Protein: Genome polyprotein [Cleaved into: Core protein precursor (Capsid protein C) (p23); Mature core protein (p21); Envelope glycoprotein E1 (gp32) (gp35); Envelope glycoprotein E2 (NS1) (gp68) (gp70); Viroporin p7; Protease NS2 (p23) (EC 3.4.22.-); Serine protease/helicase NS3 (EC 3.4.21.98) (EC 3.6.1.15) (EC 3.6.4.13) (Hepacivirin) (NS3 helicase) (NS3 protease) (NS3P) (Viroporin p70); Non-structural protein 4A (NS4A) (p8); Non-structural protein 4B (NS4B) (p27); Non-structural protein 5A (NS5A) (p56/58); RNA-directed RNA polymerase (EC 2.7.7.48) (NS5B) (p68)] (P26663)
Organism: Hepatitis C virus genotype 1b (isolate BK) (HCV)
Function: Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (Probable). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).
Subcellular location: [Core protein precursor]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P26664}; Single-pass membrane protein {ECO:0000255}. Host mitochondrion membrane {ECO:0000250|UniProtKB:P26664}; Single-pass type I membrane protein {ECO:0000255}. Note=The C-terminal transmembrane domain of the core protein precursor contains an ER signal leading the nascent polyprotein to the ER membrane.; SUBCELLULAR LOCATION: [Mature core protein]: Virion {ECO:0000250|UniProtKB:Q99IB8}. Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000269|PubMed:17188392}. Note=Only a minor proportion of core protein is present in the nucleus (By similarity). Probably present on the surface of lipid droplets (PubMed:17188392). {ECO:0000250|UniProtKB:P27958, ECO:0000269|PubMed:17188392}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E1]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E2]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Viroporin p7]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P27958}. Host cell membrane {ECO:0000250|UniProtKB:P27958}. Note=The C-terminus of p7 membrane domain acts as a signal sequence (By similarity). After cleavage by host signal peptidase, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). ER retention of p7 is leaky and a small fraction reaches the plasma membrane (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Protease NS2]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Probably present on the surface of lipid droplets. {ECO:0000250|UniProtKB:Q99IB8}.; SUBCELLULAR LOCATION: [Serine protease/helicase NS3]: Host endoplasmic reticulum membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=NS3 is associated to the ER membrane through its binding to NS4A. {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic reticulum membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Note=Host membrane insertion occurs after processing by the NS3 protease.; SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Note=A reorientation of the N-terminus into the ER lumen occurs post-translationally. {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Non-structural protein 5A]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Peripheral membrane protein {ECO:0000250|UniProtKB:P27958}. Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P26662}. Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Host membrane insertion occurs after processing by the NS3 protease (By similarity). Localizes at the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host endoplasmic reticulum membrane; Single-pass type IV membrane protein {ECO:0000250|UniProtKB:P27958}. Note=Host membrane insertion occurs after processing by the NS3 protease. {ECO:0000250|UniProtKB:P27958}.
