Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Entry version 161 (02 Jun 2021)
Sequence version 3 (23 Jan 2007)
Previous versions | rss
Add a publicationFeedback
Protein

Genome polyprotein

Gene
N/A
Organism
Hepatitis C virus genotype 3b (isolate Tr-Kj) (HCV)
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>
-Protein inferred from homologyi <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

Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity).

Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity).

Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity).

Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity).

Activates STAT3 leading to cellular transformation (By similarity).

Regulates the activity of cellular genes, including c-myc and c-fos (By similarity).

May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity).

Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity).

Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (By similarity).

Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity).

Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity).

Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).

By similarityCurated

Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity).

Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity).

E1/E2 heterodimer binds host apolipoproteins such as APOB and ApoE thereby forming a lipo-viro-particle (LVP) (By similarity).

APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity).

The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity).

E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity).

Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity).

By similarity

Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity).

Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity).

The interaction between envelope glycoprotein E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (By similarity).

This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (By similarity).

E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity).

APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity).

The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity).

E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity).

Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity).

Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity).

Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (By similarity).

These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (By similarity).

The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (By similarity).

By similarity

Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (By similarity).

Regulates the host cell secretory pathway, which induces the intracellular retention of viral glycoproteins and favors assembly of viral particles (By similarity).

Creates a pore in acidic organelles and releases Ca2+ and H+ in the cytoplasm of infected cells, leading to a productive viral infection (By similarity).

High levels of cytoplasmic Ca2+ may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). This ionic imbalance induces the assembly of the inflammasome complex, which triggers the maturation of pro-IL-1beta into IL-1beta through the action of caspase-1 (By similarity).

Targets also host mitochondria and induces mitochondrial depolarization (By similarity).

In addition of its role as a viroporin, acts as a lipid raft adhesion factor (By similarity).

By similarityCurated

Cysteine protease required for the proteolytic auto-cleavage between the non-structural proteins NS2 and NS3 (By similarity).

The N-terminus of NS3 is required for the function of NS2 protease (active region NS2-3) (By similarity).

Promotes the initiation of viral particle assembly by mediating the interaction between structural and non-structural proteins (By similarity).

By similarity

Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (By similarity).

NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (By similarity).

The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity).

The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity).

NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (By similarity).

Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (By similarity).

Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity).

Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (By similarity).

Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (By similarity).

By similarity

Peptide cofactor which forms a non-covalent complex with the N-terminal of NS3 serine protease (By similarity).

The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity).

The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity).

By similarity

Induces a specific membrane alteration that serves as a scaffold for the virus replication complex (By similarity).

This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity).

NS4B self-interaction contributes to its function in membranous web formation (By similarity).

Promotes host TRIF protein degradation in a CASP8-dependent manner thereby inhibiting host TLR3-mediated interferon signaling (By similarity).

Disrupts the interaction between STING and TBK1 contributing to the inhibition of interferon signaling (By similarity).

By similarity

Phosphorylated protein that is indispensable for viral replication and assembly (By similarity).

Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity).

The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity).

Involved in RNA-binding and especially in binding to the viral genome (By similarity).

Zinc is essential for RNA-binding (By similarity).

Participates in the viral particle production as a result of its interaction with the mature viral core protein (By similarity).

Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity).

Down-regulates viral IRES translation initiation (By similarity).

Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (By similarity).

Prevents BIN1-induced apoptosis (By similarity).

Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity).

Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (By similarity).

Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By similarity).

By similarity

RNA-dependent RNA polymerase that performs primer-template recognition and RNA synthesis during viral replication.

By similarity

Miscellaneous

Viral particle assembly takes place at the surface of ER-derived membranes in close proximity to lipid droplets. NS2 associates with E1/E2 glycoproteins, NS3 and NS5A, which interacts with the viral RNA and core protein to promote genome encapsidation. The nucleocapsid buds at the ER membrane where E1/E2 glycoproteins are anchored and afterward associate with nascent lipid droplet to acquire APOE and APOC. Secretion of viral particles is probably regulated by viroporin p7.Curated
Cell culture adaptation of the virus leads to mutations in NS5A, reducing its inhibitory effect on replication.Curated
Exerts viral interference on hepatitis B virus when HCV and HBV coinfect the same cell, by suppressing HBV gene expression, RNA encapsidation and budding.By similarity

Caution

The core gene probably also codes for alternative reading frame proteins (ARFPs). Many functions depicted for the core protein might belong to the ARFPs.Curated

<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 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Protease NS2:
Zn2+By similarityNote: Activity of protease NS2 is dependent on zinc ions and completely inhibited by EDTA. This is probably due to the fact that NS2 protease activity needs NS3 N-terminus that binds a zinc atom (active region NS2-3).By similarity
RNA-directed RNA polymerase:
Mg2+By similarityNote: Binds 2 magnesium ion that constitute a dinuclear catalytic metal center.By similarity
Serine protease/helicase NS3:
Zn2+By similarity, Mg2+By similarityNote: Binds 1 zinc ion, which has a structural role (By similarity). The magnesium ion is essential for the helicase activity (By similarity).By similarity

<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 by the antiviral drug hexamethylene amiloride (By similarity). Inhibition by amantadine appears to be genotype-dependent (By similarity). Also inhibited by long-alkyl-chain iminosugar derivatives (By similarity).By similarity
Activity is up-regulated by PRK2/PKN2-mediated phosphorylation.By similarity

