General information | DisProt: | DP00615 | Name: | Genome polyprotein | Synonym(s): | POLG_HCVCO
Core protein p21 [cleavage product 1]
Capsid protein C
p21
Core protein p19 [cleavage product 2]
Envelope glycoprotein E1 [cleavage product 3]
gp32
gp35
Envelope glycoprotein E2 [cleavage product 4]
NS1
gp68
gp70
p7 [cleavage product 5]
Protease NS2-3 [cleavage product 6]
p23
Serine protease/NTPase/helicase NS3 [cleavage product 7]
Hepacivirin
NS3P
p70
Non-structural protein 4A [cleavage product 8]
NS4A
p8
Non-structural protein 4B [cleavage product 9]
NS4B
p27
Non-structural protein 5A [cleavage product 10]
NS5A
p56
RNA-directed RNA polymerase [cleavage product 11]
NS5B
p68
| First appeared in release: | Release 5.4 (10/14/2010) | UniProt: | Q9WMX2 | UniGene: | | SwissProt: | POLG_HCVCO | TrEMBL: | | NCBI (GI): | | Source organism: | Hepatitis C virus genotype 1b (isolate Con1) (HCV) | Sequence length: | 3010 | Percent disordered: | -1% | Homologues: | |
Native sequence |
10 20 30 40 50 60 | | | | | | MSTNPKPQRK TKRNTNRRPQ DVKFPGGGQI VGGVYLLPRR GPRLGVRATR KTSERSQPRG - 60 RRQPIPKARQ PEGRAWAQPG YPWPLYGNEG LGWAGWLLSP RGSRPSWGPT DPRRRSRNLG - 120 KVIDTLTCGF ADLMGYIPLV GAPLGGAARA LAHGVRVLED GVNYATGNLP GCSFSIFLLA - 180 LLSCLTIPAS AYEVRNVSGV YHVTNDCSNA SIVYEAADMI MHTPGCVPCV RENNSSRCWV - 240 ALTPTLAARN ASVPTTTIRR HVDLLVGAAA LCSAMYVGDL CGSVFLVAQL FTFSPRRHET - 300 VQDCNCSIYP GHVTGHRMAW DMMMNWSPTA ALVVSQLLRI PQAVVDMVAG AHWGVLAGLA - 360 YYSMVGNWAK VLIVMLLFAG VDGGTYVTGG TMAKNTLGIT SLFSPGSSQK IQLVNTNGSW - 420 HINRTALNCN DSLNTGFLAA LFYVHKFNSS GCPERMASCS PIDAFAQGWG PITYNESHSS - 480 DQRPYCWHYA PRPCGIVPAA QVCGPVYCFT PSPVVVGTTD RFGVPTYSWG ENETDVLLLN - 540 NTRPPQGNWF GCTWMNSTGF TKTCGGPPCN IGGIGNKTLT CPTDCFRKHP EATYTKCGSG - 600 PWLTPRCLVH YPYRLWHYPC TVNFTIFKVR MYVGGVEHRL EAACNWTRGE RCNLEDRDRS - 660 ELSPLLLSTT EWQVLPCSFT TLPALSTGLI HLHQNVVDVQ YLYGIGSAVV SFAIKWEYVL - 720 LLFLLLADAR VCACLWMMLL IAQAEAALEN LVVLNAASVA GAHGILSFLV FFCAAWYIKG - 780 RLVPGAAYAL YGVWPLLLLL LALPPRAYAM DREMAASCGG AVFVGLILLT LSPHYKLFLA - 840 RLIWWLQYFI TRAEAHLQVW IPPLNVRGGR DAVILLTCAI HPELIFTITK ILLAILGPLM - 900 VLQAGITKVP YFVRAHGLIR ACMLVRKVAG GHYVQMALMK LAALTGTYVY DHLTPLRDWA - 960 HAGLRDLAVA VEPVVFSDME TKVITWGADT AACGDIILGL PVSARRGREI HLGPADSLEG - 1020 QGWRLLAPIT AYSQQTRGLL GCIITSLTGR DRNQVEGEVQ VVSTATQSFL ATCVNGVCWT - 1080 VYHGAGSKTL AGPKGPITQM YTNVDQDLVG WQAPPGARSL TPCTCGSSDL YLVTRHADVI - 1140 PVRRRGDSRG SLLSPRPVSY LKGSSGGPLL CPSGHAVGIF RAAVCTRGVA KAVDFVPVES - 1200 METTMRSPVF TDNSSPPAVP QTFQVAHLHA PTGSGKSTKV PAAYAAQGYK VLVLNPSVAA - 1260 TLGFGAYMSK AHGIDPNIRT GVRTITTGAP ITYSTYGKFL ADGGCSGGAY DIIICDECHS - 1320 TDSTTILGIG TVLDQAETAG ARLVVLATAT PPGSVTVPHP NIEEVALSST GEIPFYGKAI - 1380 