P27958 · POLG_HCV77
- ProteinGenome polyprotein
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids3011 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Mature core protein
Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (PubMed:18033802).
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) (PubMed:23799612).
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 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 (PubMed:11086025, PubMed:17881511).
Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (PubMed:14602201).
Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (PubMed:14602201).
Envelope glycoprotein E1
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 (PubMed:16533059, PubMed:24698129, PubMed:29505618).
E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (PubMed:24838241, PubMed:25122793, PubMed:29695434).
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) (PubMed:12356718, PubMed:12913001, PubMed:12970454, PubMed:22767607, PubMed:28404852).
The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (PubMed:12913001, PubMed:22767607).
E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (PubMed:22855500).
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) (PubMed:12913001, PubMed:12970454, PubMed:19182773, PubMed:20375010, PubMed:24038151).
Envelope glycoprotein E2
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 (PubMed:16533059, PubMed:24698129, PubMed:29505618).
The interaction between E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (PubMed:25122793, PubMed:29695434).
This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (PubMed:29695434).
E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (PubMed:24838241, PubMed:25122793, PubMed:29695434).
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) (PubMed:12356718, PubMed:12913001, PubMed:12970454, PubMed:22767607, PubMed:28404852).
The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (PubMed:12913001, PubMed:22767607).
E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity) (PubMed:12913001, PubMed:12970454, PubMed:19182773, PubMed:20375010, PubMed:22855500, PubMed:24038151).
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) (PubMed:12913001, PubMed:12970454, PubMed:19182773, PubMed:20375010, PubMed:24038151).
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 DCs, and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (PubMed:15371595).
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 (PubMed:15371595).
The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (PubMed:30341327).
Viroporin p7
Participates in virus envelopment by coordinating the encounter between NS5A and NS2-based assembly sites loaded with E1/E2 heterodimer, which subsequently leads to nucleocapsid envelopment (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 (Probable) (PubMed:20824094).
High levels of cytoplasmic Ca2+ may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). The release of Ca2+ may also activate the inflamasome leading to chronic inflammation (Probable) (PubMed:31801866).
Targets also host mitochondria and induces mitochondrial depolarization (PubMed:29039530).
In addition of its role as a viroporin, acts as a lipid raft adhesion factor (PubMed:27320856).
Protease NS2
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 (PubMed:21147927).
Serine protease/helicase NS3
NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (PubMed:8035505, PubMed:8189513, PubMed:8386278).
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 (PubMed:30341327).
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 (Probable). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (PubMed:21940894).
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 (PubMed:16177806, PubMed:16301520).
Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (PubMed:15710891).
Non-structural protein 4A
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 (PubMed:30341327).
Non-structural protein 4B
This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (PubMed:12021330).
NS4B self-interaction contributes to its function in membranous web formation (PubMed:16731940).
Promotes host TRIF protein degradation in a CASP8-dependent manner thereby inhibiting host TLR3-mediated interferon signaling (PubMed:29782532).
Disrupts the interaction between STING and TBK1 contributing to the inhibition of interferon signaling (PubMed:23542348).
Non-structural protein 5A
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 (Probable). Zinc is essential for RNA-binding (PubMed:20926572).
Participates in the viral particle production as a result of its interaction with the viral mature 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 (PubMed:16951545).
Prevents BIN1-induced apoptosis (PubMed:16530520).
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 (PubMed:31801866).
Modulates TNFRSF21/DR6 signaling pathway for viral propagation (PubMed:28743875).
RNA-directed RNA polymerase
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 (PubMed:37407817), thereby evading activation of antiviral pathways.
Miscellaneous
Non-structural protein 5A
Mature core protein
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
Protease NS2
Zn2+ (UniProtKB | Rhea| CHEBI:29105 )Serine protease/helicase NS3
Zn2+ (UniProtKB | Rhea| CHEBI:29105 )Mg2+ (UniProtKB | Rhea| CHEBI:18420 )
The magnesium ion is essential for the helicase activity (By similarity).
RNA-directed RNA polymerase
Mg2+ (UniProtKB | Rhea| CHEBI:18420 )Activity regulation
Viroporin p7
Inhibited by amantadine (PubMed:12560074).
Inhibition by amantadine appears to be genotype-dependent (By similarity).
Also inhibited by long-alkyl-chain iminosugar derivatives (PubMed:12719519).
RNA-directed RNA polymerase
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: AY | ||||||
Site | 383-384 | Cleavage; by host signal peptidase | ||||
Sequence: AE | ||||||
Site | 746-747 | Cleavage; by host signal peptidase | ||||
Sequence: AA | ||||||
Site | 809-810 | Cleavage; by host signal peptidase | ||||
Sequence: AL | ||||||
Active site | 952 | For protease NS2 activity; shared with dimeric partner | ||||
Sequence: H | ||||||
Active site | 972 | For protease NS2 activity; shared with dimeric partner | ||||
Sequence: E | ||||||
Active site | 993 | For protease NS2 activity; shared with dimeric partner | ||||
Sequence: C | ||||||
Site | 1026-1027 | Cleavage; by protease NS2 | ||||
Sequence: LA | ||||||
Active site | 1083 | Charge relay system; for serine protease NS3 activity | ||||
Sequence: H | ||||||
Active site | 1107 | Charge relay system; for serine protease NS3 activity | ||||
Sequence: D | ||||||
Binding site | 1123 | Zn2+ 1 (UniProtKB | ChEBI); structural; for NS3 protease activity and NS2/3 auto-cleavage activity | ||||
Sequence: C | ||||||
Binding site | 1125 | Zn2+ 1 (UniProtKB | ChEBI); structural; for NS3 protease activity and NS2/3 auto-cleavage activity | ||||
Sequence: C | ||||||
Active site | 1165 | Charge relay system; for serine protease NS3 activity | ||||
Sequence: S | ||||||
Binding site | 1171 | Zn2+ 1 (UniProtKB | ChEBI); structural; for NS3 protease activity and NS2/3 auto-cleavage activity | ||||
Sequence: C | ||||||
Binding site | 1175 | Zn2+ 1 (UniProtKB | ChEBI); structural; for NS3 protease activity and NS2/3 auto-cleavage activity | ||||
Sequence: H | ||||||
Binding site | 1230-1237 | ATP (UniProtKB | ChEBI) | ||||
Sequence: APTGSGKS | ||||||
Binding site | 1237 | Mg2+ 1 (UniProtKB | ChEBI); catalytic; for NS3 helicase activity | ||||
Sequence: S | ||||||
Binding site | 1317 | Mg2+ 1 (UniProtKB | ChEBI); catalytic; for NS3 helicase activity | ||||
Sequence: E | ||||||
Site | 1657-1658 | Cleavage; by serine protease/helicase NS3 | ||||
Sequence: TS | ||||||
Site | 1711-1712 | Cleavage; by serine protease/helicase NS3 | ||||
Sequence: CS | ||||||
Site | 1972-1973 | Cleavage; by serine protease/helicase NS3 | ||||
Sequence: CS | ||||||
Binding site | 2011 | Zn2+ 2 (UniProtKB | ChEBI); structural | ||||
Sequence: C | ||||||
Binding site | 2029 | Zn2+ 2 (UniProtKB | ChEBI); structural | ||||
Sequence: C | ||||||
Binding site | 2031 | Zn2+ 2 (UniProtKB | ChEBI); structural | ||||
Sequence: C | ||||||
Binding site | 2052 | Zn2+ 2 (UniProtKB | ChEBI); structural | ||||
Sequence: C | ||||||
Site | 2420-2421 | Cleavage; by serine protease/helicase NS3 | ||||
Sequence: CS | ||||||
Binding site | 2640 | Mg2+ 2 (UniProtKB | ChEBI); catalytic; for RNA-directed RNA polymerase activity | ||||
Sequence: D | ||||||
Binding site | 2738 | Mg2+ 2 (UniProtKB | ChEBI); catalytic; for RNA-directed RNA polymerase activity | ||||
Sequence: D | ||||||
Binding site | 2739 | Mg2+ 2 (UniProtKB | ChEBI); catalytic; for RNA-directed RNA polymerase activity | ||||
Sequence: D |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameGenome polyprotein
- Cleaved into 11 chains
Organism names
- Strain
- Taxonomic lineageViruses > Riboviria > Orthornavirae > Kitrinoviricota > Flasuviricetes > Amarillovirales > Flaviviridae > Hepacivirus > Hepacivirus hominis > hepatitis C virus genotype 1a
- Virus hosts
Accessions
- Primary accessionP27958
- Secondary accessions
Proteomes
Subcellular Location
Core protein precursor
Mature core protein
Envelope glycoprotein E1
After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (PubMed:10729138).
