| IED ID | IndEnz0002018501 |
| Enzyme Type ID | protease018501 |
| 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 | Homo sapiens (Human) |
| 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 Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MKKKLVVLGLLAVVLVLVIVGLCLWLPSASKEPDNHVYTRAAVAADAKQCSKIGRDALRDGGSAVDAAIAALLCVGLMNAHSMGIGGGLFLTIYNSTTRKAEVINAREVAPRLAFATMFNSSEQSQKGGLSVAVPGEIRGYELAHQRHGRLPWARLFQPSIQLARQGFPVGKGLAAALENKRTVIEQQPVLCEVFCRDRKVLREGERLTLPQLADTYETLAIEGAQAFYNGSLTAQIVKDIQAAGGIVTAEDLNNYRAELIEHPLNISLGDVVLYMPSAPLSGPVLALILNILKGYNFSRESVESPEQKGLTYHRIVEAFRFAYAKRTLLGDPKFVDVTEVVRNMTSEFFAAQLRAQISDDTTHPISYYKPEFYTPDDGGTAHLSVVAEDGSAVSATSTINLYFGSKVRSPVSGILFNNEMDDFSSPSITNEFGVPPSPANFIQPGKQPLSSMCPTIMVGQDGQVRMVVGAAGGTQITTATALAIIYNLWFGYDVKRAVEEPRLHNQLLPNVTTVERNIDQAVTAALETRHHHTQIASTFIAVVQAIVRTAGGWAAASDSRKGGEPAGY |
| Enzyme Length | 569 |
| Uniprot Accession Number | P19440 |
| Absorption | |
| Active Site | ACT_SITE 381; /note="Nucleophile"; /evidence="ECO:0000269|PubMed:17924658, ECO:0000269|PubMed:26013825" |
| Activity Regulation | ACTIVITY REGULATION: Activated by autocatalytic cleavage (PubMed:23682772). Inhibited by serine-borate (PubMed:21447318). {ECO:0000269|PubMed:21447318, ECO:0000269|PubMed:23682772}. |
| Binding Site | BINDING 107; /note=Glutamate; /evidence=ECO:0000269|PubMed:24047895; BINDING 423; /note=Glutamate; /evidence=ECO:0000269|PubMed:26013825; BINDING 474; /note=Glutamate; via amide nitrogen; /evidence=ECO:0000269|PubMed:26013825 |
| 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:17924658, ECO:0000269|PubMed:21447318, ECO:0000269|PubMed:23682772, ECO:0000269|PubMed:7673200, ECO:0000269|PubMed:7759490, ECO:0000269|PubMed:8095045, ECO:0000269|PubMed:8827453}; 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:17924658, ECO:0000269|PubMed:21447318};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28808; Evidence={ECO:0000305|PubMed:21447318}; 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:17924658, ECO:0000269|PubMed:21447318};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59469; Evidence={ECO:0000305|PubMed:21447318}; 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:21447318};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31564; Evidence={ECO:0000305}; |
| 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 (PubMed:17924658, PubMed:7673200, PubMed:7759490, PubMed:8095045, PubMed:8827453, PubMed:21447318). Contributes to cysteine homeostasis, glutathione homeostasis and in the conversion of the leukotriene LTC4 to LTD4. {ECO:0000269|PubMed:17924658, ECO:0000269|PubMed:20622017, ECO:0000269|PubMed:21447318, ECO:0000269|PubMed:24047895, ECO:0000269|PubMed:7673200, ECO:0000269|PubMed:7759490, ECO:0000269|PubMed:8095045, ECO:0000269|PubMed:8827453}.; FUNCTION: [Isoform 3]: Seems to be inactive. {ECO:0000269|PubMed:7689219}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Lipid metabolism; leukotriene D4 biosynthesis. {ECO:0000269|PubMed:21447318}.; PATHWAY: Sulfur metabolism; glutathione metabolism. {ECO:0000269|PubMed:21447318}. |
| nucleotide Binding | |
| Features | Active site (1); Alternative sequence (3); Beta strand (20); Binding site (3); Chain (2); Disulfide bond (2); Erroneous initiation (1); Glycosylation (7); Helix (24); Mutagenesis (22); Natural variant (6); Region (2); Sequence conflict (6); Topological domain (2); Transmembrane (1); Turn (6) |
| Keywords | 3D-structure;Acyltransferase;Alternative promoter usage;Alternative splicing;Cell membrane;Direct protein sequencing;Disulfide bond;Glutathione biosynthesis;Glycoprotein;Hydrolase;Lipid metabolism;Membrane;Mental retardation;Protease;Reference proteome;Sialic acid;Signal-anchor;Transferase;Transmembrane;Transmembrane helix;Zymogen |
| Interact With | Q92993; Q8TAP4-4; P17252; Q15047-2; P61981 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23682772, ECO:0000269|PubMed:8095045}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:P07314}. |
| Modified Residue | |
| Post Translational Modification | PTM: N-glycosylated on both chains. Contains hexoses, hexosamines and sialic acid residues. Glycosylation profiles tested in kidney and liver tissues reveal the presence of tissue-specific and site-specific glycan composition, despite the overlap in composition among the N-glycans. A total of 36 glycan compositions, with 40 unique structures are observed. Up to 15 different glycans are observed at a single site, with site-specific variation in glycan composition. The difference in glycosylation profiles in the 2 tissues do not affect the enzyme activity. {ECO:0000269|PubMed:15084671, ECO:0000269|PubMed:17924658, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19349973, ECO:0000269|PubMed:19463, ECO:0000269|PubMed:20622017, ECO:0000269|PubMed:23682772, ECO:0000269|PubMed:24047895, ECO:0000269|PubMed:2900635}.; 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:0000269|PubMed:23682772}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (7) |
| Cross Reference PDB | 4GDX; 4GG2; 4Z9O; 4ZBK; 4ZC6; 4ZCG; 5V4Q; |
| Mapped Pubmed ID | 10391245; 10462554; 10851239; 12235216; 17601350; 18357469; 18464913; 18486613; 18940312; 18977241; 20711500; 21712391; 2573352; 28378915; 6122208; 8813074; 9080; |
| Motif | |
| Gene Encoded By | |
| Mass | 61,410 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=11 mM for glycylglycine {ECO:0000269|PubMed:7759490}; KM=10.6 uM for glutathione {ECO:0000269|PubMed:21447318}; KM=8.8 uM for oxidized-glutathione {ECO:0000269|PubMed:21447318}; KM=1.3 mM for D-gamma-glutamyl-p-nitroanalide {ECO:0000269|PubMed:7759490}; KM=9.9 uM for S-methylglutathion {ECO:0000269|PubMed:21447318}; KM=33.4 uM for gamma-glutamyl leucine {ECO:0000269|PubMed:21447318}; KM=10.8 uM for leukotriene C4 {ECO:0000269|PubMed:21447318}; |
| Metal Binding | |
| Rhea ID | RHEA:23904; RHEA:28807; RHEA:28808; RHEA:59468; RHEA:59469; RHEA:31563; RHEA:31564 |
| Cross Reference Brenda |