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Entry version 116 (07 Apr 2021)
Sequence version 1 (10 Jun 2008)
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Replicase polyprotein 1ab



Severe acute respiratory syndrome coronavirus (SARS-CoV)
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.
Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response (PubMed:23035226). May disrupt nuclear pore function by binding and displacing host NUP93 (PubMed:30943371).2 Publications
May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.1 Publication
Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates (PubMed:17692280). Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3 (PubMed:19369340, PubMed:24622840). Prevents also host NF-kappa-B signaling.1 Publication4 Publications
Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Alone appears incapable to induce membrane curvature, but together with nsp3 is able to induce paired membranes. Nsp3, nsp4 and nsp6 together are sufficient to form DMV.1 Publication1 Publication
Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Also able to bind an ADP-ribose-1''-phosphate (ADRP). May cleave host ATP6V1G1 thereby modifying host vacuoles intracellular pH.PROSITE-ProRule annotation1 Publication
Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes (PubMed:24991833).1 Publication1 Publication
Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.1 Publication
Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.1 Publication
May participate in viral replication by acting as a ssRNA-binding protein.1 Publication
Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.1 Publication
Responsible for replication and transcription of the viral RNA genome.1 Publication
Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium.2 Publications
Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity (PubMed:16549795, PubMed:20421945, PubMed:22635272). Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens (PubMed:23966862, PubMed:29511076, PubMed:21593585).6 Publications
Mn2+-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.
Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system.Curated2 Publications


Isolates SZ3 and SZ16 have been isolated from Paguma larvata and are described as SARS-like in literature.Curated

<p>This subsection of the <a href="">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the <a href="">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Inhibited by Remdesivir (GS-5734).1 Publication

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

The kinetic parameters are studied for the 3C-like proteinase domain.
  1. KM=1.15 mM for peptide TSAVLQSGFRK-NH21 Publication
  2. KM=0.58 mM for peptide SGVTFQGKFKK1 Publication
  3. KM=1.44 mM for peptide ATVRLQAGNAT1 Publication

    pH dependencei

    Optimum pH is 7.0 for 3C-like proteinase activity.1 Publication


    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei1651For PL-PRO activityPROSITE-ProRule annotation1
    Active sitei1812For PL-PRO activityPROSITE-ProRule annotation1
    Active sitei3281For 3CL-PRO activityPROSITE-ProRule annotation1
    Active sitei3385For 3CL-PRO activityPROSITE-ProRule annotation1
    <p>This subsection of the <a href="">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi4304Zinc1
    Metal bindingi4304Zinc 1PROSITE-ProRule annotation1
    Metal bindingi4307Zinc1
    Metal bindingi4307Zinc 1PROSITE-ProRule annotation1
    Metal bindingi4313Zinc1
    Metal bindingi4313Zinc 1PROSITE-ProRule annotation1
    Metal bindingi4320Zinc1
    Metal bindingi4320Zinc 1PROSITE-ProRule annotation1
    Metal bindingi4347Zinc1
    Metal bindingi4347Zinc 2PROSITE-ProRule annotation1
    Metal bindingi4350Zinc1
    Metal bindingi4350Zinc 2PROSITE-ProRule annotation1
    Metal bindingi4358Zinc1
    Metal bindingi4358Zinc 2PROSITE-ProRule annotation1
    Metal bindingi4360Zinc 2PROSITE-ProRule annotation1
    Active sitei5128PROSITE-ProRule annotation1
    Active sitei5129PROSITE-ProRule annotation1
    Active sitei5130PROSITE-ProRule annotation1
    Metal bindingi5306Zinc 3PROSITE-ProRule annotation1
    Metal bindingi5309Zinc 3PROSITE-ProRule annotation1
    Metal bindingi5317Zinc 4PROSITE-ProRule annotation1
    Metal bindingi5320Zinc 3PROSITE-ProRule annotation1
    Metal bindingi5327Zinc 3PROSITE-ProRule annotation1
    Metal bindingi5330Zinc 4PROSITE-ProRule annotation1
    Metal bindingi5334Zinc 4PROSITE-ProRule annotation1
    Metal bindingi5340Zinc 4PROSITE-ProRule annotation1
    Metal bindingi5351Zinc 5PROSITE-ProRule annotation1
    Metal bindingi5356Zinc 5PROSITE-ProRule annotation1
    Metal bindingi5373Zinc 5PROSITE-ProRule annotation1
    Metal bindingi5376Zinc 5PROSITE-ProRule annotation1
    Active sitei5992PROSITE-ProRule annotation1
    Active sitei5994PROSITE-ProRule annotation1
    Active sitei6093PROSITE-ProRule annotation1
    Metal bindingi6109Zinc 6PROSITE-ProRule annotation1
    Metal bindingi6112Zinc 6PROSITE-ProRule annotation1
    Metal bindingi6128Zinc 6PROSITE-ProRule annotation1
    Metal bindingi6131Zinc 6PROSITE-ProRule annotation1
    Metal bindingi6159Zinc 7PROSITE-ProRule annotation1
    Metal bindingi6163Zinc 7PROSITE-ProRule annotation1
    Metal bindingi6166Zinc 7PROSITE-ProRule annotation1
    Active sitei6170PROSITE-ProRule annotation1
    Active sitei6175PROSITE-ProRule annotation1
    Metal bindingi6181Zinc 7PROSITE-ProRule annotation1
    Metal bindingi6354Zinc 8PROSITE-ProRule annotation1
    Metal bindingi6375Zinc 8PROSITE-ProRule annotation1
    Metal bindingi6386Zinc 8PROSITE-ProRule annotation1
    Metal bindingi6389Zinc 8PROSITE-ProRule annotation1
    Active sitei6821PROSITE-ProRule annotation1
    Active sitei6905PROSITE-ProRule annotation1
    Active sitei6945PROSITE-ProRule annotation1
    Active sitei6978PROSITE-ProRule annotation1


