GenomeNet

Database: UniProt
Entry: O92532
LinkDB: O92532
Original site: O92532 
ID   POLG_HCVVP              Reviewed;        3015 AA.
AC   O92532;
DT   10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   11-DEC-2019, entry version 150.
DE   RecName: Full=Genome polyprotein;
DE   Contains:
DE     RecName: Full=Core protein p21;
DE     AltName: Full=Capsid protein C;
DE     AltName: Full=p21;
DE   Contains:
DE     RecName: Full=Core protein p19;
DE   Contains:
DE     RecName: Full=Envelope glycoprotein E1;
DE     AltName: Full=gp32;
DE     AltName: Full=gp35;
DE   Contains:
DE     RecName: Full=Envelope glycoprotein E2;
DE     AltName: Full=NS1;
DE     AltName: Full=gp68;
DE     AltName: Full=gp70;
DE   Contains:
DE     RecName: Full=p7;
DE   Contains:
DE     RecName: Full=Protease NS2-3;
DE              Short=p23;
DE              EC=3.4.22.-;
DE   Contains:
DE     RecName: Full=Serine protease NS3;
DE              EC=3.4.21.98;
DE              EC=3.6.1.15;
DE              EC=3.6.4.13;
DE     AltName: Full=Hepacivirin;
DE     AltName: Full=NS3P;
DE     AltName: Full=p70;
DE   Contains:
DE     RecName: Full=Non-structural protein 4A;
DE              Short=NS4A;
DE     AltName: Full=p8;
DE   Contains:
DE     RecName: Full=Non-structural protein 4B;
DE              Short=NS4B;
DE     AltName: Full=p27;
DE   Contains:
DE     RecName: Full=Non-structural protein 5A;
DE              Short=NS5A;
DE     AltName: Full=p56;
DE   Contains:
DE     RecName: Full=RNA-directed RNA polymerase;
DE              EC=2.7.7.48;
DE     AltName: Full=NS5B;
DE     AltName: Full=p68;
OS   Hepatitis C virus genotype 6h (isolate VN004) (HCV).
OC   Viruses; Riboviria; Flaviviridae; Hepacivirus.
OX   NCBI_TaxID=356424;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=9714232; DOI=10.1099/0022-1317-79-8-1847;
RA   Tokita H., Okamoto H., Iizuka H., Kishimoto J., Tsuda F., Miyakawa Y.,
RA   Mayumi M.;
RT   "The entire nucleotide sequences of three hepatitis C virus isolates in
RT   genetic groups 7-9 and comparison with those in the other eight genetic
RT   groups.";
RL   J. Gen. Virol. 79:1847-1857(1998).
RN   [2]
RP   REVIEW.
RX   PubMed=10718937; DOI=10.1046/j.1365-2893.2000.00201.x;
RA   McLauchlan J.;
RT   "Properties of the hepatitis C virus core protein: a structural protein
RT   that modulates cellular processes.";
RL   J. Viral Hepat. 7:2-14(2000).
RN   [3]
RP   REVIEW, AND SUBCELLULAR LOCATION.
RX   PubMed=14752815; DOI=10.1002/hep.20032;
RA   Penin F., Dubuisson J., Rey F.A., Moradpour D., Pawlotsky J.-M.;
RT   "Structural biology of hepatitis C virus.";
RL   Hepatology 39:5-19(2004).
RN   [4]
RP   INTERACTION WITH HNRNPA1 AND SEPT6.
RX   PubMed=17229681; DOI=10.1128/jvi.01311-06;
RA   Kim C.S., Seol S.K., Song O.-K., Park J.H., Jang S.K.;
RT   "An RNA-binding protein, hnRNP A1, and a scaffold protein, septin 6,
RT   facilitate hepatitis C virus replication.";
RL   J. Virol. 81:3852-3865(2007).
CC   -!- FUNCTION: Core protein packages viral RNA to form a viral nucleocapsid,
CC       and promotes virion budding. Modulates viral translation initiation by
CC       interacting with HCV IRES and 40S ribosomal subunit. Also regulates
CC       many host cellular functions such as signaling pathways and apoptosis.
CC       Prevents the establishment of cellular antiviral state by blocking the
CC       interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways
CC       and by inducing human STAT1 degradation. Thought to play a role in
CC       virus-mediated cell transformation leading to hepatocellular
CC       carcinomas. Interacts with, and activates STAT3 leading to cellular
CC       transformation. May repress the promoter of p53, and sequester CREB3
CC       and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle
CC       negative regulating factor CDKN1A, thereby interrupting an important
CC       check point of normal cell cycle regulation. Targets transcription
CC       factors involved in the regulation of inflammatory responses and in the
CC       immune response: suppresses NK-kappaB activation, and activates AP-1.
CC       Could mediate apoptotic pathways through association with TNF-type
CC       receptors TNFRSF1A and LTBR, although its effect on death receptor-
CC       induced apoptosis remains controversial. Enhances TRAIL mediated
CC       apoptosis, suggesting that it might play a role in immune-mediated
CC       liver cell injury. Seric core protein is able to bind C1QR1 at the T-
CC       cell surface, resulting in down-regulation of T-lymphocytes
CC       proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and
CC       SV40 promoters. May suppress the human FOS and HIV-1 LTR activity.
