intrinsically disordered region. The betaSM/G2M domain is part of the predicted PLnc domain (made up of 385 amino acids) of SARS-CoV Nsp3 that may function as a replication/transcription scaffold, with interactions to Nsp5, Nsp12, Nsp13, Nsp14, and Nsp16. : Pssm-ID: 409629 Cd Length: 116 Bit Score: 228.99 E-value: 4.77e-69
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| bCoV_SUD_M super family | cl13138 | Betacoronavirus single-stranded poly(A) binding domain; This domain identifies non-structural ... |
1368-1493 | 6.90e-67 | |||||||||||||
Betacoronavirus single-stranded poly(A) binding domain; This domain identifies non-structural protein NSP3, the product of ORF1a in group 2 coronavirus. It is found in human SARS coronavirus polyprotein 1a and 1ab, and in related coronavirus polyproteins. NSP3 binds to viral RNA, nucleocapsid protein, as well as other viral proteins, and participates in polyprotein processing. The domain exhibits a macrodomain fold containing the nsp3 residues 528 to 648, with a flexibly extended N-terminal tail from residues 513 to 527 and a C-terminal flexible tail of residues 649 to 651. SUD-M(527-651) binds single-stranded poly(A); the contact area with this RNA on the protein surface, and the electrophoretic mobility shift assays confirm that SUD-M has higher affinity for purine bases than for pyrimidine bases. The actual alignment was detected with superfamily member pfam11633: Pssm-ID: 431970 Cd Length: 126 Bit Score: 223.47 E-value: 6.90e-67
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| Macro_SF super family | cl00019 | macrodomain superfamily; Macrodomains are found in a variety of proteins with diverse cellular ... |
1233-1358 | 1.55e-65 | |||||||||||||
macrodomain superfamily; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. Macrodomains include the yeast macrodomain Poa1 which is a phosphatase of ADP-ribose-1"-phosphate, a by-product of tRNA splicing. Some macrodomains have ADPr-unrelated binding partners such as the coronavirus SUD-N (N-terminal subdomain) and SUD-M (middle subdomain) of the SARS-unique domain (SUD) which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). Macrodomains regulate a wide variety of cellular and organismal processes, including DNA damage repair, signal transduction, and immune response. The actual alignment was detected with superfamily member cd21562: Pssm-ID: 469581 Cd Length: 126 Bit Score: 219.32 E-value: 1.55e-65
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| ZBD_cv_Nsp13-like | cd21401 | Cys/His rich zinc-binding domain (CH/ZBD) of coronavirus SARS NSP13 helicase and related ... |
5322-5416 | 9.61e-61 | |||||||||||||
Cys/His rich zinc-binding domain (CH/ZBD) of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. This coronavirus family includes Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) non-structural protein 13 (SARS-Nsp13) and belongs to helicase superfamily 1 (SF1) and to a family of nindoviral replication helicases. SARS-Nsp13 has an N-terminal CH/ZBD, a stalk domain, a 1B regulatory domain, and SF1 helicase core. The CH/ZBD has 3 zinc-finger (ZnF1-3) motifs. SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). The SARS-Nsp13 CH/ZBD is indispensable for helicase activity and interacts with SARS-Nsp12, the RNA-dependent RNA polymerase (RdRp). Structural studies of a stable SARS-CoV-2 RTC which included two molecules of Nsp13, the RdRp holoenzyme (Nsp7, two molecules of Nsp8, Nsp12), and an RNA template product, show that one Nsp13 CH/ZBD domain interacts with Nsp12, and both Nsp13-CH/ZBD domains interact with the Nsp8. This stable SARS-CoV-2 RTC suggests that the Nsp13 helicase may drive RTC backtracking, affecting proofreading and template switching. : Pssm-ID: 439168 Cd Length: 95 Bit Score: 204.54 E-value: 9.61e-61
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| betaCoV_Nsp9 | cd21898 | betacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ... |
4138-4250 | 1.29e-57 | |||||||||||||
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: 196.08 E-value: 1.29e-57
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| M_alpha_beta_cv_Nsp15-like | cd21167 | middle domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related ... |
6514-6645 | 5.02e-56 | |||||||||||||
middle domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. Coronavirus Nsp15 NendoUs have an N-terminal domain, a middle (M) domain and a C-terminal catalytic (NendoU) domain. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. This middle domain harbors residues involved in hexamer formation and in trimer stability. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of the other coronaviruses; it has been shown to exist as a dimer and a monomer in solution. : Pssm-ID: 439161 Cd Length: 127 Bit Score: 192.16 E-value: 5.02e-56
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| bCoV_NSP3_N super family | cl13772 | Betacoronavirus replicase NSP3, N-terminal; This domain family corresponds to the N-terminal ... |
880-1050 | 8.20e-50 | |||||||||||||
Betacoronavirus replicase NSP3, N-terminal; This domain family corresponds to the N-terminal domain of NSP3 (non-structural protein 3, also known as nsp3) found in Betacoronavirus, which is encoded on the replicase polyprotein. This family includes the NSP3a domain which has the ubiquitin-like 1 (UB1) and glutamic acid-rich acidic (AC) hypervariable domains. NSP3a interacts with numerous other proteins involved in replication and transcription and may serve as a scaffolding protein for these processes. The N-terminal NSP3a domain interacts with N (nucleocapsid) protein to colocalize genomic RNA with the nascent replicase-transcriptase complex at the earliest stages of infection, essential for the virus. The C-terminal Glu-rich subdomain is best described as a flexible tail attached to the globular UB1 subdomain. The family is found in association with pfam08716, pfam01661, pfam05409, pfam06471, pfam08717, pfam06478, pfam09401, pfam06460, pfam08715, pfam08710. The actual alignment was detected with superfamily member pfam12379: Pssm-ID: 432517 Cd Length: 149 Bit Score: 175.37 E-value: 8.20e-50
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| Macro_X_Nsp3-like | cd21557 | X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The ... |
1054-1177 | 1.63e-48 | |||||||||||||
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: 170.81 E-value: 1.63e-48
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| 1B_cv_Nsp13-like | cd21409 | 1B domain of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze ... |
5471-5549 | 2.03e-47 | |||||||||||||
1B domain of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. Members of this subfamily belong to helicase superfamily 1 (SF1) and include coronavirus helicases such as Severe Acute Respiratory Syndrome coronavirus (SARS) non-structural protein 13 (SARS-Nsp13). SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). Structural studies of a stable RTC which included the RNA-dependent RNA polymerase holoenzyme (Nsp7, two molecules of Nsp82, Nsp12), two molecules of Nsp13 helicase accessory factor and an RNA template product suggests that the Nsp13 helicase may drive RTC backtracking, affecting proofreading and template switching. SARS-Nsp13 is a multidomain protein; its other domains include an N-terminal Cys/His rich zinc-binding domain (CH/ZBD) and a SF1 helicase core. The 1B domain is involved in nucleic acid substrate binding; the 1B domain of the related Equine arteritis virus (EAV) Nsp10 undergoes large conformational change upon substrate binding, and together with the 1A and 2A domains of the helicase core form a channel that accommodates the single stranded nucleic acids. : Pssm-ID: 394817 Cd Length: 79 Bit Score: 165.60 E-value: 2.03e-47
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| CoV_NSP4_C | pfam16348 | Coronavirus replicase NSP4, C-terminal; This is the C-terminal domain of the coronavirus ... |
3169-3261 | 1.94e-43 | |||||||||||||
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: 154.99 E-value: 1.94e-43
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| NendoU_XendoU-like | cd21144 | Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural ... |
6682-6792 | 2.75e-43 | |||||||||||||
Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural protein 15 (Nsp15), arterivirus Nsp11, torovirus endoribonuclease, Xenopus laevis endoribonuclease XendoU, and related proteins; Nidovirus endoribonucleases (NendoUs) and eukaryotic Xenopus laevis-like endoribonucleases (XendoUs) are uridylate-specific endoribonucleases which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. XendoU is involved in the processing of intron-encoded box C/D U16 small, nucleolar RNA. Except for turkey coronavirus (TCoV) Nsp15, Mn2+ is generally essential for the catalytic activity of coronavirus Nsp15. Mn2+ is dispensable, and to some extent inhibits the activity of arterivirus (Porcine Reproductive and Respiratory Syndrome virus) PRRSV Nsp11. XendoU also requires Mn2+. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and murine hepatitis virus (MHV) forms a functional hexamer while Porcine DeltaCoronavirus (PDCoV) Nsp15 has been shown to exist as a dimer and a monomer in solution. Nsp11 from the arterivirus PRRSV is a dimer. : Pssm-ID: 439156 Cd Length: 113 Bit Score: 155.47 E-value: 2.75e-43
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| betaCoV_Nsp7 | cd21827 | betacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ... |
3857-3939 | 2.72e-41 | |||||||||||||
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: 148.36 E-value: 2.72e-41
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| SUD_C_SARS-CoV_Nsp3 | cd21525 | C-terminal SARS-Unique Domain (SUD) of non-structural protein 3 (Nsp3) from Severe Acute ... |
1496-1561 | 3.04e-37 | |||||||||||||
C-terminal SARS-Unique Domain (SUD) of non-structural protein 3 (Nsp3) from Severe Acute Respiratory Syndrome coronavirus and related betacoronaviruses in the B lineage; This subfamily contains the SUD-C of Severe Acute Respiratory Syndrome (SARS) coronavirus (CoV) non-structural protein 3 (Nsp3) and other Nsp3s from betacoronaviruses in the sarbecovirus subgenera (B lineage), such as SARS-CoV-2 and related bat CoVs. Non-structural protein 3 (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. Nsp3 of the Severe Acute Respiratory Syndrome (SARS) coronavirus includes a SARS-unique domain (SUD) consisting of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. SUD-N and SUD-M are macro domains which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). The SUD-C domain adopts a frataxin-like fold and has structural similarity to DNA-binding domains of DNA-modifying enzymes. It binds to single-stranded RNA and recognizes purine bases more strongly than pyrimidine bases. SUD-C also regulates the RNA binding behavior of the SUD-M macrodomain. : Pssm-ID: 394841 Cd Length: 67 Bit Score: 136.14 E-value: 3.04e-37
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| NTD_alpha_betaCoV_Nsp15-like | cd21171 | N-terminal domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related ... |
6450-6510 | 3.30e-33 | |||||||||||||
N-terminal domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related proteins; Coronavirus (CoV) Nsp15 is a nidovirus endoribonuclease (NendoU). NendoUs are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include CoV Nsp15 and arterivirus Nsp11, both of which may participate in the viral replication process and in the evasion of the host immune system. This small NTD structure, present in coronavirus Nsp15, is missing in Nsp11. CoV Nsp15 has an N-terminal domain, a middle (M) domain, and a C-terminal catalytic (NendoU) domain. Nsp15 from Severe Acute Respiratory Syndrome (SARS)-CoV, human CoV229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. Residues in this N-terminal domain are important for hexamer (dimer of trimers) formation. : Pssm-ID: 439163 Cd Length: 61 Bit Score: 124.60 E-value: 3.30e-33
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| SARS-CoV-like_Nsp1_C | cd22662 | C-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related ... |
128-180 | 7.76e-32 | |||||||||||||
C-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the C-terminal domain of non-structural protein 1 (Nsp1) from betacoronaviruses in the sarbecovirus subgenus (B lineage), including highly pathogenic coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). 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. SARS-CoV Nsp1 enhances virus replication by binding to a stem-loop structure in the 5'-UTR of its genome. When the SARS-CoV-2 5' UTR is bound to the Nsp1 N-terminus, the covalently linked Nsp1 C-terminus cannot bind the 40S ribosome, suggesting a bipartite mechanism whereby SARS-CoV-2 Nsp1 suppresses host but not viral translation. : Pssm-ID: 439355 Cd Length: 53 Bit Score: 120.36 E-value: 7.76e-32
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| stalk_CoV_Nsp13-like | cd21689 | stalk domain of coronavirus Nsp13 helicase and related proteins; This model represents the ... |
5420-5467 | 1.02e-24 | |||||||||||||
stalk domain of coronavirus Nsp13 helicase and related proteins; This model represents the stalk domain of coronavirus non-structural protein 13 (Nsp13) helicase, found in the Nsp3s of alpha-, beta-, gamma-, and deltacoronaviruses, including Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), SARS-CoV-2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome coronavirus (MERS-CoV). Helicases are classified based on the arrangement of conserved motifs into six superfamilies; coronavirus helicases in this family belong to superfamily 1 (SF1). Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It consists of an N-terminal ZBD (Cys/His rich zinc-binding domain), a stalk domain, a 1B regulatory domain, and SF1 helicase core. The stalk domain lies between the ZBD domain and the 1B domain; a short loop connects the ZBD to the stalk domain. The stalk domain is comprised of three tightly-interacting alpha-helices connected to the 1B domain, transferring the effect from the ZBD domain onto the helicase core domains. The ZBD and stalk domains are critical for the helicase activity of SARS-CoV Nsp13. : Pssm-ID: 410205 Cd Length: 48 Bit Score: 99.99 E-value: 1.02e-24
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| Name | Accession | Description | Interval | E-value | |||||||||||||
| SARS-CoV-like_RdRp | cd21591 | Severe acute respiratory syndrome coronavirus RNA-dependent RNA polymerase, also known as ... |
4394-5321 | 0e+00 | |||||||||||||
Severe acute respiratory syndrome coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the B lineage: responsible for replication and transcription of the viral RNA genome; This group contains the RNA-dependent RNA polymerase (RdRp) of Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 (also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus), and similar proteins from betacoronaviruses in the sarbecovirus subgenera (B lineage). 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. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which shows potential for the treatment of SARS-CoV-2 viral infections. The structure of SARS-CoV-2 Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. Recent studies have shown that the SARS-CoV-2 RdRp requires two iron-sulfur clusters to function optimally. Earlier studies had mistakenly identified these iron-sulfur cluster binding sites for zinc-binding sites, likely because iron-sulfur clusters degrade easily under standard experimental conditions.The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. Pssm-ID: 394895 Cd Length: 928 Bit Score: 1951.81 E-value: 0e+00
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| betaCoV_Nsp2_SARS-like | cd21516 | betacoronavirus non-structural protein 2 (Nsp2) similar to SARS-CoV Nsp2, and related proteins ... |
182-818 | 0e+00 | |||||||||||||
betacoronavirus non-structural protein 2 (Nsp2) similar to SARS-CoV Nsp2, and related proteins from betacoronaviruses in the B lineage; Non-structural proteins (Nsps) from Severe acute respiratory syndrome coronavirus (SARS-CoV) and betacoronaviruses in the sarbecovirus subgenus (B lineage) are encoded in ORF1a and ORF1b. Post infection, the SARS-CoV genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (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. The function of Nsp2 remains unknown. Deletion of Nsp2 from the SARS-CoV genome results in only a modest reduction in viral titers. Rather than playing a role in viral replication, SARS-CoV Nsp2 may be involved in altering the host cell environment; 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. Pssm-ID: 439199 Cd Length: 637 Bit Score: 1155.68 E-value: 0e+00
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| TM_Y_SARS-CoV-like_Nsp3_C | cd21717 | C-terminus of non-structural protein 3, including transmembrane and Y domains, from Severe ... |
2232-2762 | 0e+00 | |||||||||||||
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: 1153.97 E-value: 0e+00
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| betaCoV_Nsp14 | cd21659 | nonstructural protein 14 of betacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus ... |
5927-6337 | 0e+00 | |||||||||||||
nonstructural protein 14 of betacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The association of Nsp14 with Nsp10 stimulates its ExoN activity; the 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. The Nsp10/Nsp14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. Nsp14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or Nsp14 has been found to interfere with protein translation of cellular mRNAs. Pssm-ID: 394958 Cd Length: 519 Bit Score: 822.05 E-value: 0e+00
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| CoV_ExoN | pfam06471 | Coronavirus proofreading exoribonuclease; This region of coronavirus polyproteins encodes the ... |
5925-6337 | 0e+00 | |||||||||||||
Coronavirus proofreading exoribonuclease; This region of coronavirus polyproteins encodes the NSP14 protein. Its N-terminal exoribonuclease (ExoN) domain plays a proofreading role for prevention of lethal mutagenesis, and the C-terminal domain functions as a (guanine-N7) methyl transferase (N7-MTase) for mRNA capping. NSP14 forms the nsp14-nsp10 complex involved in RNA viral proofreading. Pssm-ID: 399465 Cd Length: 515 Bit Score: 750.83 E-value: 0e+00
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| betaCoV_Nsp13-helicase | cd21722 | helicase domain of betacoronavirus non-structural protein 13; This model represents the ... |
5572-5911 | 0e+00 | |||||||||||||
helicase domain of betacoronavirus non-structural protein 13; This model represents the helicase domain of non-structural protein 13 (Nsp13) from betacoronavirus, including pathogenic human viruses such as Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. CoV Nsp13 is a member of the helicase superfamily 1 (SF1); SF1 and SF2 helicases do not form toroidal structures, while SF3-6 helicases do. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It is a multidomain protein containing a Cys/His rich zinc-binding domain (CH/ZBD), a stalk domain, a 1B domain involved in nucleic acid substrate binding, and a SF1 helicase core. Pssm-ID: 409655 [Multi-domain] Cd Length: 340 Bit Score: 702.71 E-value: 0e+00
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| CoV_RPol_N | pfam06478 | Coronavirus RNA-dependent RNA polymerase, N-terminal; This family covers the N-terminal region ... |
4403-4755 | 0e+00 | |||||||||||||
Coronavirus RNA-dependent RNA polymerase, N-terminal; This family covers the N-terminal region of the coronavirus RNA-directed RNA Polymerase which corresponds to the nonstructural protein 12 (NSP12) produced by cleavage of ORF1b. NSP12 contains a polymerase domain that assumes a structure resembling a cupped 'right hand', similar to other polymerases, containing a fingers domain, a palm domain and a thumb domain. Coronavirus NSP12 also contains a nidovirus-unique N-terminal extension that possesses a kinase-like fold allowing the binding of NSP12 to NSP7 and NSP8. NSP12 possesses some minimal activity on its own, but the addition of the NSP7 and NSP8 co-factors greatly stimulates polymerase activity. Pssm-ID: 461929 Cd Length: 353 Bit Score: 666.08 E-value: 0e+00
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| betaCoV_Nsp5_Mpro | cd21666 | betacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ... |
3267-3563 | 0e+00 | |||||||||||||
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: 579.74 E-value: 0e+00
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| Peptidase_C30 | pfam05409 | Coronavirus endopeptidase C30; This Coronavirus (CoV) domain, peptidase C30, is also known as ... |
3292-3569 | 8.24e-162 | |||||||||||||
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: 501.59 E-value: 8.24e-162
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| CoV_NSP3_C | pfam19218 | Coronavirus replicase NSP3, C-terminal; This family represents the C-terminal region of ... |
2263-2749 | 2.57e-153 | |||||||||||||
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: 485.69 E-value: 2.57e-153
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| cv_Nsp4_TM | cd21473 | coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in ... |
2777-3157 | 9.49e-151 | |||||||||||||
coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in coronavirus-induced membrane remodeling. In order to assemble the replication-transcription complex (RTC), coronavirus induces the rearrangement of host endoplasmic reticulum (ER) membrane into double membrane vesicles (DMVs), zippered ER, or ER spherules. DMV formation has been observed in SARS-CoV cells overexpressing the three transmembrane-containing non-structural proteins of viral replicase polyprotein 1ab: Nsp3, Nsp4 and Nsp6. Together, Nsp3, Nsp4, and Nsp6 have the ability to induce the formation of DMVs that are similar to those seen in SARS-CoV-infected cells. Pssm-ID: 394836 Cd Length: 376 Bit Score: 474.77 E-value: 9.49e-151
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| betaCoV_PLPro | cd21732 | betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ... |
1566-1868 | 2.08e-149 | |||||||||||||
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: 467.45 E-value: 2.08e-149
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| betaCoV-Nsp6 | cd21560 | betacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell ... |
3570-3856 | 1.26e-137 | |||||||||||||
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: 433.21 E-value: 1.26e-137
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| CoV_peptidase | pfam08715 | Coronavirus papain-like peptidase; This entry contains coronavirus cysteine endopeptidases ... |
1564-1882 | 2.54e-127 | |||||||||||||
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: 404.75 E-value: 2.54e-127
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| CoV_NSP4_N | pfam19217 | Coronavirus replicase NSP4, N-terminal; This is the N-terminal domain of the coronavirus ... |
2788-3142 | 3.87e-120 | |||||||||||||
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: 385.47 E-value: 3.87e-120
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| CoV_Methyltr_2 | pfam06460 | Coronavirus 2'-O-methyltransferase; This domain covers the NSP16 region of the coronavirus ... |
6797-7092 | 5.21e-119 | |||||||||||||