    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="">Function</a> section specifies the position(s) and type(s) of zinc fingers within the protein.<p><a href='/help/zn_fing' target='_top'>More...</a></p>Zinc fingeri1729 – 1766C4-typePROSITE-ProRule annotationAdd BLAST38
    Zinc fingeri4304 – 4320Add BLAST17
    Zinc fingeri4347 – 4360Add BLAST14
    <p>This subsection of the <a href="">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi5583 – 5590ATPBy similarity8

    <p>The <a href="">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

    GO - Biological processi

    <p>UniProtKB Keywords constitute a <a href="">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

    Molecular functionEndonuclease, Exonuclease, Helicase, Hydrolase, Methyltransferase, Nuclease, Nucleotidyltransferase, Protease, RNA-binding, RNA-directed RNA polymerase, Thiol protease, Transferase
    Biological processActivation of host autophagy by virus, Decay of host mRNAs by virus, Eukaryotic host gene expression shutoff by virus, Eukaryotic host translation shutoff by virus, Host gene expression shutoff by virus, Host mRNA suppression by virus, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host ISG15 by virus, Inhibition of host NF-kappa-B by virus, Modulation of host ubiquitin pathway by viral deubiquitinase, Modulation of host ubiquitin pathway by virus, Ubl conjugation pathway, Viral immunoevasion, Viral RNA replication
    LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

    Enzyme and pathway databases

    BRENDA Comprehensive Enzyme Information System

    BRENDAi, 7599
    3.4.22.B14, 7599, 7599

    Reactome - a knowledgebase of biological pathways and processes

    R-HSA-9679504, Translation of Replicase and Assembly of the Replication Transcription Complex
    R-HSA-9682706, Replication of the SARS-CoV-1 genome
    R-HSA-9682708, Transcription of SARS-CoV-1 sgRNAs
    R-HSA-9683439, Assembly of the SARS-CoV-1 Replication-Transcription Complex (RTC)
    R-HSA-9684325, Maturation of replicase proteins

