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). Probably affects various cell signaling pathways, host immunity and lipid metabolism (Probable). 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). 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). May function as a multimeric ion channel protein (viroporin). 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). Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (PubMed:10497107). 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). 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). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (PubMed:17093192). 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). Phosphorylated protein that is indispensable for viral replication and assembly. RNA-dependent RNA polymerase that performs primer-template recognition and RNA synthesis during viral replication. 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'. a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate ATP + H2O = ADP + H(+) + phosphate a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1) 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). Binds 1 zinc ion, which has a structural role (By similarity). Magnesium or manganese ions are essential for the helicase activity (PubMed:10497107). Stable from 6 to 8.5. Homooligomer (By similarity). Interacts with E1 (via C-terminus) (By similarity). Interacts with the non-structural protein 5A (By similarity). Part of the viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the core protein (By similarity). Forms a heterodimer with envelope glycoprotein E2 (By similarity). Interacts with the core protein (By similarity). Interacts with protease NS2 (By similarity). Part of the viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the core protein (By similarity). Forms a heterodimer with envelope glycoprotein E1 (By similarity). Part of the viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the core protein (By similarity). Homodimer (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 core protein (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). Interacts with host MAVS; this interaction leads to the cleavage and inhibition of host MAVS (Probable). 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 core protein (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 core protein (By similarity). Monomer (By similarity). Homodimer; dimerization is required for RNA-binding (By similarity). Interacts with the 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 core protein (By similarity). Part of the replication complex composed of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA polymerase (By similarity). Only a minor proportion of core protein is present in the nucleus (By similarity). Probably present on the surface of lipid droplets (By similarity). 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). 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). Probably present on the surface of lipid droplets. NS3 is associated to the ER membrane through its binding to NS4A. Host membrane insertion occurs after processing by the NS3 protease. A reorientation of the N-terminus into the ER lumen occurs post-translationally. Host membrane insertion occurs after processing by the NS3 protease (By similarity). Localizes at the surface of lipid droplets (By similarity). Host membrane insertion occurs after processing by the NS3 protease. The transmembrane regions of envelope E1 and E2 glycoproteins are involved in heterodimer formation, ER localization, and assembly of these proteins. The transmembrane regions of envelope E1 and E2 glycoproteins are involved in heterodimer formation, ER localization, and assembly of these proteins. 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 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). Contains a glycine zipper region that critically contributes to the biogenesis of functional ER-derived replication organelles. The N-terminus of NS5A acts as membrane anchor. 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 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). P13 may be further cleaved into p6 and p7 if the internal cleavage site is used (PubMed:15060070, PubMed:16492760). Highly N-glycosylated. Highly N-glycosylated. Palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions. Of all animal viruses, GBV-B is the most closely related to HCV. The core gene probably also codes for alternative reading frame proteins (ARFPs). Many functions depicted for the core protein might belong to the ARFPs.