Coronavirus 2'-O-methyltransferase; This domain covers the NSP16 region of the coronavirus polyprotein. The SARS-CoV RNA cap SAM-dependent (nucleoside-2'-O-)-methyltransferase (2'-O-MTase) is a heterodimer comprising SARS-CoV nsp10 and nsp16. When bound to nsp10, nsp16 is active as a type-0 RNA cap-dependent 2'-O-MTase, ie., active only when the cap guanine is methylated at its N7 position. Nsp10 binds to nsp16 through an activation surface area in nsp10, and the resulting complex exhibits RNA cap (nucleoside-2'-O)-methyltransferase activity. Nsp10 is a double zinc finger protein together with nsp4, nsp5, nsp12, nsp14, and nsp16, nsp10 has been found to be essential in the assembly of a functional replication/transcription complex. Nsp16 adopts a typical fold of the S-adenosylmethionine-dependent methyltransferase (SAM) family as defined initially for the catechol O-MTase but it lacks several elements of the canonical MTase fold, such as helices B and C. The nsp16 topology matches those of dengue virus NS5 N-terminal domain and of vaccinia virus VP39 MTases. Pssm-ID: 461919 Cd Length: 296 Bit Score: 379.90 E-value: 5.21e-119
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| CoV_NSP8 | pfam08717 | Coronavirus replicase NSP8; Viral NSP8 (non structural protein 8) forms a hexadecameric ... |
3940-4136 | 4.24e-111 | |||||||||||||
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: 353.00 E-value: 4.24e-111
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| betaCoV_Nsp8 | cd21831 | betacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ... |
3943-4137 | 1.30e-108 | |||||||||||||
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: 345.62 E-value: 1.30e-108
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| capping_2-OMTase_betaCoV_Nsp16 | cd23528 | Cap-0 specific (nucleoside-2'-O-)-methyltransferase of betacoronavirus, also called ... |
6824-6962 | 1.19e-94 | |||||||||||||
Cap-0 specific (nucleoside-2'-O-)-methyltransferase of betacoronavirus, also called non-structural protein 16; Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) catalyzes the methylation of Cap-0 (m7GpppNp) at the 2'-hydroxyl of the ribose of the first nucleotide, using S-adenosyl-L-methionine (AdoMet) as the methyl donor. This reaction is the fourth and last step in mRNA capping, the creation of the stabilizing five-prime cap (5' cap) on mRNA. The betacoronavirus (betaCoV) 2'OMTase activity is located in the non-structural protein 16 (Nsp16). 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. Nsp16 requires Nsp10 to bind both m7GpppA-RNA substrate and SAM cofactor; the structure suggests that Nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of Nsp16. Pssm-ID: 467740 Cd Length: 216 Bit Score: 306.62 E-value: 1.19e-94
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| alpha_betaCoV_Nsp10 | cd21901 | alphacoronavirus and betacoronavirus non-structural protein 10; This model represents the ... |
4251-4381 | 8.40e-81 | |||||||||||||
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: 263.37 E-value: 8.40e-81
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| SARS-CoV-like_Nsp1_N | cd21796 | N-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related ... |
13-127 | 1.29e-77 | |||||||||||||
N-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the N-terminal domain of non-structural protein 1 (Nsp1) from betacoronaviruses in the sarbecovirus subgenus (B lineage), including highly pathogenic coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). 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: 439285 Cd Length: 115 Bit Score: 253.66 E-value: 1.29e-77
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| CoV_NSP10 | pfam09401 | Coronavirus RNA synthesis protein NSP10; Non-structural protein 10 (NSP10) is involved in RNA ... |
4262-4381 | 2.68e-72 | |||||||||||||
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: 238.49 E-value: 2.68e-72
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| SARS-CoV-like_Nsp3_NAB | cd21822 | nucleic acid binding domain of non-structural protein 3 from Severe acute respiratory ... |
1913-2019 | 1.03e-69 | |||||||||||||
nucleic acid binding domain of non-structural protein 3 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the nucleic acid binding (NAB) domain of non-structural protein 3 (Nsp3) from betacoronavirus in the sarbecovirus subgenus (B lineage) and hibecovirus subgenus, including highly pathogenic human coronaviruses (CoVs) such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). The NAB domain represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. NAB is a cytoplasmic domain located between the papain-like protease (PLPro) and betacoronavirus-specific marker (betaSM) domains of CoV Nsp3. 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. The NAB domain both binds ssRNA and unwinds dsDNA. It prefers to bind ssRNA containing repeats of three consecutive guanines. A group of residues that form a positively charged patch on the protein surface of SARS-CoV Nsp3 NAB serves as the binding site of nucleic acids. This site is conserved in the NAB of Nsp3 from betacoronavirus in the B lineage. Pssm-ID: 409348 Cd Length: 107 Bit Score: 230.50 E-value: 1.03e-69
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| SARS-CoV-like_Nsp3_betaSM | cd21814 | betacoronavirus-specific marker of non-structural protein 3 from Severe acute respiratory ... |
2044-2159 | 4.77e-69 | |||||||||||||
betacoronavirus-specific marker of non-structural protein 3 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the betacoronavirus-specific marker (betaSM), also called group 2-specific marker (G2M), 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). The betaSM/G2M is located C-terminal to the nucleic acid-binding (NAB) domain. This region is absent in alpha- and deltacoronavirus Nsp3; there is a gammacoronavirus-specific marker (gammaSM) at this position in gammacoronavirus Nsp3. 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. Little is known about the betaSM/G2M domain; it is predicted to be non-enzymatic and may be an intrinsically disordered region. The betaSM/G2M domain is part of the predicted PLnc domain (made up of 385 amino acids) of SARS-CoV Nsp3 that may function as a replication/transcription scaffold, with interactions to Nsp5, Nsp12, Nsp13, Nsp14, and Nsp16. Pssm-ID: 409629 Cd Length: 116 Bit Score: 228.99 E-value: 4.77e-69
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| bCoV_SUD_M | pfam11633 | Betacoronavirus single-stranded poly(A) binding domain; This domain identifies non-structural ... |
1368-1493 | 6.90e-67 | |||||||||||||
Betacoronavirus single-stranded poly(A) binding domain; This domain identifies non-structural protein NSP3, the product of ORF1a in group 2 coronavirus. It is found in human SARS coronavirus polyprotein 1a and 1ab, and in related coronavirus polyproteins. NSP3 binds to viral RNA, nucleocapsid protein, as well as other viral proteins, and participates in polyprotein processing. The domain exhibits a macrodomain fold containing the nsp3 residues 528 to 648, with a flexibly extended N-terminal tail from residues 513 to 527 and a C-terminal flexible tail of residues 649 to 651. SUD-M(527-651) binds single-stranded poly(A); the contact area with this RNA on the protein surface, and the electrophoretic mobility shift assays confirm that SUD-M has higher affinity for purine bases than for pyrimidine bases. Pssm-ID: 431970 Cd Length: 126 Bit Score: 223.47 E-value: 6.90e-67
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| Macro_cv_SUD-N_Nsp3-like | cd21562 | SUD-N macrodomain (or Mac2 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural ... |
1233-1358 | 1.55e-65 | |||||||||||||
SUD-N macrodomain (or Mac2 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural protein 3 and related macrodomains; This subfamily includes the macrodomain referred to as SUD-N (N-terminal subdomain) of the SARS-unique domain (SUD) which binds G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). It is found in the non-structural protein 3 (Nsp3) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and highly related coronaviruses. SUD consists of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. Among these, SUD-N and SUD-M are macrodomains: the SUD-M domain (not represented in this subfamily) is a related macrodomain which also binds G-quadruplexes. SUD-N (also called Mac2) is specific to the Nsp3 of SARS and betacoronaviruses of the sarbecovirus subgenera (B lineage), while SUD-M (also called Mac3) is present in most Nsp3 proteins except the Nsp3 from betacoronaviruses of the embecovirus subgenera (A lineage). SUD-C adopts a frataxin-like fold, has structural similarity to DNA-binding domains of DNA-modifying enzymes, binds single-stranded RNA, and regulates the RNA binding behavior of the SUD-M macrodomain. SARS-CoV Nsp3 contains a third macrodomain (the X-domain or Mac1) which is also not represented in this subfamily. The X-domain may function as a module binding poly(ADP-ribose); however, SUD-N and SUD-M do not bind ADP-ribose, as the triple glycine sequence involved in its binding is not conserved in these. Pssm-ID: 394883 Cd Length: 126 Bit Score: 219.32 E-value: 1.55e-65
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| ZBD_cv_Nsp13-like | cd21401 | Cys/His rich zinc-binding domain (CH/ZBD) of coronavirus SARS NSP13 helicase and related ... |
5322-5416 | 9.61e-61 | |||||||||||||
Cys/His rich zinc-binding domain (CH/ZBD) of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. This coronavirus family includes Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) non-structural protein 13 (SARS-Nsp13) and belongs to helicase superfamily 1 (SF1) and to a family of nindoviral replication helicases. SARS-Nsp13 has an N-terminal CH/ZBD, a stalk domain, a 1B regulatory domain, and SF1 helicase core. The CH/ZBD has 3 zinc-finger (ZnF1-3) motifs. SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). The SARS-Nsp13 CH/ZBD is indispensable for helicase activity and interacts with SARS-Nsp12, the RNA-dependent RNA polymerase (RdRp). Structural studies of a stable SARS-CoV-2 RTC which included two molecules of Nsp13, the RdRp holoenzyme (Nsp7, two molecules of Nsp8, Nsp12), and an RNA template product, show that one Nsp13 CH/ZBD domain interacts with Nsp12, and both Nsp13-CH/ZBD domains interact with the Nsp8. This stable SARS-CoV-2 RTC suggests that the Nsp13 helicase may drive RTC backtracking, affecting proofreading and template switching. Pssm-ID: 439168 Cd Length: 95 Bit Score: 204.54 E-value: 9.61e-61
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| CoV_NSP6 | pfam19213 | Coronavirus replicase NSP6; This entry represents proteins found in Coronaviruses and includes ... |
3598-3856 | 2.77e-58 | |||||||||||||
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: 204.02 E-value: 2.77e-58
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| betaCoV_Nsp9 | cd21898 | betacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ... |
4138-4250 | 1.29e-57 | |||||||||||||
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: 196.08 E-value: 1.29e-57
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| M_alpha_beta_cv_Nsp15-like | cd21167 | middle domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related ... |
6514-6645 | 5.02e-56 | |||||||||||||
middle domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. Coronavirus Nsp15 NendoUs have an N-terminal domain, a middle (M) domain and a C-terminal catalytic (NendoU) domain. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. This middle domain harbors residues involved in hexamer formation and in trimer stability. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of the other coronaviruses; it has been shown to exist as a dimer and a monomer in solution. Pssm-ID: 439161 Cd Length: 127 Bit Score: 192.16 E-value: 5.02e-56
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| CoV_NSP9 | pfam08710 | Coronavirus replicase NSP9; Nsp9 is a single-stranded RNA-binding viral protein involved in ... |
4138-4250 | 8.66e-55 | |||||||||||||
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: 188.07 E-value: 8.66e-55
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| Macro_cv_SUD-M_Nsp3-like | cd21563 | SUD-M macrodomain (or Mac3 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural ... |
1369-1489 | 9.93e-54 | |||||||||||||
SUD-M macrodomain (or Mac3 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural protein 3 and related macrodomains; This subfamily includes the macrodomain referred to as SUD-M (middle SUD subdomain) of the SARS-unique domain (SUD) which binds G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). It is found in non-structural protein 3 (Nsp3) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and related coronaviruses. SUD consists of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. Among these, SUD-N and SUD-M are macrodomains: The SUD-N domain (not represented in this subfamily) is a related macrodomain which also binds G-quadruplexes. While SUD-N (also called Mac2) is specific to the Nsp3 of SARS and betacoronaviruses of the sarbecovirus subgenera (B lineage), SUD-M (also called Mac3) is present in most Nsp3 proteins except the Nsp3 from betacoronaviruses of the embecovirus subgenera (A lineage). SUD-M, despite its name, is not specific to SARS. SUD-C adopts a frataxin-like fold, has structural similarity to DNA-binding domains of DNA-modifying enzymes, binds single-stranded RNA, and regulates the RNA binding behavior of the SUD-M macrodomain. SARS-CoV Nsp3 contains a third macrodomain (the X-domain or Mac1) which is also not represented in this subfamily. The X-domain may function as a module binding poly(ADP-ribose); however, SUD-N and SUD-M do not bind ADP-ribose, as the triple glycine sequence involved in its binding is not conserved in these. Pssm-ID: 394884 Cd Length: 120 Bit Score: 185.19 E-value: 9.93e-54
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| bCoV_NAB | pfam16251 | Betacoronavirus nucleic acid-binding (NAB); This is the nucleic acid-binding domain (NAB) from ... |
1907-2019 | 1.07e-52 | |||||||||||||
Betacoronavirus nucleic acid-binding (NAB); This is the nucleic acid-binding domain (NAB) from the multidomain nonstructural protein NSP3, and described as NSP3e domain. NSP3 is part of Orf1a polyproteins in SARS-CoV. It is an essential component of the replication/transcription complex. The global domain of the NAB represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands and a group of residues form a positively charged patch on the protein surface as the binding site responsible for binding affinity for nucleic acids. When binding to ssRNA, the NAB prefers sequences with repeats of three consecutive Gs, such as (GGGA)5 and (GGGA)2. A positively charged surface patch (Lys75, Lys76, Lys99, and Arg106) is involved in RNA binding. Pssm-ID: 406621 Cd Length: 129 Bit Score: 182.75 E-value: 1.07e-52
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| bCoV_NSP3_N | pfam12379 | Betacoronavirus replicase NSP3, N-terminal; This domain family corresponds to the N-terminal ... |
880-1050 | 8.20e-50 | |||||||||||||
Betacoronavirus replicase NSP3, N-terminal; This domain family corresponds to the N-terminal domain of NSP3 (non-structural protein 3, also known as nsp3) found in Betacoronavirus, which is encoded on the replicase polyprotein. This family includes the NSP3a domain which has the ubiquitin-like 1 (UB1) and glutamic acid-rich acidic (AC) hypervariable domains. NSP3a interacts with numerous other proteins involved in replication and transcription and may serve as a scaffolding protein for these processes. The N-terminal NSP3a domain interacts with N (nucleocapsid) protein to colocalize genomic RNA with the nascent replicase-transcriptase complex at the earliest stages of infection, essential for the virus. The C-terminal Glu-rich subdomain is best described as a flexible tail attached to the globular UB1 subdomain. The family is found in association with pfam08716, pfam01661, pfam05409, pfam06471, pfam08717, pfam06478, pfam09401, pfam06460, pfam08715, pfam08710. Pssm-ID: 432517 Cd Length: 149 Bit Score: 175.37 E-value: 8.20e-50
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| Macro_X_Nsp3-like | cd21557 | X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The ... |
1054-1177 | 1.63e-48 | |||||||||||||
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: 170.81 E-value: 1.63e-48
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| 1B_cv_Nsp13-like | cd21409 | 1B domain of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze ... |
5471-5549 | 2.03e-47 | |||||||||||||
1B domain of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. Members of this subfamily belong to helicase superfamily 1 (SF1) and include coronavirus helicases such as Severe Acute Respiratory Syndrome coronavirus (SARS) non-structural protein 13 (SARS-Nsp13). SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). Structural studies of a stable RTC which included the RNA-dependent RNA polymerase holoenzyme (Nsp7, two molecules of Nsp82, Nsp12), two molecules of Nsp13 helicase accessory factor and an RNA template product suggests that the Nsp13 helicase may drive RTC backtracking, affecting proofreading and template switching. SARS-Nsp13 is a multidomain protein; its other domains include an N-terminal Cys/His rich zinc-binding domain (CH/ZBD) and a SF1 helicase core. The 1B domain is involved in nucleic acid substrate binding; the 1B domain of the related Equine arteritis virus (EAV) Nsp10 undergoes large conformational change upon substrate binding, and together with the 1A and 2A domains of the helicase core form a channel that accommodates the single stranded nucleic acids. Pssm-ID: 394817 Cd Length: 79 Bit Score: 165.60 E-value: 2.03e-47
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| CoV_NSP4_C | pfam16348 | Coronavirus replicase NSP4, C-terminal; This is the C-terminal domain of the coronavirus ... |
3169-3261 | 1.94e-43 | |||||||||||||
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: 154.99 E-value: 1.94e-43
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| NendoU_XendoU-like | cd21144 | Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural ... |
6682-6792 | 2.75e-43 | |||||||||||||
Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural protein 15 (Nsp15), arterivirus Nsp11, torovirus endoribonuclease, Xenopus laevis endoribonuclease XendoU, and related proteins; Nidovirus endoribonucleases (NendoUs) and eukaryotic Xenopus laevis-like endoribonucleases (XendoUs) are uridylate-specific endoribonucleases which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. XendoU is involved in the processing of intron-encoded box C/D U16 small, nucleolar RNA. Except for turkey coronavirus (TCoV) Nsp15, Mn2+ is generally essential for the catalytic activity of coronavirus Nsp15. Mn2+ is dispensable, and to some extent inhibits the activity of arterivirus (Porcine Reproductive and Respiratory Syndrome virus) PRRSV Nsp11. XendoU also requires Mn2+. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and murine hepatitis virus (MHV) forms a functional hexamer while Porcine DeltaCoronavirus (PDCoV) Nsp15 has been shown to exist as a dimer and a monomer in solution. Nsp11 from the arterivirus PRRSV is a dimer. Pssm-ID: 439156 Cd Length: 113 Bit Score: 155.47 E-value: 2.75e-43
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| betaCoV_Nsp7 | cd21827 | betacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ... |
3857-3939 | 2.72e-41 | |||||||||||||
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: 148.36 E-value: 2.72e-41
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| bCoV_NSP1 | pfam11501 | Betacoronavirus replicase NSP1; This entry represents the non structural protein NSP1 from ... |
9-144 | 1.78e-39 | |||||||||||||
Betacoronavirus replicase NSP1; This entry represents the non structural protein NSP1 from Betacoronavirus NSP1 is the N-terminal cleavage product from the viral replicase that mediates RNA replication and processing. Structurally, the protein consists of a mixed parallel/antiparallel 6-stranded beta barrel with an alpha helix covering one end of the barrel and another helix alongside the barrel. NSP1 binds to the 40S ribosomal subunit and inhibits translation, and it also induces a template-dependent endonucleolytic cleavage of host mRNAs. NSP1 also suppresses the host innate immune functions by inhibiting type I interferon expression and host antiviral signalling pathways. Pssm-ID: 431911 Cd Length: 138 Bit Score: 145.22 E-value: 1.78e-39
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| CoV_NSP7 | pfam08716 | Coronavirus replicase NSP7; NSP7 (non structural protein 7) has been implicated in viral RNA ... |
3857-3939 | 1.91e-38 | |||||||||||||
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: 140.28 E-value: 1.91e-38
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| SUD_C_SARS-CoV_Nsp3 | cd21525 | C-terminal SARS-Unique Domain (SUD) of non-structural protein 3 (Nsp3) from Severe Acute ... |
1496-1561 | 3.04e-37 | |||||||||||||
C-terminal SARS-Unique Domain (SUD) of non-structural protein 3 (Nsp3) from Severe Acute Respiratory Syndrome coronavirus and related betacoronaviruses in the B lineage; This subfamily contains the SUD-C of Severe Acute Respiratory Syndrome (SARS) coronavirus (CoV) non-structural protein 3 (Nsp3) and other Nsp3s from betacoronaviruses in the sarbecovirus subgenera (B lineage), such as SARS-CoV-2 and related bat CoVs. Non-structural protein 3 (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. Nsp3 of the Severe Acute Respiratory Syndrome (SARS) coronavirus includes a SARS-unique domain (SUD) consisting of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. SUD-N and SUD-M are macro domains which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). The SUD-C domain adopts a frataxin-like fold and has structural similarity to DNA-binding domains of DNA-modifying enzymes. It binds to single-stranded RNA and recognizes purine bases more strongly than pyrimidine bases. SUD-C also regulates the RNA binding behavior of the SUD-M macrodomain. Pssm-ID: 394841 Cd Length: 67 Bit Score: 136.14 E-value: 3.04e-37
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| NTD_alpha_betaCoV_Nsp15-like | cd21171 | N-terminal domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related ... |
6450-6510 | 3.30e-33 | |||||||||||||
N-terminal domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related proteins; Coronavirus (CoV) Nsp15 is a nidovirus endoribonuclease (NendoU). NendoUs are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include CoV Nsp15 and arterivirus Nsp11, both of which may participate in the viral replication process and in the evasion of the host immune system. This small NTD structure, present in coronavirus Nsp15, is missing in Nsp11. CoV Nsp15 has an N-terminal domain, a middle (M) domain, and a C-terminal catalytic (NendoU) domain. Nsp15 from Severe Acute Respiratory Syndrome (SARS)-CoV, human CoV229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. Residues in this N-terminal domain are important for hexamer (dimer of trimers) formation. Pssm-ID: 439163 Cd Length: 61 Bit Score: 124.60 E-value: 3.30e-33
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| CoV_NSP15_C | pfam19215 | Coronavirus replicase NSP15, uridylate-specific endoribonuclease; This entry represents the ... |
6682-6793 | 8.28e-33 | |||||||||||||
Coronavirus replicase NSP15, uridylate-specific endoribonuclease; This entry represents the C-terminal domain of coronavirus non-structural protein 15 (NSP15 or nsp15). NSP15 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. This domain exhibits endoribonuclease activity designated EndoU, highly conserved in all known CoVs and is part of the replicase-transcriptase complex that plays important roles in virus replication and transcription. NSP15 is a Uridylate-specific endoribonuclease that cleaves the 5'-polyuridines from negative-sense viral RNA, termed PUN RNA either upstream or downstream of uridylates, at GUU or GU to produce molecules with 2',3'-cyclic phosphate ends. PUN RNA is a CoV MDA5-dependent pathogen-associated molecular pattern (PAMP). Pssm-ID: 465999 Cd Length: 155 Bit Score: 127.06 E-value: 8.28e-33