PIETIKGGRH LIFCHSKKKC DELAAKLSGL GLNAVAYYRG LDVSVIPTSG DVIVVATDAL - 1440 MTGFTGDFDS VIDCNTCVTQ TVDFSLDPTF TIETTTVPQD AVSRSQRRGR TGRGRMGIYR - 1500 FVTPGERPSG MFDSSVLCEC YDAGCAWYEL TPAETSVRLR AYLNTPGLPV CQDHLEFWES - 1560 VFTGLTHIDA HFLSQTKQAG DNFPYLVAYQ ATVCARAQAP PPSWDQMWKC LIRLKPTLHG - 1620 PTPLLYRLGA VQNEVTTTHP ITKYIMACMS ADLEVVTSTW VLVGGVLAAL AAYCLTTGSV - 1680 VIVGRIILSG KPAIIPDREV LYREFDEMEE CASHLPYIEQ GMQLAEQFKQ KAIGLLQTAT - 1740 KQAEAAAPVV ESKWRTLEAF WAKHMWNFIS GIQYLAGLST LPGNPAIASL MAFTASITSP - 1800 LTTQHTLLFN ILGGWVAAQL APPSAASAFV GAGIAGAAVG SIGLGKVLVD ILAGYGAGVA - 1860 GALVAFKVMS GEMPSTEDLV NLLPAILSPG ALVVGVVCAA ILRRHVGPGE GAVQWMNRLI - 1920 AFASRGNHVS PTHYVPESDA AARVTQILSS LTITQLLKRL HQWINEDCST PCSGSWLRDV - 1980 WDWICTVLTD FKTWLQSKLL PRLPGVPFFS CQRGYKGVWR GDGIMQTTCP CGAQITGHVK - 2040 NGSMRIVGPR TCSNTWHGTF PINAYTTGPC TPSPAPNYSR ALWRVAAEEY VEVTRVGDFH - 2100 YVTGMTTDNV KCPCQVPAPE FFTEVDGVRL HRYAPACKPL LREEVTFLVG LNQYLVGSQL - 2160 PCEPEPDVAV LTSMLTDPSH ITAETAKRRL ARGSPPSLAS SSASQLSAPS LKATCTTRHD - 2220 SPDADLIEAN LLWRQEMGGN ITRVESENKV VILDSFEPLQ AEEDEREVSV PAEILRRSRK - 2280 FPRAMPIWAR PDYNPPLLES WKDPDYVPPV VHGCPLPPAK APPIPPPRRK RTVVLSESTV - 2340 SSALAELATK TFGSSESSAV DSGTATASPD QPSDDGDAGS DVESYSSMPP LEGEPGDPDL - 2400 SDGSWSTVSE EASEDVVCCS MSYTWTGALI TPCAAEETKL PINALSNSLL RHHNLVYATT - 2460 SRSASLRQKK VTFDRLQVLD DHYRDVLKEM KAKASTVKAK LLSVEEACKL TPPHSARSKF - 2520 GYGAKDVRNL SSKAVNHIRS VWKDLLEDTE TPIDTTIMAK NEVFCVQPEK GGRKPARLIV - 2580 FPDLGVRVCE KMALYDVVST LPQAVMGSSY GFQYSPGQRV EFLVNAWKAK KCPMGFAYDT - 2640 RCFDSTVTEN DIRVEESIYQ CCDLAPEARQ AIRSLTERLY IGGPLTNSKG QNCGYRRCRA - 2700 SGVLTTSCGN TLTCYLKAAA ACRAAKLQDC TMLVCGDDLV VICESAGTQE DEASLRAFTE - 2760 AMTRYSAPPG DPPKPEYDLE LITSCSSNVS VAHDASGKRV YYLTRDPTTP LARAAWETAR - 2820 HTPVNSWLGN IIMYAPTLWA RMILMTHFFS ILLAQEQLEK ALDCQIYGAC YSIEPLDLPQ - 2880 IIQRLHGLSA FSLHSYSPGE INRVASCLRK LGVPPLRVWR HRARSVRARL LSQGGRAATC - 2940 GKYLFNWAVR TKLKLTPIPA ASQLDLSSWF VAGYSGGDIY HSLSRARPRW FMWCLLLLSV - 3000 GVGIYLLPNR
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Functional narrative |
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.
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.
NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication. (UniProt)
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Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
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Comments |
NOTE on Organism: DP00588 is organism Hepatitis C virus genotype 1a (isolate H) (HCV), aka HCVH; DP00615 is Hepatitis C virus genotype 1b (isolate Con1) (HCV) aka HCV1b or HCVCO. These entries share 85% identity.
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