Q5I2N3 · POLG_HCV6A
- ProteinGenome polyprotein
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids3019 (go to sequence)
- Protein existenceInferred from homology
- Annotation score5/5
Function
function
Mature core protein
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).
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).
Envelope glycoprotein E1
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).
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).
Envelope glycoprotein E2
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).
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).
Viroporin p7
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).
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).
Protease NS2
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).
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).
Serine protease/helicase NS3
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).
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).
Non-structural protein 4B
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).
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).
Non-structural protein 5A
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).
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).
RNA-directed RNA polymerase
RNA-dependent RNA polymerase that performs primer-template recognition and RNA synthesis during viral replication. Initiates RNA transcription/replication at a flavin adenine dinucleotide (FAD), resulting in a 5'- FAD cap on viral RNAs. In this way, recognition of viral 5' RNA by host pattern recognition receptors can be bypassed, thereby evading activation of antiviral pathways.
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.
Non-structural protein 5A
Cell culture adaptation of the virus leads to mutations in NS5A, reducing its inhibitory effect on replication.
Mature core protein
Exerts viral interference on hepatitis B virus when HCV and HBV coinfect the same cell, by suppressing HBV gene expression, RNA encapsidation and budding.
Catalytic activity
Serine protease/helicase NS3
Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.Serine protease/helicase NS3
a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H+ + phosphateSerine protease/helicase NS3
ATP + H2O = ADP + H+ + phosphateRNA-directed RNA polymerase
a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1)
Cofactor
Protein has several cofactor binding sites:
Protease NS2
Zn2+ (UniProtKB | Rhea| CHEBI:29105 )Note: 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).
Serine protease/helicase NS3
Zn2+ (UniProtKB | Rhea| CHEBI:29105 )Mg2+ (UniProtKB | Rhea| CHEBI:18420 )
Note: Binds 1 zinc ion, which has a structural role (By similarity).
The magnesium ion is essential for the helicase activity (By similarity).
The magnesium ion is essential for the helicase activity (By similarity).
RNA-directed RNA polymerase
Mg2+ (UniProtKB | Rhea| CHEBI:18420 )Note: Binds 2 magnesium ion that constitute a dinuclear catalytic metal center.
Activity regulation
Viroporin p7
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).
Inhibition by amantadine appears to be genotype-dependent (By similarity).
Also inhibited by long-alkyl-chain iminosugar derivatives (By similarity).
RNA-directed RNA polymerase
Activity is up-regulated by PRK2/PKN2-mediated phosphorylation.
Features
Showing features for site, active site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 177-178 | Cleavage; by host signal peptide peptidase | ||||
Sequence: FL | ||||||
Site | 191-192 | Cleavage; by host signal peptidase | ||||
Sequence: AL | ||||||
Site | 383-384 | Cleavage; by host signal peptidase | ||||
Sequence: AT | ||||||
Site | 751-752 | Cleavage; by host signal peptidase | ||||
Sequence: AA | ||||||
Site | 814-815 | Cleavage; by host signal peptidase | ||||
Sequence: AM | ||||||
Active site | 957 | For protease NS2 activity; shared with dimeric partner | ||||
Sequence: H | ||||||
Active site | 977 | For protease NS2 activity; shared with dimeric partner | ||||
Sequence: E | ||||||
Active site | 998 | For protease NS2 activity; shared with dimeric partner | ||||
Sequence: C | ||||||
Site | 1031-1032 | Cleavage; by protease NS2 | ||||
Sequence: LA | ||||||
Active site | 1088 | Charge relay system; for serine protease NS3 activity | ||||
Sequence: H | ||||||
Active site | 1112 | Charge relay system; for serine protease NS3 activity | ||||
Sequence: D | ||||||
Binding site | 1128 | Zn2+ 1 (UniProtKB | ChEBI); structural; for NS3 protease activity and NS2/3 auto-cleavage activity | ||||
Sequence: C | ||||||
Binding site | 1130 | Zn2+ 1 (UniProtKB | ChEBI); structural; for NS3 protease activity and NS2/3 auto-cleavage activity | ||||
Sequence: C | ||||||
Active site | 1170 | Charge relay system; for serine protease NS3 activity | ||||
Sequence: S | ||||||
Binding site | 1176 | Zn2+ 1 (UniProtKB | ChEBI); structural; for NS3 protease activity and NS2/3 auto-cleavage activity | ||||
Sequence: C | ||||||
Binding site | 1180 | Zn2+ 1 (UniProtKB | ChEBI); structural; for NS3 protease activity and NS2/3 auto-cleavage activity | ||||
Sequence: H | ||||||
Binding site | 1235-1242 | ATP (UniProtKB | ChEBI) | ||||
Sequence: APTGSGKS | ||||||
Binding site | 1242 | Mg2+ 1 (UniProtKB | ChEBI); catalytic; for NS3 helicase activity | ||||
Sequence: S | ||||||
Binding site | 1322 | Mg2+ 1 (UniProtKB | ChEBI); catalytic; for NS3 helicase activity | ||||
Sequence: E | ||||||
Site | 1662-1663 | Cleavage; by serine protease NS3 | ||||
Sequence: TS | ||||||
Site | 1716-1717 | Cleavage; by serine protease NS3 | ||||
Sequence: CS | ||||||
Site | 1977-1978 | Cleavage; by serine protease NS3 | ||||
Sequence: CA | ||||||
Binding site | 2016 | Zn2+ 2 (UniProtKB | ChEBI); structural | ||||
Sequence: C | ||||||
Binding site | 2034 | Zn2+ 2 (UniProtKB | ChEBI); structural | ||||
Sequence: C | ||||||
Binding site | 2036 | Zn2+ 2 (UniProtKB | ChEBI); structural | ||||
Sequence: C | ||||||
Binding site | 2057 | Zn2+ 2 (UniProtKB | ChEBI); structural | ||||
Sequence: C | ||||||
Site | 2428-2429 | Cleavage; by serine protease NS3 | ||||
Sequence: CS | ||||||
Binding site | 2648 | Mg2+ 2 (UniProtKB | ChEBI); catalytic; for RNA-directed RNA polymerase activity | ||||
Sequence: D | ||||||
Binding site | 2746 | Mg2+ 2 (UniProtKB | ChEBI); catalytic; for RNA-directed RNA polymerase activity | ||||
Sequence: D | ||||||
Binding site | 2747 | Mg2+ 2 (UniProtKB | ChEBI); catalytic; for RNA-directed RNA polymerase activity | ||||
Sequence: D |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameGenome polyprotein
- Cleaved into 11 chains
Organism names
- Taxonomic lineageViruses > Riboviria > Orthornavirae > Kitrinoviricota > Flasuviricetes > Amarillovirales > Flaviviridae > Hepacivirus > Hepacivirus hominis
- Virus hosts
Accessions
- Primary accessionQ5I2N3
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Core protein precursor
Host endoplasmic reticulum membrane ; Single-pass membrane protein
Host mitochondrion membrane ; Single-pass type I membrane protein
Note: The C-terminal transmembrane domain of the core protein precursor contains an ER signal leading the nascent polyprotein to the ER membrane.
