ID POLG_HCVGL Reviewed; 829 AA. AC Q5EG65; DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 126. DE RecName: Full=Genome polyprotein; DE Contains: DE RecName: Full=Core protein precursor; DE AltName: Full=Capsid protein C; DE AltName: Full=p23; DE Contains: DE RecName: Full=Mature core protein; DE AltName: Full=p21; DE Contains: DE RecName: Full=Envelope glycoprotein E1; DE AltName: Full=gp32; DE AltName: Full=gp35; DE Contains: DE RecName: Full=Envelope glycoprotein E2; DE AltName: Full=NS1; DE AltName: Full=gp68; DE AltName: Full=gp70; DE Contains: DE RecName: Full=Viroporin p7; DE Contains: DE RecName: Full=Protease NS2; DE Short=p23; DE EC=3.4.22.- {ECO:0000250|UniProtKB:P26663}; DE AltName: Full=Non-structural protein 2; DE Short=NS2; DE Flags: Fragment; OS Hepatitis C virus (isolate Glasgow) (HCV). OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes; OC Amarillovirales; Flaviviridae; Hepacivirus; Hepacivirus hominis. OX NCBI_TaxID=329389; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=10423136; DOI=10.1099/0022-1317-80-7-1681; RA Patel J., Patel A.H., McLauchlan J.; RT "Covalent interactions are not required to permit or stabilize the non- RT covalent association of hepatitis C virus glycoproteins E1 and E2."; RL J. Gen. Virol. 80:1681-1690(1999). RN [2] RP INTERACTION WITH HOST DDX3X (MATURE CORE PROTEIN). RX PubMed=10329544; DOI=10.1006/viro.1999.9659; RA Owsianka A.M., Patel A.H.; RT "Hepatitis C virus core protein interacts with a human DEAD box protein RT DDX3."; RL Virology 257:330-340(1999). RN [3] RP CLEAVAGE BY THE SIGNAL PEPTIDASE (CORE PROTEIN P21), SUBCELLULAR LOCATION, RP AND MUTAGENESIS OF 180-ALA--CYS-184. RX PubMed=12145199; DOI=10.1093/emboj/cdf414; RA McLauchlan J., Lemberg M.K., Hope G., Martoglio B.; RT "Intramembrane proteolysis promotes trafficking of hepatitis C virus core RT protein to lipid droplets."; RL EMBO J. 21:3980-3988(2002). RN [4] RP REVIEW. RX PubMed=10718937; DOI=10.1046/j.1365-2893.2000.00201.x; RA McLauchlan J.; RT "Properties of the hepatitis C virus core protein: a structural protein RT that modulates cellular processes."; RL J. Viral Hepat. 7:2-14(2000). RN [5] RP REVIEW, AND SUBCELLULAR LOCATION. RX PubMed=14752815; DOI=10.1002/hep.20032; RA Penin F., Dubuisson J., Rey F.A., Moradpour D., Pawlotsky J.-M.; RT "Structural biology of hepatitis C virus."; RL Hepatology 39:5-19(2004). CC -!- FUNCTION: [Mature core protein]: Packages viral RNA to form a viral CC nucleocapsid, and promotes virion budding (Probable). Participates in CC the viral particle production as a result of its interaction with the CC non-structural protein 5A (By similarity). Binds RNA and may function CC as a RNA chaperone to induce the RNA structural rearrangements taking CC place during virus replication (By similarity). Modulates viral CC translation initiation by interacting with viral IRES and 40S ribosomal CC subunit (By similarity). Affects various cell signaling pathways, host CC immunity and lipid metabolism (Probable). Prevents the establishment of CC cellular antiviral state by blocking the interferon-alpha/beta (IFN- CC alpha/beta) and IFN-gamma signaling pathways and by blocking the CC formation of phosphorylated STAT1 and promoting ubiquitin-mediated CC proteasome-dependent degradation of STAT1 (By similarity). Activates CC STAT3 leading to cellular transformation (By similarity). Regulates the CC activity of cellular genes, including c-myc and c-fos (By similarity). CC May repress the promoter of p53, and sequester CREB3 and SP110 isoform CC 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle CC negative regulating factor CDKN1A, thereby interrupting an important CC check point of normal cell cycle regulation (By similarity). Targets CC transcription factors involved in the regulation of inflammatory CC responses and in the immune response: suppresses TNF-induced NF-kappa-B CC activation, and activates AP-1 (By similarity). Binds to dendritic CC cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes CC proliferation (By similarity). Alters lipid metabolism by interacting CC with hepatocellular proteins involved in lipid accumulation and storage CC (By similarity). Induces up-regulation of FAS promoter activity, and CC thereby contributes to the increased triglyceride accumulation in CC hepatocytes (steatosis) (By similarity). {ECO:0000250|UniProtKB:P26662, CC ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, CC ECO:0000250|UniProtKB:P29846, ECO:0000250|UniProtKB:Q99IB8, CC ECO:0000305}. CC -!