Genome polyprotein
Details
- Name
- Genome polyprotein
- Synonyms
- 3.4.22.-
- p23
- Gene Name
- Not Available
- Organism
- HCV
- Amino acid sequence
>lcl|BSEQ0021293|Genome polyprotein MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRAPRKTSERSQPRG RRQPIPKARRPEGRTWAQPGYPWPLYGNEGLGWAGWLLSPRGSRPSWGPTDPRRRSRNLG KVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLPGCSFSIFLLA LLSCLTTPASAYEVHNVSGIYHVTNDCSNASIVYEAADLIMHTPGCVPCVREGNSSRCWV ALTPTLAARNVTIPTTTIRRHVDLLVGAAAFCSAMYVGDLCGSVFLVSQLFTFSPRRHVT LQDCNCSIYPGHVSGHRMAWDMMMNWSPTTALVVSQLLRIPQAVVDMVAGAHWGVLAGLA YYSMAGNWAKVLIVMLLFAGVDGDTHVTGGAQAKTTNRLVSMFASGPSQKIQLINTNGSW HINRTALNCNDSLQTGFLAALFYTHSFNSSGCPERMAQCRTIDKFDQGWGPITYAESSRS DQRPYCWHYPPPQCTIVPASEVCGPVYCFTPSPVVVGTTDRFGVPTYRWGENETDVLLLN NTRPPQGNWFGCTWMNSTGFTKTCGGPPCNIGGVGNNTLTCPTDCFRKHPEATYTKCGSG PWLTPRCMVDYPYRLWHYPCTVNFTIFKVRMYVGGVEHRLNAACNWTRGERCDLEDRDRP ELSPLLLSTTEWQVLPCSFTTLPALSTGLIHLHQNIVDVQYLYGIGSAVVSFAIKWEYVL LLFLLLADARVCACLWMMLLIAQAEAALENLVVLNSASVAGAHGILSFLVFFCAAWYIKG RLVPGATYALYGVWPLLLLLLALPPRAYAMDREMAASCGGAVFVGLVLLTLSPYYKVFLA RLIWWLQYFTTRAEADLHVWIPPLNARGGRDAIILLMCAVHPELIFDITKLLIAILGPLM VLQAGITRVPYFVRAQGLIHACMLVRKVAGGHYVQMAFMKLGALTGTYIYNHLTPLRDWP RAGLRDLAVAVEPVVFSDMETKIITWGADTAACGDIILGLPVSARRGKEILLGPADSLEG RGLRLLAPITAYSQQTRGLLGCIITSLTGRDKNQVEGEVQVVSTATQSFLATCVNGVCWT VYHGAGSKTLAAPKGPITQMYTNVDQDLVGWPKPPGARSLTPCTCGSSDLYLVTRHADVI PVRRRGDSRGSLLSPRPVSYLKGSSGGPLLCPFGHAVGIFRAAVCTRGVAKAVDFVPVES METTMRSPVFTDNSSPPAVPQSFQVAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAA TLGFGAYMSKAHGIDPNIRTGVRTITTGAPVTYSTYGKFLADGGCSGGAYDIIICDECHS TDSTTILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALSNTGEIPFYGKAI PIEAIRGGRHLIFCHSKKKCDELAAKLSGLGINAVAYYRGLDVSVIPTIGDVVVVATDAL MTGYTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGRRGIYR FVTPGERPSGMFDSSVLCECYDAGCAWYELTPAETSVRLRAYLNTPGLPVCQDHLEFWES VFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARAQAPPPSWDQMWKCLIRLKPTLHG PTPLLYRLGAVQNEVTLTHPITKYIMACMSADLEVVTSTWVLVGGVLAALAAYCLTTGSV VIVGRIILSGRPAIVPDRELLYQEFDEMEECASHLPYIEQGMQLAEQFKQKALGLLQTAT KQAEAAAPVVESKWRALETFWAKHMWNFISGIQYLAGLSTLPGNPAIASLMAFTASITSP LTTQSTLLFNILGGWVAAQLAPPSAASAFVGAGIAGAAVGSIGLGKVLVDILAGYGAGVA GALVAFKVMSGEMPSTEDLVNLLPAILSPGALVVGVVCAAILRRHVGPGEGAVQWMNRLI AFASRGNHVSPTHYVPESDAAARVTQILSSLTITQLLKRLHQWINEDCSTPCSGSWLRDV WDWICTVLTDFKTWLQSKLLPQLPGVPFFSCQRGYKGVWRGDGIMQTTCPCGAQITGHVK NGSMRIVGPKTCSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAAEEYVEVTRVGDFH YVTGMTTDNVKCPCQVPAPEFFSEVDGVRLHRYAPACRPLLREEVTFQVGLNQYLVGSQL PCEPEPDVAVLTSMLTDPSHITAETAKRRLARGSPPSLASSSASQLSAPSLKATCTTHHV SPDADLIEANLLWRQEMGGNITRVESENKVVVLDSFDPLRAEEDEREVSVPAEILRKSKK FPAAMPIWARPDYNPPLLESWKDPDYVPPVVHGCPLPPIKAPPIPPPRRKRTVVLTESSV SSALAELATKTFGSSESSAVDSGTATALPDQASDDGDKGSDVESYSSMPPLEGEPGDPDL SDGSWSTVSEEASEDVVCCSMSYTWTGALITPCAAEESKLPINALSNSLLRHHNMVYATT SRSAGLRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSVEEACKLTPPHSAKSKF GYGAKDVRNLSSKAVNHIHSVWKDLLEDTVTPIDTTIMAKNEVFCVQPEKGGRKPARLIV FPDLGVRVCEKMALYDVVSTLPQVVMGSSYGFQYSPGQRVEFLVNTWKSKKNPMGFSYDT RCFDSTVTENDIRVEESIYQCCDLAPEARQAIKSLTERLYIGGPLTNSKGQNCGYRRCRA SGVLTTSCGNTLTCYLKASAACRAAKLQDCTMLVNGDDLVVICESAGTQEDAASLRVFTE AMTRYSAPPGDPPQPEYDLELITSCSSNVSVAHDASGKRVYYLTRDPTTPLARAAWETAR HTPVNSWLGNIIMYAPTLWARMILMTHFFSILLAQEQLEKALDCQIYGACYSIEPLDLPQ IIERLHGLSAFSLHSYSPGEINRVASCLRKLGVPPLRVWRHRARSVRARLLSQGGRAATC GKYLFNWAVKTKLKLTPIPAASRLDLSGWFVAGYSGGDIYHSLSRARPRWFMLCLLLLSV GVGIYLLPNR
