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UniProtKB - P0DTC1 (R1A_SARS2)

Entry version 11 (25 May 2022)
Sequence version 1 (22 Apr 2020)
Previous versions | rss
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Protein

Replicase polyprotein 1a

Gene
N/A
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 associating with the open head conformation of the 40S subunit (PubMed:33479166, PubMed:33080218, PubMed:32680882, PubMed:32908316).

The C-terminus binds to and obstructs ribosomal mRNA entry tunnel (PubMed:33479166, PubMed:33080218, PubMed:32680882, PubMed:32908316).

Thereby inhibits antiviral response triggered by innate immunity or interferons (PubMed:33080218, 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, PubMed:33080218).

By similarity5 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 antiviral protein IFIH1 (MDA5), but not DDX58 (RIG-I) (PubMed:33727702).

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

By similarity4 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).

Interacts with ribosome signal recognition particle RNA (SRP) (PubMed:33080218).

Together with NSP9, suppress protein integration into the cell membrane, thereby disrupting host immune defenses (PubMed:33080218).

By similarity5 Publications

May participate in viral replication by acting as a ssRNA-binding protein (By similarity).

Interacts with ribosome signal recognition particle RNA (SRP) (PubMed:33080218).

Together with NSP9, suppress protein integration into the cell membrane, thereby disrupting host immune defenses (PubMed:33080218).

By similarity1 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.

By similarity

Miscellaneous

Produced by conventional translation.By similarity

<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 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 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 bindingi200Zinc 1PROSITE-ProRule annotation1
Metal bindingi231Zinc 1PROSITE-ProRule annotation1
Metal bindingi234Zinc 1PROSITE-ProRule annotation1
Metal bindingi236Zinc 1PROSITE-ProRule annotation1
Metal bindingi323Zinc 2PROSITE-ProRule annotation1
Metal bindingi326Zinc 2PROSITE-ProRule annotation1
Metal bindingi341Zinc 2PROSITE-ProRule annotation1
Metal bindingi344Zinc 2PROSITE-ProRule annotation1
Metal bindingi370Zinc 3PROSITE-ProRule annotation1
Metal bindingi373Zinc 3PROSITE-ProRule annotation1
Metal bindingi382Zinc 3PROSITE-ProRule annotation1
Metal bindingi416Zinc 3PROSITE-ProRule annotation1
<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 sitei3408For 3CL-PRO activityPROSITE-ProRule annotation1 Publication1
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

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>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

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<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, Hydrolase, Nuclease, Protease, RNA-binding, Thiol protease
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 RLR pathway by virus, Modulation of host ubiquitin pathway by viral deubiquitinase, Modulation of host ubiquitin pathway by virus, Ubl conjugation pathway, Viral immunoevasion
LigandMetal-binding, Zinc

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

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

SABIO-RK: Biochemical Reaction Kinetics Database

More...SABIO-RKi		P0DTC1

<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 1a
Short name:
pp1a
Alternative name(s):
ORF1a polyprotein
Cleaved into the following 11 chains:
Host translation inhibitor nsp1
Alternative name(s):
Leader protein
Non-structural protein 1
Short name:
nsp1
Non-structural protein 2
Short name:
nsp2
Alternative name(s):
p65 homolog
Papain-like protease nsp31 Publication (EC:3.4.19.121 Publication, EC:3.4.22.-)
Alternative name(s):
Non-structural protein 3
Short name:
nsp3
PL2-PRO
Papain-like proteinase
Short name:
PL-PRO
Non-structural protein 4
Short name:
nsp4
3C-like proteinase nsp5 (EC:3.4.22.69)
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
Non-structural protein 11
Short name:
nsp11
<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 lineageiViruses › Riboviria › Orthornavirae › Pisuviricota › Pisoniviricetes › Nidovirales › Cornidovirineae › Coronaviridae › Orthocoronavirinae › Betacoronavirus › Sarbecovirus ›
<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 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
Transmembranei2318 – 2338HelicalSequence analysisAdd BLAST21
Transmembranei2339 – 2359HelicalSequence analysisAdd BLAST21
Transmembranei2361 – 2381HelicalSequence analysisAdd BLAST21
Transmembranei2776 – 2796HelicalSequence analysisAdd BLAST21
Transmembranei3045 – 3065HelicalSequence analysisAdd BLAST21
Transmembranei3077 – 3097HelicalSequence analysisAdd BLAST21
Transmembranei3100 – 3120HelicalSequence analysisAdd BLAST21
Transmembranei3128 – 3148HelicalSequence analysisAdd BLAST21
Transmembranei3165 – 3185HelicalSequence analysisAdd BLAST21
Transmembranei3587 – 3607HelicalSequence analysisAdd BLAST21
Transmembranei3609 – 3629HelicalSequence analysisAdd BLAST21
Transmembranei3635 – 3655HelicalSequence analysisAdd BLAST21
Transmembranei3674 – 3694HelicalSequence analysisAdd BLAST21
Transmembranei3730 – 3750HelicalSequence analysisAdd BLAST21
Transmembranei3779 – 3799HelicalSequence analysisAdd BLAST21