    SABIO-RK: Biochemical Reaction Kinetics Database


    Protein family/group databases

    MEROPS protease database


    <p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

    <p>This subsection of the <a href="">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
    Recommended name:
    Replicase polyprotein 1ab
    Short name:
    Alternative name(s):
    ORF1ab polyprotein
    Cleaved into the following 15 chains:
    Alternative name(s):
    Leader protein
    Non-structural protein 1
    Short name:
    Non-structural protein 2
    Short name:
    Alternative name(s):
    p65 homolog
    Non-structural protein 3 (EC:, EC:
    Short name:
    Alternative name(s):
    Papain-like proteinase
    Short name:
    Non-structural protein 4
    Short name:
    3C-like proteinase (EC:3.4.22.-)
    Short name:
    Short name:
    Alternative name(s):
    Main protease
    Short name:
    Non-structural protein 5
    Short name:
    SARS coronavirus main proteinase
    Non-structural protein 6
    Short name:
    Non-structural protein 7
    Short name:
    Non-structural protein 8
    Short name:
    Non-structural protein 9
    Short name:
    Non-structural protein 10
    Short name:
    Alternative name(s):
    Growth factor-like peptide
    Short name:
    RNA-directed RNA polymerase (EC:
    Short name:
    Short name:
    Alternative name(s):
    Non-structural protein 12
    Short name:
    Helicase (EC:, EC:
    Short name:
    Alternative name(s):
    Non-structural protein 13
    Short name:
    Proofreading exoribonuclease2 Publications (EC:2.1.1.-, EC:3.1.13.-)
    Short name:
    Alternative name(s):
    Guanine-N7 methyltransferase
    Non-structural protein 14
    Short name:
    Uridylate-specific endoribonuclease (EC:3.1.-.-)
    Alternative name(s):
    Non-structural protein 15
    Short name:
    2'-O-methyltransferase (EC:2.1.1.-)
    Alternative name(s):
    Non-structural protein 16
    Short name:
    <p>This subsection of the <a href="">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
    ORF Names:1a-1b
    <p>This subsection of the <a href="">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiSevere acute respiratory syndrome coronavirus (SARS-CoV)
    <p>This subsection of the <a href="">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri694009 [NCBI]
    <p>This subsection of the <a href="">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiVirusesRiboviriaOrthornaviraePisuviricotaPisoniviricetesNidoviralesCornidovirineaeCoronaviridaeOrthocoronavirinaeBetacoronavirusSarbecovirus
    <p>This subsection of the <a href="">Names and taxonomy</a> section only exists in viral entries and indicates the host(s) either as a specific organism or taxonomic group of organisms that are susceptible to be infected by a virus.<p><a href='/help/virus_host' target='_top'>More...</a></p>Virus hostiHomo sapiens (Human) [TaxID: 9606]
    Paguma larvata (Masked palm civet) [TaxID: 9675]
    <p>This subsection of the <a href="">Names and taxonomy</a> section is present for entries that are part of a <a href="">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi

    <p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

    • host perinuclear region By similarity
    • Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity).By similarity
    • host perinuclear region By similarity
    • Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity).By similarity
    • host perinuclear region By similarity
    • Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity).By similarity


    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini1 – 2202CytoplasmicCuratedAdd BLAST2202
    <p>This subsection of the <a href="">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei2203 – 2223HelicalSequence analysisAdd BLAST21
    Topological domaini2224 – 2303LumenalCuratedAdd BLAST80
    Transmembranei2304 – 2324HelicalSequence analysisAdd BLAST21
    Topological domaini2325 – 2350CytoplasmicCuratedAdd BLAST26
    Transmembranei2351 – 2371HelicalSequence analysisAdd BLAST21
    Topological domaini2372 – 2754LumenalCuratedAdd BLAST383
    Transmembranei2755 – 2775HelicalSequence analysisAdd BLAST21
    Topological domaini2776 – 2991CytoplasmicCuratedAdd BLAST216
    Transmembranei2992 – 3012HelicalSequence analysisAdd BLAST21
    Topological domaini3013 – 3021LumenalCurated9
    Transmembranei3022 – 3042HelicalSequence analysisAdd BLAST21
    Topological domaini3043 – 3053CytoplasmicCuratedAdd BLAST11
    Transmembranei3054 – 3074HelicalSequence analysisAdd BLAST21
    Topological domaini3075 – 3076LumenalCurated2
    Transmembranei3077 – 3097HelicalSequence analysisAdd BLAST21
    Topological domaini3098 – 3104CytoplasmicCurated7
    Transmembranei3105 – 3125HelicalSequence analysisAdd BLAST21
    Topological domaini3126 – 3141LumenalCuratedAdd BLAST16
    Transmembranei3142 – 3162HelicalSequence analysisAdd BLAST21
    Topological domaini3163 – 3563CytoplasmicCuratedAdd BLAST401
    Transmembranei3564 – 3584HelicalSequence analysisAdd BLAST21
    Topological domaini3585LumenalCurated1
    Transmembranei3586 – 3606HelicalSequence analysisAdd BLAST21
    Topological domaini3607 – 3611CytoplasmicCurated5
    Transmembranei3612 – 3632HelicalSequence analysisAdd BLAST21
    Topological domaini3633 – 3657LumenalCuratedAdd BLAST25
    Transmembranei3658 – 3678HelicalSequence analysisAdd BLAST21
    Topological domaini3679 – 3684CytoplasmicCurated6
    Transmembranei3685 – 3704HelicalSequence analysisAdd BLAST20
    Topological domaini3705 – 3727LumenalCuratedAdd BLAST23
    Transmembranei3728 – 3748HelicalSequence analysisAdd BLAST21
    Topological domaini3749 – 3755CytoplasmicCurated7
    Transmembranei3756 – 3776HelicalSequence analysisAdd BLAST21
    Topological domaini3777 – 7073LumenalCuratedAdd BLAST3297