- FUNCTION: [Envelope glycoprotein E1]: Forms a heterodimer with envelope CC glycoprotein E2, which mediates virus attachment to the host cell, CC virion internalization through clathrin-dependent endocytosis and CC fusion with host membrane (By similarity). Fusion with the host cell is CC most likely mediated by both E1 and E2, through conformational CC rearrangements of the heterodimer required for fusion rather than a CC classical class II fusion mechanism (By similarity). E1/E2 heterodimer CC binds host apolipoproteins such as APOB and ApoE thereby forming a CC lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP CC allows the initial virus attachment to cell surface receptors such as CC the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan- CC 1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger CC receptor class B type I (SCARB1) (By similarity). The cholesterol CC transfer activity of SCARB1 allows E2 exposure and binding of E2 to CC SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer CC binding on CD81 activates the epithelial growth factor receptor (EGFR) CC signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR- CC SCARB1-CD81 to the cell lateral membrane allows further interaction CC with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry CC (By similarity). {ECO:0000250|UniProtKB:P27958}. CC -!- FUNCTION: [Envelope glycoprotein E2]: Forms a heterodimer with envelope CC glycoprotein E1, which mediates virus attachment to the host cell, CC virion internalization through clathrin-dependent endocytosis and CC fusion with host membrane (By similarity). Fusion with the host cell is CC most likely mediated by both E1 and E2, through conformational CC rearrangements of the heterodimer required for fusion rather than a CC classical class II fusion mechanism (By similarity). The interaction CC between envelope glycoprotein E2 and host apolipoprotein E/APOE allows CC the proper assembly, maturation and infectivity of the viral particles CC (By similarity). This interaction is probably promoted via the up- CC regulation of cellular autophagy by the virus (By similarity). E1/E2 CC heterodimer binds host apolipoproteins such as APOB and APOE thereby CC forming a lipo-viro-particle (LVP) (By similarity). APOE associated to CC the LVP allows the initial virus attachment to cell surface receptors CC such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), CC syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and CC scavenger receptor class B type I (SCARB1) (By similarity). The CC cholesterol transfer activity of SCARB1 allows E2 exposure and binding CC of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 CC heterodimer binding on CD81 activates the epithelial growth factor CC receptor (EGFR) signaling pathway (By similarity). Diffusion of the CC complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows CC further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to CC finally trigger HCV entry (By similarity). Inhibits host EIF2AK2/PKR CC activation, preventing the establishment of an antiviral state (By CC similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which CC are respectively found on dendritic cells (DCs), and on liver CC sinusoidal endothelial cells and macrophage-like cells of lymph node CC sinuses (By similarity). These interactions allow the capture of CC circulating HCV particles by these cells and subsequent facilitated CC transmission to permissive cells such as hepatocytes and lymphocyte CC subpopulations (By similarity). {ECO:0000250|UniProtKB:P26664, CC ECO:0000250|UniProtKB:P27958}. CC -!