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 sitei960For protease NS2 activity; shared with dimeric partnerPROSITE-ProRule annotation1
Active sitei980For protease NS2 activity; shared with dimeric partnerPROSITE-ProRule annotation1
Active sitei1001For protease NS2 activity; shared with dimeric partnerPROSITE-ProRule annotation1
Active sitei1091Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation1
Active sitei1115Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation1
<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 bindingi1131Zinc; structural; required for NS3 protease activity and NS2/3 auto-cleavage activityPROSITE-ProRule annotation1
Metal bindingi1133Zinc; structural; required for NS3 protease activity and NS2/3 auto-cleavage activityPROSITE-ProRule annotation1
Active sitei1173Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation1
Metal bindingi1179Zinc; structural; required for NS3 protease activity and NS2/3 auto-cleavage activityPROSITE-ProRule annotation1
Metal bindingi1183Zinc; required for NS3 protease activityPROSITE-ProRule annotation1
Metal bindingi1245Magnesium; catalytic; for NS3 helicase activityBy similarity1
Metal bindingi1325Magnesium; catalytic; for NS3 helicase activityBy similarity1
Metal bindingi2019Zinc; structuralBy similarity1
Metal bindingi2037Zinc; structuralBy similarity1
Metal bindingi2039Zinc; structuralBy similarity1
Metal bindingi2060Zinc; structuralBy similarity1
Metal bindingi2652Magnesium; catalytic; for RNA-directed RNA polymerase activityBy similarity1
Metal bindingi2750Magnesium; catalytic; for RNA-directed RNA polymerase activityBy similarity1
Metal bindingi2751Magnesium; catalytic; for RNA-directed RNA polymerase activityBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<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 bindingi1238 – 1245ATPPROSITE-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 functionHelicase, Hydrolase, Ion channel, Multifunctional enzyme, Nucleotidyltransferase, Protease, Ribonucleoprotein, RNA-binding, RNA-directed RNA polymerase, Serine protease, Thiol protease, Transferase, Viral ion channel, Viral nucleoprotein
Biological processActivation of host autophagy by virus, Apoptosis, Clathrin-mediated endocytosis of virus by host, Fusion of virus membrane with host endosomal membrane, Fusion of virus membrane with host membrane, G1/S host cell cycle checkpoint dysregulation by virus, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host MAVS by virus, Inhibition of host RLR pathway by virus, Inhibition of host STAT1 by virus, Inhibition of host TRAFs by virus, Interferon antiviral system evasion, Ion transport, Modulation of host cell cycle by virus, Transcription, Transcription regulation, Transport, Viral attachment to host cell, Viral immunoevasion, Viral penetration into host cytoplasm, Viral RNA replication, Virus endocytosis by host, Virus entry into host cell
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Protein family/group databases

MEROPS protease database

More...
MEROPSi
C18.001

<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:
Genome polyprotein
Cleaved into the following 11 chains:
Alternative name(s):
Capsid protein C
p23
Alternative name(s):
p21
Alternative name(s):
gp32
gp35
Alternative name(s):
NS1
gp68
gp70
Protease NS2 (EC:3.4.22.-By similarity)
Short name:
p23
Alternative name(s):
Non-structural protein 2
Short name:
NS2
Serine protease/helicase NS3 (EC:3.4.21.98By similarity, EC:3.6.1.15By similarity, EC:3.6.4.13By similarity)
Alternative name(s):
Hepacivirin
NS3 helicaseBy similarity
NS3 proteaseBy similarity
NS3P
Viroporin p70
Alternative name(s):
p8
Alternative name(s):
p27
Alternative name(s):
p56/58
RNA-directed RNA polymerase (EC:2.7.7.48By similarity)
Alternative name(s):
NS5B
p68
<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>OrganismiHepatitis C virus genotype 3b (isolate Tr-Kj) (HCV)
<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 identifieri357355 [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 lineageiVirusesRiboviriaOrthornaviraeKitrinoviricotaFlasuviricetesAmarilloviralesFlaviviridaeHepacivirus
<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
  • UP000007534 <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 domaini2 – 168CytoplasmicSequence analysisAdd BLAST167
<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>Transmembranei169 – 189HelicalSequence analysisAdd BLAST21
Topological domaini190 – 359LumenalBy similarityAdd BLAST170
Transmembranei360 – 380HelicalBy similarityAdd BLAST21
Topological domaini381 – 733LumenalBy similarityAdd BLAST353
Transmembranei734 – 754HelicalBy similarityAdd BLAST21
Topological domaini755 – 765LumenalBy similarityAdd BLAST11
Transmembranei766 – 786HelicalBy similarityAdd BLAST21
Topological domaini787 – 790CytoplasmicBy similarity4
Transmembranei791 – 811HelicalBy similarityAdd BLAST21
Topological domaini812 – 821LumenalBy similarity10
Transmembranei822 – 842HelicalBy similarityAdd BLAST21
Topological domaini843 – 889CytoplasmicBy similarityAdd BLAST47
Transmembranei890 – 910HelicalBy similarityAdd BLAST21
Topological domaini911 – 936LumenalBy similarityAdd BLAST26
Transmembranei937 – 957HelicalBy similarityAdd BLAST21
Topological domaini958 – 1665CytoplasmicBy similarityAdd BLAST708
Transmembranei1666 – 1686HelicalSequence analysisAdd BLAST21
Topological domaini1687 – 1813CytoplasmicSequence analysisAdd BLAST127
Transmembranei1814 – 1834HelicalSequence analysisAdd BLAST21
Topological domaini1835 – 1836LumenalBy similarity2
Transmembranei1837 – 1857HelicalSequence analysisAdd BLAST21
Topological domaini1858CytoplasmicSequence analysis1
Transmembranei1859 – 1879HelicalSequence analysisAdd BLAST21
Topological domaini1880 – 1889LumenalSequence analysis10
Transmembranei1890 – 1910HelicalSequence analysisAdd BLAST21
Topological domaini1911 – 1980CytoplasmicSequence analysisAdd BLAST70
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a region that is buried within a membrane, but does not cross it.<p><a href='/help/intramem' target='_top'>More...</a></p>Intramembranei1981 – 2010By similarityAdd BLAST30
Topological domaini2011 – 3002CytoplasmicBy similarityAdd BLAST992
Transmembranei3003 – 3023HelicalBy similarityAdd BLAST21

