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Entry version 8 (02 Jun 2021)
Sequence version 1 (22 Apr 2020)
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Protein

Replicase polyprotein 1ab

Gene

rep

Organism
Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) (SARS-CoV-2)
Status
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.

By similarity

Inhibits host translation by interacting with binds to the host 40S subunit in ribosomal complexes, including the 43S pre-initiation complex and the non-translating 80S ribosome (PubMed:32680882,PubMed:32908316).

The C-terminus binds to and obstructs ribosomal mRNA entry tunnel (PubMed:32680882,PubMed:32908316).

Thereby inhibits antiviral response triggered by innate immunity or interferons (PubMed:32680882,PubMed:32979938).

The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation (By similarity).

Viral mRNAs less susceptible to nsp1-mediated inhibition of translation, because of their 5'-end leader sequence (PubMed:32908316).

By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response (By similarity).

By similarity3 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.

By similarity

Responsible for the cleavages located at the N-terminus of the replicase polyprotein. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication (By similarity).

Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3 (PubMed:32733001).

Prevents also host NF-kappa-B signaling (By similarity).

In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates (PubMed:32726803).

Cleaves preferentially ISG15 from substrates in vitro (PubMed:32726803).

Can play a role in host ADP-ribosylation by binding ADP-ribose (PubMed:32578982).

By similarity3 Publications

Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.

By similarity

Cleaves the C-terminus of replicase polyprotein at 11 sites (PubMed:32321856).

Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN] (PubMed:32198291, PubMed:32272481).

Also able to bind an ADP-ribose-1''-phosphate (ADRP) (By similarity) (PubMed:32198291, PubMed:32272481).

By similarity3 Publications

Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic (By similarity).

Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes (By similarity).

Binds to host TBK1 without affecting TBK1 phosphorylation; the interaction with TBK1 decreases IRF3 phosphorylation, which leads to reduced IFN-beta production (PubMed:32979938).

By similarity1 Publication

Plays a role in viral RNA synthesis (PubMed:32358203, PubMed:32277040, PubMed:32438371, PubMed:32526208).

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 (By similarity).

By similarity4 Publications

Plays a role in viral RNA synthesis (PubMed:32358203, PubMed:32277040, PubMed:32438371, PubMed:32526208).

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 (By similarity).

By similarity4 Publications

May participate in viral replication by acting as a ssRNA-binding protein.

By similarity

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.

By similarity

Responsible for replication and transcription of the viral RNA genome.

4 Publications

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 (By similarity).

Binds to host TBK1 and inhibits TBK1 phosphorylation; the interaction with TBK1 decreases IRF3 phosphorylation, which leads to reduced IFN-beta production (PubMed:32979938).

By similarity1 Publication

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. Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens.

By similarity

Mn2+-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.

By similarity

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.