- FUNCTION: [Viroporin p7]: Ion channel protein that acts as a viroporin CC and plays an essential role in the assembly, envelopment and secretion CC of viral particles (By similarity). Regulates the host cell secretory CC pathway, which induces the intracellular retention of viral CC glycoproteins and favors assembly of viral particles (By similarity). CC Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the CC cytoplasm of infected cells, leading to a productive viral infection CC (By similarity). High levels of cytoplasmic Ca(2+) may trigger membrane CC trafficking and transport of viral ER-associated proteins to CC viroplasms, sites of viral genome replication (Probable). This ionic CC imbalance induces the assembly of the inflammasome complex, which CC triggers the maturation of pro-IL-1beta into IL-1beta through the CC action of caspase-1 (By similarity). Targets also host mitochondria and CC induces mitochondrial depolarization (By similarity). In addition of CC its role as a viroporin, acts as a lipid raft adhesion factor (By CC similarity). {ECO:0000250|UniProtKB:P27958, CC ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}. CC -!- FUNCTION: [Protease NS2]: Cysteine protease required for the CC proteolytic auto-cleavage between the non-structural proteins NS2 and CC NS3 (By similarity). The N-terminus of NS3 is required for the function CC of NS2 protease (active region NS2-3) (By similarity). Promotes the CC initiation of viral particle assembly by mediating the interaction CC between structural and non-structural proteins (By similarity). CC {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:P27958}. CC -!- COFACTOR: [Protease NS2]: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:P26663}; CC Note=Activity of protease NS2 is dependent on zinc ions and completely CC inhibited by EDTA. This is probably due to the fact that NS2 protease CC activity needs NS3 N-terminus that binds a zinc atom (active region CC NS2-3). {ECO:0000250|UniProtKB:P26663}; CC -!- ACTIVITY REGULATION: [Viroporin p7]: Inhibited by the antiviral drug CC hexamethylene amiloride (By similarity). Inhibition by amantadine CC appears to be genotype-dependent (By similarity). Also inhibited by CC long-alkyl-chain iminosugar derivatives (By similarity). CC {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P27958}. CC -!- SUBUNIT: [Mature core protein]: Homooligomer (By similarity). Interacts CC with E1 (via C-terminus) (By similarity). Interacts with the non- CC structural protein 5A (By similarity). Interacts (via N-terminus) with CC host STAT1 (via SH2 domain); this interaction results in decreased CC STAT1 phosphorylation and ubiquitin-mediated proteasome-dependent STAT1 CC degradation, leading to decreased IFN-stimulated gene transcription (By CC similarity). Interacts with host STAT3; this interaction constitutively CC activates STAT3 (By similarity). Interacts with host LTBR receptor (By CC similarity). Interacts with host TNFRSF1A receptor and possibly induces CC apoptosis (By similarity). Interacts with host HNRPK (By similarity). CC Interacts with host YWHAE (By similarity). Interacts with host CC UBE3A/E6AP (By similarity). Interacts with host DDX3X CC (PubMed:10329544). Interacts with host APOA2 (By similarity). Interacts CC with host RXRA protein (By similarity). Interacts with host SP110 CC isoform 3/Sp110b; this interaction sequesters the transcriptional CC corepressor SP110 away from the nucleus (By similarity). Interacts with CC host CREB3 nuclear transcription protein; this interaction triggers CC cell transformation (By similarity). Interacts with host ACY3 (By CC similarity). Interacts with host C1QR1 (By similarity). Interacts with CC host RBM24; this interaction, which enhances the interaction of the CC mature core protein with 5'-UTR, may inhibit viral translation and CC favor replication (By similarity). Interacts with host EIF2AK2/PKR; CC this interaction induces the autophosphorylation of EIF2AK2 (By CC similarity). Part of the viral assembly initiation complex composed of CC NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein (By CC similarity). {ECO:0000250|UniProtKB:P26662, CC ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, CC ECO:0000250|UniProtKB:P29846, ECO:0000250|UniProtKB:Q03463, CC ECO:0000250|UniProtKB:Q99IB8, ECO:0000269|PubMed:10329544}. CC -!