Mature core protein
Note: Only a minor proportion of core protein is present in the nucleus (By similarity).
Probably present on the surface of lipid droplets (By similarity).
Probably present on the surface of lipid droplets (By similarity).
Envelope glycoprotein E1
Virion membrane ; Single-pass type I membrane protein
Host endoplasmic reticulum membrane ; Single-pass type I membrane protein
Note: The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity).
After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity).
A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity).
These events explain the final topology of the protein (By similarity).
After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity).
A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity).
These events explain the final topology of the protein (By similarity).
Envelope glycoprotein E2
Virion membrane ; Single-pass type I membrane protein
Host endoplasmic reticulum membrane ; Single-pass type I membrane protein
Note: The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity).
After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity).
A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity).
These events explain the final topology of the protein (By similarity).
After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity).
A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity).
These events explain the final topology of the protein (By similarity).
Viroporin p7
Host endoplasmic reticulum membrane ; Multi-pass membrane protein
Note: The C-terminus of p7 membrane domain acts as a signal sequence (By similarity).
After cleavage by host signal peptidase, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity).
ER retention of p7 is leaky and a small fraction reaches the plasma membrane (By similarity).
After cleavage by host signal peptidase, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity).
ER retention of p7 is leaky and a small fraction reaches the plasma membrane (By similarity).
Protease NS2
Host endoplasmic reticulum membrane ; Multi-pass membrane protein
Note: Probably present on the surface of lipid droplets.
Serine protease/helicase NS3
Host endoplasmic reticulum membrane ; Peripheral membrane protein
Note: NS3 is associated to the ER membrane through its binding to NS4A.
Non-structural protein 4A
Host endoplasmic reticulum membrane ; Single-pass type I membrane protein
Note: Host membrane insertion occurs after processing by the NS3 protease.
Non-structural protein 4B
Host endoplasmic reticulum membrane ; Multi-pass membrane protein
Note: A reorientation of the N-terminus into the ER lumen occurs post-translationally.
Non-structural protein 5A
Host endoplasmic reticulum membrane ; Peripheral membrane protein
Note: Host membrane insertion occurs after processing by the NS3 protease (By similarity).
Localizes at the surface of lipid droplets (By similarity).
Localizes at the surface of lipid droplets (By similarity).
RNA-directed RNA polymerase
Host endoplasmic reticulum membrane ; Single-pass type IV membrane protein
Note: Host membrane insertion occurs after processing by the NS3 protease.
Features
Showing features for topological domain, transmembrane, intramembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 2-168 | Cytoplasmic | ||||
Sequence: STLPKPQRKTKRNTNRRPMDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARQPQGRHWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPHWGPNDPRRRSRNLGKVIDTLTCGFADLMGYIPVVGAPLGGVAAALAHGVRAIEDGINYATGN | ||||||
Transmembrane | 169-189 | Helical | ||||
Sequence: LPGCSFSIFLLALLSCLTTPA | ||||||
Topological domain | 190-358 | Lumenal | ||||
Sequence: SALTYGNSSGLYHLTNDCPNSSIVLEADAMILHLPGCLPCVKVGNQSTCWHAVSPTLAIPNASTPATGFRRHVDLLAGAAVVCSSLYIGDLCGSLFLAGQLFTFQPRRHWTVQECNCSIYTGHVTGHRMAWDMMMSWSPTTTLVLSSILRVPEICASVIFGGHWGILLA | ||||||