A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (PubMed:12065403).
These events explain the final topology of the protein (PubMed:12065403).
Envelope glycoprotein E2
After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (PubMed:10729138).
A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (PubMed:12065403).
These events explain the final topology of the protein (PubMed:12065403).
Viroporin p7
After cleavage by host signal peptidase, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (PubMed:11907211).
ER retention of p7 is leaky and a small fraction reaches the plasma membrane (PubMed:11907211).
Protease NS2
Serine protease/helicase NS3
Non-structural protein 4A
Non-structural protein 4B
Non-structural protein 5A
Localizes at the surface of lipid droplets (By similarity).
RNA-directed RNA polymerase
Features
Showing features for topological domain, transmembrane, intramembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 2-168 | Cytoplasmic | ||||
Sequence: STNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGN | ||||||
Transmembrane | 169-189 | Helical | ||||
Sequence: LPGCSFSIFLLALLSCLTVPA | ||||||
Topological domain | 190-358 | Lumenal | ||||
Sequence: SAYQVRNSSGLYHVTNDCPNSSVVYEAADAILHTPGCVPCVREGNASRCWVAVTPTVATRDGKLPTTQLRRHIDLLVGSATLCSALYVGDLCGSVFLVGQLFTFSPRHHWTTQDCNCSIYPGHITGHRMAWNMMMNWSPTAALVVAQLLRIPQAIMDMIAGAHWGVLAG | ||||||
Transmembrane | 359-379 | Helical | ||||
Sequence: IKYFSMVGNWAKVLVVLLLFA | ||||||
Topological domain | 380-725 | Lumenal | ||||
Sequence: GVDAETHVTGGNAGRTTAGLVGLLTPGAKQNIQLINTNGSWHINSTALNCNESLNTGWLAGLFYQHKFNSSGCPERLASCRRLTDFAQGWGPISYANGSGLDERPYCWHYPPRPCGIVPAKSVCGPVYCFTPSPVVVGTTDRSGAPTYSWGANDTDVFVLNNTRPPLGNWFGCTWMNSTGFTKVCGAPPCVIGGVGNNTLLCPTDCFRKYPEATYSRCGSGPRITPRCMVDYPYRLWHYPCTINYTIFKVRMYVGGVEHRLEAACNWTRGERCDLEDRDRSELSPLLLSTTQWQVLPCSFTTLPALSTGLIHLHQNIVDVQYLYGVGSSIASWAIKWEYVVLLFLL | ||||||
Transmembrane | 726-746 | Helical | ||||
Sequence: LADARVCSCLWMMLLISQAEA | ||||||
Topological domain | 747-757 | Lumenal | ||||
Sequence: ALENLVILNAA | ||||||
Transmembrane | 758-778 | Helical | ||||
Sequence: SLAGTHGLVSFLVFFCFAWYL | ||||||
Topological domain | 779-781 | Cytoplasmic | ||||
Sequence: KGR | ||||||
Transmembrane | 782-803 | Helical | ||||
Sequence: WVPGAVYALYGMWPLLLLLLAL | ||||||
Topological domain | 804-813 | Lumenal | ||||
Sequence: PQRAYALDTE | ||||||
Transmembrane | 814-834 | Helical | ||||
Sequence: VAASCGGVVLVGLMALTLSPY | ||||||
Topological domain | 835-838 | Cytoplasmic | ||||
Sequence: YKRY | ||||||
Transmembrane | 839-859 | Helical | ||||
Sequence: ISWCMWWLQYFLTRVEAQLHV | ||||||
Topological domain | 860-881 | Lumenal | ||||
Sequence: WVPPLNVRGGRDAVILLTCVVH | ||||||
Transmembrane | 882-902 | Helical | ||||
Sequence: PALVFDITKLLLAIFGPLWIL | ||||||
Topological domain | 903-1657 | Cytoplasmic | ||||
Sequence: QASLLKVPYFVRVQGLLRICALARKIAGGHYVQMAIIKLGALTGTCVYNHLAPLRDWAHNGLRDLAVAVEPVVFSRMETKLITWGADTAACGDIINGLPVSARRGQEILLGPADGMVSKGWRLLAPITAYAQQTRGLLGCIITSLTGRDKNQVEGEVQIVSTATQTFLATCINGVCWTVYHGAGTRTIASPKGPVIQTYTNVDQDLVGWPAPQGSRSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGGPLLCPTGHAVGLFRAAVCTRGVAKAVDFIPVENLETTMRSPVFTDNSSPPAVPQSFQVAHLHAPTGSGKSTKVPAAYAAKGYKVLVLNPSVAATLGFGAYMSKAHGVDPNIRTGVRTITTGSPITYSTYGKFLADAGCSGGAYDIIICDECHSTDATSISGIGTVLDQAETAGARLVVLATATPPGSVTVSHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRHLIFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVVSTDALMTGFTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGKPGIYRFVAPGERPSGMFDSSVLCECYDAGCAWYELTPAETTVRLRAYMNTPGLPVCQDHLGFWEGVFTGLTHIDAHFLSQTKQSGENFPYLVAYQATVCARAQAPPPSWDQMRKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMTCMSADLEVVT | ||||||
Transmembrane | 1658-1678 | Helical | ||||
Sequence: STWVLVGGVLAALAAYCLSTG | ||||||
Topological domain | 1679-1805 | Cytoplasmic | ||||
Sequence: CVVIVGRIVLSGKPAIIPDREVLYQEFDEMEECSQHLPYIEQGMMLAEQFKQKALGLLQTASRHAEVITPAVQTNWQKLEVFWAKHMWNFISGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTGQ | ||||||
Transmembrane | 1806-1824 | Helical | ||||
Sequence: TLLFNILGGWVAAQLAAPG | ||||||
Topological domain | 1825-1828 | Lumenal | ||||
Sequence: AATA | ||||||
Transmembrane | 1829-1849 | Helical | ||||
Sequence: FVGAGLAGAALDSVGLGKVLV | ||||||
Topological domain | 1850 | Cytoplasmic | ||||
Sequence: D | ||||||
Transmembrane | 1851-1871 | Helical | ||||
Sequence: ILAGYGAGVAGALVAFKIMSG | ||||||
Topological domain | 1872-1881 | Lumenal | ||||
Sequence: EVPSTEDLVN | ||||||
Transmembrane | 1882-1902 | Helical | ||||
Sequence: LLPAILSPGALAVGVVFASIL | ||||||
Topological domain | 1903-1972 | Cytoplasmic | ||||
Sequence: RRRVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTAILSSLTVTQLLRRLHQWISSECTTPC | ||||||
Intramembrane | 1973-2003 | |||||
Sequence: SGSWLRDIWDWICEVLSDFKTWLKAKLMPQL | ||||||
Topological domain | 2004-2990 | Cytoplasmic | ||||
Sequence: PGIPFVSCQRGYRGVWRGDGIMHTRCHCGAEITGHVKNGTMRIVGPRTCKNMWSGTFFINAYTTGPCTPLPAPNYKFALWRVSAEEYVEIRRVGDFHYVSGMTTDNLKCPCQIPSPEFFTELDGVRLHRFAPPCKPLLREEVSFRVGLHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAAGRRLARGSPPSMASSSASQLSAPSLKATCTANHDSPDAELIEANLLWRQEMGGNITRVESENKVVILDSFDPLVAEEDEREVSVPAEILRKSRRFAPALPVWARPDYNPLLVETWKKPDYEPPVVHGCPLPPPRSPPVPPPRKKRTVVLTESTLPTALAELATKSFGSSSTSGITGDNTTTSSEPAPSGCPPDSDVESYSSMPPLEGEPGDPDLSDGSWSTVSSGADTEDVVCCSMSYSWTGALVTPCAAEEQKLPINALSNSLLRHHNLVYSTTSRSACQRKKKVTFDRLQVLDSHYQDVLKEVKAAASKVKANLLSVEEACSLAPPHSAKSKFGYGAKDVRCHARKAVAHINSVWKDLLEDSVTPIDTTIMAKNEVFCVQPEKGGRKPARLIVFPDLGVRVCEKMALYDVVSKLPLAVMGSSYGFQYSPGQRVEFLVQAWKSKKTPMGLSYDTRCFDSTVTESDIRTEEAIYQCCDLDPQARVAIKSLTERLYVGGPLTNSRGENCGYRRCRASRVLTTSCGNTLTRYIKARAACRAAGLQDCTMLVCGDDLVVICESAGVQEDAASLRAFTEAMTRYSAPPGDPPQPEYDLELITSCSSNVSVAHDGAGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMFAPTLWARMILMTHFFSVLIARDQLEQALNCEIYGACYSIEPLDLPPIIQRLHGLSAFSLHSYSPGEINRVAACLRKLGVPPLRAWRHRAWSVRARLLARGGKAAICGKYLFNWAVRTKLKLTPITAAGRLDLSGWFTAGYSGGDIYHSVSHARPR | ||||||