- Number of residues
- 3010
- Molecular Weight
- 327190.435
- Theoretical pI
- 8.14
- GO Classification
- FunctionsATP binding / ATP-dependent helicase activity / cysteine-type endopeptidase activity / identical protein binding / ion channel activity / protease binding / RNA binding / RNA-directed RNA polymerase activity / serine-type endopeptidase activity / serine-type peptidase activity / structural molecule activity / zinc ion bindingProcessesapoptotic process / clathrin-mediated endocytosis of virus by host cell / fusion of virus membrane with host endosome membrane / induction by virus of host autophagy / modulation by virus of host G1/S transition checkpoint / pore formation by virus in membrane of host cell / protein oligomerization / proteolysis / regulation of transcription, DNA-templated / suppression by virus of host MAVS activity / suppression by virus of host STAT1 activity / suppression by virus of host TRAF activity / suppression by virus of host type I interferon-mediated signaling pathway / transcription, DNA-templated / transformation of host cell by virus / viral RNA genome replication / virion attachment to host cellComponentsextracellular region / host cell cytoplasm / host cell cytosol / host cell endoplasmic reticulum membrane / host cell lipid particle / host cell mitochondrial membrane / host cell nucleus / host cell perinuclear region of cytoplasm / host cell plasma membrane / integral component of membrane / integral to membrane of host cell / viral envelope / viral nucleocapsid / virion membrane
- General Function
- Zinc ion binding
- Specific Function
- Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity).P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity (By similarity).Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS (By similarity).NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity).NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity).NS5B is an RNA-dependent RNA polymerase that plays an essential role in the virus replication.
- Pfam Domain Function
- Transmembrane Regions
- 169-189 359-379 726-746 758-778 783-803 814-834 882-902 929-949 1658-1678 1806-1826 1829-1849 1851-1871 1882-1902 2990-3010
- Cellular Location
- Host endoplasmic reticulum membrane
- Gene sequence
>lcl|BSEQ0002933|9033 bp ATGAGCACGAATCCTAAACCTCAAAGAAAAACCAAACGTAACACCAACCGCCGCCCACAG GACGTCAAGTTCCCGGGCGGTGGTCAGATCGTTGGTGGAGTTTACCTGTTGCCGCGCAGG GGCCCCAGGTTGGGTGTGCGCGCGCCCAGGAAGACTTCCGAGCGGTCGCAACCTCGTGGA AGGCGACAACCTATCCCCAAGGCTCGCCGGCCCGAGGGCAGGACCTGGGCTCAGCCCGGG TACCCTTGGCCTCTCTATGGCAATGAGGGCTTAGGGTGGGCAGGATGGCTCCTGTCACCC CGCGGCTCCCGGCCTAGTTGGGGCCCCACGGACCCCCGGCGTAGGTCGCGTAATTTGGGT AAGGTCATCGATACCCTCACATGCGGCTTCGCCGATCTCATGGGGTACATTCCGCTCGTC GGCGCCCCCCTGGGGGGCGCTGCCAGGGCCCTGGCACATGGTGTCCGGGTTCTGGAGGAC GGCGTGAACTATGCAACAGGGAATCTGCCCGGTTGCTCTTTTTCTATCTTCCTCTTGGCT CTGCTGTCCTGCCTGACCACCCCAGCTTCCGCTTACGAAGTGCACAACGTGTCCGGGATA TATCATGTCACGAACGACTGCTCCAACGCAAGCATTGTGTATGAGGCAGCGGACTTGATC