Cysteine/Serine proteases

Cysteine/serine proteases in viruses act in the processing of polyproteins, maturation of capsid/virion or modulation of host immune response. They are a type of enzyme that catalyze the hydrolysis of peptide bonds and use a cysteine or serine residue in their active site to perform this hydrolysis reaction. (Wikipedia:Serine peptidase, Cysteine peptidase)

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Enzymatic reaction:

  • Ser-endopeptidase EC.3.4.21.-
  • Cys-endopeptidase EC.3.4.22.-

Mechanism The active site of a cysteine/serine protease consists of three key amino acids: cysteine/serine, histidine, and aspartate. Together, these residues form a catalytic triad that facilitates the cleavage of peptide bonds in proteins. The cysteine/serine residue acts as a nucleophile, attacking the carbonyl carbon of the peptide bond, while the histidine and aspartate residues assist the process by stabilizing the reaction intermediates.

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GenomeOrderFamilyFunctionTypeMEROPS familyDistribution (low incidence)Clan (fold)InterproUniProt exemplar
dsDNA Chitovirales imageimage Poxviridae Virion maturation Cysteine Peptidase C57 Virus CE (Papain fold)
IPR004970 Core protease OPG083
dsDNA Rowavirales imageimage Adenoviridae Virion maturation Cysteine Peptidase C5 Virus, (animals, bacteria) CE (Papain fold)
IPR000855 Adenain
dsDNA Lefavirales image Baculoviridae Host cell liquefaction Cysteine Peptidase C1A Animals, plant, protozoa, bacteria, archaea, virus CA (Papain fold)
IPR013128 Cathepsin
dsDNA Pimascovirales image Ascoviridae Unknown Cysteine Peptidase C14 Animals, plant, protozoa, bacteria, archaea, virus CD (Caspase fold)
IPR011600 Caspase-like protein
dsDNA Asfuvirales image Asfarviridae Virion maturation Cysteine Peptidase C48 Animals, plant, protozoa, bacteria, archaea, virus CE (Papain fold)
IPR003653 Cysteine protease S273R
dsDNA Pimascovirales image Iridoviridae Unknown Cysteine Peptidase C1A Animals, plant, protozoa, bacteria, archaea, virus CA (Papain fold)
IPR013128 Cysteine proteinase 024R
dsDNA Imitervirales image Mimiviridae Unknown Cysteine Peptidase C48 Animals, plant, protozoa, bacteria, archaea, virus CE (Papain fold)
IPR003653 Thiol protease R355
dsDNA unassigned image Pandoravirus Unknown Cysteine Peptidase C1A Animals, plant, protozoa, bacteria, archaea, virus CA (Papain fold)
IPR013128 Peptidase
ssRNA+ Hepevirales imageimage Hepeviridae Polyprotein major protease Cysteine ND Virus unasigned, CA?
IPR008748 POLN
ssRNA+ Hepevirales image Benyviridae Polyprotein major protease Cysteine Peptidase C36 Virus unassigned
IPR008746 ORF1
ssRNA+ Hepevirales image Matonaviridae Polyprotein major protease Cysteine Peptidase C27 Virus unassigned
IPR008738 NSpolyprotein
ssRNA+ Martellivirales image Closteroviridae Polyprotein major protease Cysteine Peptidase C42 Virus unassigned
IPR008749 Replicase polyprotein
ssRNA+ Martellivirales image Kitaviridae Polyprotein major protease Cysteine papain-like Virus CA (Papain fold) IPR038765 Protease
ssRNA+ Martellivirales imageimage Togaviridae Polyprotein major protease Cysteine Peptidase C9 Virus CN
IPR002620 POLN
ssRNA+ Nidovirales imageimage Coronaviridae Polyprotein major protease Cysteine Peptidase C30 Virus PA (chymotrypsin fold)
IPR008740 polyprotein 1ab, 3CL pro
