Family C9

Family

Summary Holotypes Alignment Tree Genomes Structure Literature Architecture

Summary for family C9

Family type peptidase	C09.001 - sindbis virus-type nsP2 peptidase (Sindbis virus), MEROPS Accession MER0000823 (peptidase unit: 969-1347)
Content of family	Peptidase family C9 contains viral cysteine endopeptidases.
History	Identifier created: Biochem.J. 290:205-218 (1993)
Catalytic type	Cysteine
Active site residues	C1021 H1098
Active site	The 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 specificities	The 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[]%>).
Inhibitors	Inhibitors have not been described.
Molecular structure	The 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.
Clan	CN
Basis of clan assignment	Active 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 functions	The 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 C9	Sequences:	81
	Identifiers:	2
	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 peptidase	C09.001	Yes
equine encephalitis alphavirus nsP2 peptidase	C09.002	Yes
Family C09 non-peptidase homologues	non-peptidase homologue	-
Family C09 unassigned peptidases	unassigned	-