Family C3

Family

Summary Holotypes Alignment Tree Genomes Structure Literature

C3A

Summary Holotypes Alignment Tree Genomes Literature

C3B

Summary Holotypes Alignment Tree Genomes Literature

C3C

Summary Holotypes Alignment Tree Genomes Literature

C3D

Summary Holotypes Alignment Tree Genomes Literature

C3E

Summary Holotypes Alignment Tree Genomes Literature

C3F

Summary Holotypes Alignment Tree Genomes Literature

C3G

Summary Holotypes Alignment Tree Genomes Literature

C3H

Summary Holotypes Alignment Tree Genomes Literature

Summary for family C3

NamePeptidase family C3 (picornain family)
Family type peptidaseC03.001 - poliovirus-type picornain 3C (human poliovirus 1), MEROPS Accession MER0000748 (peptidase unit: 1564-1745)
Content of familyPeptidase family C3 contains processing endopeptidases of RNA viruses.
History Identifier created: Biochem.J. 290:205-218 (1993)
In the mid-1980"s, the surprising discovery was made that the 3C processing peptidases of poliovirus and other picornaviruses have some similarities in sequence to chymotrypsin and its relatives (Bazan & Fletterick, 1988; Gorbalenya et al., 1989). The relationship was confirmed by the crystallographic structure of picornain 3C from human hepatitis A virus (e.g. Matthews et al., 1994). This was the first indication that a peptidase of one catalytic type can evolve into one of another, and led to the creation of clan PA in MEROPS. (The 'P' in the clan identifier indicates that this is a clan containing mixed types of Protein nucleophile peptidase families.)
Catalytic typeCysteine
Active siteConfirmed catalytic residues are His1603 and Cys1710 (see the Alignment). Asp1634 is close to the position expected for the third member of a catalytic triad analogous to those in family S1. In the hepatitis A virus enzyme it is unlikely to fill this role because the orientation of its side chain in the crystal structure is not as expected, and an ordered water molecule occupies the position of the carboxylate of the third member of a typical catalytic triad (Bergmann, 2004).
Activities and specificitiesBonds cleaved in processing the viral polyprotein are commonly -GlnGly-. A biologically-significant substrate in addition to the viral polyprotein is the eukaryotic initiation factor 4G (Foeger et al., 2003). Cleavage of eIF4G probably contributes to the viral takeover of protein synthesis in the host cell.
InhibitorsMany synthetic inhibitors have been designed as possible leads to antiviral drugs; the structures of these commonly mimic glutamine (e.g. Ramtohul et al., 2002).
Molecular structureThe predominant feature of the protein folds of the peptidases in family C3, in common with others in clan PA, is a pair of beta-barrels ar right-angles, with the catalytic residues between them.
ClanPA
SubclanPA(C)
Basis of clan assignmentProtein fold of the peptidase unit for members of this family resembles that of chymotrypsin, the type example for clan PA.
Distribution of family Bacteria -  
Archaea -  
Protozoa -  
Fungi -  
Plants -  
Animals details  
Viruses details  
Biological functionsThe picornains are components of the polyproteins of small RNA viruses of the Picornaviridae group (picornaviruses, aphthoviruses, nepoviruses and comoviruses). Maturation of the viruses requires the processing of the polyproteins that is commonly mediated by endopeptidases of family C3.
Pharmaceutical and biotech relevanceThe enzymes are potential targets for antiviral drugs. Among the many diseases that might be tackled in this way are poliomyelitis, the common cold, hepatitis A and foot-and-mouth disease.
Statistics for family C3Sequences:679
Identifiers:19
Identifiers with PDB entries:11
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Subfamily C3A
Name Peptidase subfamily C3A
Subfamily type peptidase C03.001 - poliovirus-type picornain 3C (human poliovirus 1), MEROPS Accession MER0000748 (peptidase unit: 1564-1745)
Active site residues H1604 D,E1635 C1711 
Statistics Sequences: 284
Identifiers: 5
Identifiers with PDB entries: 5
Other databases CATH 2.40.10.10
HOMSTRAD Cys-protease-3C
HSSP 1l1n
INTERPRO IPR000199
PFAM PF00548
SCOP 50603
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
poliovirus-type picornain 3CC03.001Yes
human rhinovirus 2-type picornain 3CC03.007Yes
Coxsackievirus-type picornain 3CC03.011Yes
human rhinovirus 14-type 3C peptidaseC03.013-
human enterovirus 71 3C peptidaseC03.014-