Transmembrane | 2991-3011 | Helical | ||||
Sequence: WFWFCLLLLAAGVGIYLLPNR |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | 212 | in strain: Isolate H77 | ||||
Sequence: V → I | ||||||
Natural variant | 297 | in strain: Isolate H77 | ||||
Sequence: H → R | ||||||
Natural variant | 303 | in strain: Isolate H77 | ||||
Sequence: D → S | ||||||
Natural variant | 321 | in strain: Isolate H77 | ||||
Sequence: N → D | ||||||
Natural variant | 360 | in strain: Isolate H77 | ||||
Sequence: K → A | ||||||
Natural variant | 391 | in strain: Isolate H77 | ||||
Sequence: N → S | ||||||
Natural variant | 394 | in strain: Isolate H77 | ||||
Sequence: R → H | ||||||
Mutagenesis | 399 | Complete loss of E2 binding to host SCARB1; 5-10-fold decrease of infectivity for the viral particles. | ||||
Sequence: L → R | ||||||
Mutagenesis | 429 | Complete loss of infectivity. | ||||
Sequence: C → A | ||||||
Natural variant | 431 | in strain: Isolate H77 | ||||
Sequence: E → D | ||||||
Natural variant | 434 | in strain: Isolate H77 | ||||
Sequence: N → T | ||||||
Natural variant | 444 | in strain: Isolate H77 | ||||
Sequence: Q → R | ||||||
Mutagenesis | 452 | Complete loss of infectivity. Loss of heterodimerization with E1. No effect on CD81-binding function. | ||||
Sequence: C → A | ||||||
Natural variant | 457 | in strain: Isolate H77 | ||||
Sequence: A → T | ||||||
Mutagenesis | 459 | Complete loss of infectivity. Loss of heterodimerization with E1. 78% loss of CD81-binding function. | ||||
Sequence: C → A | ||||||
Mutagenesis | 486 | Complete loss of infectivity. No effect on CD81-binding function. Loss of heterodimerization with E1. | ||||
Sequence: C → A | ||||||
Mutagenesis | 494 | Complete loss of infectivity and CD81-binding function. Loss of heterodimerization with E1. | ||||
Sequence: C → A | ||||||
Mutagenesis | 503 | Complete loss of infectivity and CD81-binding function. | ||||
Sequence: C → A | ||||||
Mutagenesis | 508 | Complete loss of infectivity and CD81-binding function. | ||||
Sequence: C → A | ||||||
Mutagenesis | 552 | Complete loss of infectivity. | ||||
Sequence: C → A | ||||||
Mutagenesis | 564 | Complete loss of infectivity and CD81-binding function. | ||||
Sequence: C → A | ||||||
Natural variant | 564-566 | in strain: Isolate H77 | ||||
Sequence: CGA → RGV | ||||||
Mutagenesis | 569 | Complete loss of infectivity. No effect on CD81-binding function. Loss of heterodimerization with E1. | ||||
Sequence: C → A | ||||||
Mutagenesis | 581 | Complete loss of infectivity. No effect on CD81-binding function. Loss of heterodimerization with E1. | ||||
Sequence: C → A | ||||||
Mutagenesis | 585 | Complete loss of infectivity. No effect on CD81-binding function. Loss of heterodimerization with E1. | ||||
Sequence: C → A | ||||||
Natural variant | 589 | in strain: Isolate H77 | ||||
Sequence: Y → H | ||||||
Mutagenesis | 597 | Complete loss of infectivity. Reduced CD81-binding function. | ||||
Sequence: C → A | ||||||
Natural variant | 602 | in strain: Isolate H77 | ||||
Sequence: R → W | ||||||
Mutagenesis | 607 | Complete loss of infectivity. Complete loss of E2 expression probably due to the disruption of the global conformation of the protein. | ||||
Sequence: C → A | ||||||
Mutagenesis | 620 | Complete loss of infectivity. Reduced CD81-binding function. | ||||
Sequence: C → A | ||||||
Mutagenesis | 644 | Complete loss of infectivity. Complete loss of E2 expression probably due to the disruption of the global conformation of the protein. | ||||
Sequence: C → A | ||||||
Natural variant | 650 | in strain: Isolate H77 | ||||
Sequence: E → G | ||||||
Mutagenesis | 652 | Complete loss of infectivity. Reduced heterodimerization with E1. No effect on CD81-binding function. | ||||
Sequence: C → A | ||||||
Mutagenesis | 677 | Complete loss of infectivity. Reduced heterodimerization with E1. No effect on CD81-binding function. | ||||
Sequence: C → A | ||||||
Mutagenesis | 720 | Increases processing between E2 and p7. | ||||
Sequence: V → L | ||||||
Natural variant | 773 | in strain: Isolate H77 | ||||
Sequence: C → R | ||||||
Mutagenesis | 779 | Virus can no longer infect chimpanzee. | ||||
Sequence: K → I | ||||||
Mutagenesis | 781 | Virus can no longer infect chimpanzee. | ||||
Sequence: R → S | ||||||
Natural variant | 787 | in strain: Isolate H77 | ||||
Sequence: V → A | ||||||
Natural variant | 790 | in strain: Isolate H77 | ||||
Sequence: L → F | ||||||
Natural variant | 877 | in strain: Isolate H77 | ||||
Sequence: T → M | ||||||
Natural variant | 883 | in strain: Isolate H77 | ||||
Sequence: A → T | ||||||
Mutagenesis | 922 | Complete loss of palmitoylation of NS2. | ||||
Sequence: C → S | ||||||
Natural variant | 948 | in strain: Isolate H77 | ||||
Sequence: C → Y | ||||||
Mutagenesis | 952 | Complete loss of NS2-NS3 cleavage. | ||||
Sequence: H → A | ||||||
Natural variant | 954 | in strain: Isolate H77 | ||||
Sequence: A → T | ||||||
Mutagenesis | 993 | Complete loss of NS2-NS3 cleavage. | ||||
Sequence: C → A | ||||||
Natural variant | 1026 | in strain: Isolate H77 | ||||
Sequence: L → Q | ||||||
Natural variant | 1033 | in strain: Isolate H77 | ||||
Sequence: A → T | ||||||
Natural variant | 1049 | in strain: Isolate H77 | ||||
Sequence: G → S | ||||||
Mutagenesis | 1083 | Complete loss of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B cleavages. | ||||
