Gene/Proteome Database (LMPD)
LMPD ID
LMP001635
Gene ID
Species
Homo sapiens (Human)
Gene Name
gamma-glutamyltransferase 1
Gene Symbol
Synonyms
CD224; D22S672; D22S732; GGT; GGT 1; GTG
Alternate Names
gamma-glutamyltranspeptidase 1; glutathione hydrolase 1; leukotriene-C4 hydrolase
Chromosome
22
Map Location
22q11.23
EC Number
2.3.2.2
Summary
The enzyme encoded by this gene is a type I gamma-glutamyltransferase that catalyzes the transfer of the glutamyl moiety of glutathione to a variety of amino acids and dipeptide acceptors. The enzyme is composed of a heavy chain and a light chain, which are derived from a single precursor protein. It is expressed in tissues involved in absorption and secretion and may contribute to the etiology of diabetes and other metabolic disorders. Multiple alternatively spliced variants have been identified. There are a number of related genes present on chromosomes 20 and 22, and putative pseudogenes for this gene on chromosomes 2, 13, and 22. [provided by RefSeq, Jan 2014]
Orthologs
Proteins
| gamma-glutamyltranspeptidase 1 precursor | |
|---|---|
| Refseq ID | NP_001275762 |
| Protein GI | 572152963 |
| UniProt ID | P19440 |
| mRNA ID | NM_001288833 |
| Length | 569 |
| RefSeq Status | REVIEWED |
| MKKKLVVLGLLAVVLVLVIVGLCLWLPSASKEPDNHVYTRAAVAADAKQCSKIGRDALRDGGSAVDAAIAALLCVGLMNAHSMGIGGGLFLTIYNSTTRKAEVINAREVAPRLAFATMFNSSEQSQKGGLSVAVPGEIRGYELAHQRHGRLPWARLFQPSIQLARQGFPVGKGLAAALENKRTVIEQQPVLCEVFCRDRKVLREGERLTLPQLADTYETLAIEGAQAFYNGSLTAQIVKDIQAAGGIVTAEDLNNYRAELIEHPLNISLGDVVLYMPSAPLSGPVLALILNILKGYNFSRESVESPEQKGLTYHRIVEAFRFAYAKRTLLGDPKFVDVTEVVRNMTSEFFAAQLRAQISDDTTHPISYYKPEFYTPDDGGTAHLSVVAEDGSAVSATSTINLYFGSKVRSPVSGILFNNEMDDFSSPSITNEFGVPPSPANFIQPGKQPLSSMCPTIMVGQDGQVRMVVGAAGGTQITTATALAIIYNLWFGYDVKRAVEEPRLHNQLLPNVTTVERNIDQAVTAALETRHHHTQIASTFIAVVQAIVRTAGGWAAASDSRKGGEPAGY | |
| gamma-glutamyltranspeptidase 1 precursor | |
|---|---|
| Refseq ID | NP_038265 |
| Protein GI | 572153074 |
| UniProt ID | P19440 |
| mRNA ID | NM_013421 |
| Length | 569 |
| RefSeq Status | REVIEWED |
| Protein sequence is identical to GI:572152963 (mRNA isoform) | |
| gamma-glutamyltranspeptidase 1 precursor | |
|---|---|
| Refseq ID | NP_038347 |
| Protein GI | 73915092 |
| UniProt ID | P19440 |
| mRNA ID | NM_013430 |
| Length | 569 |
| RefSeq Status | REVIEWED |
| Protein sequence is identical to GI:572152963 (mRNA isoform) | |
| mat_peptide: 1..380 product: Gamma-glutamyltranspeptidase 1 heavy chain experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (P19440.2) calculated_mol_wt: 41431 peptide sequence: MKKKLVVLGLLAVVLVLVIVGLCLWLPSASKEPDNHVYTRAAVAADAKQCSKIGRDALRDGGSAVDAAIAALLCVGLMNAHSMGIGGGLFLTIYNSTTRKAEVINAREVAPRLAFATMFNSSEQSQKGGLSVAVPGEIRGYELAHQRHGRLPWARLFQPSIQLARQGFPVGKGLAAALENKRTVIEQQPVLCEVFCRDRKVLREGERLTLPQLADTYETLAIEGAQAFYNGSLTAQIVKDIQAAGGIVTAEDLNNYRAELIEHPLNISLGDVVLYMPSAPLSGPVLALILNILKGYNFSRESVESPEQKGLTYHRIVEAFRFAYAKRTLLGDPKFVDVTEVVRNMTSEFFAAQLRAQISDDTTHPISYYKPEFYTPDDGG