    Keywords - Cellular componenti

    Host cytoplasm, Host membrane, Membrane

    <p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi


    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi4217G → E: Complete loss of nsp9 dimerization. 1 Publication1
    Mutagenesisi4221G → E: Complete loss of nsp9 dimerization. 1 Publication1

    Chemistry databases

    ChEMBL database of bioactive drug-like small molecules


    Drug and drug target database

    DB08748, 4-(Dimethylamino)benzoic acid
    DB08656, 5-amino-2-methyl-N-[(1R)-1-naphthalen-1-ylethyl]benzamide
    DB07293, benzyl (2-oxopropyl)carbamate
    DB15686, GS-441524
    DB14761, Remdesivir



    <p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000373091 – 180Host translation inhibitor nsp1By similarityAdd BLAST180
    ChainiPRO_0000037310181 – 818Non-structural protein 2By similarityAdd BLAST638
    ChainiPRO_0000037311819 – 2740Non-structural protein 3By similarityAdd BLAST1922
    ChainiPRO_00002838412741 – 3240Non-structural protein 4Sequence analysisAdd BLAST500
    ChainiPRO_00000373123241 – 35463C-like proteinaseBy similarityAdd BLAST306
    ChainiPRO_00000373133547 – 3836Non-structural protein 6By similarityAdd BLAST290
    ChainiPRO_00000373143837 – 3919Non-structural protein 7By similarityAdd BLAST83
    ChainiPRO_00000373153920 – 4117Non-structural protein 8By similarityAdd BLAST198
    ChainiPRO_00000373164118 – 4230Non-structural protein 9By similarityAdd BLAST113
    ChainiPRO_00000373174231 – 4369Non-structural protein 10By similarityAdd BLAST139
    ChainiPRO_00000373184370 – 5301RNA-directed RNA polymeraseBy similarityAdd BLAST932
    ChainiPRO_00000373195302 – 5902HelicaseBy similarityAdd BLAST601
    ChainiPRO_00000373205903 – 6429Proofreading exoribonucleaseBy similarityAdd BLAST527
    ChainiPRO_00000373216430 – 6775Uridylate-specific endoribonucleaseBy similarityAdd BLAST346
    ChainiPRO_00000373226776 – 70732'-O-methyltransferaseBy similarityAdd BLAST298

    <p>This subsection of the <a href="">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

    Specific enzymatic cleavages in vivo by its own proteases yield mature proteins (PubMed:32083638). 3CL-PRO and PL-PRO proteinases are autocatalytically processed (By similarity).By similarity1 Publication


    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei180 – 181CleavageBy similarity2
    Sitei818 – 819Cleavage; by PL-PROBy similarity2
    Sitei2740 – 2741Cleavage; by PL-PROBy similarity2
    Sitei3240 – 3241Cleavage; by 3CL-PROBy similarity2
    Sitei3546 – 3547Cleavage; by 3CL-PROBy similarity2
    Sitei3836 – 3837Cleavage; by 3CL-PRO1 Publication2
    Sitei3919 – 3920Cleavage; by 3CL-PRO1 Publication2
    Sitei4117 – 4118Cleavage; by 3CL-PRO1 Publication2
    Sitei4230 – 4231Cleavage; by 3CL-PRO1 Publication2
    Sitei4369 – 4370Cleavage; by 3CL-PROBy similarity2
    Sitei5301 – 5302Cleavage; by 3CL-PROBy similarity2
    Sitei5902 – 5903Cleavage; by 3CL-PROBy similarity2
    Sitei6429 – 6430Cleavage; by 3CL-PROBy similarity2
    Sitei6775 – 6776Cleavage; by 3CL-PROBy similarity2

    Proteomic databases

    PRoteomics IDEntifications database


    <p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

    <p>This subsection of the <a href="">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

    Interacts with host PHB and PHB2.

    1 Publication

    Interacts with PL-PRO and nsp6.

    1 Publication

    Exists as monomer and homodimer. Only the homodimer shows catalytic activity.

    2 Publications

    Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling ring structure.

    1 Publication

    Interacts with ORF6 protein.

    1 Publication


    1 Publication

    Forms a dodecamer and interacts with nsp14 and nsp16; these interactions enhance nsp14 and nsp16 enzymatic activities.

    3 Publications

    Interacts (via N-terminus) with DDX1.