Sequence: H → A | ||||||
Natural variant | 1100 | in strain: Isolate H77 | ||||
Sequence: T → M | ||||||
Natural variant | 1121 | in strain: Isolate H77 | ||||
Sequence: T → A | ||||||
Mutagenesis | 1165 | Complete loss of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B cleavages. | ||||
Sequence: S → A | ||||||
Natural variant | 1173 | in strain: Isolate H77 | ||||
Sequence: T → A | ||||||
Natural variant | 1202 | in strain: Isolate H77 | ||||
Sequence: E → G | ||||||
Natural variant | 1214 | in strain: Isolate H77 | ||||
Sequence: S → P | ||||||
Natural variant | 1247 | in strain: Isolate H77 | ||||
Sequence: K → Q | ||||||
Natural variant | 1303 | in strain: Isolate H77 | ||||
Sequence: A → G | ||||||
Natural variant | 1327 | in strain: Isolate H77 | ||||
Sequence: S → L | ||||||
Natural variant | 1556 | in strain: Isolate H77 | ||||
Sequence: G → E | ||||||
Natural variant | 1608 | in strain: Isolate H77 | ||||
Sequence: R → W | ||||||
Natural variant | 1742 | in strain: Isolate H77 | ||||
Sequence: H → Q | ||||||
Natural variant | 1839-1840 | in strain: Isolate H77 | ||||
Sequence: LD → IG | ||||||
Natural variant | 1893 | in strain: Isolate H77 | ||||
Sequence: A → V | ||||||
Natural variant | 1898-1900 | in strain: Isolate H77 | ||||
Sequence: FAS → CAA | ||||||
Natural variant | 1905 | in strain: Isolate H77 | ||||
Sequence: R → H | ||||||
Natural variant | 1940 | in strain: Isolate H77 | ||||
Sequence: A → V | ||||||
Mutagenesis | 1968 | Strong decrease in NS4B palmitoylation. | ||||
Sequence: C → A | ||||||
Mutagenesis | 1972 | Slight decrease in NS4B palmitoylation. | ||||
Sequence: C → A | ||||||
Natural variant | 2043 | in strain: Isolate H77 | ||||
Sequence: T → A | ||||||
Natural variant | 2053 | in strain: Isolate H77 | ||||
Sequence: K → R | ||||||
Natural variant | 2061 | in strain: Isolate H77 | ||||
Sequence: F → L | ||||||
Natural variant | 2102 | in strain: Isolate H77 | ||||
Sequence: V → I | ||||||
Natural variant | 2185 | in strain: Isolate H77 | ||||
Sequence: A → E | ||||||
Natural variant | 2283 | in strain: Isolate H77 | ||||
Sequence: P → R | ||||||
Natural variant | 2296 | in strain: Isolate H77 | ||||
Sequence: L → P | ||||||
Mutagenesis | 2321 | Loss of phosphorylation. | ||||
Sequence: S → A | ||||||
Natural variant | 2341 | in strain: Isolate H77 | ||||
Sequence: P → S | ||||||
Natural variant | 2355 | in strain: Isolate H77 | ||||
Sequence: S → P | ||||||
Natural variant | 2400 | in strain: Isolate H77 | ||||
Sequence: L → F | ||||||
Natural variant | 2425 | in strain: Isolate H77 | ||||
Sequence: S → T | ||||||
Natural variant | 2469 | in strain: Isolate H77 | ||||
Sequence: K → Q | ||||||
Natural variant | 2512 | in strain: Isolate H77 | ||||
Sequence: A → T | ||||||
Natural variant | 2637 | in strain: Isolate H77 | ||||
Sequence: L → F | ||||||
Natural variant | 2703 | in strain: Isolate H77 | ||||
Sequence: R → G | ||||||
Natural variant | 2715 | in strain: Isolate H77 | ||||
Sequence: R → C | ||||||
Natural variant | 2755 | in strain: Isolate H77 | ||||
Sequence: S → N | ||||||
Natural variant | 2925 | in strain: Isolate H77 | ||||
Sequence: W → R | ||||||
Natural variant | 2933 | in strain: Isolate H77 | ||||
Sequence: A → S | ||||||
Natural variant | 2937 | in strain: Isolate H77 | ||||
Sequence: K → R | ||||||
Natural variant | 2960 | in strain: Isolate H77 | ||||
Sequence: T → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 62 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Chemistry
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_0000037567 | 2-177 | Mature core protein | |||
Sequence: STNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLPGCSFSIF | ||||||
Chain | PRO_0000037566 | 2-191 | Core protein precursor | |||
Sequence: STNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLPGCSFSIFLLALLSCLTVPASA | ||||||
Chain | PRO_0000450854 | 2-3011 | Genome polyprotein | |||
Sequence: STNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLPGCSFSIFLLALLSCLTVPASAYQVRNSSGLYHVTNDCPNSSVVYEAADAILHTPGCVPCVREGNASRCWVAVTPTVATRDGKLPTTQLRRHIDLLVGSATLCSALYVGDLCGSVFLVGQLFTFSPRHHWTTQDCNCSIYPGHITGHRMAWNMMMNWSPTAALVVAQLLRIPQAIMDMIAGAHWGVLAGIKYFSMVGNWAKVLVVLLLFAGVDAETHVTGGNAGRTTAGLVGLLTPGAKQNIQLINTNGSWHINSTALNCNESLNTGWLAGLFYQHKFNSSGCPERLASCRRLTDFAQGWGPISYANGSGLDERPYCWHYPPRPCGIVPAKSVCGPVYCFTPSPVVVGTTDRSGAPTYSWGANDTDVFVLNNTRPPLGNWFGCTWMNSTGFTKVCGAPPCVIGGVGNNTLLCPTDCFRKYPEATYSRCGSGPRITPRCMVDYPYRLWHYPCTINYTIFKVRMYVGGVEHRLEAACNWTRGERCDLEDRDRSELSPLLLSTTQWQVLPCSFTTLPALSTGLIHLHQNIVDVQYLYGVGSSIASWAIKWEYVVLLFLLLADARVCSCLWMMLLISQAEAALENLVILNAASLAGTHGLVSFLVFFCFAWYLKGRWVPGAVYALYGMWPLLLLLLALPQRAYALDTEVAASCGGVVLVGLMALTLSPYYKRYISWCMWWLQYFLTRVEAQLHVWVPPLNVRGGRDAVILLTCVVHPALVFDITKLLLAIFGPLWILQASLLKVPYFVRVQGLLRICALARKIAGGHYVQMAIIKLGALTGTCVYNHLAPLRDWAHNGLRDLAVAVEPVVFSRMETKLITWGADTAACGDIINGLPVSARRGQEILLGPADGMVSKGWRLLAPITAYAQQTRGLLGCIITSLTGRDKNQVEGEVQIVSTATQTFLATCINGVCWTVYHGAGTRTIASPKGPVIQTYTNVDQDLVGWPAPQGSRSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGGPLLCPTGHAVGLFRAAVCTRGVAKAVDFIPVENLETTMRSPVFTDNSSPPAVPQSFQVAHLHAPTGSGKSTKVPAAYAAKGYKVLVLNPSVAATLGFGAYMSKAHGVDPNIRTGVRTITTGSPITYSTYGKFLADAGCSGGAYDIIICDECHSTDATSISGIGTVLDQAETAGARLVVLATATPPGSVTVSHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRHLIFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVVSTDALMTGFTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGKPGIYRFVAPGERPSGMFDSSVLCECYDAGCAWYELTPAETTVRLRAYMNTPGLPVCQDHLGFWEGVFTGLTHIDAHFLSQTKQSGENFPYLVAYQATVCARAQAPPPSWDQMRKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMTCMSADLEVVTSTWVLVGGVLAALAAYCLSTGCVVIVGRIVLSGKPAIIPDREVLYQEFDEMEECSQHLPYIEQGMMLAEQFKQKALGLLQTASRHAEVITPAVQTNWQKLEVFWAKHMWNFISGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTGQTLLFNILGGWVAAQLAAPGAATAFVGAGLAGAALDSVGLGKVLVDILAGYGAGVAGALVAFKIMSGEVPSTEDLVNLLPAILSPGALAVGVVFASILRRRVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTAILSSLTVTQLLRRLHQWISSECTTPCSGSWLRDIWDWICEVLSDFKTWLKAKLMPQLPGIPFVSCQRGYRGVWRGDGIMHTRCHCGAEITGHVKNGTMRIVGPRTCKNMWSGTFFINAYTTGPCTPLPAPNYKFALWRVSAEEYVEIRRVGDFHYVSGMTTDNLKCPCQIPSPEFFTELDGVRLHRFAPPCKPLLREEVSFRVGLHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAAGRRLARGSPPSMASSSASQLSAPSLKATCTANHDSPDAELIEANLLWRQEMGGNITRVESENKVVILDSFDPLVAEEDEREVSVPAEILRKSRRFAPALPVWARPDYNPLLVETWKKPDYEPPVVHGCPLPPPRSPPVPPPRKKRTVVLTESTLPTALAELATKSFGSSSTSGITGDNTTTSSEPAPSGCPPDSDVESYSSMPPLEGEPGDPDLSDGSWSTVSSGADTEDVVCCSMSYSWTGALVTPCAAEEQKLPINALSNSLLRHHNLVYSTTSRSACQRKKKVTFDRLQVLDSHYQDVLKEVKAAASKVKANLLSVEEACSLAPPHSAKSKFGYGAKDVRCHARKAVAHINSVWKDLLEDSVTPIDTTIMAKNEVFCVQPEKGGRKPARLIVFPDLGVRVCEKMALYDVVSKLPLAVMGSSYGFQYSPGQRVEFLVQAWKSKKTPMGLSYDTRCFDSTVTESDIRTEEAIYQCCDLDPQARVAIKSLTERLYVGGPLTNSRGENCGYRRCRASRVLTTSCGNTLTRYIKARAACRAAGLQDCTMLVCGDDLVVICESAGVQEDAASLRAFTEAMTRYSAPPGDPPQPEYDLELITSCSSNVSVAHDGAGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMFAPTLWARMILMTHFFSVLIARDQLEQALNCEIYGACYSIEPLDLPPIIQRLHGLSAFSLHSYSPGEINRVAACLRKLGVPPLRAWRHRAWSVRARLLARGGKAAICGKYLFNWAVRTKLKLTPITAAGRLDLSGWFTAGYSGGDIYHSVSHARPRWFWFCLLLLAAGVGIYLLPNR | ||||||
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_0000037568 | 178-191 | ER anchor for the core protein, removed in mature form by host signal peptidase | |||
Sequence: LLALLSCLTVPASA | ||||||
Chain | PRO_0000037569 | 192-383 | Envelope glycoprotein E1 | |||
Sequence: YQVRNSSGLYHVTNDCPNSSVVYEAADAILHTPGCVPCVREGNASRCWVAVTPTVATRDGKLPTTQLRRHIDLLVGSATLCSALYVGDLCGSVFLVGQLFTFSPRHHWTTQDCNCSIYPGHITGHRMAWNMMMNWSPTAALVVAQLLRIPQAIMDMIAGAHWGVLAGIKYFSMVGNWAKVLVVLLLFAGVDA | ||||||
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 | 305 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Chain | PRO_0000037570 | 384-746 | Envelope glycoprotein E2 | |||
Sequence: ETHVTGGNAGRTTAGLVGLLTPGAKQNIQLINTNGSWHINSTALNCNESLNTGWLAGLFYQHKFNSSGCPERLASCRRLTDFAQGWGPISYANGSGLDERPYCWHYPPRPCGIVPAKSVCGPVYCFTPSPVVVGTTDRSGAPTYSWGANDTDVFVLNNTRPPLGNWFGCTWMNSTGFTKVCGAPPCVIGGVGNNTLLCPTDCFRKYPEATYSRCGSGPRITPRCMVDYPYRLWHYPCTINYTIFKVRMYVGGVEHRLEAACNWTRGERCDLEDRDRSELSPLLLSTTQWQVLPCSFTTLPALSTGLIHLHQNIVDVQYLYGVGSSIASWAIKWEYVVLLFLLLADARVCSCLWMMLLISQAEA | ||||||
Glycosylation | 417 | N-linked (GlcNAc...) (high mannose) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 423 | N-linked (GlcNAc...) (high mannose) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 429↔552 | |||||
Sequence: CNESLNTGWLAGLFYQHKFNSSGCPERLASCRRLTDFAQGWGPISYANGSGLDERPYCWHYPPRPCGIVPAKSVCGPVYCFTPSPVVVGTTDRSGAPTYSWGANDTDVFVLNNTRPPLGNWFGC | ||||||
Glycosylation | 430 | N-linked (GlcNAc...) (high mannose) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 448 | N-linked (GlcNAc...) (high mannose) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 452↔459 | |||||
Sequence: CPERLASC | ||||||
Glycosylation | 476 | N-linked (GlcNAc...) (high mannose) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 486↔494 | |||||
Sequence: CWHYPPRPC | ||||||
Disulfide bond | 503↔508 | |||||
Sequence: CGPVYC | ||||||
Glycosylation | 532 | N-linked (GlcNAc...) (high mannose) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 540 | N-linked (GlcNAc...) (high mannose) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 556 | N-linked (GlcNAc...) (high mannose) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 564↔569 | |||||
Sequence: CGAPPC | ||||||
Glycosylation | 576 | N-linked (GlcNAc...) (high mannose) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 581↔585 | |||||
Sequence: CPTDC | ||||||
Disulfide bond | 597↔620 | |||||
Sequence: CGSGPRITPRCMVDYPYRLWHYPC | ||||||
Disulfide bond | 607↔644 | |||||
Sequence: CMVDYPYRLWHYPCTINYTIFKVRMYVGGVEHRLEAAC | ||||||
Glycosylation | 623 | N-linked (GlcNAc...) (high mannose) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 645 | N-linked (GlcNAc...) (high mannose) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 652↔677 | |||||
Sequence: CDLEDRDRSELSPLLLSTTQWQVLPC | ||||||
Chain | PRO_0000037571 | 747-809 | Viroporin p7 | |||
Sequence: ALENLVILNAASLAGTHGLVSFLVFFCFAWYLKGRWVPGAVYALYGMWPLLLLLLALPQRAYA | ||||||
Chain | PRO_0000037572 | 810-1026 | Protease NS2 | |||
Sequence: LDTEVAASCGGVVLVGLMALTLSPYYKRYISWCMWWLQYFLTRVEAQLHVWVPPLNVRGGRDAVILLTCVVHPALVFDITKLLLAIFGPLWILQASLLKVPYFVRVQGLLRICALARKIAGGHYVQMAIIKLGALTGTCVYNHLAPLRDWAHNGLRDLAVAVEPVVFSRMETKLITWGADTAACGDIINGLPVSARRGQEILLGPADGMVSKGWRLL | ||||||
Lipidation | 922 | S-palmitoyl cysteine; by host | ||||
Sequence: C | ||||||
Chain | PRO_0000037573 | 1027-1657 | Serine protease/helicase NS3 | |||
Sequence: APITAYAQQTRGLLGCIITSLTGRDKNQVEGEVQIVSTATQTFLATCINGVCWTVYHGAGTRTIASPKGPVIQTYTNVDQDLVGWPAPQGSRSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGGPLLCPTGHAVGLFRAAVCTRGVAKAVDFIPVENLETTMRSPVFTDNSSPPAVPQSFQVAHLHAPTGSGKSTKVPAAYAAKGYKVLVLNPSVAATLGFGAYMSKAHGVDPNIRTGVRTITTGSPITYSTYGKFLADAGCSGGAYDIIICDECHSTDATSISGIGTVLDQAETAGARLVVLATATPPGSVTVSHPNIEEVALSTTGEIPFYGKAIPLEVIKGGRHLIFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVVSTDALMTGFTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTLPQDAVSRTQRRGRTGRGKPGIYRFVAPGERPSGMFDSSVLCECYDAGCAWYELTPAETTVRLRAYMNTPGLPVCQDHLGFWEGVFTGLTHIDAHFLSQTKQSGENFPYLVAYQATVCARAQAPPPSWDQMRKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMTCMSADLEVVT | ||||||
Chain | PRO_0000037574 | 1658-1711 | Non-structural protein 4A | |||