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 → A: Unable to remove host IFIH1 (MDA5) ISGylation. 1 Publication1
Mutagenesisi1674C → S: Complete loss of PL-pro activity. 1 Publication1
Mutagenesisi1831Y → G or T: Reduced inhibition by GRL-0617. 1 Publication1

Chemistry databases

Drug and drug target database

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

<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_00004496341 – 4405Replicase polyprotein 1aBy similarityAdd BLAST4405
ChainiPRO_00004496351 – 180Host translation inhibitor nsp1By similarityAdd BLAST180
ChainiPRO_0000449636181 – 818Non-structural protein 2By similarityAdd BLAST638
ChainiPRO_0000449637819 – 2763Papain-like protease nsp3By similarityAdd BLAST1945
ChainiPRO_00004496382764 – 3263Non-structural protein 4By similarityAdd BLAST500
ChainiPRO_00004496393264 – 35693C-like proteinase nsp5By similarityAdd BLAST306
ChainiPRO_00004496403570 – 3859Non-structural protein 6By similarityAdd BLAST290
ChainiPRO_00004496413860 – 3942Non-structural protein 7By similarityAdd BLAST83
ChainiPRO_00004496423943 – 4140Non-structural protein 8By similarityAdd BLAST198
ChainiPRO_00004496434141 – 4253Non-structural protein 9By similarityAdd BLAST113
ChainiPRO_00004496444254 – 4392Non-structural protein 10By similarityAdd BLAST139
ChainiPRO_00004496454393 – 4405Non-structural protein 11By similarityAdd BLAST13

<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

<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 IRF3 phosphorylation by 57%, 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

<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

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		4383866, 89 interactors

Protein interaction database and analysis system

More...IntActi		P0DTC1, 47 interactors

<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

14405
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Small Angle Scattering Biological Data Bank

More...SASBDBi		P0DTC1

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

More...SMRi		P0DTC1

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

<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="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">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>Domaini12 – 127CoV Nsp1 globularPROSITE-ProRule annotationAdd BLAST116
Domaini148 – 179BetaCoV Nsp1 C-terminalPROSITE-ProRule annotationAdd BLAST32
Domaini183 – 456CoV Nsp2 N-terminalPROSITE-ProRule annotationAdd BLAST274
Domaini458 – 688CoV Nsp2 middlePROSITE-ProRule annotationAdd BLAST231
Domaini690 – 818CoV Nsp2 C-terminalPROSITE-ProRule annotationAdd BLAST129
Domaini821 – 929Ubiquitin-like 1PROSITE-ProRule annotationAdd BLAST109
Domaini1025 – 1194Macro 1PROSITE-ProRule annotationAdd BLAST170
Domaini1231 – 1359Macro 2PROSITE-ProRule annotationAdd BLAST129
Domaini1367 – 1494Macro 3PROSITE-ProRule annotationAdd BLAST128
Domaini1496 – 1561DPUPPROSITE-ProRule annotationAdd BLAST66
Domaini1565 – 1620Ubiquitin-like 2PROSITE-ProRule annotationAdd BLAST56
Domaini1634 – 1898Peptidase C16PROSITE-ProRule annotationAdd BLAST265
Domaini1911 – 2021Nucleic acid-bindingPROSITE-ProRule annotationAdd BLAST111
Domaini2046 – 2155G2MPROSITE-ProRule annotationAdd BLAST110
Domaini2660 – 2763CoV Nsp3 Y3PROSITE-ProRule annotationAdd BLAST104
Domaini3165 – 3263Nsp4CPROSITE-ProRule annotationAdd BLAST99
Domaini3264 – 3569Peptidase C30PROSITE-ProRule annotationAdd BLAST306
Domaini3860 – 3942RdRp Nsp7 cofactorPROSITE-ProRule annotationAdd BLAST83
Domaini3943 – 4140RdRp Nsp8 cofactorPROSITE-ProRule annotationAdd BLAST198
Domaini4141 – 4253Nsp9 ssRNA-bindingPROSITE-ProRule annotationAdd BLAST113
Domaini4254 – 4392ExoN/MTase coactivatorPROSITE-ProRule annotationAdd BLAST139

Region

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>Regioni154 – 180Binding to 40s ribosome mRNA entry channel1 PublicationAdd BLAST27
Regioni200 – 236C2H2PROSITE-ProRule annotationAdd BLAST37
Regioni323 – 344C4PROSITE-ProRule annotationAdd BLAST22
Regioni370 – 416C2HCPROSITE-ProRule annotationAdd BLAST47
Regioni926 – 999DisorderedSequence analysisAdd BLAST74

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 type of amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi927 – 947Acidic residuesSequence analysisAdd BLAST21
Compositional biasi984 – 999Polar residuesSequence analysisAdd BLAST16

<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.By similarity

<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

Belongs to the coronaviruses polyprotein 1ab family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1752 – 1789C4-typePROSITE-ProRule annotationAdd BLAST38

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix, Zinc-finger

Family and domain databases

Conserved Domains Database

More...CDDi		cd21560, betaCoV-Nsp6, 1 hit
cd21666, betaCoV_Nsp5_Mpro, 1 hit
cd21516, cv_beta_Nsp2_SARS-like, 1 hit
cd21473, cv_Nsp4_TM, 1 hit
cd21563, Macro_cv_SUD-M_Nsp3-like, 1 hit
cd21557, Macro_X_Nsp3-like, 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