Transmembrane | 359-379 | Helical | ||||
Sequence: VAYFGMAGNWLKVLAVLFLFA | ||||||
Topological domain | 380-730 | Lumenal | ||||
Sequence: GVEATTTVGHGVARTTAGITGLFSPGASQNLQLIKNGSSWHINRTALNCNDSLQTGFLASLFYVRKFNSSGCPERMAVCKSLADFRQGWGQITYKVNISGPSDDRPYCWHYAPRPCDVVPASTVCGPVYCFTPSPVVIGTTDRRGNPTYTWGENETDVFMLESLRPPTGGWFGCTWMNSTGFTKTCGAPPCQIIPGDYNSSANELLCPTDCFRKHPEATYQRCGSGPWVTPRCLVDYPYRLWHYPCTVNFTVHKVRMFVGGIEHRFDAACNWTRGERCELHDRDRIEMSPLLFSTTQLAILPCSFSTMPALSTGLIHLHQNIVDVQYLYGVSSSVTSWVVKWEYIVLMFLV | ||||||
Transmembrane | 731-751 | Helical | ||||
Sequence: LADARICTCLWLMLLISNVEA | ||||||
Topological domain | 752-762 | Lumenal | ||||
Sequence: AVERLVVLNAA | ||||||
Transmembrane | 763-783 | Helical | ||||
Sequence: SAAGTAGWWWAVLFLCCVWYV | ||||||
Topological domain | 784-786 | Cytoplasmic | ||||
Sequence: KGR | ||||||
Transmembrane | 787-808 | Helical | ||||
Sequence: LVPACTYMALGMWPLLLTILAL | ||||||
Topological domain | 809-818 | Lumenal | ||||
Sequence: PHRAYAMDNE | ||||||
Transmembrane | 819-839 | Helical | ||||
Sequence: QAASLGAVGLLAITIFTITPT | ||||||
Topological domain | 840-843 | Cytoplasmic | ||||
Sequence: YKKL | ||||||
Transmembrane | 844-863 | Helical | ||||
Sequence: LTCFIWWNQYFLARAEAMVH | ||||||
Topological domain | 864-886 | Lumenal | ||||
Sequence: EWVPDLRVRGGRDSIILLTCLLH | ||||||
Transmembrane | 887-907 | Helical | ||||
Sequence: PQLGFEVTKILLAILAPLYIL | ||||||
Topological domain | 908-1662 | Cytoplasmic | ||||
Sequence: QYSLLKVPYFVRAHILLRACLLVRRLAGGRYVQACLLRLGAWTGTFIYDHLAPLSDWASDGLRDLAVAVEPVIFSPMEKKIITWGADTAACGDILSGLPVSARLGNLVLLGPADDMQRGGWKLLAPITAYAQQTRGLVGTIVTSLTGRDKNEVEGEVQVVSTATQSFLATSINGVMWTVYHGAGSKTLAGPKGPVCQMYTNVDKDLVGWPSPPGARSLTPCTCGSSDLYLVTREADVIPARRRGDNRAALLSPRPISTLKGSSGGPVMCPSGHVVGLFRAAVCTRGVAKSLDFIPVENMETTMRSPSFTDNSTPPAVPQTYQVGYLHAPTGSGKSTRVPAAYASQGYKVLVLNPSVAATLSFGSYMRQAYGVEPNVRTGVRTVTTGGAITYSTYGKFLADGGCSGGAYDIIICDECHSTDPTTVLGIGTVLDQAETAGARLTVLATATPPGSITVPHPNITETALPTTGEIPFYGKAIPLEYIKGGRHLIFCHSKKKCDELAGKLKSLGLNAVAFYRGVDVSVIPTSGDVVICATDALMTGYTGDFDSVIDCNVAVTQVVDFSLDPTFSIETTTVPQDAVSRSQRRGRTGRGKPGVYRFVSQGERPSGMFDTVVLCEAYDTGCAWYELTPSETTVRLRAYMNTPGLPVCQDHLEFWEGVFTGLTHIDAHFLSQTKQGGENFAYLVAYQATVCARAKAPPPSWDTMWKCLIRLKPTLTGPTPLLYRLGAVQNEIITTHPITKYIMTCMSADLEVIT | ||||||
Transmembrane | 1663-1683 | Helical | ||||
Sequence: STWVLVGGVLAALAAYCLSVG | ||||||
Topological domain | 1684-1810 | Cytoplasmic | ||||
Sequence: CVVICGRITLTGKPAVVPDREILYQQFDEMEECSRHIPYLAEGQQIAEQFRQKVLGLLQASAKQAEELKPAVHSAWPRMEEFWRKHMWNFVSGIQYLAGLSTLPGNPAVASLMSFTASLTSPLRTSQ | ||||||
Transmembrane | 1811-1829 | Helical | ||||
Sequence: TLLLNILGGWIAAQVAPPP | ||||||
Topological domain | 1830-1833 | Lumenal | ||||
Sequence: ASTA | ||||||
Transmembrane | 1834-1854 | Helical | ||||
Sequence: FVVSGLAGAAVGSIRLGRVLV | ||||||
Topological domain | 1855 | Cytoplasmic | ||||
Sequence: D | ||||||
Transmembrane | 1856-1876 | Helical | ||||
Sequence: VLAGYGAGVSGALVAFKIMSG | ||||||
Topological domain | 1877-1886 | Lumenal | ||||
Sequence: DCPTTEDMVN | ||||||
Transmembrane | 1887-1907 | Helical | ||||
Sequence: LLPALLSPGALVVGVVCAAIL | ||||||
Topological domain | 1908-1977 | Cytoplasmic | ||||
Sequence: RRHVGPAEGANQWMNRLIAFASRGNHVSPTHYVPETDASKNVTQILTSLTITSLLRRLHQWVNEDTATPC | ||||||
Intramembrane | 1978-2007 | |||||
Sequence: ATSWLRDVWDWVCTVLSDFKVWLQAKLFPR | ||||||
Topological domain | 2008-2998 | Cytoplasmic | ||||