Keywords - Cellular componenti

Capsid protein, Host cell membrane, Host cytoplasm, Host endoplasmic reticulum, Host lipid droplet, Host membrane, Host mitochondrion, Host nucleus, Membrane, Viral envelope protein, Virion

<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

Keywords - Diseasei

Oncogene

<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 <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemoved; by hostBy similarity
<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_00004509272 – 3023Genome polyproteinAdd BLAST3022
ChainiPRO_00000456882 – 191Core protein precursorSequence analysisAdd BLAST190
ChainiPRO_00000456892 – 177Mature core proteinAdd BLAST176
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes a propeptide, which is a part of a protein that is cleaved during maturation or activation. Once cleaved, a propeptide generally has no independent biological function.<p><a href='/help/propep' target='_top'>More...</a></p>PropeptideiPRO_0000045690178 – 191ER anchor for the core protein, removed in mature form by host signal peptidaseAdd BLAST14
ChainiPRO_0000045691192 – 384Envelope glycoprotein E1Add BLAST193
ChainiPRO_0000045692385 – 754Envelope glycoprotein E2Add BLAST370
ChainiPRO_0000045693755 – 817Viroporin p7Add BLAST63
ChainiPRO_0000045694818 – 1034Protease NS2PROSITE-ProRule annotationAdd BLAST217
ChainiPRO_00000456951035 – 1665Serine protease/helicase NS3Add BLAST631
ChainiPRO_00000456961666 – 1719Non-structural protein 4AAdd BLAST54
ChainiPRO_00000456971720 – 1980Non-structural protein 4BAdd BLAST261
ChainiPRO_00000456981981 – 2432Non-structural protein 5AAdd BLAST452
ChainiPRO_00000456992433 – 3023RNA-directed RNA polymeraseAdd BLAST591

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei2N-acetylserine; by hostBy similarity1
Modified residuei53Phosphoserine; by hostBy similarity1
Modified residuei116Phosphoserine; by hostBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi196N-linked (GlcNAc...) asparagine; by hostBy similarity1
Glycosylationi209N-linked (GlcNAc...) asparagine; by hostBy similarity1
Glycosylationi235N-linked (GlcNAc...) asparagine; by hostBy similarity1
Glycosylationi306N-linked (GlcNAc...) asparagine; by hostBy similarity1
Glycosylationi418N-linked (GlcNAc...) (high mannose) asparagine; by hostBy similarity1
Glycosylationi424N-linked (GlcNAc...) (high mannose) asparagine; by hostBy similarity1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi430 ↔ 554By similarity
Glycosylationi431N-linked (GlcNAc...) (high mannose) asparagine; by hostBy similarity1
Glycosylationi449N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Disulfide bondi453 ↔ 460By similarity
Glycosylationi477N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Disulfide bondi488 ↔ 496By similarity
Disulfide bondi505 ↔ 510By similarity
Glycosylationi534N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi558N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Disulfide bondi566 ↔ 571By similarity
Disulfide bondi589 ↔ 593By similarity
Disulfide bondi605 ↔ 628By similarity
Disulfide bondi615 ↔ 652By similarity
Glycosylationi631N-linked (GlcNAc...) (high mannose) asparagine; by hostBy similarity1
Glycosylationi653N-linked (GlcNAc...) (high mannose) asparagine; by hostBy similarity1
Disulfide bondi660 ↔ 685By similarity
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position(s) and the type of covalently attached lipid group(s).<p><a href='/help/lipid' target='_top'>More...</a></p>Lipidationi930S-palmitoyl cysteine; by hostBy similarity1
Lipidationi1980S-palmitoyl cysteine; by hostBy similarity1
Modified residuei2202Phosphoserine; by hostBy similarity1
Modified residuei2205Phosphoserine; by hostBy similarity1
Modified residuei2209Phosphoserine; by hostBy similarity1
Modified residuei2212Phosphoserine; by hostBy similarity1
Modified residuei2215Phosphoserine; by hostBy similarity1
Modified residuei2218Phosphoserine; by hostBy similarity1
Modified residuei2461Phosphoserine; by hostBy similarity1
Modified residuei2474Phosphoserine; by hostBy similarity1

<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 yield mature proteins (By similarity). The structural proteins, core, E1, E2 and p7 are produced by proteolytic processing by host signal peptidases (By similarity). The core protein precursor is synthesized as a 23 kDa, which is retained in the ER membrane through the hydrophobic signal peptide (By similarity). Cleavage by the signal peptidase releases the 21 kDa mature core protein (By similarity). The cleavage of the core protein precursor occurs between aminoacids 176 and 188 but the exact cleavage site is not known (By similarity). Some degraded forms of the core protein appear as well during the course of infection (By similarity). The other proteins (p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B) are cleaved by the viral proteases (By similarity). Autoprocessing between NS2 and NS3 is mediated by the NS2 cysteine protease catalytic domain and regulated by the NS3 N-terminal domain (By similarity).By similarity
Phosphorylated by host PKC and PKA.By similarity
Ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation.By similarity
Highly N-glycosylated.By similarity
Highly N-glycosylated.By similarity
Palmitoylation is required for NS2/3 autoprocessing and E2 recruitment to membranes.By similarity
Palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions.By similarity
Phosphorylated on serines in a basal form termed p56 (By similarity). p58 is a hyperphosphorylated form of p56 (By similarity). p56 and p58 coexist in the cell in roughly equivalent amounts (By similarity). Hyperphosphorylation is dependent on the presence of NS4A (By similarity). Host CSNK1A1/CKI-alpha or RPS6KB1 kinases may be responsible for NS5A phosphorylation (By similarity).By similarity
Tyrosine phosphorylation is essential for the interaction with host SRC.By similarity
The N-terminus is phosphorylated by host PRK2/PKN2.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>Sitei177 – 178Cleavage; by host signal peptide peptidaseBy similarity2
Sitei191 – 192Cleavage; by host signal peptidaseBy similarity2
Sitei384 – 385Cleavage; by host signal peptidaseBy similarity2
Sitei754 – 755Cleavage; by host signal peptidase2
Sitei817 – 818Cleavage; by host signal peptidase2
Sitei1034 – 1035Cleavage; by protease NS2PROSITE-ProRule annotation2
Sitei1665 – 1666Cleavage; by serine protease NS3By similarity2
Sitei1719 – 1720Cleavage; by serine protease NS3By similarity2
Sitei1980 – 1981Cleavage; by serine protease NS3By similarity2
Sitei2432 – 2433Cleavage; by serine protease NS3By similarity2

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein, Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

<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

Homooligomer (By similarity).