ATGCATACTCCTGGGTGCGTGCCCTGCGTTCGGGAAGGCAACTCCTCCCGCTGCTGGGTA GCGCTCACTCCCACGCTCGCAGCCAGGAACGTCACCATCCCCACCACGACGATACGACGC CACGTCGATCTGCTCGTTGGGGCGGCTGCTTTCTGTTCCGCTATGTACGTGGGGGACCTC TGCGGATCTGTTTTCCTCGTCTCTCAGCTGTTCACCTTCTCGCCTCGCCGGCATGTGACA TTACAGGACTGTAACTGCTCAATTTATCCCGGCCATGTGTCGGGTCACCGTATGGCTTGG GACATGATGATGAACTGGTCGCCCACAACAGCCCTAGTGGTGTCGCAGTTACTCCGGATC CCACAAGCCGTCGTGGACATGGTGGCGGGGGCCCACTGGGGAGTCCTGGCGGGCCTTGCC TACTATTCCATGGCGGGGAACTGGGCTAAGGTTCTGATTGTGATGCTACTTTTTGCTGGC GTTGACGGGGATACCCACGTGACAGGGGGGGCGCAAGCCAAAACCACCAACAGGCTCGTG TCCATGTTCGCAAGTGGGCCGTCTCAGAAAATCCAGCTTATAAACACCAATGGGAGTTGG CACATCAACAGGACTGCCCTGAACTGCAATGACTCTCTCCAGACTGGGTTTCTTGCCGCG CTGTTCTACACACATAGTTTCAACTCGTCCGGGTGCCCAGAGCGCATGGCCCAGTGCCGC ACCATTGACAAGTTCGACCAGGGATGGGGTCCCATTACTTATGCTGAGTCTAGCAGATCA GACCAGAGGCCATATTGCTGGCACTACCCACCTCCACAATGTACCATCGTACCTGCGTCG GAGGTGTGCGGCCCAGTGTACTGCTTCACCCCAAGCCCTGTCGTCGTGGGGACGACCGAT CGTTTCGGTGTCCCTACGTATAGATGGGGGGAGAACGAGACTGACGTGCTGCTGCTCAAC AACACGCGGCCGCCGCAAGGCAACTGGTTCGGCTGCACATGGATGAATAGCACCGGGTTC ACCAAGACATGTGGGGGGCCCCCGTGTAACATCGGGGGGGTCGGCAACAACACCCTGACC TGCCCCACGGACTGCTTCCGGAAGCACCCCGAGGCTACCTACACAAAATGTGGTTCGGGG CCTTGGCTGACACCTAGGTGCATGGTTGACTATCCATACAGGCTCTGGCATTACCCCTGC ACTGTTAACTTTACCATCTTCAAGGTTAGGATGTATGTGGGGGGGGTGGAGCACAGGCTC AATGCTGCATGCAATTGGACCCGAGGAGAGCGTTGTGACTTGGAGGACAGGGATAGGCCG GAGCTCAGCCCGCTGCTGCTGTCTACAACAGAGTGGCAGGTACTGCCCTGTTCCTTCACC ACCCTACCAGCTCTGTCCACTGGCTTGATTCACCTCCATCAGAACATCGTGGACGTGCAA TACCTATACGGTATAGGGTCAGCGGTTGTCTCCTTTGCAATCAAATGGGAGTATGTCCTG TTGCTTTTCCTTCTCCTAGCGGACGCACGTGTCTGTGCCTGCTTGTGGATGATGCTGCTG ATAGCCCAGGCCGAGGCCGCCTTGGAGAACCTGGTGGTCCTCAATTCGGCGTCTGTGGCC GGCGCACATGGCATCCTCTCCTTCCTTGTGTTCTTCTGTGCCGCCTGGTACATCAAAGGC AGGCTGGTCCCTGGGGCGACATATGCTCTTTATGGCGTGTGGCCGCTGCTCCTGCTCTTG CTGGCATTACCACCGCGAGCTTACGCCATGGACCGGGAGATGGCTGCATCGTGCGGAGGC GCGGTTTTTGTGGGTCTGGTACTCCTGACTTTGTCACCATACTACAAGGTGTTCCTCGCT AGGCTCATATGGTGGTTACAATATTTTACCACCAGAGCCGAGGCGGACTTACATGTGTGG ATCCCCCCCCTCAACGCTCGGGGAGGCCGCGATGCCATCATCCTCCTCATGTGCGCAGTC CATCCAGAGCTAATCTTTGACATCACCAAACTTCTAATTGCCATACTCGGTCCGCTCATG GTGCTCCAAGCTGGCATAACCAGAGTGCCGTACTTCGTGCGCGCTCAAGGGCTCATTCAT GCATGCATGTTAGTGCGGAAGGTCGCTGGGGGTCATTATGTCCAAATGGCCTTCATGAAG CTGGGCGCGCTGACAGGCACGTACATTTACAACCATCTTACCCCGCTACGGGATTGGCCA CGCGCGGGCCTACGAGACCTTGCGGTGGCAGTGGAGCCCGTCGTCTTCTCCGACATGGAG ACCAAGATCATCACCTGGGGAGCAGACACCGCGGCGTGTGGGGACATCATCTTGGGTCTG CCCGTCTCCGCCCGAAGGGGAAAGGAGATACTCCTGGGCCCGGCCGATAGTCTTGAAGGG CGGGGGTTGCGACTCCTCGCGCCCATCACGGCCTACTCCCAACAGACGCGGGGCCTACTT GGTTGCATCATCACTAGCCTTACAGGCCGGGACAAGAACCAGGTCGAGGGAGAGGTTCAG GTGGTTTCCACCGCAACACAATCCTTCCTGGCGACCTGCGTCAACGGCGTGTGTTGGACC GTTTACCATGGTGCTGGCTCAAAGACCTTAGCCGCGCCAAAGGGGCCAATCACCCAGATG TACACTAATGTGGACCAGGACCTCGTCGGCTGGCCCAAGCCCCCCGGGGCGCGTTCCTTG ACACCATGCACCTGTGGCAGCTCAGACCTTTACTTGGTCACGAGACATGCTGACGTCATT CCGGTGCGCCGGCGGGGCGACAGTAGGGGGAGCCTGCTCTCCCCCAGGCCTGTCTCCTAC TTGAAGGGCTCTTCGGGTGGTCCACTGCTCTGCCCCTTCGGGCACGCTGTGGGCATCTTC CGGGCTGCCGTATGCACCCGGGGGGTTGCGAAGGCGGTGGACTTTGTGCCCGTAGAGTCC ATGGAAACTACTATGCGGTCTCCGGTCTTCACGGACAACTCATCCCCCCCGGCCGTACCG CAGTCATTTCAAGTGGCCCACCTACACGCTCCCACTGGCAGCGGCAAGAGTACTAAAGTG CCGGCTGCATATGCAGCCCAAGGGTACAAGGTGCTCGTCCTCAATCCGTCCGTTGCCGCT