CC       Alters lipid metabolism by interacting with hepatocellular proteins
CC       involved in lipid accumulation and storage. Core protein induces up-
CC       regulation of FAS promoter activity, and thereby probably contributes
CC       to the increased triglyceride accumulation in hepatocytes (steatosis)
CC       (By similarity). {ECO:0000250}.
CC   -!- FUNCTION: E1 and E2 glycoproteins form a heterodimer that is involved
CC       in virus attachment to the host cell, virion internalization through
CC       clathrin-dependent endocytosis and fusion with host membrane. E1/E2
CC       heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but
CC       this binding is not sufficient for infection, some additional liver
CC       specific cofactors may be needed. The fusion function may possibly be
CC       carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the
CC       establishment of an antiviral state. E2 is a viral ligand for CD209/DC-
CC       SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic
CC       cells (DCs), and on liver sinusoidal endothelial cells and macrophage-
CC       like cells of lymph node sinuses. These interactions allow capture of
CC       circulating HCV particles by these cells and subsequent transmission to
CC       permissive cells. DCs are as sentinels in various tissues where they
CC       entrap pathogens and convey them to local lymphoid tissue or lymph node
CC       for establishment of immunity. Capture of circulating HCV particles by
CC       these SIGN+ cells may facilitate virus infection of proximal
CC       hepatocytes and lymphocyte subpopulations and may be essential for the
CC       establishment of persistent infection (By similarity). {ECO:0000250}.
CC   -!- FUNCTION: P7 seems to be a heptameric ion channel protein (viroporin)
CC       and is inhibited by the antiviral drug amantadine. Also inhibited by
CC       long-alkyl-chain iminosugar derivatives. Essential for infectivity (By
CC       similarity). {ECO:0000250}.
CC   -!- FUNCTION: Protease NS2-3 is a cysteine protease responsible for the
CC       autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation
CC       following maturation (By similarity). {ECO:0000250}.
CC   -!- FUNCTION: NS3 displays three enzymatic activities: serine protease,
CC       NTPase and RNA helicase. NS3 serine protease, in association with NS4A,
CC       is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and
CC       NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human
CC       IRF3, thus preventing the establishment of dsRNA induced antiviral
CC       state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5'
CC       direction, and likely RNA stable secondary structure in the template
CC       strand. Cleaves and inhibits the host antiviral protein MAVS (By
CC       similarity). {ECO:0000250}.
CC   -!- FUNCTION: NS4B induces a specific membrane alteration that serves as a
CC       scaffold for the virus replication complex. This membrane alteration
CC       gives rise to the so-called ER-derived membranous web that contains the
CC       replication complex (By similarity). {ECO:0000250}.
CC   -!- FUNCTION: NS5A is a component of the replication complex involved in
CC       RNA-binding. Its interaction with Human VAPB may target the viral
CC       replication complex to vesicles. Down-regulates viral IRES translation
CC       initiation. Mediates interferon resistance, presumably by interacting
CC       with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by
CC       interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A
CC       is an inhibitor of viral replication (By similarity). {ECO:0000250}.
CC   -!- FUNCTION: NS5B is an RNA-dependent RNA polymerase that plays an
CC       essential role in the virus replication. {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Hydrolysis of four peptide bonds in the viral precursor
CC         polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr
CC         in P1 and Ser or Ala in P1'.; EC=3.4.21.98;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate +
CC         RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:11128, Rhea:RHEA-
CC         COMP:11129, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:83400;
CC         EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC         diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per NS3 protease domain. {ECO:0000250};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per NS5A N-terminal domain. {ECO:0000250};
CC   -!- ACTIVITY REGULATION: Activity of auto-protease NS2-3 is dependent on
CC       zinc ions and completely inhibited by EDTA. Serine protease NS3 is also
CC       activated by zinc ions (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Core protein is a homomultimer that binds the C-terminal part
CC       of E1 and interacts with numerous cellular proteins. Interaction with
CC       human STAT1 SH2 domain seems to result in decreased STAT1
CC       phosphorylation, leading to decreased IFN-stimulated gene
CC       transcription. In addition to blocking the formation of phosphorylated
CC       STAT1, the core protein also promotes ubiquitin-mediated proteasome-
CC       dependent degradation of STAT1. Interacts with, and constitutively
CC       activates human STAT3. Associates with human LTBR and TNFRSF1A
CC       receptors and possibly induces apoptosis. Binds to human SP110 isoform
CC       3/Sp110b, HNRPK, C1QR1, YWHAE, UBE3A/E6AP, DDX3X, APOA2 and RXRA
CC       proteins. Interacts with human CREB3 nuclear transcription protein,
CC       triggering cell transformation. May interact with human p53. Also binds
CC       human cytokeratins KRT8, KRT18, KRT19 and VIM (vimentin). E1 and E2
CC       glycoproteins form a heterodimer that binds to human LDLR, CLDN1, CD81
CC       and SCARB1 receptors. E2 binds and inhibits human EIF2AK2/PKR. Also
CC       binds human CD209/DC-SIGN and CLEC4M/DC-SIGNR. p7 forms a homoheptamer
CC       in vitro. NS2 forms a homodimer containing a pair of composite active
CC       sites at the dimerization interface. NS2 seems to interact with all
CC       other non-structural (NS) proteins. NS4A interacts with NS3 serine
CC       protease and stabilizes its folding. NS3-NS4A complex is essential for
CC       the activation of the latter and allows membrane anchorage of NS3. NS3
CC       interacts with human TANK-binding kinase TBK1 and MAVS. NS4B and NS5A
CC       form homodimers and seem to interact with all other non-structural (NS)
CC       proteins. NS5A also interacts with human EIF2AK2/PKR, FKBP8, GRB2,
CC       BIN1, PIK3R1, SRCAP, VAPB and with most Src-family kinases. NS5B is a
CC       homooligomer and interacts with human VAPB, HNRNPA1 and SEPT6 (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Core protein p21]: Host endoplasmic reticulum
CC       membrane {ECO:0000250}; Single-pass membrane protein {ECO:0000250}.
