| IED ID | IndEnz0002018504 |
| Enzyme Type ID | protease018504 |
| Protein Name |
Glutathione hydrolase 1 proenzyme EC 3.4.19.13 Gamma-glutamyltransferase 1 Gamma-glutamyltranspeptidase 1 GGT 1 EC 2.3.2.2 Leukotriene-C4 hydrolase EC 3.4.19.14 CD antigen CD224 Cleaved into: Glutathione hydrolase 1 heavy chain; Glutathione hydrolase 1 light chain |
| Gene Name | Ggt1 Ggt |
| Organism | Rattus norvegicus (Rat) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Rattus Rattus norvegicus (Rat) |
| Enzyme Sequence | MKNRFLVLGLVAVVLVFVIIGLCIWLPTTSGKPDHVYSRAAVATDAKRCSEIGRDMLQEGGSVVDAAIASLLCMGLINAHSMGIGGGLFFTIYNSTTRKAEVINAREMAPRLANTSMFNNSKDSEEGGLSVAVPGEIRGYELAHQRHGRLPWARLFQPSIQLARHGFPVGKGLARALDKKRDIIEKTPALCEVFCRQGKVLQEGETVTMPKLADTLQILAQEGARAFYNGSLTAQIVKDIQEAGGIMTVEDLNNYRAEVIEHPMSIGLGDSTLYVPSAPLSGPVLILILNILKGYNFSPKSVATPEQKALTYHRIVEAFRFAYAKRTMLGDPKFVDVSQVIRNMSSEFYATQLRARITDETTHPTAYYEPEFYLPDDGGTAHLSVVSEDGSAVAATSTINLYFGSKVLSRVSGILFNDEMDDFSSPNFTNQFGVAPSPANFIKPGKQPLSSMCPSIIVDKDGKVRMVVGASGGTQITTSVALAIINSLWFGYDVKRAVEEPRLHNQLLPNTTTVEKNIDQVVTAGLKTRHHHTEVTPDFIAVVQAVVRTSGGWAAASDSRKGGEPAGY |
| Enzyme Length | 568 |
| Uniprot Accession Number | P07314 |
| Absorption | |
| Active Site | ACT_SITE 380; /note=Nucleophile; /evidence=ECO:0000250|UniProtKB:P19440 |
| Activity Regulation | ACTIVITY REGULATION: Activated by autocatalytic cleavage. {ECO:0000250|UniProtKB:P19440}. |
| Binding Site | BINDING 106; /note=Glutamate; /evidence=ECO:0000250|UniProtKB:P19440; BINDING 419; /note=Glutamate; /evidence=ECO:0000250|UniProtKB:P19440; BINDING 422; /note=Glutamate; /evidence=ECO:0000250|UniProtKB:P19440; BINDING 473; /note=Glutamate; via amide nitrogen; /evidence=ECO:0000250|UniProtKB:P19440 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=an alpha-amino acid + an N-terminal (5-L-glutamyl)-[peptide] = 5-L-glutamyl amino acid + N-terminal L-alpha-aminoacyl-[peptide]; Xref=Rhea:RHEA:23904, Rhea:RHEA-COMP:9780, Rhea:RHEA-COMP:9795, ChEBI:CHEBI:77644, ChEBI:CHEBI:78597, ChEBI:CHEBI:78599, ChEBI:CHEBI:78608; EC=2.3.2.2; Evidence={ECO:0000269|PubMed:6122208}; CATALYTIC ACTIVITY: Reaction=glutathione + H2O = L-cysteinylglycine + L-glutamate; Xref=Rhea:RHEA:28807, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985, ChEBI:CHEBI:57925, ChEBI:CHEBI:61694; EC=3.4.19.13; Evidence={ECO:0000269|PubMed:6122208};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28808; Evidence={ECO:0000250|UniProtKB:P19440}; CATALYTIC ACTIVITY: Reaction=an S-substituted glutathione + H2O = an S-substituted L-cysteinylglycine + L-glutamate; Xref=Rhea:RHEA:59468, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985, ChEBI:CHEBI:90779, ChEBI:CHEBI:143103; EC=3.4.19.13; Evidence={ECO:0000269|PubMed:6122208};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59469; Evidence={ECO:0000250|UniProtKB:P19440}; CATALYTIC ACTIVITY: Reaction=H2O + leukotriene C4 = L-glutamate + leukotriene D4; Xref=Rhea:RHEA:31563, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985, ChEBI:CHEBI:57973, ChEBI:CHEBI:63166; EC=3.4.19.14; Evidence={ECO:0000269|PubMed:6122208};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31564; Evidence={ECO:0000250|UniProtKB:P19440}; |