- SUBUNIT: [Envelope glycoprotein E1]: Forms a heterodimer with envelope CC glycoprotein E2 (By similarity). Interacts with mature core protein (By CC similarity). Interacts with protease NS2 (By similarity). The CC heterodimer E1/E2 interacts with host CLDN1; this interaction plays a CC role in viral entry into host cell (By similarity). Interacts with host CC SPSB2 (via C-terminus) (By similarity). Part of the viral assembly CC initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the CC mature core protein (By similarity). {ECO:0000250|UniProtKB:P27958, CC ECO:0000250|UniProtKB:Q99IB8}. CC -!- SUBUNIT: [Envelope glycoprotein E2]: Forms a heterodimer with envelope CC glycoprotein E1 (By similarity). Interacts with host CD81 and SCARB1 CC receptors; these interactions play a role in viral entry into host cell CC (By similarity). Interacts with host EIF2AK2/PKR; this interaction CC inhibits EIF2AK2 and probably allows the virus to evade the innate CC immune response (By similarity). Interacts with host CD209/DC-SIGN and CC CLEC4M/DC-SIGNR (By similarity). Interact with host SPCS1; this CC interaction is essential for viral particle assembly (By similarity). CC Interacts with protease NS2 (By similarity). The heterodimer E1/E2 CC interacts with host CLDN1; this interaction plays a role in viral entry CC into host cell (By similarity). Part of the viral assembly initiation CC complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the mature core CC protein (By similarity). {ECO:0000250|UniProtKB:P27958, CC ECO:0000250|UniProtKB:Q99IB8}. CC -!- SUBUNIT: [Viroporin p7]: Homohexamer (By similarity). Homoheptamer (By CC similarity). Interacts with protease NS2 (By similarity). CC {ECO:0000250|UniProtKB:O92972, ECO:0000250|UniProtKB:P27958, CC ECO:0000250|UniProtKB:Q99IB8}. CC -!- SUBUNIT: [Protease NS2]: Homodimer (By similarity). Interacts with host CC SPCS1; this interaction is essential for viral particle assembly (By CC similarity). Interacts with envelope glycoprotein E1 (By similarity). CC Interacts with envelope glycoprotein E2 (By similarity). Interacts with CC viroporin p7 (By similarity). Interacts with serine protease/helicase CC NS3 (By similarity). Part of the replication complex composed of NS2, CC NS3, NS4A, NS4B, NS5A and the RNA-directed RNA polymerase embedded in CC an ER-derived membranous web (By similarity). Part of the viral CC assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A CC and the mature core protein (By similarity). CC {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8}. CC -!- INTERACTION: CC PRO_0000037559; O00571: DDX3X; Xeno; NbExp=4; IntAct=EBI-9254385, EBI-353779; CC -!- SUBCELLULAR LOCATION: [Core protein precursor]: Host endoplasmic CC reticulum membrane {ECO:0000250|UniProtKB:P26664}; Single-pass membrane CC protein {ECO:0000255}. Host mitochondrion membrane CC {ECO:0000250|UniProtKB:P26664}; Single-pass type I membrane protein CC {ECO:0000255}. Note=The C-terminal transmembrane domain of the core CC protein precursor contains an ER signal leading the nascent polyprotein CC to the ER membrane. CC -!- SUBCELLULAR LOCATION: [Mature core protein]: Virion CC {ECO:0000250|UniProtKB:Q99IB8}. Host cytoplasm CC {ECO:0000250|UniProtKB:Q99IB8}. Host nucleus CC {ECO:0000250|UniProtKB:P26662}. Host lipid droplet CC {ECO:0000250|UniProtKB:Q99IB8}. Note=Only a minor proportion of core CC protein is present in the nucleus (By similarity). Probably present on CC the surface of lipid droplets (By similarity). CC {ECO:0000250|UniProtKB:P27958}. CC -!