Interacts with E1 (via C-terminus) (By similarity).

Interacts with the non-structural protein 5A (By similarity).

Interacts (via N-terminus) with host STAT1 (via SH2 domain); this interaction results in decreased STAT1 phosphorylation and ubiquitin-mediated proteasome-dependent STAT1 degradation, leading to decreased IFN-stimulated gene transcription (By similarity).

Interacts with host STAT3; this interaction constitutively activates STAT3 (By similarity).

Interacts with host LTBR receptor (By similarity).

Interacts with host TNFRSF1A receptor and possibly induces apoptosis (By similarity).

Interacts with host HNRPK (By similarity).

Interacts with host YWHAE (By similarity).

Interacts with host UBE3A/E6AP (By similarity).

Interacts with host DDX3X (By similarity).

Interacts with host APOA2 (By similarity).

Interacts with host RXRA protein (By similarity).

Interacts with host SP110 isoform 3/Sp110b; this interaction sequesters the transcriptional corepressor SP110 away from the nucleus (By similarity).

Interacts with host CREB3 nuclear transcription protein; this interaction triggers cell transformation (By similarity).

Interacts with host ACY3 (By similarity).

Interacts with host C1QR1 (By similarity).

Interacts with host RBM24; this interaction, which enhances the interaction of the mature core protein with 5'-UTR, may inhibit viral translation and favor replication (By similarity).

Interacts with host EIF2AK2/PKR; this interaction induces the autophosphorylation of EIF2AK2 (By similarity). Part of the viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein (By similarity).

By similarity

Forms a heterodimer with envelope glycoprotein E2 (By similarity).

Interacts with mature core protein (By similarity).

Interacts with protease NS2 (By similarity). The heterodimer E1/E2 interacts with host CLDN1; this interaction plays a role in viral entry into host cell (By similarity).

Interacts with host SPSB2 (via C-terminus) (By similarity). Part of the viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein (By similarity).

By similarity

Forms a heterodimer with envelope glycoprotein E1 (By similarity).

Interacts with host CD81 and SCARB1 receptors; these interactions play a role in viral entry into host cell (By similarity).

Interacts with host EIF2AK2/PKR; this interaction inhibits EIF2AK2 and probably allows the virus to evade the innate immune response (By similarity).

Interacts with host CD209/DC-SIGN and CLEC4M/DC-SIGNR (By similarity). Interact with host SPCS1; this interaction is essential for viral particle assembly (By similarity).

Interacts with protease NS2 (By similarity). The heterodimer E1/E2 interacts with host CLDN1; this interaction plays a role in viral entry into host cell (By similarity). Part of the viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein (By similarity).

Interacts with host SLC3A2/4F2hc; the interaction may facilitate viral entry into host cell (By similarity).

Interacts with human PLSCR1 (By similarity).

By similarity

Homohexamer (By similarity). Homoheptamer (By similarity).

Interacts with protease NS2 (By similarity).

By similarity

Homodimer (By similarity).

Interacts with host SPCS1; this interaction is essential for viral particle assembly (By similarity).

Interacts with envelope glycoprotein E1 (By similarity).

Interacts with envelope glycoprotein E2 (By similarity).

Interacts with viroporin p7 (By similarity).

Interacts with serine protease/helicase NS3 (By similarity). Part of the replication complex composed of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA polymerase embedded in an ER-derived membranous web (By similarity). Part of the viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein (By similarity).

By similarity

Interacts with protease NS2 (By similarity).

Interacts with non-structural protein 4A; this interaction stabilizes the folding of NS3 serine protease (By similarity). NS3-NS4A interaction is essential for NS3 activation and allows membrane anchorage of the latter (By similarity). NS3/NS4A complex also prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity).

Interacts with host MAVS; this interaction leads to the cleavage and inhibition of host MAVS (By similarity).

Interacts with host TICAM1; this interaction leads to the cleavage and inhibition of host TICAM1 (By similarity).

Interacts with host TANK-binding kinase/TBK1; this interaction results in the inhibition of the association between TBK1 and IRF3, which leads to the inhibition of IRF3 activation (By similarity).

Interacts with host RBM24 (By similarity). Part of the replication complex composed of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA polymerase embedded in an ER-derived membranous web (By similarity). Part of the viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein (By similarity).

By similarity

Interacts with NS3 serine protease; this interaction stabilizes the folding of NS3 serine protease (By similarity). NS3-NS4A interaction is essential for NS3 activation and allows membrane anchorage of the latter (By similarity).

Interacts with non-structural protein 5A (via N-terminus) (By similarity). Part of the replication complex composed of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA polymerase embedded in an ER-derived membranous web (By similarity). Part of the viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein (By similarity).

By similarity

Homomultimer (By similarity).

Interacts with non-structural protein NS5A (By similarity).

Interacts with host PLA2G4C; this interaction likely initiates the recruitment of replication complexes to lipid droplets (By similarity).

Interacts with host STING; this interaction disrupts the interaction between STING and TBK1 thereby suppressing the interferon signaling (By similarity). Part of the replication complex composed of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA polymerase embedded in an ER-derived membranous web (By similarity).

