Genome polyprotein

Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity).

Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (Probable). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity).

Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity).

Activates STAT3 leading to cellular transformation (By similarity).

Regulates the activity of cellular genes, including c-myc and c-fos (By similarity).

May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity).

Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity).

Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NF-kappa-B activation, and activates AP-1 (By similarity).

Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity).

Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity).

Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).

By similarityCurated

Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity).

Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity).

E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity).

APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity).

The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity).

E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity).

Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity).

By similarity

Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity).

The interaction between envelope glycoprotein E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (By similarity).

This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (By similarity).

E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity).

The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity).

E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity).

Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity).

Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity).

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 (By similarity).

These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (By similarity).

The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (By similarity).

By similarity

Viroporin p7:

Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (By similarity).

Regulates the host cell secretory pathway, which induces the intracellular retention of viral glycoproteins and favors assembly of viral particles (By similarity).

Creates a pore in acidic organelles and releases Ca²⁺ and H⁺ in the cytoplasm of infected cells, leading to a productive viral infection (By similarity).

High levels of cytoplasmic Ca²⁺ may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). This ionic imbalance induces the assembly of the inflammasome complex, which triggers the maturation of pro-IL-1beta into IL-1beta through the action of caspase-1 (By similarity).

Targets also host mitochondria and induces mitochondrial depolarization (By similarity).

In addition of its role as a viroporin, acts as a lipid raft adhesion factor (By similarity).

By similarityCurated

Cysteine protease required for the proteolytic auto-cleavage between the non-structural proteins NS2 and NS3 (Probable) (PubMed:11591719).

The N-terminus of NS3 is required for the function of NS2 protease (active region NS2-3) (PubMed:11591719).

Promotes the initiation of viral particle assembly by mediating the interaction between structural and non-structural proteins (By similarity).

By similarity1 Publication1 Publication

Non-structural protein 4A:

Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (PubMed:9614113).

NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (By similarity).

The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity).

The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity).

NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (By similarity).

Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (By similarity).

Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity).

Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (By similarity).

Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (By similarity).

By similarity1 Publication

Peptide cofactor which forms a non-covalent complex with the N-terminal of NS3 serine protease (By similarity).

The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity).

The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity).

By similarity

Induces a specific membrane alteration that serves as a scaffold for the virus replication complex (By similarity).

This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity).

NS4B self-interaction contributes to its function in membranous web formation (By similarity).

Promotes host TRIF protein degradation in a CASP8-dependent manner thereby inhibiting host TLR3-mediated interferon signaling (By similarity).

Disrupts the interaction between STING and TBK1 contributing to the inhibition of interferon signaling (By similarity).

By similarity

Phosphorylated protein that is indispensable for viral replication and assembly (By similarity).

Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity).

The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity).

Involved in RNA-binding and especially in binding to the viral genome (By similarity).

Zinc is essential for RNA-binding (By similarity).

Participates in the viral particle production as a result of its interaction with the viral mature core protein (By similarity).

Its interaction with host VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation (By similarity).

Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (By similarity).

Prevents BIN1-induced apoptosis (By similarity).

Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity).

Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (By similarity).

Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By similarity).

By similarity

RNA-dependent RNA polymerase that performs primer-template recognition and RNA synthesis during viral replication.

By similarity

Miscellaneous

Viral particle assembly takes place at the surface of ER-derived membranes in close proximity to lipid droplets. NS2 associates with E1/E2 glycoproteins, NS3 and NS5A, which interacts with the viral RNA and core protein to promote genome encapsidation. The nucleocapsid buds at the ER membrane where E1/E2 glycoproteins are anchored and afterward associate with nascent lipid droplet to acquire APOE and APOC. Secretion of viral particles is probably regulated by viroporin p7.Curated

Cell culture adaptation of the virus leads to mutations in NS5A, reducing its inhibitory effect on replication.Curated

Exerts viral interference on hepatitis B virus when HCV and HBV coinfect the same cell, by suppressing HBV gene expression, RNA encapsidation and budding.By similarity

Caution

The core gene probably also codes for alternative reading frame proteins (ARFPs). Many functions depicted for the core protein might belong to the ARFPs.Curated

Catalytic activityⁱ

Serine protease/helicase NS3:
Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.
By similarity
Manual assertion inferred from sequence similarity toⁱ
- UniProtKB:P27958 (POLG_HCV77)
EC:3.4.21.98

Cofactorⁱ

Zn²⁺1 PublicationNote: Activity of protease NS2 is dependent on zinc ions and completely inhibited by EDTA. This is probably due to the fact that NS2 protease activity needs NS3 N-terminus that binds a zinc atom (active region NS2-3).1 Publication

Mg²⁺1 PublicationNote: Binds 2 magnesium ion that constitute a dinuclear catalytic metal center.1 Publication

Zn²⁺1 Publication, Mg²⁺By similarityNote: Binds 1 zinc ion which has a structural role (PubMed:8861916). The magnesium ion is essential for the helicase activity (By similarity).By similarity1 Publication

Activity regulationⁱ

Inhibited by the antiviral drug hexamethylene amiloride (By similarity). Inhibition by amantadine appears to be genotype-dependent (By similarity). Also inhibited by long-alkyl-chain iminosugar derivatives (By similarity).By similarity

Activity is up-regulated by PRK2/PKN2-mediated phosphorylation.By similarity

Activity of auto-protease NS2 is dependent on zinc ions and completely inhibited by EDTA, 1,10-phenanthroline, iodocetamide and N-ethylmaleimide. According to PubMed:9261354, completely inhibited by the serine protease inhibitors TLCK and TPCK (PubMed:9261354). According to PubMed:8189501, almost completely inhibited by TPCK and slightly inhibited by TLCK. Not inhibited by antipain, aprotinin, E64, PMSF and pepstatin. Also inhibited by NS2 and NS4A derived peptides. Serine protease/helicase NS3 is also activated by zinc ions.1 Publication

Temperature dependenceⁱ

Complete GO annotation on QuickGO ...

Optimum temperature is 20 degrees Celsius.1 Publication

Sites

Feature key	Position(s)	DescriptionActions	Length
Active siteⁱ	952	For protease NS2 activity; shared with dimeric partnerPROSITE-ProRule annotation	1
Active siteⁱ	972	For protease NS2 activity; shared with dimeric partnerPROSITE-ProRule annotation	1
Active siteⁱ	993	For protease NS2 activity; shared with dimeric partnerPROSITE-ProRule annotation	1
Active siteⁱ	1083	Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation1 Publication	1
Active siteⁱ	1107	Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation1 Publication	1
Metal bindingⁱ	1123	Zinc; structural; required for NS3 protease activity and NS2/3 auto-cleavage activityPROSITE-ProRule annotation3 Publications	1
Metal bindingⁱ	1125	Zinc; structural; required for NS3 protease activity and NS2/3 auto-cleavage activityPROSITE-ProRule annotation3 Publications	1
Active siteⁱ	1165	Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation2 Publications	1
Metal bindingⁱ	1171	Zinc; structural; required for NS3 protease activity and NS2/3 auto-cleavage activityPROSITE-ProRule annotation2 Publications	1
Metal bindingⁱ	1175	Zinc; structural; required for NS3 protease activityPROSITE-ProRule annotation2 Publications	1
Metal bindingⁱ	1237	Magnesium; catalytic; for NS3 helicase activityBy similarity	1
Metal bindingⁱ	1317	Magnesium; catalytic; for NS3 helicase activityBy similarity	1
Metal bindingⁱ	2011	Zinc; structuralBy similarity	1
Metal bindingⁱ	2029	Zinc; structuralBy similarity	1
Metal bindingⁱ	2031	Zinc; structuralBy similarity	1
Metal bindingⁱ	2052	Zinc; structuralBy similarity	1
Metal bindingⁱ	2639	Magnesium; catalytic; for RNA-directed RNA polymerase activity2 Publications	1
Metal bindingⁱ	2737	Magnesium; catalytic; for RNA-directed RNA polymerase activity2 Publications	1
Metal bindingⁱ	2738	Magnesium; catalytic; for RNA-directed RNA polymerase activity2 Publications	1

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Nucleotide bindingⁱ	1230 – 1237	ATPPROSITE-ProRule annotation		8

GO - Molecular functionⁱ

GO - Biological processⁱ

clathrin-dependent endocytosis of virus by host cell Source: UniProtKB-KW
fusion of virus membrane with host endosome membrane Source: UniProtKB-KW
induction by virus of host autophagy Source: UniProtKB-KW
modulation by virus of host G1/S transition checkpoint Source: UniProtKB-KW
pore formation by virus in membrane of host cell Source: UniProtKB-KW
protein complex oligomerization Source: UniProtKB-KW
suppression by virus of host JAK-STAT cascade via inhibition of STAT1 activity Source: UniProtKB-KW
suppression by virus of host TRAF activity Source: UniProtKB-KW
suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity Source: UniProtKB-KW
transformation of host cell by virus Source: InterPro
viral RNA genome replication Source: InterPro
virion attachment to host cell Source: UniProtKB-KW

Complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Helicase, Hydrolase, Ion channel, Multifunctional enzyme, Nucleotidyltransferase, Protease, Ribonucleoprotein, RNA-binding, RNA-directed RNA polymerase, Serine protease, Thiol protease, Transferase, Viral ion channel, Viral nucleoprotein
Biological process	Activation of host autophagy by virus, Apoptosis, Clathrin-mediated endocytosis of virus by host, Fusion of virus membrane with host endosomal membrane, Fusion of virus membrane with host membrane, G1/S host cell cycle checkpoint dysregulation by virus, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host MAVS by virus, Inhibition of host RLR pathway by virus, Inhibition of host STAT1 by virus, Inhibition of host TRAFs by virus, Interferon antiviral system evasion, Ion transport, Modulation of host cell cycle by virus, Transcription, Transcription regulation, Transport, Viral attachment to host cell, Viral immunoevasion, Viral penetration into host cytoplasm, Viral RNA replication, Virus endocytosis by host, Virus entry into host cell
Ligand	ATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAⁱ	3.4.21.98, 17002