- SUBCELLULAR LOCATION: [Envelope glycoprotein E1]: Virion membrane CC {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host CC endoplasmic reticulum membrane; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:P27958}. Note=The C-terminal transmembrane CC domain acts as a signal sequence and forms a hairpin structure before CC cleavage by host signal peptidase (By similarity). After cleavage, the CC membrane sequence is retained at the C-terminus of the protein, serving CC as ER membrane anchor (By similarity). A reorientation of the second CC hydrophobic stretch occurs after cleavage producing a single reoriented CC transmembrane domain (By similarity). These events explain the final CC topology of the protein (By similarity). CC {ECO:0000250|UniProtKB:P27958}. CC -!- SUBCELLULAR LOCATION: [Envelope glycoprotein E2]: Virion membrane CC {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host CC endoplasmic reticulum membrane; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:P27958}. Host lipid droplet CC {ECO:0000250|UniProtKB:Q9WMX2}. Note=The C-terminal transmembrane CC domain acts as a signal sequence and forms a hairpin structure before CC cleavage by host signal peptidase (By similarity). After cleavage, the CC membrane sequence is retained at the C-terminus of the protein, serving CC as ER membrane anchor (By similarity). A reorientation of the second CC hydrophobic stretch occurs after cleavage producing a single reoriented CC transmembrane domain (By similarity). These events explain the final CC topology of the protein (By similarity). CC {ECO:0000250|UniProtKB:P27958}. CC -!- SUBCELLULAR LOCATION: [Viroporin p7]: Host endoplasmic reticulum CC membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P27958}. Host mitochondrion CC {ECO:0000250|UniProtKB:P27958}. Host cell membrane CC {ECO:0000250|UniProtKB:P27958}. Note=The C-terminus of p7 membrane CC domain acts as a signal sequence (By similarity). After cleavage by CC host signal peptidase, the membrane sequence is retained at the C- CC terminus of the protein, serving as ER membrane anchor (By similarity). CC ER retention of p7 is leaky and a small fraction reaches the plasma CC membrane (By similarity). {ECO:0000250|UniProtKB:P27958}. CC -!- SUBCELLULAR LOCATION: [Protease NS2]: Host endoplasmic reticulum CC membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P27958}. Host lipid droplet CC {ECO:0000250|UniProtKB:Q9WMX2}. Note=Probably present on the surface of CC lipid droplets. {ECO:0000250|UniProtKB:Q99IB8}. CC -!- DOMAIN: [Envelope glycoprotein E1]: The transmembrane regions of CC envelope E1 and E2 glycoproteins are involved in heterodimer formation, CC ER localization, and assembly of these proteins. CC {ECO:0000250|UniProtKB:P27958}. CC -!- DOMAIN: [Envelope glycoprotein E2]: The transmembrane regions of CC envelope E1 and E2 glycoproteins are involved in heterodimer formation, CC ER localization, and assembly of these proteins (By similarity). CC Envelope E2 glycoprotein contain two highly variable regions called CC hypervariable region 1 and 2 (HVR1 and HVR2) (By similarity). E2 also CC contain two segments involved in CD81-binding (By similarity). HVR1 is CC implicated in the SCARB1-mediated cell entry and probably acts as a CC regulator of the association of particles with lipids (By similarity). CC {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:P27958}. CC -!- DOMAIN: [Protease NS2]: The N-terminus of NS3 is required for the CC catalytic activity of protease NS2 (By similarity). The minimal CC catalytic region includes the C-terminus of NS2 and the N-terminus NS3 CC protease domain (active region NS2-3) (By similarity). CC {ECO:0000250|UniProtKB:P26663}. CC -!- PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield CC mature proteins (By similarity). The structural proteins, core, E1, E2 CC and p7 are produced by proteolytic processing by host signal peptidases CC (By similarity). The core protein precursor is synthesized as a 23 kDa, CC which is retained in the ER membrane through the hydrophobic signal CC peptide (By similarity). Cleavage by the signal peptidase releases the CC 21 kDa mature core protein (By similarity). The cleavage of the core CC protein precursor occurs between aminoacids 176 and 188 but the exact CC cleavage site is not known (By similarity). Some degraded forms of the CC core protein appear as well during the course of infection (By CC similarity). The other proteins (p7, NS2, NS3, NS4A, NS4B, NS5A and CC NS5B) are cleaved by the viral proteases (By similarity). CC Autoprocessing between NS2 and NS3 is mediated by the NS2 cysteine CC protease catalytic domain and regulated by the NS3 N-terminal domain CC (By similarity). {ECO:0000250|UniProtKB:P26664, CC ECO:0000250|UniProtKB:P27958}. CC -!