Sequence: STWVLVGGVLAALAAYCLSTGCVVIVGRIVLSGKPAIIPDREVLYQEFDEMEEC | ||||||
Chain | PRO_0000037575 | 1712-1972 | Non-structural protein 4B | |||
Sequence: SQHLPYIEQGMMLAEQFKQKALGLLQTASRHAEVITPAVQTNWQKLEVFWAKHMWNFISGIQYLAGLSTLPGNPAIASLMAFTAAVTSPLTTGQTLLFNILGGWVAAQLAAPGAATAFVGAGLAGAALDSVGLGKVLVDILAGYGAGVAGALVAFKIMSGEVPSTEDLVNLLPAILSPGALAVGVVFASILRRRVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTAILSSLTVTQLLRRLHQWISSECTTPC | ||||||
Lipidation | 1968 | S-palmitoyl cysteine; by host | ||||
Sequence: C | ||||||
Lipidation | 1972 | S-palmitoyl cysteine; by host; partial | ||||
Sequence: C | ||||||
Chain | PRO_0000037576 | 1973-2420 | Non-structural protein 5A | |||
Sequence: SGSWLRDIWDWICEVLSDFKTWLKAKLMPQLPGIPFVSCQRGYRGVWRGDGIMHTRCHCGAEITGHVKNGTMRIVGPRTCKNMWSGTFFINAYTTGPCTPLPAPNYKFALWRVSAEEYVEIRRVGDFHYVSGMTTDNLKCPCQIPSPEFFTELDGVRLHRFAPPCKPLLREEVSFRVGLHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAAGRRLARGSPPSMASSSASQLSAPSLKATCTANHDSPDAELIEANLLWRQEMGGNITRVESENKVVILDSFDPLVAEEDEREVSVPAEILRKSRRFAPALPVWARPDYNPLLVETWKKPDYEPPVVHGCPLPPPRSPPVPPPRKKRTVVLTESTLPTALAELATKSFGSSSTSGITGDNTTTSSEPAPSGCPPDSDVESYSSMPPLEGEPGDPDLSDGSWSTVSSGADTEDVVCC | ||||||
Modified residue | 2194 | Phosphoserine; by host; in p56 | ||||
Sequence: S | ||||||
Modified residue | 2197 | Phosphoserine; by host; in p58 | ||||
Sequence: S | ||||||
Modified residue | 2201 | Phosphoserine; by host; in p56 and p58, regulates intracellular NS5A distribution | ||||
Sequence: S | ||||||
Modified residue | 2204 | Phosphoserine; by host; in p58 | ||||
Sequence: S | ||||||
Modified residue | 2207 | Phosphoserine; by host; in p58 | ||||
Sequence: S | ||||||
Modified residue | 2210 | Phosphoserine; by host; in p58 | ||||
Sequence: S | ||||||
Modified residue | 2321 | Phosphoserine; by host | ||||
Sequence: S | ||||||
Cross-link | 2350 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Chain | PRO_0000037577 | 2421-3011 | RNA-directed RNA polymerase | |||
Sequence: SMSYSWTGALVTPCAAEEQKLPINALSNSLLRHHNLVYSTTSRSACQRKKKVTFDRLQVLDSHYQDVLKEVKAAASKVKANLLSVEEACSLAPPHSAKSKFGYGAKDVRCHARKAVAHINSVWKDLLEDSVTPIDTTIMAKNEVFCVQPEKGGRKPARLIVFPDLGVRVCEKMALYDVVSKLPLAVMGSSYGFQYSPGQRVEFLVQAWKSKKTPMGLSYDTRCFDSTVTESDIRTEEAIYQCCDLDPQARVAIKSLTERLYVGGPLTNSRGENCGYRRCRASRVLTTSCGNTLTRYIKARAACRAAGLQDCTMLVCGDDLVVICESAGVQEDAASLRAFTEAMTRYSAPPGDPPQPEYDLELITSCSSNVSVAHDGAGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMFAPTLWARMILMTHFFSVLIARDQLEQALNCEIYGACYSIEPLDLPPIIQRLHGLSAFSLHSYSPGEINRVAACLRKLGVPPLRAWRHRAWSVRARLLARGGKAAICGKYLFNWAVRTKLKLTPITAAGRLDLSGWFTAGYSGGDIYHSVSHARPRWFWFCLLLLAAGVGIYLLPNR | ||||||
Modified residue | 2449 | Phosphoserine; by host | ||||
Sequence: S | ||||||
Modified residue | 2462 | Phosphoserine; by host | ||||
Sequence: S |
Post-translational modification
Genome polyprotein
The structural proteins, core, E1, E2 and p7 are produced by proteolytic processing by host signal peptidases (PubMed:15247249).
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 (PubMed:15247249, PubMed:7679746, PubMed:8035505, PubMed:8189513, PubMed:8386278).
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
Mature core protein
Envelope glycoprotein E1
Envelope glycoprotein E2
Protease NS2
Non-structural protein 4B
Non-structural protein 5A
Non-structural protein 5A
Ubiquitination, most probably at Lys-2350, mediated by host IFI27 and SKP2 leads to proteasomal degradation, restricting viral infection (PubMed:27194766).
Ubiquitination by host TRIM22 leads to interruption of viral replication (PubMed:25683609).
Non-structural protein 5A
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, PI4KA or RPS6KB1 kinases may be responsible for NS5A phosphorylation (By similarity).
Phosphorylated NS5A is involved in viral replication (By similarity).
Non-structural protein 5A
RNA-directed RNA polymerase
Keywords
- PTM
PTM databases
Expression
Interaction
Subunit
Mature core protein
Interacts with E1 (via C-terminus) (PubMed:8764026).
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 (PubMed:23799612).
Interacts with host STAT3; this interaction constitutively activates STAT3 (By similarity).
Associates 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 (PubMed:19486448).
Interacts with host C1QR1 (PubMed:11086025).
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 (via N-terminus) with host EIF2AK2/PKR (via N-terminus); 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
Interacts with mature core protein (PubMed:8764026).
Interacts with protease NS2 (PubMed:21147927).
The heterodimer E1/E2 interacts with host CLDN1; this interaction plays a role in viral entry into host cell (PubMed:24038151).
Interacts with host SPSB2 (via C-terminus) (PubMed:31344133).
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 (PubMed:30111563).
Envelope glycoprotein E2
Interacts with host CD81 and SCARB1 receptors; these interactions play a role in viral entry into host cell (PubMed:12356718, PubMed:12913001, PubMed:12970454).
Interacts with host EIF2AK2/PKR; this interaction inhibits EIF2AK2 and probably allows the virus to evade the innate immune response (PubMed:10390359).
Interacts with host CD209/DC-SIGN and CLEC4M/DC-SIGNR (PubMed:15371595).
Interact with host SPCS1; this interaction is essential for viral particle assembly (By similarity).
Interacts with protease NS2 (PubMed:21147927).
The heterodimer E1/E2 interacts with host CLDN1; this interaction plays a role in viral entry into host cell (PubMed:24038151).
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 (PubMed:30341327).
Interacts with human PLSCR1 (By similarity).