BRENDAⁱ

3.4.21.98, 17002

Protein family/group databases

MEROPS protease database More...MEROPSⁱ	S29.001

MEROPSⁱ

S29.001

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Genome polyprotein Cleaved into the following 11 chains: Core protein precursor Alternative name(s): Capsid protp26663ein C p23 Mature core protein Alternative name(s): p21 Envelope glycoprotein E1 Alternative name(s): gp32 gp35 Envelope glycoprotein E2 Alternative name(s): NS1 gp68 gp70 Viroporin p7 Protease NS2 (EC:3.4.22.-2 Publications) Short name: p23 Serine protease/helicase NS3 (EC:3.4.21.98By similarity, EC:3.6.1.15By similarity, EC:3.6.4.13By similarity) Alternative name(s): Hepacivirin NS3 helicaseBy similarity NS3 proteaseBy similarity NS3P Viroporin p70 Non-structural protein 4A Short name: NS4A Alternative name(s): p8 Non-structural protein 4B Short name: NS4B Alternative name(s): p27 Non-structural protein 5A Short name: NS5A Alternative name(s): p56/58 RNA-directed RNA polymerase (EC:2.7.7.482 Publications) Alternative name(s): NS5B p68
Organismⁱ	Hepatitis C virus genotype 1b (isolate BK) (HCV)
Taxonomic identifierⁱ	11105 [NCBI]
Taxonomic lineageⁱ	Viruses › Riboviria › Orthornavirae › Kitrinoviricota › Flasuviricetes › Amarillovirales › Flaviviridae › Hepacivirus › Hepacivirus C › Hepatitis C virus genotype 1 › Hepatitis C virus subtype 1b
Virus hostⁱ	Homo sapiens (Human) [TaxID: 9606]
Proteomesⁱ	UP000007413 Componentⁱ: Genome

Subcellular locationⁱ

Core protein precursor:

Host endoplasmic reticulum membrane
By similarity
Manual assertion inferred from sequence similarity toⁱ
- UniProtKB:P26664 (POLG_HCV1)
; Single-pass membrane protein Sequence analysis
Host mitochondrion membrane
By similarity
Manual assertion inferred from sequence similarity toⁱ
- UniProtKB:P26664 (POLG_HCV1)
; Single-pass type I membrane protein Sequence analysis

Note:

The C-terminal transmembrane domain of the core protein precursor contains an ER signal leading the nascent polyprotein to the ER membrane.

Note:

Only a minor proportion of core protein is present in the nucleus (By similarity). Probably present on the surface of lipid droplets (PubMed:17188392).By similarity1 Publication

Virion membrane Curated; Single-pass type I membrane protein Curated
Host endoplasmic reticulum membrane ; Single-pass type I membrane protein
By similarity
Manual assertion inferred from sequence similarity toⁱ
- UniProtKB:P27958 (POLG_HCV77)

Note:

The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity).By similarity

Virion membrane Curated; Single-pass type I membrane protein Curated
Host endoplasmic reticulum membrane ; Single-pass type I membrane protein
By similarity
Manual assertion inferred from sequence similarity toⁱ
- UniProtKB:P27958 (POLG_HCV77)
Host lipid droplet
By similarity
Manual assertion inferred from sequence similarity toⁱ
- UniProtKB:Q9WMX2 (POLG_HCVCO)

Note:

Viroporin p7:

Host endoplasmic reticulum membrane
By similarity
Manual assertion inferred from sequence similarity toⁱ
- UniProtKB:P27958 (POLG_HCV77)
; Multi-pass membrane protein
By similarity
Manual assertion inferred from sequence similarity toⁱ
- UniProtKB:P27958 (POLG_HCV77)
Host mitochondrion
By similarity
Manual assertion inferred from sequence similarity toⁱ
- UniProtKB:P27958 (POLG_HCV77)
Host cell membrane
By similarity
Manual assertion inferred from sequence similarity toⁱ
- UniProtKB:P27958 (POLG_HCV77)

Note:

The C-terminus of p7 membrane domain acts as a signal sequence (By similarity). After cleavage by host signal peptidase, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). ER retention of p7 is leaky and a small fraction reaches the plasma membrane (By similarity).By similarity

Note:

Probably present on the surface of lipid droplets.By similarity

Non-structural protein 4A:

Host endoplasmic reticulum membrane Curated; Peripheral membrane protein Curated

Note:

NS3 is associated to the ER membrane through its binding to NS4A.Curated

Host endoplasmic reticulum membrane Curated; Single-pass type I membrane protein Curated

Note:

Host membrane insertion occurs after processing by the NS3 protease.

Host endoplasmic reticulum membrane
By similarity
Manual assertion inferred from sequence similarity toⁱ
- UniProtKB:P27958 (POLG_HCV77)
; Multi-pass membrane protein
By similarity
Manual assertion inferred from sequence similarity toⁱ
- UniProtKB:P27958 (POLG_HCV77)

Note:

A reorientation of the N-terminus into the ER lumen occurs post-translationally.By similarity

Note:

Host membrane insertion occurs after processing by the NS3 protease (By similarity). Localizes at the surface of lipid droplets (By similarity).By similarity

Host cytoplasm
By similarity
Manual assertion inferred from sequence similarity toⁱ
- UniProtKB:P27958 (POLG_HCV77)
Host endoplasmic reticulum membrane ; Single-pass type IV membrane protein
By similarity
Manual assertion inferred from sequence similarity toⁱ
- UniProtKB:P27958 (POLG_HCV77)

Note:

Host membrane insertion occurs after processing by the NS3 protease.By similarity

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	190 – 358	LumenalBy similarityAdd BLAST	169
Transmembraneⁱ	359 – 379	HelicalBy similarityAdd BLAST	21
Topological domainⁱ	380 – 725	LumenalBy similarityAdd BLAST	346
Transmembraneⁱ	726 – 746	HelicalBy similarityAdd BLAST	21
Topological domainⁱ	747 – 757	LumenalBy similarityAdd BLAST	11
Transmembraneⁱ	758 – 778	HelicalBy similarityAdd BLAST	21
Topological domainⁱ	779 – 781	CytoplasmicBy similarity	3
Transmembraneⁱ	782 – 803	HelicalBy similarityAdd BLAST	22
Topological domainⁱ	804 – 813	LumenalBy similarity	10
Transmembraneⁱ	814 – 834	HelicalBy similarityAdd BLAST	21
Topological domainⁱ	835 – 838	CytoplasmicBy similarity	4
Transmembraneⁱ	839 – 859	HelicalBy similarityAdd BLAST	21
Topological domainⁱ	860 – 881	LumenalBy similarityAdd BLAST	22
Transmembraneⁱ	882 – 902	HelicalBy similarityAdd BLAST	21
Topological domainⁱ	903 – 1657	CytoplasmicBy similarityAdd BLAST	755
Transmembraneⁱ	1658 – 1678	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	1679 – 1805	CytoplasmicSequence analysisAdd BLAST	127
Transmembraneⁱ	1806 – 1826	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	1827 – 1828	LumenalSequence analysis	2
Transmembraneⁱ	1829 – 1849	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	1850	CytoplasmicSequence analysis	1
Transmembraneⁱ	1851 – 1871	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	1872 – 1881	LumenalSequence analysis	10
Transmembraneⁱ	1882 – 1902	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	1903 – 1972	CytoplasmicSequence analysisAdd BLAST	70
Intramembraneⁱ	1973 – 2003	By similarityAdd BLAST	31
Topological domainⁱ	2004 – 2989	CytoplasmicBy similarityAdd BLAST	986
Transmembraneⁱ	2990 – 3010	HelicalBy similarityAdd BLAST	21

Keywords - Cellular componentⁱ

Capsid protein, Host cell membrane, Host cytoplasm, Host endoplasmic reticulum, Host lipid droplet, Host membrane, Host mitochondrion, Host nucleus, Membrane, Viral envelope protein, Virion

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	2194	S → A: Loss of phosphorylation. 1 Publication	1
Mutagenesisⁱ	2322	P → A: Complete loss of binding to GRB2. 1 Publication	1
Mutagenesisⁱ	2323	P → A: Complete loss of binding to GRB2. 1 Publication	1
Mutagenesisⁱ	2326	P → A: Complete loss of binding to GRB2. 1 Publication	1
Mutagenesisⁱ	2639	D → C, G or N: Complete loss of RdRp activity. 1 Publication	1
Mutagenesisⁱ	2644	D → G or N: Complete loss of RdRp activity. 1 Publication	1
Mutagenesisⁱ	2702	G → D, L or R: Complete loss of RdRp activity. 1 Publication	1
Mutagenesisⁱ	2705	T → V: Almost complete loss of RdRp activity. 1 Publication	1
Mutagenesisⁱ	2706	T → C: Almost complete loss of RdRp activity. 1 Publication	1
Mutagenesisⁱ	2706	T → K: Complete loss of RdRp activity. 1 Publication	1
Mutagenesisⁱ	2710	N → K: Complete loss of RdRp activity. 1 Publication	1
Mutagenesisⁱ	2736	G → A or C: Almost complete loss of RdRp activity. 1 Publication	1
Mutagenesisⁱ	2737	D → E, H or N: Complete loss of RdRp activity. 1 Publication	1
Mutagenesisⁱ	2738	D → H: Complete loss of RdRp activity. 1 Publication	1

