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Hepatitis C virus NS3
Serine protease/NTPase/helicase NS3
HCV is a positive, single-stranded RNA virus in the Flaviviridae family. The genome is approximately 10,000 nucleotides and encodes a single polyprotein of about 3,000 amino acids. The polyprotein is processed by host cell and viral proteases into three major structural proteins including NS3, and several non-structural proteins necessary for viral replication.
The NS3 part of the polyprotein displays three enzymatic activities: serine protease, NTPase and RNA helicase.
The NS3 serine proteinase (NS3P) is a non-structural hepatitis C protein responsible for proteolytic processing of other non-structural proteins; because of this, it is also the most extensively studied protein of the Hepatitis C genome. It is responsible for proteolytic processing of the entire downstream region of the HC polyprotein, catalyzing cleavage at the NS3/NS4a, NS4a/NS4b, NS4b/NS5a, and NS5a/NS5b sites to release the mature NS3, NS4a, NS4b, NS5a, and NS5b proteins.For proper function, NS3 requires NS4a as a cofactor, but, interestingly enough, NS3 also cleaves the NS4a protein. The molecular weight of the monomer NS3P is 70 kDa.
There are over 20 different subtypes of Hepatitis C Virus; the preponderance and distribution of HCV genotypes varies globally. Genotypes 4-6 are very common in geographic areas where chronic hepatitis C is highly prevalent. Genotype 5 has a low prevalence worldwide.
HCV Genotype information is important because of the role it plays in predicting HCV medical treatment response and treatment duration. Sustained cure rates (sustained viral response) of 75% or better occur in people with genotypes HCV 2 and 3 in 24 weeks of treatment. Genotypes 1a and 1b, the most prevalent worldwide, have the poorest rates of response to the present treatment regimen, which is a combination of pegylated alfa interferon 2b with ribavirin.
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