By similarity

Monomer (By similarity). Homodimer; dimerization is required for RNA-binding (By similarity).

Interacts with mature core protein (By similarity).

Interacts (via N-terminus) with non-structural protein 4A (By similarity).

Interacts with non-structural protein 4B (By similarity).

Interacts with RNA-directed RNA polymerase (By similarity). Part of the viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein (By similarity). Part of the replication complex composed of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA polymerase (By similarity).

Interacts with host GRB2 (By similarity).

Interacts with host BIN1 (By similarity).

Interacts with host PIK3R1 (By similarity).

Interacts with host SRCAP (By similarity).

Interacts with host FKBP8 (By similarity).

Interacts with host VAPB (By similarity).

Interacts with host EIF2AK2/PKR; this interaction leads to disruption of EIF2AK2 dimerization by NS5A and probably allows the virus to evade the innate immune response (By similarity).

Interacts (via N-terminus) with host PACSIN2 (via N-terminus); this interaction attenuates protein kinase C alpha-mediated phosphorylation of PACSIN2 by disrupting the interaction between PACSIN2 and PRKCA (By similarity).

Interacts (via N-terminus) with host SRC kinase (via SH2 domain) (By similarity).

Interacts with most Src-family kinases (By similarity).

Interacts with host IFI27 and SKP2; promotes the ubiquitin-mediated proteasomal degradation of NS5A (By similarity).

Interacts with host GPS2 (By similarity).

Interacts with host TNFRSF21; this interaction allows the modulation by the virus of JNK, p38 MAPK, STAT3, and Akt signaling pathways in a DR6-dependent manner (By similarity).

Interacts (via N-terminus) with host CIDEB (via N-terminus); this interaction seems to regulate the association of HCV particles with APOE (By similarity).

Interacts with host CHKA/Choline Kinase-alpha; CHKA bridges host PI4KA and NS5A and potentiates NS5A-stimulated PI4KA activity, which then facilitates the targeting of the ternary complex to the ER for viral replication (By similarity).

Interacts with host SPSB2 (via C-terminus); this interaction targets NS5A for ubiquitination and degradation (By similarity).

Interacts with host RAB18; this interaction may promote the association of NS5A and other replicase components with lipid droplets (By similarity).

By similarity

Homooligomer (By similarity).

Interacts with non-structural protein 5A (By similarity).

Interacts with host VAPB (By similarity).

Interacts with host PRK2/PKN2 (By similarity).

Interacts with host HNRNPA1 and SEPT6; these interactions facilitate viral replication (By similarity). Part of the replication complex composed of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA polymerase (By similarity).

By similarity

GO - Molecular functioni

<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

3D structure databases

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

More...
SMRi
Q81487

Database of comparative protein structure models

More...
ModBasei
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>Domaini907 – 1034Peptidase C18PROSITE-ProRule annotationAdd BLAST128
Domaini1035 – 1216Peptidase S29PROSITE-ProRule annotationAdd BLAST182
Domaini1225 – 1377Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST153
Domaini1387 – 1546Helicase C-terminalPROSITE-ProRule annotationAdd BLAST160
Domaini2646 – 2764RdRp catalyticPROSITE-ProRule annotationAdd BLAST119

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>Regioni2 – 75DisorderedBy similarityAdd BLAST74
Regioni2 – 59Interaction with DDX3XBy similarityAdd BLAST58
Regioni2 – 58Interaction with EIF2AK2/PKRBy similarityAdd BLAST57
Regioni2 – 23Interaction with STAT1By similarityAdd BLAST22
Regioni112 – 152Important for endoplasmic reticulum and mitochondrial localizationBy similarityAdd BLAST41
Regioni122 – 173Interaction with APOA2By similarityAdd BLAST52
Regioni164 – 167Important for lipid droplets localizationBy similarity4
Regioni266 – 297Important for fusionBy similarityAdd BLAST32
Regioni386 – 413HVR1By similarityAdd BLAST28
Regioni476 – 480HVR2By similarity5
Regioni482 – 495CD81-binding 1By similarityAdd BLAST14
Regioni546 – 553CD81-binding 2By similarity8
Regioni668 – 679PKR/eIF2-alpha phosphorylation homology domain (PePHD)Add BLAST12
Regioni912 – 1214Protease NS2-3By similarityAdd BLAST303
Regioni937 – 957Interaction with host SCPS1By similarityAdd BLAST21
Regioni1494 – 1506RNA-bindingBy similarityAdd BLAST13
Regioni1687 – 1698NS3-bindingBy similarityAdd BLAST12
Regioni2128 – 2340Transcriptional activationSequence analysisAdd BLAST213
Regioni2128 – 2216FKBP8-bindingBy similarityAdd BLAST89
Regioni2143 – 2147Interaction with non-structural protein 4ABy similarity5
Regioni2195 – 2226DisorderedSequence analysisAdd BLAST32
Regioni2197 – 2450Interaction with host SKP2By similarityAdd BLAST254
Regioni2218 – 2283Interaction with EIF2AK2/PKRBy similarityAdd BLAST66
Regioni2218 – 2257ISDRBy similarityAdd BLAST40
Regioni2257 – 2314NS4B-bindingSequence analysisAdd BLAST58
Regioni2307 – 2385V3Add BLAST79
Regioni2320 – 2344DisorderedSequence analysisAdd BLAST25
Regioni2357 – 2422DisorderedSequence analysisAdd BLAST66

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi5 – 13Nuclear localization signalBy similarity9
Motifi38 – 43Nuclear localization signalBy similarity6
Motifi58 – 64Nuclear localization signalBy similarity7
Motifi66 – 71Nuclear localization signalBy similarity6
Motifi1324 – 1327DECH boxBy similarity4
Motifi2330 – 2333SH3-bindingSequence analysis4
Motifi2335 – 2343Nuclear localization signalBy similarity9

