Genome polyprotein Recombinant Protein

Recombinant Hepatitis C virus Genome polyprotein

• Purity: Greater or equal to 85% purity as determined by SDS-PAGE.
• Synonyms: Genome polyprotein; Recombinant Hepatitis C virus Genome polyprotein; Recombinant Genome polyprotein; Genome polyprotein Cleaved into the following 4 chains: 1. Core protein p21; Capsid protein C p21 Core protein p19 Envelope glycoprotein E1; gp32 gp35 Envelope glycoprotein E2; NS1 gp68 gp70; Genome polyprotein recombinant protein

• Host: E Coli or Yeast or Baculovirus or Mammalian Cell
• Purity/Purification: Greater or equal to 85% purity as determined by SDS-PAGE.
• Form/Format: Lyophilized or liquid (Format to be determined during the manufacturing process)
• Sequence Positions: 384-737
• Sequence: NTRTVAGSAAATTRGFTSMFSSGSKQNLQLINTNGSWHINRTALNCNDSLNTGFIASLFYVNRFNSSGCPHRLSVCRSIEAFRIGWGTLQYEDNVTNPEDMRPYCWHYPPKPCGIVPARSVCGPVYCFTPSPVVVGTTDARGVPTYTWGENETDVFLLNSTRPPRGSWFGCTWMNSTGFTKTCGAPPCRIRADFNASTDLLCPTDCFRKHSDATYIKCGSGPWLTPKCMVDYPYRLWHYPCTVNYSIFKIRMYVGGVEHRLTAACNFTRGDPCNLEDRDRSQLSPLLHSTTEWAILPCTYSDLPALSTGLLHLHQNIVDVQYMYGLSPALTKYVVRWEWVVLLFLLLADARVCA
• Sequence Length: 737

• Species: Hepatitis C virus (isolate HC-J5) (HCV)
• Preparation and Storage: Store at -20 degree C. For extended storage, store at -20 or -80 degree C.

NCBI and Uniprot Product Information

• NCBI GI #: 130465
• UniProt Accession #: P27960
• Molecular Weight: 81,208 Da
• NCBI Official Full Name: Genome polyprotein
• UniProt Protein Name: Genome polyprotein
• Protein Family: Genome polyprotein
• UniProt Entry Name: POLG_HCVJ5

Uniprot Description

Function: Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis)

By similarity.E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection

By similarity.

Subunit structure: Core protein is a homomultimer that binds the C-terminal part of E1 and interacts with numerous cellular proteins. Interaction with human STAT1 SH2 domain seems to result in decreased STAT1 phosphorylation, leading to decreased IFN-stimulated gene transcription. In addition to blocking the formation of phosphorylated STAT1, the core protein also promotes ubiquitin-mediated proteasome-dependent degradation of STAT1. Interacts with, and constitutively activates human STAT3. Associates with human LTBR and TNFRSF1A receptors and possibly induces apoptosis. Binds to human SP110 isoform 3/Sp110b, HNRPK, C1QR1, YWHAE, UBE3A/E6AP, DDX3X, APOA2 and RXRA proteins. Interacts with human CREB3 nuclear transcription protein, triggering cell transformation. May interact with human p53. Also binds human cytokeratins KRT8, KRT18, KRT19 and VIM (vimentin). E1 and E2 glycoproteins form a heterodimer that binds to human LDLR, CLDN1, CD81 and SCARB1 receptors. E2 binds and inhibits human EIF2AK2/PKR. Also binds human CD209/DC-SIGN and CLEC4M/DC-SIGNR

By similarity.

Subcellular location: Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein

By similarity. Host mitochondrion membrane; Single-pass type I membrane protein

By similarity. Host lipid droplet

By similarity. Note: The C-terminal transmembrane domain of core protein p21 contains an ER signal leading the nascent polyprotein to the ER membrane. Only a minor proportion of core protein is present in the nucleus and an unknown proportion is secreted

By similarity. Ref.3Core protein p19: Virion

By similarity. Host cytoplasm

By similarity. Host nucleus

By similarity. Secreted

By similarity Ref.3. Envelope glycoprotein E1: Virion membrane; Single-pass type I membrane protein

Potential. Host endoplasmic reticulum membrane; Single-pass type I membrane protein

By similarity. Note: The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase. After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor. A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain. These events explain the final topology of the protein. ER retention of E1 is leaky and, in overexpression conditions, only a small fraction reaches the plasma membrane

By similarity. Ref.3Envelope glycoprotein E2: Virion membrane; Single-pass type I membrane protein

Potential. Host endoplasmic reticulum membrane; Single-pass type I membrane protein

By similarity. Note: The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase. After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor. A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain. These events explain the final topology of the protein. ER retention of E2 is leaky and, in overexpression conditions, only a small fraction reaches the plasma membrane

By similarity. Ref.3

Domain: The transmembrane regions of envelope E1 and E2 glycoproteins are involved in heterodimer formation, ER localization, and assembly of these proteins. Envelope E2 glycoprotein contain a highly variable region called hypervariable region 1 (HVR1). E2 also contains two segments involved in CD81-binding. HVR1 is implicated in the SCARB1-mediated cell entry. CD81-binding regions may be involved in sensitivity and/or resistance to IFN-alpha therapy

By similarity.

Post-translational modification: Specific enzymatic cleavages in vivo yield mature proteins. The structural proteins, core, E1 and E2 are produced by proteolytic processing by host signal peptidases. The core protein is synthesized as a 21 kDa precursor which is retained in the ER membrane through the hydrophobic signal peptide. Cleavage by the signal peptidase releases the 19 kDa mature core protein

By similarity.Core protein is phosphorylated by host PKC and PKA.Envelope E1 and E2 glycoproteins are highly N-glycosylated

By similarity.Core protein is ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation

By similarity.

Miscellaneous: Core protein 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.

Sequence similarities: Belongs to the hepacivirus polyprotein family.

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.