Family C26


Summary Holotypes Alignment Tree Genomes Structure Literature H-seq M-seq

Summary for family C26

NamePeptidase family C26 (gamma-glutamyl hydrolase family)
Family type peptidaseC26.001 - gamma-glutamyl hydrolase (Rattus norvegicus), MEROPS Accession MER0002464 (peptidase unit: 25-293)
Content of familyPeptidase family C26 contains the omega peptidase gamma-glutamyl hydrolase.
History Identifier created: MEROPS homepage v. 1.00 (Prolysis)
gamma-Glutamyl hydrolase (C26.001) is a lysosomal cysteine peptidase not to be confused with the metallopeptidases in families M20 and M28 that also hydrolyse gamma-glutamyl bonds.
Catalytic typeCysteine
Active site residuesC133 H243 E245 
Active siteThe catalytic dyad occurs in the order Cys, His in the sequence (Chave et al., 2000) (see the Alignment).
Activities and specificitiesGamma-glutamyl hydrolase cleaves gamma-linked glutamate bonds. With a substrate such as folyl penta-gamma-glutamate, the enzyme acts as an endopeptidase, cleaving the innermost linkage to release the remainder of the side-chain (Yao et al., 1996). There is a difference in specificity between the rat and human forms of the enzyme on some substrates (Rhee et al., 1999). (The membrane-bound glutamate carboxypeptidase II (M28.010) also releases gamma-linked glutamates, but acts only as a carboxypeptidase.)
InhibitorsGlutamine analogues, such as azaserine and 6-diazo-5-oxo-L-norleucine, are inhibitory (Waltham et al., 1997).
Molecular structureThe tertiary structure of human gamma-glutamyl hydrolase is that of a class I glutamine amidotransferase (Li et al., 2002). The enzyme appears as a homodimer. The monomer shows an alpha/beta/alpha sandwich with a central, five-stranded, parallel beta sheet. Similar folds are seen in PfpI endopeptidase (family C56) and dipeptidase E (family S51). Because this fold is shared among cysteine and serine peptidases, the clan to which these peptidase families belong is of mixed catalytic type and is named clan PC. Families C26 and C56 are included in subclan PC(C).
Basis of clan assignmentProtein fold of the peptidase unit for members of this family resembles aspartyl dipeptidase, the type example for clan PC.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi -  
Plants details  
Animals details  
Viruses details  
Biological functionsGamma-glutamyl hydrolase is a lysosomal enzyme probably involved in the turnover of folyl poly-gamma-glutamates.
Pharmaceutical and biotech relevancegamma-Glutamyl hydrolase contributes to the destruction of agents such as methotrexate that are used in cancer therapy (Rhee et al., 1993; Chave et al., 2003).
ReviewsChave et al. (2004)
Statistics for family C26Sequences:21637
Identifiers with PDB entries:13
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Other databases INTERPRO IPR011697
PFAM PF00117
PFAM PF01174
PFAM PF07685
PFAM PF07722
PFAM PF09825
SCOP 52325
Peptidases and Homologues MEROPS ID Structure
gamma-glutamyl hydrolaseC26.001Yes
At1g78660 (Arabidopsis thaliana)C26.002-
At1g78680 (Arabidopsis thaliana)C26.003-
guanine 5’-monophosphate synthetaseC26.950Yes
carbamoyl-phosphate synthase (Homo sapiens-type)C26.951Yes
dihydro-orotase (N-terminal unit) (Homo sapiens-type)C26.952Yes
family C26 non-peptidase homologue (Mus musculus)C26.953-
carA proteinC26.954Yes
aminodeoxychorismate synthase, subunit IIC26.955-
carbamyl phosphate synthetaseC26.956-
GMP synthaseC26.957Yes
para-aminobenzoate synthase (fungi)C26.958-
TRP3 proteinC26.959-
TrpD protein (anthranilate synthase component II)C26.960Yes
PuuD proteinC26.961-
glutamine amidotransferaseC26.962-
carbamoyl-phosphate synthase arginine-specific small chainC26.963-
CTP synthetaseC26.964Yes
imidazole glycerol phosphate synthase subunit HisHC26.965Yes
At1g78670 (Arabidopsis thaliana)C26.A01-
At3g27740 (Arabidopsis thaliana)C26.A04-
gamma-glutamyl peptidase 1 (Arabidopsis thaliana)C26.A05-
At1g66860 (Arabidopsis thaliana)C26.A06-
At1g63660 (Arabidopsis thaliana)C26.A07-
At1g15045 (Arabidopsis thaliana)C26.A08-
At1g25220 (Arabidopsis thaliana)-like peptidaseC26.A09-
At5g38200 (Arabidopsis thaliana)C26.A10-
LD42771 protein (Drosophila melanogaster)C26.A21-
CG32155 protein (Drosophila melanogaster)C26.A22-
CG5082 protein (Drosophila melanogaster)C26.A23-
M106.4b g.p. (Caenorhabditis elegans)C26.A24-
trp1 (Schizosaccharomyces pombe)C26.A25-
SPBP8B7.29 (Schizosaccharomyces pombe)C26.A26-
PF3D7_1308200 g.p. (Plasmodium falciparum)C26.A27-
SPBPB2B2.05 (Schizosaccharomyces pombe)C26.A28-
PF3D7_1410200 g.p. (Plasmodium falciparum)C26.A29-
PFI1100w g.p. (Plasmodium falciparum)C26.A30-
GMP synthase (Pyrococcus furiosus)C26.A31Yes
imidazoleglycerol-phosphate synthase (Pyrococcus furiosus)C26.A32-
carbamoyl-phosphate synthase, small (Pyrococcus furiosus)C26.A33-
GMPS g.p. (Plasmodium falciparum)C26.A34-
pdx2 g.p. (Plasmodium falciparum)C26.A35Yes
ctps g.p. (Brachydanio rerio)C26.A36Yes
family C26 non-peptidase homologuesnon-peptidase homologue-
family C26 unassigned peptidasesunassignedYes