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 biasi44 – 69Basic and acidic residuesSequence analysisAdd BLAST26
Compositional biasi2203 – 2222Polar residuesSequence analysisAdd BLAST20
Compositional biasi2322 – 2336Pro residuesSequence analysisAdd BLAST15
Compositional biasi2363 – 2384Polar residuesSequence analysisAdd BLAST22

<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 transmembrane regions of envelope E1 and E2 glycoproteins are involved in heterodimer formation, ER localization, and assembly of these proteins.By similarity
The transmembrane regions of envelope E1 and E2 glycoproteins are involved in heterodimer formation, ER localization, and assembly of these proteins (By similarity). Envelope E2 glycoprotein contain two highly variable regions called hypervariable region 1 and 2 (HVR1 and HVR2) (By similarity). E2 also contain two segments involved in CD81-binding (By similarity). HVR1 is implicated in the SCARB1-mediated cell entry and probably acts as a regulator of the association of particles with lipids (By similarity).By similarity
The N-terminus of NS3 is required for the catalytic activity of protease NS2 (By similarity). The minimal catalytic region includes the C-terminus of NS2 and the N-terminus NS3 protease domain (active region NS2-3) (By similarity).By similarity
The N-terminal one-third contains the protease activity (By similarity). This region contains a zinc atom that does not belong to the active site, but may play a structural rather than a catalytic role (By similarity). This region is essential for the activity of protease NS2, maybe by contributing to the folding of the latter (By similarity). The NTPase/helicase activity is located in the twothirds C-terminus of NS3, this domain contains the NTPase and RNA-binding regions (By similarity).By similarity
Contains a glycine zipper region that critically contributes to the biogenesis of functional ER-derived replication organelles.By similarity
The N-terminus of NS5A acts as membrane anchor (By similarity). The central part of NS5A contains a variable region called interferon sensitivity determining region (ISDR) and seems to be intrinsically disordered and interacts with NS5B and host EIF2AK2 (By similarity). The C-terminus of NS5A contains a variable region called variable region 3 (V3) (By similarity). ISDR and V3 may be involved in sensitivity and/or resistance to IFN-alpha therapy (By similarity). The C-terminus contains a nuclear localization signal (By similarity). The SH3-binding domain is involved in the interaction with host BIN1, GRB2 and Src-family kinases (By similarity).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 hepacivirus polyprotein family.Curated

Keywords - Domaini

SH3-binding, Transmembrane, Transmembrane helix

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
1.20.1280.150, 1 hit
2.20.25.210, 1 hit
2.20.25.220, 1 hit
2.30.30.710, 1 hit
2.40.10.10, 1 hit
3.30.70.270, 1 hit

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR011492, DEAD_Flavivir
IPR043502, DNA/RNA_pol_sf
IPR002521, HCV_core_C
IPR002522, HCV_core_N
IPR002519, HCV_env
IPR002531, HCV_NS1
IPR002518, HCV_NS2
IPR042205, HCV_NS2_C
IPR042209, HCV_NS2_N
IPR000745, HCV_NS4a
IPR001490, HCV_NS4b
IPR002868, HCV_NS5a
IPR013193, HCV_NS5a_1B_dom
IPR038568, HCV_NS5A_1B_sf
IPR024350, HCV_NS5a_C
IPR014001, Helicase_ATP-bd
IPR001650, Helicase_C
IPR013192, NS5A_1a
IPR038170, NS5A_1a_sf
IPR027417, P-loop_NTPase
IPR009003, Peptidase_S1_PA
IPR043504, Peptidase_S1_PA_chymotrypsin
IPR004109, Peptidase_S29_NS3
IPR043128, Rev_trsase/Diguanyl_cyclase
IPR007094, RNA-dir_pol_PSvirus
IPR002166, RNA_pol_HCV

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF07652, Flavi_DEAD, 1 hit
PF01543, HCV_capsid, 1 hit
PF01542, HCV_core, 1 hit
PF01539, HCV_env, 1 hit
PF01560, HCV_NS1, 1 hit
PF01538, HCV_NS2, 1 hit
PF01006, HCV_NS4a, 1 hit
PF01001, HCV_NS4b, 1 hit
PF01506, HCV_NS5a, 1 hit
PF08300, HCV_NS5a_1a, 1 hit
PF08301, HCV_NS5a_1b, 1 hit
PF12941, HCV_NS5a_C, 1 hit
PF02907, Peptidase_S29, 1 hit
PF00998, RdRP_3, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM00487, DEXDc, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF50494, SSF50494, 1 hit
SSF52540, SSF52540, 2 hits
SSF56672, SSF56672, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS51693, HCV_NS2_PRO, 1 hit
PS51192, HELICASE_ATP_BIND_1, 1 hit
PS51194, HELICASE_CTER, 1 hit
PS51822, HV_PV_NS3_PRO, 1 hit
PS50507, RDRP_SSRNA_POS, 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>Sequencei

<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.

