Family T3


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

Summary for family T3

NamePeptidase family T3 (gamma-glutamyltransferase family)
Family type peptidaseT03.001 - gamma-glutamyltransferase 1 (bacterial-type) (Escherichia coli), MEROPS Accession MER0001978 (peptidase unit: 26-580)
Content of familyPeptidase family T3 contains self-processing proteins that express aminopeptidase as well as aminotransferase activities in their mature forms.
History Identifier created: MEROPS 3.1 (22 December 1998)
gamma-Glutamyltransferase, the most fully characterised peptidase in family T3, has been reviewed by Hiratake et al. (2004).
Catalytic typeThreonine
Active site residuesS,T391 
Active siteIn bacterial gamma-glutamyltransferase, Thr391 (see the Alignment) is believed to be the key catalytic residue in both the maturation of the precursor and the transglutaminase reaction (Suzuki & Kumagai, 2002). Some processing occurred in a Thr391Ser mutant. The corresponding Thr residue is probably responsible for both reactions in the mammalian enzyme also, but for this the data are less clear.
Activities and specificitiesThe precursor of gamma-glutamyltransferase (T03.001) from Escherichia coli undergoes an autolytic cleavage on the amino side of Thr391 (see the Alignment) (Suzuki & Kumagai, 2002). Mature gamma-glutamyltranferase (T03.001) catalyzes the transfer of the gamma-glutamyl moiety of gamma-glutamyl-derived peptides such as glutathione (gammaGlu-Cys-Gly), and anilides such as gamma-glutamyl-7-amido-4-methylcoumarin (gammaGlu-AMC) to acceptor molecules including water and various dipeptides (Stein et al., 2001). The only other family of peptidases in which autolytic cleavage is known to give rise to peptidases acting on other substrates is T1, also in clan PB.
InhibitorsGamma-glutamyltrasferase is inhibited by 6-diazo-5-oxo-L-norleucine and L-azaserine (Tate & Meister, 1977) as well as the serine-borate complex (Tate & Meister, 1978). The compound acivicin (L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazole acetic acid) is also effective (Stole et al., 1994; Smith et al., 1995), and the enzyme is potently inhibited by the gamma-boronic acid analogue of L-glutamic acid, 3-amino-3-carboxypropaneboronic acid (gamma-boroGlu) (Stein et al., 2001).
Molecular structureA preliminary description of the structure of Escherichia coli gamma-glutamyltranferase published by Sakai et al. (1996), shows a fold similar to that of an N-terminal nucleophile hydrolase (Brannigan et al., 1995; Suzuki & Kumagai, 2002). For this reason, family T3 is placed in clan PB. The single-chain precursor becomes a heterodimer on self-cleavage (Hashimoto et al., 1995).
Basis of clan assignmentThe active site residue for members of this family and family T1 is C-terminal to the autolytic cleavage site.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi details  
Plants details  
Animals details  
Viruses details  
Biological functionsMammalian gamma-glutamyl transferase occurs as a heterodimeric enzyme that is highly glycosylated and processed in the endoplasmic reticulum and Golgi, and then becomes attached to the external surface of cell membranes (Smith & Meister, 1994). Its physiological function is the degradation of glutathione by cleavage of the gamma-glutamyl bond, either by hydrolysis or transpeptidation (Hiratake et al., 2004). The E. coli enzyme, which is not glycosylated, is a soluble enzyme localised in the periplasmic space.
Statistics for family T3Sequences:8349
Identifiers with PDB entries:2
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
gamma-glutamyltransferase 1 (bacterial-type)T03.001Yes
gamma-glutamyltransferase CG17636 (Diptera)T03.005-
gamma-glutamyltransferase (insect)T03.007-
gamma-glutamyltransferase (plant)T03.008-
gamma-glutamyltransferase (nematode )T03.009-
gamma-glutamyltransferase CG1492 (Drosophila-type)T03.010-
gamma-glutamyltransferase (Saccharomyces-type)T03.012-
gamma-glutamyltransferase (Synechocystis-type)T03.013-
gamma-glutamyltransferase 2 (bacterial)T03.014-
gamma-glutamyltransferase 2 (Homo sapiens)T03.015-
gamma-glutamyltransferase-like protein 4T03.016-
gamma-glutamyltransferase-like protein 3T03.017-
protein similar to gamma-glutamyltransferase 1 precursorT03.018-
similar to gamma-glutamyltransferase 1 precursor (Homo sapiens)T03.019-
Mername-AA211 putative peptidaseT03.021-
9030405D14Rik putative peptidaseT03.022-
gamma-glutamyltransferase 6T03.024-
gamma-glutamyl transpeptidase homologue (chromosome 2, Homo sapiens) and similarT03.971-
At4g29210 (Arabidopsis thaliana)T03.A01-
At4g39650 (Arabidopsis thaliana)T03.A03-
CG6461 protein (Drosophila melanogaster)T03.A04-
C53D5.5 g.p. (Caenorhabditis elegans)T03.A05-
H14N18.4a g.p. (Caenorhabditis elegans)T03.A06-
Y7A9A.1 g.p. (Caenorhabditis elegans)T03.A07-
T19H12.6 g.p. (Caenorhabditis elegans)T03.A08-
GYO_3966 g.p. (Bacillus subtilis)T03.A09Yes
family T3 non-peptidase homologuesnon-peptidase homologue-
family T3 unassigned peptidasesunassigned-