{PDOC51124} {PS51124; PEPTIDASE_C16} {BEGIN} *************************************** * Peptidase family C16 domain profile * *************************************** 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 alpha-beta structural organisation known as the papain-like fold. It consists of three alpha-helices and three strands of antiparallel beta-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]. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: June 2022 / Text revised. [ 1] Ziebuhr J., Snijder E.J., Gorbalenya A.E. "Virus-encoded proteinases and proteolytic processing in the Nidovirales." J. Gen. Virol. 81:853-879(2000). PubMed=10725411 [ 2] Baker S.C., Yokomori K., Dong S., Carlisle R., Gorbalenya A.E., Koonin E.V., Lai M.M.C. "Identification of the catalytic sites of a papain-like cysteine proteinase of murine coronavirus." J. Virol. 67:6056-6063(1993). PubMed=8396668 [ 3] Dong S., Baker S.C. "Determinants of the p28 cleavage site recognized by the first papain-like cysteine proteinase of murine coronavirus." Virology 204:541-549(1994). PubMed=7941320 MEDLINE=22689675; PubMed=12805436; DOI=10.1128/JVI.77.13.7376-7382.2003 [ 4] Herold J., Siddell S.G., Gorbalenya A.E. "A human RNA viral cysteine proteinase that depends upon a unique Zn2+-binding finger connecting the two domains of a papain-like fold." J. Biol. Chem. 274:14918-14925(1999). MEDLINE=99262645; PubMed=10329692; DOI=10.1074/jbc.274.21.14918 [ 5] Ratia K., Saikatendu K.S., Santarsiero B.D., Barretto N., Baker S.C., Stevens R.C., Mesecar A.D. "Severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme." Proc. Natl. Acad. Sci. U. S. A. 103:5717-5722(2006). PubMed=16581910; DOI=10.1073/pnas.0510851103 [ 6] Barretto N., Jukneliene D., Ratia K., Chen Z., Mesecar A.D., Baker S.C. "The papain-like protease of severe acute respiratory syndrome coronavirus has deubiquitinating activity." J. Virol. 79:15189-15198(2005). PubMed=16306590; DOI=10.1128/JVI.79.24.15189-15198.2005 [ 7] Kanjanahaluethai A., Jukneliene D., Baker S.C. "Identification of the murine coronavirus MP1 cleavage site recognized by papain-like proteinase 2." J. Virol. 77:7376-7382(2003). PubMed=12805436 [ 8] Gosert R., Kanjanahaluethai A., Egger D., Bienz K., Baker S.C. "RNA replication of mouse hepatitis virus takes place at double-membrane vesicles." J. Virol. 76:3697-3708(2002). PubMed=11907209 [ 9] Kocherhans R., Bridgen A., Ackermann M., Tobler K. "Completion of the porcine epidemic diarrhoea coronavirus (PEDV) genome sequence." Virus Genes 23:137-144(2001). MEDLINE=21580790; PubMed=11724265; DOI=10.1023/A:1011831902219 [10] Ziebuhr J., Thiel V., Gorbalenya A.E. "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." J. Biol. Chem. 276:33220-33232(2001). MEDLINE=21413900; PubMed=11431476; DOI=10.1074/jbc.M104097200 [ 11] Harcourt B.H., Jukneliene D., Kanjanahaluethai A., Bechill J., Severson K.M., Smith C.M., Rota P.A., Baker S.C. "Identification of severe acute respiratory syndrome coronavirus replicase products and characterization of papain-like protease activity." J. Virol. 78:13600-13612(2004). PubMed=15564471; DOI=10.1128/JVI.78.24.13600-13612.2004 [E1] https://www.ebi.ac.uk/merops/cgi-bin/merops.cgi?id=C16;action=summary -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}