    1 Publication

    <p>This subsection of the '<a href="">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="">IntAct database</a>. It is updated at every <a href="">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

    Host translation inhibitor nsp1 (PRO_0000037309)
    E [P59637]2EBI-25475797,EBI-25487741
    CHMP2B [Q9UQN3] from Homo sapiens.2EBI-25475797,EBI-718324
    FKBP1A [P62942] from Homo sapiens.4EBI-25475797,EBI-1027571
    LAS1L [Q9Y4W2] from Homo sapiens.2EBI-25475797,EBI-1051591
    PPIA [P62937] from Homo sapiens.4EBI-25475797,EBI-437708
    PPIG [Q13427] from Homo sapiens.4EBI-25475797,EBI-396072
    PPIH [O43447] from Homo sapiens.4EBI-25475797,EBI-1055615
    RCAN3 [Q9UKA8] from Homo sapiens.2EBI-25475797,EBI-9091952
    Non-structural protein 2 (PRO_0000037310)
    Non-structural protein 11 (PRO_0000338265)2EBI-25474098,EBI-25492625
    3a [P59632]2EBI-25474098,EBI-15595051
    Non-structural protein 3 (PRO_0000037311)3EBI-25474098,EBI-25474079
    Non-structural protein 8 (PRO_0000037315)4EBI-25474098,EBI-25487941
    SERPING1 [P05155] from Homo sapiens.2EBI-25474098,EBI-1223454
    Non-structural protein 3 (PRO_0000037311)
    E [P59637]5EBI-25474079,EBI-25487741
    3C-like proteinase (PRO_0000037312)2EBI-25474079,EBI-25487250
    Non-structural protein 8 (PRO_0000037315)2EBI-25474079,EBI-25487941
    RNA-directed RNA polymerase (PRO_0000037318)3EBI-25474079,EBI-25487684
    CAMK2D [Q13557] from Homo sapiens.4EBI-25474079,EBI-351018
    IRF3 [Q14653] from Homo sapiens.5EBI-25474079,EBI-2650369
    MKRN2 [Q9H000] from Homo sapiens.2EBI-25474079,EBI-2341005
    MKRN3 [Q13064] from Homo sapiens.2EBI-25474079,EBI-2340269
    RCHY1 [Q96PM5] from Homo sapiens.9EBI-25474079,EBI-947779
    STING1 [Q86WV6] from Homo sapiens.2EBI-25474079,EBI-2800345
    3C-like proteinase (PRO_0000037312)
    Non-structural protein 8 (PRO_0000037315)2EBI-25487250,EBI-25487941
    1a [K9N638] from Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012).2EBI-25487250,EBI-25618448
    FKBP1A [P62942] from Homo sapiens.2EBI-25487250,EBI-1027571
    Non-structural protein 6 (PRO_0000037313)
    Non-structural protein 2 (PRO_0000037310)3EBI-25487192,EBI-25474098
    Non-structural protein 7 (PRO_0000037314)
    Non-structural protein 8 (PRO_0000037315)9EBI-25487672,EBI-25487941
    DDAH2 [O95865] from Homo sapiens.2EBI-25487672,EBI-749139
    MIF4GD [A9UHW6] from Homo sapiens.2EBI-25487672,EBI-373498
    Non-structural protein 8 (PRO_0000037315)
    E [P59637]2EBI-25487941,EBI-25487741
    ORF6 [Q19QW5]5EBI-25487941,EBI-25493595
    MACROH2A2 [Q9P0M6] from Homo sapiens.2EBI-25487941,EBI-3922608
    NOMO3 [P69849] from Homo sapiens.2EBI-25487941,EBI-947048
    TERF1 [P54274] from Homo sapiens.2EBI-25487941,EBI-710997
    Non-structural protein 9 (PRO_0000037316)
    Host translation inhibitor nsp1 (PRO_0000037309)2EBI-25475825,EBI-25475797
    Non-structural protein 7 (PRO_0000037314)2EBI-25475825,EBI-25487672
    Non-structural protein 8 (PRO_0000037315)4EBI-25475825,EBI-25487941
    Proofreading exoribonuclease (PRO_0000037320)2EBI-25475825,EBI-25487328
    CHMP2B [Q9UQN3] from Homo sapiens.2EBI-25475825,EBI-718324
    SNAP47 [Q5SQN1] from Homo sapiens.2EBI-25475825,EBI-10244848
    RNA-directed RNA polymerase (PRO_0000037318)
    Non-structural protein 8 (PRO_0000037315)5EBI-25487684,EBI-25487941
    Helicase (PRO_0000037319)
    Non-structural protein 3 (PRO_0000037311)2EBI-25487926,EBI-25474079
    Non-structural protein 8 (PRO_0000037315)3EBI-25487926,EBI-25487941
    RNA-directed RNA polymerase (PRO_0000037318)5EBI-25487926,EBI-25487684
    CHEK2 [O96017] from Homo sapiens.2EBI-25487926,EBI-1180783
    RYBP [Q8N488] from Homo sapiens.2EBI-25487926,EBI-752324
    Proofreading exoribonuclease (PRO_0000037320)
    9b [P59636]3EBI-25487328,EBI-9021274
    Non-structural protein 3 (PRO_0000037311)2EBI-25487328,EBI-25474079
    Non-structural protein 8 (PRO_0000037315)3EBI-25487328,EBI-25487941
    Non-structural protein 10 (PRO_0000037317)7EBI-25487328,EBI-25487277
    RNA-directed RNA polymerase (PRO_0000037318)3EBI-25487328,EBI-25487684
    SERPING1 [P05155] from Homo sapiens.2EBI-25487328,EBI-1223454
    Uridylate-specific endoribonuclease (PRO_0000037321)
    Non-structural protein 8 (PRO_0000037315)2EBI-25487301,EBI-25487941
    RB1 [P06400] from Homo sapiens.3EBI-25487301,EBI-491274
    2'-O-methyltransferase (PRO_0000037322)
    Non-structural protein 2 (PRO_0000037310)2EBI-25487235,EBI-25474098
    Non-structural protein 3 (PRO_0000037311)3EBI-25487235,EBI-25474079
    Non-structural protein 10 (PRO_0000037317)16EBI-25487235,EBI-25487277
    VHL [P40337] from Homo sapiens.7EBI-25487235,EBI-301246
    Non-structural protein 4 (PRO_0000283841)
    Non-structural protein 3 (PRO_0000037311)3EBI-25488721,EBI-25474079