ssRNA+ Nidovirales imageimage Coronaviridae Polyprotein Nter protease Cysteine Peptidase C16 Virus CA (Papain fold)
IPR013016 polyprotein 1ab, PLpro
ssRNA+ Nidovirales image Arteriviridae Host antiviral response modulation Cysteine Peptidase C31 Virus CA (Papain fold)
IPR008741 polyprotein 1ab, nsp1 alpha
ssRNA+ Nidovirales image Arteriviridae Host inhibition of translation Cysteine Peptidase C32 Virus CA (Papain fold)
IPR025773 polyprotein 1ab, nsp1 beta
ssRNA+ Nidovirales image Arteriviridae Self-cleavage N-ter polyprotein, host modulation by de-ubiquitination Cysteine Peptidase C33 Virus CA (Papain fold)
IPR008743 polyprotein 1ab, nsp2
ssRNA+ Nidovirales image Mesoniviridae Polyprotein major protease Cysteine Peptidase C107 Virus PA (chymotrypsin fold)
IPR033777 not annotated
ssRNA+ Nidovirales image Roniviridae Polyprotein major protease Cysteine Peptidase C62 Virus PA (chymotrypsin fold)
IPR024348 polyprotein 1ab
ssRNA+ Nidovirales imageimage Tobaniviridae Self-cleavage N-ter polyprotein Cysteine papain-like Virus CA (Papain fold) IPR038765 polyprotein 1ab
ssRNA+ Picornavirales image Caliciviridae Polyprotein major protease Cysteine Peptidase C37 Virus PA (chymotrypsin fold)
IPR001665 Polyprotein
ssRNA+ Picornavirales image Caliciviridae Polyprotein major protease Cysteine Peptidase C24 Virus PA (chymotrypsin fold)
IPR000317 Polyprotein
ssRNA+ Picornavirales image Dicistroviridae Polyprotein major protease Cysteine Peptidase C3 Virus, (animals) PA (chymotrypsin fold)
IPR044067 Polyprotein
ssRNA+ Picornavirales image Iflaviridae Polyprotein major protease Cysteine Peptidase C3 Virus, (animals) PA (chymotrypsin fold)
IPR044067 Polyprotein
ssRNA+ Picornavirales image Iflaviridae Polyprotein major protease Cysteine Peptidase C99 Virus PA (chymotrypsin fold)
IPR009003 Polyprotein
ssRNA+ Picornavirales image Marnaviridae Polyprotein major protease Cysteine Peptidase C3 Virus, (animals) PA (chymotrypsin fold)
IPR044067 Polyprotein
ssRNA+ Picornavirales image Picornaviridae Early polyprotein protease Cysteine Peptidase C3 Virus, (animals) PA (chymotrypsin fold)
IPR044067 Polyprotein, 2A
ssRNA+ Picornavirales image Picornaviridae Polyprotein major protease Cysteine Peptidase C3 Virus, (animals) PA (chymotrypsin fold)
IPR044067 Polyprotein, 3Cpro
ssRNA+ Picornavirales image Picornaviridae Self cleavage N-ter polyprotein, host antiviral response modulation Cysteine Peptidase C28 Virus CA (Papain fold)
IPR008739 Polyprotein, L
ssRNA+ Picornavirales image Polycipiviridae Polyprotein major protease Cysteine Peptidase Virus PA (chymotrypsin fold)
IPR044067 Polyprotein
ssRNA+ Picornavirales image Secoviridae Polyprotein major protease Cysteine Peptidase C3 Virus, (animals) PA (chymotrypsin fold)
IPR044067 Polyprotein
ssRNA+ Picornavirales image Solinviviridae Polyprotein major protease Cysteine Peptidase C3 Virus, (animals) PA (chymotrypsin fold)
IPR044067 Polyprotein
ssRNA+ Patatavirales image Potyviridae Self-cleavage N-ter polyprotein Cysteine Peptidase C6 Virus CA (Papain fold)
IPR001456 Polyprotein, HC-pro
ssRNA+ Patatavirales image Potyviridae Polyprotein major protease Cysteine Peptidase C4 Virus PA (chymotrypsin fold)
IPR001730 Polyprotein, Nla-pro
ssRNA+ Amarillovirales image Flaviviridae: Hepacivirus, Pegivirus Self cleavage N-ter polyprotein Cysteine Peptidase C18 Virus CM