mat_peptide: 381..569 product: Gamma-glutamyltranspeptidase 1 light chain experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (P19440.2) calculated_mol_wt: 19998 peptide sequence: TAHLSVVAEDGSAVSATSTINLYFGSKVRSPVSGILFNNEMDDFSSPSITNEFGVPPSPANFIQPGKQPLSSMCPTIMVGQDGQVRMVVGAAGGTQITTATALAIIYNLWFGYDVKRAVEEPRLHNQLLPNVTTVERNIDQAVTAALETRHHHTQIASTFIAVVQAIVRTAGGWAAASDSRKGGEPAGY mat_peptide: 1..380 product: Gamma-glutamyltranspeptidase 1 heavy chain experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (P19440.2) calculated_mol_wt: 41431 peptide sequence: MKKKLVVLGLLAVVLVLVIVGLCLWLPSASKEPDNHVYTRAAVAADAKQCSKIGRDALRDGGSAVDAAIAALLCVGLMNAHSMGIGGGLFLTIYNSTTRKAEVINAREVAPRLAFATMFNSSEQSQKGGLSVAVPGEIRGYELAHQRHGRLPWARLFQPSIQLARQGFPVGKGLAAALENKRTVIEQQPVLCEVFCRDRKVLREGERLTLPQLADTYETLAIEGAQAFYNGSLTAQIVKDIQAAGGIVTAEDLNNYRAELIEHPLNISLGDVVLYMPSAPLSGPVLALILNILKGYNFSRESVESPEQKGLTYHRIVEAFRFAYAKRTLLGDPKFVDVTEVVRNMTSEFFAAQLRAQISDDTTHPISYYKPEFYTPDDGG mat_peptide: 381..569 product: Gamma-glutamyltranspeptidase 1 light chain experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (P19440.2) calculated_mol_wt: 19998 peptide sequence: TAHLSVVAEDGSAVSATSTINLYFGSKVRSPVSGILFNNEMDDFSSPSITNEFGVPPSPANFIQPGKQPLSSMCPTIMVGQDGQVRMVVGAAGGTQITTATALAIIYNLWFGYDVKRAVEEPRLHNQLLPNVTTVERNIDQAVTAALETRHHHTQIASTFIAVVQAIVRTAGGWAAASDSRKGGEPAGY mat_peptide: 1..380 product: Gamma-glutamyltranspeptidase 1 heavy chain experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (P19440.2) calculated_mol_wt: 41431 peptide sequence: MKKKLVVLGLLAVVLVLVIVGLCLWLPSASKEPDNHVYTRAAVAADAKQCSKIGRDALRDGGSAVDAAIAALLCVGLMNAHSMGIGGGLFLTIYNSTTRKAEVINAREVAPRLAFATMFNSSEQSQKGGLSVAVPGEIRGYELAHQRHGRLPWARLFQPSIQLARQGFPVGKGLAAALENKRTVIEQQPVLCEVFCRDRKVLREGERLTLPQLADTYETLAIEGAQAFYNGSLTAQIVKDIQAAGGIVTAEDLNNYRAELIEHPLNISLGDVVLYMPSAPLSGPVLALILNILKGYNFSRESVESPEQKGLTYHRIVEAFRFAYAKRTLLGDPKFVDVTEVVRNMTSEFFAAQLRAQISDDTTHPISYYKPEFYTPDDGG mat_peptide: 381..569 product: Gamma-glutamyltranspeptidase 1 light chain experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (P19440.2) calculated_mol_wt: 19998 peptide sequence: TAHLSVVAEDGSAVSATSTINLYFGSKVRSPVSGILFNNEMDDFSSPSITNEFGVPPSPANFIQPGKQPLSSMCPTIMVGQDGQVRMVVGAAGGTQITTATALAIIYNLWFGYDVKRAVEEPRLHNQLLPNVTTVERNIDQAVTAALETRHHHTQIASTFIAVVQAIVRTAGGWAAASDSRKGGEPAGY | |
Gene Information
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0031362 | TAS:UniProtKB | C | anchored component of external side of plasma membrane |
| GO:0005615 | IDA:UniProt | C | extracellular space |
| GO:0070062 | IDA:UniProtKB | C | extracellular vesicular exosome |
| GO:0016021 | IEA:UniProtKB-KW | C | integral component of membrane |
| GO:0005886 | IDA:UniProtKB | C | plasma membrane |
| GO:0003840 | IDA:UniProtKB | F | gamma-glutamyltransferase activity |