    GO - Molecular functioni

    Protein-protein interaction databases

    The Biological General Repository for Interaction Datasets (BioGRID)

    4383938, 1 interactor
    4383939, 22 interactors
    4383940, 50 interactors
    4383941, 32 interactors
    4383942, 31 interactors
    4383943, 16 interactors
    4383944, 17 interactors
    4383945, 43 interactors
    4383946, 51 interactors
    4383947, 36 interactors
    4383948, 18 interactors
    4383949, 55 interactors
    4383950, 91 interactors
    4383951, 19 interactors
    4383952, 12 interactors
    4383953, 18 interactors

    ComplexPortal: manually curated resource of macromolecular complexes

    CPX-5706, SARS-CoV main protease complex
    CPX-5707, SARS-CoV 3'-5' exoribonuclease proof-reading complex
    CPX-5709, SARS-CoV NSP10-NSP16 2'-O-methyltransferase complex
    CPX-5710, SARS-CoV primase complex
    CPX-5711, SARS-CoV NSP15 complex
    CPX-5717, SARS-CoV polymerase complex
    CPX-5719, SARS-CoV NSP9 complex
    CPX-5721, SARS-CoV NSP3-NSP4-NSP6 complex

    Protein interaction database and analysis system

    P0C6X7, 340 interactors

    Molecular INTeraction database


    Chemistry databases

    BindingDB database of measured binding affinities


    <p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

    Secondary structure

    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    Biological Magnetic Resonance Data Bank