ACCTTAGGGTTTGGGGCGTATATGTCTAAGGCACACGGTATTGACCCCAACATCAGAACT GGGGTAAGGACCATTACCACAGGCGCCCCCGTCACATACTCTACCTATGGCAAGTTTCTT GCCGATGGTGGTTGCTCTGGGGGCGCTTATGACATCATAATATGTGATGAGTGCCATTCA ACTGACTCGACTACAATCTTGGGCATCGGCACAGTCCTGGACCAAGCGGAGACGGCTGGA GCGCGGCTTGTCGTGCTCGCCACCGCTACGCCTCCGGGATCGGTCACCGTGCCACACCCA AACATCGAGGAGGTGGCCCTGTCTAATACTGGAGAGATCCCCTTCTATGGCAAAGCCATC CCCATTGAAGCCATCAGGGGGGGAAGGCATCTCATTTTCTGTCATTCCAAGAAGAAGTGC GACGAGCTCGCCGCAAAGCTGTCAGGCCTCGGAATCAACGCTGTGGCGTATTACCGGGGG CTCGATGTGTCCGTCATACCAACTATCGGAGACGTCGTTGTCGTGGCAACAGACGCTCTG ATGACGGGCTATACGGGCGACTTTGACTCAGTGATCGACTGTAACACATGTGTCACCCAG ACAGTCGACTTCAGCTTGGATCCCACCTTCACCATTGAGACGACGACCGTGCCTCAAGAC GCAGTGTCGCGCTCGCAGCGGCGGGGTAGGACTGGCAGGGGTAGGAGAGGCATCTACAGG TTTGTGACTCCGGGAGAACGGCCCTCGGGCATGTTCGATTCCTCGGTCCTGTGTGAGTGC TATGACGCGGGCTGTGCTTGGTACGAGCTCACCCCGGCCGAGACCTCGGTTAGGTTGCGG GCCTACCTGAACACACCAGGGTTGCCCGTTTGCCAGGACCACCTGGAGTTCTGGGAGAGT GTCTTCACAGGCCTCACCCATATAGATGCACACTTCTTGTCCCAGACCAAGCAGGCAGGA GACAACTTCCCCTACCTGGTAGCATACCAAGCCACGGTGTGCGCCAGGGCTCAGGCCCCA CCTCCATCATGGGATCAAATGTGGAAGTGTCTCATACGGCTGAAACCTACGCTGCACGGG CCAACACCCTTGCTGTACAGGCTGGGAGCCGTCCAGAATGAGGTCACCCTCACCCACCCC ATAACCAAATACATCATGGCATGCATGTCGGCTGACCTGGAGGTCGTCACTAGCACCTGG GTGCTGGTGGGCGGAGTCCTTGCAGCTCTGGCCGCGTATTGCCTGACAACAGGCAGTGTG GTCATTGTGGGTAGGATTATCTTGTCCGGGAGGCCGGCCATTGTTCCCGACAGGGAGCTT CTCTACCAGGAGTTCGATGAAATGGAAGAGTGCGCCTCGCACCTCCCTTACATCGAGCAG GGAATGCAGCTCGCCGAGCAATTCAAGCAGAAAGCGCTCGGGTTACTGCAAACAGCCACC AAACAAGCGGAGGCTGCTGCTCCCGTGGTGGAGTCCAAGTGGCGAGCCCTTGAGACATTC TGGGCGAAGCACATGTGGAATTTCATCAGCGGGATACAGTACTTAGCAGGCTTATCCACT CTGCCTGGGAACCCCGCAATAGCATCATTGATGGCATTCACAGCCTCTATCACCAGCCCG CTCACCACCCAAAGTACCCTCCTGTTTAACATCTTGGGGGGGTGGGTGGCTGCCCAACTC GCCCCCCCCAGCGCCGCTTCGGCTTTCGTGGGCGCCGGCATCGCCGGTGCGGCTGTTGGC AGCATAGGCCTTGGGAAGGTGCTTGTGGACATTCTGGCGGGTTATGGAGCAGGAGTGGCC GGCGCGCTCGTGGCCTTTAAGGTCATGAGCGGCGAGATGCCCTCCACCGAGGACCTGGTC AATCTACTTCCTGCCATCCTCTCTCCTGGCGCCCTGGTCGTCGGGGTCGTGTGTGCAGCA ATACTGCGTCGACACGTGGGTCCGGGAGAGGGGGCTGTGCAGTGGATGAACCGGCTGATA GCGTTCGCCTCGCGGGGTAATCATGTTTCCCCCACGCACTATGTGCCTGAGAGCGACGCC GCAGCGCGTGTTACTCAGATCCTCTCCAGCCTTACCATCACTCAGCTGCTGAAAAGGCTC CACCAGTGGATTAATGAAGACTGCTCCACACCGTGTTCCGGCTCGTGGCTAAGGGATGTT TGGGACTGGATATGCACGGTGTTGACTGACTTCAAGACCTGGCTCCAGTCCAAGCTCCTG CCGCAGCTACCTGGAGTCCCTTTTTTCTCGTGCCAACGCGGGTACAAGGGAGTCTGGCGG GGAGACGGCATCATGCAAACCACCTGCCCATGTGGAGCACAGATCACCGGACATGTCAAA AACGGTTCCATGAGGATCGTCGGGCCTAAGACCTGCAGCAACACGTGGCATGGAACATTC CCCATCAACGCATACACCACGGGCCCCTGCACACCCTCTCCAGCGCCAAACTATTCTAGG GCGCTGTGGCGGGTGGCCGCTGAGGAGTACGTGGAGGTCACGCGGGTGGGGGATTTCCAC TACGTGACGGGCATGACCACTGACAACGTAAAGTGCCCATGCCAGGTTCCGGCTCCTGAA TTCTTCTCGGAGGTGGACGGAGTGCGGTTGCACAGGTACGCTCCGGCGTGCAGGCCTCTC CTACGGGAGGAGGTTACATTCCAGGTCGGGCTCAACCAATACCTGGTTGGGTCACAGCTA CCATGCGAGCCCGAACCGGATGTAGCAGTGCTCACTTCCATGCTCACCGACCCCTCCCAC ATCACAGCAGAAACGGCTAAGCGTAGGTTGGCCAGGGGGTCTCCCCCCTCCTTGGCCAGC TCTTCAGCTAGCCAGTTGTCTGCGCCTTCCTTGAAGGCGACATGCACTACCCACCATGTC TCTCCGGACGCTGACCTCATCGAGGCCAACCTCCTGTGGCGGCAGGAGATGGGCGGGAAC ATCACCCGCGTGGAGTCGGAGAACAAGGTGGTAGTCCTGGACTCTTTCGACCCGCTTCGA GCGGAGGAGGATGAGAGGGAAGTATCCGTTCCGGCGGAGATCCTGCGGAAATCCAAGAAG TTCCCCGCAGCGATGCCCATCTGGGCGCGCCCGGATTACAACCCTCCACTGTTAGAGTCC