CC       Host mitochondrion membrane {ECO:0000250}; Single-pass type I membrane
CC       protein {ECO:0000250}. Host lipid droplet {ECO:0000250}. Note=The C-
CC       terminal transmembrane domain of core protein p21 contains an ER signal
CC       leading the nascent polyprotein to the ER membrane. Only a minor
CC       proportion of core protein is present in the nucleus and an unknown
CC       proportion is secreted.
CC   -!- SUBCELLULAR LOCATION: [Core protein p19]: Virion {ECO:0000250}. Host
CC       cytoplasm {ECO:0000250}. Host nucleus {ECO:0000250}. Secreted
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Envelope glycoprotein E1]: Virion membrane
CC       {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host
CC       endoplasmic reticulum membrane {ECO:0000250}; Single-pass type I
CC       membrane protein {ECO:0000250}. Note=The C-terminal transmembrane
CC       domain acts as a signal sequence and forms a hairpin structure before
CC       cleavage by host signal peptidase. After cleavage, the membrane
CC       sequence is retained at the C-terminus of the protein, serving as ER
CC       membrane anchor. A reorientation of the second hydrophobic stretch
CC       occurs after cleavage producing a single reoriented transmembrane
CC       domain. These events explain the final topology of the protein. ER
CC       retention of E1 is leaky and, in overexpression conditions, only a
CC       small fraction reaches the plasma membrane.
CC   -!- SUBCELLULAR LOCATION: [Envelope glycoprotein E2]: Virion membrane
CC       {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host
CC       endoplasmic reticulum membrane {ECO:0000250}; Single-pass type I
CC       membrane protein {ECO:0000250}. Note=The C-terminal transmembrane
CC       domain acts as a signal sequence and forms a hairpin structure before
CC       cleavage by host signal peptidase. After cleavage, the membrane
CC       sequence is retained at the C-terminus of the protein, serving as ER
CC       membrane anchor. A reorientation of the second hydrophobic stretch
CC       occurs after cleavage producing a single reoriented transmembrane
CC       domain. These events explain the final topology of the protein. ER
CC       retention of E2 is leaky and, in overexpression conditions, only a
CC       small fraction reaches the plasma membrane.
CC   -!- SUBCELLULAR LOCATION: [p7]: Host endoplasmic reticulum membrane
CC       {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}. Host cell
CC       membrane {ECO:0000250}. Note=The C-terminus of p7 membrane domain acts
CC       as a signal sequence. After cleavage by host signal peptidase, the
CC       membrane sequence is retained at the C-terminus of the protein, serving
CC       as ER membrane anchor. Only a fraction localizes to the plasma
CC       membrane.
CC   -!- SUBCELLULAR LOCATION: [Protease NS2-3]: Host endoplasmic reticulum
CC       membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Serine protease NS3]: Host endoplasmic reticulum
CC       membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
CC       Note=NS3 is associated to the ER membrane through its binding to NS4A.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic
CC       reticulum membrane {ECO:0000305}; Single-pass type I membrane protein
CC       {ECO:0000305}. Note=Host membrane insertion occurs after processing by
CC       the NS3 protease.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic
CC       reticulum membrane {ECO:0000250}; Multi-pass membrane protein
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 5A]: Host endoplasmic
CC       reticulum membrane {ECO:0000250}; Peripheral membrane protein
CC       {ECO:0000250}. Host cytoplasm, host perinuclear region {ECO:0000250}.
CC       Host mitochondrion {ECO:0000250}. Note=Host membrane insertion occurs
CC       after processing by the NS3 protease.
CC   -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host endoplasmic
CC       reticulum membrane {ECO:0000305}; Single-pass type I membrane protein
CC       {ECO:0000305}. Note=Host membrane insertion occurs after processing by
CC       the NS3 protease.