Sequence: LPGIPFLSCQTGYRGVWAGDGVCHTTCTCGAVIAGHVKNGTMKITGPKTCSNTWHGTFPINATTTGPSTPRPAPNYQRALWRVSAEDYVEVRRLGDCHYVVGVTAEGLKCPCQVPAPEFFTEVDGVRIHRYAPPCKPLLRDEVTFSVGLSNYAIGSQLPCEPEPDVTVVTSMLTDPTHITAETASRRLKRGSPPSLASSSASQLSAPSLKATCTTSKDHPDMELIEANLLWRQEMGGNITRVESENKVVVLDSFEPLTAEYDEREISVSAECHRPPRHKFPPALPIWARPDYNPPLLQAWQMPGYEPPVVSGCAVAPPKPAPIPPPRRKRLVHLDESTVSRALAQLADKVFVEGSSDPGPSSDSGLSITSPDPPAPTTPDDACSEAESYSSMPPLEGEPGDPDLSSGSWSTVSDQDDVVCCSMSYSWTGALITPCAAEEEKLPINPLSNSLIRHHNMVYSTTSRSASLRQKKVTFDRLQVFDQHYQDVLKEIKLRASTVQARLLSIEEACDLTPSHSARSKYGYGAQDVRSHASKAINHIRSVWEDLLEDSDTPIPTTIMAKNEVFCVDPSKGGRKPARLIVYPDLGVRVCEKMALYDVTRKLPQAVMGSAYGFQYSPNQRVEYLLKMWRSKKVPMGFSYDTRCFDSTVTERDIRTENDIYQSCQLDPVARRAVSSLTERLYVGGPMVNSKGQSCGYRRCRASGVLPTSMGNTLTCYLKAQAACRAANIKDCDMLVCGDDLVVICESAGVQEDTASLRAFTDAMTRYSAPPGDVPQPTYDLELITSCSSNVSVAHDGNGKRYYYLTRDCTTPLARAAWETARHTPVNSWLGNIIMFAPTIWVRMVLMTHFFSILQSQEQLEKALDFDIYGVTYSVSPLDLPAIIQRLHGMAAFSLHGYSPTELNRVGACLRKLGVPPLRAWRHRARAVRAKLIAQGGKAAICGKYLFNWAVKTKLKLTPLVSASKLDLSGWFVAGYDGGDIYHSVSQARPR | ||||||
Transmembrane | 2999-3019 | Helical | ||||
Sequence: LLLLGLLLLTVGVGIFLVPAR |
Keywords
- Cellular component
Phenotypes & Variants
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, propeptide, glycosylation, disulfide bond, lipidation, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed; by host | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylserine; by host | ||||
Sequence: S | ||||||
Chain | PRO_0000045509 | 2-177 | Mature core protein | |||
Sequence: STLPKPQRKTKRNTNRRPMDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARQPQGRHWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPHWGPNDPRRRSRNLGKVIDTLTCGFADLMGYIPVVGAPLGGVAAALAHGVRAIEDGINYATGNLPGCSFSIF | ||||||
Chain | PRO_0000045508 | 2-191 | Core protein precursor | |||
Sequence: STLPKPQRKTKRNTNRRPMDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARQPQGRHWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPHWGPNDPRRRSRNLGKVIDTLTCGFADLMGYIPVVGAPLGGVAAALAHGVRAIEDGINYATGNLPGCSFSIFLLALLSCLTTPASA | ||||||
Chain | PRO_0000450896 | 2-3019 | Genome polyprotein | |||
Sequence: STLPKPQRKTKRNTNRRPMDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARQPQGRHWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPHWGPNDPRRRSRNLGKVIDTLTCGFADLMGYIPVVGAPLGGVAAALAHGVRAIEDGINYATGNLPGCSFSIFLLALLSCLTTPASALTYGNSSGLYHLTNDCPNSSIVLEADAMILHLPGCLPCVKVGNQSTCWHAVSPTLAIPNASTPATGFRRHVDLLAGAAVVCSSLYIGDLCGSLFLAGQLFTFQPRRHWTVQECNCSIYTGHVTGHRMAWDMMMSWSPTTTLVLSSILRVPEICASVIFGGHWGILLAVAYFGMAGNWLKVLAVLFLFAGVEATTTVGHGVARTTAGITGLFSPGASQNLQLIKNGSSWHINRTALNCNDSLQTGFLASLFYVRKFNSSGCPERMAVCKSLADFRQGWGQITYKVNISGPSDDRPYCWHYAPRPCDVVPASTVCGPVYCFTPSPVVIGTTDRRGNPTYTWGENETDVFMLESLRPPTGGWFGCTWMNSTGFTKTCGAPPCQIIPGDYNSSANELLCPTDCFRKHPEATYQRCGSGPWVTPRCLVDYPYRLWHYPCTVNFTVHKVRMFVGGIEHRFDAACNWTRGERCELHDRDRIEMSPLLFSTTQLAILPCSFSTMPALSTGLIHLHQNIVDVQYLYGVSSSVTSWVVKWEYIVLMFLVLADARICTCLWLMLLISNVEAAVERLVVLNAASAAGTAGWWWAVLFLCCVWYVKGRLVPACTYMALGMWPLLLTILALPHRAYAMDNEQAASLGAVGLLAITIFTITPTYKKLLTCFIWWNQYFLARAEAMVHEWVPDLRVRGGRDSIILLTCLLHPQLGFEVTKILLAILAPLYILQYSLLKVPYFVRAHILLRACLLVRRLAGGRYVQACLLRLGAWTGTFIYDHLAPLSDWASDGLRDLAVAVEPVIFSPMEKKIITWGADTAACGDILSGLPVSARLGNLVLLGPADDMQRGGWKLLAPITAYAQQTRGLVGTIVTSLTGRDKNEVEGEVQVVSTATQSFLATSINGVMWTVYHGAGSKTLAGPKGPVCQMYTNVDKDLVGWPSPPGARSLTPCTCGSSDLYLVTREADVIPARRRGDNRAALLSPRPISTLKGSSGGPVMCPSGHVVGLFRAAVCTRGVAKSLDFIPVENMETTMRSPSFTDNSTPPAVPQTYQVGYLHAPTGSGKSTRVPAAYASQGYKVLVLNPSVAATLSFGSYMRQAYGVEPNVRTGVRTVTTGGAITYSTYGKFLADGGCSGGAYDIIICDECHSTDPTTVLGIGTVLDQAETAGARLTVLATATPPGSITVPHPNITETALPTTGEIPFYGKAIPLEYIKGGRHLIFCHSKKKCDELAGKLKSLGLNAVAFYRGVDVSVIPTSGDVVICATDALMTGYTGDFDSVIDCNVAVTQVVDFSLDPTFSIETTTVPQDAVSRSQRRGRTGRGKPGVYRFVSQGERPSGMFDTVVLCEAYDTGCAWYELTPSETTVRLRAYMNTPGLPVCQDHLEFWEGVFTGLTHIDAHFLSQTKQGGENFAYLVAYQATVCARAKAPPPSWDTMWKCLIRLKPTLTGPTPLLYRLGAVQNEIITTHPITKYIMTCMSADLEVITSTWVLVGGVLAALAAYCLSVGCVVICGRITLTGKPAVVPDREILYQQFDEMEECSRHIPYLAEGQQIAEQFRQKVLGLLQASAKQAEELKPAVHSAWPRMEEFWRKHMWNFVSGIQYLAGLSTLPGNPAVASLMSFTASLTSPLRTSQTLLLNILGGWIAAQVAPPPASTAFVVSGLAGAAVGSIRLGRVLVDVLAGYGAGVSGALVAFKIMSGDCPTTEDMVNLLPALLSPGALVVGVVCAAILRRHVGPAEGANQWMNRLIAFASRGNHVSPTHYVPETDASKNVTQILTSLTITSLLRRLHQWVNEDTATPCATSWLRDVWDWVCTVLSDFKVWLQAKLFPRLPGIPFLSCQTGYRGVWAGDGVCHTTCTCGAVIAGHVKNGTMKITGPKTCSNTWHGTFPINATTTGPSTPRPAPNYQRALWRVSAEDYVEVRRLGDCHYVVGVTAEGLKCPCQVPAPEFFTEVDGVRIHRYAPPCKPLLRDEVTFSVGLSNYAIGSQLPCEPEPDVTVVTSMLTDPTHITAETASRRLKRGSPPSLASSSASQLSAPSLKATCTTSKDHPDMELIEANLLWRQEMGGNITRVESENKVVVLDSFEPLTAEYDEREISVSAECHRPPRHKFPPALPIWARPDYNPPLLQAWQMPGYEPPVVSGCAVAPPKPAPIPPPRRKRLVHLDESTVSRALAQLADKVFVEGSSDPGPSSDSGLSITSPDPPAPTTPDDACSEAESYSSMPPLEGEPGDPDLSSGSWSTVSDQDDVVCCSMSYSWTGALITPCAAEEEKLPINPLSNSLIRHHNMVYSTTSRSASLRQKKVTFDRLQVFDQHYQDVLKEIKLRASTVQARLLSIEEACDLTPSHSARSKYGYGAQDVRSHASKAINHIRSVWEDLLEDSDTPIPTTIMAKNEVFCVDPSKGGRKPARLIVYPDLGVRVCEKMALYDVTRKLPQAVMGSAYGFQYSPNQRVEYLLKMWRSKKVPMGFSYDTRCFDSTVTERDIRTENDIYQSCQLDPVARRAVSSLTERLYVGGPMVNSKGQSCGYRRCRASGVLPTSMGNTLTCYLKAQAACRAANIKDCDMLVCGDDLVVICESAGVQEDTASLRAFTDAMTRYSAPPGDVPQPTYDLELITSCSSNVSVAHDGNGKRYYYLTRDCTTPLARAAWETARHTPVNSWLGNIIMFAPTIWVRMVLMTHFFSILQSQEQLEKALDFDIYGVTYSVSPLDLPAIIQRLHGMAAFSLHGYSPTELNRVGACLRKLGVPPLRAWRHRARAVRAKLIAQGGKAAICGKYLFNWAVKTKLKLTPLVSASKLDLSGWFVAGYDGGDIYHSVSQARPRLLLLGLLLLTVGVGIFLVPAR | ||||||
Modified residue | 53 | Phosphoserine; by host | ||||
Sequence: S | ||||||
Modified residue | 99 | Phosphoserine; by host | ||||
Sequence: S | ||||||
Modified residue | 116 | Phosphoserine; by host PKA | ||||
Sequence: S | ||||||
Propeptide | PRO_0000045510 | 178-191 | ER anchor for the core protein, removed in mature form by host signal peptidase | |||
Sequence: LLALLSCLTTPASA | ||||||
Chain | PRO_0000045511 | 192-383 | Envelope glycoprotein E1 | |||
Sequence: LTYGNSSGLYHLTNDCPNSSIVLEADAMILHLPGCLPCVKVGNQSTCWHAVSPTLAIPNASTPATGFRRHVDLLAGAAVVCSSLYIGDLCGSLFLAGQLFTFQPRRHWTVQECNCSIYTGHVTGHRMAWDMMMSWSPTTTLVLSSILRVPEICASVIFGGHWGILLAVAYFGMAGNWLKVLAVLFLFAGVEA | ||||||
Glycosylation | 196 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 209 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 234 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 250 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 305 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Chain | PRO_0000045512 | 384-751 | Envelope glycoprotein E2 | |||
Sequence: TTTVGHGVARTTAGITGLFSPGASQNLQLIKNGSSWHINRTALNCNDSLQTGFLASLFYVRKFNSSGCPERMAVCKSLADFRQGWGQITYKVNISGPSDDRPYCWHYAPRPCDVVPASTVCGPVYCFTPSPVVIGTTDRRGNPTYTWGENETDVFMLESLRPPTGGWFGCTWMNSTGFTKTCGAPPCQIIPGDYNSSANELLCPTDCFRKHPEATYQRCGSGPWVTPRCLVDYPYRLWHYPCTVNFTVHKVRMFVGGIEHRFDAACNWTRGERCELHDRDRIEMSPLLFSTTQLAILPCSFSTMPALSTGLIHLHQNIVDVQYLYGVSSSVTSWVVKWEYIVLMFLVLADARICTCLWLMLLISNVEA | ||||||
Glycosylation | 415 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 422 | N-linked (GlcNAc...) (high mannose) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 428↔553 | |||||
Sequence: CNDSLQTGFLASLFYVRKFNSSGCPERMAVCKSLADFRQGWGQITYKVNISGPSDDRPYCWHYAPRPCDVVPASTVCGPVYCFTPSPVVIGTTDRRGNPTYTWGENETDVFMLESLRPPTGGWFGC | ||||||
Glycosylation | 429 | N-linked (GlcNAc...) (high mannose) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 447 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 451↔458 | |||||
Sequence: CPERMAVC | ||||||
Glycosylation | 476 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 487↔495 | |||||
Sequence: CWHYAPRPC | ||||||
Disulfide bond | 504↔509 | |||||
Sequence: CGPVYC | ||||||
Glycosylation | 533 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 557 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 565↔570 | |||||
Sequence: CGAPPC | ||||||
Glycosylation | 578 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 586↔590 | |||||
Sequence: CPTDC | ||||||
Disulfide bond | 602↔625 | |||||
Sequence: CGSGPWVTPRCLVDYPYRLWHYPC | ||||||
Disulfide bond | 612↔649 | |||||
Sequence: CLVDYPYRLWHYPCTVNFTVHKVRMFVGGIEHRFDAAC | ||||||
Glycosylation | 628 | N-linked (GlcNAc...) (high mannose) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 650 | N-linked (GlcNAc...) (high mannose) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 657↔682 | |||||
Sequence: CELHDRDRIEMSPLLFSTTQLAILPC | ||||||
Chain | PRO_0000045513 | 752-814 | Viroporin p7 | |||