By similarity

Miscellaneous

Produced by -1 ribosomal frameshifting at the 1a-1b genes boundary.By similarity
Variant B.1.1.7 is also called Variant Of Concern (VOC) 202012/01, Variant Under Investigation (VUI) 202012/01, or 20B/501Y.V1.1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">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="http://www.uniprot.org/help/function%5Fsection">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 in vitro by GRL-0617.1 Publication
Inhibited by Remdesivir antiviral drug (GS-5734).By similarity
Inhibited by Remdesivir antiviral drug (GS-5734) through non-obligate RNA chain termination.2 Publications
Inhibited by pyridone-containing alpha-ketoamides compounds 13a and 13b. In turn, alpha-ketoamide 13b (tert-butyl (1-((S)-1-(((S)-4-(benzylamino)-3,4-dioxo-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-2-oxo-1,2-dihydropyridin-3-yl)carbamate) inhibits SARS-CoV-2 replication in human lung cells (PubMed:32198291). Inhibited ex vivo by michael acceptor inhibitor N3 (PubMed:32272481). Inhibited ex vivo by compound 11a and 11b (PubMed:32321856).3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">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 sitei1674For PL1-PRO activityPROSITE-ProRule annotation1 Publication1
Active sitei1835For PL2-PRO activityPROSITE-ProRule annotation1
Active sitei3304For 3CL-PRO activityPROSITE-ProRule annotation1 Publication1
Active sitei3408Nucleophile; for 3CL-PRO activityPROSITE-ProRule annotation1 Publication1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">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 bindingi4327Zinc 1PROSITE-ProRule annotation1
Metal bindingi4330Zinc 1PROSITE-ProRule annotation1
Metal bindingi4336Zinc 1PROSITE-ProRule annotation1
Metal bindingi4343Zinc 1PROSITE-ProRule annotation1
Metal bindingi4370Zinc 2PROSITE-ProRule annotation1
Metal bindingi4373Zinc 2PROSITE-ProRule annotation1
Metal bindingi4381Zinc 2PROSITE-ProRule annotation1
Metal bindingi4383Zinc 2PROSITE-ProRule annotation1
Metal bindingi4687Zinc 3; structural2 Publications1
Metal bindingi4693Zinc 3; structural2 Publications1
Metal bindingi4698Zinc 3; structural2 Publications1
Metal bindingi4702Zinc 3; structural2 Publications1
Metal bindingi4879Zinc 4; structural2 Publications1
Metal bindingi5034Zinc 4; structural2 Publications1
Metal bindingi5037Zinc 4; structural2 Publications1
Metal bindingi5038Zinc 4; structural2 Publications1
Active sitei5151PROSITE-ProRule annotation1
Active sitei5152PROSITE-ProRule annotation1
Active sitei5153PROSITE-ProRule annotation1
Metal bindingi5329Zinc 5PROSITE-ProRule annotation1
Metal bindingi5332Zinc 5PROSITE-ProRule annotation1
Metal bindingi5340Zinc 6PROSITE-ProRule annotation1
Metal bindingi5343Zinc 5PROSITE-ProRule annotation1
Metal bindingi5350Zinc 5PROSITE-ProRule annotation1
Metal bindingi5353Zinc 6; via tele nitrogenPROSITE-ProRule annotation1
Metal bindingi5357Zinc 6; via pros nitrogenPROSITE-ProRule annotation1
Metal bindingi5363Zinc 6PROSITE-ProRule annotation1
Metal bindingi5374Zinc 7PROSITE-ProRule annotation1
Metal bindingi5379Zinc 7; via pros nitrogenPROSITE-ProRule annotation1
Metal bindingi5396Zinc 7PROSITE-ProRule annotation1
Metal bindingi5399Zinc 7PROSITE-ProRule annotation1
Active sitei6015PROSITE-ProRule annotation1
Active sitei6017PROSITE-ProRule annotation1
Active sitei6116PROSITE-ProRule annotation1
Metal bindingi6132Zinc 8PROSITE-ProRule annotation1
Metal bindingi6135Zinc 8PROSITE-ProRule annotation1
Metal bindingi6151Zinc 8PROSITE-ProRule annotation1
Metal bindingi6154Zinc 8PROSITE-ProRule annotation1
Metal bindingi6182Zinc 9PROSITE-ProRule annotation1
Metal bindingi6186Zinc 9PROSITE-ProRule annotation1
Metal bindingi6189Zinc 9PROSITE-ProRule annotation1
Active sitei6193PROSITE-ProRule annotation1
Active sitei6198PROSITE-ProRule annotation1
Metal bindingi6204Zinc 9PROSITE-ProRule annotation1
Metal bindingi6377Zinc 10PROSITE-ProRule annotation1
Metal bindingi6398Zinc 10PROSITE-ProRule annotation1
Metal bindingi6409Zinc 10PROSITE-ProRule annotation1
Metal bindingi6412Zinc 10PROSITE-ProRule annotation1
Active sitei6686PROSITE-ProRule annotation1
Active sitei6701PROSITE-ProRule annotation1
Active sitei6741PROSITE-ProRule annotation1
Active sitei6844PROSITE-ProRule annotation1
Active sitei6928PROSITE-ProRule annotation1
Active sitei6968PROSITE-ProRule annotation1
Active sitei7001PROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">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 fingeri1752 – 1789C4-typePROSITE-ProRule annotationAdd BLAST38
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">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 bindingi5606 – 5613NTPPROSITE-ProRule annotation8