CC   -!- DOMAIN: The transmembrane regions of envelope E1 and E2 glycoproteins
CC       are involved in heterodimer formation, ER localization, and assembly of
CC       these proteins. Envelope E2 glycoprotein contain a highly variable
CC       region called hypervariable region 1 (HVR1). E2 also contains two
CC       segments involved in CD81-binding. HVR1 is implicated in the SCARB1-
CC       mediated cell entry. CD81-binding regions may be involved in
CC       sensitivity and/or resistance to IFN-alpha therapy (By similarity).
CC       {ECO:0000250}.
CC   -!- DOMAIN: The N-terminus of NS5A act as membrane anchor. The central s
CC       part of NS5A seems to be intrinsically disordered and interacts with
CC       NS5B and host PKR (By similarity). {ECO:0000250}.
CC   -!- DOMAIN: The SH3-binding domain of NS5A is involved in the interaction
CC       with human Bin1, GRB2 and Src-family kinases. {ECO:0000250}.
CC   -!- DOMAIN: The N-terminal one-third of serine protease NS3 contains the
CC       protease activity. This region contains a zinc atom that does not
CC       belong to the active site, but may play a structural rather than a
CC       catalytic role. This region is essential for the activity of protease
CC       NS2-3, maybe by contributing to the folding of the latter. The helicase
CC       activity is located in the C-terminus of NS3 (By similarity).
CC       {ECO:0000250}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins. The
CC       structural proteins, core, E1, E2 and p7 are produced by proteolytic
CC       processing by host signal peptidases. The core protein is synthesized
CC       as a 21 kDa precursor which is retained in the ER membrane through the
CC       hydrophobic signal peptide. Cleavage by the signal peptidase releases
CC       the 19 kDa mature core protein. The other proteins (p7, NS2-3, NS3,
CC       NS4A, NS4B, NS5A and NS5B) are cleaved by the viral proteases (By
CC       similarity). {ECO:0000250}.
CC   -!- PTM: Envelope E1 and E2 glycoproteins are highly N-glycosylated.
CC       {ECO:0000250}.
CC   -!- PTM: Core protein is phosphorylated by host PKC and PKA. {ECO:0000250}.
CC   -!- PTM: NS5A is phosphorylated in a basal form termed p56. p58 is a
CC       hyperphosphorylated form of p56. p56 and p58 coexist in the cell in
CC       roughly equivalent amounts. Hyperphosphorylation is dependent on the
CC       presence of NS4A. Human AKT1, RPS6KB1/p70S6K, MAP2K1/MEK1, MAP2K6/MKK6
CC       and CSNK1A1/CKI-alpha kinases may be responsible for NS5A
CC       phosphorylation (By similarity). {ECO:0000250}.
CC   -!- PTM: NS4B is palmitoylated. This modification may play a role in its
CC       polymerization or in protein-protein interactions (By similarity).
CC       {ECO:0000250}.
CC   -!- PTM: The N-terminus of a fraction of NS4B molecules seems to be
CC       relocated post-translationally from the cytoplasm to the ER lumen, with
CC       a 5th transmembrane segment. The C-terminus of NS2 may be lumenal with
CC       a fourth transmembrane segment (By similarity). {ECO:0000250}.
CC   -!- PTM: Core protein is ubiquitinated; mediated by UBE3A and leading to
CC       core protein subsequent proteasomal degradation. {ECO:0000250}.
CC   -!- MISCELLANEOUS: Cell culture adaptation of the virus leads to mutations
CC       in NS5A, reducing its inhibitory effect on replication. {ECO:0000250}.
CC   -!- MISCELLANEOUS: Core protein exerts viral interference on hepatitis B
CC       virus when HCV and HBV coinfect the same cell, by suppressing HBV gene
CC       expression, RNA encapsidation and budding. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the hepacivirus polyprotein family.
CC       {ECO:0000305}.
CC   -!- CAUTION: The core gene probably also codes for alternative reading
CC       frame proteins (ARFPs). Many functions depicted for the core protein
CC       might belong to the ARFPs. {ECO:0000305}.
CC   -!- CAUTION: Lacks the conserved His residue in position 1084 essential for
CC       serine protease NS3 activity. Its enzyme activity is therefore unsure.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Virus Pathogen Resource;
CC       URL="http://www.viprbrc.org/brc/home.spg?decorator=flavi_hcv";
DR   EMBL; D84265; BAA32667.1; -; Genomic_RNA.
DR   SMR; O92532; -.
DR   PRIDE; O92532; -.
DR   euHCVdb; D84265; -.
DR   Proteomes; UP000008104; Genome.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0044186; C:host cell lipid droplet; IEA:UniProtKB-SubCell.
DR   GO; GO:0044191; C:host cell mitochondrial membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0044385; C:integral to membrane of host cell; IEA:UniProtKB-KW.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR   GO; GO:0005216; F:ion channel activity; IEA:UniProtKB-KW.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR   GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR   GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR   GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR   GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW.
DR   GO; GO:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
DR   GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:UniProtKB-KW.
DR   GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR   GO; GO:0039545; P:suppression by virus of host MAVS activity; IEA:UniProtKB-KW.