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		1.10.150.420, 1 hit
1.10.1840.10, 1 hit
1.10.8.1190, 1 hit
1.10.8.370, 1 hit
2.40.10.10, 2 hits
2.40.10.250, 1 hit
2.60.120.1680, 1 hit
3.10.20.350, 1 hit
3.10.20.540, 1 hit
3.30.70.3540, 1 hit
3.40.220.10, 1 hit
3.40.220.20, 1 hit
3.40.220.30, 1 hit
3.40.30.150, 1 hit
3.40.50.11020, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR043613, CoV_NSP2_C
IPR043611, CoV_NSP3_C
IPR043612, CoV_NSP4_N
IPR022733, DPUP_SUD_C_bCoV
IPR002589, Macro_dom
IPR043472, Macro_dom-like
IPR044371, Macro_X_NSP3-like
IPR042570, NAR_sf
IPR036333, NSP10_sf_CoV
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_NAB_bCoV
IPR038166, NSP3_PL2pro_sf_CoV
IPR038400, NSP3_SUD-M_sf_bCoV
IPR044864, NSP3_SUD-N_bCoV
IPR043478, NSP3_SUD-N_sf_bCoV
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
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
IPR018995, RNA_synth_NSP10_CoV

Pfam protein domain database

More...Pfami		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
PF09401, CoV_NSP10, 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
PF01661, Macro, 1 hit
PF05409, Peptidase_C30, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00506, A1pp, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF101816, SSF101816, 1 hit
SSF140367, SSF140367, 1 hit
SSF143076, SSF143076, 1 hit
SSF144246, SSF144246, 1 hit
SSF159936, SSF159936, 1 hit
SSF160099, SSF160099, 1 hit
SSF50494, SSF50494, 1 hit
SSF52949, SSF52949, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS51963, BCOV_NSP1_C, 1 hit
PS51942, BCOV_NSP3C_C, 1 hit
PS51941, BCOV_NSP3C_M, 1 hit
PS51994, BCOV_NSP3E_G2M, 1 hit
PS51945, BCOV_NSP3E_NAB, 1 hit
PS51952, COV_EXON_MTASE_COACT, 1 hit
PS51962, COV_NSP1, 1 hit
PS51991, COV_NSP2_C, 1 hit
PS51990, COV_NSP2_M, 1 hit
PS51989, COV_NSP2_N, 1 hit
PS51992, COV_NSP3_Y3, 1 hit
PS51943, COV_NSP3A_UBL, 1 hit
PS51944, COV_NSP3D_UBL, 1 hit
PS51946, COV_NSP4C, 1 hit
PS51949, COV_NSP7, 1 hit
PS51950, COV_NSP8, 1 hit
PS51951, COV_NSP9_SSRNA_BD, 1 hit
PS00867, CPSASE_2, 1 hit
PS51442, M_PRO, 1 hit
PS51154, MACRO, 1 hit
PS51124, PEPTIDASE_C16, 1 hit
PS51940, SARS_NSP3C_N, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by ribosomal frameshifting. AlignAdd to basket
Note: Normal translation results in Replicase polyprotein 1a. Ribosomal frameshifting at the end of this protein occurs at low frequency and produces Replicase polyprotein 1ab.
Isoform Replicase polyprotein 1a (identifier: P0DTC1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <p><strong>What is the canonical sequence?</strong><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MESLVPGFNE KTHVQLSLPV LQVRDVLVRG FGDSVEEVLS EARQHLKDGT 
        60         70         80         90        100
CGLVEVEKGV LPQLEQPYVF IKRSDARTAP HGHVMVELVA ELEGIQYGRS 
       110        120        130        140        150
GETLGVLVPH VGEIPVAYRK VLLRKNGNKG AGGHSYGADL KSFDLGDELG 
       160        170        180        190        200
TDPYEDFQEN WNTKHSSGVT RELMRELNGG AYTRYVDNNF CGPDGYPLEC 
       210        220        230        240        250
IKDLLARAGK ASCTLSEQLD FIDTKRGVYC CREHEHEIAW YTERSEKSYE 
       260        270        280        290        300
LQTPFEIKLA KKFDTFNGEC PNFVFPLNSI IKTIQPRVEK KKLDGFMGRI 
       310        320        330        340        350
RSVYPVASPN ECNQMCLSTL MKCDHCGETS WQTGDFVKAT CEFCGTENLT 
       360        370        380        390        400
KEGATTCGYL PQNAVVKIYC PACHNSEVGP EHSLAEYHNE SGLKTILRKG 
       410        420        430        440        450
GRTIAFGGCV FSYVGCHNKC AYWVPRASAN IGCNHTGVVG EGSEGLNDNL 
       460        470        480        490        500
LEILQKEKVN INIVGDFKLN EEIAIILASF SASTSAFVET VKGLDYKAFK 
       510        520        530        540        550
QIVESCGNFK VTKGKAKKGA WNIGEQKSIL SPLYAFASEA ARVVRSIFSR 
       560        570        580        590        600
TLETAQNSVR VLQKAAITIL DGISQYSLRL IDAMMFTSDL ATNNLVVMAY 
       610        620        630        640        650
ITGGVVQLTS QWLTNIFGTV YEKLKPVLDW LEEKFKEGVE FLRDGWEIVK 
       660        670        680        690        700
FISTCACEIV GGQIVTCAKE IKESVQTFFK LVNKFLALCA DSIIIGGAKL 