Keywords - Diseaseⁱ

Oncogene

Chemistry databases

ChEMBLⁱ	CHEMBL6040
Drug and drug target database More...DrugBankⁱ	DB08706, (2S)-({(5Z)-5-[(5-Ethyl-2-furyl)methylene]-4-oxo-4,5-dihydro-1,3-thiazol-2-yl}amino)(4-fluorophenyl)acetic acid DB03605, (2s)-2-[(2,4-Dichloro-Benzoyl)-(3-Trifluoromethyl-Benzyl)-Amino]-3-Phenyl-Propionic Acid DB02331, (2s)-2-[(5-Benzofuran-2-Yl-Thiophen-2-Ylmethyl)-(2,4-Dichloro-Benzoyl)-Amino]-3-Phenyl-Propionic Acid DB07199, (2S,4S,5R)-1-(4-TERT-BUTYLBENZOYL)-2-ISOBUTYL-5-(1,3-THIAZOL-2-YL)PYRROLIDINE-2,4-DICARBOXYLIC ACID DB07200, (2S,4S,5R)-2-ISOBUTYL-5-(2-THIENYL)-1-[4-(TRIFLUOROMETHYL)BENZOYL]PYRROLIDINE-2,4-DICARBOXYLIC ACID 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 DB08710, (5Z)-5-[(5-ethylfuran-2-yl)methylidene]-2-[[(S)-(4-fluorophenyl)-(2H-tetrazol-5-yl)methyl]amino]-1,3-thiazol-4-one DB08390, (6S)-6-CYCLOPENTYL-6-[2-(3-FLUORO-4-ISOPROPOXYPHENYL)ETHYL]-4-HYDROXY-5,6-DIHYDRO-2H-PYRAN-2-ONE DB08278, 1-(2-cyclopropylethyl)-3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-6-fluoro-4-hydroxy-2(1H)-quinolinone DB08701, 2-(3-BROMOPHENYL)-6-[(2-HYDROXYETHYL)AMINO]-1H-BENZO[DE]ISOQUINOLINE-1,3(2H)-DIONE 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 DB07570, 3-CYCLOHEXYL-1-(2-MORPHOLIN-4-YL-2-OXOETHYL)-2-PHENYL-1H-INDOLE-6-CARBOXYLIC ACID DB08279, 3-{ISOPROPYL[(TRANS-4-METHYLCYCLOHEXYL)CARBONYL]AMINO}-5-PHENYLTHIOPHENE-2-CARBOXYLIC ACID DB08581, 4-[(4-bromo-2-{[(3R,5S)-3,5-dimethylpiperidin-1-yl]carbonyl}phenyl)amino]-4-oxobutanoic acid DB08578, 4-[(5-bromopyridin-2-yl)amino]-4-oxobutanoic acid DB08580, 4-bromo-2-{[(2R)-2-(2-chlorobenzyl)pyrrolidin-1-yl]carbonyl}aniline DB08579, 4-bromo-2-{[(3R,5S)-3,5-dimethylpiperidin-1-yl]carbonyl}aniline DB08481, 4-Methyl-N-[5-(5-methyl-furan-2-ylmethylene)-4-oxo-thiazolidin-2-ylidene]-benzenesulfonamide DB06974, 5-hydroxy-4-(7-methoxy-1,1-dioxido-2H-1,2,4-benzothiadiazin-3-yl)-2-(3-methylbutyl)-6-phenylpyridazin-3(2H)-one DB07169, 5R-(3,4-DICHLOROPHENYLMETHYL)-3-(2-THIOPHENESULFONYLAMINO)-4-OXO-2-THIONOTHIAZOLIDINE DB11586, Asunaprevir DB04137, Guanosine-5'-Triphosphate DB08582, N-(4-bromo-2-{[(3R,5S)-3,5-dimethylpiperidin-1-yl]carbonyl}phenyl)-4-morpholin-4-yl-4-oxobutanamide DB08031, N-[(13-CYCLOHEXYL-6,7-DIHYDROINDOLO[1,2-D][1,4]BENZOXAZEPIN-10-YL)CARBONYL]-2-METHYL-L-ALANINE 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 DB07238, Nesbuvir DB04005, Uridine 5'-triphosphate
DrugCentral More...DrugCentralⁱ	P26663

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Length
Initiator methionineⁱ		Removed; by hostBy similarity
ChainⁱPRO_0000450852	2 – 3010	Genome polyproteinAdd BLAST	3009
ChainⁱPRO_0000037529	2 – 191	Core protein precursorAdd BLAST	190
ChainⁱPRO_0000037530	2 – 177	Mature core proteinAdd BLAST	176
PropeptideⁱPRO_0000037531	178 – 191	ER anchor for the core protein, removed in mature form by host signal peptidaseBy similarityAdd BLAST	14
ChainⁱPRO_0000037532	192 – 383	Envelope glycoprotein E1Add BLAST	192
ChainⁱPRO_0000037533	384 – 746	Envelope glycoprotein E2Add BLAST	363
ChainⁱPRO_0000037534	747 – 809	Viroporin p7Add BLAST	63
ChainⁱPRO_0000037535	810 – 1026	Protease NS2PROSITE-ProRule annotationAdd BLAST	217
ChainⁱPRO_0000037536	1027 – 1657	Serine protease/helicase NS3Add BLAST	631
ChainⁱPRO_0000037537	1658 – 1711	Non-structural protein 4AAdd BLAST	54
ChainⁱPRO_0000037538	1712 – 1972	Non-structural protein 4BAdd BLAST	261
ChainⁱPRO_0000037539	1973 – 2419	Non-structural protein 5AAdd BLAST	447
ChainⁱPRO_0000037540	2420 – 3010	RNA-directed RNA polymeraseAdd BLAST	591

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	2	N-acetylserine; by hostBy similarity	1
Modified residueⁱ	53	Phosphoserine; by hostBy similarity	1
Modified residueⁱ	99	Phosphoserine; by hostBy similarity	1
Modified residueⁱ	116	Phosphoserine; by host PKABy similarity	1
Glycosylationⁱ	196	N-linked (GlcNAc...) asparagine; by host1 Publication	1
Glycosylationⁱ	209	N-linked (GlcNAc...) asparagine; by hostBy similarity	1
Glycosylationⁱ	234	N-linked (GlcNAc...) asparagine; by hostBy similarity	1
Glycosylationⁱ	250	N-linked (GlcNAc...) asparagine; by hostBy similarity	1
Glycosylationⁱ	305	N-linked (GlcNAc...) asparagine; by hostSequence analysis	1
Glycosylationⁱ	417	N-linked (GlcNAc...) asparagine; by hostSequence analysis	1
Glycosylationⁱ	423	N-linked (GlcNAc...) (high mannose) asparagine; by hostBy similarity	1
Disulfide bondⁱ	429 ↔ 552	By similarity
Glycosylationⁱ	430	N-linked (GlcNAc...) (high mannose) asparagine; by hostBy similarity	1
Glycosylationⁱ	448	N-linked (GlcNAc...) (high mannose) asparagine; by hostBy similarity	1
Disulfide bondⁱ	452 ↔ 459	By similarity
Disulfide bondⁱ	486 ↔ 494	By similarity
Disulfide bondⁱ	503 ↔ 508	By similarity
Glycosylationⁱ	532	N-linked (GlcNAc...) (high mannose) asparagine; by hostBy similarity	1
Glycosylationⁱ	540	N-linked (GlcNAc...) (high mannose) asparagine; by hostBy similarity	1
Glycosylationⁱ	556	N-linked (GlcNAc...) (high mannose) asparagine; by hostBy similarity	1
Disulfide bondⁱ	564 ↔ 569	By similarity
Glycosylationⁱ	576	N-linked (GlcNAc...) (high mannose) asparagine; by hostBy similarity	1
Disulfide bondⁱ	581 ↔ 585	By similarity
Disulfide bondⁱ	597 ↔ 620	By similarity
Disulfide bondⁱ	607 ↔ 644	By similarity
Glycosylationⁱ	623	N-linked (GlcNAc...) (high mannose) asparagine; by hostBy similarity	1
Glycosylationⁱ	645	N-linked (GlcNAc...) (high mannose) asparagine; by hostBy similarity	1
Disulfide bondⁱ	652 ↔ 677	By similarity
Lipidationⁱ	922	S-palmitoyl cysteine; by hostBy similarity	1
Lipidationⁱ	1968	S-palmitoyl cysteine; by hostBy similarity	1
Lipidationⁱ	1972	S-palmitoyl cysteine; by hostBy similarity	1
Modified residueⁱ	2194	Phosphoserine; by host; in p561 Publication	1
Modified residueⁱ	2197	Phosphoserine; by host; in p58By similarity	1
Modified residueⁱ	2201	Phosphoserine; by host; in p58By similarity	1
Modified residueⁱ	2204	Phosphoserine; by host; in p58By similarity	1
Modified residueⁱ	2207	Phosphoserine; by host; in p58By similarity	1
Modified residueⁱ	2210	Phosphoserine; by host; in p58By similarity	1
Cross-linkⁱ	2350	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residueⁱ	2448	Phosphoserine; by hostBy similarity	1
Modified residueⁱ	2461	Phosphoserine; by hostBy similarity	1

Post-translational modificationⁱ

Genome polyprotein:

Specific enzymatic cleavages in vivo yield mature proteins (By similarity). The structural proteins, core, E1, E2 and p7 are produced by proteolytic processing by host signal peptidases (By similarity). The core protein precursor is synthesized as a 23 kDa, which is retained in the ER membrane through the hydrophobic signal peptide (PubMed:8862403). Cleavage by the signal peptidase releases the 21 kDa mature core protein (PubMed:8862403). The cleavage of the core protein precursor occurs between aminoacids 176 and 188 but the exact cleavage site is not known (PubMed:8862403). Some degraded forms of the core protein appear as well during the course of infection (PubMed:8862403). The other proteins (p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B) are cleaved by the viral proteases (By similarity). Autoprocessing between NS2 and NS3 is mediated by the NS2 cysteine protease catalytic domain and regulated by the NS3 N-terminal domain (PubMed:11591719).By similarity2 Publications

Phosphorylated by host PKC and PKA.By similarity

Ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation.By similarity

Highly N-glycosylated.By similarity

Highly N-glycosylated.By similarity

Palmitoylation is required for NS2/3 autoprocessing and E2 recruitment to membranes.By similarity

Palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions.By similarity

Phosphorylated on serines in a basal form termed p56 (PubMed:11118372). p58 is a hyperphosphorylated form of p56 (By similarity). p56 and p58 coexist in the cell in roughly equivalent amounts (By similarity). Hyperphosphorylation is dependent on the presence of NS4A (By similarity). Host CSNK1A1/CKI-alpha or RPS6KB1 kinases may be responsible for NS5A phosphorylation (PubMed:15016873, PubMed:16943283).By similarity3 Publications

Tyrosine phosphorylation is essential for the interaction with host SRC.By similarity

The N-terminus is phosphorylated by host PRK2/PKN2.By similarity

Sites

Feature key	Position(s)	DescriptionActions	Length
Siteⁱ	177 – 178	Cleavage; by host signal peptide peptidaseBy similarity	2
Siteⁱ	191 – 192	Cleavage; by host signal peptidaseBy similarity	2
Siteⁱ	383 – 384	Cleavage; by host signal peptidaseBy similarity	2
Siteⁱ	746 – 747	Cleavage; by host signal peptidaseBy similarity	2
Siteⁱ	809 – 810	Cleavage; by host signal peptidaseBy similarity	2
Siteⁱ	1026 – 1027	Cleavage; by protease NS2PROSITE-ProRule annotation	2
Siteⁱ	1657 – 1658	Cleavage; by serine protease/helicase NS3By similarity	2
Siteⁱ	1711 – 1712	Cleavage; by serine protease/helicase NS3By similarity	2
Siteⁱ	1972 – 1973	Cleavage; by serine protease/helicase NS3By similarity	2
Siteⁱ	2419 – 2420	Cleavage; by serine protease/helicase NS3By similarity	2

Keywords - PTMⁱ

Acetylation, Disulfide bond, Glycoprotein, Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

PTM databases

iPTMnetⁱ	P26663

iPTMnetⁱ

Interactionⁱ

Subunit structureⁱ

Homooligomer (By similarity).