- PTM: [Mature core protein]: Phosphorylated by host PKC and PKA. CC {ECO:0000250|UniProtKB:Q01403}. CC -!- PTM: [Mature core protein]: Ubiquitinated; mediated by UBE3A and CC leading to core protein subsequent proteasomal degradation. CC {ECO:0000250|UniProtKB:Q03463}. CC -!- PTM: [Envelope glycoprotein E1]: Highly N-glycosylated. CC {ECO:0000250|UniProtKB:P27958}. CC -!- PTM: [Envelope glycoprotein E2]: Highly N-glycosylated. CC {ECO:0000250|UniProtKB:P27958}. CC -!- PTM: [Protease NS2]: Palmitoylation is required for NS2/3 CC autoprocessing and E2 recruitment to membranes. CC {ECO:0000250|UniProtKB:P27958}. CC -!- MISCELLANEOUS: Viral particle assembly takes place at the surface of CC ER-derived membranes in close proximity to lipid droplets. NS2 CC associates with E1/E2 glycoproteins, NS3 and NS5A, which interacts with CC the viral RNA and core protein to promote genome encapsidation. The CC nucleocapsid buds at the ER membrane where E1/E2 glycoproteins are CC anchored and afterward associate with nascent lipid droplet to acquire CC APOE and APOC. Secretion of viral particles is probably regulated by CC viroporin p7. {ECO:0000305}. CC -!- MISCELLANEOUS: [Mature core protein]: Exerts viral interference on CC hepatitis B virus when HCV and HBV coinfect the same cell, by CC suppressing HBV gene expression, RNA encapsidation and budding. CC {ECO:0000250|UniProtKB:P26662}. CC -!- SIMILARITY: Belongs to the hepacivirus polyprotein family. CC {ECO:0000305}. CC -!- CAUTION: The core gene probably also codes for alternative reading CC frame proteins (ARFPs). Many functions depicted for the core protein CC might belong to the ARFPs. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Virus Pathogen Resource; CC URL="https://www.viprbrc.org/brc/home.spg?decorator=flavi_hcv"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY885238; AAW78019.1; -; Genomic_RNA. DR PDB; 4GAG; X-ray; 1.80 A; P=412-423. DR PDB; 5VXR; X-ray; 1.40 A; P=412-423. DR PDBsum; 4GAG; -. DR PDBsum; 5VXR; -. DR SMR; Q5EG65; -. DR IntAct; Q5EG65; 1. DR ABCD; Q5EG65; 1 sequenced antibody. DR euHCVdb; AY885238; -. DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0044186; C:host cell lipid droplet; IEA:UniProtKB-SubCell. DR GO; GO:0044191; C:host cell mitochondrial membrane; IEA:UniProtKB-SubCell. DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW. DR GO; GO:1990904; C:ribonucleoprotein complex; IEA:UniProtKB-KW. DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW. DR GO; GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-KW. DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell. DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW. DR GO; GO:0005216; F:monoatomic ion channel activity; IEA:UniProtKB-KW. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro. DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW. DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW. DR GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW. DR GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-KW. DR GO; GO:0039707; P:virus-mediated pore formation in host cell membrane; IEA:UniProtKB-KW. DR CDD; cd20903; HCV_p7; 1. DR Gene3D; 6.10.250.1750; -; 1. DR Gene3D; 3.30.160.890; Hepatitis C virus envelope glycoprotein E1, chain C; 1. DR InterPro; IPR002521; HCV_Core_C. DR InterPro; IPR044896; HCV_core_chain_A. DR InterPro; IPR002522; HCV_core_N. DR InterPro; IPR002519; HCV_Env. DR InterPro; IPR002531; HCV_NS1. DR Pfam; PF01543; HCV_capsid; 1. DR Pfam; PF01542; HCV_core; 1. DR Pfam; PF01539; HCV_env; 1. DR Pfam; PF01560; HCV_NS1; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Apoptosis; Capsid protein; KW Clathrin-mediated endocytosis of virus by host; Disulfide bond; KW Fusion of virus membrane with host endosomal membrane; KW Fusion of virus membrane