       710        720        730        740        750
KALNLGETFV THSKGLYRKC VKSREETGLL MPLKAPKEII FLEGETLPTE 
       760        770        780        790        800
VLTEEVVLKT GDLQPLEQPT SEAVEAPLVG TPVCINGLML LEIKDTEKYC 
       810        820        830        840        850
ALAPNMMVTN NTFTLKGGAP TKVTFGDDTV IEVQGYKSVN ITFELDERID 
       860        870        880        890        900
KVLNEKCSAY TVELGTEVNE FACVVADAVI KTLQPVSELL TPLGIDLDEW 
       910        920        930        940        950
SMATYYLFDE SGEFKLASHM YCSFYPPDED EEEGDCEEEE FEPSTQYEYG 
       960        970        980        990       1000
TEDDYQGKPL EFGATSAALQ PEEEQEEDWL DDDSQQTVGQ QDGSEDNQTT 
      1010       1020       1030       1040       1050
TIQTIVEVQP QLEMELTPVV QTIEVNSFSG YLKLTDNVYI KNADIVEEAK 
      1060       1070       1080       1090       1100
KVKPTVVVNA ANVYLKHGGG VAGALNKATN NAMQVESDDY IATNGPLKVG 
      1110       1120       1130       1140       1150
GSCVLSGHNL AKHCLHVVGP NVNKGEDIQL LKSAYENFNQ HEVLLAPLLS 
      1160       1170       1180       1190       1200
AGIFGADPIH SLRVCVDTVR TNVYLAVFDK NLYDKLVSSF LEMKSEKQVE 
      1210       1220       1230       1240       1250
QKIAEIPKEE VKPFITESKP SVEQRKQDDK KIKACVEEVT TTLEETKFLT 
      1260       1270       1280       1290       1300
ENLLLYIDIN GNLHPDSATL VSDIDITFLK KDAPYIVGDV VQEGVLTAVV 
      1310       1320       1330       1340       1350
IPTKKAGGTT EMLAKALRKV PTDNYITTYP GQGLNGYTVE EAKTVLKKCK 
      1360       1370       1380       1390       1400
SAFYILPSII SNEKQEILGT VSWNLREMLA HAEETRKLMP VCVETKAIVS 
      1410       1420       1430       1440       1450
TIQRKYKGIK IQEGVVDYGA RFYFYTSKTT VASLINTLND LNETLVTMPL 
      1460       1470       1480       1490       1500
GYVTHGLNLE EAARYMRSLK VPATVSVSSP DAVTAYNGYL TSSSKTPEEH 
      1510       1520       1530       1540       1550
FIETISLAGS YKDWSYSGQS TQLGIEFLKR GDKSVYYTSN PTTFHLDGEV 
      1560       1570       1580       1590       1600
ITFDNLKTLL SLREVRTIKV FTTVDNINLH TQVVDMSMTY GQQFGPTYLD 
      1610       1620       1630       1640       1650
GADVTKIKPH NSHEGKTFYV LPNDDTLRVE AFEYYHTTDP SFLGRYMSAL 
      1660       1670       1680       1690       1700
NHTKKWKYPQ VNGLTSIKWA DNNCYLATAL LTLQQIELKF NPPALQDAYY 
      1710       1720       1730       1740       1750
RARAGEAANF CALILAYCNK TVGELGDVRE TMSYLFQHAN LDSCKRVLNV 
      1760       1770       1780       1790       1800
VCKTCGQQQT TLKGVEAVMY MGTLSYEQFK KGVQIPCTCG KQATKYLVQQ 
      1810       1820       1830       1840       1850
ESPFVMMSAP PAQYELKHGT FTCASEYTGN YQCGHYKHIT SKETLYCIDG 
      1860       1870       1880       1890       1900
ALLTKSSEYK GPITDVFYKE NSYTTTIKPV TYKLDGVVCT EIDPKLDNYY 
      1910       1920       1930       1940       1950
KKDNSYFTEQ PIDLVPNQPY PNASFDNFKF VCDNIKFADD LNQLTGYKKP 
      1960       1970       1980       1990       2000
ASRELKVTFF PDLNGDVVAI DYKHYTPSFK KGAKLLHKPI VWHVNNATNK 
      2010       2020       2030       2040       2050
ATYKPNTWCI RCLWSTKPVE TSNSFDVLKS EDAQGMDNLA CEDLKPVSEE 
      2060       2070       2080       2090       2100
VVENPTIQKD VLECNVKTTE VVGDIILKPA NNSLKITEEV GHTDLMAAYV 
      2110       2120       2130       2140       2150
DNSSLTIKKP NELSRVLGLK TLATHGLAAV NSVPWDTIAN YAKPFLNKVV 
      2160       2170       2180       2190       2200
STTTNIVTRC LNRVCTNYMP YFFTLLLQLC TFTRSTNSRI KASMPTTIAK 
      2210       2220       2230       2240       2250
NTVKSVGKFC LEASFNYLKS PNFSKLINII IWFLLLSVCL GSLIYSTAAL 
      2260       2270       2280       2290       2300
GVLMSNLGMP SYCTGYREGY LNSTNVTIAT YCTGSIPCSV CLSGLDSLDT 
      2310       2320       2330       2340       2350
YPSLETIQIT ISSFKWDLTA FGLVAEWFLA YILFTRFFYV LGLAAIMQLF 
      2360       2370       2380       2390       2400
FSYFAVHFIS NSWLMWLIIN LVQMAPISAM VRMYIFFASF YYVWKSYVHV 
      2410       2420       2430       2440       2450
VDGCNSSTCM MCYKRNRATR VECTTIVNGV RRSFYVYANG GKGFCKLHNW 
      2460       2470       2480       2490       2500
NCVNCDTFCA GSTFISDEVA RDLSLQFKRP INPTDQSSYI VDSVTVKNGS 
      2510       2520       2530       2540       2550
IHLYFDKAGQ KTYERHSLSH FVNLDNLRAN NTKGSLPINV IVFDGKSKCE 