TGGAAGGACCCGGACTACGTCCCTCCGGTGGTGCACGGGTGCCCGTTGCCACCTATCAAG GCCCCTCCAATACCACCTCCACGGAGAAAGAGGACGGTTGTCCTAACAGAGTCCTCCGTG TCTTCTGCCTTAGCGGAGCTCGCTACTAAGACCTTCGGCAGCTCCGAATCATCGGCCGTC GACAGCGGCACGGCGACCGCCCTTCCTGACCAGGCCTCCGACGACGGTGACAAAGGATCC GACGTTGAGTCGTACTCCTCCATGCCCCCCCTTGAGGGGGAACCGGGGGACCCCGATCTC AGTGACGGGTCTTGGTCTACCGTGAGCGAGGAAGCTAGTGAGGATGTCGTCTGCTGCTCA ATGTCCTACACATGGACAGGCGCCTTGATCACGCCATGCGCTGCGGAGGAAAGCAAGCTG CCCATCAACGCGTTGAGCAACTCTTTGCTGCGCCACCATAACATGGTTTATGCCACAACA TCTCGCAGCGCAGGCCTGCGGCAGAAGAAGGTCACCTTTGACAGACTGCAAGTCCTGGAC GACCACTACCGGGACGTGCTCAAGGAGATGAAGGCGAAGGCGTCCACAGTTAAGGCTAAA CTCCTATCCGTAGAGGAAGCCTGCAAGCTGACGCCCCCACATTCGGCCAAATCCAAGTTT GGCTATGGGGCAAAGGACGTCCGGAACCTATCCAGCAAGGCCGTTAACCACATCCACTCC GTGTGGAAGGACTTGCTGGAAGACACTGTGACACCAATTGACACCACCATCATGGCAAAA AATGAGGTTTTCTGTGTCCAACCAGAGAAAGGAGGCCGTAAGCCAGCCCGCCTTATCGTA TTCCCAGATCTGGGAGTCCGTGTATGCGAGAAGATGGCCCTCTATGATGTGGTCTCCACC CTTCCTCAGGTCGTGATGGGCTCCTCATACGGATTCCAGTACTCTCCTGGGCAGCGAGTC GAGTTCCTGGTGAATACCTGGAAATCAAAGAAAAACCCCATGGGCTTTTCATATGACACT CGCTGTTTCGACTCAACGGTCACCGAGAACGACATCCGTGTTGAGGAGTCAATTTACCAA TGTTGTGACTTGGCCCCCGAAGCCAGACAGGCCATAAAATCGCTCACAGAGCGGCTTTAT ATCGGGGGTCCTCTGACTAATTCAAAAGGGCAGAACTGCGGTTATCGCCGGTGCCGCGCG AGCGGCGTGCTGACGACTAGCTGCGGTAACACCCTCACATGTTACTTGAAGGCCTCTGCA GCCTGTCGAGCTGCGAAGCTCCAGGACTGCACGATGCTCGTGAACGGAGACGACCTCGTC GTTATCTGTGAAAGCGCGGGAACCCAAGAGGACGCGGCGAGCCTACGAGTCTTCACGGAG GCTATGACTAGGTACTCCGCCCCCCCCGGGGACCCGCCCCAACCAGAATACGACTTGGAG CTGATAACATCATGTTCCTCCAATGTGTCGGTCGCCCACGATGCATCAGGCAAAAGGGTG TACTACCTCACCCGTGATCCCACCACCCCCCTAGCACGGGCTGCGTGGGAGACAGCTAGA CACACTCCAGTTAACTCCTGGCTAGGCAACATTATTATGTATGCGCCCACTTTGTGGGCA AGGATGATTCTGATGACTCACTTCTTCTCCATCCTTCTAGCGCAGGAGCAACTTGAAAAA GCCCTGGACTGCCAGATCTACGGGGCCTGTTACTCCATTGAGCCACTTGACCTACCTCAG ATCATTGAACGACTCCATGGCCTTAGCGCATTTTCACTCCATAGTTACTCTCCAGGTGAG ATCAATAGGGTGGCTTCATGCCTCAGGAAACTTGGGGTACCACCCTTGCGAGTCTGGAGA CATCGGGCCAGGAGCGTCCGCGCTAGGCTACTGTCCCAGGGAGGGAGGGCCGCCACTTGT GGCAAATACCTCTTCAACTGGGCAGTAAAAACCAAACTTAAACTCACTCCAATCCCGGCT GCGTCCCGGCTGGACTTGTCCGGCTGGTTCGTTGCTGGTTACAGCGGGGGAGACATATAT CACAGCCTGTCTCGTGCCCGACCCCGTTGGTTCATGCTGTGCCTACTCCTACTTTCTGTA GGGGTAGGCATCTACCTGCTCCCCAACCGATGA
- Chromosome Location
- Not Available
- Locus
- Not Available
- External Identifiers
Resource Link UniProtKB ID P26663 UniProtKB Entry Name POLG_HCVBK GenBank Protein ID 329771 GenBank Gene ID M58335 - General References
- Takamizawa A, Mori C, Fuke I, Manabe S, Murakami S, Fujita J, Onishi E, Andoh T, Yoshida I, Okayama H: Structure and organization of the hepatitis C virus genome isolated from human carriers. J Virol. 1991 Mar;65(3):1105-13. [Article]
- Borowski P, Heiland M, Oehlmann K, Becker B, Kornetzky L, Feucht H, Laufs R: Non-structural protein 3 of hepatitis C virus inhibits phosphorylation mediated by cAMP-dependent protein kinase. Eur J Biochem. 1996 May 1;237(3):611-8. [Article]
- Santolini E, Migliaccio G, La Monica N: Biosynthesis and biochemical properties of the hepatitis C virus core protein. J Virol. 1994 Jun;68(6):3631-41. [Article]
- Pieroni L, Santolini E, Fipaldini C, Pacini L, Migliaccio G, La Monica N: In vitro study of the NS2-3 protease of hepatitis C virus. J Virol. 1997 Sep;71(9):6373-80. [Article]