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| SARS-CoV-like_Nsp1_C | cd22662 | C-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related ... |
128-180 | 7.76e-32 | |||||||||||||
C-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the C-terminal domain of non-structural protein 1 (Nsp1) from betacoronaviruses in the sarbecovirus subgenus (B lineage), including highly pathogenic coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). 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. SARS-CoV Nsp1 enhances virus replication by binding to a stem-loop structure in the 5'-UTR of its genome. When the SARS-CoV-2 5' UTR is bound to the Nsp1 N-terminus, the covalently linked Nsp1 C-terminus cannot bind the 40S ribosome, suggesting a bipartite mechanism whereby SARS-CoV-2 Nsp1 suppresses host but not viral translation. Pssm-ID: 439355 Cd Length: 53 Bit Score: 120.36 E-value: 7.76e-32
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| Ubl1_cv_Nsp3_N-like | cd21467 | first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV ... |
838-924 | 2.77e-31 | |||||||||||||
first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model. Pssm-ID: 394822 Cd Length: 89 Bit Score: 119.98 E-value: 2.77e-31
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| CoV_NSP15_M | pfam19216 | Coronavirus replicase NSP15, middle domain; This entry represents the non-catalytic middle ... |
6511-6634 | 4.60e-29 | |||||||||||||
Coronavirus replicase NSP15, middle domain; This entry represents the non-catalytic middle domain from coronavirus non-structural protein 15 (NSP15). NSP15 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. This domain is formed by ten beta strands organized into three beta hairpins. Pssm-ID: 466000 Cd Length: 118 Bit Score: 114.74 E-value: 4.60e-29
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| CoV_NSP15_N | pfam19219 | Coronavirus replicase NSP15, N-terminal oligomerization; This is the N-terminal domain of the ... |
6450-6510 | 5.40e-28 | |||||||||||||
Coronavirus replicase NSP15, N-terminal oligomerization; This is the N-terminal domain of the coronavirus nonstructural protein 15 (NSP15), which is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. NSP15, is a nidoviral RNA uridylate-specific endoribonuclease (NendoU) carrying C-terminal catalytic domain belonging to the EndoU family. The SARS-CoV-2 NendoU monomers assemble into a double-ring hexamer, generated by a dimer of trimers. The hexamer is stabilized by the interactions of N-terminal oligomerization domain. Pssm-ID: 466003 Cd Length: 61 Bit Score: 109.71 E-value: 5.40e-28
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| bCoV_SUD_C | pfam12124 | Betacoronavirus SUD-C domain; This domain is found in betacoronavirus non-structural protein ... |
1498-1561 | 1.66e-27 | |||||||||||||
Betacoronavirus SUD-C domain; This domain is found in betacoronavirus non-structural protein NSP3, and is about 65 amino acids in length. It was originally thought to exist only in SARS-coronaviruses, and so was termed the SARS-unique domain (SUD), however this has since been shown to be incorrect. The domain is also known as DPUP (domain preceding Ubl2 and PL2pro). NSP3 is the product of ORF1a, proteolytically released from the pp1a/1ab polyprotein. The SUD domain has three globular domains, SUD-N (N-terminal), SUD-M (middle region of SUD), and SUD-C (C-terminal). SUD-C adopts a fold consisting of seven beta-strands arranged in an anti-parallel beta-sheet, and two alpha-helices which are packed against the same side of the beta-sheet. It adopts a frataxin like fold with structural similarities to DNA-binding domains. It has been shown that SUD-C binds to single-stranded RNA and recognizes purine bases more strongly than pyrimidine bases, but these interactions are stabilized in the presence of SUD-M. The function of this domain is not clear but studies of structural homologs of SUD-C suggest that it could be related to metal, adenylate and nucleic acid binding. Pssm-ID: 288939 Cd Length: 66 Bit Score: 108.63 E-value: 1.66e-27
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| stalk_CoV_Nsp13-like | cd21689 | stalk domain of coronavirus Nsp13 helicase and related proteins; This model represents the ... |
5420-5467 | 1.02e-24 | |||||||||||||
stalk domain of coronavirus Nsp13 helicase and related proteins; This model represents the stalk domain of coronavirus non-structural protein 13 (Nsp13) helicase, found in the Nsp3s of alpha-, beta-, gamma-, and deltacoronaviruses, including Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), SARS-CoV-2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome coronavirus (MERS-CoV). Helicases are classified based on the arrangement of conserved motifs into six superfamilies; coronavirus helicases in this family belong to superfamily 1 (SF1). Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It consists of an N-terminal ZBD (Cys/His rich zinc-binding domain), a stalk domain, a 1B regulatory domain, and SF1 helicase core. The stalk domain lies between the ZBD domain and the 1B domain; a short loop connects the ZBD to the stalk domain. The stalk domain is comprised of three tightly-interacting alpha-helices connected to the 1B domain, transferring the effect from the ZBD domain onto the helicase core domains. The ZBD and stalk domains are critical for the helicase activity of SARS-CoV Nsp13. Pssm-ID: 410205 Cd Length: 48 Bit Score: 99.99 E-value: 1.02e-24
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| DNA2 | COG1112 | Superfamily I DNA and/or RNA helicase [Replication, recombination and repair]; |
5684-5911 | 3.67e-23 | |||||||||||||
Superfamily I DNA and/or RNA helicase [Replication, recombination and repair]; Pssm-ID: 440729 [Multi-domain] Cd Length: 819 Bit Score: 109.83 E-value: 3.67e-23
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| Macro | pfam01661 | Macro domain; The Macro or A1pp domain is a module of about 180 amino acids which can bind ... |
1058-1165 | 5.64e-22 | |||||||||||||
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: 94.55 E-value: 5.64e-22
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| YmdB | COG2110 | O-acetyl-ADP-ribose deacetylase (regulator of RNase III), contains Macro domain [Translation, ... |
1038-1184 | 2.09e-19 | |||||||||||||
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: 89.08 E-value: 2.09e-19
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| PRK00431 | PRK00431 | ADP-ribose-binding protein; |
1056-1196 | 1.57e-17 | |||||||||||||
ADP-ribose-binding protein; Pssm-ID: 234759 Cd Length: 177 Bit Score: 83.74 E-value: 1.57e-17
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| CoV_NSP2_N | pfam19211 | Coronavirus replicase NSP2, N-terminal; This entry corresponds to the N-terminal region of ... |
183-423 | 2.91e-16 | |||||||||||||
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: 81.24 E-value: 2.91e-16
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| A1pp | smart00506 | Appr-1"-p processing enzyme; Function determined by Martzen et al. Extended family detected by ... |
1051-1164 | 4.35e-15 | |||||||||||||
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: 75.42 E-value: 4.35e-15
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| AAA_12 | pfam13087 | AAA domain; This family of domains contain a P-loop motif that is characteriztic of the AAA ... |
5764-5901 | 6.49e-12 | |||||||||||||
AAA domain; This family of domains contain a P-loop motif that is characteriztic of the AAA superfamily. Many of the proteins in this family are conjugative transfer proteins. Pssm-ID: 463780 [Multi-domain] Cd Length: 196 Bit Score: 68.34 E-value: 6.49e-12
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| AAA | smart00382 | ATPases associated with a variety of cellular activities; AAA - ATPases associated with a ... |
5601-5733 | 4.83e-03 | |||||||||||||
ATPases associated with a variety of cellular activities; AAA - ATPases associated with a variety of cellular activities. This profile/alignment only detects a fraction of this vast family. The poorly conserved N-terminal helix is missing from the alignment. Pssm-ID: 214640 [Multi-domain] Cd Length: 148 Bit Score: 41.20 E-value: 4.83e-03
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| Name | Accession | Description | Interval | E-value | |||||||||||||
| SARS-CoV-like_RdRp | cd21591 | Severe acute respiratory syndrome coronavirus RNA-dependent RNA polymerase, also known as ... |
4394-5321 | 0e+00 | |||||||||||||
Severe acute respiratory syndrome coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the B lineage: responsible for replication and transcription of the viral RNA genome; This group contains the RNA-dependent RNA polymerase (RdRp) of Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 (also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus), and similar proteins from betacoronaviruses in the sarbecovirus subgenera (B lineage). 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. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which shows potential for the treatment of SARS-CoV-2 viral infections. The structure of SARS-CoV-2 Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. Recent studies have shown that the SARS-CoV-2 RdRp requires two iron-sulfur clusters to function optimally. Earlier studies had mistakenly identified these iron-sulfur cluster binding sites for zinc-binding sites, likely because iron-sulfur clusters degrade easily under standard experimental conditions.The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. Pssm-ID: 394895 Cd Length: 928 Bit Score: 1951.81 E-value: 0e+00
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| betaCoV_RdRp | cd21589 | betacoronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: ... |
4394-5321 | 0e+00 | |||||||||||||
betacoronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: responsible for replication and transcription of the viral RNA genome; This subfamily contains the RNA-dependent RNA polymerase (RdRp) of betacoronaviruses, including the RdRps from three highly pathogenic human coronaviruses (CoVs) such as Middle East respiratory syndrome (MERS)-related CoV, Severe acute respiratory syndrome (SARS) CoV, and SARS-CoV-2, also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus. 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. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which shows potential for the treatment of SARS-CoV-2 viral infections. The structure of SARS-CoV-2 Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. Pssm-ID: 438016 Cd Length: 925 Bit Score: 1867.53 E-value: 0e+00
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| CoV_RdRp | cd21530 | coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: responsible ... |
4394-5321 | 0e+00 | |||||||||||||
coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: responsible for replication and transcription of the viral RNA genome; This family contains the RNA-dependent RNA polymerase of alpha-, beta-, gamma-, delta-coronaviruses, including three highly pathogenic human coronaviruses (CoVs) such as Middle East respiratory syndrome (MERS)-related CoV, Severe acute respiratory syndrome (SARS) CoV, and SARS-CoV-2, also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus. 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. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which shows potential for the treatment of SARS-CoV-2 viral infections. The structure of SARS-CoV-2 Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. Pssm-ID: 438015 Cd Length: 928 Bit Score: 1846.41 E-value: 0e+00
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| MERS-CoV-like_RdRp | cd21592 | Middle East respiratory syndrome-related coronavirus RNA-dependent RNA polymerase, also known ... |
4395-5321 | 0e+00 | |||||||||||||
Middle East respiratory syndrome-related coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the C lineage: responsible for replication and transcription of the viral RNA genome; This group contains the RNA-dependent RNA polymerase (RdRp) of Middle East respiratory syndrome (MERS)-related CoV, bat-CoV HKU5, and similar proteins from betacoronaviruses in the merbecovirus subgenera (C lineage). 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. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which has been shown to potently inhibit MERS RdRp. Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. Pssm-ID: 394896 Cd Length: 931 Bit Score: 1604.32 E-value: 0e+00
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| batCoV-HKU9-like_RdRp | cd21596 | Bat coronavirus HKU9 RNA-dependent RNA polymerase, also known as non-structural protein 12, ... |
4396-5321 | 0e+00 | |||||||||||||
Bat coronavirus HKU9 RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the D lineage: responsible for replication and transcription of the viral RNA genome; This group contains the RNA-dependent RNA polymerase (RdRp) of bat coronavirus HKU9 and similar proteins from betacoronaviruses in the nobecovirus subgenera (D lineage). 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. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir. Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. Pssm-ID: 394898 Cd Length: 929 Bit Score: 1550.39 E-value: 0e+00
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| alphaCoV_RdRp | cd21588 | alphacoronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: ... |
4394-5321 | 0e+00 | |||||||||||||
alphacoronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: responsible for replication and transcription of the viral RNA genome; This subfamily contains the RNA-dependent RNA polymerase (RdRp) of alphacoronaviruses, including human coronaviruses (HCoVs), HCoV-NL63, and HCoV-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. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir. Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. Pssm-ID: 394892 Cd Length: 924 Bit Score: 1500.77 E-value: 0e+00
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| HCoV_HKU1-like_RdRp | cd21593 | human coronavirus HKU1 RNA-dependent RNA polymerase, also known as non-structural protein 12, ... |
4395-5321 | 0e+00 | |||||||||||||
human coronavirus HKU1 RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the A lineage: responsible for replication and transcription of the viral RNA genome; This group contains the RNA-dependent RNA polymerase (RdRp) of human coronavirus HKU1, murine hepatitis virus, and similar proteins from betacoronaviruses in the embecovirus subgenera (A lineage). 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. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir. Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. Pssm-ID: 394897 Cd Length: 925 Bit Score: 1480.59 E-value: 0e+00
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| gammaCoV_RdRp | cd21587 | gammacoronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: ... |
4394-5321 | 0e+00 | |||||||||||||
gammacoronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: responsible for replication and transcription of the viral RNA genome; This subfamily contains the RNA-dependent RNA polymerase (RdRp) of gammacoronaviruses, including the RdRp of avian infectious bronchitis virus (IBV) and similar proteins. 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. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir. Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. Pssm-ID: 394891 Cd Length: 931 Bit Score: 1365.72 E-value: 0e+00
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| betaCoV_Nsp2_SARS-like | cd21516 | betacoronavirus non-structural protein 2 (Nsp2) similar to SARS-CoV Nsp2, and related proteins ... |
182-818 | 0e+00 | |||||||||||||
betacoronavirus non-structural protein 2 (Nsp2) similar to SARS-CoV Nsp2, and related proteins from betacoronaviruses in the B lineage; Non-structural proteins (Nsps) from Severe acute respiratory syndrome coronavirus (SARS-CoV) and betacoronaviruses in the sarbecovirus subgenus (B lineage) are encoded in ORF1a and ORF1b. Post infection, the SARS-CoV genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (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. The function of Nsp2 remains unknown. Deletion of Nsp2 from the SARS-CoV genome results in only a modest reduction in viral titers. Rather than playing a role in viral replication, SARS-CoV Nsp2 may be involved in altering the host cell environment; 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. Pssm-ID: 439199 Cd Length: 637 Bit Score: 1155.68 E-value: 0e+00
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| TM_Y_SARS-CoV-like_Nsp3_C | cd21717 | C-terminus of non-structural protein 3, including transmembrane and Y domains, from Severe ... |
2232-2762 | 0e+00 | |||||||||||||
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: 1153.97 E-value: 0e+00
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| deltaCoV_RdRp | cd21590 | deltacoronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: ... |
4395-5321 | 0e+00 | |||||||||||||
deltacoronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12: responsible for replication and transcription of the viral RNA genome; This subfamily contains the RNA-dependent RNA polymerase (RdRp) of 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. A key component, the RNA-dependent RNA polymerase (RdRp, also known as Nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of CoV, possibly interacting with its co-factors, Nsp7 and Nsp8. RdRp is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which has been shown to inhibit human endemic and zoonotic deltacoronaviruses with a highly divergent RdRp. Nsp12 contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. Pssm-ID: 394894 Cd Length: 928 Bit Score: 1082.19 E-value: 0e+00
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| TM_Y_betaCoV_Nsp3_C | cd21713 | C-terminus of betacoronavirus non-structural protein 3, including transmembrane and Y domains; ... |
2232-2762 | 0e+00 | |||||||||||||
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: 880.68 E-value: 0e+00
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| betaCoV_Nsp14 | cd21659 | nonstructural protein 14 of betacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus ... |
5927-6337 | 0e+00 | |||||||||||||
nonstructural protein 14 of betacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The association of Nsp14 with Nsp10 stimulates its ExoN activity; the 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. The Nsp10/Nsp14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. Nsp14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or Nsp14 has been found to interfere with protein translation of cellular mRNAs. Pssm-ID: 394958 Cd Length: 519 Bit Score: 822.05 E-value: 0e+00
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| betaCoV_Nsp2_SARS_MHV-like | cd21515 | betacoronavirus non-structural protein 2 (Nsp2), similar to SARS-CoV Nsp2 and MHV Nsp2 (p65), ... |
182-783 | 0e+00 | |||||||||||||
betacoronavirus non-structural protein 2 (Nsp2), similar to SARS-CoV Nsp2 and MHV Nsp2 (p65), and related proteins; Coronavirus non-structural proteins (Nsps) are encoded in ORF1a and ORF1b. Post infection, the genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (pp), pp1a and pp1ab, which are then autoproteolytically cleaved by two viral proteases Nsp3 and Nsp5 into smaller subunits. Nsp2 is one of these subunits. This family includes 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. Pssm-ID: 439198 Cd Length: 562 Bit Score: 806.30 E-value: 0e+00
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| CoV_Nsp14 | cd21528 | nonstructural protein 14 of coronavirus; Nonstructural protein 14 (Nsp14) of coronavirus (CoV) ... |
5927-6337 | 0e+00 | |||||||||||||
nonstructural protein 14 of coronavirus; Nonstructural protein 14 (Nsp14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The association of Nsp14 with Nsp10 stimulates its ExoN activity; the 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. The Nsp10/Nsp14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. Nsp14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or Nsp14 has been found to interfere with protein translation of cellular mRNAs. Pssm-ID: 394955 Cd Length: 518 Bit Score: 758.15 E-value: 0e+00
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| CoV_ExoN | pfam06471 | Coronavirus proofreading exoribonuclease; This region of coronavirus polyproteins encodes the ... |
5925-6337 | 0e+00 | |||||||||||||
Coronavirus proofreading exoribonuclease; This region of coronavirus polyproteins encodes the NSP14 protein. Its N-terminal exoribonuclease (ExoN) domain plays a proofreading role for prevention of lethal mutagenesis, and the C-terminal domain functions as a (guanine-N7) methyl transferase (N7-MTase) for mRNA capping. NSP14 forms the nsp14-nsp10 complex involved in RNA viral proofreading. Pssm-ID: 399465 Cd Length: 515 Bit Score: 750.83 E-value: 0e+00
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| betaCoV_Nsp13-helicase | cd21722 | helicase domain of betacoronavirus non-structural protein 13; This model represents the ... |
5572-5911 | 0e+00 | |||||||||||||
helicase domain of betacoronavirus non-structural protein 13; This model represents the helicase domain of non-structural protein 13 (Nsp13) from betacoronavirus, including pathogenic human viruses such as Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. CoV Nsp13 is a member of the helicase superfamily 1 (SF1); SF1 and SF2 helicases do not form toroidal structures, while SF3-6 helicases do. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It is a multidomain protein containing a Cys/His rich zinc-binding domain (CH/ZBD), a stalk domain, a 1B domain involved in nucleic acid substrate binding, and a SF1 helicase core. Pssm-ID: 409655 [Multi-domain] Cd Length: 340 Bit Score: 702.71 E-value: 0e+00
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| CoV_Nsp13-helicase | cd21718 | helicase domain of coronavirus non-structural protein 13; This model represents the helicase ... |
5572-5911 | 0e+00 | |||||||||||||
helicase domain of coronavirus non-structural protein 13; This model represents the helicase domain of non-structural protein 13 (Nsp13) from alpha-, beta-, gamma-, and deltacoronavirus, including pathogenic human viruses such as Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. CoV Nsp13 is a member of the helicase superfamily 1 (SF1); SF1 and SF2 helicases do not form toroidal structures, while SF3-6 helicases do. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It is a multidomain protein containing a Cys/His rich zinc-binding domain (CH/ZBD), a stalk domain, a 1B domain involved in nucleic acid substrate binding, and a SF1 helicase core. Pssm-ID: 409652 [Multi-domain] Cd Length: 341 Bit Score: 670.01 E-value: 0e+00
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| CoV_RPol_N | pfam06478 | Coronavirus RNA-dependent RNA polymerase, N-terminal; This family covers the N-terminal region ... |
4403-4755 | 0e+00 | |||||||||||||
Coronavirus RNA-dependent RNA polymerase, N-terminal; This family covers the N-terminal region of the coronavirus RNA-directed RNA Polymerase which corresponds to the nonstructural protein 12 (NSP12) produced by cleavage of ORF1b. NSP12 contains a polymerase domain that assumes a structure resembling a cupped 'right hand', similar to other polymerases, containing a fingers domain, a palm domain and a thumb domain. Coronavirus NSP12 also contains a nidovirus-unique N-terminal extension that possesses a kinase-like fold allowing the binding of NSP12 to NSP7 and NSP8. NSP12 possesses some minimal activity on its own, but the addition of the NSP7 and NSP8 co-factors greatly stimulates polymerase activity. Pssm-ID: 461929 Cd Length: 353 Bit Score: 666.08 E-value: 0e+00