DR   GO; GO:0039563; P:suppression by virus of host STAT1 activity; IEA:UniProtKB-KW.
DR   GO; GO:0039547; P:suppression by virus of host TRAF activity; IEA:UniProtKB-KW.
DR   GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0019087; P:transformation of host cell by virus; IEA:InterPro.
DR   GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR   Gene3D; 1.20.1280.150; -; 1.
DR   Gene3D; 2.20.25.210; -; 1.
DR   Gene3D; 2.20.25.220; -; 1.
DR   Gene3D; 2.30.30.710; -; 1.
DR   InterPro; IPR011492; DEAD_Flavivir.
DR   InterPro; IPR002521; HCV_core_C.
DR   InterPro; IPR002522; HCV_core_N.
DR   InterPro; IPR002519; HCV_env.
DR   InterPro; IPR002531; HCV_NS1.
DR   InterPro; IPR002518; HCV_NS2.
DR   InterPro; IPR042205; HCV_NS2_C.
DR   InterPro; IPR042209; HCV_NS2_N.
DR   InterPro; IPR000745; HCV_NS4a.
DR   InterPro; IPR001490; HCV_NS4b.
DR   InterPro; IPR002868; HCV_NS5a.
DR   InterPro; IPR013193; HCV_NS5a_1B_dom.
DR   InterPro; IPR038568; HCV_NS5A_1B_sf.
DR   InterPro; IPR024350; HCV_NS5a_C.
DR   InterPro; IPR014001; Helicase_ATP-bd.
DR   InterPro; IPR001650; Helicase_C.
DR   InterPro; IPR013192; NS5A_1a.
DR   InterPro; IPR038170; NS5A_1a_sf.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR004109; Peptidase_S29_NS3.
DR   InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR   InterPro; IPR002166; RNA_pol_HCV.
DR   Pfam; PF07652; Flavi_DEAD; 1.
DR   Pfam; PF01543; HCV_capsid; 1.
DR   Pfam; PF01542; HCV_core; 1.
DR   Pfam; PF01539; HCV_env; 1.
DR   Pfam; PF01560; HCV_NS1; 1.
DR   Pfam; PF01538; HCV_NS2; 1.
DR   Pfam; PF01006; HCV_NS4a; 1.
DR   Pfam; PF01001; HCV_NS4b; 1.
DR   Pfam; PF01506; HCV_NS5a; 1.
DR   Pfam; PF08300; HCV_NS5a_1a; 1.
DR   Pfam; PF08301; HCV_NS5a_1b; 1.
DR   Pfam; PF12941; HCV_NS5a_C; 1.
DR   Pfam; PF02907; Peptidase_S29; 1.
DR   Pfam; PF00998; RdRP_3; 1.
DR   SMART; SM00487; DEXDc; 1.
DR   SUPFAM; SSF50494; SSF50494; 1.
DR   SUPFAM; SSF52540; SSF52540; 2.
DR   PROSITE; PS51693; HCV_NS2_PRO; 1.
DR   PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR   PROSITE; PS51194; HELICASE_CTER; 1.
DR   PROSITE; PS51822; HV_PV_NS3_PRO; 1.
DR   PROSITE; PS50507; RDRP_SSRNA_POS; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Activation of host autophagy by virus; Apoptosis; ATP-binding;
KW   Capsid protein; Clathrin-mediated endocytosis of virus by host;
KW   Disulfide bond; Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane;
KW   G1/S host cell cycle checkpoint dysregulation by virus; Glycoprotein;
KW   Helicase; Host cell membrane; Host cytoplasm; Host endoplasmic reticulum;
KW   Host lipid droplet; Host membrane; Host mitochondrion; Host nucleus;
KW   Host-virus interaction; Hydrolase;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host interferon signaling pathway by virus;
KW   Inhibition of host MAVS by virus; Inhibition of host RLR pathway by virus;
KW   Inhibition of host STAT1 by virus; Inhibition of host TRAFs by virus;
KW   Interferon antiviral system evasion; Ion channel; Ion transport;
KW   Lipoprotein; Membrane; Metal-binding;
KW   Modulation of host cell cycle by virus; Multifunctional enzyme;
KW   Nucleotide-binding; Nucleotidyltransferase; Oncogene; Palmitate;
KW   Phosphoprotein; Protease; Ribonucleoprotein; RNA-binding;
KW   RNA-directed RNA polymerase; Secreted; Serine protease; SH3-binding;
KW   Thiol protease; Transcription; Transcription regulation; Transferase;
KW   Transmembrane; Transmembrane helix; Transport; Ubl conjugation;
KW   Viral attachment to host cell; Viral envelope protein; Viral immunoevasion;
KW   Viral ion channel; Viral nucleoprotein;
KW   Viral penetration into host cytoplasm; Viral RNA replication; Virion;
KW   Virus endocytosis by host; Virus entry into host cell; Zinc.