with host membrane; Glycoprotein; KW Host cell membrane; Host cytoplasm; Host endoplasmic reticulum; KW Host lipid droplet; Host membrane; Host mitochondrion; Host nucleus; KW Host-virus interaction; Hydrolase; KW Inhibition of host innate immune response by virus; KW Interferon antiviral system evasion; Ion channel; Ion transport; KW Isopeptide bond; Magnesium; Membrane; Oncogene; Phosphoprotein; Protease; KW Ribonucleoprotein; RNA-binding; Thiol protease; Transmembrane; KW Transmembrane helix; Transport; Ubl conjugation; KW Viral attachment to host cell; Viral envelope protein; Viral immunoevasion; KW Viral ion channel; Viral nucleoprotein; KW Viral penetration into host cytoplasm; Virion; Virus endocytosis by host; KW Virus entry into host cell; Zinc. FT INIT_MET 1 FT /note="Removed; by host" FT /evidence="ECO:0000250|UniProtKB:P26664" FT CHAIN 2..>829 FT /note="Genome polyprotein" FT /id="PRO_0000450903" FT CHAIN 2..191 FT /note="Core protein precursor" FT /id="PRO_0000037559" FT CHAIN 2..177 FT /note="Mature core protein" FT /id="PRO_0000037560" FT PROPEP 178..191 FT /note="ER anchor for the core protein, removed in mature FT form by host signal peptidase" FT /id="PRO_0000037561" FT CHAIN 192..383 FT /note="Envelope glycoprotein E1" FT /id="PRO_0000037562" FT CHAIN 384..746 FT /note="Envelope glycoprotein E2" FT /id="PRO_0000037563" FT CHAIN 747..809 FT /note="Viroporin p7" FT /id="PRO_0000037564" FT CHAIN 810..>829 FT /note="Protease NS2" FT /id="PRO_0000037565" FT TOPO_DOM 2..168 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 169..189 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 190..358 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:P27958" FT TRANSMEM 359..379 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:P27958" FT TOPO_DOM 380..725 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:P27958" FT TRANSMEM 726..746 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:P27958" FT TOPO_DOM 747..757 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:P27958" FT TRANSMEM 758..778 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:P27958" FT TOPO_DOM 779..781 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P27958" FT TRANSMEM 782..803 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:P27958" FT TOPO_DOM 804..813 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:P27958" FT TRANSMEM 814..>829 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9WMX2" FT REGION 2..75 FT /note="Disordered" FT /evidence="ECO:0000250|UniProtKB:P27958" FT REGION 2..59 FT /note="Interaction with DDX3X" FT /evidence="ECO:0000269|PubMed:10329544" FT REGION 2..58 FT /note="Interaction with EIF2AK2/PKR" FT /evidence="ECO:0000250|UniProtKB:P26662" FT REGION 2..23 FT /note="Interaction with STAT1" FT /evidence="ECO:0000250|UniProtKB:P26662" FT REGION 112..152 FT /note="Important for endoplasmic reticulum and FT mitochondrial localization" FT /evidence="ECO:0000250|UniProtKB:P26662" FT REGION 122..173 FT /note="Interaction with APOA2" FT /evidence="ECO:0000250|UniProtKB:P29846" FT REGION 164..167 FT /note="Important for lipid droplets localization" FT /evidence="ECO:0000250|UniProtKB:P27958" FT REGION 265..296 FT /note="Important for fusion" FT /evidence="ECO:0000250|UniProtKB:P27958" FT REGION 385..411 FT /note="HVR1" FT /evidence="ECO:0000250|UniProtKB:P27958" FT REGION 474..479 FT /note="HVR2" FT /evidence="ECO:0000250|UniProtKB:P27958" FT REGION 480..493 FT /note="CD81-binding 1" FT /evidence="ECO:0000250|UniProtKB:P26663" FT REGION 544..551 FT /note="CD81-binding 2" FT /evidence="ECO:0000250|UniProtKB:P26663" FT REGION 660..671 FT /note="PKR/eIF2-alpha phosphorylation homology domain FT (PePHD)" FT /evidence="ECO:0000250" FT MOTIF 5..13 FT /note="Nuclear localization signal" FT /evidence="ECO:0000250|UniProtKB:Q99IB8" FT MOTIF 38..43 FT /note="Nuclear localization signal" FT /evidence="ECO:0000250|UniProtKB:Q99IB8" FT MOTIF 58..64 FT /note="Nuclear localization signal" FT /evidence="ECO:0000250|UniProtKB:Q99IB8" FT MOTIF 66..71 FT /note="Nuclear localization signal" FT /evidence="ECO:0000250|UniProtKB:Q99IB8" FT