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| TM_Y_CoV_Nsp3_C | cd21686 | C-terminus of coronavirus non-structural protein 3, including transmembrane and Y domains; ... |
2232-2762 | 0e+00 | |||||||||||||
C-terminus of coronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from alpha-, beta-, gamma-, and deltacoronavirus, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In SARS-CoV and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain. Pssm-ID: 409657 Cd Length: 476 Bit Score: 623.83 E-value: 0e+00
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| betaCoV_Nsp5_Mpro | cd21666 | betacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ... |
3267-3563 | 0e+00 | |||||||||||||
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: 579.74 E-value: 0e+00
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| alphaCoV_Nsp14 | cd21660 | nonstructural protein 14 of alphacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus ... |
5927-6337 | 0e+00 | |||||||||||||
nonstructural protein 14 of alphacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The association of Nsp14 with Nsp10 stimulates its ExoN activity; the 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. The Nsp10/Nsp14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. Nsp14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or Nsp14 has been found to interfere with protein translation of cellular mRNAs. Pssm-ID: 394959 Cd Length: 510 Bit Score: 573.90 E-value: 0e+00
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| alphaCoV_Nsp13-helicase | cd21723 | helicase domain of alphacoronavirus non-structural protein 13; This model represents the ... |
5573-5911 | 0e+00 | |||||||||||||
helicase domain of alphacoronavirus non-structural protein 13; This model represents the helicase domain of non-structural protein 13 (Nsp13) from alphacoronavirus, including Porcine epidemic diarrhea virus and Human coronavirus (CoV) NL63. Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. CoV Nsp13 is a member of the helicase superfamily 1 (SF1); SF1 and SF2 helicases do not form toroidal structures, while SF3-6 helicases do. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It is a multidomain protein containing a Cys/His rich zinc-binding domain (CH/ZBD), a stalk domain, a 1B domain involved in nucleic acid substrate binding, and a SF1 helicase core. Pssm-ID: 409656 [Multi-domain] Cd Length: 340 Bit Score: 560.51 E-value: 0e+00
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| CoV_Nsp5_Mpro | cd21646 | coronavirus non-structural protein 5, also called Main protease (Mpro); This family contains ... |
3267-3562 | 1.65e-172 | |||||||||||||
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: 533.15 E-value: 1.65e-172
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| gammaCoV_Nsp14 | cd21658 | nonstructural protein 14 of gammacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus ... |
5927-6337 | 1.46e-171 | |||||||||||||
nonstructural protein 14 of gammacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The association of Nsp14 with Nsp10 stimulates its ExoN activity; the 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. The Nsp10/Nsp14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. Nsp14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or Nsp14 has been found to interfere with protein translation of cellular mRNAs. Pssm-ID: 394957 Cd Length: 518 Bit Score: 540.60 E-value: 1.46e-171
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| Peptidase_C30 | pfam05409 | Coronavirus endopeptidase C30; This Coronavirus (CoV) domain, peptidase C30, is also known as ... |
3292-3569 | 8.24e-162 | |||||||||||||
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: 501.59 E-value: 8.24e-162
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| CoV_NSP3_C | pfam19218 | Coronavirus replicase NSP3, C-terminal; This family represents the C-terminal region of ... |
2263-2749 | 2.57e-153 | |||||||||||||
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: 485.69 E-value: 2.57e-153
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| cv_Nsp4_TM | cd21473 | coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in ... |
2777-3157 | 9.49e-151 | |||||||||||||
coronavirus non-structural protein 4 (Nsp4) transmembrane domain; Nsp4 may be involved in coronavirus-induced membrane remodeling. In order to assemble the replication-transcription complex (RTC), coronavirus induces the rearrangement of host endoplasmic reticulum (ER) membrane into double membrane vesicles (DMVs), zippered ER, or ER spherules. DMV formation has been observed in SARS-CoV cells overexpressing the three transmembrane-containing non-structural proteins of viral replicase polyprotein 1ab: Nsp3, Nsp4 and Nsp6. Together, Nsp3, Nsp4, and Nsp6 have the ability to induce the formation of DMVs that are similar to those seen in SARS-CoV-infected cells. Pssm-ID: 394836 Cd Length: 376 Bit Score: 474.77 E-value: 9.49e-151
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| betaCoV_PLPro | cd21732 | betacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ... |
1566-1868 | 2.08e-149 | |||||||||||||
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: 467.45 E-value: 2.08e-149
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| TM_Y_MERS-CoV-like_Nsp3_C | cd21716 | C-terminus of non-structural protein 3, including transmembrane and Y domains, from Middle ... |
2253-2757 | 6.44e-142 | |||||||||||||
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: 457.35 E-value: 6.44e-142
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| alpha_betaCoV_Nsp2 | cd21511 | alpha- and betacoronavirus non-structural protein 2; Coronavirus Nsps are encoded in ORF1a and ... |
182-687 | 9.69e-141 | |||||||||||||
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: 447.00 E-value: 9.69e-141
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| TM_Y_HKU9-like_Nsp3_C | cd21715 | C-terminus of non-structural protein 3, including transmembrane and Y domains, from Rousettus ... |
2230-2762 | 7.04e-139 | |||||||||||||
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: 447.00 E-value: 7.04e-139
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| gammaCoV_Nsp13-helicase | cd21720 | helicase domain of gammacoronavirus non-structural protein 13; This model represents the ... |
5573-5911 | 5.24e-138 | |||||||||||||
helicase domain of gammacoronavirus non-structural protein 13; This model represents the helicase domain of non-structural protein 13 (Nsp13) from gammacoronavirus, including Avian infectious bronchitis virus. Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. Coronavirus (CoV) Nsp13 is a member of the helicase superfamily 1 (SF1); SF1 and SF2 helicases do not form toroidal structures, while SF3-6 helicases do. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It is a multidomain protein containing a Cys/His rich zinc-binding domain (CH/ZBD), a stalk domain, a 1B domain involved in nucleic acid substrate binding, and a SF1 helicase core. Pssm-ID: 409653 [Multi-domain] Cd Length: 343 Bit Score: 436.66 E-value: 5.24e-138
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| betaCoV-Nsp6 | cd21560 | betacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell ... |
3570-3856 | 1.26e-137 | |||||||||||||
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: 433.21 E-value: 1.26e-137
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| DEXSMc_CoV_Nsp13 | cd22649 | DEXSM-box helicase domain of coronavirus Nsp13 helicase; Helicases catalyze the NTP-dependent ... |
5563-5764 | 1.49e-134 | |||||||||||||
DEXSM-box helicase domain of coronavirus Nsp13 helicase; Helicases catalyze the NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified into six superfamilies based on the arrangement of conserved motifs. This family contains coronavirus (CoV) non-structural protein 13 (Nsp13) helicase, including those from highly pathogenic human betaCoVs such as Severe Acute Respiratory Syndrome coronavirus (SARS) and SARS-CoV-2 (also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus). Nsp13 helicase is a component of the viral RNA synthesis replication and transcription complex (RTC). SARS-Nsp13 is strongly inhibited by natural flavonoids, myricetin and scutellarein, and is emerging as a target for development of anti-SARS medications. It contains an N-terminal Cys/His rich zinc-binding domain (CH/ZBD), a stalk domain, a 1B regulatory domain, and an SF1 helicase core that carries a DEAD-box helicase domain. Nsp13 belongs to the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region. Pssm-ID: 438713 [Multi-domain] Cd Length: 202 Bit Score: 420.27 E-value: 1.49e-134
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| deltaCoV_Nsp13-helicase | cd21721 | helicase domain of deltacoronavirus non-structural protein 13; This model represents the ... |
5589-5911 | 9.39e-130 | |||||||||||||
helicase domain of deltacoronavirus non-structural protein 13; This model represents the helicase domain of non-structural protein 13 (Nsp13) from deltacoronavirus, including Bulbul coronavirus (CoV) HKU11 and Common moorhen CoV HKU21. Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. CoV Nsp13 is a member of the helicase superfamily 1 (SF1); SF1 and SF2 helicases do not form toroidal structures, while SF3-6 helicases do. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It is a multidomain protein containing a Cys/His rich zinc-binding domain (CH/ZBD), a stalk domain, a 1B domain involved in nucleic acid substrate binding, and a SF1 helicase core. Pssm-ID: 409654 [Multi-domain] Cd Length: 342 Bit Score: 412.78 E-value: 9.39e-130
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| deltaCoV_Nsp14 | cd21657 | nonstructural protein 14 of deltacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus ... |
5927-6325 | 7.21e-128 | |||||||||||||
nonstructural protein 14 of deltacoronavirus; Nonstructural protein 14 (Nsp14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain. ExoN is important for proofreading and therefore, the prevention of lethal mutations. The association of Nsp14 with Nsp10 stimulates its ExoN activity; the 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. The Nsp10/Nsp14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. Nsp14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or Nsp14 has been found to interfere with protein translation of cellular mRNAs. Pssm-ID: 394956 Cd Length: 508 Bit Score: 414.64 E-value: 7.21e-128
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| ps-ssRNAv_Nidovirales_RdRp | cd23168 | catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the order Nidovirales of ... |
4927-5281 | 1.37e-127 | |||||||||||||
catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the order Nidovirales of positive-sense single-stranded RNA [(+)ssRNA] viruses; This family contains the catalytic core domain of RdRP of Nidovirales, an order of enveloped, (+)ssRNA viruses which infect vertebrates and invertebrates. Host organisms include mammals, birds, reptiles, amphibians, fish, arthropods, mollusks, and helminths. The order Nidovirales currently comprises 88 formally recognized virus species of (+)ssRNA viruses which are classified into nine virus families: Abyssoviridae, Arteriviridae, Coronaviridae, Euroniviridae, Medioniviridae, Mesoniviridae, Mononiviridae, Roniviridae, and Tobaniviridae. Based on the genome size, the members of the order Nidovirales can be divided into two groups, large and small nidoviruses. The genomes of the large nidoviruses are well over 25 kb in length with size differences in the 5 kb range. Planarian secretory cell nidovirus (PSCNV), only member of the Mononiviridae family, has the largest known non-segmented RNA genome of 41.1 kb; its host is the planarian flatworm. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. Pssm-ID: 438018 [Multi-domain] Cd Length: 310 Bit Score: 405.21 E-value: 1.37e-127
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| CoV_peptidase | pfam08715 | Coronavirus papain-like peptidase; This entry contains coronavirus cysteine endopeptidases ... |
1564-1882 | 2.54e-127 | |||||||||||||
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: 404.75 E-value: 2.54e-127
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| CoV_NSP4_N | pfam19217 | Coronavirus replicase NSP4, N-terminal; This is the N-terminal domain of the coronavirus ... |
2788-3142 | 3.87e-120 | |||||||||||||
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: 385.47 E-value: 3.87e-120
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| CoV_Methyltr_2 | pfam06460 | Coronavirus 2'-O-methyltransferase; This domain covers the NSP16 region of the coronavirus ... |
6797-7092 | 5.21e-119 | |||||||||||||
Coronavirus 2'-O-methyltransferase; This domain covers the NSP16 region of the coronavirus polyprotein. The SARS-CoV RNA cap SAM-dependent (nucleoside-2'-O-)-methyltransferase (2'-O-MTase) is a heterodimer comprising SARS-CoV nsp10 and nsp16. When bound to nsp10, nsp16 is active as a type-0 RNA cap-dependent 2'-O-MTase, ie., active only when the cap guanine is methylated at its N7 position. Nsp10 binds to nsp16 through an activation surface area in nsp10, and the resulting complex exhibits RNA cap (nucleoside-2'-O)-methyltransferase activity. Nsp10 is a double zinc finger protein together with nsp4, nsp5, nsp12, nsp14, and nsp16, nsp10 has been found to be essential in the assembly of a functional replication/transcription complex. Nsp16 adopts a typical fold of the S-adenosylmethionine-dependent methyltransferase (SAM) family as defined initially for the catechol O-MTase but it lacks several elements of the canonical MTase fold, such as helices B and C. The nsp16 topology matches those of dengue virus NS5 N-terminal domain and of vaccinia virus VP39 MTases. Pssm-ID: 461919 Cd Length: 296 Bit Score: 379.90 E-value: 5.21e-119
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| CoV_PLPro | cd21688 | Coronavirus (CoV) papain-like protease (PLPro); This model represents the papain-like protease ... |
1567-1868 | 1.20e-114 | |||||||||||||
Coronavirus (CoV) papain-like protease (PLPro); This model represents the papain-like protease (PLPro) found in non-structural protein 3 (Nsp3) of alpha-, beta-, gamma-, and deltacoronavirus, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. PLPro is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. PLPro, which belongs to the MEROPS peptidase C16 family, participates in the proteolytic processing of the N-terminal region of the replicase polyprotein; it can cleave Nsp1|Nsp2, Nsp2|Nsp3, and Nsp3|Nsp4 sites and its activity is dependent on zinc. Besides cleaving the polyproteins, PLPro also possesses a related enzymatic activity to promote virus replication: deubiquitinating (DUB) and de-ISGylating activities. Both, ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15), are involved in preventing viral infection; coronaviruses utilize Ubl-conjugating pathways to counter the pro-inflammatory properties of Ubl-conjugated host proteins via the action of PLPro, which processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. The Nsp3 PLPro domain in many of these CoVs has also been shown to antagonize host innate immune induction of type I interferon by interacting with IRF3 and blocking its activation. Pssm-ID: 409647 Cd Length: 299 Bit Score: 367.58 E-value: 1.20e-114
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| TM_Y_MHV-like_Nsp3_C | cd21714 | C-terminus of non-structural protein 3, including transmembrane and Y domains, from murine ... |
2255-2762 | 1.68e-113 | |||||||||||||
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: 374.86 E-value: 1.68e-113
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| CoV_Nsp6 | cd21526 | coronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell ... |
3575-3856 | 3.85e-112 | |||||||||||||
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: 359.92 E-value: 3.85e-112
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| CoV_NSP8 | pfam08717 | Coronavirus replicase NSP8; Viral NSP8 (non structural protein 8) forms a hexadecameric ... |
3940-4136 | 4.24e-111 | |||||||||||||
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: 353.00 E-value: 4.24e-111
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| betaCoV_Nsp8 | cd21831 | betacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ... |
3943-4137 | 1.30e-108 | |||||||||||||
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: 345.62 E-value: 1.30e-108
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| alphaCoV_Nsp5_Mpro | cd21665 | alphacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ... |
3266-3565 | 2.22e-108 | |||||||||||||
alphacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in alphacoronaviruses. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs. Pssm-ID: 394886 Cd Length: 296 Bit Score: 349.67 E-value: 2.22e-108
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| CoV_Nsp8 | cd21816 | Coronavirus non-structural protein 8; This model represents the non-structural protein 8 (Nsp8) ... |
3943-4137 | 2.60e-101 | |||||||||||||
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: 324.86 E-value: 2.60e-101
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| capping_2-OMTase_betaCoV_Nsp16 | cd23528 | Cap-0 specific (nucleoside-2'-O-)-methyltransferase of betacoronavirus, also called ... |
6824-6962 | 1.19e-94 | |||||||||||||
Cap-0 specific (nucleoside-2'-O-)-methyltransferase of betacoronavirus, also called non-structural protein 16; Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) catalyzes the methylation of Cap-0 (m7GpppNp) at the 2'-hydroxyl of the ribose of the first nucleotide, using S-adenosyl-L-methionine (AdoMet) as the methyl donor. This reaction is the fourth and last step in mRNA capping, the creation of the stabilizing five-prime cap (5' cap) on mRNA. The betacoronavirus (betaCoV) 2'OMTase activity is located in the non-structural protein 16 (Nsp16). 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. Nsp16 requires Nsp10 to bind both m7GpppA-RNA substrate and SAM cofactor; the structure suggests that Nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of Nsp16. Pssm-ID: 467740 Cd Length: 216 Bit Score: 306.62 E-value: 1.19e-94
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| gammaCoV_Nsp5_Mpro | cd21667 | gammacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ... |
3265-3569 | 5.71e-86 | |||||||||||||
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: 285.53 E-value: 5.71e-86
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| alphaCoV_Nsp8 | cd21830 | alphacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ... |
3940-4137 | 1.29e-81 | |||||||||||||
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: 268.45 E-value: 1.29e-81
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| alpha_betaCoV_Nsp10 | cd21901 | alphacoronavirus and betacoronavirus non-structural protein 10; This model represents the ... |
4251-4381 | 8.40e-81 | |||||||||||||
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: 263.37 E-value: 8.40e-81
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| CoV_Nsp10 | cd21872 | coronavirus non-structural protein 10; This model represents the non-structural protein 10 ... |
4251-4381 | 1.23e-80 | |||||||||||||
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: 262.79 E-value: 1.23e-80
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| SARS-CoV-like_Nsp1_N | cd21796 | N-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related ... |
13-127 | 1.29e-77 | |||||||||||||
N-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the N-terminal domain of non-structural protein 1 (Nsp1) from betacoronaviruses in the sarbecovirus subgenus (B lineage), including highly pathogenic coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). 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: 439285 Cd Length: 115 Bit Score: 253.66 E-value: 1.29e-77
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| TM_Y_alphaCoV_Nsp3_C | cd21712 | C-terminus of alphacoronavirus non-structural protein 3, including transmembrane and Y domains; ... |
2232-2762 | 7.24e-76 | |||||||||||||
C-terminus of alphacoronavirus non-structural protein 3, including transmembrane and Y domains; This model represents the C-terminus of non-structural protein 3 (Nsp3) from alphacoronavirus, including Porcine epidemic diarrhea virus and Human coronavirus 229E, among others. This conserved C-terminus includes two transmembrane (TM) regions TM1 and TM2, an ectodomain (3Ecto) between the TM1 and TM2 that is glycosylated and located on the lumenal side of the ER, an amphiphatic region (AH1) that is not membrane-spanning, and a large Y domain of approximately 370 residues. Nsp3 is a large multi-functional multi-domain protein that is an essential component of the replication/transcription complex (RTC), which carries out RNA synthesis, RNA processing, and interference with the host cell innate immune system. In the related betacoronaviruses, Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and murine hepatitis virus (MHV), the TM1, 3Ecto and TM2 domains are important for the papain-like protease (PL2pro) domain to process Nsp3-Nsp4 cleavage. It has also been shown that the interaction of 3Ecto with the lumenal loop of Nsp4 is essential for ER rearrangements in cells infected with SARS-CoV or MHV. The Y domain, located at the cytosolic side of the ER, consists of the Y1 and CoV-Y subdomains, which are conserved in nidovirus and coronavirus, respectively. Functional information about the Y domain is limited; it has been shown that Nsp3 binding to Nsp4 is less efficient without the Y domain. Pssm-ID: 409660 Cd Length: 501 Bit Score: 263.72 E-value: 7.24e-76
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| CoV_NSP10 | pfam09401 | Coronavirus RNA synthesis protein NSP10; Non-structural protein 10 (NSP10) is involved in RNA ... |
4262-4381 | 2.68e-72 | |||||||||||||
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: 238.49 E-value: 2.68e-72
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| capping_2-OMTase_CoV_Nsp16 | cd23526 | Cap-0 specific (nucleoside-2'-O-)-methyltransferase of Coronavirus, also called non-structural ... |
6838-6962 | 2.06e-71 | |||||||||||||
Cap-0 specific (nucleoside-2'-O-)-methyltransferase of Coronavirus, also called non-structural protein 16; Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) catalyzes the methylation of Cap-0 (m7GpppNp) at the 2'-hydroxyl of the ribose of the first nucleotide, using S-adenosyl-L-methionine (AdoMet) as the methyl donor. This reaction is the fourth and last step in mRNA capping, the creation of the stabilizing five-prime cap (5' cap) on mRNA. Coronavirus (CoV) 2'OMTase activity is located in the non-structural protein 16 (Nsp16). 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. Nsp16 requires Nsp10 to bind both m7GpppA-RNA substrate and SAM cofactor; the structure suggests that Nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of Nsp16. Pssm-ID: 467738 Cd Length: 191 Bit Score: 238.90 E-value: 2.06e-71
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| SARS-CoV-like_Nsp3_NAB | cd21822 | nucleic acid binding domain of non-structural protein 3 from Severe acute respiratory ... |
1913-2019 | 1.03e-69 | |||||||||||||
nucleic acid binding domain of non-structural protein 3 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the nucleic acid binding (NAB) domain of non-structural protein 3 (Nsp3) from betacoronavirus in the sarbecovirus subgenus (B lineage) and hibecovirus subgenus, including highly pathogenic human coronaviruses (CoVs) such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). The NAB domain represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. NAB is a cytoplasmic domain located between the papain-like protease (PLPro) and betacoronavirus-specific marker (betaSM) domains of CoV Nsp3. 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. The NAB domain both binds ssRNA and unwinds dsDNA. It prefers to bind ssRNA containing repeats of three consecutive guanines. A group of residues that form a positively charged patch on the protein surface of SARS-CoV Nsp3 NAB serves as the binding site of nucleic acids. This site is conserved in the NAB of Nsp3 from betacoronavirus in the B lineage. Pssm-ID: 409348 Cd Length: 107 Bit Score: 230.50 E-value: 1.03e-69
