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PROSITE documentation PDOC51124 [for PROSITE entry PS51124]

Peptidase family C16 domain profile





Description

Peptidase family C16 (EC 3.4.22.-) contains the coronaviruses cysteine endopeptidases involved in viral polyprotein processing [E1]. All coronaviruses encodes between one and two accessory cysteine proteinases that recognize and process one or two sites in the amino-terminal half of the replicase polyprotein during assembly of the viral replication complex. MHV, HCoV and TGEV encode two accesssory proteinases, called coronavirus papain-like proteinase 1 and 2 (PL1-PRO and PL2-PRO). IBV and SARS encodes only one called PL-PRO [1]. Coronaviruses papain-like proteinases 1 and 2 have restricted specificities, cleaving respectively two and one bond(s)in the polyprotein. This restricted activity may be due to extended specificity sites: Arg or Lys at the cleavage site position P5 are required for PL1-PRO [2], and Phe at the cleavage site position P6 is required for PL2-PRO [3]. PL1-PRO releases p28 and p65 from the N-terminus of the polyprotein; PL2-PRO cleaves between p210 and p150.

The peptidase family C16 domain is about 260 amino acids in length. This domain is predicted to have an α-β structural organisation known as the papain-like fold. It consists of three α-helices and three strands of antiparallel β-sheet [4]. The active site of the peptidase family C16 domain consists of a catalytic triad of cysteine, histidine, and aspartic acid residues [1,2,4,5,6]. The nucleophilic Cys occurs in the motif Asn-Cys-Xaa-Yaa in which Xaa is an aromatic, hydrophobic residue and Yaa is an aliphatic hydrophobic amino acid. There is little conservation around the general base His. The aspartic acid plays a significant, although not essential role, in orienting and/or stabilizing the substrate in the active site [5]. This peptidase domain also contains Cys residues involved in the formation of a zinc-binding finger which connects the left and right hand domains of a papain-like fold, and may be involved in substrate binding or control the movement of the catalytic domain [4].

Some proteins known to contain a peptidase C16 domain are listed below:

  • Murine hepatitis coronavirus (MHV) papain-like endopeptidase 2 (PLP2) (C16.006) [3,7].
  • Human coronavirus (HCoV) 229E papain-like endopeptidase 1 (C16.002) [4].
  • Murine hepatitis coronavirus (MHV) papain-like endopeptidase 1 (PLP1) (C16.001) [8].
  • Porcine epidemic diarrhea virus (PEDV) papain-like endopeptidase 1 (C16.003) [9].
  • Avian infectious bronchitis coronavirus (IBV) papain-like endopeptidase 1 (C16.005) [10].
  • SARS coronavirus papain-like endopeptidase (C16.009) [11].
Last update:

June 2022 / Text revised.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

PEPTIDASE_C16, PS51124; Peptidase family C16 domain profile  (MATRIX)


References

1AuthorsZiebuhr J. Snijder E.J. Gorbalenya A.E.
TitleVirus-encoded proteinases and proteolytic processing in the Nidovirales.
SourceJ. Gen. Virol. 81:853-879(2000).
PubMed ID10725411

2AuthorsBaker S.C. Yokomori K. Dong S. Carlisle R. Gorbalenya A.E. Koonin E.V. Lai M.M.C.
TitleIdentification of the catalytic sites of a papain-like cysteine proteinase of murine coronavirus.
SourceJ. Virol. 67:6056-6063(1993).
PubMed ID8396668

3AuthorsDong S. Baker S.C.
TitleDeterminants of the p28 cleavage site recognized by the first papain-like cysteine proteinase of murine coronavirus.
SourceVirology 204:541-549(1994).
PubMed ID12805436
DOI10.1128/JVI.77.13.7376-7382.2003

4AuthorsHerold J. Siddell S.G. Gorbalenya A.E.
TitleA human RNA viral cysteine proteinase that depends upon a unique Zn2+-binding finger connecting the two domains of a papain-like fold.
SourceJ. Biol. Chem. 274:14918-14925(1999).
PubMed ID10329692
DOI10.1074/jbc.274.21.14918

5AuthorsRatia K. Saikatendu K.S. Santarsiero B.D. Barretto N. Baker S.C. Stevens R.C. Mesecar A.D.
TitleSevere acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme.
SourceProc. Natl. Acad. Sci. U. S. A. 103:5717-5722(2006).
PubMed ID16581910
DOI10.1073/pnas.0510851103

6AuthorsBarretto N. Jukneliene D. Ratia K. Chen Z. Mesecar A.D. Baker S.C.
TitleThe papain-like protease of severe acute respiratory syndrome coronavirus has deubiquitinating activity.
SourceJ. Virol. 79:15189-15198(2005).
PubMed ID16306590
DOI10.1128/JVI.79.24.15189-15198.2005

7AuthorsKanjanahaluethai A. Jukneliene D. Baker S.C.
TitleIdentification of the murine coronavirus MP1 cleavage site recognized by papain-like proteinase 2.
SourceJ. Virol. 77:7376-7382(2003).
PubMed ID12805436

8AuthorsGosert R. Kanjanahaluethai A. Egger D. Bienz K. Baker S.C.
TitleRNA replication of mouse hepatitis virus takes place at double-membrane vesicles.
SourceJ. Virol. 76:3697-3708(2002).
PubMed ID11907209

9AuthorsKocherhans R. Bridgen A. Ackermann M. Tobler K.
TitleCompletion of the porcine epidemic diarrhoea coronavirus (PEDV) genome sequence.
SourceVirus Genes 23:137-144(2001).
PubMed ID11724265
DOI10.1023/A:1011831902219

10AuthorsZiebuhr J. Thiel V. Gorbalenya A.E.
TitleThe autocatalytic release of a putative RNA virus transcription factor from its polyprotein precursor involves two paralogous papain- like proteases that cleave the same peptide bond.
SourceJ. Biol. Chem. 276:33220-33232(2001).
PubMed ID11431476
DOI10.1074/jbc.M104097200

11AuthorsHarcourt B.H. Jukneliene D. Kanjanahaluethai A. Bechill J. Severson K.M. Smith C.M. Rota P.A. Baker S.C.
TitleIdentification of severe acute respiratory syndrome coronavirus replicase products and characterization of papain-like protease activity.
SourceJ. Virol. 78:13600-13612(2004).
PubMed ID15564471
DOI10.1128/JVI.78.24.13600-13612.2004

E1Titlehttps://www.ebi.ac.uk/merops/cgi-bin/merops.cgi?id=C16;action=summary



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