FT   INIT_MET        1
FT                   /note="Removed; by host"
FT                   /evidence="ECO:0000250"
FT   CHAIN           2..191
FT                   /note="Core protein p21"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000045736"
FT   CHAIN           2..177
FT                   /note="Core protein p19"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000045737"
FT   PROPEP          178..191
FT                   /note="ER anchor for the core protein, removed in mature
FT                   form by host signal peptidase"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000045738"
FT   CHAIN           192..383
FT                   /note="Envelope glycoprotein E1"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000045739"
FT   CHAIN           384..747
FT                   /note="Envelope glycoprotein E2"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000045740"
FT   CHAIN           748..810
FT                   /note="p7"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000045741"
FT   CHAIN           811..1027
FT                   /note="Protease NS2-3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01030"
FT                   /id="PRO_0000045742"
FT   CHAIN           1028..1658
FT                   /note="Serine protease NS3"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000045743"
FT   CHAIN           1659..1712
FT                   /note="Non-structural protein 4A"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000045744"
FT   CHAIN           1713..1973
FT                   /note="Non-structural protein 4B"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000045745"
FT   CHAIN           1974..2424
FT                   /note="Non-structural protein 5A"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000045746"
FT   CHAIN           2425..3015
FT                   /note="RNA-directed RNA polymerase"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000045747"
FT   TOPO_DOM        2..168
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        169..189
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        190..358
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        359..379
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        380..726
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        727..747
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        748..758
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        759..779
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        780..783
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        784..804
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        805..814
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        815..835
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        836..882
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        883..903
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        904..929
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        930..950
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        951..1658
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1659..1679
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1680..1806
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1807..1827
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1828..1829
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1830..1850
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1851
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1852..1872
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1873..1882
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1883..1903
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1904..1973
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        1974..2003
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        2004..2994
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2995..3015
FT                   /note="Helical"
FT                   /evidence="ECO:0000250"
FT   DOMAIN          904..1027
FT                   /note="Peptidase C18"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01030"
FT   DOMAIN          1028..1209
FT                   /note="Peptidase S29"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01166"
FT   DOMAIN          1218..1370
FT                   /note="Helicase ATP-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT   DOMAIN          2638..2756
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   NP_BIND         1231..1238
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT   REGION          2..59
FT                   /note="Interaction with DDX3X"
FT                   /evidence="ECO:0000250"
FT   REGION          2..23
FT                   /note="Interaction with STAT1"
FT                   /evidence="ECO:0000250"
FT   REGION          122..173
FT                   /note="Interaction with APOA2"
FT                   /evidence="ECO:0000250"
FT   REGION          150..159
FT                   /note="Mitochondrial targeting signal"
FT                   /evidence="ECO:0000250"
FT   REGION          164..167
FT                   /note="Important for lipid droplets localization"
FT                   /evidence="ECO:0000250"
FT   REGION          265..296
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255"
FT   REGION          384..410
FT                   /note="HVR1"
FT                   /evidence="ECO:0000250"