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| SARS-CoV-like_Nsp3_betaSM | cd21814 | betacoronavirus-specific marker of non-structural protein 3 from Severe acute respiratory ... |
2044-2159 | 4.77e-69 | |||||||||||||
betacoronavirus-specific marker of non-structural protein 3 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the betacoronavirus-specific marker (betaSM), also called group 2-specific marker (G2M), 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). The betaSM/G2M is located C-terminal to the nucleic acid-binding (NAB) domain. This region is absent in alpha- and deltacoronavirus Nsp3; there is a gammacoronavirus-specific marker (gammaSM) at this position in gammacoronavirus Nsp3. 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. Little is known about the betaSM/G2M domain; it is predicted to be non-enzymatic and may be an intrinsically disordered region. The betaSM/G2M domain is part of the predicted PLnc domain (made up of 385 amino acids) of SARS-CoV Nsp3 that may function as a replication/transcription scaffold, with interactions to Nsp5, Nsp12, Nsp13, Nsp14, and Nsp16. Pssm-ID: 409629 Cd Length: 116 Bit Score: 228.99 E-value: 4.77e-69
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| bCoV_SUD_M | pfam11633 | Betacoronavirus single-stranded poly(A) binding domain; This domain identifies non-structural ... |
1368-1493 | 6.90e-67 | |||||||||||||
Betacoronavirus single-stranded poly(A) binding domain; This domain identifies non-structural protein NSP3, the product of ORF1a in group 2 coronavirus. It is found in human SARS coronavirus polyprotein 1a and 1ab, and in related coronavirus polyproteins. NSP3 binds to viral RNA, nucleocapsid protein, as well as other viral proteins, and participates in polyprotein processing. The domain exhibits a macrodomain fold containing the nsp3 residues 528 to 648, with a flexibly extended N-terminal tail from residues 513 to 527 and a C-terminal flexible tail of residues 649 to 651. SUD-M(527-651) binds single-stranded poly(A); the contact area with this RNA on the protein surface, and the electrophoretic mobility shift assays confirm that SUD-M has higher affinity for purine bases than for pyrimidine bases. Pssm-ID: 431970 Cd Length: 126 Bit Score: 223.47 E-value: 6.90e-67
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| capping_2-OMTase_alphaCoV_Nsp16 | cd23527 | Cap-0 specific (nucleoside-2'-O-)-methyltransferase of alphacoronavirus, also called ... |
6838-6962 | 7.95e-66 | |||||||||||||
Cap-0 specific (nucleoside-2'-O-)-methyltransferase of alphacoronavirus, also called non-structural protein 16; Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) catalyzes the methylation of Cap-0 (m7GpppNp) at the 2'-hydroxyl of the ribose of the first nucleotide, using S-adenosyl-L-methionine (AdoMet) as the methyl donor. This reaction is the fourth and last step in mRNA capping, the creation of the stabilizing five-prime cap (5' cap) on mRNA. The alphacoronavirus (alphaCoV) 2'OMTase activity is located in the non-structural protein 16 (Nsp16). 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. Nsp16 requires Nsp10 to bind both m7GpppA-RNA substrate and SAM cofactor; the structure suggests that Nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of Nsp16. Pssm-ID: 467739 Cd Length: 193 Bit Score: 223.06 E-value: 7.95e-66
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| Macro_cv_SUD-N_Nsp3-like | cd21562 | SUD-N macrodomain (or Mac2 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural ... |
1233-1358 | 1.55e-65 | |||||||||||||
SUD-N macrodomain (or Mac2 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural protein 3 and related macrodomains; This subfamily includes the macrodomain referred to as SUD-N (N-terminal subdomain) of the SARS-unique domain (SUD) which binds G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). It is found in the non-structural protein 3 (Nsp3) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and highly related coronaviruses. SUD consists of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. Among these, SUD-N and SUD-M are macrodomains: the SUD-M domain (not represented in this subfamily) is a related macrodomain which also binds G-quadruplexes. SUD-N (also called Mac2) is specific to the Nsp3 of SARS and betacoronaviruses of the sarbecovirus subgenera (B lineage), while SUD-M (also called Mac3) is present in most Nsp3 proteins except the Nsp3 from betacoronaviruses of the embecovirus subgenera (A lineage). SUD-C adopts a frataxin-like fold, has structural similarity to DNA-binding domains of DNA-modifying enzymes, binds single-stranded RNA, and regulates the RNA binding behavior of the SUD-M macrodomain. SARS-CoV Nsp3 contains a third macrodomain (the X-domain or Mac1) which is also not represented in this subfamily. The X-domain may function as a module binding poly(ADP-ribose); however, SUD-N and SUD-M do not bind ADP-ribose, as the triple glycine sequence involved in its binding is not conserved in these. Pssm-ID: 394883 Cd Length: 126 Bit Score: 219.32 E-value: 1.55e-65
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| deltaCoV_Nsp5_Mpro | cd21668 | deltacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ... |
3263-3562 | 1.09e-64 | |||||||||||||
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: 224.31 E-value: 1.09e-64
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| ZBD_cv_Nsp13-like | cd21401 | Cys/His rich zinc-binding domain (CH/ZBD) of coronavirus SARS NSP13 helicase and related ... |
5322-5416 | 9.61e-61 | |||||||||||||
Cys/His rich zinc-binding domain (CH/ZBD) of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. This coronavirus family includes Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) non-structural protein 13 (SARS-Nsp13) and belongs to helicase superfamily 1 (SF1) and to a family of nindoviral replication helicases. SARS-Nsp13 has an N-terminal CH/ZBD, a stalk domain, a 1B regulatory domain, and SF1 helicase core. The CH/ZBD has 3 zinc-finger (ZnF1-3) motifs. SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). The SARS-Nsp13 CH/ZBD is indispensable for helicase activity and interacts with SARS-Nsp12, the RNA-dependent RNA polymerase (RdRp). Structural studies of a stable SARS-CoV-2 RTC which included two molecules of Nsp13, the RdRp holoenzyme (Nsp7, two molecules of Nsp8, Nsp12), and an RNA template product, show that one Nsp13 CH/ZBD domain interacts with Nsp12, and both Nsp13-CH/ZBD domains interact with the Nsp8. This stable SARS-CoV-2 RTC suggests that the Nsp13 helicase may drive RTC backtracking, affecting proofreading and template switching. Pssm-ID: 439168 Cd Length: 95 Bit Score: 204.54 E-value: 9.61e-61
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| CoV_NSP6 | pfam19213 | Coronavirus replicase NSP6; This entry represents proteins found in Coronaviruses and includes ... |
3598-3856 | 2.77e-58 | |||||||||||||
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: 204.02 E-value: 2.77e-58
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| betaCoV_Nsp9 | cd21898 | betacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ... |
4138-4250 | 1.29e-57 | |||||||||||||
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: 196.08 E-value: 1.29e-57
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| M_alpha_beta_cv_Nsp15-like | cd21167 | middle domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related ... |
6514-6645 | 5.02e-56 | |||||||||||||
middle domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. Coronavirus Nsp15 NendoUs have an N-terminal domain, a middle (M) domain and a C-terminal catalytic (NendoU) domain. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. This middle domain harbors residues involved in hexamer formation and in trimer stability. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of the other coronaviruses; it has been shown to exist as a dimer and a monomer in solution. Pssm-ID: 439161 Cd Length: 127 Bit Score: 192.16 E-value: 5.02e-56
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| CoV_Nsp9 | cd21881 | coronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) ... |
4138-4250 | 4.04e-55 | |||||||||||||
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: 188.88 E-value: 4.04e-55
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| CoV_NSP9 | pfam08710 | Coronavirus replicase NSP9; Nsp9 is a single-stranded RNA-binding viral protein involved in ... |
4138-4250 | 8.66e-55 | |||||||||||||
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: 188.07 E-value: 8.66e-55
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| Macro_cv_SUD-M_Nsp3-like | cd21563 | SUD-M macrodomain (or Mac3 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural ... |
1369-1489 | 9.93e-54 | |||||||||||||
SUD-M macrodomain (or Mac3 domain) of the SARS Unique Domain (SUD) of SARS-CoV non-structural protein 3 and related macrodomains; This subfamily includes the macrodomain referred to as SUD-M (middle SUD subdomain) of the SARS-unique domain (SUD) which binds G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). It is found in non-structural protein 3 (Nsp3) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and related coronaviruses. SUD consists of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. Among these, SUD-N and SUD-M are macrodomains: The SUD-N domain (not represented in this subfamily) is a related macrodomain which also binds G-quadruplexes. While SUD-N (also called Mac2) is specific to the Nsp3 of SARS and betacoronaviruses of the sarbecovirus subgenera (B lineage), SUD-M (also called Mac3) is present in most Nsp3 proteins except the Nsp3 from betacoronaviruses of the embecovirus subgenera (A lineage). SUD-M, despite its name, is not specific to SARS. SUD-C adopts a frataxin-like fold, has structural similarity to DNA-binding domains of DNA-modifying enzymes, binds single-stranded RNA, and regulates the RNA binding behavior of the SUD-M macrodomain. SARS-CoV Nsp3 contains a third macrodomain (the X-domain or Mac1) which is also not represented in this subfamily. The X-domain may function as a module binding poly(ADP-ribose); however, SUD-N and SUD-M do not bind ADP-ribose, as the triple glycine sequence involved in its binding is not conserved in these. Pssm-ID: 394884 Cd Length: 120 Bit Score: 185.19 E-value: 9.93e-54
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| bCoV_NAB | pfam16251 | Betacoronavirus nucleic acid-binding (NAB); This is the nucleic acid-binding domain (NAB) from ... |
1907-2019 | 1.07e-52 | |||||||||||||
Betacoronavirus nucleic acid-binding (NAB); This is the nucleic acid-binding domain (NAB) from the multidomain nonstructural protein NSP3, and described as NSP3e domain. NSP3 is part of Orf1a polyproteins in SARS-CoV. It is an essential component of the replication/transcription complex. The global domain of the NAB represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands and a group of residues form a positively charged patch on the protein surface as the binding site responsible for binding affinity for nucleic acids. When binding to ssRNA, the NAB prefers sequences with repeats of three consecutive Gs, such as (GGGA)5 and (GGGA)2. A positively charged surface patch (Lys75, Lys76, Lys99, and Arg106) is involved in RNA binding. Pssm-ID: 406621 Cd Length: 129 Bit Score: 182.75 E-value: 1.07e-52
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| capping_2-OMTase_gammaCoV_Nsp16 | cd23529 | Cap-0 specific (nucleoside-2'-O-)-methyltransferase of gammacoronavirus, also called ... |
6838-6961 | 4.18e-50 | |||||||||||||
Cap-0 specific (nucleoside-2'-O-)-methyltransferase of gammacoronavirus, also called non-structural protein 16; Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) catalyzes the methylation of Cap-0 (m7GpppNp) at the 2'-hydroxyl of the ribose of the first nucleotide, using S-adenosyl-L-methionine (AdoMet) as the methyl donor. This reaction is the fourth and last step in mRNA capping, the creation of the stabilizing five-prime cap (5' cap) on mRNA. The gammacoronavirus (gammaCoV) 2'OMTase activity is located in the non-structural protein 16 (Nsp16). 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. Nsp16 requires Nsp10 to bind both m7GpppA-RNA substrate and SAM cofactor; the structure suggests that Nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of Nsp16. Pssm-ID: 467741 Cd Length: 196 Bit Score: 178.15 E-value: 4.18e-50
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| bCoV_NSP3_N | pfam12379 | Betacoronavirus replicase NSP3, N-terminal; This domain family corresponds to the N-terminal ... |
880-1050 | 8.20e-50 | |||||||||||||
Betacoronavirus replicase NSP3, N-terminal; This domain family corresponds to the N-terminal domain of NSP3 (non-structural protein 3, also known as nsp3) found in Betacoronavirus, which is encoded on the replicase polyprotein. This family includes the NSP3a domain which has the ubiquitin-like 1 (UB1) and glutamic acid-rich acidic (AC) hypervariable domains. NSP3a interacts with numerous other proteins involved in replication and transcription and may serve as a scaffolding protein for these processes. The N-terminal NSP3a domain interacts with N (nucleocapsid) protein to colocalize genomic RNA with the nascent replicase-transcriptase complex at the earliest stages of infection, essential for the virus. The C-terminal Glu-rich subdomain is best described as a flexible tail attached to the globular UB1 subdomain. The family is found in association with pfam08716, pfam01661, pfam05409, pfam06471, pfam08717, pfam06478, pfam09401, pfam06460, pfam08715, pfam08710. Pssm-ID: 432517 Cd Length: 149 Bit Score: 175.37 E-value: 8.20e-50
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| gammaCoV_Nsp10 | cd21902 | gammacoronavirus non-structural protein 10; This model represents the non-structural protein ... |
4252-4381 | 8.72e-50 | |||||||||||||
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: 174.70 E-value: 8.72e-50
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| gammaCoV_Nsp8 | cd21832 | gammacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ... |
3940-4129 | 2.31e-49 | |||||||||||||
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: 176.68 E-value: 2.31e-49
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| alphaCoV-Nsp6 | cd21558 | alphacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ... |
3554-3856 | 4.90e-49 | |||||||||||||
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: 178.93 E-value: 4.90e-49
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| Macro_X_Nsp3-like | cd21557 | X-domain (or Mac1 domain) of viral non-structural protein 3 and related macrodomains; The ... |
1054-1177 | 1.63e-48 | |||||||||||||
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: 170.81 E-value: 1.63e-48
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| M_cv-Nsp15-like | cd21165 | middle domain of coronavirus Nonstructural protein 15 (Nsp15), and related proteins; Nidovirus ... |
6514-6645 | 5.13e-48 | |||||||||||||
middle domain of coronavirus Nonstructural protein 15 (Nsp15), and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. Coronavirus Nsp15 NendoUs have an N-terminal domain, a middle (M) domain and a C-terminal catalytic (NendoU) domain. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of the other coronavirus members; it has been shown to exist as a dimer and a monomer in solution. Pssm-ID: 439160 Cd Length: 126 Bit Score: 169.38 E-value: 5.13e-48
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| 1B_cv_Nsp13-like | cd21409 | 1B domain of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze ... |
5471-5549 | 2.03e-47 | |||||||||||||
1B domain of coronavirus SARS NSP13 helicase and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. Members of this subfamily belong to helicase superfamily 1 (SF1) and include coronavirus helicases such as Severe Acute Respiratory Syndrome coronavirus (SARS) non-structural protein 13 (SARS-Nsp13). SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). Structural studies of a stable RTC which included the RNA-dependent RNA polymerase holoenzyme (Nsp7, two molecules of Nsp82, Nsp12), two molecules of Nsp13 helicase accessory factor and an RNA template product suggests that the Nsp13 helicase may drive RTC backtracking, affecting proofreading and template switching. SARS-Nsp13 is a multidomain protein; its other domains include an N-terminal Cys/His rich zinc-binding domain (CH/ZBD) and a SF1 helicase core. The 1B domain is involved in nucleic acid substrate binding; the 1B domain of the related Equine arteritis virus (EAV) Nsp10 undergoes large conformational change upon substrate binding, and together with the 1A and 2A domains of the helicase core form a channel that accommodates the single stranded nucleic acids. Pssm-ID: 394817 Cd Length: 79 Bit Score: 165.60 E-value: 2.03e-47
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| CoV_NSP4_C | pfam16348 | Coronavirus replicase NSP4, C-terminal; This is the C-terminal domain of the coronavirus ... |
3169-3261 | 1.94e-43 | |||||||||||||
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: 154.99 E-value: 1.94e-43
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| NendoU_XendoU-like | cd21144 | Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural ... |
6682-6792 | 2.75e-43 | |||||||||||||
Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural protein 15 (Nsp15), arterivirus Nsp11, torovirus endoribonuclease, Xenopus laevis endoribonuclease XendoU, and related proteins; Nidovirus endoribonucleases (NendoUs) and eukaryotic Xenopus laevis-like endoribonucleases (XendoUs) are uridylate-specific endoribonucleases which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. XendoU is involved in the processing of intron-encoded box C/D U16 small, nucleolar RNA. Except for turkey coronavirus (TCoV) Nsp15, Mn2+ is generally essential for the catalytic activity of coronavirus Nsp15. Mn2+ is dispensable, and to some extent inhibits the activity of arterivirus (Porcine Reproductive and Respiratory Syndrome virus) PRRSV Nsp11. XendoU also requires Mn2+. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and murine hepatitis virus (MHV) forms a functional hexamer while Porcine DeltaCoronavirus (PDCoV) Nsp15 has been shown to exist as a dimer and a monomer in solution. Nsp11 from the arterivirus PRRSV is a dimer. Pssm-ID: 439156 Cd Length: 113 Bit Score: 155.47 E-value: 2.75e-43
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| NendoU_cv_Nsp15-like | cd21161 | Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural ... |
6682-6793 | 3.69e-43 | |||||||||||||
Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural Protein 15 (Nsp15) and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. Except for turkey coronavirus (TCoV) Nsp15, Mn2+ is generally essential for the catalytic activity of coronavirus Nsp15. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and murine hepatitis virus (MHV) form a functional hexamer while Porcine DeltaCoronavirus (PDCoV) Nsp15 has been shown to exist as a dimer and a monomer in solution. NendoUs are distantly related to Xenopus laevis Mn(2+)-dependent uridylate-specific endoribonuclease (XendoU) which is involved in the processing of intron-encoded box C/D U16 small, nucleolar RNA. Pssm-ID: 439158 Cd Length: 151 Bit Score: 156.27 E-value: 3.69e-43
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| NendoU_nv | cd21158 | Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural ... |
6682-6793 | 8.98e-42 | |||||||||||||
Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural protein 15 (Nsp15), arterivirus Nsp11, torovirus endoribonuclease, and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. This family also includes torovirus NendoUs. Except for turkey coronavirus (TCoV) Nsp15, Mn2+ is generally essential for the catalytic activity of coronavirus Nsp15. Mn2+ is dispensable, and to some extent inhibits the activity of arterivirus (Porcine Reproductive and Respiratory Syndrome virus) PRRSV Nsp11. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and murine hepatitis virus (MHV) form a functional hexamer while Porcine DeltaCoronavirus (PDCoV) Nsp15 has been shown to exist as a dimer and monomer in solution. Nsp11 from the arterivirus PRRSV is a dimer. NendoUs are distantly related to Xenopus laevis Mn(2+)-dependent uridylate-specific endoribonuclease (XendoU) which is involved in the processing of intron-encoded box C/D U16 small, nucleolar RNA. Pssm-ID: 439157 Cd Length: 151 Bit Score: 152.41 E-value: 8.98e-42
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| betaCoV_Nsp7 | cd21827 | betacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ... |
3857-3939 | 2.72e-41 | |||||||||||||
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: 148.36 E-value: 2.72e-41
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| Macro_cv_SUD-N-M_Nsp3-like | cd21556 | SUD-N and SUD-M macrodomains of the SARS-Unique Domain (SUD) of SARS-CoV non-structural ... |
1369-1477 | 1.42e-40 | |||||||||||||
SUD-N and SUD-M macrodomains of the SARS-Unique Domain (SUD) of SARS-CoV non-structural protein 3 and related macrodomains; This family includes two macrodomains referred to as the SUD-N (N-terminal subdomain) and SUD-M (middle SUD subdomain) of the SARS-unique domain (SUD) which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). It is found in non-structural protein 3 (Nsp3) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and highly related coronaviruses. SUD consists of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. Among these, SUD-N and SUD-M are macrodomains. SUD-N (also called Mac2) is specific to the Nsp3 of SARS and betacoronaviruses of the sarbecovirus subgenera (B lineage), while SUD-M (also called Mac3) is present in most Nsp3 proteins except the Nsp3 from betacoronaviruses of the embecovirus subgenera (A lineage). SUD-C adopts a frataxin-like fold, has structural similarity to DNA-binding domains of DNA-modifying enzymes, binds single-stranded RNA, and regulates the RNA binding behavior of the SUD-M macrodomain. SARS-CoV Nsp3 contains a third macrodomain (the X-domain or Mac1) which is not included in this family. The X-domain may function as a module binding poly(ADP-ribose); however, SUD-N and SUD-M do not bind ADP-ribose, as the triple glycine sequence involved in its binding is not conserved in these. Pssm-ID: 438956 Cd Length: 108 Bit Score: 147.43 E-value: 1.42e-40
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| bCoV_NSP1 | pfam11501 | Betacoronavirus replicase NSP1; This entry represents the non structural protein NSP1 from ... |
9-144 | 1.78e-39 | |||||||||||||
Betacoronavirus replicase NSP1; This entry represents the non structural protein NSP1 from Betacoronavirus NSP1 is the N-terminal cleavage product from the viral replicase that mediates RNA replication and processing. Structurally, the protein consists of a mixed parallel/antiparallel 6-stranded beta barrel with an alpha helix covering one end of the barrel and another helix alongside the barrel. NSP1 binds to the 40S ribosomal subunit and inhibits translation, and it also induces a template-dependent endonucleolytic cleavage of host mRNAs. NSP1 also suppresses the host innate immune functions by inhibiting type I interferon expression and host antiviral signalling pathways. Pssm-ID: 431911 Cd Length: 138 Bit Score: 145.22 E-value: 1.78e-39