- Gale M Jr, Blakely CM, Kwieciszewski B, Tan SL, Dossett M, Tang NM, Korth MJ, Polyak SJ, Gretch DR, Katze MG: Control of PKR protein kinase by hepatitis C virus nonstructural 5A protein: molecular mechanisms of kinase regulation. Mol Cell Biol. 1998 Sep;18(9):5208-18. [Article]
- Tan SL, Nakao H, He Y, Vijaysri S, Neddermann P, Jacobs BL, Mayer BJ, Katze MG: NS5A, a nonstructural protein of hepatitis C virus, binds growth factor receptor-bound protein 2 adaptor protein in a Src homology 3 domain/ligand-dependent manner and perturbs mitogenic signaling. Proc Natl Acad Sci U S A. 1999 May 11;96(10):5533-8. [Article]
- Katze MG, Kwieciszewski B, Goodlett DR, Blakely CM, Neddermann P, Tan SL, Aebersold R: Ser(2194) is a highly conserved major phosphorylation site of the hepatitis C virus nonstructural protein NS5A. Virology. 2000 Dec 20;278(2):501-13. [Article]
- Thibeault D, Maurice R, Pilote L, Lamarre D, Pause A: In vitro characterization of a purified NS2/3 protease variant of hepatitis C virus. J Biol Chem. 2001 Dec 7;276(49):46678-84. Epub 2001 Oct 8. [Article]
- He Y, Nakao H, Tan SL, Polyak SJ, Neddermann P, Vijaysri S, Jacobs BL, Katze MG: Subversion of cell signaling pathways by hepatitis C virus nonstructural 5A protein via interaction with Grb2 and P85 phosphatidylinositol 3-kinase. J Virol. 2002 Sep;76(18):9207-17. [Article]
- Hofmann WP, Sarrazin C, Kronenberger B, Schonberger B, Bruch K, Zeuzem S: Mutations within the CD81-binding sites and hypervariable region 2 of the envelope 2 protein: correlation with treatment response in hepatitis C virus-infected patients. J Infect Dis. 2003 Mar 15;187(6):982-7. Epub 2003 Mar 6. [Article]
- Coito C, Diamond DL, Neddermann P, Korth MJ, Katze MG: High-throughput screening of the yeast kinome: identification of human serine/threonine protein kinases that phosphorylate the hepatitis C virus NS5A protein. J Virol. 2004 Apr;78(7):3502-13. [Article]
- Vuillermoz I, Khattab E, Sablon E, Ottevaere I, Durantel D, Vieux C, Trepo C, Zoulim F: Genetic variability of hepatitis C virus in chronically infected patients with viral breakthrough during interferon-ribavirin therapy. J Med Virol. 2004 Sep;74(1):41-53. [Article]
- Ahn J, Chung KS, Kim DU, Won M, Kim L, Kim KS, Nam M, Choi SJ, Kim HC, Yoon M, Chae SK, Hoe KL: Systematic identification of hepatocellular proteins interacting with NS5A of the hepatitis C virus. J Biochem Mol Biol. 2004 Nov 30;37(6):741-8. [Article]
- Nanda SK, Herion D, Liang TJ: The SH3 binding motif of HCV [corrected] NS5A protein interacts with Bin1 and is important for apoptosis and infectivity. Gastroenterology. 2006 Mar;130(3):794-809. [Article]
- Jackel-Cram C, Babiuk LA, Liu Q: Up-regulation of fatty acid synthase promoter by hepatitis C virus core protein: genotype-3a core has a stronger effect than genotype-1b core. J Hepatol. 2007 Jun;46(6):999-1008. Epub 2006 Nov 27. [Article]
- McLauchlan J: Properties of the hepatitis C virus core protein: a structural protein that modulates cellular processes. J Viral Hepat. 2000 Jan;7(1):2-14. [Article]
- Penin F, Dubuisson J, Rey FA, Moradpour D, Pawlotsky JM: Structural biology of hepatitis C virus. Hepatology. 2004 Jan;39(1):5-19. [Article]