Q81487-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSTLPKPKRQ TKRNTLRRPK NVKFPAGGQI VGEVYVLPRR GPQLGVREVR
60 70 80 90 100
KTSERSQPRG RRQPTPKARP REGRSWAQPG YPWPLYGNEG CGWAGWLLPP
110 120 130 140 150
RGSRPSWGQN DPRRRSRNLG KVIDTLTCGF ADLMGYIPLI GAPVGGVARA
160 170 180 190 200
LAHGVRALED GVNYATGNLP GCSFSIFLLA LFSCLTCPAS SLEYRNASGL
210 220 230 240 250
YLLTNDCSNR SIVYEADDVI LHLPGCVPCV ETDNNNTSCW TPISPTVAVK
260 270 280 290 300
HPGVTTASIR NHVNMLVAPP TLCSALYVED AFGAVSLVGQ AFTFRPRQHK
310 320 330 340 350
TVQTCNCSIY PGHVSGHRMA WDMMMNWSPA IGLVISHLMR LPQTFFDLVV
360 370 380 390 400
GAHWGVMAGL AYFSMQGNWA KVVIVLIMFS GVDATTHTTG GSAAQATAGF
410 420 430 440 450
TSFFTRGPSQ NLQLVNSNGS WHINSTALNC NDSLNTGFIA GLFYYHKFNS
460 470 480 490 500
SGCPERMSSC KPITYFNQGW GPLTDANING PSEDRPYCWH YPPRPCNITK
510 520 530 540 550
PLNVCGPVYC FTPSPVVVGT TDIKGLPTYR FGVNESDVFL LTSLRPPQGR
560 570 580 590 600
WFGCVWMNST GFVKTCGAPP CNIYGGMKDI EANQTHLKCP TDCFRKHHDA
610 620 630 640 650
TFTRCGSGPW LTPRCLVDYP YRLWHYPCTV NFSIFKVRMF VGGHEHRFSA
660 670 680 690 700
ACNWTRGERC DLEDRDRSEQ QPLLHSTTDS LILPCSFTPM RRLSTGLIHL
710 720 730 740 750
HQNIVDVQYL YGVGSAVVGW ALKWEFVVLV FLLLADARVC VALWMMLLIS
760 770 780 790 800
QAEAAMENLV MLNALSAAGQ QGYVWYLVAF CAAWHIRGKL VPLITYGLTG
810 820 830 840 850
LWPLALLDLL LPQRAYAWTG EDDATIGAGV LLLLGFFTLS PWYKHWIGRL
860 870 880 890 900
IWWNQYAICR GEAALQVWVP PLLVRGSRDS VILLASLLYP SLIFDITKLL
910 920 930 940 950
IAVLGPLYLI QAALTSTPYF VRAHVLIRIC MLVRSAMGGK YVQMAVLTVG
960 970 980 990 1000
RWFNTYLYDH LSPIQDWAAE GLKGLAVATE PVIFSPMEIK VITWGADTAA
1010 1020 1030 1040 1050
CGDILCGLPV SARLGRELLL GPADDYKKMG WRLLSPISAY AQQTRGLFGT
1060 1070 1080 1090 1100
IVTSLTGRDK NVVTGEVQVL STATQTFLGT TVGGVMWTVY HGAGSRTLAG
1110 1120 1130 1140 1150
NKRPALQMYT NVDQDLVGWP APAGTKSLDP CTCGSSDLYL VTREADVLPA
1160 1170 1180 1190 1200
RRRGDSTASL LSTRPLSCLK GSSGGPVMCP SGHVVGIFRA AVCTRGVAKA
1210 1220 1230 1240 1250
LQFIPVETLS TQVRSPSFSD NSTPPAVPES YQVGYLHAPT GSGKSTKVPA
1260 1270 1280 1290 1300
AYVAQGYSVL VLNPSVAATL GFGTYMSKAY GIDPNIRTGT RTITTGAKLT
1310 1320 1330 1340 1350
YSTYGKFLAD GGCSGGAYDV IICDECHAQD ATSILGIGTV LDQAETAGVR
1360 1370 1380 1390 1400
LTVLATATPP GSITVPHPNI EEVGLTSDGE IPFYGKALPL AMIKGGRHLV
1410 1420 1430 1440 1450
FCHSKEKCDE LASKLRGMGV NAVAFYRGLD VSVIPVSGDV VVCATDALMT
1460 1470 1480 1490 1500
GYTGDFDTVI DCNVAVEQYV DFSLDPTFSI ETRTVPQDAV SRSQRRGRTG
1510 1520 1530 1540 1550
RGRPGIYRFV TPGERPSGMF DSVVLCECYD AGCSWYDLQP AETTVRLRAY
1560 1570 1580 1590 1600
LSTPGLPVCQ DHLDFWERVF TGLTHIDAHF LSQAKQQGLN FAYLVAYQAT
1610 1620 1630 1640 1650
VCARAKASPP CWDEMWKCLI RLKPTLQGPT PLLYRLGAIQ NDICMTHPIT
1660 1670 1680 1690 1700
KYIMACMSAD LEVTTSAWVL VGGVLAALAA YCLSVGCVVI VGHIELGGKP
1710 1720 1730 1740 1750
ALVPDRQVLY QQYDEMEECS QSAPYIEQAQ AIAQQFKDKV LGLLQRASQQ
1760 1770 1780 1790 1800
EAEIRPIVQS QWQKAEAFWQ QHMWNFVSGI QYLAGLSTLP GNPAVASLMA
1810 1820 1830 1840 1850
FTASVTSPLT TNQTMFFNIL GGWVATHLAG PAASSAFVVS GLAGAAVGGI
1860 1870 1880 1890 1900
GIGRVLLDVL AGYGAGVSGA LVAFKIMGGE LPTTEDMVNL LPAILSPGAL
1910 1920 1930 1940 1950
VVGVICAAVL RRHVGPGEGA VQWMNRLIAF ASRGNHVSPT HYVPESDAAA
1960 1970 1980 1990 2000
KVTALLSSLT VTRLLRRLHQ WINEDYPSPC NGDWLHDIWD WVCIVLSDFK
2010 2020 2030 2040 2050
TWLSAKIMPK VPGIPFLSCQ KGYKGVWRGD GVMTTRCPCG EDFTGHVRNG
2060 2070 2080 2090 2100
SMRIAGSGLC ANMWHGTFPI NEYTTGPSTP VPAHNYSRAL WRVTSDSYVE
2110 2120 2130 2140 2150
VRRVGDTHYV VGATNDGLKI PCQVPAPEFF TELDGVRLHR YAPPCKPLLR
2160 2170 2180 2190 2200
DEITFSVGLH SYANGSQLSC EPEPDVAVLT SMLRDPAHIT AATAARRLAR
2210 2220 2230 2240 2250
GSPPSEASSS ASQLSAPSLK ATCQTHRPHP DAELIDANLL WRQEMGSNIT
2260 2270 2280 2290 2300
RVESETKVVI LDSFEPLRAE EDDTELSIPA ECFKKPPKYP PALPIWARPD
2310 2320 2330 2340 2350
YNPPLLPSWK DPTYEPPAVH GCALPPTRPA PVPPPRRKRT IKLDGSNVSA
2360 2370 2380 2390 2400
ALLALAERSF PSTKPEGTGT SSSGVGTEST AESGDSPETG EESDVESYSS
2410 2420 2430 2440 2450
MPPLEGEPGD PDLDADSWST VSDSEEQSVV CCSMSYSWTG AIITPCSAEE
2460 2470 2480 2490 2500
EKLPISPLSN SLLRHHNLVY STSSRSAAAR QKKVTFDRLQ VLDDHYKNVL
2510 2520 2530 2540 2550
KEVKERASGV KGRLLSFEEA CSLVPPHSGR SKYGYSAKDV RSLSSKAMNQ
2560 2570 2580 2590 2600
IRSVWEDLLE DNSTPIPTTI MAKNEVFSVN PAKGGRKPAR LIVYPDLGVR
2610 2620 2630 2640 2650
VCEKRALYDV IQKLSIATMG PAYGFQYSPK QRVEHLLKMW TSKKTPLGFS
2660 2670 2680 2690 2700
YDTRCFDSTV TEHDIRTEEG IYQCCDLEPE ARKAISALTE RLYIGGPMYN
2710 2720 2730 2740 2750
SKGLQCGYRR CRASGVLPTS FGNTITCYIK ATAASRAAGL KNPSFLVCGD
2760 2770 2780 2790 2800
DLVVISESCG VEEDRTALRA FTEAMTRYSA PPGDAPQPTY DLELISSCSS
2810 2820 2830 2840 2850
NVSVACDGAG KRYYYLTRDP ETPLARAAWE TARHTPVNSW LGNIIMFAPT
2860 2870 2880 2890 2900
IWVRMVLITH FFSILQAQEQ LERALDFEMY GATYSVTPLD LPAIIERLHG
2910 2920 2930 2940 2950
LSAFSLHGYS PTELNRVAGA LRKLGIPPLR AWRHRARAVR AKLIAQGGKA
2960 2970 2980 2990 3000
RICGLYLFNW AVRTKTKLTP LPTAGQLDLS SWFTVGVGGN DIYHSVSRAR
3010 3020
TRHLLLCLLL LTVGVGIFLL PAR
Length:3,023
Mass (Da):329,739
Last modified:January 23, 2007 - v3
<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:i5268D1EC410AC545
GO