    SWISS-MODEL Repository - a database of annotated 3D protein structure models


    Database of comparative protein structure models


    Protein Data Bank in Europe - Knowledge Base


    Miscellaneous databases

    Relative evolutionary importance of amino acids within a protein sequence


    <p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini821 – 930Ubiquitin-like 1PROSITE-ProRule annotationAdd BLAST110
    Domaini1003 – 1169Macro 1PROSITE-ProRule annotationAdd BLAST167
    Domaini1207 – 1335Macro 2PROSITE-ProRule annotationAdd BLAST129
    Domaini1343 – 1470Macro 3PROSITE-ProRule annotationAdd BLAST128
    Domaini1472 – 1538DPUPPROSITE-ProRule annotationAdd BLAST67
    Domaini1542 – 1597Ubiquitin-like 2PROSITE-ProRule annotationAdd BLAST56
    Domaini1611 – 1875Peptidase C16PROSITE-ProRule annotationAdd BLAST265
    Domaini1888 – 1998Nucleic acid-bindingPROSITE-ProRule annotationAdd BLAST111
    Domaini3142 – 3240Nsp4CPROSITE-ProRule annotationAdd BLAST99
    Domaini3241 – 3546Peptidase C30PROSITE-ProRule annotationAdd BLAST306
    Domaini3837 – 3919RdRp Nsp7 cofactorPROSITE-ProRule annotationAdd BLAST83
    Domaini3920 – 4117RdRp Nsp8 cofactorPROSITE-ProRule annotationAdd BLAST198
    Domaini4118 – 4230Nsp9 ssRNA-bindingPROSITE-ProRule annotationAdd BLAST113
    Domaini4231 – 4369ExoN/MTase coactivatorPROSITE-ProRule annotationAdd BLAST139
    Domaini4376 – 4630NiRANPROSITE-ProRule annotationAdd BLAST255
    Domaini4734 – 5301Nsp12 RNA-dependent RNA polymerasePROSITE-ProRule annotationAdd BLAST568
    Domaini4981 – 5143RdRp catalyticPROSITE-ProRule annotationAdd BLAST163
    Domaini5302 – 5385CV ZBDPROSITE-ProRule annotationAdd BLAST84
    Domaini5558 – 5739(+)RNA virus helicase ATP-bindingAdd BLAST182
    Domaini5740 – 5909(+)RNA virus helicase C-terminalAdd BLAST170
    Domaini5974 – 6189ExoNPROSITE-ProRule annotationAdd BLAST216
    Domaini6198 – 6429N7-MTasePROSITE-ProRule annotationAdd BLAST232
    Domaini6777 – 7071Nidovirus-type SAM-dependent 2'-O-MTasePROSITE-ProRule annotationAdd BLAST295


    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni2092 – 2371HD1Add BLAST280
    Regioni2755 – 3162HD2Add BLAST408
    Regioni3564 – 3776HD3Add BLAST213
    Regioni6233 – 6239SAM-bindingPROSITE-ProRule annotation7
    Regioni6316 – 6330GpppA-bindingPROSITE-ProRule annotationAdd BLAST15

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Family and Domains' section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi930 – 1001Glu-richAdd BLAST72
    Compositional biasi2210 – 2213Poly-Leu4
    Compositional biasi3766 – 3769Poly-Cys4

    <p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

    The hydrophobic domains (HD) could mediate the membrane association of the replication complex and thereby alter the architecture of the host cell membrane.

    <p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

    Zinc finger

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Zinc fingeri1729 – 1766C4-typePROSITE-ProRule annotationAdd BLAST38
    Zinc fingeri4304 – 4320Add BLAST17
    Zinc fingeri4347 – 4360Add BLAST14

    Keywords - Domaini

    Repeat, Transmembrane, Transmembrane helix, Zinc-finger

    Family and domain databases

    Conserved Domains Database

    cd21409, 1B_cv_Nsp13-like, 1 hit
    cd21560, betaCoV-Nsp6, 1 hit
    cd21659, betaCoV_Nsp14, 1 hit
    cd21666, betaCoV_Nsp5_Mpro, 1 hit
    cd20762, capping_2-OMTase_Nidovirales, 1 hit
    cd21516, cv_beta_Nsp2_SARS-like, 1 hit
    cd21473, cv_Nsp4_TM, 1 hit
    cd21167, M_alpha_beta_cv_Nsp15-like, 1 hit
    cd21562, Macro_cv_SUD-N_Nsp3-like, 1 hit
    cd21557, Macro_X_Nsp3-like, 1 hit
    cd21161, NendoU_cv_Nsp15-like, 1 hit
    cd21171, NTD_alpha_beta_cv_Nsp15-like, 1 hit
    cd21591, SARS-CoV-like_RdRp, 1 hit
    cd21525, SUD_C_SARS-CoV_Nsp3, 1 hit
    cd21467, Ubl1_cv_Nsp3_N-like, 1 hit
    cd21466, Ubl2_cv_PLpro_N_Nsp3-like, 1 hit
    cd21401, ZBD_cv_Nsp13-like, 1 hit

    Gene3D Structural and Functional Annotation of Protein Families

    Gene3Di, 1 hit
    1.10.1840.10, 1 hit, 1 hit, 1 hit, 1 hit, 1 hit, 2 hits, 1 hit, 1 hit, 1 hit, 1 hit, 1 hit, 1 hit, 1 hit, 1 hit, 1 hit, 1 hit

