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Information on EC 3.4.21.114 - equine arterivirus serine peptidase and Organism(s) Equine arteritis virus and UniProt Accession P19811
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3.4.21.114 equine arterivirus serine peptidaseSpecify your search results
Word Map
- 3.4.21.114
- rotavirus
- enterotoxin
- prrsv
- gastroenteritis
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chikungunya
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replicase
- vp4
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chikvs
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rotavirus-infected
- nsp3
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viroporins
- astrovirus
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hp-prrsv
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anti-prrsv
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rv-induced
The taxonomic range for the selected organisms is: Equine arteritis virus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
cleavage of (Glu/Gln)-/-(Gly/Ser/Ala) in arterivirus replicase translation products ORF1a and ORF1ab
Synonyms
nonstructural protein 4, non-structural protein 4, 3c-like serine protease, 3clsp, nsp4 serine protease, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
equine arteritis virus serine endopeptidase
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
cleavage of C-N-linkage
CAS REGISTRY NUMBER
COMMENTARY
97162-88-4
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
arterivirus replicase ORF1ab + H2O
?
-
cleavage sites are the junctions at nsp3/4, Nsp4/5, 2 internal nsp5 sites, nsp5/6, p80/p50, p50/p26, p26/p12, enzyme cleaves between Glu and Gly, Glu and Ser or Glu and Lys
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?
arterivirus replicase ORF1a protein + H2O
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nsp4 and an unidentified protease is responsible for the cleavage sites nsp2/3, nsp3/4, nsp4/5 and nsp5/6 in the ORF1a protein
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?
arterivirus replicase ORF1a + H2O
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cleavage sites are Glu1430/Gly and Glu1452/Ser
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?
arterivirus replicase ORF1a + H2O
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ORF1a can be cleaved following two alternative pathways. In the majority nsp3-8 precursors are cleaved at the nsp4/5 site yielding nsp3-4 and nsp5-8. The latter product is then cleaved at nsp7/8 only. In the alternative proteolytic cascade the nsp4/5 site remains uncleaved while the nsp5/6 and nsp6/7 sites are processed. nsp3-8 has to interact with cleaved nsp2 to allow processing of the nsp4/5 junction, when nsp2 cofactor is absent the alternative pathway is used
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?
arterivirus replicase ORF1b + H2O
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protein is processed by nsp4 serine protease
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?
arterivirus replicase ORF1b + H2O
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protein is processed by nsp4 serine protease at the following sites: nsp9/10 i.e. p80/p50, cleavage occurs between Glu2370 and Ser, nsp10/11 i.e. p50/p26, cleavage occurs between Gln2837 and Ser, nsp11/12 i.e. nsp26/p12, cleavage between Glu3056 and Gly
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?
additional information
?
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nsp4 cleaves multiple GluX(Gly/Ser/Ala) sites, X: cleavage site
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?
additional information
?
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nsp4 cleaves multiple GluX(Gly/Ser/Ala) sites, X: cleavage site
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?
additional information
?
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protease has a specificity for Glu/Gly or Glu/Ser substrates
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?
additional information
?
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enzyme is the main viral protease
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?
additional information
?
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the enzyme controls the maturation of the replicase complex. The C-terminal domain has a modulating role in nsp4-mediated autoprocessing of the arterivirus replicase polyproteins
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?
additional information
?
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the enzyme cleaves the cognate nsp6/7- and nsp7/8 site in in vitro synthesized substrates
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
arterivirus replicase ORF1a + H2O
?
-
ORF1a can be cleaved following two alternative pathways. In the majority nsp3-8 precursors are cleaved at the nsp4/5 site yielding nsp3-4 and nsp5-8. The latter product is then cleaved at nsp7/8 only. In the alternative proteolytic cascade the nsp4/5 site remains uncleaved while the nsp5/6 and nsp6/7 sites are processed. nsp3-8 has to interact with cleaved nsp2 to allow processing of the nsp4/5 junction, when nsp2 cofactor is absent the alternative pathway is used
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?
additional information
?
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-
enzyme is the main viral protease
-
?
additional information
?
-
-
the enzyme controls the maturation of the replicase complex. The C-terminal domain has a modulating role in nsp4-mediated autoprocessing of the arterivirus replicase polyproteins
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-
?