Interacts with E1 (via C-terminus) (By similarity).

Interacts with the non-structural protein 5A (By similarity).

Interacts (via N-terminus) with host STAT1 (via SH2 domain); this interaction results in decreased STAT1 phosphorylation and ubiquitin-mediated proteasome-dependent STAT1 degradation, leading to decreased IFN-stimulated gene transcription (By similarity).

Interacts with host STAT3; this interaction constitutively activates STAT3 (By similarity). Associates with host LTBR receptor (By similarity).

Interacts with host TNFRSF1A receptor and possibly induces apoptosis (By similarity).

Interacts with host HNRPK (By similarity).

Interacts with host YWHAE (By similarity).

Interacts with host UBE3A/E6AP (By similarity).

Interacts with host DDX3X (By similarity).

Interacts with host APOA2 (By similarity).

Interacts with host RXRA protein (By similarity).

Interacts with host SP110 isoform 3/Sp110b; this interaction sequesters the transcriptional corepressor SP110 away from the nucleus (By similarity).

Interacts with host CREB3 nuclear transcription protein; this interaction triggers cell transformation (By similarity).

Interacts with host ACY3 (By similarity).

Interacts with host C1QR1 (By similarity).

Interacts with host RBM24; this interaction, which enhances the interaction of the mature core protein with 5'-UTR, may inhibit viral translation and favor replication (By similarity).

Interacts (via N-terminus) with host EIF2AK2/PKR (via N-terminus); this interaction induces the autophosphorylation of EIF2AK2 (By similarity). Part of the viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein (By similarity).

By similarity

Forms a heterodimer with envelope glycoprotein E2 (By similarity).

Interacts with mature core protein (By similarity).

Interacts with protease NS2 (By similarity). The heterodimer E1/E2 interacts with host CLDN1; this interaction plays a role in viral entry into host cell (By similarity).

Interacts with host SPSB2 (via C-terminus) (By similarity). Part of the viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein (By similarity).

By similarity

Forms a heterodimer with envelope glycoprotein E1 (By similarity).

Interacts with host CD81 and SCARB1 receptors; these interactions play a role in viral entry into host cell (By similarity).

Interacts with host EIF2AK2/PKR; this interaction inhibits EIF2AK2 and probably allows the virus to evade the innate immune response (By similarity).

Interacts with host CD209/DC-SIGN and CLEC4M/DC-SIGNR (By similarity). Interact with host SPCS1; this interaction is essential for viral particle assembly (By similarity).

Interacts with protease NS2 (By similarity). The heterodimer E1/E2 interacts with host CLDN1; this interaction plays a role in viral entry into host cell (By similarity). Part of the viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein (By similarity).

Interacts with host SLC3A2/4F2hc; the interaction may facilitate viral entry into host cell (By similarity).

Interacts with human PLSCR1 (By similarity).

By similarity

Viroporin p7:

Homohexamer (By similarity). Homoheptamer (By similarity).

Interacts with protease NS2 (By similarity).

By similarity

Homodimer (By similarity).

Interacts with host SPCS1; this interaction is essential for viral particle assembly (By similarity).

Interacts with envelope glycoprotein E1 (By similarity).

Interacts with envelope glycoprotein E2 (By similarity).

Interacts with viroporin p7 (By similarity).

Interacts with serine protease/helicase NS3 (By similarity). Part of the replication complex composed of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA polymerase embedded in an ER-derived membranous web (By similarity). Part of the viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein (By similarity).

By similarity

Non-structural protein 4A:

Interacts with protease NS2 (By similarity).

Interacts with non-structural protein 4A; this interaction stabilizes the folding of NS3 serine protease (PubMed:9568891, PubMed:10366511). NS3-NS4A interaction is essential for NS3 activation and allows membrane anchorage of the latter (PubMed:9568891). NS3/NS4A complex also prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity).

Interacts with host MAVS; this interaction leads to the cleavage and inhibition of host MAVS (By similarity).

Interacts with host TICAM1; this interaction leads to the cleavage and inhibition of host TICAM1 (By similarity).

Interacts with host TANK-binding kinase/TBK1; this interaction results in the inhibition of the association between TBK1 and IRF3, which leads to the inhibition of IRF3 activation (By similarity).

Interacts with host RBM24 (By similarity). Part of the replication complex composed of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA polymerase embedded in an ER-derived membranous web (By similarity). Part of the viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein (By similarity).

By similarity2 Publications

Interacts with NS3 serine protease; this interaction stabilizes the folding of NS3 serine protease (PubMed:9568891, PubMed:10366511). NS3-NS4A interaction is essential for NS3 activation and allows membrane anchorage of the latter (PubMed:9568891).

Interacts with non-structural protein 5A (via N-terminus) (By similarity). Part of the replication complex composed of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA polymerase embedded in an ER-derived membranous web (By similarity). Part of the viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein (By similarity).

By similarity2 Publications

Monomer (By similarity). Homodimer; dimerization is required for RNA-binding (By similarity).

Interacts with the mature core protein (By similarity).

Interacts (via N-terminus) with non-structural protein 4A (By similarity).

Interacts with non-structural protein 4B (By similarity).

Interacts with RNA-directed RNA polymerase (By similarity). Part of the viral assembly initiation complex composed of NS2, E1, E2, NS3, NS4A, NS5A and the mature core protein (By similarity). Part of the replication complex composed of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA polymerase embedded in an ER-derived membranous web (By similarity).

Interacts with host GRB2 (PubMed:10318918).

Interacts with host BIN1 (By similarity).

Interacts with host PIK3R1 (PubMed:12186904).

Interacts with host SRCAP (By similarity).

Interacts with host FKBP8 (By similarity).

Interacts with host VAPB (By similarity).

Interacts with host EIF2AK2/PKR; this interaction leads to disruption of EIF2AK2 dimerization by NS5A and probably allows the virus to evade the innate immune response (PubMed:9710605).

Interacts (via N-terminus) with host PACSIN2 (via N-terminus); this interaction attenuates protein kinase C alpha-mediated phosphorylation of PACSIN2 by disrupting the interaction between PACSIN2 and PRKCA (By similarity).

Interacts (via N-terminus) with host SRC kinase (via SH2 domain) (By similarity).

Interacts with most Src-family kinases (By similarity).

Interacts with host IFI27 and SKP2; promotes the ubiquitin-mediated proteasomal degradation of NS5A (By similarity).

Interacts with host GPS2 (By similarity).

Interacts with host TNFRSF21; this interaction allows the modulation by the virus of JNK, p38 MAPK, STAT3, and Akt signaling pathways in a DR6-dependent manner (By similarity).

Interacts (via N-terminus) with host CIDEB (via N-terminus); this interaction seems to regulate the association of HCV particles with APOE (By similarity).

Interacts with host CHKA/Choline Kinase-alpha; CHKA bridges host PI4KA and NS5A and potentiates NS5A-stimulated PI4KA activity, which then facilitates the targeting of the ternary complex to the ER for viral replication (By similarity).

Interacts with host SPSB2 (via C-terminus); this interaction targets NS5A for ubiquitination and degradation (By similarity).

Interacts with host RAB18; this interaction may promote the association of NS5A and other replicase components with lipid droplets (By similarity).

By similarity3 Publications

Complete GO annotation on QuickGO ...

Homooligomer.

Interacts with non-structural protein 5A (By similarity).

Interacts with host VAPB (By similarity).

Interacts with host PRK2/PKN2 (By similarity).

Interacts with host HNRNPA1 and SEPT6; these interactions facilitate the viral replication (By similarity). Part of the replication complex composed of NS2, NS3, NS4A, NS4B, NS5A and the RNA-directed RNA polymerase embedded in an ER-derived membranous web (By similarity).

