AC   PRU01166;
DC   Domain;
TR   PROSITE; PS51822; HV_PV_NS3_PRO; 1; level=0
XX
Names: 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.
XX
case <FTGroup:1>
DE   Contains:
DE     RecName: Full=Serine protease NS3;
DE              EC=3.4.21.98;
DE     AltName: Full=Hepacivirin;
DE     AltName: Full=NS3P;
DE     AltName: Full=p70;
end case
case <FTGroup:1> and <AnyFeature:PS51192> and <AnyFeature:PS51194>
XX
CC   -!- FUNCTION: NS3 displays three enzymatic activities: serine protease,
CC       NTPase and RNA helicase. NS3 serine protease, in association with NS4A,
CC       is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and
CC       NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human
CC       IRF3, thus preventing the establishment of dsRNA induced antiviral
CC       state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5'
CC       direction, and likely RNA stable secondary structure in the template
CC       strand. Cleaves and inhibits the host antiviral protein MAVS.
end case
case <FTGroup:1>
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Hydrolysis of four peptide bonds in the viral precursor
CC         polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr
CC         in P1 and Ser or Ala in P1'.; EC=3.4.21.98;
end case
case <FTGroup:2>
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC       Note=Binds 1 zinc ion per NS3 protease domain;
end case
case <FTGroup:1> and <AnyFeature:PS51693>
CC   -!- ACTIVITY REGULATION: Activity of auto-protease NS2-3 is dependent on
CC       zinc ions and completely inhibited by EDTA. Serine protease NS3 is also
CC       activated by zinc ions.
end case
case <FTGroup:1> and <AnyFeature:PS51192> and <AnyFeature:PS51194>
CC   -!- DOMAIN: The N-terminal one-third of serine protease NS3 contains the
CC       protease activity. This region contains a zinc atom that does not
CC       belong to the active site, but may play a structural rather than a
CC       catalytic role. This region is essential for the activity of protease
CC       NS2-3, maybe by contributing to the folding of the latter. The helicase
CC       activity is located in the C-terminus of NS3.
end case
XX
case <FTGroup:2>
GO   GO:0008270; F:zinc ion binding
end case
case <FTGroup:1>
GO   GO:0004252; F:serine-type endopeptidase activity
GO   GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway
GO   GO:0039545; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity
end case
XX
case <FTGroup:2>
KW   Metal-binding
KW   Zinc
end case
case <FTGroup:1>
KW   Hydrolase
KW   Protease
KW   Serine protease
KW   Viral immunoevasion
KW   Interferon antiviral system evasion
KW   Inhibition of host RLR pathway by virus
KW   Inhibition of host innate immune response by virus
KW   Inhibition of host interferon signaling pathway by virus
KW   Inhibition of host MAVS by virus
end case
XX
FT   From: PS51822
FT   DOMAIN          from..to
FT                   /note="Peptidase S29 #"
FT   ACT_SITE        57
FT                   /note="Charge relay system; for serine protease NS3
FT                   activity"
FT   Group: 1; Condition: H
FT   ACT_SITE        81
FT                   /note="Charge relay system; for serine protease NS3
FT                   activity"
FT   Group: 1; Condition: D
FT   ACT_SITE        139
FT                   /note="Charge relay system; for serine protease NS3
FT                   activity"
FT   Group: 1; Condition: S
FT   BINDING         97
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT   Group: 2; Condition: C
FT   BINDING         99
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT   Group: 2; Condition: C
FT   BINDING         145
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT   Group: 2; Condition: C
FT   BINDING         149
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT   Group: 2; Condition: H
XX
Chop: Nter=0; Cter=0;
Size: 172-192;
Related: None;
Repeats: 1;
Topology: Undefined;
Example: Q9WMX2;
Scope:
 Viruses; Hepacivirus
Comments: None;
XX
# Revision 1.9 2022/11/19
//