| DNA Binding | |
| EC Number | 3.4.19.13; 2.3.2.2; 3.4.19.14 |
| Enzyme Function | FUNCTION: Cleaves the gamma-glutamyl bond of extracellular glutathione (gamma-Glu-Cys-Gly), glutathione conjugates and other gamma-glutamyl compounds, such as leukotriene C4 (LTC4). The metabolism of glutathione by GGT1 releases free glutamate and the dipeptide cysteinyl-glycine, which is hydrolyzed to cysteine and glycine by dipeptidases. In the presence of high concentrations of dipeptides and some amino acids, can also catalyze a transpeptidation reaction, transferring the gamma-glutamyl moiety to an acceptor amino acid to form a new gamma-glutamyl compound. Contributes to cysteine homeostasis, glutathione homeostasis and in the conversion of the leukotriene LTC4 to LTD4. {ECO:0000250|UniProtKB:P19440}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Sulfur metabolism; glutathione metabolism. {ECO:0000250|UniProtKB:P19440}. |
| nucleotide Binding | |
| Features | Active site (1); Binding site (4); Chain (2); Disulfide bond (2); Frameshift (1); Glycosylation (7); Region (2); Sequence conflict (11); Topological domain (2); Transmembrane (1) |
| Keywords | Acyltransferase;Cell membrane;Direct protein sequencing;Disulfide bond;Glutathione biosynthesis;Glycoprotein;Hydrolase;Membrane;Protease;Reference proteome;Sialic acid;Signal-anchor;Transferase;Transmembrane;Transmembrane helix;Zymogen |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P19440}; Single-pass type II membrane protein {ECO:0000305|PubMed:6136502}. |
| Modified Residue | |
| Post Translational Modification | PTM: N-glycosylated on both chains; contains sialic acid residues. It is not known if the sialic acid residues are present on N-linked or on O-linked glycans. {ECO:0000269|PubMed:6142889}.; PTM: O-glycosylated; close to the membrane anchor on the heavy chain and on the light chain. The sugar moieties are localized to the stretch Thr-28 to Ser-30. Contains sialic acid residues. It is not known if the sialic acid residues are present on N-linked or on O-linked glycans. {ECO:0000269|PubMed:2573604}.; PTM: Cleaved by autocatalysis into a large and a small subunit and the autocatalytic cleavage is essential to the functional activation of the enzyme. {ECO:0000250|UniProtKB:P19440}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10934156; 11601992; 16973162; 18075840; 18291430; 18309775; 19699728; 2567161; 6113606; 9559866; |
| Motif | |
| Gene Encoded By | |
| Mass | 61,610 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=5.9 uM for leukotriene C(4) {ECO:0000269|PubMed:6122208}; KM=5.7 uM for glutathione {ECO:0000269|PubMed:6122208}; KM=5.8 uM for gamma-glutamyl-p-anilide {ECO:0000269|PubMed:6122208}; |
| Metal Binding | |
| Rhea ID | RHEA:23904; RHEA:28807; RHEA:28808; RHEA:59468; RHEA:59469; RHEA:31563; RHEA:31564 |
| Cross Reference Brenda | 2.3.2.2; |