By similarity

Binary interactionsⁱ

Hide details

P26663

With	#Exp.	IntAct
Pkm [P52480] from Mus musculus.	3	EBI-6857429,EBI-647785
Sos1 [Q62245] from Mus musculus.	2	EBI-6857429,EBI-1693

Serine protease/helicase NS3 (PRO_0000037536)

With	#Exp.	IntAct
Non-structural protein 4A (PRO_0000037537)	6	EBI-6838571,EBI-6838576
TP53 [P04637] from Homo sapiens.	9	EBI-6838571,EBI-366083

RNA-directed RNA polymerase (PRO_0000037540)

With	#Exp.	IntAct
itself	2	EBI-6874437,EBI-6874437
Serine protease/helicase NS3 (PRO_0000037548) from Hepatitis C virus genotype 1b (isolate Con1).	5	EBI-6874437,EBI-6863741

GO - Molecular functionⁱ

Protein-protein interaction databases

IntActⁱ	P26663, 6 interactors
Molecular INTeraction database More...MINTⁱ	P26663

Chemistry databases

BindingDBⁱ

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	413 – 416	Combined sources	4
Beta strandⁱ	419 – 422	Combined sources	4
Beta strandⁱ	1017 – 1023	Combined sources	7
Beta strandⁱ	1031 – 1035	Combined sources	5
Helixⁱ	1039 – 1048	Combined sources	10
Beta strandⁱ	1057 – 1063	Combined sources	7
Beta strandⁱ	1068 – 1074	Combined sources	7
Beta strandⁱ	1077 – 1080	Combined sources	4
Helixⁱ	1082 – 1085	Combined sources	4
Beta strandⁱ	1090 – 1092	Combined sources	3
Beta strandⁱ	1095 – 1097	Combined sources	3
Beta strandⁱ	1100 – 1103	Combined sources	4
Turnⁱ	1104 – 1107	Combined sources	4
Beta strandⁱ	1108 – 1112	Combined sources	5
Beta strandⁱ	1128 – 1133	Combined sources	6
Beta strandⁱ	1135 – 1137	Combined sources	3
Beta strandⁱ	1139 – 1144	Combined sources	6
Beta strandⁱ	1146 – 1157	Combined sources	12
Helixⁱ	1158 – 1161	Combined sources	4
Beta strandⁱ	1168 – 1170	Combined sources	3
Turnⁱ	1172 – 1174	Combined sources	3
Beta strandⁱ	1176 – 1186	Combined sources	11
Beta strandⁱ	1189 – 1197	Combined sources	9
Helixⁱ	1198 – 1206	Combined sources	9
Beta strandⁱ	1224 – 1229	Combined sources	6
Beta strandⁱ	1232 – 1235	Combined sources	4
Turnⁱ	1236 – 1238	Combined sources	3
Helixⁱ	1239 – 1246	Combined sources	8
Beta strandⁱ	1251 – 1256	Combined sources	6
Helixⁱ	1258 – 1272	Combined sources	15
Beta strandⁱ	1277 – 1279	Combined sources	3
Beta strandⁱ	1290 – 1295	Combined sources	6
Helixⁱ	1296 – 1301	Combined sources	6
Beta strandⁱ	1307 – 1309	Combined sources	3
Beta strandⁱ	1311 – 1315	Combined sources	5
Turnⁱ	1316 – 1319	Combined sources	4
Helixⁱ	1323 – 1335	Combined sources	13
Turnⁱ	1336 – 1340	Combined sources	5
Beta strandⁱ	1342 – 1350	Combined sources	9
Beta strandⁱ	1362 – 1366	Combined sources	5
Beta strandⁱ	1371 – 1375	Combined sources	5
Beta strandⁱ	1378 – 1380	Combined sources	3
Helixⁱ	1382 – 1384	Combined sources	3
Beta strandⁱ	1386 – 1393	Combined sources	8
Helixⁱ	1397 – 1409	Combined sources	13
Beta strandⁱ	1414 – 1417	Combined sources	4
Beta strandⁱ	1419 – 1421	Combined sources	3
Helixⁱ	1423 – 1425	Combined sources	3
Beta strandⁱ	1428 – 1430	Combined sources	3
Beta strandⁱ	1432 – 1436	Combined sources	5
Helixⁱ	1438 – 1441	Combined sources	4
Turnⁱ	1442 – 1444	Combined sources	3
Beta strandⁱ	1448 – 1453	Combined sources	6
Beta strandⁱ	1456 – 1463	Combined sources	8
Beta strandⁱ	1467 – 1469	Combined sources	3
Beta strandⁱ	1471 – 1478	Combined sources	8
Helixⁱ	1481 – 1488	Combined sources	8
Beta strandⁱ	1493 – 1495	Combined sources	3
Beta strandⁱ	1497 – 1503	Combined sources	7
Beta strandⁱ	1509 – 1511	Combined sources	3
Helixⁱ	1514 – 1526	Combined sources	13
Helixⁱ	1532 – 1544	Combined sources	13
Helixⁱ	1555 – 1563	Combined sources	9
Helixⁱ	1570 – 1579	Combined sources	10
Helixⁱ	1584 – 1596	Combined sources	13
Helixⁱ	1606 – 1611	Combined sources	6
Turnⁱ	1612 – 1614	Combined sources	3
Helixⁱ	1615 – 1617	Combined sources	3
Beta strandⁱ	1625 – 1629	Combined sources	5
Beta strandⁱ	1635 – 1637	Combined sources	3
Helixⁱ	1640 – 1650	Combined sources	11
Turnⁱ	1653 – 1655	Combined sources	3
Beta strandⁱ	1680 – 1688	Combined sources	9
Beta strandⁱ	1690 – 1693	Combined sources	4
Beta strandⁱ	2421 – 2425	Combined sources	5
Helixⁱ	2446 – 2449	Combined sources	4
Helixⁱ	2453 – 2455	Combined sources	3
Beta strandⁱ	2456 – 2458	Combined sources	3
Helixⁱ	2461 – 2463	Combined sources	3
Helixⁱ	2464 – 2471	Combined sources	8
Helixⁱ	2481 – 2494	Combined sources	14
Helixⁱ	2504 – 2509	Combined sources	6
Turnⁱ	2519 – 2521	Combined sources	3
Helixⁱ	2524 – 2528	Combined sources	5
Helixⁱ	2532 – 2547	Combined sources	16
Beta strandⁱ	2549 – 2551	Combined sources	3
Beta strandⁱ	2555 – 2559	Combined sources	5
Beta strandⁱ	2563 – 2565	Combined sources	3
Turnⁱ	2568 – 2571	Combined sources	4
Beta strandⁱ	2578 – 2581	Combined sources	4
Helixⁱ	2584 – 2606	Combined sources	23
Helixⁱ	2607 – 2609	Combined sources	3
Helixⁱ	2611 – 2613	Combined sources	3
Helixⁱ	2616 – 2629	Combined sources	14
Beta strandⁱ	2630 – 2638	Combined sources	9
Helixⁱ	2643 – 2646	Combined sources	4
Helixⁱ	2649 – 2659	Combined sources	11
Helixⁱ	2666 – 2678	Combined sources	13
Turnⁱ	2679 – 2681	Combined sources	3
Beta strandⁱ	2683 – 2686	Combined sources	4
Beta strandⁱ	2688 – 2690	Combined sources	3
Beta strandⁱ	2692 – 2696	Combined sources	5
Beta strandⁱ	2701 – 2703	Combined sources	3
Helixⁱ	2706 – 2724	Combined sources	19
Beta strandⁱ	2728 – 2735	Combined sources	8
Beta strandⁱ	2738 – 2744	Combined sources	7
Helixⁱ	2748 – 2764	Combined sources	17
Beta strandⁱ	2769 – 2771	Combined sources	3
Beta strandⁱ	2776 – 2778	Combined sources	3
Helixⁱ	2779 – 2781	Combined sources	3
Beta strandⁱ	2787 – 2793	Combined sources	7
Beta strandⁱ	2795 – 2797	Combined sources	3
Beta strandⁱ	2799 – 2804	Combined sources	6
Helixⁱ	2808 – 2819	Combined sources	12
Helixⁱ	2826 – 2833	Combined sources	8
Turnⁱ	2834 – 2836	Combined sources	3
Helixⁱ	2838 – 2842	Combined sources	5
Helixⁱ	2844 – 2854	Combined sources	11
Beta strandⁱ	2858 – 2860	Combined sources	3
Beta strandⁱ	2862 – 2866	Combined sources	5
Beta strandⁱ	2869 – 2873	Combined sources	5
Helixⁱ	2875 – 2877	Combined sources	3
Helixⁱ	2878 – 2886	Combined sources	9
Helixⁱ	2888 – 2891	Combined sources	4
Helixⁱ	2898 – 2911	Combined sources	14
Helixⁱ	2916 – 2933	Combined sources	18
Helixⁱ	2935 – 2944	Combined sources	10
Helixⁱ	2946 – 2948	Combined sources	3
Beta strandⁱ	2949 – 2951	Combined sources	3
Helixⁱ	2959 – 2962	Combined sources	4
Turnⁱ	2967 – 2970	Combined sources	4
Beta strandⁱ	2976 – 2978	Combined sources	3
Beta strandⁱ	2980 – 2982	Combined sources	3

Show more details

3D structure databases

BMRBⁱ	P26663
SMRⁱ	P26663
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	P26663

EvolutionaryTraceⁱ

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Length
Domainⁱ	903 – 1026	Peptidase C18PROSITE-ProRule annotationAdd BLAST	124
Domainⁱ	1027 – 1208	Peptidase S29PROSITE-ProRule annotationAdd BLAST	182
Domainⁱ	1217 – 1369	Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST	153
Domainⁱ	2633 – 2751	RdRp catalyticPROSITE-ProRule annotationAdd BLAST	119

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	2 – 75	Disordered1 PublicationAdd BLAST	74
Regionⁱ	2 – 59	Interaction with DDX3XBy similarityAdd BLAST	58
Regionⁱ	2 – 58	Interaction with EIF2AK2/PKRBy similarityAdd BLAST	57
Regionⁱ	2 – 23	Interaction with STAT1By similarityAdd BLAST	22
Regionⁱ	112 – 152	Important for endoplasmic reticulum and mitochondrial localizationBy similarityAdd BLAST	41
Regionⁱ	122 – 173	Interaction with APOA2By similarityAdd BLAST	52
Regionⁱ	164 – 167	Important for lipid droplets localizationBy similarity	4
Regionⁱ	265 – 296	Important for fusionBy similarityAdd BLAST	32
Regionⁱ	385 – 411	HVR1By similarityAdd BLAST	27
Regionⁱ	474 – 482	HVR2By similarity	9
Regionⁱ	480 – 494	CD81-binding 11 PublicationAdd BLAST	15
Regionⁱ	544 – 552	CD81-binding 21 Publication	9
Regionⁱ	660 – 671	EIF2AK2/eIF2-alpha phosphorylation homology domain (PePHD)Add BLAST	12
Regionⁱ	904 – 1206	Protease NS2-31 PublicationAdd BLAST	303
Regionⁱ	929 – 949	Interaction with host SCPS1By similarityAdd BLAST	21
Regionⁱ	1486 – 1497	RNA-binding1 PublicationAdd BLAST	12
Regionⁱ	1679 – 1690	NS3-bindingBy similarityAdd BLAST	12
Regionⁱ	1833 – 1861	Glycine zipperBy similarityAdd BLAST	29
Regionⁱ	1978 – 1998	Membrane-bindingBy similarityAdd BLAST	21
Regionⁱ	2005 – 2221	RNA-bindingBy similarityAdd BLAST	217
Regionⁱ	2120 – 2332	Transcriptional activationSequence analysisAdd BLAST	213
Regionⁱ	2120 – 2208	FKBP8-bindingBy similarityAdd BLAST	89
Regionⁱ	2135 – 2139	Interaction with non-structural protein 4ABy similarity	5
Regionⁱ	2189 – 2441	Interaction with host SKP2By similarityAdd BLAST	253
Regionⁱ	2210 – 2275	EIF2AK2/PKR-binding1 PublicationAdd BLAST	66
Regionⁱ	2210 – 2249	ISDR1 PublicationAdd BLAST	40
Regionⁱ	2249 – 2306	NS4B-bindingSequence analysisAdd BLAST	58
Regionⁱ	2332 – 2441	Interaction with host IFI27By similarityAdd BLAST	110
Regionⁱ	2351 – 2407	DisorderedSequence analysisAdd BLAST	57
Regionⁱ	2354 – 2377	V3Add BLAST	24