IPR002518 Polyprotein, ns2
ssRNA+ Amarillovirales image Flaviviridae: Pestivirus Self-cleavage N-ter polyprotein, host innate immune response inhibition Cysteine Peptidase C53 Virus CQ
IPR008751 Polyprotein, Nterm-pro
ssRNA+ Amarillovirales image Flaviviridae: Pestivirus Self-cleavage N-ter polyprotein Cysteine Peptidase C74 Virus PA (chymotrypsin fold)
IPR022120 Polyprotein, ns2
ssRNA+ Tymovirales image Tymoviridae Polyprotein major protease Cysteine Peptidase C21 Virus CA (Papain fold)
IPR043181 Polyprotein
ssRNA+ Tymovirales image Betaflexviridae Polyprotein major protease Cysteine Peptidase C23 Virus Unassigned
IPR008041 Polyprotein
ssRNA+ Durnavirales image Hypoviridae Self cleavage N-ter, Host immune response inhibition Cysteine Peptidase C7 Virus unassigned
IPR002704 Papain-like protease p29
ssRNA+ Durnavirales image Hypoviridae Self cleavage N-ter, Host immune response inhibition Cysteine Peptidase C8 Virus unassigned
IPR005315 Papain-like protease p48
dsDNA Caudoviricetes image Ravinvirus Virion maturation Cysteine Peptidase C40 Fungi, bacteria, archaea, virus CO (Papain fold)
IPR000064 Tail tip assembly protein K
dsDNA Caudoviricetes image Peduoviridae Virion maturation Serine Peptidase S73 Fungi, bacteria, archaea, virus SH
IPR009228 Capsid assembly scaffolding protein
dsDNA Caudoviricetes image Leisingerviridae Host cell lysis Cysteine Peptidase C71 Virus CA (Papain fold)
IPR022119 Pseudomurein endoisopeptidase
dsDNA Caudoviricetes image Ackermanviridae Host cell lysis Cysteine Peptidase C51 Animals, bacteria, archaea, virus CA (Papain fold) IPR007921 Tail lysozyme
dsDNA Caudoviricetes image Herelleviridae Unknown Cysteine Peptidase C51 Animals, bacteria, archaea, virus CA (Papain fold) IPR007921 Peptidase
dsDNA Caudoviricetes image Autographiviridae Host cell lysis Cysteine Peptidase C51 Animals, bacteria, archaea, virus CA (Papain fold) IPR007921 Endolysin
dsDNA Caudoviricetes image Rountreeviridae Host cell lysis? Cysteine Peptidase C51 Animals, bacteria, archaea, virus CA (Papain fold) IPR007921 Peptidase
dsDNA Herpesvirales image Herpesviridae Virion maturation Serine Peptidase S21 Virus, (animals) SH
IPR001847 Assemblin
dsDNA Herpesvirales image Alloherpesviridae Unknown Serine Peptidase S8/S53 Animals, plant, protozoa, bacteria, archaea, virus subtilisin SB IPR036852 Subtilisin-like
dsDNA Herpesvirales image Herpesviridae Host cell cycle modulation Serine Peptidase C76 Virus CA (Papain fold) IPR006928 Large tegument protein deneddylase
dsDNA Lefavirales image Nudiviridae Unknown Serine Peptidase S1 Animals, plant, protozoa, bacteria, archaea, virus PA (chymotrypsin fold)
IPR001314 Protease
dsDNA Imitervirales image Mimiviridae Unknown Serine Peptidase S54 Animals, plant, protozoa, bacteria, archaea, virus ST IPR022764 L523
dsDNA Imitervirales image Mimiviridae Unknown Serine Peptidase S16 Animals, plant, protozoa, bacteria, archaea, virus SJ IPR027065 Protease
dsDNA Algavirales image Phycodnaviridae Unknown Serine Peptidase S74 Animals, bacteria, archaea, virus SO IPR030392 Protease
dsDNA Priklausovirales image Lavidaviridae unknown Serine Peptidase S74 Animals, bacteria, archaea, virus SO IPR030392 Protease
dsDNA Pimascovirales image Marseilleviridae Unknown Serine Peptidase S74 Animals, bacteria, archaea, virus SO IPR030392 Protease