Viroporin p7
Homoheptamer (By similarity).
Interacts with protease NS2 (By similarity).
Protease NS2
Interacts with host SPCS1; this interaction is essential for viral particle assembly (By similarity).
Interacts with envelope glycoprotein E1 (PubMed:21147927).
Interacts with envelope glycoprotein E2 (PubMed:21147927).
Interacts with viroporin p7 (By similarity).
Interacts with serine protease/helicase NS3 (PubMed:21147927).
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 (PubMed:12692242, PubMed:12692249).
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 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 (PubMed:7769699, PubMed:8861917).
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 (PubMed:16177806, PubMed:16301520).
Interacts with host TICAM1; this interaction leads to the cleavage and inhibition of host TICAM1 (PubMed:16177806, PubMed:16301520).
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 (PubMed:12021330, PubMed:12692242, PubMed:12692249).
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
NS3-NS4A interaction is essential for NS3 activation and allows membrane anchorage of the latter (PubMed:7769699, PubMed:8861917).
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 (PubMed:12021330, PubMed:12692242, PubMed:12692249).
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
Interacts with non-structural protein NS5A (PubMed:23868571).
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 (PubMed:23542348).
Interacts with host METTL22; this interaction may promote the recruitment of NS4B in the proximity of lipid droplet (PubMed:26185986).
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 (PubMed:12021330, PubMed:12692242, PubMed:12692249).
Non-structural protein 5A
Homodimer; dimerization is required for RNA-binding (PubMed:20926572).
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 (PubMed:23868571).
Interacts (via region D2) with RNA-directed RNA polymerase (Probable). 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 (PubMed:12021330, PubMed:12692242, PubMed:12692249).
Interacts with host GRB2 (By similarity).
Interacts with host BIN1 (PubMed:16530520).
Interacts with host PIK3R1 (By similarity).
Interacts with host SRCAP (PubMed:10702287).
Interacts with host FKBP8 (By similarity).
Interacts (via C-terminus) with host VAPB (via MSP domain) (Probable) (PubMed:22720086).
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 (Probable). 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 (PubMed:31801866).
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 (PubMed:27194766).
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 (PubMed:28743875).
Interacts (via N-terminus) with host CIDEB (via N-terminus); this interaction seems to regulate the association of HCV particles with APOE (PubMed:27282740).
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 (PubMed:31344133).
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 (Probable). Interacts with host TRIM14; this interaction induces the degradation of NS5A (PubMed:27578425).
RNA-directed RNA polymerase
Interacts with host VAPB (By similarity).
Interacts with host PRK2/PKN2 (PubMed:15364941).
Interacts with host HNRNPA1 and SEPT6; these interactions facilitate the viral replication (PubMed:17229681).
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 (PubMed:12021330, PubMed:12692242, PubMed:12692249).
Binary interactions
Protein-protein interaction databases
Chemistry
Structure
Family & Domains
Features
Showing features for region, motif, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 2-23 | Interaction with STAT1 | ||||
Sequence: STNPKPQRKTKRNTNRRPQDVK | ||||||
Region | 2-58 | Interaction with EIF2AK2/PKR | ||||
Sequence: STNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQP | ||||||
Region | 2-59 | Interaction with DDX3X | ||||
Sequence: STNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPR | ||||||
Region | 2-75 | Disordered | ||||
Sequence: STNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRT | ||||||
Motif | 5-13 | Nuclear localization signal | ||||
Sequence: PKPQRKTKR | ||||||
Motif | 38-43 | Nuclear localization signal | ||||
Sequence: PRRGPR | ||||||
Compositional bias | 47-69 | Basic and acidic residues | ||||
Sequence: RATRKTSERSQPRGRRQPIPKAR | ||||||
Motif | 58-64 | Nuclear localization signal | ||||
Sequence: PRGRRQP | ||||||
Motif | 66-71 | Nuclear localization signal | ||||
Sequence: PKARRP | ||||||
Region | 112-152 | Important for endoplasmic reticulum and mitochondrial localization | ||||
Sequence: PRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALA | ||||||
Region | 122-173 | Interaction with APOA2 | ||||
Sequence: VIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLPGCS | ||||||
Region | 164-167 | Important for lipid droplets localization | ||||
Sequence: YATG | ||||||
Region | 265-296 | Important for fusion | ||||
Sequence: LVGSATLCSALYVGDLCGSVFLVGQLFTFSPR | ||||||
Region | 385-411 | HVR1 | ||||
Sequence: THVTGGNAGRTTAGLVGLLTPGAKQNI | ||||||
Region | 474-479 | HVR2 | ||||
Sequence: YANGSG | ||||||
Region | 480-493 | CD81-binding 1 | ||||
Sequence: LDERPYCWHYPPRP | ||||||
Region | 544-551 | CD81-binding 2 | ||||
Sequence: PPLGNWFG | ||||||
Region | 660-671 | EIF2AK2/eIF2-alpha phosphorylation homology domain (PePHD) | ||||
Sequence: SELSPLLLSTTQ | ||||||
Domain | 899-1026 | Peptidase C18 | ||||
Sequence: LWILQASLLKVPYFVRVQGLLRICALARKIAGGHYVQMAIIKLGALTGTCVYNHLAPLRDWAHNGLRDLAVAVEPVVFSRMETKLITWGADTAACGDIINGLPVSARRGQEILLGPADGMVSKGWRLL | ||||||
Region | 904-1206 | Protease NS2-3 | ||||
Sequence: ASLLKVPYFVRVQGLLRICALARKIAGGHYVQMAIIKLGALTGTCVYNHLAPLRDWAHNGLRDLAVAVEPVVFSRMETKLITWGADTAACGDIINGLPVSARRGQEILLGPADGMVSKGWRLLAPITAYAQQTRGLLGCIITSLTGRDKNQVEGEVQIVSTATQTFLATCINGVCWTVYHGAGTRTIASPKGPVIQTYTNVDQDLVGWPAPQGSRSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGGPLLCPTGHAVGLFRAAVCTRGVAKAVDFIPVENLETTMR | ||||||
Region | 929-949 | Interaction with host SCPS1 | ||||
Sequence: AGGHYVQMAIIKLGALTGTCV | ||||||
Domain | 1027-1208 | Peptidase S29 | ||||
Sequence: APITAYAQQTRGLLGCIITSLTGRDKNQVEGEVQIVSTATQTFLATCINGVCWTVYHGAGTRTIASPKGPVIQTYTNVDQDLVGWPAPQGSRSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPISYLKGSSGGPLLCPTGHAVGLFRAAVCTRGVAKAVDFIPVENLETTMRSP | ||||||
Domain | 1217-1369 | Helicase ATP-binding | ||||