Motif

Feature key	Position(s)	DescriptionActions	Length
Motifⁱ	5 – 13	Nuclear localization signalBy similarity	9
Motifⁱ	38 – 43	Nuclear localization signalBy similarity	6
Motifⁱ	58 – 64	Nuclear localization signalBy similarity	7
Motifⁱ	66 – 71	Nuclear localization signalBy similarity	6
Motifⁱ	1316 – 1319	DECH boxBy similarity	4
Motifⁱ	2322 – 2325	SH3-bindingSequence analysis	4
Motifⁱ	2326 – 2334	Nuclear localization signalBy similarity	9

Compositional bias

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Compositional biasⁱ	47 – 69	Basic and acidic residuesSequence analysisAdd BLAST		23
Compositional biasⁱ	2351 – 2369	Polar residuesSequence analysisAdd BLAST		19

Domainⁱ

The transmembrane regions of envelope E1 and E2 glycoproteins are involved in heterodimer formation, ER localization, and assembly of these proteins.By similarity

The transmembrane regions of envelope E1 and E2 glycoproteins are involved in heterodimer formation, ER localization, and assembly of these proteins (By similarity). Envelope E2 glycoprotein contain two highly variable regions called hypervariable region 1 and 2 (HVR1 and HVR2) (By similarity). E2 also contain two segments involved in CD81-binding (PubMed:12660945). HVR1 is implicated in the SCARB1-mediated cell entry and probably acts as a regulator of the association of particles with lipids (By similarity).By similarity1 Publication

The N-terminus of NS3 is required for the catalytic activity of protease NS2 (PubMed:9261354, PubMed:11591719). The minimal catalytic region includes the C-terminus of NS2 and the N-terminus NS3 protease domain (active region NS2-3) (PubMed:11591719).2 Publications

The N-terminal one-third of serine protease/helicase NS3 contains the protease activity (PubMed:9261354, PubMed:11591719). This region contains a zinc atom that does not belong to the active site, but may play a structural rather than a catalytic role (By similarity). This region is essential for the activity of protease NS2, maybe by contributing to the folding of the latter (By similarity). The NTPase/helicase activity is located in the twothirds C-terminus of NS3, this domain contains the NTPase and RNA-binding regions (PubMed:9614113).By similarity3 Publications

Contains a glycine zipper region that critically contributes to the biogenesis of functional ER-derived replication organelles.By similarity

SH3-binding, Transmembrane, Transmembrane helix

The N-terminus of NS5A acts as membrane anchor (By similarity). The central part of NS5A contains a variable region called interferon sensitivity determining region (ISDR) and seems to be intrinsically disordered and interacts with NS5B and host EIF2AK2 (Probable). The C-terminus of NS5A contains a variable region called variable region 3 (V3) (By similarity). ISDR and V3 may be involved in sensitivity and/or resistance to IFN-alpha therapy (By similarity). The C-terminus contains a nuclear localization signal (By similarity). The SH3-binding domain is involved in the interaction with host BIN1, GRB2 and Src-family kinases (By similarity).By similarity1 Publication

Sequence similaritiesⁱ

Belongs to the hepacivirus polyprotein family.Curated

Keywords - Domainⁱ

Family and domain databases

Gene3Dⁱ	1.20.1280.150, 1 hit 2.20.25.210, 1 hit 2.20.25.220, 1 hit 2.30.30.710, 1 hit 2.40.10.10, 1 hit 3.30.70.270, 2 hits 3.40.50.300, 2 hits 4.10.710.10, 1 hit
InterProⁱ	View protein in InterPro IPR011492, DEAD_Flavivir IPR043502, DNA/RNA_pol_sf IPR002521, HCV_core_C IPR044896, HCV_core_chain_A IPR002522, HCV_core_N IPR002519, HCV_env IPR002531, HCV_NS1 IPR002518, HCV_NS2 IPR042205, HCV_NS2_C IPR042209, HCV_NS2_N IPR000745, HCV_NS4a IPR001490, HCV_NS4b IPR002868, HCV_NS5a IPR013193, HCV_NS5a_1B_dom IPR038568, HCV_NS5A_1B_sf IPR024350, HCV_NS5a_C IPR014001, Helicase_ATP-bd IPR001650, Helicase_C IPR013192, NS5A_1a IPR038170, NS5A_1a_sf IPR027417, P-loop_NTPase IPR009003, Peptidase_S1_PA IPR043504, Peptidase_S1_PA_chymotrypsin IPR004109, Peptidase_S29_NS3 IPR043128, Rev_trsase/Diguanyl_cyclase IPR007094, RNA-dir_pol_PSvirus IPR002166, RNA_pol_HCV
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF07652, Flavi_DEAD, 1 hit PF01543, HCV_capsid, 1 hit PF01542, HCV_core, 1 hit PF01539, HCV_env, 1 hit PF01560, HCV_NS1, 1 hit PF01538, HCV_NS2, 1 hit PF01006, HCV_NS4a, 1 hit PF01001, HCV_NS4b, 1 hit PF01506, HCV_NS5a, 1 hit PF08300, HCV_NS5a_1a, 1 hit PF08301, HCV_NS5a_1b, 1 hit PF12941, HCV_NS5a_C, 1 hit PF02907, Peptidase_S29, 1 hit PF00998, RdRP_3, 1 hit
SMARTⁱ	View protein in SMART SM00487, DEXDc, 1 hit
SUPFAMⁱ	SSF50494, SSF50494, 1 hit SSF52540, SSF52540, 2 hits SSF56672, SSF56672, 1 hit
PROSITEⁱ	View protein in PROSITE PS51693, HCV_NS2_PRO, 1 hit PS51192, HELICASE_ATP_BIND_1, 1 hit PS51194, HELICASE_CTER, 1 hit PS51822, HV_PV_NS3_PRO, 1 hit PS50507, RDRP_SSRNA_POS, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

Sequence processingⁱ: The displayed sequence is further processed into a mature form.