    Integrated resource of protein families, domains and functional sites

    View protein in InterPro
    IPR027351, (+)RNA_virus_helicase_core_dom
    IPR043608, CoV_NSP15_M
    IPR043606, CoV_NSP15_N
    IPR043613, CoV_NSP2_C
    IPR043611, CoV_NSP3_C
    IPR043612, CoV_NSP4_N
    IPR043502, DNA/RNA_pol_sf
    IPR022733, DPUP_SUD_C_bCoV
    IPR037227, EndoU-like
    IPR002589, Macro_dom
    IPR043472, Macro_dom-like
    IPR044371, Macro_X_NSP3-like
    IPR042570, NAR_sf
    IPR043609, NendoU_nidovirus
    IPR036333, NSP10_sf_CoV
    IPR044343, NSP13_1B_dom_CoV
    IPR027352, NSP13_ZBD_CoV-like
    IPR044315, NSP14_betaCoV
    IPR009466, NSP14_CoV
    IPR044330, NSP15_alpha_betaCoV_N
    IPR044322, NSP15_M_alpha_beta_CoV
    IPR043174, NSP15_middle_sf
    IPR042515, NSP15_N_CoV
    IPR044401, NSP15_NendoU_CoV
    IPR009461, NSP16_CoV-like
    IPR021590, NSP1_bCoV
    IPR038030, NSP1_sf_bCoV
    IPR043615, NSP2_N_CoV
    IPR044389, NSP2_SARS-CoV-like
    IPR024375, NSP3_bCoV
    IPR024358, NSP3_N_bCoV
    IPR032592, NSP3_NAR_bCoV
    IPR038166, NSP3_PL2pro_sf_CoV
    IPR038400, NSP3_SUD-M_sf_bCoV
    IPR043478, NSP3_SUD-N_bCoV
    IPR044374, NSP3_SUD-N_SARS-CoV
    IPR044357, NSP3_Ubl1_dom_CoV
    IPR044353, Nsp3_Ubl2_dom_CoV
    IPR038083, NSP3A-like
    IPR032505, NSP4_C_CoV
    IPR038123, NSP4_C_sf_CoV
    IPR044367, NSP6_betaCoV
    IPR043610, NSP6_CoV
    IPR014828, NSP7_CoV
    IPR037204, NSP7_sf_CoV
    IPR014829, NSP8_CoV-like
    IPR037230, NSP8_sf_CoV
    IPR014822, NSP9_CoV
    IPR036499, NSP9_sf_CoV
    IPR027417, P-loop_NTPase
    IPR013016, Peptidase_C16_CoV
    IPR008740, Peptidase_C30_CoV
    IPR043477, Peptidase_C30_dom3_CoV
    IPR009003, Peptidase_S1_PA
    IPR043504, Peptidase_S1_PA_chymotrypsin
    IPR043177, PLpro_N_sf_CoV
    IPR043503, PLpro_palm_finger_dom_CoV
    IPR043178, PLpro_thumb_sf_CoV
    IPR044351, RdRp_SARS-CoV-like
    IPR001205, RNA-dir_pol_C
    IPR007094, RNA-dir_pol_PSvirus
    IPR009469, RNA_pol_N_coronovir
    IPR018995, RNA_synth_NSP10_CoV
    IPR029063, SAM-dependent_MTases

    Pfam protein domain database

    View protein in Pfam
    PF16251, bCoV_NAR, 1 hit
    PF11501, bCoV_NSP1, 1 hit
    PF12379, bCoV_NSP3_N, 1 hit
    PF12124, bCoV_SUD_C, 1 hit
    PF11633, bCoV_SUD_M, 1 hit
    PF06471, CoV_Methyltr_1, 1 hit
    PF06460, CoV_Methyltr_2, 1 hit
    PF09401, CoV_NSP10, 1 hit
    PF19215, CoV_NSP15_C, 1 hit
    PF19216, CoV_NSP15_M, 1 hit
    PF19219, CoV_NSP15_N, 1 hit
    PF19212, CoV_NSP2_C, 1 hit
    PF19211, CoV_NSP2_N, 1 hit
    PF19218, CoV_NSP3_C, 1 hit
    PF16348, CoV_NSP4_C, 1 hit
    PF19217, CoV_NSP4_N, 1 hit
    PF19213, CoV_NSP6, 1 hit
    PF08716, CoV_NSP7, 1 hit
    PF08717, CoV_NSP8, 1 hit
    PF08710, CoV_NSP9, 1 hit
    PF08715, CoV_peptidase, 1 hit
    PF06478, CoV_RPol_N, 1 hit
    PF01661, Macro, 1 hit
    PF05409, Peptidase_C30, 1 hit
    PF00680, RdRP_1, 1 hit
    PF01443, Viral_helicase1, 1 hit

    Simple Modular Architecture Research Tool; a protein domain database

    View protein in SMART
    SM00506, A1pp, 1 hit

    Superfamily database of structural and functional annot