FT   REGION          482..494
FT                   /note="CD81-binding 1"
FT                   /evidence="ECO:0000255"
FT   REGION          522..553
FT                   /note="CD81-binding 2"
FT                   /evidence="ECO:0000255"
FT   REGION          661..672
FT                   /note="PKR/eIF2-alpha phosphorylation homology domain
FT                   (PePHD)"
FT                   /evidence="ECO:0000250"
FT   REGION          1680..1691
FT                   /note="NS3-binding (by NS4A)"
FT                   /evidence="ECO:0000255"
FT   REGION          2201..2251
FT                   /note="Basal phosphorylation"
FT                   /evidence="ECO:0000250"
FT   REGION          2211..2276
FT                   /note="PKR-binding"
FT                   /evidence="ECO:0000255"
FT   REGION          2250..2308
FT                   /note="NS4B-binding"
FT                   /evidence="ECO:0000255"
FT   REGION          2353..2424
FT                   /note="Basal phosphorylation"
FT                   /evidence="ECO:0000250"
FT   MOTIF           5..13
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000255"
FT   MOTIF           38..43
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000255"
FT   MOTIF           58..64
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000255"
FT   MOTIF           66..71
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000255"
FT   MOTIF           1317..1320
FT                   /note="DECH box"
FT                   /evidence="ECO:0000250"
FT   MOTIF           2324..2327
FT                   /note="SH3-binding"
FT                   /evidence="ECO:0000255"
FT   MOTIF           2329..2337
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        797..804
FT                   /note="Poly-Leu"
FT   COMPBIAS        2278..2329
FT                   /note="Pro-rich"
FT   COMPBIAS        2996..3003
FT                   /note="Poly-Leu"
FT   ACT_SITE        953
FT                   /note="For protease NS2-3 activity; shared with dimeric
FT                   partner"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01030"
FT   ACT_SITE        973
FT                   /note="For protease NS2-3 activity; shared with dimeric
FT                   partner"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01030"
FT   ACT_SITE        994
FT                   /note="For protease NS2-3 activity; shared with dimeric
FT                   partner"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01030"
FT   ACT_SITE        1108
FT                   /note="Charge relay system; for serine protease NS3
FT                   activity"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        1166
FT                   /note="Charge relay system; for serine protease NS3
FT                   activity"
FT                   /evidence="ECO:0000250"
FT   METAL           1124
FT                   /note="Zinc"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01166"
FT   METAL           1126
FT                   /note="Zinc"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01166"
FT   METAL           1172
FT                   /note="Zinc"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01166"
FT   METAL           1176
FT                   /note="Zinc"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01166"
FT   METAL           2012
FT                   /note="Zinc"
FT                   /evidence="ECO:0000250"
FT   METAL           2030
FT                   /note="Zinc"
FT                   /evidence="ECO:0000250"
FT   METAL           2032
FT                   /note="Zinc"
FT                   /evidence="ECO:0000250"
FT   METAL           2053
FT                   /note="Zinc"
FT                   /evidence="ECO:0000250"
FT   SITE            177..178
FT                   /note="Cleavage; by host signal peptidase"
FT                   /evidence="ECO:0000250"
FT   SITE            191..192
FT                   /note="Cleavage; by host signal peptidase"
FT                   /evidence="ECO:0000255"
FT   SITE            383..384
FT                   /note="Cleavage; by host signal peptidase"
FT                   /evidence="ECO:0000255"
FT   SITE            747..748
FT                   /note="Cleavage; by host signal peptidase"
FT                   /evidence="ECO:0000250"
FT   SITE            810..811
FT                   /note="Cleavage; by host signal peptidase"
FT                   /evidence="ECO:0000250"
FT   SITE            1027..1028
FT                   /note="Cleavage; by protease NS2-3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01030"
FT   SITE            1658..1659
FT                   /note="Cleavage; by serine protease NS3"
FT                   /evidence="ECO:0000255"
FT   SITE            1712..1713
FT                   /note="Cleavage; by serine protease NS3"
FT                   /evidence="ECO:0000255"
FT   SITE            1973..1974
FT                   /note="Cleavage; by serine protease NS3"
FT                   /evidence="ECO:0000255"
FT   SITE            2424..2425
FT                   /note="Cleavage; by serine protease NS3"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         2
FT                   /note="N-acetylserine; by host"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         53
FT                   /note="Phosphoserine; by host"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         99
FT                   /note="Phosphoserine; by host"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         116