P26663-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MSTNPKPQRK TKRNTNRRPQ DVKFPGGGQI VGGVYLLPRR GPRLGVRAPR 
        60         70         80         90        100
KTSERSQPRG RRQPIPKARR PEGRTWAQPG YPWPLYGNEG LGWAGWLLSP 
       110        120        130        140        150
RGSRPSWGPT DPRRRSRNLG KVIDTLTCGF ADLMGYIPLV GAPLGGAARA 
       160        170        180        190        200
LAHGVRVLED GVNYATGNLP GCSFSIFLLA LLSCLTTPAS AYEVHNVSGI 
       210        220        230        240        250
YHVTNDCSNA SIVYEAADLI MHTPGCVPCV REGNSSRCWV ALTPTLAARN 
       260        270        280        290        300
VTIPTTTIRR HVDLLVGAAA FCSAMYVGDL CGSVFLVSQL FTFSPRRHVT 
       310        320        330        340        350
LQDCNCSIYP GHVSGHRMAW DMMMNWSPTT ALVVSQLLRI PQAVVDMVAG 
       360        370        380        390        400
AHWGVLAGLA YYSMAGNWAK VLIVMLLFAG VDGDTHVTGG AQAKTTNRLV 
       410        420        430        440        450
SMFASGPSQK IQLINTNGSW HINRTALNCN DSLQTGFLAA LFYTHSFNSS 
       460        470        480        490        500
GCPERMAQCR TIDKFDQGWG PITYAESSRS DQRPYCWHYP PPQCTIVPAS 
       510        520        530        540        550
EVCGPVYCFT PSPVVVGTTD RFGVPTYRWG ENETDVLLLN NTRPPQGNWF 
       560        570        580        590        600
GCTWMNSTGF TKTCGGPPCN IGGVGNNTLT CPTDCFRKHP EATYTKCGSG 
       610        620        630        640        650
PWLTPRCMVD YPYRLWHYPC TVNFTIFKVR MYVGGVEHRL NAACNWTRGE 
       660        670        680        690        700
RCDLEDRDRP ELSPLLLSTT EWQVLPCSFT TLPALSTGLI HLHQNIVDVQ 
       710        720        730        740        750
YLYGIGSAVV SFAIKWEYVL LLFLLLADAR VCACLWMMLL IAQAEAALEN 
       760        770        780        790        800
LVVLNSASVA GAHGILSFLV FFCAAWYIKG RLVPGATYAL YGVWPLLLLL 
       810        820        830        840        850
LALPPRAYAM DREMAASCGG AVFVGLVLLT LSPYYKVFLA RLIWWLQYFT 
       860        870        880        890        900
TRAEADLHVW IPPLNARGGR DAIILLMCAV HPELIFDITK LLIAILGPLM 
       910        920        930        940        950
VLQAGITRVP YFVRAQGLIH ACMLVRKVAG GHYVQMAFMK LGALTGTYIY 
       960        970        980        990       1000
NHLTPLRDWP RAGLRDLAVA VEPVVFSDME TKIITWGADT AACGDIILGL 
      1010       1020       1030       1040       1050
PVSARRGKEI LLGPADSLEG RGLRLLAPIT AYSQQTRGLL GCIITSLTGR 
      1060       1070       1080       1090       1100
DKNQVEGEVQ VVSTATQSFL ATCVNGVCWT VYHGAGSKTL AAPKGPITQM 
      1110       1120       1130       1140       1150
YTNVDQDLVG WPKPPGARSL TPCTCGSSDL YLVTRHADVI PVRRRGDSRG 
      1160       1170       1180       1190       1200
SLLSPRPVSY LKGSSGGPLL CPFGHAVGIF RAAVCTRGVA KAVDFVPVES 
      1210       1220       1230       1240       1250
METTMRSPVF TDNSSPPAVP QSFQVAHLHA PTGSGKSTKV PAAYAAQGYK 
      1260       1270       1280       1290       1300
VLVLNPSVAA TLGFGAYMSK AHGIDPNIRT GVRTITTGAP VTYSTYGKFL 
      1310       1320       1330       1340       1350
ADGGCSGGAY DIIICDECHS TDSTTILGIG TVLDQAETAG ARLVVLATAT 
      1360       1370       1380       1390       1400
PPGSVTVPHP NIEEVALSNT GEIPFYGKAI PIEAIRGGRH LIFCHSKKKC 
      1410       1420       1430       1440       1450
DELAAKLSGL GINAVAYYRG LDVSVIPTIG DVVVVATDAL MTGYTGDFDS 
      1460       1470       1480       1490       1500
VIDCNTCVTQ TVDFSLDPTF TIETTTVPQD AVSRSQRRGR TGRGRRGIYR 
      1510       1520       1530       1540       1550
FVTPGERPSG MFDSSVLCEC YDAGCAWYEL TPAETSVRLR AYLNTPGLPV 
      1560       1570       1580       1590       1600
CQDHLEFWES VFTGLTHIDA HFLSQTKQAG DNFPYLVAYQ ATVCARAQAP 
      1610       1620       1630       1640       1650
PPSWDQMWKC LIRLKPTLHG PTPLLYRLGA VQNEVTLTHP ITKYIMACMS 
      1660       1670       1680       1690       1700
ADLEVVTSTW VLVGGVLAAL AAYCLTTGSV VIVGRIILSG RPAIVPDREL 
      1710       1720       1730       1740       1750
LYQEFDEMEE CASHLPYIEQ GMQLAEQFKQ KALGLLQTAT KQAEAAAPVV 
      1760       1770       1780       1790       1800
ESKWRALETF WAKHMWNFIS GIQYLAGLST LPGNPAIASL MAFTASITSP 
      1810       1820       1830       1840       1850
LTTQSTLLFN ILGGWVAAQL APPSAASAFV GAGIAGAAVG SIGLGKVLVD 
      1860       1870       1880       1890       1900
ILAGYGAGVA GALVAFKVMS GEMPSTEDLV NLLPAILSPG ALVVGVVCAA 
      1910       1920       1930       1940       1950
ILRRHVGPGE GAVQWMNRLI AFASRGNHVS PTHYVPESDA AARVTQILSS 
      1960       1970       1980       1990       2000
LTITQLLKRL HQWINEDCST PCSGSWLRDV WDWICTVLTD FKTWLQSKLL 
      2010       2020       2030       2040       2050
PQLPGVPFFS CQRGYKGVWR GDGIMQTTCP CGAQITGHVK NGSMRIVGPK 
      2060       2070       2080       2090       2100
TCSNTWHGTF PINAYTTGPC TPSPAPNYSR ALWRVAAEEY VEVTRVGDFH 
      2110       2120       2130       2140       2150
YVTGMTTDNV KCPCQVPAPE FFSEVDGVRL HRYAPACRPL LREEVTFQVG 
      2160       2170       2180       2190       2200
LNQYLVGSQL PCEPEPDVAV LTSMLTDPSH ITAETAKRRL ARGSPPSLAS 
      2210       2220       2230       2240       2250
SSASQLSAPS LKATCTTHHV SPDADLIEAN LLWRQEMGGN ITRVESENKV 
      2260       2270       2280       2290       2300
VVLDSFDPLR AEEDEREVSV PAEILRKSKK FPAAMPIWAR PDYNPPLLES 
      2310       2320       2330       2340       2350
WKDPDYVPPV VHGCPLPPIK APPIPPPRRK RTVVLTESSV SSALAELATK 
      2360       2370       2380       2390       2400
TFGSSESSAV DSGTATALPD QASDDGDKGS DVESYSSMPP LEGEPGDPDL 
      2410       2420       2430       2440       2450
SDGSWSTVSE EASEDVVCCS MSYTWTGALI TPCAAEESKL PINALSNSLL 
      2460       2470       2480       2490       2500
RHHNMVYATT SRSAGLRQKK VTFDRLQVLD DHYRDVLKEM KAKASTVKAK 
      2510       2520       2530       2540       2550
LLSVEEACKL TPPHSAKSKF GYGAKDVRNL SSKAVNHIHS VWKDLLEDTV 
      2560       2570       2580       2590       2600
TPIDTTIMAK NEVFCVQPEK GGRKPARLIV FPDLGVRVCE KMALYDVVST 
      2610       2620       2630       2640       2650
LPQVVMGSSY GFQYSPGQRV EFLVNTWKSK KNPMGFSYDT RCFDSTVTEN 
      2660       2670       2680       2690       2700
DIRVEESIYQ CCDLAPEARQ AIKSLTERLY IGGPLTNSKG QNCGYRRCRA 
      2710       2720       2730       2740       2750
SGVLTTSCGN TLTCYLKASA ACRAAKLQDC TMLVNGDDLV VICESAGTQE 
      2760       2770       2780       2790       2800
DAASLRVFTE AMTRYSAPPG DPPQPEYDLE LITSCSSNVS VAHDASGKRV 
      2810       2820       2830       2840       2850
YYLTRDPTTP LARAAWETAR HTPVNSWLGN IIMYAPTLWA RMILMTHFFS 
      2860       2870       2880       2890       2900
ILLAQEQLEK ALDCQIYGAC YSIEPLDLPQ IIERLHGLSA FSLHSYSPGE 
      2910       2920       2930       2940       2950
INRVASCLRK LGVPPLRVWR HRARSVRARL LSQGGRAATC GKYLFNWAVK 
      2960       2970       2980       2990       3000
TKLKLTPIPA ASRLDLSGWF VAGYSGGDIY HSLSRARPRW FMLCLLLLSV 
      3010
GVGIYLLPNR

Length:3,010

Mass (Da):327,194

Last modified:January 23, 2007 - v3

Checksum:ⁱF8422D5ECCFDFD9C

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	M58335 Genomic RNA Translation: AAA72945.1
PIRⁱ	A38465, GNWVTC

Protein	Similar proteins		Species	Score	Length	Source
P26663	RNA-directed RNA polymerase (Fragment)		9HEPC		112	UniRef100_P26663
Polyprotein (Fragment)		Hepatitis C virus subtype 1b		40
RNA-directed RNA polymerase (Fragment)		9HEPC		120
RNA-directed RNA polymerase (Fragment)		9HEPC		120
Core protein (Fragment)		9HEPC		117
+26

Protein	Similar proteins		Species	Score	Length	Source
P26663	Genome polyprotein		HCVJT		3010	UniRef90_P26663
RNA-directed RNA polymerase (Fragment)		9HEPC		112
Polyprotein (Fragment)		Hepatitis C virus subtype 1b		40
Genome polyprotein (Fragment)		Hepatitis C virus genotype 2		59
Envelope 2 protein (Fragment)		Hepatitis C virus subtype 1a		27
+938

Protein	Similar proteins		Species	Score	Length	Source
P26663	Genome polyprotein	)	HCVJA		3010	UniRef50_P26662
Genome polyprotein	)	HCVTW		3010
Genome polyprotein		HCVR6		3010
Genome polyprotein	)	HCVCO		3010
Genome polyprotein	)	HCVJ4		3010
+23394

Cross-referencesⁱ

Web resourcesⁱ

Virus Pathogen Resource

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	M58335 Genomic RNA Translation: AAA72945.1
PIRⁱ	A38465, GNWVTC