      2560       2570       2580       2590       2600
ESSAKSASVY YSQLMCQPIL LLDQALVSDV GDSAEVAVKM FDAYVNTFSS 
      2610       2620       2630       2640       2650
TFNVPMEKLK TLVATAEAEL AKNVSLDNVL STFISAARQG FVDSDVETKD 
      2660       2670       2680       2690       2700
VVECLKLSHQ SDIEVTGDSC NNYMLTYNKV ENMTPRDLGA CIDCSARHIN 
      2710       2720       2730       2740       2750
AQVAKSHNIA LIWNVKDFMS LSEQLRKQIR SAAKKNNLPF KLTCATTRQV 
      2760       2770       2780       2790       2800
VNVVTTKIAL KGGKIVNNWL KQLIKVTLVF LFVAAIFYLI TPVHVMSKHT 
      2810       2820       2830       2840       2850
DFSSEIIGYK AIDGGVTRDI ASTDTCFANK HADFDTWFSQ RGGSYTNDKA 
      2860       2870       2880       2890       2900
CPLIAAVITR EVGFVVPGLP GTILRTTNGD FLHFLPRVFS AVGNICYTPS 
      2910       2920       2930       2940       2950
KLIEYTDFAT SACVLAAECT IFKDASGKPV PYCYDTNVLE GSVAYESLRP 
      2960       2970       2980       2990       3000
DTRYVLMDGS IIQFPNTYLE GSVRVVTTFD SEYCRHGTCE RSEAGVCVST 
      3010       3020       3030       3040       3050
SGRWVLNNDY YRSLPGVFCG VDAVNLLTNM FTPLIQPIGA LDISASIVAG 
      3060       3070       3080       3090       3100
GIVAIVVTCL AYYFMRFRRA FGEYSHVVAF NTLLFLMSFT VLCLTPVYSF 
      3110       3120       3130       3140       3150
LPGVYSVIYL YLTFYLTNDV SFLAHIQWMV MFTPLVPFWI TIAYIICIST 
      3160       3170       3180       3190       3200
KHFYWFFSNY LKRRVVFNGV SFSTFEEAAL CTFLLNKEMY LKLRSDVLLP 
      3210       3220       3230       3240       3250
LTQYNRYLAL YNKYKYFSGA MDTTSYREAA CCHLAKALND FSNSGSDVLY 
      3260       3270       3280       3290       3300
QPPQTSITSA VLQSGFRKMA FPSGKVEGCM VQVTCGTTTL NGLWLDDVVY 
      3310       3320       3330       3340       3350
CPRHVICTSE DMLNPNYEDL LIRKSNHNFL VQAGNVQLRV IGHSMQNCVL 
      3360       3370       3380       3390       3400
KLKVDTANPK TPKYKFVRIQ PGQTFSVLAC YNGSPSGVYQ CAMRPNFTIK 
      3410       3420       3430       3440       3450
GSFLNGSCGS VGFNIDYDCV SFCYMHHMEL PTGVHAGTDL EGNFYGPFVD 
      3460       3470       3480       3490       3500
RQTAQAAGTD TTITVNVLAW LYAAVINGDR WFLNRFTTTL NDFNLVAMKY 
      3510       3520       3530       3540       3550
NYEPLTQDHV DILGPLSAQT GIAVLDMCAS LKELLQNGMN GRTILGSALL 
      3560       3570       3580       3590       3600
EDEFTPFDVV RQCSGVTFQS AVKRTIKGTH HWLLLTILTS LLVLVQSTQW 
      3610       3620       3630       3640       3650
SLFFFLYENA FLPFAMGIIA MSAFAMMFVK HKHAFLCLFL LPSLATVAYF 
      3660       3670       3680       3690       3700
NMVYMPASWV MRIMTWLDMV DTSLSGFKLK DCVMYASAVV LLILMTARTV 
      3710       3720       3730       3740       3750
YDDGARRVWT LMNVLTLVYK VYYGNALDQA ISMWALIISV TSNYSGVVTT 
      3760       3770       3780       3790       3800
VMFLARGIVF MCVEYCPIFF ITGNTLQCIM LVYCFLGYFC TCYFGLFCLL 
      3810       3820       3830       3840       3850
NRYFRLTLGV YDYLVSTQEF RYMNSQGLLP PKNSIDAFKL NIKLLGVGGK 
      3860       3870       3880       3890       3900
PCIKVATVQS KMSDVKCTSV VLLSVLQQLR VESSSKLWAQ CVQLHNDILL 
      3910       3920       3930       3940       3950
AKDTTEAFEK MVSLLSVLLS MQGAVDINKL CEEMLDNRAT LQAIASEFSS 
      3960       3970       3980       3990       4000
LPSYAAFATA QEAYEQAVAN GDSEVVLKKL KKSLNVAKSE FDRDAAMQRK 
      4010       4020       4030       4040       4050
LEKMADQAMT QMYKQARSED KRAKVTSAMQ TMLFTMLRKL DNDALNNIIN 
      4060       4070       4080       4090       4100
NARDGCVPLN IIPLTTAAKL MVVIPDYNTY KNTCDGTTFT YASALWEIQQ 
      4110       4120       4130       4140       4150
VVDADSKIVQ LSEISMDNSP NLAWPLIVTA LRANSAVKLQ NNELSPVALR 
      4160       4170       4180       4190       4200
QMSCAAGTTQ TACTDDNALA YYNTTKGGRF VLALLSDLQD LKWARFPKSD 
      4210       4220       4230       4240       4250
GTGTIYTELE PPCRFVTDTP KGPKVKYLYF IKGLNNLNRG MVLGSLAATV 
      4260       4270       4280       4290       4300
RLQAGNATEV PANSTVLSFC AFAVDAAKAY KDYLASGGQP ITNCVKMLCT 
      4310       4320       4330       4340       4350
HTGTGQAITV TPEANMDQES FGGASCCLYC RCHIDHPNPK GFCDLKGKYV 
      4360       4370       4380       4390       4400
QIPTTCANDP VGFTLKNTVC TVCGMWKGYG CSCDQLREPM LQSADAQSFL 