- Kim CS, Seol SK, Song OK, Park JH, Jang SK: An RNA-binding protein, hnRNP A1, and a scaffold protein, septin 6, facilitate hepatitis C virus replication. J Virol. 2007 Apr;81(8):3852-65. Epub 2007 Jan 17. [Article]
- Love RA, Parge HE, Wickersham JA, Hostomsky Z, Habuka N, Moomaw EW, Adachi T, Hostomska Z: The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site. Cell. 1996 Oct 18;87(2):331-42. [Article]
- Yan Y, Li Y, Munshi S, Sardana V, Cole JL, Sardana M, Steinkuehler C, Tomei L, De Francesco R, Kuo LC, Chen Z: Complex of NS3 protease and NS4A peptide of BK strain hepatitis C virus: a 2.2 A resolution structure in a hexagonal crystal form. Protein Sci. 1998 Apr;7(4):837-47. [Article]
- Cho HS, Ha NC, Kang LW, Chung KM, Back SH, Jang SK, Oh BH: Crystal structure of RNA helicase from genotype 1b hepatitis C virus. A feasible mechanism of unwinding duplex RNA. J Biol Chem. 1998 Jun 12;273(24):15045-52. [Article]
- Yao N, Reichert P, Taremi SS, Prosise WW, Weber PC: Molecular views of viral polyprotein processing revealed by the crystal structure of the hepatitis C virus bifunctional protease-helicase. Structure. 1999 Nov 15;7(11):1353-63. [Article]
- Barbato G, Cicero DO, Nardi MC, Steinkuhler C, Cortese R, De Francesco R, Bazzo R: The solution structure of the N-terminal proteinase domain of the hepatitis C virus (HCV) NS3 protein provides new insights into its activation and catalytic mechanism. J Mol Biol. 1999 Jun 4;289(2):371-84. [Article]
- Bressanelli S, Tomei L, Roussel A, Incitti I, Vitale RL, Mathieu M, De Francesco R, Rey FA: Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus. Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13034-9. [Article]
- Lesburg CA, Cable MB, Ferrari E, Hong Z, Mannarino AF, Weber PC: Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site. Nat Struct Biol. 1999 Oct;6(10):937-43. [Article]
- Ago H, Adachi T, Yoshida A, Yamamoto M, Habuka N, Yatsunami K, Miyano M: Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus. Structure. 1999 Nov 15;7(11):1417-26. [Article]
- Bressanelli S, Tomei L, Rey FA, De Francesco R: Structural analysis of the hepatitis C virus RNA polymerase in complex with ribonucleotides. J Virol. 2002 Apr;76(7):3482-92. [Article]
- Wang M, Ng KK, Cherney MM, Chan L, Yannopoulos CG, Bedard J, Morin N, Nguyen-Ba N, Alaoui-Ismaili MH, Bethell RC, James MN: Non-nucleoside analogue inhibitors bind to an allosteric site on HCV NS5B polymerase. Crystal structures and mechanism of inhibition. J Biol Chem. 2003 Mar 14;278(11):9489-95. Epub 2002 Dec 30. [Article]
- Love RA, Parge HE, Yu X, Hickey MJ, Diehl W, Gao J, Wriggers H, Ekker A, Wang L, Thomson JA, Dragovich PS, Fuhrman SA: Crystallographic identification of a noncompetitive inhibitor binding site on the hepatitis C virus NS5B RNA polymerase enzyme. J Virol. 2003 Jul;77(13):7575-81. [Article]
Drug Relations
- Drug Relations