Sequence: MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRAPRKTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGLGWAGWLLSPRGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLPGCSFSIFLLALLSCLTTPASAYEVHNVSGIYHVTNDCSNASIVYEAADLIMHTPGCVPCVREGNSSRCWVALTPTLAARNVTIPTTTIRRHVDLLVGAAAFCSAMYVGDLCGSVFLVSQLFTFSPRRHVTLQDCNCSIYPGHVSGHRMAWDMMMNWSPTTALVVSQLLRIPQAVVDMVAGAHWGVLAGLAYYSMAGNWAKVLIVMLLFAGVDGDTHVTGGAQAKTTNRLVSMFASGPSQKIQLINTNGSWHINRTALNCNDSLQTGFLAALFYTHSFNSSGCPERMAQCRTIDKFDQGWGPITYAESSRSDQRPYCWHYPPPQCTIVPASEVCGPVYCFTPSPVVVGTTDRFGVPTYRWGENETDVLLLNNTRPPQGNWFGCTWMNSTGFTKTCGGPPCNIGGVGNNTLTCPTDCFRKHPEATYTKCGSGPWLTPRCMVDYPYRLWHYPCTVNFTIFKVRMYVGGVEHRLNAACNWTRGERCDLEDRDRPELSPLLLSTTEWQVLPCSFTTLPALSTGLIHLHQNIVDVQYLYGIGSAVVSFAIKWEYVLLLFLLLADARVCACLWMMLLIAQAEAALENLVVLNSASVAGAHGILSFLVFFCAAWYIKGRLVPGATYALYGVWPLLLLLLALPPRAYAMDREMAASCGGAVFVGLVLLTLSPYYKVFLARLIWWLQYFTTRAEADLHVWIPPLNARGGRDAIILLMCAVHPELIFDITKLLIAILGPLMVLQAGITRVPYFVRAQGLIHACMLVRKVAGGHYVQMAFMKLGALTGTYIYNHLTPLRDWPRAGLRDLAVAVEPVVFSDMETKIITWGADTAACGDIILGLPVSARRGKEILLGPADSLEGRGLRLLAPITAYSQQTRGLLGCIITSLTGRDKNQVEGEVQVVSTATQSFLATCVNGVCWTVYHGAGSKTLAAPKGPITQMYTNVDQDLVGWPKPPGARSLTPCTCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPVSYLKGSSGGPLLCPFGHAVGIFRAAVCTRGVAKAVDFVPVESMETTMRSPVFTDNSSPPAVPQSFQVAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTITTGAPVTYSTYGKFLADGGCSGGAYDIIICDECHSTDSTTILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALSNTGEIPFYGKAIPIEAIRGGRHLIFCHSKKKCDELAAKLSGLGINAVAYYRGLDVSVIPTIGDVVVVATDALMTGYTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGRRGIYRFVTPGERPSGMFDSSVLCECYDAGCAWYELTPAETSVRLRAYLNTPGLPVCQDHLEFWESVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARAQAPPPSWDQMWKCLIRLKPTLHGPTPLLYRLGAVQNEVTLTHPITKYIMACMSADLEVVTSTWVLVGGVLAALAAYCLTTGSVVIVGRIILSGRPAIVPDRELLYQEFDEMEECASHLPYIEQGMQLAEQFKQKALGLLQTATKQAEAAAPVVESKWRALETFWAKHMWNFISGIQYLAGLSTLPGNPAIASLMAFTASITSPLTTQSTLLFNILGGWVAAQLAPPSAASAFVGAGIAGAAVGSIGLGKVLVDILAGYGAGVAGALVAFKVMSGEMPSTEDLVNLLPAILSPGALVVGVVCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQILSSLTITQLLKRLHQWINEDCSTPCSGSWLRDVWDWICTVLTDFKTWLQSKLLPQLPGVPFFSCQRGYKGVWRGDGIMQTTCPCGAQITGHVKNGSMRIVGPKTCSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAAEEYVEVTRVGDFHYVTGMTTDNVKCPCQVPAPEFFSEVDGVRLHRYAPACRPLLREEVTFQVGLNQYLVGSQLPCEPEPDVAVLTSMLTDPSHITAETAKRRLARGSPPSLASSSASQLSAPSLKATCTTHHVSPDADLIEANLLWRQEMGGNITRVESENKVVVLDSFDPLRAEEDEREVSVPAEILRKSKKFPAAMPIWARPDYNPPLLESWKDPDYVPPVVHGCPLPPIKAPPIPPPRRKRTVVLTESSVSSALAELATKTFGSSESSAVDSGTATALPDQASDDGDKGSDVESYSSMPPLEGEPGDPDLSDGSWSTVSEEASEDVVCCSMSYTWTGALITPCAAEESKLPINALSNSLLRHHNMVYATTSRSAGLRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSVEEACKLTPPHSAKSKFGYGAKDVRNLSSKAVNHIHSVWKDLLEDTVTPIDTTIMAKNEVFCVQPEKGGRKPARLIVFPDLGVRVCEKMALYDVVSTLPQVVMGSSYGFQYSPGQRVEFLVNTWKSKKNPMGFSYDTRCFDSTVTENDIRVEESIYQCCDLAPEARQAIKSLTERLYIGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKASAACRAAKLQDCTMLVNGDDLVVICESAGTQEDAASLRVFTEAMTRYSAPPGDPPQPEYDLELITSCSSNVSVAHDASGKRVYYLTRDPTTPLARAAWETARHTPVNSWLGNIIMYAPTLWARMILMTHFFSILLAQEQLEKALDCQIYGACYSIEPLDLPQIIERLHGLSAFSLHSYSPGEINRVASCLRKLGVPPLRVWRHRARSVRARLLSQGGRAATCGKYLFNWAVKTKLKLTPIPAASRLDLSGWFVAGYSGGDIYHSLSRARPRWFMLCLLLLSVGVGIYLLPNR
InterPro domains: - IPR002518: Hepatitis C virus, Non-structural protein NS2 (domain) [811-1026]
- IPR004109: Hepatitis C virus, NS3 protease (domain) [1027-1208]
- IPR002521: Hepatitis C virus, Core protein, C-terminal (domain) [116-190]
- IPR038170: NS5A domain 1a superfamily (homologous_superfamily) [2014-2074]
- IPR009003: Peptidase S1, PA clan (homologous_superfamily) [1027-1212]
- IPR001490: Hepatitis C virus, Non-structural protein NS4b (domain) [1728-1921]
- IPR002522: Hepatitis C virus, Core protein, N-terminal (domain) [2-115]
- IPR001650: Helicase, C-terminal domain-like (domain) [1361-1538]
- IPR002868: Hepatitis C virus, Non-structural 5a protein (domain) [1974-1996]
- IPR002531: Hepatitis C virus, Non-structural protein E2/NS1 (domain) [386-729]
- IPR013193: Hepatitis C virus non-structural 5a, 1B domain (domain) [2068-2168]
- IPR011492: Non-structural protein NS3-like, DEAD-box helicase, flavivirus (domain) [1294-1355]
- IPR027417: P-loop containing nucleoside triphosphate hydrolase (homologous_superfamily) [1206-1650]
- IPR014001: Helicase superfamily 1/2, ATP-binding domain (domain) [1213-1385]
- IPR002166: RNA dependent RNA polymerase, hepatitis C virus (family) [2422-2932]
- IPR000745: Hepatitis C virus, Non-structural protein NS4a (domain) [1658-1711]