<p>The <a href="http://www.geneontology.org/">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="http://www.uniprot.org/keywords">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 IRF3 by virus, Inhibition of host ISG15 by virus, Inhibition of host NF-kappa-B by virus, Inhibition of host RLR pathway by virus, Inhibition of host TBK1 by virus, Inhibition of host TLR pathway 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

More...
BRENDAi
2.7.7.48, 16869

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-9694271, Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC) [P0DTD1-1]
R-HSA-9694301, Maturation of replicase proteins [P0DTD1-1]
R-HSA-9694676, Translation of Replicase and Assembly of the Replication Transcription Complex [P0DTD1-1]
R-HSA-9694686, Replication of the SARS-CoV-2 genome [P0DTD1-1]
R-HSA-9694786, Transcription of SARS-CoV-2 sgRNAs [P0DTD1-1]

SABIO-RK: Biochemical Reaction Kinetics Database

More...
SABIO-RKi
P0DTD1

<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="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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:
pp1ab
Alternative name(s):
ORF1ab polyprotein
Cleaved into the following 15 chains:
Alternative name(s):
Leader protein
Non-structural protein 1
Short name:
nsp1
Non-structural protein 2
Short name:
nsp2
Alternative name(s):
p65 homolog
Non-structural protein 3 (EC:3.4.19.121 Publication, EC:3.4.22.-)
Short name:
nsp3
Alternative name(s):
PL2-PRO
Papain-like protease1 Publication
Papain-like proteinase
Short name:
PL-PRO
Non-structural protein 4
Short name:
nsp4
3C-like proteinase (EC:3.4.22.692 Publications)
Short name:
3CL-PRO
Short name:
3CLp
Alternative name(s):
Main protease
Short name:
Mpro1 Publication
Non-structural protein 5
Short name:
nsp5
SARS coronavirus main proteinase
Non-structural protein 6
Short name:
nsp6
Non-structural protein 7
Short name:
nsp7
Non-structural protein 8
Short name:
nsp8
Non-structural protein 9
Short name:
nsp9
Non-structural protein 10
Short name:
nsp10
Alternative name(s):
Growth factor-like peptide
Short name:
GFL
RNA-directed RNA polymerase (EC:2.7.7.48)
Short name:
Pol
Short name:
RdRp
Alternative name(s):
Non-structural protein 12
Short name:
nsp12
Helicase (EC:3.6.4.12, EC:3.6.4.13)
Short name:
Hel
Alternative name(s):
Non-structural protein 13
Short name:
nsp13
Proofreading exoribonuclease (EC:3.1.13.-)
Short name:
ExoN
Alternative name(s):
Guanine-N7 methyltransferase
Non-structural protein 14
Short name:
nsp14
Uridylate-specific endoribonuclease (EC:3.1.-.-)
Alternative name(s):
NendoU
Non-structural protein 15
Short name:
nsp15
2'-O-methyltransferase (EC:2.1.1.-)
Alternative name(s):
Non-structural protein 16
Short name:
nsp16
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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
Name:rep
ORF Names:1a-1b
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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 2 (2019-nCoV) (SARS-CoV-2)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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 identifieri2697049 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">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
  • UP000464024 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Genome