Sequence: AVERLVVLNAASAAGTAGWWWAVLFLCCVWYVKGRLVPACTYMALGMWPLLLTILALPHRAYA | ||||||
Chain | PRO_0000045514 | 815-1031 | Protease NS2 | |||
Sequence: MDNEQAASLGAVGLLAITIFTITPTYKKLLTCFIWWNQYFLARAEAMVHEWVPDLRVRGGRDSIILLTCLLHPQLGFEVTKILLAILAPLYILQYSLLKVPYFVRAHILLRACLLVRRLAGGRYVQACLLRLGAWTGTFIYDHLAPLSDWASDGLRDLAVAVEPVIFSPMEKKIITWGADTAACGDILSGLPVSARLGNLVLLGPADDMQRGGWKLL | ||||||
Lipidation | 927 | S-palmitoyl cysteine; by host | ||||
Sequence: C | ||||||
Chain | PRO_0000045515 | 1032-1662 | Serine protease/helicase NS3 | |||
Sequence: APITAYAQQTRGLVGTIVTSLTGRDKNEVEGEVQVVSTATQSFLATSINGVMWTVYHGAGSKTLAGPKGPVCQMYTNVDKDLVGWPSPPGARSLTPCTCGSSDLYLVTREADVIPARRRGDNRAALLSPRPISTLKGSSGGPVMCPSGHVVGLFRAAVCTRGVAKSLDFIPVENMETTMRSPSFTDNSTPPAVPQTYQVGYLHAPTGSGKSTRVPAAYASQGYKVLVLNPSVAATLSFGSYMRQAYGVEPNVRTGVRTVTTGGAITYSTYGKFLADGGCSGGAYDIIICDECHSTDPTTVLGIGTVLDQAETAGARLTVLATATPPGSITVPHPNITETALPTTGEIPFYGKAIPLEYIKGGRHLIFCHSKKKCDELAGKLKSLGLNAVAFYRGVDVSVIPTSGDVVICATDALMTGYTGDFDSVIDCNVAVTQVVDFSLDPTFSIETTTVPQDAVSRSQRRGRTGRGKPGVYRFVSQGERPSGMFDTVVLCEAYDTGCAWYELTPSETTVRLRAYMNTPGLPVCQDHLEFWEGVFTGLTHIDAHFLSQTKQGGENFAYLVAYQATVCARAKAPPPSWDTMWKCLIRLKPTLTGPTPLLYRLGAVQNEIITTHPITKYIMTCMSADLEVIT | ||||||
Chain | PRO_0000045516 | 1663-1716 | Non-structural protein 4A | |||
Sequence: STWVLVGGVLAALAAYCLSVGCVVICGRITLTGKPAVVPDREILYQQFDEMEEC | ||||||
Chain | PRO_0000045517 | 1717-1977 | Non-structural protein 4B | |||
Sequence: SRHIPYLAEGQQIAEQFRQKVLGLLQASAKQAEELKPAVHSAWPRMEEFWRKHMWNFVSGIQYLAGLSTLPGNPAVASLMSFTASLTSPLRTSQTLLLNILGGWIAAQVAPPPASTAFVVSGLAGAAVGSIRLGRVLVDVLAGYGAGVSGALVAFKIMSGDCPTTEDMVNLLPALLSPGALVVGVVCAAILRRHVGPAEGANQWMNRLIAFASRGNHVSPTHYVPETDASKNVTQILTSLTITSLLRRLHQWVNEDTATPC | ||||||
Lipidation | 1977 | S-palmitoyl cysteine; by host | ||||
Sequence: C | ||||||
Chain | PRO_0000045518 | 1978-2428 | Non-structural protein 5A | |||
Sequence: ATSWLRDVWDWVCTVLSDFKVWLQAKLFPRLPGIPFLSCQTGYRGVWAGDGVCHTTCTCGAVIAGHVKNGTMKITGPKTCSNTWHGTFPINATTTGPSTPRPAPNYQRALWRVSAEDYVEVRRLGDCHYVVGVTAEGLKCPCQVPAPEFFTEVDGVRIHRYAPPCKPLLRDEVTFSVGLSNYAIGSQLPCEPEPDVTVVTSMLTDPTHITAETASRRLKRGSPPSLASSSASQLSAPSLKATCTTSKDHPDMELIEANLLWRQEMGGNITRVESENKVVVLDSFEPLTAEYDEREISVSAECHRPPRHKFPPALPIWARPDYNPPLLQAWQMPGYEPPVVSGCAVAPPKPAPIPPPRRKRLVHLDESTVSRALAQLADKVFVEGSSDPGPSSDSGLSITSPDPPAPTTPDDACSEAESYSSMPPLEGEPGDPDLSSGSWSTVSDQDDVVCC | ||||||
Modified residue | 2199 | Phosphoserine; by host; in p56 | ||||
Sequence: S | ||||||
Modified residue | 2202 | Phosphoserine; by host; in p58 | ||||
Sequence: S | ||||||
Modified residue | 2206 | Phosphoserine; by host; in p58 | ||||
Sequence: S | ||||||
Modified residue | 2209 | Phosphoserine; by host; in p58 | ||||
Sequence: S | ||||||
Modified residue | 2212 | Phosphoserine; by host; in p58 | ||||
Sequence: S | ||||||
Modified residue | 2215 | Phosphoserine; by host; in p58 | ||||
Sequence: S | ||||||
Cross-link | 2356 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Chain | PRO_0000045519 | 2429-3019 | RNA-directed RNA polymerase | |||
Sequence: SMSYSWTGALITPCAAEEEKLPINPLSNSLIRHHNMVYSTTSRSASLRQKKVTFDRLQVFDQHYQDVLKEIKLRASTVQARLLSIEEACDLTPSHSARSKYGYGAQDVRSHASKAINHIRSVWEDLLEDSDTPIPTTIMAKNEVFCVDPSKGGRKPARLIVYPDLGVRVCEKMALYDVTRKLPQAVMGSAYGFQYSPNQRVEYLLKMWRSKKVPMGFSYDTRCFDSTVTERDIRTENDIYQSCQLDPVARRAVSSLTERLYVGGPMVNSKGQSCGYRRCRASGVLPTSMGNTLTCYLKAQAACRAANIKDCDMLVCGDDLVVICESAGVQEDTASLRAFTDAMTRYSAPPGDVPQPTYDLELITSCSSNVSVAHDGNGKRYYYLTRDCTTPLARAAWETARHTPVNSWLGNIIMFAPTIWVRMVLMTHFFSILQSQEQLEKALDFDIYGVTYSVSPLDLPAIIQRLHGMAAFSLHGYSPTELNRVGACLRKLGVPPLRAWRHRARAVRAKLIAQGGKAAICGKYLFNWAVKTKLKLTPLVSASKLDLSGWFVAGYDGGDIYHSVSQARPRLLLLGLLLLTVGVGIFLVPAR | ||||||
Modified residue | 2457 | Phosphoserine; by host | ||||
Sequence: S | ||||||
Modified residue | 2470 | Phosphoserine; by host | ||||
Sequence: S |
Post-translational modification
Genome polyprotein
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).
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).