NGFAV
Length:4,405
Mass (Da):489,989
Last modified:April 22, 2020 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i7F8A21148A7A7E2A
GO
Isoform Replicase polyprotein 1ab (identifier: P0DTD1-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry P0DTD1.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:7,096
Mass (Da):794,058
GO

<p>This subsection of the 'Sequence' section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement%5Fin%5Fdisease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi

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
Variant Omicron/BA.1 and BA.2 belong to a lineage first isolated in South Africa (November 2021).Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural varianti135S → R in strain: Omicron/BA.2. Curated1
Natural varianti265T → I in strain: Iota/B.1.526, Beta/B.1.351 and Epsilon/B.1.427/B.1.429. Curated1
Natural varianti842T → I in strain: Omicron/BA.2. Curated1
Natural varianti856K → R in strain: Omicron/BA.1. Curated1
Natural varianti1001T → I in strain: Alpha/B.1.1.7. 1 Publication1
Natural varianti1055T → A in strain: Mu/B.1.621. Curated1
Natural varianti1188S → L in strain: Gamma/P.1. Curated1
Natural varianti1246T → I in strain: Lambda/C.37. Curated1
Natural varianti1307G → S in strain: Omicron/BA.2. 1
Natural varianti1538T → I in strain: Mu/B.1.621. Curated1
Natural varianti1554D → G in strain: Theta/P.3. Curated1
Natural varianti1567T → I in strain: Kappa/B.1.617.1. Curated1
Natural varianti1655K → N in strain: Beta/B.1.351. Curated1
Natural varianti1708A → D in strain: Alpha/B.1.1.7. 1 Publication1
Natural varianti1795K → Q in strain: Gamma/P.1. Curated1
Natural varianti2007T → I in strain: Eta/B.1.525. Curated1
Natural varianti2083 – 2084SL → I in strain:Omicron/BA.1. Curated2
Natural varianti2230I → T in strain: Alpha/B.1.1.7. 1 Publication1
Natural varianti2287P → S in strain: Lambda/C.37. Curated1
Natural varianti2387F → V in strain: Lambda/C.37. Curated1
Natural varianti2625S → F in strain: Theta/P.3. Curated1
Natural varianti2710A → T in strain:Omicron/BA.1. Curated1
Natural varianti2980D → N in strain: Theta/P.3. Curated1
Natural varianti3027L → F in strain: Omicron/BA.2. Curated1
Natural varianti3090T → I in strain: Omicron/BA.2. Curated1
Natural varianti3201L → F in strain: Omicron/BA.2. Curated1
Natural varianti3201L → P in strain: Iota/B.1.526, Lambda/C.37 and Theta/P.3. Curated1
Natural varianti3255T → I in strain: Lambda/C.37, Mu/B.1.621, Omicron/BA.1, Omicron/BA.2. Curated1
Natural varianti3353K → R in strain: Beta/B.1.351. Curated1
Natural varianti3395P → H in strain: Omicron/BA.1, Omicron/BA.2. Curated1
Natural varianti3468L → V in strain: Zeta/P.2. Curated1
Natural varianti3646T → A in strain: Kappa/B.1.617.1. 1
Natural varianti3674 – 3676Missing in strain: Omicron/BA.1. Curated3
Natural varianti3675 – 3677Missing in strain: Omicron/BA.2. Curated3
Natural varianti3675S → K in strain: Alpha/B.1.1.7, Beta/B.1.351, Gamma/P.1, Eta/B.1.525, Iota/B.1.526 and Lambda/C.37. Curated1
Natural varianti3676 – 3678Missing in strain: Alpha/B.1.1.7, Beta/B.1.351, Gamma/P.1, Eta/B.1.525, Iota/B.1.526 and Lambda/C.37. Curated3
Natural varianti3681D → E in strain: Theta/P.3. Curated1
Natural varianti3729Q → R in strain: Mu/B.1.621. Curated1
Natural varianti3758I → V in strain: Omicron/BA.1. Curated1
Natural varianti3930L → F in strain: Theta/P.3 and Zeta/P.2. Curated1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
MN908947 Genomic RNA Translation: QHD43415.1 Frameshift.