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| betaCoV_Nsp3_NAB | cd21795 | nucleic acid binding domain of betacoronavirus non-structural protein 3; This model represents ... |
1913-2019 | 3.63e-39 | |||||||||||||
nucleic acid binding domain of betacoronavirus non-structural protein 3; This model represents the nucleic acid binding (NAB) domain of non-structural protein 3 (Nsp3) from betacoronavirus including highly pathogenic human coronaviruses (CoVs) such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). The NAB domain represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. NAB is a cytoplasmic domain located between the papain-like protease (PLPro) and betacoronavirus-specific marker (betaSM) domains of CoV Nsp3. 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. The NAB domain both binds ssRNA and unwinds dsDNA. It prefers to bind ssRNA containing repeats of three consecutive guanines. A group of residues that form a positively charged patch on the protein surface of SARS-CoV Nsp3 NAB serves as the binding site of nucleic acids. This site is conserved in the NAB of Nsp3 from betacoronavirus in the sarbecovirus subgenus (B lineage), but may not be conserved in the Nsp3 NAB from betacoronaviruses in other lineages. Pssm-ID: 409347 Cd Length: 110 Bit Score: 143.48 E-value: 3.63e-39
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| TM_Y_gammaCoV_Nsp3_C | cd21710 | C-terminus of gammacoronavirus non-structural protein 3, including transmembrane and Y domains; ... |
2281-2758 | 4.74e-39 | |||||||||||||
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: 156.45 E-value: 4.74e-39
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| betaCoV_Nsp1 | cd21876 | non-structural protein 1 from betacoronavirus; This model represents the non-structural ... |
13-127 | 8.77e-39 | |||||||||||||
non-structural protein 1 from betacoronavirus; This model represents the non-structural protein 1 (Nsp1) from betacoronaviruses, including highly pathogenic coronaviruses 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. 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: 409338 Cd Length: 114 Bit Score: 142.55 E-value: 8.77e-39
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| CoV_NSP7 | pfam08716 | Coronavirus replicase NSP7; NSP7 (non structural protein 7) has been implicated in viral RNA ... |
3857-3939 | 1.91e-38 | |||||||||||||
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: 140.28 E-value: 1.91e-38
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| betaCoV_Nsp3_betaSM | cd21727 | betacoronavirus-specific marker of betacoronavirus non-structural protein 3; This model ... |
2044-2159 | 1.20e-37 | |||||||||||||
betacoronavirus-specific marker of betacoronavirus non-structural protein 3; This model represents the betacoronavirus-specific marker (betaSM), also called group 2-specific marker (G2M), of non-structural protein 3 (Nsp3) from betacoronavirus, 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). The betaSM/G2M is located C-terminal to the nucleic acid-binding (NAB) domain. This region is absent in alpha- and deltacoronavirus Nsp3; there is a gammacoronavirus-specific marker (gammaSM) at this position in gammacoronavirus Nsp3. 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. Little is known about the betaSM/G2M domain; it is predicted to be non-enzymatic and may be an intrinsically disordered region. The betaSM/G2M domain is part of the predicted PLnc domain (made up of 385 amino acids) of SARS-CoV Nsp3 that may function as a replication/transcription scaffold, with interactions to Nsp5, Nsp12, Nsp13, Nsp14, and Nsp16. Pssm-ID: 409626 Cd Length: 125 Bit Score: 139.59 E-value: 1.20e-37
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| CoV_Nsp7 | cd21811 | coronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) ... |
3857-3939 | 2.78e-37 | |||||||||||||
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: 136.85 E-value: 2.78e-37
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| SUD_C_SARS-CoV_Nsp3 | cd21525 | C-terminal SARS-Unique Domain (SUD) of non-structural protein 3 (Nsp3) from Severe Acute ... |
1496-1561 | 3.04e-37 | |||||||||||||
C-terminal SARS-Unique Domain (SUD) of non-structural protein 3 (Nsp3) from Severe Acute Respiratory Syndrome coronavirus and related betacoronaviruses in the B lineage; This subfamily contains the SUD-C of Severe Acute Respiratory Syndrome (SARS) coronavirus (CoV) non-structural protein 3 (Nsp3) and other Nsp3s from betacoronaviruses in the sarbecovirus subgenera (B lineage), such as SARS-CoV-2 and related bat CoVs. Non-structural protein 3 (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. Nsp3 of the Severe Acute Respiratory Syndrome (SARS) coronavirus includes a SARS-unique domain (SUD) consisting of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. SUD-N and SUD-M are macro domains which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). The SUD-C domain adopts a frataxin-like fold and has structural similarity to DNA-binding domains of DNA-modifying enzymes. It binds to single-stranded RNA and recognizes purine bases more strongly than pyrimidine bases. SUD-C also regulates the RNA binding behavior of the SUD-M macrodomain. Pssm-ID: 394841 Cd Length: 67 Bit Score: 136.14 E-value: 3.04e-37
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| M_cv_Nsp15-NTD_av_Nsp11-like | cd21163 | middle (M) domain of coronavirus Nonstructural protein 15 (Nsp15) and the N-terminal domain ... |
6514-6645 | 1.99e-36 | |||||||||||||
middle (M) domain of coronavirus Nonstructural protein 15 (Nsp15) and the N-terminal domain (NTD) of arterivirus Nsp11 and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. Coronavirus Nsp15 NendoUs have an N-terminal domain, a middle (M) domain, and a C-terminal catalytic (NendoU) domain. Arterivirus Nsp11 has an N-terminal domain (NTD) and a C-terminal catalytic (NendoU) domain. The NTD of Nsp11 superimposes onto the M-domain of coronavirus Nsp15. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of other coronavirus members; it has been shown to exist as a dimer and a monomer in solution. Nsp11 from the arterivirus PRRSV functions as a dimer. Pssm-ID: 439159 Cd Length: 123 Bit Score: 135.92 E-value: 1.99e-36
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| deltaCoV_Nsp10 | cd21903 | deltacoronavirus non-structural protein 10; This model represents the non-structural protein ... |
4252-4380 | 6.22e-36 | |||||||||||||
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: 134.99 E-value: 6.22e-36
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| Tobaniviridae_RdRp | cd23186 | catalytic core domain of RNA-dependent RNA polymerase (RdRP) in the Tobaniviridae family of ... |
4905-5313 | 1.21e-34 | |||||||||||||
catalytic core domain of RNA-dependent RNA polymerase (RdRP) in the Tobaniviridae family of positive-sense single-stranded RNA [(+)ssRNA] viruses; This group contains the catalytic core domain of RdRp of RNA viruses belonging to the family Tobaniviridae, order Nidovirales. Tobaniviridae RNA viruses infect vertebrates; their host organisms include mammals, fish, and snakes. Member viruses have a viral envelope and (+)ssRNA genome. The genome size of Tobaniviruses ranges from 20 to 32 kilobases. The family is the only member of the suborder Tornidovirineae. The family Tobaniviridae has four subfamilies (Piscanivirinae, Remotovirinae, Remotovirinae, and Torovirinae) and eight genera (Bafinivirus, Oncotshavirus, Bostovirus, Infratovirus, Pregotovirus, Sectovirus, Tiruvirus, and Torovirus). The Tobaniviridae family belongs to the order Nidovirales, which currently comprises 88 formally recognized virus species of (+)ssRNA viruses, which are classified into nine virus families across seven different suborders. The structure of Tobaniviridae RdRp contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. Pssm-ID: 438036 Cd Length: 401 Bit Score: 140.22 E-value: 1.21e-34
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| NTD_alpha_betaCoV_Nsp15-like | cd21171 | N-terminal domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related ... |
6450-6510 | 3.30e-33 | |||||||||||||
N-terminal domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related proteins; Coronavirus (CoV) Nsp15 is a nidovirus endoribonuclease (NendoU). NendoUs are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include CoV Nsp15 and arterivirus Nsp11, both of which may participate in the viral replication process and in the evasion of the host immune system. This small NTD structure, present in coronavirus Nsp15, is missing in Nsp11. CoV Nsp15 has an N-terminal domain, a middle (M) domain, and a C-terminal catalytic (NendoU) domain. Nsp15 from Severe Acute Respiratory Syndrome (SARS)-CoV, human CoV229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. Residues in this N-terminal domain are important for hexamer (dimer of trimers) formation. Pssm-ID: 439163 Cd Length: 61 Bit Score: 124.60 E-value: 3.30e-33
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| CoV_NSP15_C | pfam19215 | Coronavirus replicase NSP15, uridylate-specific endoribonuclease; This entry represents the ... |
6682-6793 | 8.28e-33 | |||||||||||||
Coronavirus replicase NSP15, uridylate-specific endoribonuclease; This entry represents the C-terminal domain of coronavirus non-structural protein 15 (NSP15 or nsp15). NSP15 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. This domain exhibits endoribonuclease activity designated EndoU, highly conserved in all known CoVs and is part of the replicase-transcriptase complex that plays important roles in virus replication and transcription. NSP15 is a Uridylate-specific endoribonuclease that cleaves the 5'-polyuridines from negative-sense viral RNA, termed PUN RNA either upstream or downstream of uridylates, at GUU or GU to produce molecules with 2',3'-cyclic phosphate ends. PUN RNA is a CoV MDA5-dependent pathogen-associated molecular pattern (PAMP). Pssm-ID: 465999 Cd Length: 155 Bit Score: 127.06 E-value: 8.28e-33
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| capping_2-OMTase_Nidovirales | cd20762 | Cap-0 specific (nucleoside-2'-O-)-methyltransferase of nidovirales; Cap-0 specific ... |
6838-6962 | 1.26e-32 | |||||||||||||
Cap-0 specific (nucleoside-2'-O-)-methyltransferase of nidovirales; Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) catalyzes the methylation of Cap-0 (m7GpppNp) at the 2'-hydroxyl of the ribose of the first nucleotide, using S-adenosyl-L-methionine (AdoMet) as the methyl donor. This reaction is the fourth and last step in mRNA capping, the creation of the stabilizing five-prime cap (5' cap) on mRNA. Nidovirales viruses, which comprise a family of ss(+)RNA viruses, cap their mRNAs. For one member, coronavirus, the 2'OMTase activity is located in the non-structural protein 16 (Nsp16). For others, the 2'OMTase activity may be located in replicase polyprotein 1ab. Pssm-ID: 467737 Cd Length: 175 Bit Score: 127.05 E-value: 1.26e-32
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| SARS-CoV-like_Nsp1_C | cd22662 | C-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related ... |
128-180 | 7.76e-32 | |||||||||||||
C-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage; This model represents the C-terminal domain of non-structural protein 1 (Nsp1) from betacoronaviruses in the sarbecovirus subgenus (B lineage), including highly pathogenic coronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV). 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. SARS-CoV Nsp1 enhances virus replication by binding to a stem-loop structure in the 5'-UTR of its genome. When the SARS-CoV-2 5' UTR is bound to the Nsp1 N-terminus, the covalently linked Nsp1 C-terminus cannot bind the 40S ribosome, suggesting a bipartite mechanism whereby SARS-CoV-2 Nsp1 suppresses host but not viral translation. Pssm-ID: 439355 Cd Length: 53 Bit Score: 120.36 E-value: 7.76e-32
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| Ubl1_cv_Nsp3_N-like | cd21467 | first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV ... |
838-924 | 2.77e-31 | |||||||||||||
first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model. Pssm-ID: 394822 Cd Length: 89 Bit Score: 119.98 E-value: 2.77e-31
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| deltaCoV_Nsp8 | cd21833 | deltacoronavirus non-structural protein 8; This model represents the non-structural protein 8 ... |
3940-4129 | 2.11e-30 | |||||||||||||
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: 121.27 E-value: 2.11e-30
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| alphaCoV_Nsp9 | cd21897 | alphacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ... |
4138-4250 | 3.95e-30 | |||||||||||||
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: 117.42 E-value: 3.95e-30
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| ZBD_nv_SF1_Hel-like | cd21399 | Cys/His rich zinc-binding domain (CH/ZBD) of nidovirus helicases including coronavirus Nsp13 ... |
5324-5396 | 4.37e-29 | |||||||||||||
Cys/His rich zinc-binding domain (CH/ZBD) of nidovirus helicases including coronavirus Nsp13 and arterivirus Nsp10, and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. This nidovirus family includes Severe Acute Respiratory Syndrome coronavirus (SARS) non-structural protein 13 (SARS-Nsp13) and equine arteritis virus (EAV) Nsp10 helicase, and belongs to helicase superfamily 1 (SF1). The CH/ZBD has 3 zinc-finger (ZnF1-3) motifs. SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). The SARS-Nsp13 CH/ZBD is indispensable for helicase activity and interacts with SARS-Nsp12, the RNA-dependent RNA polymerase. SARS-Nsp12 can enhance the helicase activity of SARS-Nsp13. SARS-Nsp13 and EAV Nsp10 are multidomain proteins; their other domains include a 1B regulatory domain and a SF1 helicase core. Pssm-ID: 394806 Cd Length: 71 Bit Score: 113.05 E-value: 4.37e-29
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| CoV_NSP15_M | pfam19216 | Coronavirus replicase NSP15, middle domain; This entry represents the non-catalytic middle ... |
6511-6634 | 4.60e-29 | |||||||||||||
Coronavirus replicase NSP15, middle domain; This entry represents the non-catalytic middle domain from coronavirus non-structural protein 15 (NSP15). NSP15 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. This domain is formed by ten beta strands organized into three beta hairpins. Pssm-ID: 466000 Cd Length: 118 Bit Score: 114.74 E-value: 4.60e-29
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| Macro_Af1521_BAL-like | cd02907 | macrodomain, Af1521-like family; Macrodomains are found in a variety of proteins with diverse ... |
1037-1168 | 2.36e-28 | |||||||||||||
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: 114.12 E-value: 2.36e-28
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| CoV_NSP15_N | pfam19219 | Coronavirus replicase NSP15, N-terminal oligomerization; This is the N-terminal domain of the ... |
6450-6510 | 5.40e-28 | |||||||||||||
Coronavirus replicase NSP15, N-terminal oligomerization; This is the N-terminal domain of the coronavirus nonstructural protein 15 (NSP15), which is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. NSP15, is a nidoviral RNA uridylate-specific endoribonuclease (NendoU) carrying C-terminal catalytic domain belonging to the EndoU family. The SARS-CoV-2 NendoU monomers assemble into a double-ring hexamer, generated by a dimer of trimers. The hexamer is stabilized by the interactions of N-terminal oligomerization domain. Pssm-ID: 466003 Cd Length: 61 Bit Score: 109.71 E-value: 5.40e-28
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| bCoV_SUD_C | pfam12124 | Betacoronavirus SUD-C domain; This domain is found in betacoronavirus non-structural protein ... |
1498-1561 | 1.66e-27 | |||||||||||||
Betacoronavirus SUD-C domain; This domain is found in betacoronavirus non-structural protein NSP3, and is about 65 amino acids in length. It was originally thought to exist only in SARS-coronaviruses, and so was termed the SARS-unique domain (SUD), however this has since been shown to be incorrect. The domain is also known as DPUP (domain preceding Ubl2 and PL2pro). NSP3 is the product of ORF1a, proteolytically released from the pp1a/1ab polyprotein. The SUD domain has three globular domains, SUD-N (N-terminal), SUD-M (middle region of SUD), and SUD-C (C-terminal). SUD-C adopts a fold consisting of seven beta-strands arranged in an anti-parallel beta-sheet, and two alpha-helices which are packed against the same side of the beta-sheet. It adopts a frataxin like fold with structural similarities to DNA-binding domains. It has been shown that SUD-C binds to single-stranded RNA and recognizes purine bases more strongly than pyrimidine bases, but these interactions are stabilized in the presence of SUD-M. The function of this domain is not clear but studies of structural homologs of SUD-C suggest that it could be related to metal, adenylate and nucleic acid binding. Pssm-ID: 288939 Cd Length: 66 Bit Score: 108.63 E-value: 1.66e-27
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| capping_2-OMTase_deltaCoV_Nsp16 | cd23530 | Cap-0 specific (nucleoside-2'-O-)-methyltransferase of deltacoronavirus, also called ... |
6838-6962 | 4.26e-27 | |||||||||||||
Cap-0 specific (nucleoside-2'-O-)-methyltransferase of deltacoronavirus, also called non-structural protein 16; Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) catalyzes the methylation of Cap-0 (m7GpppNp) at the 2'-hydroxyl of the ribose of the first nucleotide, using S-adenosyl-L-methionine (AdoMet) as the methyl donor. This reaction is the fourth and last step in mRNA capping, the creation of the stabilizing five-prime cap (5' cap) on mRNA. The deltacoronavirus (deltaCoV) 2'OMTase activity is located in the non-structural protein 16 (Nsp16). 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. Nsp16 requires Nsp10 to bind both m7GpppA-RNA substrate and SAM cofactor; the structure suggests that Nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of Nsp16. Pssm-ID: 467742 Cd Length: 183 Bit Score: 111.80 E-value: 4.26e-27
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| NTD_CoV_Nsp15-like | cd21170 | N-terminal domain of coronavirus Nonstructural protein 15 (Nsp15) and related proteins; ... |
6451-6510 | 2.55e-26 | |||||||||||||
N-terminal domain of coronavirus Nonstructural protein 15 (Nsp15) and related proteins; Coronavirus (CoV) Nsp15 is a nidovirus endoribonuclease (NendoU). NendoUs are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include CoV Nsp15 and arterivirus Nsp11, both of which may participate in the viral replication process and in the evasion of the host immune system. This NTD structure (approximately 60 residues) present in CoV Nsp15, is missing in Nsp11. CoV Nsp15 has an N-terminal domain, a middle (M) domain, and a C-terminal catalytic (NendoU) domain. Nsp15 from Severe Acute Respiratory Syndrome (SARS)-CoV, human CoV 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from the Nsp15 of these alpha- and beta-coronavirus; it has been shown to exist as dimers and monomers in solution, and to function as a dimer. Nsp15 from Turkey CoV (TCoV), a gammaCoV, has been reported to be a homohexamer. Pssm-ID: 439162 Cd Length: 60 Bit Score: 104.78 E-value: 2.55e-26
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| ZBD_UPF1_nv_SF1_Hel-like | cd21343 | Cys/His rich zinc-binding domain (CH/ZBD) of eukaryotic UPF1 helicase, nidovirus SF1 helicases ... |
5325-5396 | 3.61e-26 | |||||||||||||
Cys/His rich zinc-binding domain (CH/ZBD) of eukaryotic UPF1 helicase, nidovirus SF1 helicases including coronavirus Nsp13 and arterivirus Nsp10, and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands, and are classified based on the arrangement of conserved motifs into six superfamilies. Members of this family belong to helicase superfamily 1 (SF1) and include nidoviral helicases such as Severe Acute Respiratory Syndrome coronavirus (SARS) non-structural protein 13 (SARS-Nsp13) and equine arteritis virus (EAV) Nsp10, as well as eukaryotic UPF1 helicase. The CH/ZBD has 3 zinc-finger (ZnF1-3) motifs. UPF1 participates in nonsense-mediated mRNA decay (NMD), a pathway which degrades transcripts with premature termination codons. The CH/ZBD of UPF1 interacts with UPF2, a factor also involved in NMD. SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). The SARS-Nsp13 CH/ZBD is indispensable for helicase activity and interacts with SARS-Nsp12, the RNA-dependent RNA polymerase. SARS-Nsp12 can enhance the helicase activity of SARS-Nsp13. UPF1, SARS-Nsp13 and EAV Nsp10 are multidomain proteins; their other domains include a 1B regulatory domain and a SF1 helicase core. Pssm-ID: 439166 Cd Length: 70 Bit Score: 104.88 E-value: 3.61e-26
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| gammaCoV-Nsp6 | cd21559 | gammacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ... |
3557-3856 | 1.26e-25 | |||||||||||||
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: 111.40 E-value: 1.26e-25
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| capping_2-OMTase_viral | cd20754 | viral Cap-0 specific (nucleoside-2'-O-)-methyltransferase; Cap-0 specific (nucleoside-2'-O-) ... |
6839-6961 | 3.29e-25 | |||||||||||||
viral Cap-0 specific (nucleoside-2'-O-)-methyltransferase; Cap-0 specific (nucleoside-2'-O-)-methyltransferase (2'OMTase) catalyzes the methylation of Cap-0 (m7GpppNp) at the 2'-hydroxyl of the ribose of the first nucleotide, using S-adenosyl-L-methionine (AdoMet) as the methyl donor. This reaction is the fourth and last step in mRNA capping, the creation of the stabilizing five-prime cap (5' cap) on mRNA. Some dsDNA and dsRNA viruses, like the bluetongue virus (BTV), a member of the Reoviridae family, and Vaccinia virus, a member of the Poxviridae family, as well as some ss(+)RNA viruses, like Flaviviridae and Nidovirales, cap their mRNAs and encode their own 2'OMTase. In BTV, all four reactions are catalyzed by a single protein, VP4. In Vaccinia, the activity is located in the processing factor of the poly(A) polymerase, VP39. Pssm-ID: 467730 Cd Length: 179 Bit Score: 105.99 E-value: 3.29e-25
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| Mesoniviridae_RdRp | cd23187 | catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the Mesoniviridae family of ... |
4890-5283 | 3.37e-25 | |||||||||||||
catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the Mesoniviridae family of positive-sense single-stranded RNA [(+)ssRNA] viruses; This group contains the catalytic core domain of RdRp of RNA viruses belonging to the family Mesoniviridae, order Nidovirales. Member viruses have a viral envelope and (+)ssRNA genome. The family is named after the size of the genomes relative to other nidoviruses, which is intermediate between that of the families Arteriviridae and Coronaviridae, with meso- coming from the Greek word mesos, which means medium, while -ni is an abbreviation of nido. The family Mesoniviridae comprises of mosquito-specific viruses with extensive geographic distribution and host range. The family has only one subfamily, Hexponivirinae, which contains only one genus, Alphamesonivirus. There are 8 subgenera (Casualivirus, Enselivirus, Hanalivirus, Kadilivirus, Karsalivirus, Menolivirus, Namcalivirus, and Ofalivirus) and 10 species in Alphamesonivirus. The structure of Mesoniviridae RdRp contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. Pssm-ID: 438037 Cd Length: 424 Bit Score: 112.68 E-value: 3.37e-25
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| stalk_CoV_Nsp13-like | cd21689 | stalk domain of coronavirus Nsp13 helicase and related proteins; This model represents the ... |
5420-5467 | 1.02e-24 | |||||||||||||