Mature core protein
Phosphorylated by host PKC and PKA.
Mature core protein
Ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation.
Envelope glycoprotein E1
Highly N-glycosylated.
Envelope glycoprotein E2
Highly N-glycosylated.
Protease NS2
Palmitoylation is required for NS2/3 autoprocessing and E2 recruitment to membranes.
Non-structural protein 4B
Palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions.
Non-structural protein 5A
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).
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).
Non-structural protein 5A
Tyrosine phosphorylation is essential for the interaction with host SRC.
RNA-directed RNA polymerase
The N-terminus is phosphorylated by host PRK2/PKN2.
Keywords
- PTM
Interaction
Subunit
Mature core protein
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).
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).
Envelope glycoprotein E1
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).
Interacts with host NEURL3; this interaction prevents E1 binding to 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).
Interacts with host NEURL3; this interaction prevents E1 binding to glycoprotein E2 (By similarity).
Envelope glycoprotein E2
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).
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).
Viroporin p7
Homohexamer (By similarity).
Homoheptamer (By similarity).
Interacts with protease NS2 (By similarity).
Homoheptamer (By similarity).
Interacts with protease NS2 (By similarity).
Protease NS2
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).
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).
Serine protease/helicase NS3
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).
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).
Non-structural protein 4A
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).
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).
Non-structural protein 4B
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).
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).
Non-structural protein 5A
Monomer. Homodimer; dimerization is required for RNA-binding (By similarity).
Interacts with the mature core protein (By similarity).
Interacts (via N-terminus) with non-structural protein 4A (By similarity).
Interacts with non-structural protein 4B. Interacts (via region D2) 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 embedded in an ER-derived membranous web (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 (via C-terminus) with host VAPB (via MSP domain). 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. 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. 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).
Interacts (via region D2) with host PPIA/CYPA; the interaction stimulates RNA-binding ability of NS5A and is dependent on the peptidyl-prolyl cis-trans isomerase activity of PPIA/CYPA. Interacts with host TRIM14; this interaction induces the degradation of NS5A (By similarity).
Interacts with the mature core protein (By similarity).
Interacts (via N-terminus) with non-structural protein 4A (By similarity).
Interacts with non-structural protein 4B. Interacts (via region D2) 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 embedded in an ER-derived membranous web (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 (via C-terminus) with host VAPB (via MSP domain). 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. 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. 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).
Interacts (via region D2) with host PPIA/CYPA; the interaction stimulates RNA-binding ability of NS5A and is dependent on the peptidyl-prolyl cis-trans isomerase activity of PPIA/CYPA. Interacts with host TRIM14; this interaction induces the degradation of NS5A (By similarity).
RNA-directed RNA polymerase
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).
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).
Family & Domains
Features
Showing features for region, motif, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 2-23 | Interaction with STAT1 | ||||
Sequence: STLPKPQRKTKRNTNRRPMDVK | ||||||
Region | 2-58 | Interaction with EIF2AK2/PKR | ||||
Sequence: STLPKPQRKTKRNTNRRPMDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQP | ||||||
Region | 2-59 | Interaction with DDX3X | ||||
Sequence: STLPKPQRKTKRNTNRRPMDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPR | ||||||
Region | 2-75 | Disordered | ||||
Sequence: STLPKPQRKTKRNTNRRPMDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARQPQGRH | ||||||
Motif | 5-13 | Nuclear localization signal | ||||
Sequence: PKPQRKTKR | ||||||
Motif | 38-43 | Nuclear localization signal | ||||
Sequence: PRRGPR | ||||||
Compositional bias | 47-61 | Basic and acidic residues | ||||
Sequence: RATRKTSERSQPRGR | ||||||
Motif | 58-64 | Nuclear localization signal | ||||
Sequence: PRGRRQP | ||||||
Motif | 66-71 | Nuclear localization signal | ||||
Sequence: PKARQP | ||||||
Region | 112-152 | Important for endoplasmic reticulum and mitochondrial localization | ||||
Sequence: PRRRSRNLGKVIDTLTCGFADLMGYIPVVGAPLGGVAAALA | ||||||
Region | 122-173 | Interaction with APOA2 | ||||
Sequence: VIDTLTCGFADLMGYIPVVGAPLGGVAAALAHGVRAIEDGINYATGNLPGCS | ||||||
Region | 164-167 | Important for lipid droplets localization | ||||