NCBI Reference Sequences

More...RefSeqi		YP_009725295.1, NC_045512.2

Genome annotation databases

Database of genes from NCBI RefSeq genomes

More...GeneIDi		43740578

Keywords - Coding sequence diversityi

Ribosomal frameshifting

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
MN908947 Genomic RNA Translation: QHD43415.1 Frameshift.
RefSeqiYP_009725295.1, NC_045512.2

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6Y2EX-ray1.75A3264-3569[»]
6Y2FX-ray2.16A3264-3569[»]
6Y2GX-ray2.16A3264-3569[»]
6YHUX-ray2.00A/C3860-3930[»]
B/D4018-4134[»]
6YYTelectron microscopy2.90B3948-4133[»]
C3860-3932[»]
7BV2electron microscopy2.50C3860-3942[»]
B3943-4140[»]
7C33X-ray3.83A/B/C/D1025-1195[»]
7CZ4X-ray2.64A/B1025-1195[»]
7D3IX-ray2.00A3264-3569[»]
7D47X-ray1.97A/B1564-1880[»]
7D64X-ray2.45A3264-3569[»]
7D6HX-ray1.60A1563-1878[»]
7DATX-ray2.75A3264-3569[»]
7DAUX-ray1.72A3264-3569[»]
7DAVX-ray1.77A3264-3569[»]
7DCDX-ray2.57A/C/E/G3860-3942[»]
B/D/F/H4019-4140[»]
7DGBX-ray1.68A3264-3569[»]
7DGFX-ray1.64A3264-3569[»]
7DGGX-ray2.00A/B3264-3569[»]
7DGHX-ray1.97A3264-3569[»]
7DGIX-ray1.90A/B3264-3569[»]
7DHJX-ray1.96A3264-3569[»]
7DJRX-ray1.45A3264-3569[»]
7DK1X-ray1.90A/B3264-3569[»]
7DPPX-ray2.10A3264-3564[»]
7DPUX-ray1.75A/B3264-3569[»]
7DPVX-ray2.35A/B/C/D3264-3569[»]
7E35X-ray2.40A/B1564-1878[»]
7EINX-ray1.70A/B3264-3569[»]
7EIZelectron microscopy-C3860-3942[»]
7EXMX-ray1.96A/B/C/D181-456[»]
7FAYX-ray2.10A3264-3569[»]
7FAZX-ray2.10A/B3264-3569[»]
7JIRX-ray2.09A1564-1878[»]
7JITX-ray1.95A1564-1878[»]
7JIVX-ray2.05A1564-1878[»]
7JIWX-ray2.30A1564-1878[»]
7JN2X-ray1.93A1564-1878[»]
7JRNX-ray2.48A/J1564-1878[»]
7KOJX-ray2.02A1564-1878[»]
7KOKX-ray2.00A1564-1878[»]
7KOLX-ray2.58A1564-1878[»]
7KRXX-ray2.72A1564-1878[»]
7M1YX-ray2.02A/B1564-1878[»]
7NT1X-ray2.85A/B3264-3569[»]
7NT2X-ray2.15A/B3264-3569[»]
7NT3X-ray2.33A/B3264-3569[»]
7NTVX-ray2.06A/B3264-3569[»]
7NUKX-ray2.19A/B3264-3569[»]
7NW2X-ray2.10A/B3264-3569[»]
7NWXX-ray1.80A3264-3569[»]
7NXHX-ray2.10A3264-3569[»]
7OFSX-ray1.90A1564-1878[»]
7OFTX-ray1.95A1564-1878[»]
7OFUX-ray1.72AAA1564-1878[»]
7P51X-ray1.47A3264-3569[»]
7RBRX-ray1.88A1564-1878[»]
7RBSX-ray2.98A/C/E/G/I1564-1878[»]
7RZCX-ray2.04A/B/C1564-1878[»]
7SDRX-ray2.72A/B/C1564-1878[»]
7SGUX-ray1.79A1564-1878[»]
7SGVX-ray2.00A1564-1878[»]
7SGWX-ray1.95A1564-1878[»]
7SQEX-ray2.00A/B/C1564-1878[»]
7TLLX-ray1.63A/B3264-3569[»]
7VH8X-ray1.59A3264-3569[»]
7VJWX-ray2.20A/B3264-3569[»]
7VJXX-ray2.20A/B3264-3569[»]
7VJYX-ray1.90A3264-3569[»]
7VJZX-ray1.90A3264-3569[»]
7VK0X-ray2.10A/B3264-3569[»]
7VK1X-ray1.93A3264-3569[»]
7VK2X-ray2.00A3264-3569[»]
7VK3X-ray2.10A/B3264-3569[»]
7VK4X-ray2.10A/B3264-3569[»]
7VK5X-ray2.17A/B3264-3569[»]
7VK6X-ray2.25A/B3264-3569[»]
7VK7X-ray2.40A/B3264-3569[»]
7VK8X-ray2.40A3264-3569[»]
SASBDBiP0DTC1
SMRiP0DTC1
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi4383866, 89 interactors
IntActiP0DTC1, 47 interactors

