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annotation rule: PRU01166

General rule information [?]

Accession PRU01166
Dates 28-NOV-2016 (Created)
22-NOV-2019 (Last updated, Version 6)
Data class Domain
Predictors PROSITE; PS51822; HV_PV_NS3_PRO
Name Hepacivirus/Pegivirus NS3 protease domain
Function The NS3/A4 protease is not only essential for generating mature viral proteins required for viral replication, but also hydrolyzes proteins, which are part of the innate immune system, thereby confounding the innate immune response to viral infection.

Propagated annotation [?]

Description [?]

case <FTGroup:1>
Contains: RecName: Full=Serine protease NS3; EC; AltName: Full=Hepacivirin; AltName: Full=NS3P; AltName: Full=p70;
end case

Comments [?]

case <FTGroup:1> and <AnyFeature:PS51192> and <AnyFeature:PS51194>
Function NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS.
end case

case <FTGroup:1>
Catalytic activity Reaction=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'.; EC=;
end case

case <FTGroup:2>
Cofactor Zn(2+)
Note: Binds 1 zinc ion per NS3 protease domain;
end case

case <FTGroup:1> and <AnyFeature:PS51693>
Activity regulation Activity of auto-protease NS2-3 is dependent on zinc ions and completely inhibited by EDTA. Serine protease NS3 is also activated by zinc ions.
end case

case <FTGroup:1> and <AnyFeature:PS51192> and <AnyFeature:PS51194>
Domain The N-terminal one-third of serine protease NS3 contains the protease activity. This region contains a zinc atom that does not belong to the active site, but may play a structural rather than a catalytic role. This region is essential for the activity of protease NS2-3, maybe by contributing to the folding of the latter. The helicase activity is located in the C-terminus of NS3.
end case

Gene Ontology [?]

case <FTGroup:2>
GO:0008270; Molecular function: zinc ion binding.
end case

case <FTGroup:1>
GO:0004252; Molecular function: serine-type endopeptidase activity.
GO:0039502; Biological process: suppression by virus of host type I interferon-mediated signaling pathway.
GO:0039545; Biological process: suppression by virus of host MAVS activity.
end case

Keywords [?]

case <FTGroup:2>
end case

case <FTGroup:1>
end case

Features [?]

From: PS51822
Key     From     To       Description   Tag   Condition   FTGroup
DOMAIN     from     to       Peptidase S29 #        
ACT_SITE     57     57       Charge relay system; for serine protease NS3 activity     H   1
ACT_SITE     81     81       Charge relay system; for serine protease NS3 activity     D   1
ACT_SITE     139     139       Charge relay system; for serine protease NS3 activity     S   1
METAL     97     97       Zinc     C   2
METAL     99     99       Zinc     C   2
METAL     145     145       Zinc     C   2
METAL     149     149       Zinc     H   2

Additional information [?]

Size range 172-192 amino acids
Related rules None
Repeats 1
Topology Undefined
Viruses; Hepacivirus
Comments None


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UniProtKB rule member sequences [?]