Sequence: PAVPQSFQVAHLHAPTGSGKSTKVPAAYAAKGYKVLVLNPSVAATLGFGAYMSKAHGVDPNIRTGVRTITTGSPITYSTYGKFLADAGCSGGAYDIIICDECHSTDATSISGIGTVLDQAETAGARLVVLATATPPGSVTVSHPNIEEVALST | ||||||
Motif | 1316-1319 | DECH box | ||||
Sequence: DECH | ||||||
Region | 1486-1497 | RNA-binding | ||||
Sequence: QRRGRTGRGKPG | ||||||
Region | 1679-1690 | NS3-binding | ||||
Sequence: CVVIVGRIVLSG | ||||||
Region | 1833-1861 | Glycine zipper | ||||
Sequence: GLAGAALDSVGLGKVLVDILAGYGAGVAG | ||||||
Region | 1978-1998 | Membrane-binding | ||||
Sequence: RDIWDWICEVLSDFKTWLKAK | ||||||
Region | 2005-2221 | D1; RNA-binding | ||||
Sequence: GIPFVSCQRGYRGVWRGDGIMHTRCHCGAEITGHVKNGTMRIVGPRTCKNMWSGTFFINAYTTGPCTPLPAPNYKFALWRVSAEEYVEIRRVGDFHYVSGMTTDNLKCPCQIPSPEFFTELDGVRLHRFAPPCKPLLREEVSFRVGLHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAAGRRLARGSPPSMASSSASQLSAPSLKATCTANHDS | ||||||
Region | 2120-2208 | FKBP8-binding | ||||
Sequence: EFFTELDGVRLHRFAPPCKPLLREEVSFRVGLHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAAGRRLARGSPPSMASSSASQLSA | ||||||
Region | 2120-2332 | Transcriptional activation | ||||
Sequence: EFFTELDGVRLHRFAPPCKPLLREEVSFRVGLHEYPVGSQLPCEPEPDVAVLTSMLTDPSHITAEAAGRRLARGSPPSMASSSASQLSAPSLKATCTANHDSPDAELIEANLLWRQEMGGNITRVESENKVVILDSFDPLVAEEDEREVSVPAEILRKSRRFAPALPVWARPDYNPLLVETWKKPDYEPPVVHGCPLPPPRSPPVPPPRKKRT | ||||||
Region | 2135-2139 | Interaction with non-structural protein 4A | ||||
Sequence: PPCKP | ||||||
Region | 2189-2441 | Interaction with host SKP2 | ||||
Sequence: RLARGSPPSMASSSASQLSAPSLKATCTANHDSPDAELIEANLLWRQEMGGNITRVESENKVVILDSFDPLVAEEDEREVSVPAEILRKSRRFAPALPVWARPDYNPLLVETWKKPDYEPPVVHGCPLPPPRSPPVPPPRKKRTVVLTESTLPTALAELATKSFGSSSTSGITGDNTTTSSEPAPSGCPPDSDVESYSSMPPLEGEPGDPDLSDGSWSTVSSGADTEDVVCCSMSYSWTGALVTPCAAEEQKL | ||||||
Region | 2210-2249 | ISDR | ||||
Sequence: SLKATCTANHDSPDAELIEANLLWRQEMGGNITRVESENK | ||||||
Region | 2210-2275 | Interaction with EIF2AK2/PKR | ||||
Sequence: SLKATCTANHDSPDAELIEANLLWRQEMGGNITRVESENKVVILDSFDPLVAEEDEREVSVPAEIL | ||||||
Region | 2223-2315 | D2 | ||||
Sequence: DAELIEANLLWRQEMGGNITRVESENKVVILDSFDPLVAEEDEREVSVPAEILRKSRRFAPALPVWARPDYNPLLVETWKKPDYEPPVVHGCP | ||||||
Region | 2224-2315 | Disordered | ||||
Sequence: AELIEANLLWRQEMGGNITRVESENKVVILDSFDPLVAEEDEREVSVPAEILRKSRRFAPALPVWARPDYNPLLVETWKKPDYEPPVVHGCP | ||||||
Region | 2249-2306 | NS4B-binding | ||||
Sequence: KVVILDSFDPLVAEEDEREVSVPAEILRKSRRFAPALPVWARPDYNPLLVETWKKPDY | ||||||
Region | 2281-2297 | Interaction with human PPIA/CYPA | ||||
Sequence: FAPALPVWARPDYNPLL | ||||||
Compositional bias | 2312-2329 | Pro residues | ||||
Sequence: HGCPLPPPRSPPVPPPRK | ||||||
Motif | 2322-2325 | SH3-binding | ||||
Sequence: PPVP | ||||||
Motif | 2326-2334 | Nuclear localization signal | ||||
Sequence: PPRKKRTVV | ||||||
Region | 2329-2420 | D3 | ||||
Sequence: KKRTVVLTESTLPTALAELATKSFGSSSTSGITGDNTTTSSEPAPSGCPPDSDVESYSSMPPLEGEPGDPDLSDGSWSTVSSGADTEDVVCC | ||||||
Region | 2332-2441 | Interaction with host IFI27 | ||||
Sequence: TVVLTESTLPTALAELATKSFGSSSTSGITGDNTTTSSEPAPSGCPPDSDVESYSSMPPLEGEPGDPDLSDGSWSTVSSGADTEDVVCCSMSYSWTGALVTPCAAEEQKL | ||||||
Compositional bias | 2346-2374 | Polar residues | ||||
Sequence: ELATKSFGSSSTSGITGDNTTTSSEPAPS | ||||||
Region | 2346-2409 | Disordered | ||||
Sequence: ELATKSFGSSSTSGITGDNTTTSSEPAPSGCPPDSDVESYSSMPPLEGEPGDPDLSDGSWSTVS | ||||||
Region | 2354-2377 | V3 | ||||
Sequence: SSSTSGITGDNTTTSSEPAPSGCP | ||||||
Region | 2367-2417 | Interaction with host VAPB | ||||
Sequence: TSSEPAPSGCPPDSDVESYSSMPPLEGEPGDPDLSDGSWSTVSSGADTEDV | ||||||
Domain | 2634-2752 | RdRp catalytic | ||||
Sequence: PMGLSYDTRCFDSTVTESDIRTEEAIYQCCDLDPQARVAIKSLTERLYVGGPLTNSRGENCGYRRCRASRVLTTSCGNTLTRYIKARAACRAAGLQDCTMLVCGDDLVVICESAGVQED |
Domain
Mature core protein
This disordered region also seems to play an important role in mediating RNA chaperoning (PubMed:18033802).
Envelope glycoprotein E1
Envelope glycoprotein E2
Envelope E2 glycoprotein contain two highly variable regions called hypervariable region 1 and 2 (HVR1 and HVR2) (PubMed:11356980).
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 (PubMed:22767607).
Protease NS2
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
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 (PubMed:1658800).
Non-structural protein 4B
Non-structural protein 5A
The C-terminus contains a nuclear localization signal (PubMed:8982089).
Non-structural protein 5A
ISDR and V3 may be involved in sensitivity and/or resistance to IFN-alpha therapy (By similarity).
Non-structural protein 5A
Non-structural protein 5A
Non-structural protein 5A
The largely disordered region D3 mediates the interaction with several host proteins and is involved in virion assembly (PubMed:22720086, PubMed:26727512, PubMed:27194766).
Sequence similarities
Keywords
- Domain
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Ribosomal frameshifting. The exact location of the ribosomal frameshift is unknown. The F protein seems to be generated by a -2 ribosomal frameshift located in the vicinity of codon 11 of the core protein coding sequence. However, some F proteins may also be generated by +1 ribosomal frameshift. Since the core gene encodes alternative reading frame proteins (ARFPs), many functions depicted for the core protein might belong to the ARFPs.
P27958-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- NameGenome polyprotein
- Length3,011
- Mass (Da)327,146
- Last updated2007-01-23 v3
- Checksum772CBB29CCD94753
P0C045-1
The sequence of this isoform can be found in the external entry linked below. Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
View isoform- NameF protein
- SynonymsFrameshifted protein
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 47-69 | Basic and acidic residues | ||||
Sequence: RATRKTSERSQPRGRRQPIPKAR | ||||||
Compositional bias | 2312-2329 | Pro residues | ||||
Sequence: HGCPLPPPRSPPVPPPRK | ||||||
Compositional bias | 2346-2374 | Polar residues | ||||
Sequence: ELATKSFGSSSTSGITGDNTTTSSEPAPS |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M67463 EMBL· GenBank· DDBJ | AAA45534.1 EMBL· GenBank· DDBJ | Genomic RNA | ||
AF009606 EMBL· GenBank· DDBJ | AAB66324.1 EMBL· GenBank· DDBJ | Genomic RNA | ||
AF011751 EMBL· GenBank· DDBJ | AAB67036.1 EMBL· GenBank· DDBJ | Genomic RNA | ||
AF011752 EMBL· GenBank· DDBJ | AAB67037.1 EMBL· GenBank· DDBJ | Genomic RNA | ||
AF011753 EMBL· GenBank· DDBJ | AAB67038.1 EMBL· GenBank· DDBJ | Genomic RNA |