Sequence: YATG | ||||||
Region | 265-296 | Important for fusion | ||||
Sequence: LAGAAVVCSSLYIGDLCGSLFLAGQLFTFQPR | ||||||
Region | 385-411 | HVR1 | ||||
Sequence: TTVGHGVARTTAGITGLFSPGASQNLQ | ||||||
Region | 474-479 | HVR2 | ||||
Sequence: KVNISG | ||||||
Region | 481-494 | CD81-binding 1 | ||||
Sequence: SDDRPYCWHYAPRP | ||||||
Region | 545-552 | CD81-binding 2 | ||||
Sequence: PPTGGWFG | ||||||
Region | 665-676 | PKR/eIF2-alpha phosphorylation homology domain (PePHD) | ||||
Sequence: IEMSPLLFSTTQ | ||||||
Domain | 908-1031 | Peptidase C18 | ||||
Sequence: QYSLLKVPYFVRAHILLRACLLVRRLAGGRYVQACLLRLGAWTGTFIYDHLAPLSDWASDGLRDLAVAVEPVIFSPMEKKIITWGADTAACGDILSGLPVSARLGNLVLLGPADDMQRGGWKLL | ||||||
Region | 909-1211 | Protease NS2-3 | ||||
Sequence: YSLLKVPYFVRAHILLRACLLVRRLAGGRYVQACLLRLGAWTGTFIYDHLAPLSDWASDGLRDLAVAVEPVIFSPMEKKIITWGADTAACGDILSGLPVSARLGNLVLLGPADDMQRGGWKLLAPITAYAQQTRGLVGTIVTSLTGRDKNEVEGEVQVVSTATQSFLATSINGVMWTVYHGAGSKTLAGPKGPVCQMYTNVDKDLVGWPSPPGARSLTPCTCGSSDLYLVTREADVIPARRRGDNRAALLSPRPISTLKGSSGGPVMCPSGHVVGLFRAAVCTRGVAKSLDFIPVENMETTMR | ||||||
Region | 934-954 | Interaction with host SCPS1 | ||||
Sequence: AGGRYVQACLLRLGAWTGTFI | ||||||
Domain | 1032-1213 | Peptidase S29 | ||||
Sequence: APITAYAQQTRGLVGTIVTSLTGRDKNEVEGEVQVVSTATQSFLATSINGVMWTVYHGAGSKTLAGPKGPVCQMYTNVDKDLVGWPSPPGARSLTPCTCGSSDLYLVTREADVIPARRRGDNRAALLSPRPISTLKGSSGGPVMCPSGHVVGLFRAAVCTRGVAKSLDFIPVENMETTMRSP | ||||||
Domain | 1222-1374 | Helicase ATP-binding | ||||
Sequence: PAVPQTYQVGYLHAPTGSGKSTRVPAAYASQGYKVLVLNPSVAATLSFGSYMRQAYGVEPNVRTGVRTVTTGGAITYSTYGKFLADGGCSGGAYDIIICDECHSTDPTTVLGIGTVLDQAETAGARLTVLATATPPGSITVPHPNITETALPT | ||||||
Motif | 1321-1324 | DECH box | ||||
Sequence: DECH | ||||||
Region | 1491-1503 | RNA-binding | ||||
Sequence: QRRGRTGRGKPGV | ||||||
Region | 1684-1695 | NS3-binding | ||||
Sequence: CVVICGRITLTG | ||||||
Region | 2125-2213 | FKBP8-binding | ||||
Sequence: EFFTEVDGVRIHRYAPPCKPLLRDEVTFSVGLSNYAIGSQLPCEPEPDVTVVTSMLTDPTHITAETASRRLKRGSPPSLASSSASQLSA | ||||||
Region | 2125-2338 | Transcriptional activation | ||||
Sequence: EFFTEVDGVRIHRYAPPCKPLLRDEVTFSVGLSNYAIGSQLPCEPEPDVTVVTSMLTDPTHITAETASRRLKRGSPPSLASSSASQLSAPSLKATCTTSKDHPDMELIEANLLWRQEMGGNITRVESENKVVVLDSFEPLTAEYDEREISVSAECHRPPRHKFPPALPIWARPDYNPPLLQAWQMPGYEPPVVSGCAVAPPKPAPIPPPRRKRL | ||||||
Region | 2140-2144 | Interaction with non-structural protein 4A | ||||
Sequence: PPCKP | ||||||
Region | 2189-2223 | Disordered | ||||
Sequence: ETASRRLKRGSPPSLASSSASQLSAPSLKATCTTS | ||||||
Region | 2194-2446 | Interaction with host SKP2 | ||||
Sequence: RLKRGSPPSLASSSASQLSAPSLKATCTTSKDHPDMELIEANLLWRQEMGGNITRVESENKVVVLDSFEPLTAEYDEREISVSAECHRPPRHKFPPALPIWARPDYNPPLLQAWQMPGYEPPVVSGCAVAPPKPAPIPPPRRKRLVHLDESTVSRALAQLADKVFVEGSSDPGPSSDSGLSITSPDPPAPTTPDDACSEAESYSSMPPLEGEPGDPDLSSGSWSTVSDQDDVVCCSMSYSWTGALITPCAAEE | ||||||
Compositional bias | 2199-2222 | Polar residues | ||||
Sequence: SPPSLASSSASQLSAPSLKATCTT | ||||||
Region | 2215-2254 | ISDR | ||||
Sequence: SLKATCTTSKDHPDMELIEANLLWRQEMGGNITRVESENK | ||||||
Region | 2215-2280 | Interaction with EIF2AK2/PKR | ||||
Sequence: SLKATCTTSKDHPDMELIEANLLWRQEMGGNITRVESENKVVVLDSFEPLTAEYDEREISVSAECH | ||||||
Region | 2254-2312 | NS4B-binding | ||||
Sequence: KVVVLDSFEPLTAEYDEREISVSAECHRPPRHKFPPALPIWARPDYNPPLLQAWQMPGY | ||||||
Region | 2305-2383 | V3 | ||||
Sequence: QAWQMPGYEPPVVSGCAVAPPKPAPIPPPRRKRLVHLDESTVSRALAQLADKVFVEGSSDPGPSSDSGLSITSPDPPAP | ||||||
Motif | 2328-2331 | SH3-binding | ||||
Sequence: APIP | ||||||
Motif | 2333-2341 | Nuclear localization signal | ||||
Sequence: PRRKRLVHL | ||||||
Region | 2359-2418 | Disordered | ||||
Sequence: VEGSSDPGPSSDSGLSITSPDPPAPTTPDDACSEAESYSSMPPLEGEPGDPDLSSGSWST | ||||||
Compositional bias | 2364-2378 | Polar residues | ||||
Sequence: DPGPSSDSGLSITSP | ||||||
Domain | 2642-2760 | RdRp catalytic | ||||
Sequence: PMGFSYDTRCFDSTVTERDIRTENDIYQSCQLDPVARRAVSSLTERLYVGGPMVNSKGQSCGYRRCRASGVLPTSMGNTLTCYLKAQAACRAANIKDCDMLVCGDDLVVICESAGVQED |
Domain
Envelope glycoprotein E1
The transmembrane regions of envelope E1 and E2 glycoproteins are involved in heterodimer formation, ER localization, and assembly of these proteins.
Envelope glycoprotein E2
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).
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).
Protease NS2
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).
The minimal catalytic region includes the C-terminus of NS2 and the N-terminus NS3 protease domain (active region NS2-3) (By similarity).
Serine protease/helicase NS3
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).
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).
Non-structural protein 4B
Contains a glycine zipper region that critically contributes to the biogenesis of functional ER-derived replication organelles.
Non-structural protein 5A
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).
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).
Sequence similarities
Belongs to the hepacivirus polyprotein family.
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Length3,019
- Mass (Da)328,857
- Last updated2007-01-23 v3
- ChecksumFF1161164B164DF3
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 47-61 | Basic and acidic residues | ||||
Sequence: RATRKTSERSQPRGR | ||||||
Compositional bias | 2199-2222 | Polar residues | ||||
Sequence: SPPSLASSSASQLSAPSLKATCTT | ||||||
Compositional bias | 2364-2378 | Polar residues | ||||
Sequence: DPGPSSDSGLSITSP |