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PROSITE documentation PDOC51124
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)

Sequences in UniProtKB/Swiss-Prot known to belong to this class: 60
- detected by PS51124: 60 (true positives)
- undetected by PS51124: 0 (false negative or 'partial')
Other sequence(s) in UniProtKB/Swiss-Prot detected by PS51124:
NONE.
Domain architecture view of Swiss-Prot proteins matching PS51124
Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
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Retrieve the sequence logo from the alignment
Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS51124
Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS51124
Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS51124
View ligand binding statistics of PS51124
Matching PDB structures: 2FE8 3E9S 3MJ5 3MP2 ... [ALL]

References

1	Authors	Ziebuhr J. Snijder E.J. Gorbalenya A.E.
	Title	Virus-encoded proteinases and proteolytic processing in the Nidovirales.
	Source	J. Gen. Virol. 81:853-879(2000).
	PubMed ID	10725411

2	Authors	Baker S.C. Yokomori K. Dong S. Carlisle R. Gorbalenya A.E. Koonin E.V. Lai M.M.C.
	Title	Identification of the catalytic sites of a papain-like cysteine proteinase of murine coronavirus.
	Source	J. Virol. 67:6056-6063(1993).
	PubMed ID	8396668

3	Authors	Dong S. Baker S.C.
	Title	Determinants of the p28 cleavage site recognized by the first papain-like cysteine proteinase of murine coronavirus.
	Source	Virology 204:541-549(1994).
	PubMed ID	12805436
	DOI	10.1128/JVI.77.13.7376-7382.2003

4	Authors	Herold J. Siddell S.G. Gorbalenya A.E.
	Title	A human RNA viral cysteine proteinase that depends upon a unique Zn2+-binding finger connecting the two domains of a papain-like fold.
	Source	J. Biol. Chem. 274:14918-14925(1999).
	PubMed ID	10329692
	DOI	10.1074/jbc.274.21.14918

5	Authors	Ratia K. Saikatendu K.S. Santarsiero B.D. Barretto N. Baker S.C. Stevens R.C. Mesecar A.D.
	Title	Severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme.
	Source	Proc. Natl. Acad. Sci. U. S. A. 103:5717-5722(2006).
	PubMed ID	16581910
	DOI	10.1073/pnas.0510851103

6	Authors	Barretto N. Jukneliene D. Ratia K. Chen Z. Mesecar A.D. Baker S.C.
	Title	The papain-like protease of severe acute respiratory syndrome coronavirus has deubiquitinating activity.
	Source	J. Virol. 79:15189-15198(2005).
	PubMed ID	16306590
	DOI	10.1128/JVI.79.24.15189-15198.2005

7	Authors	Kanjanahaluethai A. Jukneliene D. Baker S.C.
	Title	Identification of the murine coronavirus MP1 cleavage site recognized by papain-like proteinase 2.
	Source	J. Virol. 77:7376-7382(2003).
	PubMed ID	12805436

8	Authors	Gosert R. Kanjanahaluethai A. Egger D. Bienz K. Baker S.C.
	Title	RNA replication of mouse hepatitis virus takes place at double-membrane vesicles.
	Source	J. Virol. 76:3697-3708(2002).
	PubMed ID	11907209

9	Authors	Kocherhans R. Bridgen A. Ackermann M. Tobler K.
	Title	Completion of the porcine epidemic diarrhoea coronavirus (PEDV) genome sequence.
	Source	Virus Genes 23:137-144(2001).
	PubMed ID	11724265
	DOI	10.1023/A:1011831902219

10	Authors	Ziebuhr J. Thiel V. Gorbalenya A.E.
	Title	The 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.
	Source	J. Biol. Chem. 276:33220-33232(2001).
	PubMed ID	11431476
	DOI	10.1074/jbc.M104097200

11	Authors	Harcourt B.H. Jukneliene D. Kanjanahaluethai A. Bechill J. Severson K.M. Smith C.M. Rota P.A. Baker S.C.
	Title	Identification of severe acute respiratory syndrome coronavirus replicase products and characterization of papain-like protease activity.
	Source	J. Virol. 78:13600-13612(2004).
	PubMed ID	15564471
	DOI	10.1128/JVI.78.24.13600-13612.2004

Title

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

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PROSITE documentation PDOC51124Peptidase family C16 domain profile

PROSITE documentation PDOC51124
Peptidase family C16 domain profile