non-peptidase homologueYes
subfamily C3A unassigned peptidasesunassignedYes
Subfamily C3B
Name Peptidase subfamily C3B
Subfamily type peptidase C03.020 - enterovirus picornain 2A (human poliovirus 1), MEROPS Accession MER0000766 (peptidase unit: 882-1030)
Active site residues H900 D,E918 C989 
Statistics Sequences: 437
Identifiers: 2
Identifiers with PDB entries: 2
Other databases HOMSTRAD hs2hrva
INTERPRO IPR000081
PFAM PF00947
SCOP 50603
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
enterovirus picornain 2AC03.020Yes
rhinovirus picornain 2AC03.021Yes
subfamily C3B non-peptidase homologuesnon-peptidase homologue-
subfamily C3B unassigned peptidasesunassigned-
Subfamily C3C
Name Peptidase subfamily C3C
Subfamily type peptidase C03.008 - foot-and-mouth disease virus picornain 3C (foot-and-mouth disease virus), MEROPS Accession MER0001662 (peptidase unit: 1653-1837)
Active site residues H1695 D,E1733 C1812 
Statistics Sequences: 26
Identifiers: 3
Identifiers with PDB entries: 2
Other databases CATH 2.40.10.10
HOMSTRAD Cys-protease-3C
INTERPRO IPR009003
PFAM PF00548
PFAM PF12381
SCOP 159189
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
foot-and-mouth disease virus picornain 3CC03.008Yes
cardiovirus picornain 3CC03.009-
Theiler’s murine encephalomyelitis virus picornain 3CC03.010-
subfamily C3C non-peptidase homologuesnon-peptidase homologue-
subfamily C3C unassigned peptidasesunassignedYes
Subfamily C3D
Name Peptidase subfamily C3D
Subfamily type peptidase C03.003 - cowpea mosaic comovirus-type picornain 3C (cowpea mosaic virus), MEROPS Accession MER0000784 (peptidase unit: 948-1155)
Active site residues H987 D,E1023 C1113 
Statistics Sequences: 25
Identifiers: 1
Identifiers with PDB entries: 0
Other databases INTERPRO IPR009003
PFAM PF00548
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
cowpea mosaic comovirus-type picornain 3CC03.003-
non-peptidase homologue-
subfamily C3D unassigned peptidasesunassigned-
Subfamily C3E
Name Peptidase subfamily C3E
Subfamily type peptidase C03.005 - hepatitis A virus-type picornain 3C (hepatitis A virus), MEROPS Accession MER0001665 (peptidase unit: 1519-1737)
Active site residues H1562 D1602 C1690 
Statistics Sequences: 7
Identifiers: 1
Identifiers with PDB entries: 1
Other databases CATH 2.40.10.10
HOMSTRAD Cys-protease-3C
HSSP 1hav
INTERPRO IPR009003
PFAM PF00548
SCOP 50603
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
hepatitis A virus-type picornain 3CC03.005Yes
subfamily C3E unassigned peptidasesunassigned-
Subfamily C3F
Name Peptidase subfamily C3F
Subfamily type peptidase C03.023 - parechovirus picornain 3C (human parechovirus 1), MEROPS Accession MER0014763 (peptidase unit: 1512-1711)
Active site residues H1558 C1596 
Statistics Sequences: 5
Identifiers: 1
Identifiers with PDB entries: 1
Other databases INTERPRO IPR009003
PFAM PF00548
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
parechovirus picornain 3CC03.023Yes
non-peptidase homologue-
subfamily C3F unassigned peptidasesunassigned-
Subfamily C3G
Name Peptidase subfamily C3G
Subfamily type peptidase C03.024 - rice tungro spherical virus-type peptidase (rice tungro spherical virus), MEROPS Accession MER0005895 (peptidase unit: 2664-2852)
Active site residues H2677 D,E2719 C2808 
Statistics Sequences: 12
Identifiers: 3
Identifiers with PDB entries: 0
Other databases INTERPRO IPR009003
PFAM PF12381
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
Plautia stali intestine virus picornain C3C03.015-
tomato marchitez virus 3C peptidaseC03.016-
rice tungro spherical virus-type peptidaseC03.024-
subfamily C3G unassigned peptidasesnon-peptidase homologue-
subfamily C3G unassigned peptidasesunassigned-
Subfamily C3H
Name Peptidase subfamily C3H
Subfamily type peptidase C03.004 - grapevine fanleaf-type nepovirus picornain 3C (grapevine fanleaf virus), MEROPS Accession MER0000787 (peptidase unit: 1245-1461)
Active site residues H1284 D,E1328 C1420 
Statistics Sequences: 18
Identifiers: 2
Identifiers with PDB entries: 0
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
grapevine fanleaf-type nepovirus picornain 3CC03.004-
tomato black ring virus-type picornainC03.025-
subfamily C3H unassigned peptidasesunassigned-
Peptidases not assigned to subfamily
Peptidases and Homologues MEROPS ID Structure
tomato ringspot nepovirus picornain 3CC03.012-
subfamily C3 non-peptidase homologuesnon-peptidase homologue-
family C3 unassigned peptidasesunassigned-