Family C9


Summary Holotypes Alignment Tree Genomes Structure Literature Architecture

Summary for family C9

Family type peptidaseC09.001 - sindbis virus-type nsP2 peptidase (Sindbis virus), MEROPS Accession MER0000823 (peptidase unit: 969-1347)
Content of familyPeptidase family C9 contains viral cysteine endopeptidases.
History Identifier created: Biochem.J. 290:205-218 (1993)
Catalytic typeCysteine
Active site residuesC1021 H1098 
Active siteThe catalytic dyad of the Sindbis virus nsP2 peptidase has been identified by site-specific mutagenesis as Cys1021 and His1098 (Strauss et al., 1992). The Cys/His order of these residues places family C9 in clan CA, although no equivalents of Gln and Asn residues that also contribute to catalysis in the majority of families in the clan have yet been recognised.
Activities and specificitiesThe consensus cleavage site in the viral nonstructural polyproteins has been described as (Ala/Ile)-Gly-(Ala/Cys/Gly)(Ala/Tyr) (Strauss & Strauss, 2004). In the Semliki Forst virus, cleavage at the Nsp3/4 site occurs first in cis or trans; release of Nsp1 occurs next in cis. Cleavage at the Nsp2/3 site requires a free Nsp2 N-terminus (<%Vasiljeva et al., 2003[]%>).
InhibitorsInhibitors have not been described.
Molecular structureThe tertiary structure has been determined for the nsP2 peptidase from Venezuelan equine encephalitis virus and shows a two domain structure with the peptidase unit entirely confined to the N-terminal domain. This domain consists of a helical bundle flanked by two, short beta-hairpins. The catalytic Cys is at the N-terminal end of a helix and the catalytic His is part of a beta-strand, but although the catalytic dyad arrangement is similar to that of papain (C01.001) the tertiary structures of the two peptidases are unrelated (Russo et al., 2006). The nsP2 peptidase therefore becomes the type structure for clan CN.
Basis of clan assignmentActive site residues for members of this family and family C1 occur in the same order in the sequence: C, H.
Distribution of family Bacteria -  
Archaea -  
Protozoa -  
Fungi -  
Plants -  
Animals details  
Viruses details  
Biological functionsThe virus-specific components of Semliki Forest virus RNA polymerase are synthesized as a large polyprotein that is cleaved by the nsP2 peptidase (Vasiljeva et al., 2001). The Semliki Forest virus nsP2 endopeptidase is a bifunctional molecule with the peptidase unit at the C-terminus and an N-terminal unit that is probably involved in RNA-binding during replication. In the Venezuelan equine encephalitis virus, the peptidase unit is located at the N-terminus of the nsp2 protein (Russo et al., 2006).
Statistics for family C9Sequences:81
Identifiers with PDB entries:2
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Other databases INTERPRO IPR002620
PFAM PF01707
Peptidases and Homologues MEROPS ID Structure
sindbis virus-type nsP2 peptidaseC09.001Yes
equine encephalitis alphavirus nsP2 peptidaseC09.002Yes
Family C09 non-peptidase homologuesnon-peptidase homologue-
Family C09 unassigned peptidasesunassigned-