FT                   /note="Phosphoserine; by host PKA"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         2195
FT                   /note="Phosphoserine; by host; in p56"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         2198
FT                   /note="Phosphoserine; by host; in p58"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         2202
FT                   /note="Phosphoserine; by host; in p58"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         2205
FT                   /note="Phosphoserine; by host; in p58"
FT                   /evidence="ECO:0000250"
FT   LIPID           1973
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        196
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        209
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        234
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        250
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        305
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        416
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        422
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        429
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        447
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        475
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        532
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        556
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        576
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        624
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        646
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   DISULFID        2115..2163
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   3015 AA;  327978 MW;  69108DD32B5DA012 CRC64;
     MSTLPKPQRK TKRNTNRRPM DVKFPGGGQI VGGVYLLPRR GPRLGVRATR KTSERSQPRG
     RRQPIPKARQ PIGRSWGQPG YPWPLYGNEG CGWAGWLLSP RGSRPNWGPN DPRRRSRNLG
     KVIDTLTCGL ADLMGYIPVL GGPLGGVAAA LAHGVRAIED GVNYATGNLP GCSFSIFLLA
     LLSCLTTPAS AIQVRNASGI YHLTNDCSNN SIVFEAETII LHLPGCVPCI KVGNGSRCWL
     SVSPTLAVPN SSVPIHGFRR HVDLLVGAAA FCSAMYIGDL CGSVFLVGQL FTFRPKHHQV
     TQDCNCSIYA GHITGHRMAW DMMLNWSPTV SYVVSSALRV PQLLLEVITG AHWGVLGALL
     YFSMVANWAK VIAVLFLFAG ADATTYTGSA VSSTTGAFVS LFSPGPTQNL QLVNSNGSWH
     INRTALNCND SLQTGFIAGL FARYKFNSTG CPERMSKCRP LHSFEQGWGP ISYVNISGSS
     EDKPYCWHYA PRPCGIVPAR NVCGPVYCFT PSPVVVGTTD QRGIPTYTWG ENVSDVFLLH
     SARPPLGAWF GCTWMNSSGF VKTCGAPPCR IKPTINETDL VCPTDCFRKH PDASFVKCGS
     GPWLTPRCMV DYPYRLWHYP CTVNFTIHKV RVFVGGVEHR FNAACNWTRG DRCELDDRDR
     FEMSPLLFST TQLAILPCSF TTMPALSTGL IHLHQNIVDI QYLYGVSTAV VSWAMKWEYV
     VLAFLVLADA RVCACLWLMF LVGQAEAALE NVIVLNAASA ASCQGLLWGL IFICCAWHVR
     GRAVPVTTYA LLQLWPLLLL ILALPRRAYA FDSEQAASAG LLVLGLITIF TLTPAYKQLL
     ISMLWWIQYF IALTEAQLHQ WVPSLLVRGG RDAVILLACL FHPQLGFEVT KILLALLGPL
     YLLQYSLLKT PYFVRAHILL RACMFFRGMA RGRYAQAILL RIGAWTGTYI YDHLAPLSDW
     ACDGLRDLAV AVEPVVFSPM EKKVITWGAD TAACGDIIAG LPVAARRGNL LFLGPADDVK
     GKGWRLLAPI TAYAQQTRGI VGTIVTSLTG RDKNEVEGEI QVVSTATQSF LATAVNGVLW
     TVYYGAGSKT LAGPKGPVCQ MYTNVDQDLV GWPAPAGARS LTPCSCGSSD LYLVTRNADV
     IPARRRGDNR AALLSPRPIS TLKGSSGGPM LCPSGHVAGI FRAAVCTRGV AKSLDFAPVE
     SMQSSQRSPS FSDNTSPPAV PQTYQVGYLH APTGSGKSTK VPAAYAAQGY KVLVLNPSVA
     ATLGFGSYMS TSHGIDPNIR TGVRTITTGG AITYSTYGKF LADGGCSGGA YDVIICDECH
     STDPTTVSGI GTVLDQAETS GVRLTVLATA TPPGSVTVPH PNITESALPT TGEIPFYGKA
     VPLEYIKGGR HLIFCHPKKK CDELAKQLVS LGLNAVAFYR GVDVSVIPTS GDVVVCATDA
     LMTGYTGDFD SVIDCNVTVT QVVDFSLDPT FTIETTTVPQ DAVSRSQRRG RTGRGKHGVY
     RYVSQGERPS GMFDSVILCE AYDTGCAWYE LTPAETTVRL RAYLNTPGLP VCQDHLEFWE
     GVFTGLTHID AHFLSQTKQA EENFAYLVAY QATVCARAKA PPPSWDTMWK CLIRLKPMLT
     GPTPLLYRLG PVQNEVVTTH PITKYIMTCM SADLEVITST WVLVGGVVAA LAAYCLSVGC
     VVICGRISTS GKPVLIPDRE VLYQQFDEME ECSRHIPYLA EGHLIAEQFK QKVLGLIQST
     SKQAEELKPA VHAAWPKLEQ FWQKQLWNFV SGIQYLAGLS TLPGNPAIAS LMSFSASLTS
     PLSTHQTLLL NILGGWVASQ LANPTASTAF VVSGLAGAAV GSIGLGRVIV DVLAGYGAGV
     SGALVAFKIM CGETPSAEDM VNLLPALLSP GALVVGVVCA AILRRHAGPS EGATQWMNRL
     IAFASRGNHV SPTHYVPETD TSRQIMTILS SLTVTSLLRK LHEWINTDWS TPCSSSWLRD
     IWDWVCEVLS DFKTWLKAKL VPALPGVPFL SCQRGFRGTW RGDGICHTTC PCGSEITGHV
     KNGTMKISGP RWCSNVSHRT FPINATTTGP SVPIPEPNYT RALWRVSAEE YVEVKRVGDS
     HFVVGATTDN LKCPCQVPAP EFFTEVDGVR LHRYAPRCKP LLRDEVSFSV GLSSYAVGSQ
     LPCEPEPDVT VVTSMLIDPS HVTAEAAARR LARGSPPSLA SSSASQLSAP SLKATCTMHG
     AHPDAELIEA NLLWRQEMGG NITRVESENK VVILDSFDPL VPEFEEREMS VPAECHRPRR
     PKFPPALPIW ATPGYNPPVL ETWKSPTYEP PVVHGCALPP SGPPPIPPPR RKKVVQLDSS
     NVSAALAQLA AKTFETPSSP TTGYGSDQPD HSTESSEHDR DDGVASEAES YSSMPPLEGE
     PGDPDLSSGS WSTVSEEGDS VVCCSYSYSW TGALVTPCAA EEEKLPINPL SNSLIRHHNL
     VYSTSSRSAA TRQKKVTFDR VQLLDQHYYD TVKEIKLRAS HVKAQLLSTE EACDLTPPHS
     ARSKFGYGAK DVRSHASKAI NHINSVWADL LEDTQTPIPT TIMAKNEVFC VDASKGGRKS
     ARLIVYPDLG VRVCEKRALF DVTRKLPTAI MGDAYGFQYS PQQRVDRLLK MWRSKKTPMG
     FSYDTRCFDS TVTERDIRTE QDIYLSCQLD PEARKVIESL TERLYVGGPM YNSKGQLCGQ
     RRCRASGVLP TSMGNTVTCF LKATAACRAA GFTDYDMLVC GDDLVVVTES AGVNEDIANL
     RAFTEAMTRY SATPGDEPSP TYDLELITSC SSNVSVAHDG DGRRYYYLTR DPVTPLARAA
     WETARHTPVN SWLGNIIMYA PTIWVRMVLM THFFQILQAQ ETLDRALDFD IYGVTYSITP
     LDLPVIIQRL HGMAAFSLHG YSPDELNRVA SCLRKLGAPP LRAWRHRARA VRAKLIAQGG
     KAAVCGKYLF NWAIKTKLRL TPLRGASALD LSGWFTSGYG GGDVYHSASR ARPRFLLLCL
     LLLSVGVGIF LLPAR
//
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