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
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nsp4 inhibits virus-induced IFN-beta production by targeting NF-kappaB essential modulator NEMO for proteolytic cleavage. The scission occurs at sites E166, E171, Q205, and E349
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
proteolytic modification
ORF1a is subject to at least 5 proteolytic cleavages, resulting in five non-structural protein 1-6
proteolytic modification
replicase of EAV processed by at least 3 viral proteases, resulting in the generation of non-structural proteins Nsp1-6
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D1129E
mutant is able to cleave the Nsp4/5 site with wild-type efficiently but does not process the Nsp3/4 and Nsp5/6 junctions
T1179N
retains wild-type activity towards Nsp4/5, cleaves Nsp5/6 with increased efficiency
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
large scale production of recombinant nsp4 in Escherichia coli. The nsp4 proteinase is expressed either fused to maltose binding protein or carrying a C-terminal hexahistidine tag
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Snijder, E.J.; Wassenaar, A.L.; Spaan, W.J.
Proteolytic processing of the N-terminal region of the equine arteritis virus replicase
Adv. Exp. Med. Biol.
342
227-232
1993
equine arteritis virus (P19811)
Snijder, E.J.; Wassenaar, A.L.; van Dinten, L.C.; Spaan, W.J.; Gorbalenya, A.E.
The arterivirus nsp4 protease is the prototype of a novel group of chymotrypsin-like enzymes, the 3C-like serine proteases
J. Biol. Chem.
271
4864-4871
1996
equine arteritis virus (P19811), equine arteritis virus, equine arteritis virus Bucyrus (P19811)
Barrette-Ng, I.H.; Ng, K.K.; Mark, B.L.; Van Aken, D.; Cherney, M.M.; Garen, C.; Kolodenko, Y.; Gorbalenya, A.E.; Snijder, E.J.; James, M.N.
Structure of arterivirus nsp4. The smallest chymotrypsin-like proteinase with an alpha/beta C-terminal extension and alternate conformations of the oxyanion hole
J. Biol. Chem.
277
39960-39966
2002
equine arteritis virus (P19811), equine arteritis virus
den Boon, J.A.; Snijder, E.J.; Chirnside, E.D.; de Vries, A.A.; Horzinek, M.C.; Spaan, W.J.
Equine arteritis virus is not a togavirus but belongs to the coronaviruslike superfamily
J. Virol.
65
2910-2920
1991
equine arteritis virus (P19811)
van Dinten, L.C.; Wassenaar, A.L.; Gorbalenya, A.E.; Spaan, W.J.; Snijder, E.J.
Processing of the equine arteritis virus replicase ORF1b protein: identification of cleavage products containing the putative viral polymerase and helicase domains
J. Virol.
70
6625-6633
1996
equine arteritis virus, equine arteritis virus Bucyrus
Wassenaar, A.L.; Spaan, W.J.; Gorbalenya, A.E.; Snijder, E.J.
Alternative proteolytic processing of the arterivirus replicase ORF1a polyprotein: evidence that NSP2 acts as a cofactor for the NSP4 serine protease
J. Virol.
71
9313-9322
1997
equine arteritis virus
van Dinten, L.C.; Rensen, S.; Gorbalenya, A.E.; Snijder, E.J.
Proteolytic processing of the open reading frame 1b-encoded part of arterivirus replicase is mediated by nsp4 serine protease and Is essential for virus replication
J. Virol.
73
2027-2037
1999
equine arteritis virus
van Aken, D.; Snijder, E.J.; Gorbalenya, A.E.
Mutagenesis analysis of the nsp4 main proteinase reveals determinants of arterivirus replicase polyprotein autoprocessing
J. Virol.
80
3428-3437
2006
equine arteritis virus
van Aken, D.; Benckhuijsen, W.E.; Drijfhout, J.W.; Wassenaar, A.L.; Gorbalenya, A.E.; Snijder, E.J.
Expression, purification, and in vitro activity of an arterivirus main proteinase
Virus Res.
120
97-106
2006
equine arteritis virus
Chen, J.; Wang, D.; Sun, Z.; Gao, L.; Zhu, X.; Guo, J.; Xu, S.; Fang, L.; Li, K.; Xiaoa, S.
Arterivirus nsp4 antagonizes interferon beta production by proteolytically cleaving NEMO at multiple sites
J. Virol.
93
e00385
2019
equine arteritis virus, porcine reproductive and respiratory syndrome virus (E3V2B5)
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