COMPBIAS 47..61 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 177..178 FT /note="Cleavage; by host signal peptide peptidase" FT /evidence="ECO:0000250|UniProtKB:P26662" FT SITE 191..192 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000250|UniProtKB:P26662" FT SITE 383..384 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000250|UniProtKB:P26662" FT SITE 746..747 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000250" FT SITE 809..810 FT /note="Cleavage; by host signal peptidase" FT /evidence="ECO:0000250" FT MOD_RES 2 FT /note="N-acetylserine; by host" FT /evidence="ECO:0000250|UniProtKB:Q913V3" FT MOD_RES 53 FT /note="Phosphoserine; by host" FT /evidence="ECO:0000250|UniProtKB:Q01403" FT MOD_RES 99 FT /note="Phosphoserine; by host" FT /evidence="ECO:0000250|UniProtKB:Q01403" FT MOD_RES 116 FT /note="Phosphoserine; by host PKA" FT /evidence="ECO:0000250|UniProtKB:Q01403" FT CARBOHYD 196 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000250|UniProtKB:P27958" FT CARBOHYD 209 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000250|UniProtKB:P27958" FT CARBOHYD 234 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000250|UniProtKB:P27958" FT CARBOHYD 305 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 417 FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by FT host" FT /evidence="ECO:0000250|UniProtKB:P27958" FT CARBOHYD 423 FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by FT host" FT /evidence="ECO:0000250|UniProtKB:P27958" FT CARBOHYD 430 FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by FT host" FT /evidence="ECO:0000250|UniProtKB:P27958" FT CARBOHYD 448 FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by FT host" FT /evidence="ECO:0000250|UniProtKB:P27958" FT CARBOHYD 540 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 556 FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by FT host" FT /evidence="ECO:0000250|UniProtKB:P27958" FT CARBOHYD 576 FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by FT host" FT /evidence="ECO:0000250|UniProtKB:P27958" FT CARBOHYD 623 FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by FT host" FT /evidence="ECO:0000250|UniProtKB:P27958" FT CARBOHYD 645 FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by FT host" FT /evidence="ECO:0000250|UniProtKB:P27958" FT DISULFID 429..552 FT /evidence="ECO:0000250|UniProtKB:P27958" FT DISULFID 452..459 FT /evidence="ECO:0000250|UniProtKB:P27958" FT DISULFID 486..494 FT /evidence="ECO:0000250|UniProtKB:P27958" FT DISULFID 503..508 FT /evidence="ECO:0000250|UniProtKB:P27958" FT DISULFID 564..569 FT /evidence="ECO:0000250|UniProtKB:P27958" FT DISULFID 581..585 FT /evidence="ECO:0000250|UniProtKB:P27958" FT DISULFID 597..620 FT /evidence="ECO:0000250|UniProtKB:P27958" FT DISULFID 607..644 FT /evidence="ECO:0000250|UniProtKB:P27958" FT DISULFID 652..677 FT /evidence="ECO:0000250|UniProtKB:P27958" FT MUTAGEN 180..184 FT /note="ALLSC->VLLLV: Complete loss of processing." FT /evidence="ECO:0000269|PubMed:12145199" FT NON_TER 829 FT STRAND 414..416 FT /evidence="ECO:0007829|PDB:5VXR" FT STRAND 419..421 FT /evidence="ECO:0007829|PDB:5VXR" SQ SEQUENCE 829 AA; 90587 MW; 17AD3868F50B4AD4 CRC64; MSTNPKPQRK TKRNTNRRPQ DVKFPGGGQI VGGVYLLPRR GPRLGVRATR KTSERSQPRG RRQPIPKARR PKGRNWAQPG YPWPLYGNEG CGWAGWLPSP RGSRPSWGPN DPRRRSRNLG KVIDTLTCGF VDLMGYIPLV GAPLRGAARA LAHGVRVLED GVNYATGNLP GCSFSIFLLA LLSCLTVPAS AYQVRNSTGL YHVTNDCPNS SIVYEAVDAI LHTPGCVPCV REGNASRCWV AMTPTVATRD GRLPTTQLRR HIDLLVGSAT LCSALYVGDL CGSVFLVGQL FTFSPRRHWT TQGCNCSIYP GHITGHRMAW DMMMNWSPTT ALVVAQLLRI PQAILDMIAG AHWGVLAGMA YFSMVGNWAK VLAVLLLFAG VDAETHVTGG AAARSTLQLA GLFQPGAKQN VQLINTNGSW HVNRTALNCN DSLNTGWIAG LFYYHGFNSS GCSERLASCR SLTDFDQGWG PISYAGGGGP DHRPYCWHYP PKPCGIVPAK SVCGPVYCFT PSPVVVGTTD RSGAPTYSWG ADDTDVFVLN NTRPPLGNWF GCTWMNSTGF TKVCGAPPCV IGGVGNNTLH CPTDCFRKHP EATYSRCGSG PWLTPRCLVD YPYRLWHYPC TINHSIFKVR MYVGGVEHRL DAACNWTRGE RCDLEDRDRS ELSPLLLSTT QWQVLPCSFT TLPALSTGLI HLHQNIVDVQ YLYGVGSSIA SWAIKWEYVV LLFLLLADAR VCSCLWMMLL ISQAEAALEN LVVLNAASLA GTHGLVSFLV FFCFAWFLRG KWVPGAVYAL YGMWPLLLLL LALPQRAYAL DTEVAASCGG VVLVGLMAL //