<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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'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 – 2225CytoplasmicCuratedAdd BLAST2225
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'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>Transmembranei2226 – 2246HelicalSequence analysisAdd BLAST21
Topological domaini2247 – 2317LumenalCuratedAdd BLAST71
Transmembranei2318 – 2338HelicalSequence analysisAdd BLAST21
Topological domaini2339 – 2775CytoplasmicCuratedAdd BLAST437
Transmembranei2776 – 2796HelicalSequence analysisAdd BLAST21
Topological domaini2797 – 3044LumenalCuratedAdd BLAST248
Transmembranei3045 – 3065HelicalSequence analysisAdd BLAST21
Topological domaini3066 – 3099CytoplasmicCuratedAdd BLAST34
Transmembranei3100 – 3120HelicalSequence analysisAdd BLAST21
Topological domaini3121 – 3127LumenalCurated7
Transmembranei3128 – 3148HelicalSequence analysisAdd BLAST21
Topological domaini3149 – 3586CytoplasmicCuratedAdd BLAST438
Transmembranei3587 – 3607HelicalSequence analysisAdd BLAST21
Topological domaini3608LumenalCurated1
Transmembranei3609 – 3629HelicalSequence analysisAdd BLAST21
Topological domaini3630 – 3634CytoplasmicCurated5
Transmembranei3635 – 3655HelicalSequence analysisAdd BLAST21
Topological domaini3656 – 3673LumenalCuratedAdd BLAST18
Transmembranei3674 – 3694HelicalSequence analysisAdd BLAST21
Topological domaini3695 – 3729CytoplasmicCuratedAdd BLAST35
Transmembranei3730 – 3750HelicalSequence analysisAdd BLAST21
Topological domaini3751 – 3778LumenalCuratedAdd BLAST28
Transmembranei3779 – 3799HelicalSequence analysisAdd BLAST21
Topological domaini3800 – 7096CytoplasmicCuratedAdd BLAST3297

Keywords - Cellular componenti

Host cytoplasm, Host endoplasmic reticulum, Host endosome, Host Golgi apparatus, 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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'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>Mutagenesisi154 – 157YEDF → AEDA: Complete loss of ribosome binding and cellular translation inhibition. 1 Publication4
Mutagenesisi164 – 165KH → AA: Complete loss of ribosome binding and cellular translation inhibition. 1 Publication2
Mutagenesisi164K → A: Complete loss of ribosome binding and cellular translation inhibition. 1 Publication1
Mutagenesisi165H → A: Complete loss of ribosome binding and cellular translation inhibition. 1 Publication1
Mutagenesisi171 – 175RELMR → EELME: Complete loss of ribosome binding and cellular translation inhibition. 1 Publication5
Mutagenesisi1629V → A: Partial loss of ISG15 cleavage in vitro. 1 Publication1
Mutagenesisi1632F → A: Partial loss of ISG15 cleavage in vitro. 1 Publication1
Mutagenesisi1638T → A: Partial loss of ubiquitin cleavage in vitro; no effect on ISG15 cleavage in vitro. 1 Publication1
Mutagenesisi1638T → L: Increased cleavage of ubiquitin in vitro; no effect on ISG15 cleavage in vitro. 1 Publication1
Mutagenesisi1674C → S: Complete loss of PL-pro activity. 1 Publication1
Mutagenesisi1831Y → G or T: Reduced inhibition by GRL-0617. 1 Publication1
Mutagenesisi5253S → A: Reduces RdRp inhibition by remdesivir. 1 Publication1

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL4523582

Drug and drug target database

More...
DrugBanki
DB15797, GC-373
DB15796, GC-376 free acid
DB14761, Remdesivir

DrugCentral

More...
DrugCentrali
P0DTD1

<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_00004496181 – 7096Replicase polyprotein 1abAdd BLAST7096
ChainiPRO_00004496191 – 180Host translation inhibitor nsp1By similarityAdd BLAST180
ChainiPRO_0000449620181 – 818Non-structural protein 2By similarityAdd BLAST638
ChainiPRO_0000449621819 – 2763Non-structural protein 3By similarityAdd BLAST1945
ChainiPRO_00004496222764 – 3263Non-structural protein 4By similarityAdd BLAST500
ChainiPRO_00004496233264 – 35693C-like proteinaseBy similarityAdd BLAST306
ChainiPRO_00004496243570 – 3859Non-structural protein 6By similarityAdd BLAST290
ChainiPRO_00004496253860 – 3942Non-structural protein 7By similarityAdd BLAST83
ChainiPRO_00004496263943 – 4140Non-structural protein 8By similarityAdd BLAST198
ChainiPRO_00004496274141 – 4253Non-structural protein 9By similarityAdd BLAST113
ChainiPRO_00004496284254 – 4392Non-structural protein 10By similarityAdd BLAST139
ChainiPRO_00004496294393 – 5324RNA-directed RNA polymeraseBy similarityAdd BLAST932
ChainiPRO_00004496305325 – 5925HelicaseBy similarityAdd BLAST601
ChainiPRO_00004496315926 – 6452Proofreading exoribonucleaseBy similarityAdd BLAST527
ChainiPRO_00004496326453 – 6798Uridylate-specific endoribonucleaseBy similarityAdd BLAST346
ChainiPRO_00004496336799 – 70962'-O-methyltransferaseBy similarityAdd BLAST298