dsDNA Caudovirales image Ravinvirus Unknown Serine Peptidase S74 Animals, bacteria, archaea, virus SO IPR030392 Protease
dsDNA Caudoviricetes image PhiKZvirus Virion maturation Serine Peptidase S80 Virus SH IPR045405 Protease
dsDNA Caudoviricetes image Ackermanviridae Virion maturation Serine Peptidase S77 Virus, (plant, bacteria, archaea) SH IPR005082 Prohead core protease
dsDNA Caudoviricetes image Chaseviridae Virion maturation Serine Peptidase S77 Virus, (plant, bacteria, archaea) SH IPR005082 Prohead core protease
dsDNA Caudoviricetes image Kyanoviridae Virion maturation Serine Peptidase S77 Virus, (plant, bacteria, archaea) SH IPR005082 Prohead core protease
dsDNA Caudoviricetes image Herelleviridae, Demerecviridae Virion maturation Serine Peptidase S78 Virus, (plant, bacteria, archaea) SH IPR006433 Prohead core protease
dsDNA Caudoviricetes image Straboviridae Virion maturation Serine Peptidase S77 Virus, (plant, bacteria, archaea) SH IPR005082 Prohead core protease
dsDNA Caudoviricetes image Casjensviridae: Lambdavirus, Ravinvirus Virion maturation Serine Peptidase S49 Animals, plant, protozoa, bacteria, archaea, virus SK IPR002142 Prohead core protease
dsDNA Caudoviricetes image Ravinvirus Unknown Serine Peptidase S24 Animals, plant, protozoa, bacteria, archaea, virus SF IPR000129 Protease
dsDNA unassigned image Birnaviridae Virion maturation Serine Peptidase S50 Virus, (bacteria) SJ IPR002664 Virion maturation
dsDNA Caudoviricetes image Demerecviridae Unknown Serine Peptidase S74 Animals, bacteria, virus SO PF13884 Tail fiber protease
ssRNA+ Amarillovirales image Flaviviridae: Hepacivirus, Pegivirus Polyprotein major protease Serine Peptidase S29 Virus PA (chymotrypsin fold)
IPR004109 NS3
ssRNA+ Amarillovirales image Flaviviridae: Flavivirus Polyprotein major protease Serine Peptidase S7 Virus, (animals, bacteria) PA (chymotrypsin fold)
IPR001850 NS3
ssRNA+ Amarillovirales imageimage Flaviviridae: Pestivirus Polyprotein major protease Serine Peptidase S31 Virus PA (chymotrypsin fold)
IPR000280 NS3
ssRNA+ Nidovirales image Arteriviridae Polyprotein major protease Serine Peptidase S32 Virus PA (chymotrypsin fold)
IPR008760 NSP4
ssRNA+ Nidovirales imageimage Tobaniviridae, Torovirus Polyprotein major protease Serine Peptidase S65 Virus PA (chymotrypsin fold)
IPR009003 Polyprotein 1ab
ssRNA+ Nidovirales imageimage Tobaniviridae, Bafinivirus Polyprotein major protease Serine Peptidase S75 Virus PA (chymotrypsin fold)
IPR009003 Polyprotein 1ab
ssRNA+ Sobelivirales image Alvernaviridae Unknown Serine unknown Virus
ssRNA+ Sobelivirales image Barnaviridae Polyprotein major protease Serine Peptidase S39 Virus PA (chymotrypsin fold)
IPR000382 Polyprotein
ssRNA+ Sobelivirales image Solemoviridae Polyprotein major protease Serine Peptidase S39 Virus PA (chymotrypsin fold)
IPR000382 ORF2
ssRNA+ Stellavirales image Astroviridae Polyprotein major protease Serine Peptidase PA Virus PA (chymotrypsin fold)
IPR009003 Polyprotein
ssRNA+ Patatavirales image Potyviridae Self-cleavage N-ter polyprotein Serine Peptidase S30 Virus PA (chymotrypsin fold)
IPR002540 P1 proteinase
ssRNA+ Martellivirales image Togaviridae Self-cleavage Nter-POLS Serine Peptidase S3 Virus PA (chymotrypsin fold)
IPR000930 Capsid
ssRNA- Bunyavirales image Nairoviridae Deubiquitinylating Peptidase Cysteine Peptidase C87 Virus CA (Papain fold) IPR003323 L

Cysteine proteases