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
D49374 Genomic RNA Translation: BAA08372.1

<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

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Virus Pathogen Resource

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D49374 Genomic RNA Translation: BAA08372.1

3D structure databases

SMRiQ81487
ModBaseiSearch...

Protein family/group databases

MEROPSiC18.001

Organism-specific databases

European Hepatitis C Virus Database

More...
euHCVdbi
D49374

Family and domain databases

Gene3Di1.20.1280.150, 1 hit
2.20.25.210, 1 hit
2.20.25.220, 1 hit
2.30.30.710, 1 hit
2.40.10.10, 1 hit
3.30.70.270, 1 hit
InterProiView protein in InterPro
IPR011492, DEAD_Flavivir
IPR043502, DNA/RNA_pol_sf
IPR002521, HCV_core_C
IPR002522, HCV_core_N
IPR002519, HCV_env
IPR002531, HCV_NS1
IPR002518, HCV_NS2
IPR042205, HCV_NS2_C
IPR042209, HCV_NS2_N
IPR000745, HCV_NS4a
IPR001490, HCV_NS4b
IPR002868, HCV_NS5a
IPR013193, HCV_NS5a_1B_dom
IPR038568, HCV_NS5A_1B_sf
IPR024350, HCV_NS5a_C
IPR014001, Helicase_ATP-bd
IPR001650, Helicase_C
IPR013192, NS5A_1a
IPR038170, NS5A_1a_sf
IPR027417, P-loop_NTPase
IPR009003, Peptidase_S1_PA
IPR043504, Peptidase_S1_PA_chymotrypsin
IPR004109, Peptidase_S29_NS3
IPR043128, Rev_trsase/Diguanyl_cyclase
IPR007094, RNA-dir_pol_PSvirus
IPR002166, RNA_pol_HCV
PfamiView protein in Pfam
PF07652, Flavi_DEAD, 1 hit
PF01543, HCV_capsid, 1 hit
PF01542, HCV_core, 1 hit
PF01539, HCV_env, 1 hit
PF01560, HCV_NS1, 1 hit
PF01538, HCV_NS2, 1 hit
PF01006, HCV_NS4a, 1 hit
PF01001, HCV_NS4b, 1 hit
PF01506, HCV_NS5a, 1 hit
PF08300, HCV_NS5a_1a, 1 hit
PF08301, HCV_NS5a_1b, 1 hit
PF12941, HCV_NS5a_C, 1 hit
PF02907, Peptidase_S29, 1 hit
PF00998, RdRP_3, 1 hit
SMARTiView protein in SMART
SM00487, DEXDc, 1 hit
SUPFAMiSSF50494, SSF50494, 1 hit
SSF52540, SSF52540, 2 hits
SSF56672, SSF56672, 1 hit
PROSITEiView protein in PROSITE
PS51693, HCV_NS2_PRO, 1 hit
PS51192, HELICASE_ATP_BIND_1, 1 hit
PS51194, HELICASE_CTER, 1 hit
PS51822, HV_PV_NS3_PRO, 1 hit
PS50507, RDRP_SSRNA_POS, 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 nameiPOLG_HCVTR
<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: Q81487
<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: January 10, 2006
Last sequence update: January 23, 2007
Last modified: June 2, 2021
This is version 161 of the entry and version 3 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again