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">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. 3CL-PRO and PL-PRO proteinases are autocatalytically processed.By similarity

Sites

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 – 181Cleavage; by PL-PROBy similarity2
Sitei818 – 819Cleavage; by PL-PROBy similarity2
Sitei2763 – 2764Cleavage; by PL-PROBy similarity2
Sitei3263 – 3264Cleavage; by 3CL-PROBy similarity2
Sitei3569 – 3570Cleavage; by 3CL-PROBy similarity2
Sitei3859 – 3860Cleavage; by 3CL-PROBy similarity2
Sitei3942 – 3943Cleavage; by 3CL-PROBy similarity2
Sitei4140 – 4141Cleavage; by 3CL-PROBy similarity2
Sitei4253 – 4254Cleavage; by 3CL-PROBy similarity2
Sitei4392 – 4393Cleavage; by 3CL-PROBy similarity2
Sitei5324 – 5325Cleavage; by 3CL-PROBy similarity2
Sitei5925 – 5926Cleavage; by 3CL-PROBy similarity2
Sitei6452 – 6453Cleavage; by 3CL-PROBy similarity2
Sitei6798 – 6799Cleavage; by 3CL-PROBy similarity2

<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="http://www.uniprot.org/help/interaction%5Fsection">'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="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts with host PHB and PHB2.

By similarity

3CL-PRO exists as monomer and homodimer. Only the homodimer shows catalytic activity.

1 Publication

Interacts with PL-PRO and nsp6.

By similarity

Interacts with host TBK1; this interaction decreases by 57% IRF3 phosphorylation, which leads to reduced IFN-beta production.

1 Publication

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

Interacts with RNA-directed RNA polymerase (PubMed:32277040, PubMed:32358203, PubMed:32438371, PubMed:32526208).

By similarity4 Publications

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

Interacts with RNA-directed RNA polymerase (PubMed:32277040, PubMed:32358203, PubMed:32438371, PubMed:32526208).

By similarity4 Publications

Is a dimer.

By similarity

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

By similarity

Interacts with nsp7 and nsp8.

4 Publications

Interacts with host TBK1; this interaction inhibits TBK1 phosphorylation and decreases by 75% IRF3 phosphorylation, which leads to reduced IFN-beta production.

1 Publication

Interacts (via N-terminus) with DDX1.

Interacts with nsp10.

By similarity

Interacts with nsp10.

By similarity

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">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="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

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GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

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BioGRIDi
4383850, 56 interactors
4383851, 262 interactors
4383852, 275 interactors
4383853, 1319 interactors
4383854, 215 interactors
4383855, 1178 interactors
4383856, 442 interactors
4383857, 175 interactors
4383858, 154 interactors
4383859, 103 interactors
4383860, 270 interactors
4383861, 322 interactors
4383862, 173 interactors
4383863, 178 interactors
4383864, 367 interactors

ComplexPortal: manually curated resource of macromolecular complexes

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ComplexPortali
CPX-5685, SARS-CoV-2 main protease complex
CPX-5687, SARS-CoV-2 NSP9 complex
CPX-5688, SARS-CoV-2 NSP10-NSP16 2'-O-methyltransferase complex
CPX-5689, SARS-CoV-2 NSP15 complex
CPX-5690, SARS-CoV-2 primase complex
CPX-5691, SARS-CoV-2 NSP3-NSP4-NSP6 complex
CPX-5692, SARS-CoV-2 3'-5' exoribonuclease proof-reading complex
CPX-5742, SARS-CoV-2 polymerase complex

Protein interaction database and analysis system

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IntActi
P0DTD1, 642 interactors

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
P0DTD1

<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