Chemistry databases

DrugBankiDB15797, GC-373
DB15796, GC-376 free acid

Protocols and materials databases

The DNASU plasmid repository

More...DNASUi		43740578

Genome annotation databases

GeneIDi43740578

Enzyme and pathway databases

ReactomeiR-HSA-9694271, Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC)
R-HSA-9694301, Maturation of replicase proteins
R-HSA-9694676, Translation of Replicase and Assembly of the Replication Transcription Complex
R-HSA-9694686, Replication of the SARS-CoV-2 genome
R-HSA-9694786, Transcription of SARS-CoV-2 sgRNAs
SABIO-RKiP0DTC1

Family and domain databases

CDDicd21560, betaCoV-Nsp6, 1 hit
cd21666, betaCoV_Nsp5_Mpro, 1 hit
cd21516, cv_beta_Nsp2_SARS-like, 1 hit
cd21473, cv_Nsp4_TM, 1 hit
cd21563, Macro_cv_SUD-M_Nsp3-like, 1 hit
cd21557, Macro_X_Nsp3-like, 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
Gene3Di1.10.150.420, 1 hit
1.10.1840.10, 1 hit
1.10.8.1190, 1 hit
1.10.8.370, 1 hit
2.40.10.10, 2 hits
2.40.10.250, 1 hit
2.60.120.1680, 1 hit
3.10.20.350, 1 hit
3.10.20.540, 1 hit
3.30.70.3540, 1 hit
3.40.220.10, 1 hit
3.40.220.20, 1 hit
3.40.220.30, 1 hit
3.40.30.150, 1 hit
3.40.50.11020, 1 hit
InterProiView protein in InterPro
IPR043613, CoV_NSP2_C
IPR043611, CoV_NSP3_C
IPR043612, CoV_NSP4_N
IPR022733, DPUP_SUD_C_bCoV
IPR002589, Macro_dom
IPR043472, Macro_dom-like
IPR044371, Macro_X_NSP3-like
IPR042570, NAR_sf
IPR036333, NSP10_sf_CoV
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_NAB_bCoV
IPR038166, NSP3_PL2pro_sf_CoV
IPR038400, NSP3_SUD-M_sf_bCoV
IPR044864, NSP3_SUD-N_bCoV
IPR043478, NSP3_SUD-N_sf_bCoV
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
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
IPR018995, RNA_synth_NSP10_CoV
PfamiView 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
PF09401, CoV_NSP10, 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
PF01661, Macro, 1 hit
PF05409, Peptidase_C30, 1 hit
SMARTiView protein in SMART
SM00506, A1pp, 1 hit
SUPFAMiSSF101816, SSF101816, 1 hit
SSF140367, SSF140367, 1 hit
SSF143076, SSF143076, 1 hit
SSF144246, SSF144246, 1 hit
SSF159936, SSF159936, 1 hit
SSF160099, SSF160099, 1 hit
SSF50494, SSF50494, 1 hit
SSF52949, SSF52949, 1 hit
PROSITEiView protein in PROSITE
PS51963, BCOV_NSP1_C, 1 hit
PS51942, BCOV_NSP3C_C, 1 hit
PS51941, BCOV_NSP3C_M, 1 hit
PS51994, BCOV_NSP3E_G2M, 1 hit
PS51945, BCOV_NSP3E_NAB, 1 hit
PS51952, COV_EXON_MTASE_COACT, 1 hit
PS51962, COV_NSP1, 1 hit
PS51991, COV_NSP2_C, 1 hit
PS51990, COV_NSP2_M, 1 hit
PS51989, COV_NSP2_N, 1 hit
PS51992, COV_NSP3_Y3, 1 hit
PS51943, COV_NSP3A_UBL, 1 hit
PS51944, COV_NSP3D_UBL, 1 hit
PS51946, COV_NSP4C, 1 hit
PS51949, COV_NSP7, 1 hit
PS51950, COV_NSP8, 1 hit
PS51951, COV_NSP9_SSRNA_BD, 1 hit
PS00867, CPSASE_2, 1 hit
PS51442, M_PRO, 1 hit
PS51154, MACRO, 1 hit
PS51124, PEPTIDASE_C16, 1 hit
PS51940, SARS_NSP3C_N, 1 hit

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiR1A_SARS2
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P0DTC1
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 22, 2020
Last sequence update: April 22, 2020
Last modified: May 25, 2022
This is version 11 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
UniProt is an ELIXIR core data resource
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