Detail Information for IndEnz0002018501
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