stalk domain of coronavirus Nsp13 helicase and related proteins; This model represents the stalk domain of coronavirus non-structural protein 13 (Nsp13) helicase, found in the Nsp3s of alpha-, beta-, gamma-, and deltacoronaviruses, including Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), SARS-CoV-2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome coronavirus (MERS-CoV). Helicases are classified based on the arrangement of conserved motifs into six superfamilies; coronavirus helicases in this family belong to superfamily 1 (SF1). Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It consists of an N-terminal ZBD (Cys/His rich zinc-binding domain), a stalk domain, a 1B regulatory domain, and SF1 helicase core. The stalk domain lies between the ZBD domain and the 1B domain; a short loop connects the ZBD to the stalk domain. The stalk domain is comprised of three tightly-interacting alpha-helices connected to the 1B domain, transferring the effect from the ZBD domain onto the helicase core domains. The ZBD and stalk domains are critical for the helicase activity of SARS-CoV Nsp13. Pssm-ID: 410205 Cd Length: 48 Bit Score: 99.99 E-value: 1.02e-24
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| DEXXQc_Upf1-like | cd17934 | DEXXQ-box helicase domain of Upf1-like helicase; The Upf1-like helicase family includes UPF1, ... |
5598-5764 | 1.08e-23 | |||||||||||||
DEXXQ-box helicase domain of Upf1-like helicase; The Upf1-like helicase family includes UPF1, HELZ, Mov10L1, Aquarius, IGHMBP2 (SMUBP2), coronavirus Nsp13, and similar proteins. They belong to the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region. Pssm-ID: 438708 [Multi-domain] Cd Length: 121 Bit Score: 99.62 E-value: 1.08e-23
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| DNA2 | COG1112 | Superfamily I DNA and/or RNA helicase [Replication, recombination and repair]; |
5684-5911 | 3.67e-23 | |||||||||||||
Superfamily I DNA and/or RNA helicase [Replication, recombination and repair]; Pssm-ID: 440729 [Multi-domain] Cd Length: 819 Bit Score: 109.83 E-value: 3.67e-23
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| alpha_betaCoV_Nsp1 | cd21874 | non-structural protein 1 from alpha- and betacoronavirus; This model represents the ... |
13-125 | 1.16e-22 | |||||||||||||
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: 96.12 E-value: 1.16e-22
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| betaCoV_Nsp2_MERS-like | cd21517 | betacoronavirus non-structural protein 2 (Nsp2) similar to MERS-CoV Nsp2, and related proteins ... |
186-818 | 1.18e-22 | |||||||||||||
betacoronavirus non-structural protein 2 (Nsp2) similar to MERS-CoV Nsp2, and related proteins from betacoronaviruses in the C lineage; Coronavirus non-structural proteins (Nsps) are encoded in ORF1a and ORF1b. Post infection, the genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (pp), pp1a and pp1ab, which are then autoproteolytically cleaved by two viral proteases Nsp3 and Nsp5 into smaller subunits. Nsp2 is one of these subunits. This subgroup includes Nsp2 from Middle East respiratory syndrome-related coronavirus (MERS-CoV) and betacoronaviruses in the merbecovirus subgenus (C lineage). It belongs to a family which includes Severe acute respiratory syndrome coronavirus (SARS-CoV) 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. Pssm-ID: 394868 Cd Length: 660 Bit Score: 107.51 E-value: 1.18e-22
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| gammaCoV_Nsp9 | cd21899 | gammacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ... |
4136-4250 | 1.54e-22 | |||||||||||||
gammacoronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) from gammacoronaviruses such as Avian infectious bronchitis virus (IBV). CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for coronavirus replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication. Pssm-ID: 409332 Cd Length: 113 Bit Score: 96.08 E-value: 1.54e-22
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| TM_Y_deltaCoV_Nsp3_C | cd21711 | C-terminus of deltacoronavirus non-structural protein 3, including transmembrane and Y domains; ... |
2226-2747 | 5.53e-22 | |||||||||||||
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: 104.02 E-value: 5.53e-22
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| Macro | pfam01661 | Macro domain; The Macro or A1pp domain is a module of about 180 amino acids which can bind ... |
1058-1165 | 5.64e-22 | |||||||||||||
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: 94.55 E-value: 5.64e-22
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| alphaCoV_Nsp7 | cd21826 | alphacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ... |
3857-3939 | 1.52e-21 | |||||||||||||
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: 92.04 E-value: 1.52e-21
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| YmdB | COG2110 | O-acetyl-ADP-ribose deacetylase (regulator of RNase III), contains Macro domain [Translation, ... |
1038-1184 | 2.09e-19 | |||||||||||||
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: 89.08 E-value: 2.09e-19
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| deltaCoV-Nsp6 | cd21561 | deltacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ... |
3616-3856 | 3.27e-19 | |||||||||||||
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: 92.04 E-value: 3.27e-19
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| gammaCoV_Nsp7 | cd21828 | gammacoronavirus non-structural protein 7; This model represents the non-structural protein 7 ... |
3857-3939 | 3.22e-18 | |||||||||||||
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: 82.53 E-value: 3.22e-18
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| Medioniviridae_RdRp | cd23188 | catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the Medioniviridae family of ... |
4890-5282 | 4.19e-18 | |||||||||||||
catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the Medioniviridae family of positive-sense single-stranded RNA [(+)ssRNA] viruses; This group contains the catalytic core domain of RdRp of RNA viruses belonging to the family Medioniviridae, order Nidovirales. Member viruses have a viral envelope and (+)ssRNA genome. The Medioniviridae subgenera includes Turrinivirus and Balbicanovirus. The structure of Medioniviridae RdRp contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. Pssm-ID: 438038 Cd Length: 391 Bit Score: 90.52 E-value: 4.19e-18
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| PRK00431 | PRK00431 | ADP-ribose-binding protein; |
1056-1196 | 1.57e-17 | |||||||||||||
ADP-ribose-binding protein; Pssm-ID: 234759 Cd Length: 177 Bit Score: 83.74 E-value: 1.57e-17
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| Macro_cv_SUD-N-M_Nsp3-like | cd21556 | SUD-N and SUD-M macrodomains of the SARS-Unique Domain (SUD) of SARS-CoV non-structural ... |
1247-1357 | 9.48e-17 | |||||||||||||
SUD-N and SUD-M macrodomains of the SARS-Unique Domain (SUD) of SARS-CoV non-structural protein 3 and related macrodomains; This family includes two macrodomains referred to as the SUD-N (N-terminal subdomain) and SUD-M (middle SUD subdomain) of the SARS-unique domain (SUD) which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). It is found in non-structural protein 3 (Nsp3) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and highly related coronaviruses. SUD consists of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. Among these, SUD-N and SUD-M are macrodomains. SUD-N (also called Mac2) is specific to the Nsp3 of SARS and betacoronaviruses of the sarbecovirus subgenera (B lineage), while SUD-M (also called Mac3) is present in most Nsp3 proteins except the Nsp3 from betacoronaviruses of the embecovirus subgenera (A lineage). SUD-C adopts a frataxin-like fold, has structural similarity to DNA-binding domains of DNA-modifying enzymes, binds single-stranded RNA, and regulates the RNA binding behavior of the SUD-M macrodomain. SARS-CoV Nsp3 contains a third macrodomain (the X-domain or Mac1) which is not included in this family. The X-domain may function as a module binding poly(ADP-ribose); however, SUD-N and SUD-M do not bind ADP-ribose, as the triple glycine sequence involved in its binding is not conserved in these. Pssm-ID: 438956 Cd Length: 108 Bit Score: 79.25 E-value: 9.48e-17
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| 1B_UPF1_nv_SF1_Hel-like | cd21344 | 1B domain of eukaryotic UPF1 helicase, nidovirus SF1 helicases including coronavirus Nsp13 and ... |
5471-5549 | 2.03e-16 | |||||||||||||
1B domain of eukaryotic UPF1 helicase, nidovirus SF1 helicases including coronavirus Nsp13 and arterivirus Nsp10, and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. Members of this family belong to helicase superfamily 1 (SF1) and include nidoviral helicases such as Severe Acute Respiratory Syndrome coronavirus (SARS) non-structural protein 13 (SARS-Nsp13), Equine arteritis virus (EAV) Nsp10, and eukaryotic UPF1 RNA helicase. SARS-Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). UPF1 participates in nonsense-mediated mRNA decay (NMD), a pathway which degrades transcripts with premature termination codons. UPF1, EAV Nsp10 and SARS-Nsp13 are multidomain proteins with an N-terminal Cys/His rich zinc-binding domain (CH/ZBD), a 1B domain and a SF1 helicase core. The 1B domain is involved in nucleic acid substrate binding; the 1B domain of EAV Nsp10 undergoes large conformational change upon substrate binding, and together with the 1A and 2A domains of the helicase core form a channel that accommodates the single stranded nucleic acids. Pssm-ID: 439170 Cd Length: 86 Bit Score: 77.74 E-value: 2.03e-16
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| CoV_NSP2_N | pfam19211 | Coronavirus replicase NSP2, N-terminal; This entry corresponds to the N-terminal region of ... |
183-423 | 2.91e-16 | |||||||||||||
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: 81.24 E-value: 2.91e-16
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| Macro_SF | cd02749 | macrodomain superfamily; Macrodomains are found in a variety of proteins with diverse cellular ... |
1055-1164 | 3.25e-15 | |||||||||||||
macrodomain superfamily; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. Macrodomains include the yeast macrodomain Poa1 which is a phosphatase of ADP-ribose-1"-phosphate, a by-product of tRNA splicing. Some macrodomains have ADPr-unrelated binding partners such as the coronavirus SUD-N (N-terminal subdomain) and SUD-M (middle subdomain) of the SARS-unique domain (SUD) which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). Macrodomains regulate a wide variety of cellular and organismal processes, including DNA damage repair, signal transduction, and immune response. Pssm-ID: 394871 Cd Length: 121 Bit Score: 75.51 E-value: 3.25e-15
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| A1pp | smart00506 | Appr-1"-p processing enzyme; Function determined by Martzen et al. Extended family detected by ... |
1051-1164 | 4.35e-15 | |||||||||||||
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: 75.42 E-value: 4.35e-15
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| deltaCoV_Nsp9 | cd21900 | deltacoronavirus non-structural protein 9; This model represents the non-structural protein 9 ... |
4138-4250 | 1.46e-14 | |||||||||||||
deltacoronavirus non-structural protein 9; This model represents the non-structural protein 9 (Nsp9) from deltacoronaviruses such as the Porcine delta coronavirus (PDCoV) Porcine coronavirus HKU15. CoVs utilize a multi-subunit replication/transcription machinery assembled from a set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins. All of these Nsps, except for Nsp1 and Nsp2, are considered essential for transcription, replication, and translation of the viral RNA. Nsp9, with Nsp7, Nsp8, and Nsp10, localizes within the replication complex. Nsp9 is an essential single-stranded RNA-binding protein for coronavirus replication; it shares structural similarity to the oligosaccharide-binding (OB) fold, which is characteristic of proteins that bind to ssDNA or ssRNA. Nsp9 requires dimerization for binding and orienting RNA for subsequent use by the replicase machinery. CoV Nsp9s have diverse forms of dimerization that promote their biological function, which may help elucidate the mechanism underlying CoVs replication and contribute to the development of antiviral drugs. Generally, dimers are formed via interaction of the parallel alpha-helices containing the protein-protein interaction motif GXXXG; additionally, the N-finger region may also play a critical role in dimerization as seen in porcine delta coronavirus (PDCoV) Nsp9. As a member of the replication complex, Nsp9 may not have a specific RNA-binding sequence but may act in conjunction with other Nsps as a processivity factor, as shown by mutation studies indicating that Nsp9 is a key ingredient that intimately engages other proteins in the replicase complex to mediate efficient virus transcription and replication. Pssm-ID: 409333 Cd Length: 109 Bit Score: 73.24 E-value: 1.46e-14
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| gammaCoV_PLPro | cd21733 | gammacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ... |
1569-1836 | 3.21e-13 | |||||||||||||
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: 74.39 E-value: 3.21e-13
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| CoV_NSP2_C | pfam19212 | Coronavirus replicase NSP2, C-terminal; This entry corresponds to a presumed domain found at ... |
652-818 | 3.99e-13 | |||||||||||||
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: 70.37 E-value: 3.99e-13
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| MERS-CoV-like_Nsp3_NAB | cd21823 | nucleic acid binding domain of non-structural protein 3 from Middle East respiratory ... |
1906-2019 | 2.12e-12 | |||||||||||||
nucleic acid binding domain of non-structural protein 3 from Middle East respiratory syndrome-related coronavirus and betacoronavirus in the C lineage; This model represents the nucleic acid binding (NAB) domain 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. The NAB domain represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. NAB is a cytoplasmic domain located between the papain-like protease (PLPro) and betacoronavirus-specific marker (betaSM) domains of CoV Nsp3. 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. The NAB domain both binds ssRNA and unwinds dsDNA. It prefers to bind ssRNA containing repeats of three consecutive guanines. A group of residues that form a positively charged patch on the protein surface of SARS-CoV Nsp3 NAB serves as the binding site of nucleic acids. This site is conserved in the NAB of Nsp3 from betacoronavirus in the sarbecovirus subgenus (B lineage), and appears to be partially conserved in the Nsp3 NAB from betacoronaviruses in the C lineage. Pssm-ID: 409349 Cd Length: 123 Bit Score: 67.46 E-value: 2.12e-12
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| NTD_gammaCoV_Nsp15-like | cd22650 | N-terminal domain of gammacoronavirus Nonstructural protein 15 (Nsp15), and related proteins; ... |
6451-6510 | 3.37e-12 | |||||||||||||
N-terminal domain of gammacoronavirus Nonstructural protein 15 (Nsp15), and related proteins; Coronavirus (CoV) Nsp15 is a nidovirus endoribonuclease (NendoU). NendoUs are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include coronavirus Nsp15 and arterivirus Nsp11, both of which may participate in the viral replication process and in the evasion of the host immune system. This NTD structure (approximately 60 residues) present in coronavirus Nsp15, is missing in Nsp11. CoV Nsp15 has an N-terminal domain, a middle (M) domain, and a C-terminal catalytic (NendoU) domain. Nsp15 from alpha- and betaCoVs such as Severe Acute Respiratory Syndrome (SARS)-CoV, human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. The active form of the Nsp15 of Turkey CoV (TCoV), a gammaCoV, has been reported to be a homohexamer. Residues in this N-terminal domain may be important for hexamer formation. Pssm-ID: 439165 Cd Length: 60 Bit Score: 64.50 E-value: 3.37e-12
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| AAA_12 | pfam13087 | AAA domain; This family of domains contain a P-loop motif that is characteriztic of the AAA ... |
5764-5901 | 6.49e-12 | |||||||||||||
AAA domain; This family of domains contain a P-loop motif that is characteriztic of the AAA superfamily. Many of the proteins in this family are conjugative transfer proteins. Pssm-ID: 463780 [Multi-domain] Cd Length: 196 Bit Score: 68.34 E-value: 6.49e-12
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| SF1_C_Upf1 | cd18808 | C-terminal helicase domain of Upf1-like family helicases; The Upf1-like helicase family ... |
5765-5902 | 9.06e-12 | |||||||||||||
C-terminal helicase domain of Upf1-like family helicases; The Upf1-like helicase family includes UPF1, HELZ, Mov10L1, Aquarius, IGHMBP2 (SMUBP2), and similar proteins. They are DEAD-like helicases belonging to superfamily (SF)1, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. Similar to SF2 helicases, SF1 helicases do not form toroidal structures like SF3-6 helicases. Their helicase core consists of two similar protein domains that resemble the fold of the recombination protein RecA. This model describes the C-terminal domain, also called HelicC. Pssm-ID: 350195 [Multi-domain] Cd Length: 184 Bit Score: 67.26 E-value: 9.06e-12
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| M_gcv_Nsp15-like | cd21168 | middle domain of gammacoronavirus Nonstructural protein 15 (Nsp15), and related proteins; ... |
6515-6645 | 9.26e-12 | |||||||||||||
middle domain of gammacoronavirus Nonstructural protein 15 (Nsp15), and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include Nsp15 from coronaviruses and Nsp11 from arteriviruses, both of which may participate in the viral replication process and in the evasion of the host immune system. Coronavirus Nsp15 NendoUs have an N-terminal domain, a middle (M) domain and a C-terminal catalytic (NendoU) domain. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. This middle domain harbors residues involved in hexamer formation and in trimer stability. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of the other coronaviruses; it has been shown to exist as a dimer and a monomer in solution. Pssm-ID: 394906 Cd Length: 123 Bit Score: 65.65 E-value: 9.26e-12
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| HKU9-like_Nsp3_NAB | cd21825 | nucleic acid binding domain of non-structural protein 3 from Rousettus bat coronavirus HKU9 ... |
1906-2028 | 2.97e-11 | |||||||||||||
nucleic acid binding domain of non-structural protein 3 from Rousettus bat coronavirus HKU9 and betacoronavirus in the D lineage; This model represents the nucleic acid binding (NAB) domain of non-structural protein 3 (Nsp3) from betacoronavirus in the nobecovirus subgenus (D lineage), including Rousettus bat coronavirus HKU9. The NAB domain represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. NAB is a cytoplasmic domain located between the papain-like protease (PLPro) and betacoronavirus-specific marker (betaSM) domains of CoV Nsp3. 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. The NAB domain both binds ssRNA and unwinds dsDNA. It prefers to bind ssRNA containing repeats of three consecutive guanines. A group of residues that form a positively charged patch on the protein surface of SARS-CoV Nsp3 NAB serves as the binding site of nucleic acids. This site is conserved in the NAB of Nsp3 from betacoronavirus in the sarbecovirus subgenus (B lineage), but is not conserved in the Nsp3 NAB from betacoronaviruses in the D lineage. Pssm-ID: 409351 Cd Length: 117 Bit Score: 64.09 E-value: 2.97e-11
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| Macro_OAADPr_deacetylase | cd02908 | macrodomain, O-acetyl-ADP-ribose (OAADPr) family; Macrodomains are found in a variety of ... |
1038-1186 | 1.44e-10 | |||||||||||||
macrodomain, O-acetyl-ADP-ribose (OAADPr) family; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. This family includes eukaryotic macrodomain proteins such as human MacroD1 and MacroD2, and bacterial proteins such as Escherichia coli YmdB; these have been shown to be O-acetyl-ADP-ribose (OAADPr) deacetylases that efficiently catalyze the hydrolysis of OAADPr to produce ADP-ribose and free acetate. OAADPr is a sirtuin reaction product generated from the NAD+-dependent protein deacetylation reactions and has been implicated as a signaling molecule. By acting on mono-ADP-ribosylated substrates, OAADPr deacetylases may reverse cellular ADP-ribosylation. Pssm-ID: 438955 Cd Length: 166 Bit Score: 63.30 E-value: 1.44e-10
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| NTD_deltaCoV_Nsp15-like | cd21172 | N-terminal domain of deltacoronavirus Nonstructural protein 15 (Nsp15), and related proteins; ... |
6451-6510 | 7.61e-10 | |||||||||||||
N-terminal domain of deltacoronavirus Nonstructural protein 15 (Nsp15), and related proteins; Coronavirus (CoV) Nsp15 is a nidovirus endoribonuclease (NendoU). NendoUs are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. NendoUs include coronavirus Nsp15 and arterivirus Nsp11, both of which may participate in the viral replication process and in the evasion of the host immune system. This small NTD structure, present in CoV Nsp15, is missing in Nsp11. CoV Nsp15 has an N-terminal domain, a middle (M) domain, and a C-terminal catalytic (NendoU) domain. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from the Nsp15 of alpha- and beta-coronavirus, such as Severe Acute Respiratory Syndrome (SARS)-CoV and Murine Hepatitis Virus (MHV) which form functional hexamers; PDCoV Nsp15 has been shown to exist as dimers and monomers in solution, and to function as a dimer. Pssm-ID: 439164 Cd Length: 60 Bit Score: 57.94 E-value: 7.61e-10
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| SUD_C_DPUP_CoV_Nsp3 | cd21513 | C-terminal SARS-Unique Domain (SUD) of betacoronavirus non-structural protein 3 (Nsp3); This ... |
1496-1561 | 1.80e-08 | |||||||||||||
C-terminal SARS-Unique Domain (SUD) of betacoronavirus non-structural protein 3 (Nsp3); This family contains the SUD-C of Nsp3 from Severe Acute Respiratory Syndrome (SARS) coronavirus (CoV), Middle East respiratory syndrome-related (MERS) CoV, and Rousettus bat CoV HKU9, as well as the DPUP (domain preceding Ubl2 and PLP2) of murine hepatitis virus (MHV) Nsp3. Though structurally similar, there is little sequence similarity between these four domain subfamilies: SARS SUD-C, MERS SUD-C, HKU9 SUD-C, and MHV DPUP. Non-structural protein 3 (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. Nsp3 of SARS coronavirus includes a SARS-unique domain (SUD) consisting of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C. SUD-N and SUD-M are macro domains which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). The SUD-C domain adopts a frataxin-like fold and has structural similarity to DNA-binding domains of DNA-modifying enzymes. It binds to single-stranded RNA and recognizes purine bases more strongly than pyrimidine bases. SUD-C also regulates the RNA binding behavior of the SUD-M macrodomain. SUD-C is not as specific to SARS CoV Nsp3 as originally thought, and is conserved in the Nsp3s of all four lineages (A-D) of betacoronavirus. Pssm-ID: 394838 Cd Length: 71 Bit Score: 54.48 E-value: 1.80e-08
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| DEXXQc_SETX | cd18042 | DEXXQ-box helicase domain of SETX; The RNA/DNA helicase senataxin (SETX) plays a role in ... |
5594-5728 | 2.11e-08 | |||||||||||||