DrugBank ID Name Drug group Pharmacological action? Actions Details DB02331 (2s)-2-[(5-Benzofuran-2-Yl-Thiophen-2-Ylmethyl)-(2,4-Dichloro-Benzoyl)-Amino]-3-Phenyl-Propionic Acid experimental unknown Details DB03605 (2s)-2-[(2,4-Dichloro-Benzoyl)-(3-Trifluoromethyl-Benzyl)-Amino]-3-Phenyl-Propionic Acid experimental unknown Details DB04005 Uridine 5'-triphosphate experimental, investigational unknown Details DB04137 Guanosine-5'-Triphosphate experimental unknown Details DB04298 3-(4-Amino-2-Tert-Butyl-5-Methyl-Phenylsulfanyl)-6-Cyclopentyl-4-Hydroxy-6-[2-(4-Hydroxy-Phenyl)-Ethyl]-5,6-Dihydro-Pyran-2-One experimental unknown Details DB06974 5-hydroxy-4-(7-methoxy-1,1-dioxido-2H-1,2,4-benzothiadiazin-3-yl)-2-(3-methylbutyl)-6-phenylpyridazin-3(2H)-one experimental unknown Details DB07062 N-{3-[4-Hydroxy-1-(3-methylbutyl)-2-oxo-1,2-dihydropyrrolo[1,2-b]pyridazin-3-yl]-1,1-dioxido-2H-1,2,4-benzothiadiazin-7-yl}methanesulfonamide experimental unknown Details DB07169 5R-(3,4-DICHLOROPHENYLMETHYL)-3-(2-THIOPHENESULFONYLAMINO)-4-OXO-2-THIONOTHIAZOLIDINE experimental unknown Details DB07199 (2S,4S,5R)-1-(4-TERT-BUTYLBENZOYL)-2-ISOBUTYL-5-(1,3-THIAZOL-2-YL)PYRROLIDINE-2,4-DICARBOXYLIC ACID experimental unknown Details DB07200 (2S,4S,5R)-2-ISOBUTYL-5-(2-THIENYL)-1-[4-(TRIFLUOROMETHYL)BENZOYL]PYRROLIDINE-2,4-DICARBOXYLIC ACID experimental unknown Details DB07238 Nesbuvir investigational unknown Details DB07414 (5S)-1-benzyl-3-(1,1-dioxido-1,2-benzisothiazol-3-yl)-4-hydroxy-5-(1-methylethyl)-1,5-dihydro-2H-pyrrol-2-one experimental unknown Details DB07570 3-CYCLOHEXYL-1-(2-MORPHOLIN-4-YL-2-OXOETHYL)-2-PHENYL-1H-INDOLE-6-CARBOXYLIC ACID experimental unknown Details DB08031 N-[(13-CYCLOHEXYL-6,7-DIHYDROINDOLO[1,2-D][1,4]BENZOXAZEPIN-10-YL)CARBONYL]-2-METHYL-L-ALANINE experimental unknown Details DB08278 1-(2-cyclopropylethyl)-3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-6-fluoro-4-hydroxy-2(1H)-quinolinone experimental unknown Details DB08279 3-{ISOPROPYL[(TRANS-4-METHYLCYCLOHEXYL)CARBONYL]AMINO}-5-PHENYLTHIOPHENE-2-CARBOXYLIC ACID experimental unknown Details DB08390 (6S)-6-CYCLOPENTYL-6-[2-(3-FLUORO-4-ISOPROPOXYPHENYL)ETHYL]-4-HYDROXY-5,6-DIHYDRO-2H-PYRAN-2-ONE experimental unknown Details DB08481 4-Methyl-N-[5-(5-methyl-furan-2-ylmethylene)-4-oxo-thiazolidin-2-ylidene]-benzenesulfonamide experimental unknown Details DB08578 4-[(5-bromopyridin-2-yl)amino]-4-oxobutanoic acid experimental unknown Details DB08579 4-bromo-2-{[(3R,5S)-3,5-dimethylpiperidin-1-yl]carbonyl}aniline experimental unknown Details DB08580 4-bromo-2-{[(2R)-2-(2-chlorobenzyl)pyrrolidin-1-yl]carbonyl}aniline experimental unknown Details DB08581 4-[(4-bromo-2-{[(3R,5S)-3,5-dimethylpiperidin-1-yl]carbonyl}phenyl)amino]-4-oxobutanoic acid experimental unknown Details DB08582 N-(4-bromo-2-{[(3R,5S)-3,5-dimethylpiperidin-1-yl]carbonyl}phenyl)-4-morpholin-4-yl-4-oxobutanamide experimental unknown Details DB08701 2-(3-BROMOPHENYL)-6-[(2-HYDROXYETHYL)AMINO]-1H-BENZO[DE]ISOQUINOLINE-1,3(2H)-DIONE experimental unknown Details DB08706 (2S)-({(5Z)-5-[(5-Ethyl-2-furyl)methylene]-4-oxo-4,5-dihydro-1,3-thiazol-2-yl}amino)(4-fluorophenyl)acetic acid experimental unknown Details DB08710 (5Z)-5-[(5-ethylfuran-2-yl)methylidene]-2-[[(S)-(4-fluorophenyl)-(2H-tetrazol-5-yl)methyl]amino]-1,3-thiazol-4-one experimental unknown Details DB11586 Asunaprevir approved, investigational, withdrawn yes inhibitor Details