ProRule PRU01166

General rule information [?]

Accession PRU01166
Dates 28-NOV-2016 (Created)
1-MAR-2024 (Last updated, Version 10)
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.
Scope(s) Viruses
Example(s) Q9WMX2 (POLG_HCVCO);

Propagated annotation [?]

Identifier, protein and gene names [?]

case <FTGroup:1>
Protein name Contains:
RecName: Full=Serine protease NS3;
AltName: Full=Hepacivirin;
AltName: Full=NS3P;
AltName: Full=p70;
end case
case <FTGroup:1> and <AnyFeature:PS51192> and <AnyFeature:PS51194>

Comments [?]

FUNCTIONNS3 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 Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per NS3 protease domain;
end case
case <FTGroup:1> and <AnyFeature:PS51693>
ACTIVITY REGULATIONActivity 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>
DOMAINThe 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

Keywords [?]

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:symbiont-mediated suppression of host type I interferon-mediated signaling pathway
GO:0039545; Biological process:symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity
end case

Features [?]

From: PS51822
Key From To Description Tag Condition FTGroup
DOMAIN from to /note="Peptidase S29 #"
ACT_SITE 57 57 /note="Charge relay system; for serine protease NS3 activity" H 1
ACT_SITE 81 81 /note="Charge relay system; for serine protease NS3 activity" D 1
ACT_SITE 139 139 /note="Charge relay system; for serine protease NS3 activity" S 1
BINDING 97 97 /ligand="Zn(2+)"
C 2
BINDING 99 99 /ligand="Zn(2+)"
C 2
BINDING 145 145 /ligand="Zn(2+)"
C 2
BINDING 149 149 /ligand="Zn(2+)"
H 2

Additional information [?]

Size range 172-192 amino acids
Related rules None
Fusion None
Repeats 1
Topology Undefined


PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.

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UniProtKB rule member sequences [?]