DEXXQ-box helicase domain of SETX; The RNA/DNA helicase senataxin (SETX) plays a role in transcription, neurogenesis, and antiviral response. SEXT is an R-loop-associated protein that is thought to function as an RNA/DNA helicase. R-loops consist of RNA/DNA hybrids, formed during transcription when nascent RNA hybridizes to the DNA template strand, displacing the non-template DNA strand. Mutations in SETX are linked to two neurodegenerative disorders: ataxia with oculomotor apraxia type 2 (AOA2) and amyotrophic lateral sclerosis type 4 (ALS4). S. cerevisiae homolog splicing endonuclease 1 (Sen1) is an exclusively nuclear protein, important for nucleolar organization. S. cerevisiae Sen1 and its ortholog, the Schizosaccharomyces pombe Sen1, share conserved domains and belong to the family I class of helicases. Both proteins translocate 5' to 3' and unwind both DNA and RNA duplexes and also RNA/DNA hybrids in vitro. SETX is a member of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region. Pssm-ID: 438712 [Multi-domain] Cd Length: 218 Bit Score: 58.38 E-value: 2.11e-08
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| alphaCoV_PLPro | cd21731 | alphacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ... |
1567-1765 | 3.34e-08 | |||||||||||||
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: 58.79 E-value: 3.34e-08
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| Euroniviridae_RdRp | cd23191 | catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the family Eunroniviridae of ... |
4927-5258 | 6.84e-08 | |||||||||||||
catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the family Eunroniviridae of positive-sense single-stranded RNA [(+)ssRNA] viruses; This group contains the catalytic core domain of RdRp of RNA viruses belonging to the family Eunroniviridae, order Nidovirales. Member viruses have a viral envelope and (+)ssRNA genome. Eunroniviridae is a closely related family of crustacean nidoviruses, within the suborder Ronidovirineae, which also includes the family Roniviridae. Ronidovirineae, named "rod-shaped nidovirus", is 150-200 nm long and approximately 60 nm thick. There are 3 viral species in the Euroniviridae family, all of which have been detected in crustaceans. The structure of Euroniviridae RdRp contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. Pssm-ID: 438041 Cd Length: 345 Bit Score: 58.76 E-value: 6.84e-08
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| RdRP_1 | pfam00680 | Viral RNA-dependent RNA polymerase; This family represents the RNA-directed RNA polymerase ... |
4886-5227 | 2.42e-07 | |||||||||||||
Viral RNA-dependent RNA polymerase; This family represents the RNA-directed RNA polymerase found in many positive strand RNA eukaryotic viruses. Structural studies indicate that these proteins form the "right hand" structure found in all oligonucleotide polymerases, containing thumb, finger and palm domains, and also the additional bridging finger and thumb domains unique to RNA-directed RNA polymerases. Pssm-ID: 425815 Cd Length: 450 Bit Score: 57.42 E-value: 2.42e-07
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| deltaCoV_PLPro | cd21734 | deltacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) ... |
1643-1740 | 2.85e-07 | |||||||||||||
deltacoronavirus papain-like protease; This model represents the papain-like protease (PLPro) found in the non-structural protein 3 (Nsp3) region of deltacoronavirus, including Porcine deltacoronavirus, Bulbul coronavirus HKU11, and Common moorhen coronavirus HKU21. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. PLPro is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. PLPro, which belongs to the MEROPS peptidase C16 family, participates in the proteolytic processing of the N-terminal region of the replicase polyprotein; it can cleave Nsp1|Nsp2, Nsp2|Nsp3, and Nsp3|Nsp4 sites and its activity is dependent on zinc. Besides cleaving the polyproteins, PLPro also possesses a related enzymatic activity to promote virus replication: deubiquitinating (DUB) and de-ISGylating activities. Both, ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15), are involved in preventing viral infection; coronaviruses utilize Ubl-conjugating pathways to counter the pro-inflammatory properties of Ubl-conjugated host proteins via the action of PLPro, which processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. The Nsp3 PLPro domain in many of these CoVs has also been shown to antagonize host innate immune induction of type I interferon by interacting with IRF3 and blocking its activation. Pssm-ID: 409651 Cd Length: 313 Bit Score: 56.28 E-value: 2.85e-07
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| ZBD_tv_SF1_Hel-like | cd21403 | Cys/His rich zinc-binding domain (CH/ZBD) of tornidovirus SF1 helicase and related proteins; ... |
5322-5404 | 3.21e-07 | |||||||||||||
Cys/His rich zinc-binding domain (CH/ZBD) of tornidovirus SF1 helicase and related proteins; Helicases catalyze NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. This tornidovirus group includes White bream virus (WBV) SF1 helicase encoded on ORF1b and belongs to helicase superfamily 1 (SF1). The CH/ZBD has 3 zinc-finger (ZnF1-3) motifs. Members of this group belong to a family of nindoviral replication helicases which include includes Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) non-structural protein 13 (SARS-Nsp13), a component of the viral RNA synthesis replication and transcription complex (RTC). The SARS-Nsp13 CH/ZBD is indispensable for helicase activity and interacts with SARS-Nsp12, the RNA-dependent RNA polymerase. Pssm-ID: 394810 Cd Length: 95 Bit Score: 51.58 E-value: 3.21e-07
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| DEXXQc_SF1 | cd18043 | DEXXQ-box helicase domain of Superfamily 1 helicases; Superfamily 1 (SF1) helicases are ... |
5601-5733 | 3.99e-07 | |||||||||||||
DEXXQ-box helicase domain of Superfamily 1 helicases; Superfamily 1 (SF1) helicases are nucleic acid motor proteins that couple ATP hydrolysis to translocation along with the concomitant unwinding of DNA or RNA. This is central to many aspects of cellular DNA and RNA metabolism and accordingly, they are implicated in a wide range of nucleic acid processing events including DNA replication, recombination, and repair as well as many aspects of RNA metabolism. Superfamily 1 helicases are members of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region. Pssm-ID: 350801 [Multi-domain] Cd Length: 127 Bit Score: 52.58 E-value: 3.99e-07
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| betaCoV_Nsp2_HKU9-like | cd21518 | betacoronavirus non-structural protein 2 (Nsp2) similar to bat coronavirus HKU9 Nsp2, and ... |
271-764 | 4.33e-07 | |||||||||||||
betacoronavirus non-structural protein 2 (Nsp2) similar to bat coronavirus HKU9 Nsp2, and related proteins from betacoronaviruses in the D lineage; Coronavirus non-structural proteins (Nsps) are encoded in ORF1a and ORF1b. Post infection, the genomic RNA is released into the cytoplasm of the cell and translated into two long polyproteins (pp), pp1a and pp1ab, which are then autoproteolytically cleaved by two viral proteases Nsp3 and Nsp5 into smaller subunits. Nsp2 is one of these subunits. This subgroup includes Nsp2 from Rousettus bat coronavirus HKU9 and betacoronaviruses in the nobecovirus subgenus (D lineage). It belongs to a family which includes Severe acute respiratory syndrome coronavirus (SARS-CoV) 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. Pssm-ID: 394869 Cd Length: 597 Bit Score: 57.08 E-value: 4.33e-07
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| Macro_H2A-like | cd02904 | macrodomain, macroH2A-like family; Macrodomains are found in a variety of proteins with ... |
1033-1137 | 6.61e-07 | |||||||||||||
macrodomain, macroH2A-like family; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. Members of this family are similar to macroH2A, a variant of the major-type core histone H2A, which contains an N-terminal H2A domain and a C-terminal nonhistone macrodomain. Histone macroH2A is enriched on the inactive X chromosome of mammalian female cells. It does not bind poly ADP-ribose, but does bind the monomeric SirT1 metabolite O-acetyl-ADP-ribose (OAADPR) with high affinity through its macrodomain. This family also includes the ADP-ribose binding macrodomain of the macroH2A variant, macroH2A1.1. The macroH2A1.1 isoform inhibits PARP1-dependent DNA-damage induced chromatin dynamics. The putative ADP-ribose binding pocket of the human macroH2A2 macrodomain exhibits marked structural differences compared with the macroH2A1.1 variant. Pssm-ID: 394875 Cd Length: 188 Bit Score: 53.47 E-value: 6.61e-07
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| Macro_Ttha0132-like | cd03330 | Macrodomain, uncharacterized family similar to Thermus thermophilus hypothetical protein ... |
1056-1167 | 1.75e-06 | |||||||||||||
Macrodomain, uncharacterized family similar to Thermus thermophilus hypothetical protein Ttha0132; Macrodomains are found in a variety of proteins with diverse cellular functions, as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose polymerases). Macrodomains can recognize ADP-ribose (ADPr) in both its free and protein-linked forms, in related ligands, such as O-acyl-ADP-ribose (OAADPr), and even in ligands unrelated to ADPr. Macrodomains include the yeast macrodomain Poa1 which is a phosphatase of ADP-ribose-1"-phosphate, a by-product of tRNA splicing. Some macrodomains have ADPr-unrelated binding partners such as the coronavirus SUD-N (N-terminal subdomain) and SUD-M (middle subdomain) of the SARS-unique domain (SUD) which bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides). Macrodomains regulate a wide variety of cellular and organismal processes, including DNA damage repair, signal transduction, and immune response. This family is composed of uncharacterized proteins containing a stand-alone macrodomain, similar to Thermus thermophilus hypothetical protein Ttha0132. Pssm-ID: 394879 Cd Length: 147 Bit Score: 51.28 E-value: 1.75e-06
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| DEXXQc_SMUBP2 | cd18044 | DEXXQ-box helicase domain of SMUBP2; SMUBP2 (also called immunoglobulin mu-binding protein 2, ... |
5601-5727 | 3.21e-06 | |||||||||||||
DEXXQ-box helicase domain of SMUBP2; SMUBP2 (also called immunoglobulin mu-binding protein 2, or IGHMBP2) is a 5' to 3' helicase that unwinds RNA and DNA duplexes in an ATP-dependent reaction. It is a DNA-binding protein specific to 5'-phosphorylated single-stranded guanine-rich sequence (5'-GGGCT-3') related to the immunoglobulin mu chain switch region. The IGHMBP2 gene is responsible for Charcot-Marie-Tooth disease (CMT) type 2S and spinal muscular atrophy with respiratory distress type 1 (SMARD1). It is also thought to play a role in frontotemporal dementia (FTD) with amyotrophic lateral sclerosis (ALS) and major depressive disorder (MDD). SMUBP2 is a member of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region. Pssm-ID: 350802 [Multi-domain] Cd Length: 191 Bit Score: 51.46 E-value: 3.21e-06
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| SF1_C | cd18786 | C-terminal helicase domain of superfamily 1 DEAD/H-box helicases; Superfamily (SF)1 family ... |
5819-5893 | 3.16e-05 | |||||||||||||
C-terminal helicase domain of superfamily 1 DEAD/H-box helicases; Superfamily (SF)1 family members include UvrD/Rep, Pif1-like, and Upf-1-like proteins. Similar to SF2 helicases, they do not form toroidal, predominantly hexameric structures like SF3-6. SF1 helicases are a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. Their helicase core is surrounded by C- and N-terminal domains with specific functions such as nucleases, RNA or DNA binding domains, or domains engaged in protein-protein interactions. The core consists of two similar protein domains that resemble the fold of the recombination protein RecA. This model describes the C-terminal domain, also called HelicC. Pssm-ID: 350173 [Multi-domain] Cd Length: 89 Bit Score: 45.89 E-value: 3.16e-05
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| AAA_11 | pfam13086 | AAA domain; This family of domains contain a P-loop motif that is characteriztic of the AAA ... |
5601-5654 | 6.04e-05 | |||||||||||||
AAA domain; This family of domains contain a P-loop motif that is characteriztic of the AAA superfamily. Many of the proteins in this family are conjugative transfer proteins. Pssm-ID: 404072 [Multi-domain] Cd Length: 248 Bit Score: 48.49 E-value: 6.04e-05
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| DEXXQc_DNA2 | cd18041 | DEXXQ-box helicase domain of DNA2; DNA2 (DNA Replication Helicase/Nuclease 2) possesses ... |
5589-5727 | 1.81e-04 | |||||||||||||
DEXXQ-box helicase domain of DNA2; DNA2 (DNA Replication Helicase/Nuclease 2) possesses different enzymatic activities, such as single-stranded DNA (ssDNA)-dependent ATPase, 5-3 helicase, and endonuclease activities, and is involved in DNA replication and DNA repair in the nucleus and mitochondrion. It is involved in Okazaki fragment processing by cleaving long flaps that escape FEN1: flaps that are longer than 27 nucleotides are coated by replication protein A complex (RPA), leading to recruit DNA2 which cleaves the flap until it is too short to bind RPA and becomes a substrate for FEN1. It is also involved in 5-end resection of DNA during double-strand break (DSB) repair; it is recruited by BLM and mediates the cleavage of 5-ssDNA, while the 3-ssDNA cleavage is prevented by the presence of RPA. DNA2 is a member of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region. Pssm-ID: 350799 [Multi-domain] Cd Length: 203 Bit Score: 46.46 E-value: 1.81e-04
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| NendoU_tv_PToV-like | cd21162 | Nidoviral uridylate-specific endoribonuclease (NendoU) domain of Porcine torovirus (PToV) ... |
6738-6793 | 2.40e-04 | |||||||||||||
Nidoviral uridylate-specific endoribonuclease (NendoU) domain of Porcine torovirus (PToV) endoribonuclease and related proteins; Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. The Porcine torovirus (PToV) strain PToV-NPL/2013 NendoU domain is located at the N-terminus of the ORF1ab replicase polyprotein, between regions annotated as Nonstructural proteins 11 (Nsp11) and 13 (Nsp13). This subfamily belongs to a family which includes Nsp15 from coronaviruses and Nsp11 from arteriviruses, which may participate in the viral replication process and in the evasion of the host immune system. These vary in their requirement for Mn2+. Coronavirus Nsp15 generally form functional hexamers, with the exception of Porcine DeltaCoronavirus (PDCoV) Nsp15 which exists as a dimer and a monomer in solution. Arterivirus (Porcine Reproductive and Respiratory Syndrome virus) PRRSV Nsp11 is a dimer. NendoUs are distantly related to Xenopus laevis Mn(2+)-dependent uridylate-specific endoribonuclease (XendoU) which is involved in the processing of intron-encoded box C/D U16 small, nucleolar RNA. Pssm-ID: 394913 Cd Length: 133 Bit Score: 44.50 E-value: 2.40e-04
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| UvrD_C_2 | pfam13538 | UvrD-like helicase C-terminal domain; This domain is found at the C-terminus of a wide variety ... |
5853-5890 | 3.29e-04 | |||||||||||||
UvrD-like helicase C-terminal domain; This domain is found at the C-terminus of a wide variety of helicase enzymes. This domain has a AAA-like structural fold. Pssm-ID: 463913 [Multi-domain] Cd Length: 52 Bit Score: 41.79 E-value: 3.29e-04
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| HKU9-like_Nsp1 | cd21877 | non-structural protein 1 from Rousettus bat coronavirus HKU9 and betacoronavirus in the D ... |
28-160 | 3.54e-04 | |||||||||||||
non-structural protein 1 from Rousettus bat coronavirus HKU9 and betacoronavirus in the D lineage; This model represents the non-structural protein 1 (Nsp1) from betacoronavirus in the nobecovirus subgenus (D lineage), including Rousettus bat coronavirus HKU9. 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: 409339 Cd Length: 165 Bit Score: 44.71 E-value: 3.54e-04
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| AAA_30 | pfam13604 | AAA domain; This family of domains contain a P-loop motif that is characteriztic of the AAA ... |
5598-5728 | 5.40e-04 | |||||||||||||
AAA domain; This family of domains contain a P-loop motif that is characteriztic of the AAA superfamily. Many of the proteins in this family are conjugative transfer proteins. There is a Walker A and Walker B. Pssm-ID: 433343 [Multi-domain] Cd Length: 191 Bit Score: 44.86 E-value: 5.40e-04
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| ps-ssRNAv_RdRp-like | cd23167 | conserved catalytic core domain of RNA-dependent RNA polymerase (RdRp) from the positive-sense ... |
5002-5156 | 8.03e-04 | |||||||||||||
conserved catalytic core domain of RNA-dependent RNA polymerase (RdRp) from the positive-sense single-stranded RNA [(+)ssRNA] viruses and closely related viruses; This family contains the catalytic core domain of RdRp of RNA viruses which belong to Group IV of the Baltimore classification system, and are a group of related viruses that have positive-sense (+), single-stranded (ss) genomes made of ribonucleic acid (RNA). RdRp (also known as RNA replicase) catalyzes the replication of RNA from an RNA template; specifically, it catalyzes the synthesis of the RNA strand complementary to a given RNA template. The Baltimore Classification is divided into 7 classes, 3 of which include RNA viruses: Group IV (+) RNA viruses, Group III double-stranded (ds) RNA viruses, and Group V negative-sense (-) RNA viruses. Baltimore groups of viruses differ with respect to the nature of their genome (i.e., the nucleic acid form that is packaged into virions) and correspond to distinct strategies of genome replication and expression. (+) viral RNA is similar to mRNA and thus can be immediately translated by the host cell. (+)ssRNA viruses can also produce (+) copies of the genome from (-) strands of an intermediate dsRNA genome. This acts as both a transcription and a replication process since the replicated RNA is also mRNA. RdRps belong to the expansive class of polymerases containing so-called palm catalytic domains along with the accessory fingers and thumb domains. All RdRps also have six conserved structural motifs (A-F), located in its majority in the palm subdomain (A-E motifs) and the F motif is located on the finger subdomain. All these motifs have been shown to be implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. In addition to Group IV viruses, this model also includes Picobirnaviruses (PBVs), members of the family Picobirnaviridae of dsRNA viruses (Baltimore classification Group III), which are bi-segmented dsRNA viruses. The phylogenetic tree of the RdRps of RNA viruses (realm Riboviria) showed that picobirnaviruses are embedded in the branch of diverse (+)RNA viruses; sometimes they are collectively referred to as the picornavirus supergroup. RdRps of members of the family Permutatetraviridae, a distinct group of RNA viruses that encompass a circular permutation within the RdRp palm domain, are not included in this model. Pssm-ID: 438017 [Multi-domain] Cd Length: 73 Bit Score: 41.56 E-value: 8.03e-04
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| Roniviridae_RdRp | cd23190 | catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the family Roniviridae of ... |
4975-5263 | 9.74e-04 | |||||||||||||
catalytic core domain of RNA-dependent RNA polymerase (RdRp) in the family Roniviridae of positive-sense single-stranded RNA [(+)ssRNA] viruses; This group contains the catalytic core domain of RdRp of RNA viruses belonging to the family Roniviridae, order Nidovirales. Member viruses have a viral envelope and (+)ssRNA genome. The family Roniviridae includes a single genus (Okavirus) for three species of viruses (Yellow head virus, Gill-associated virus and Okavirus 1) with enveloped, rod-shaped virions. Roniviruses infect penaeid and palaemonid shrimp. Natural infections are usually without apparent clinical signs. One member of the family (yellow head virus) is highly pathogenic for shrimp. Roniviruses are most closely related to other nidoviruses infecting arthropods, including members of the families Mesoniviridae (from mosquitoes) and Euroniviridae (from crustaceans). The structure of Roniviridae RdRp contains a RdRp domain as well as a large N-terminal extension that adopts a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) architecture. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. Pssm-ID: 438040 Cd Length: 379 Bit Score: 45.42 E-value: 9.74e-04
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| MHV-like_Nsp3_NAB | cd21824 | nucleic acid binding domain of non-structural protein 3 from murine hepatitis virus and ... |
1925-2029 | 1.07e-03 | |||||||||||||
nucleic acid binding domain of non-structural protein 3 from murine hepatitis virus and betacoronavirus in the A lineage; This model represents the nucleic acid binding (NAB) domain of non-structural protein 3 (Nsp3) from betacoronavirus in the embecovirus subgenus (A lineage), including murine hepatitis virus (MHV) and Human coronavirus HKU1. The NAB domain represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. NAB is a cytoplasmic domain located between the papain-like protease (PLPro) and betacoronavirus-specific marker (betaSM) domains of CoV Nsp3. 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. The NAB domain both binds ssRNA and unwinds dsDNA. It prefers to bind ssRNA containing repeats of three consecutive guanines. A group of residues that form a positively charged patch on the protein surface of SARS-CoV Nsp3 NAB serves as the binding site of nucleic acids. This site is conserved in the NAB of Nsp3 from betacoronavirus in the sarbecovirus subgenus (B lineage), but is not conserved in the Nsp3 NAB from betacoronaviruses in the A lineage. Pssm-ID: 409350 Cd Length: 119 Bit Score: 42.44 E-value: 1.07e-03
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| Bac_rhodopsin | pfam01036 | Bacteriorhodopsin-like protein; The bacterial opsins are retinal-binding proteins that provide ... |
3614-3794 | 1.65e-03 | |||||||||||||
Bacteriorhodopsin-like protein; The bacterial opsins are retinal-binding proteins that provide light- dependent ion transport and sensory functions to a family of halophilic bacteria. They are integral membrane proteins believed to contain seven transmembrane (TM) domains, the last of which contains the attachment point for retinal (a conserved lysine). This family also includes distantly related proteins that do not contain the retinal binding lysine and so cannot function as opsins. Some fungal examples are: Swiss:O74870, Swiss:P25619, Swiss:P38079, Swiss:Q12117. Pssm-ID: 460037 Cd Length: 224 Bit Score: 43.88 E-value: 1.65e-03
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| AAA | smart00382 | ATPases associated with a variety of cellular activities; AAA - ATPases associated with a ... |
5601-5733 | 4.83e-03 | |||||||||||||
ATPases associated with a variety of cellular activities; AAA - ATPases associated with a variety of cellular activities. This profile/alignment only detects a fraction of this vast family. The poorly conserved N-terminal helix is missing from the alignment. Pssm-ID: 214640 [Multi-domain] Cd Length: 148 Bit Score: 41.20 E-value: 4.83e-03
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| DEXXQc_Helz-like | cd18038 | DEXXQ/H-box helicase domain of Helz-like helicase; This subfamily contains HELZ, Mov10L1, and ... |
5603-5650 | 7.69e-03 | |||||||||||||
DEXXQ/H-box helicase domain of Helz-like helicase; This subfamily contains HELZ, Mov10L1, and similar proteins. Helicase with zinc finger (HELZ) acts as a helicase that plays a role in RNA metabolism during development. Moloney leukemia virus 10-like protein 1 (Mov10L1) binds Piwi-interacting RNA (piRNA) precursors to initiate piRNA processing. All are members of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region. Pssm-ID: 350796 [Multi-domain] Cd Length: 229 Bit Score: 41.84 E-value: 7.69e-03
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