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	1A1Q	X-ray	2.40	A/B/C	1027-1215	[»]
	1BT7	NMR	-	A	1027-1206	[»]
	1C2P	X-ray	1.90	A/B	2422-2989	[»]
	1CSJ	X-ray	2.80	A/B	2420-2950	[»]
	1CU1	X-ray	2.50	A/B	1029-1657	[»]
	1GX5	X-ray	1.70	A	2420-2955	[»]
	1GX6	X-ray	1.85	A	2420-2950	[»]
	1JXP	X-ray	2.20	A/B	1027-1206	[»]
				C/D	1678-1691	[»]
	1NHU	X-ray	2.00	A/B	2420-2989	[»]
	1NHV	X-ray	2.90	A/B	2420-2989	[»]
	1NS3	X-ray	2.80	A/B	1029-1206	[»]
				C/D	1678-1689	[»]
	1OS5	X-ray	2.20	A	2420-2989	[»]
	1QUV	X-ray	2.50	A	2420-2989	[»]
	2AWZ	X-ray	2.15	A/B	2420-2989	[»]
	2AX0	X-ray	2.00	A/B	2420-2989	[»]
	2AX1	X-ray	2.10	A/B	2420-2989	[»]
	2BRK	X-ray	2.30	A	2420-2955	[»]
	2BRL	X-ray	2.40	A	2420-2955	[»]
	2DXS	X-ray	2.20	A/B	2420-2963	[»]
	2GIQ	X-ray	1.65	A/B	2421-2981	[»]
	2GIR	X-ray	1.90	A/B	2421-2981	[»]
	2HAI	X-ray	1.58	A	2420-2988	[»]
	2HWH	X-ray	2.30	A/B	2422-2989	[»]
	2HWI	X-ray	2.00	A/B	2422-2989	[»]
	2I1R	X-ray	2.20	A/B	2422-2989	[»]
	2JC0	X-ray	2.20	A/B	2420-2989	[»]
	2JC1	X-ray	2.00	A/B	2420-2989	[»]
	2O5D	X-ray	2.20	A/B	2422-2989	[»]
	2WCX	X-ray	2.00	A	2420-2955	[»]
	2WHO	X-ray	2.00	A/B	2420-2955	[»]
	2WRM	X-ray	1.95	A	2420-2955	[»]
	2XWY	X-ray	2.53	A	2420-2955	[»]
	2ZKU	X-ray	1.95	A/B/C/D	2420-2989	[»]
	3BR9	X-ray	2.30	A/B	2420-2989	[»]
	3BSA	X-ray	2.30	A/B	2420-2989	[»]
	3BSC	X-ray	2.65	A/B	2420-2989	[»]
	3CDE	X-ray	2.10	A/B	2420-2989	[»]
	3CIZ	X-ray	1.87	A/B	2421-2989	[»]
	3CJ0	X-ray	1.90	A/B	2421-2989	[»]
	3CJ2	X-ray	1.75	A/B	2421-2989	[»]
	3CJ3	X-ray	1.87	A/B	2421-2989	[»]
	3CJ4	X-ray	2.07	A/B	2421-2989	[»]
	3CJ5	X-ray	1.92	A/B	2421-2989	[»]
	3CO9	X-ray	2.10	A/B	2420-2989	[»]
	3CVK	X-ray	2.31	A/B	2420-2989	[»]
	3CWJ	X-ray	2.40	A/B	2420-2989	[»]
	3D28	X-ray	2.30	A/B	2420-2989	[»]
	3D5M	X-ray	2.20	A/B	2420-2989	[»]
	3E51	X-ray	1.90	A/B	2420-2989	[»]
	3FQK	X-ray	2.20	A/B	2421-2989	[»]
	3FRZ	X-ray	1.86	A	2420-2989	[»]
	3G86	X-ray	2.20	A/B	2421-2989	[»]
	3GYN	X-ray	2.15	A/B	2420-2989	[»]
	3H2L	X-ray	1.90	A/B	2420-2989	[»]
	3H59	X-ray	2.10	A/B	2421-2989	[»]
	3H5S	X-ray	2.00	A/B	2421-2989	[»]
	3H5U	X-ray	1.95	A/B	2421-2989	[»]
	3H98	X-ray	1.90	A/B	2421-2989	[»]
	3IGV	X-ray	2.60	A/B	2420-2989	[»]
	3MF5	X-ray	2.00	A/B	2421-2989	[»]
	3RVB	X-ray	2.20	A	1186-1657	[»]
3UA7	X-ray	1.50	E/F	2321-2331	[»]
3UDL	X-ray	2.17	A/B/C/D	2420-2989	[»]
3VQS	X-ray	1.90	A/B/C/D	2420-2989	[»]
4A92	X-ray	2.73	A/B	1029-1657	[»]
			A/B	1678-1690	[»]
4B6E	X-ray	2.46	A/B	1029-1657	[»]
4B6F	X-ray	2.89	A/B	1029-1657	[»]
4B71	X-ray	2.50	A/B	1029-1657	[»]
4B73	X-ray	2.50	A/B	1029-1657	[»]
4B74	X-ray	2.18	A/B	1029-1657	[»]
4B75	X-ray	2.53	A/B	1029-1655	[»]
4B76	X-ray	2.14	A/B	1029-1657	[»]
4DGV	X-ray	1.80	A	412-423	[»]
4DGY	X-ray	1.80	A	412-423	[»]
4EO6	X-ray	1.79	A/B	2422-2989	[»]
4EO8	X-ray	1.80	A/B	2422-2989	[»]
4IH5	X-ray	1.90	A/B	2421-2989	[»]
4IH6	X-ray	2.20	A/B	2421-2989	[»]
4IH7	X-ray	2.30	A/B	2421-2989	[»]
4K8B	X-ray	2.80	C/D	1678-1689	[»]
4KAI	X-ray	2.30	A/B	2420-2989	[»]
4KB7	X-ray	1.85	A/B	2420-2989	[»]
4KBI	X-ray	2.06	A/B	2420-2989	[»]
4KE5	X-ray	2.11	A/B	2420-2989	[»]
4MIA	X-ray	2.80	A/B	2421-2989	[»]
4MIB	X-ray	2.30	A/B	2421-2989	[»]
4MK7	X-ray	2.80	A/B	2421-2989	[»]
4MK8	X-ray	2.09	A/B	2421-2989	[»]
4MK9	X-ray	2.05	A/B	2421-2989	[»]
4MKA	X-ray	2.05	A/B	2421-2989	[»]
4MKB	X-ray	1.90	A/B	2421-2989	[»]
4TN2	X-ray	2.70	A	2422-2989	[»]
4WXP	X-ray	2.08	A	1206-1656	[»]
5FPS	X-ray	2.68	A/B	1029-1657	[»]
5FPT	X-ray	2.72	A/B	1029-1657	[»]
5FPY	X-ray	2.52	A/B	1029-1657	[»]
5KZP	X-ray	2.26	A/B/C/D	412-423	[»]
5W2E	X-ray	2.80	A/B	2422-2989	[»]
6MVP	X-ray	2.00	A/B	2420-2989	[»]
6W4G	X-ray	1.95	A/B	2421-2981	[»]
8OHM	X-ray	2.30	A	1216-1650	[»]
BMRBⁱ	P26663
SMRⁱ	P26663
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Protein-protein interaction databases

IntActⁱ	P26663, 6 interactors
MINTⁱ	P26663

Chemistry databases

BindingDBⁱ	P26663
ChEMBLⁱ	CHEMBL6040
DrugBankⁱ	DB08706, (2S)-({(5Z)-5-[(5-Ethyl-2-furyl)methylene]-4-oxo-4,5-dihydro-1,3-thiazol-2-yl}amino)(4-fluorophenyl)acetic acid DB03605, (2s)-2-[(2,4-Dichloro-Benzoyl)-(3-Trifluoromethyl-Benzyl)-Amino]-3-Phenyl-Propionic Acid DB02331, (2s)-2-[(5-Benzofuran-2-Yl-Thiophen-2-Ylmethyl)-(2,4-Dichloro-Benzoyl)-Amino]-3-Phenyl-Propionic Acid DB07199, (2S,4S,5R)-1-(4-TERT-BUTYLBENZOYL)-2-ISOBUTYL-5-(1,3-THIAZOL-2-YL)PYRROLIDINE-2,4-DICARBOXYLIC ACID DB07200, (2S,4S,5R)-2-ISOBUTYL-5-(2-THIENYL)-1-[4-(TRIFLUOROMETHYL)BENZOYL]PYRROLIDINE-2,4-DICARBOXYLIC ACID 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 DB08710, (5Z)-5-[(5-ethylfuran-2-yl)methylidene]-2-[[(S)-(4-fluorophenyl)-(2H-tetrazol-5-yl)methyl]amino]-1,3-thiazol-4-one DB08390, (6S)-6-CYCLOPENTYL-6-[2-(3-FLUORO-4-ISOPROPOXYPHENYL)ETHYL]-4-HYDROXY-5,6-DIHYDRO-2H-PYRAN-2-ONE DB08278, 1-(2-cyclopropylethyl)-3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-6-fluoro-4-hydroxy-2(1H)-quinolinone DB08701, 2-(3-BROMOPHENYL)-6-[(2-HYDROXYETHYL)AMINO]-1H-BENZO[DE]ISOQUINOLINE-1,3(2H)-DIONE 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 DB07570, 3-CYCLOHEXYL-1-(2-MORPHOLIN-4-YL-2-OXOETHYL)-2-PHENYL-1H-INDOLE-6-CARBOXYLIC ACID DB08279, 3-{ISOPROPYL[(TRANS-4-METHYLCYCLOHEXYL)CARBONYL]AMINO}-5-PHENYLTHIOPHENE-2-CARBOXYLIC ACID DB08581, 4-[(4-bromo-2-{[(3R,5S)-3,5-dimethylpiperidin-1-yl]carbonyl}phenyl)amino]-4-oxobutanoic acid DB08578, 4-[(5-bromopyridin-2-yl)amino]-4-oxobutanoic acid DB08580, 4-bromo-2-{[(2R)-2-(2-chlorobenzyl)pyrrolidin-1-yl]carbonyl}aniline DB08579, 4-bromo-2-{[(3R,5S)-3,5-dimethylpiperidin-1-yl]carbonyl}aniline DB08481, 4-Methyl-N-[5-(5-methyl-furan-2-ylmethylene)-4-oxo-thiazolidin-2-ylidene]-benzenesulfonamide DB06974, 5-hydroxy-4-(7-methoxy-1,1-dioxido-2H-1,2,4-benzothiadiazin-3-yl)-2-(3-methylbutyl)-6-phenylpyridazin-3(2H)-one DB07169, 5R-(3,4-DICHLOROPHENYLMETHYL)-3-(2-THIOPHENESULFONYLAMINO)-4-OXO-2-THIONOTHIAZOLIDINE DB11586, Asunaprevir DB04137, Guanosine-5'-Triphosphate DB08582, N-(4-bromo-2-{[(3R,5S)-3,5-dimethylpiperidin-1-yl]carbonyl}phenyl)-4-morpholin-4-yl-4-oxobutanamide DB08031, N-[(13-CYCLOHEXYL-6,7-DIHYDROINDOLO[1,2-D][1,4]BENZOXAZEPIN-10-YL)CARBONYL]-2-METHYL-L-ALANINE 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 DB07238, Nesbuvir DB04005, Uridine 5'-triphosphate
DrugCentralⁱ	P26663

Protein family/group databases

MEROPSⁱ	S29.001

MEROPSⁱ

S29.001

PTM databases

iPTMnetⁱ	P26663

iPTMnetⁱ

Protocols and materials databases

ABCDⁱ	P26663, 4 sequenced antibodies

ABCDⁱ

P26663, 4 sequenced antibodies

Organism-specific databases

euHCVdbⁱ	M58335

euHCVdbⁱ

M58335

Enzyme and pathway databases

BRENDAⁱ	3.4.21.98, 17002

BRENDAⁱ

3.4.21.98, 17002

Miscellaneous databases

EvolutionaryTraceⁱ	P26663

EvolutionaryTraceⁱ