- IPR007094: RNA-directed RNA polymerase, catalytic domain (domain) [2633-2751]
- IPR002519: Hepatitis C virus, Envelope glycoprotein E1 (domain) [193-382]
- IPR024350: Hepatitus C virus, Non-structural 5a protein, C-terminal (domain) [2179-2419]
- IPR013192: Hepatitis C virus, Non-structural 5a protein, domain 1a (domain) [2006-2067]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0048519 (negative regulation of biological process), GO:0016032 (viral process), GO:0065008 (regulation of biological quality), GO:0044068 (modulation by symbiont of host cellular process), GO:0019222 (regulation of metabolic process), GO:0050794 (regulation of cellular process), GO:0035821 (modulation of process of another organism), GO:0019048 (modulation by virus of host process), GO:0044403 (biological process involved in symbiotic interaction), GO:0048523 (negative regulation of cellular process), GO:0009892 (negative regulation of metabolic process), GO:0048522 (positive regulation of cellular process), GO:0051701 (biological process involved in interaction with host), GO:0051726 (regulation of cell cycle), GO:0031341 (regulation of cell killing), GO:0009894 (regulation of catabolic process), GO:0010942 (positive regulation of cell death), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0043487 (regulation of RNA stability), GO:0052040 (modulation by symbiont of host programmed cell death), GO:0060548 (negative regulation of cell death), GO:0010941 (regulation of cell death), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0044003 (modulation by symbiont of host process), GO:0031343 (positive regulation of cell killing), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0045786 (negative regulation of cell cycle), GO:0031323 (regulation of cellular metabolic process), GO:0009895 (negative regulation of catabolic process), GO:0051709 (regulation of killing of cells of another organism), GO:0080090 (regulation of primary metabolic process), GO:0019054 (modulation by virus of host cellular process), GO:0051712 (positive regulation of killing of cells of another organism), GO:0010948 (negative regulation of cell cycle process), GO:0031324 (negative regulation of cellular metabolic process), GO:0010564 (regulation of cell cycle process), GO:0052150 (modulation by symbiont of host apoptotic process), GO:0043069 (negative regulation of programmed cell death), GO:0043489 (RNA stabilization), GO:0043067 (regulation of programmed cell death), GO:0043068 (positive regulation of programmed cell death), GO:0031330 (negative regulation of cellular catabolic process), GO:1901987 (regulation of cell cycle phase transition), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0051252 (regulation of RNA metabolic process), GO:0039526 (modulation by virus of host apoptotic process), GO:0031329 (regulation of cellular catabolic process), GO:0051253 (negative regulation of RNA metabolic process), GO:0001907 (killing by symbiont of host cells), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0010468 (regulation of gene expression), GO:1901988 (negative regulation of cell cycle phase transition), GO:0043065 (positive regulation of apoptotic process), GO:0042981 (regulation of apoptotic process), GO:0010608 (post-transcriptional regulation of gene expression), GO:1902806 (regulation of cell cycle G1/S phase transition), GO:1902807 (negative regulation of cell cycle G1/S phase transition), GO:0043066 (negative regulation of apoptotic process), GO:1902369 (negative regulation of RNA catabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0018995 (host cellular component), GO:0033643 (host cell part), GO:0043657 (host cell), GO:0033644 (host cell membrane), GO:0033646 (host intracellular part), GO:0043656 (host intracellular region), GO:0033655 (host cell cytoplasm part), GO:0033647 (host intracellular organelle), GO:0030430 (host cell cytoplasm), GO:0033648 (host intracellular membrane-bounded organelle), GO:0044164 (host cell cytosol), GO:0042025 (host cell nucleus)