Core protein p21 [cleavage product 1]
Capsid protein C
Core protein p19 [cleavage product 2]
Envelope glycoprotein E1 [cleavage product 3]
Envelope glycoprotein E2 [cleavage product 4]
p7 [cleavage product 5]
Protease NS2-3 [cleavage product 6]
Serine protease/NTPase/helicase NS3 [cleavage product 7]
Non-structural protein 4A [cleavage product 8]
Non-structural protein 4B [cleavage product 9]
Non-structural protein 5A [cleavage product 10]
RNA-directed RNA polymerase [cleavage product 11]
| First appeared in release:
|Release 5.4 (10/14/2010)
|Hepatitis C virus genotype 1b (isolate Con1) (HCV)
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
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)
|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.
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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