| GO:0036374 | IDA:UniProtKB | F | glutathione hydrolase activity |
| GO:0019369 | TAS:Reactome | P | arachidonic acid metabolic process |
| GO:0006520 | TAS:ProtInc | P | cellular amino acid metabolic process |
| GO:0019344 | ISS:UniProtKB | P | cysteine biosynthetic process |
| GO:0006536 | IDA:UniProtKB | P | glutamate metabolic process |
| GO:0006750 | ISS:UniProtKB | P | glutathione biosynthetic process |
| GO:0006751 | IDA:UniProtKB | P | glutathione catabolic process |
| GO:1901687 | TAS:Reactome | P | glutathione derivative biosynthetic process |
| GO:0006749 | TAS:UniProtKB | P | glutathione metabolic process |
| GO:0019370 | IMP:UniProtKB | P | leukotriene biosynthetic process |
| GO:0006691 | TAS:Reactome | P | leukotriene metabolic process |
| GO:0002682 | ISS:UniProtKB | P | regulation of immune system process |
| GO:0050727 | ISS:UniProtKB | P | regulation of inflammatory response |
| GO:0044281 | TAS:Reactome | P | small molecule metabolic process |
| GO:0007283 | ISS:UniProtKB | P | spermatogenesis |
| GO:0006805 | TAS:Reactome | P | xenobiotic metabolic process |
| GO:0031638 | IDA:UniProtKB | P | zymogen activation |
BIOCYC Pathway Links
| BIOCYC Pathway ID | Description |
|---|---|
| PWY66-375 | leukotriene biosynthesis |
REACTOME Pathway Links
| REACTOME Pathway ID | Description |
|---|---|
| REACT_228214 | Aflatoxin activation and detoxification |
| REACT_150420 | Synthesis of Leukotrienes (LT) and Eoxins (EX) |
Domain Information
UniProt Annotations
Entry Information
Comments
| Comment Type | Description |
|---|---|
| Alternative Products | Event=Alternative promoter usage, Alternative splicing; Named isoforms=3; Name=1; IsoId=P19440-1; Sequence=Displayed; Note=Produced by alternative promoter usage.; Name=2; IsoId=P19440-2; Sequence=VSP_001746, VSP_001747; Note=Produced by alternative splicing of isoform 1.; Name=3; IsoId=P19440-3; Sequence=VSP_008132; Note=Produced by alternative promoter usage.; |
| Catalytic Activity | A (5-L-glutamyl)-peptide + an amino acid = a peptide + a 5-L-glutamyl amino acid. |
| Catalytic Activity | Glutathione + H(2)O = L-cysteinylglycine + L- glutamate. |
| Catalytic Activity | Leukotriene C(4) + H(2)O = leukotriene D(4) + L-glutamate. |
| Disease | Glutathionuria (GLUTH) [MIM |
| Enzyme Regulation | Activated by autocatalytic cleavage. |
| Function | Cleaves the gamma-glutamyl bond of extracellular glutathione (gamma-Glu-Cys-Gly), glutathione conjugates, and other gamma-glutamyl compounds. The metabolism of glutathione 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. Initiates extracellular glutathione (GSH) breakdown, provides cells with a local cysteine supply and contributes to maintain intracellular GSH level. It is part of the cell antioxidant defense mechanism. Isoform 3 seems to be inactive. {ECO |
| Miscellaneous | Chloride ions bound in the active site cavity may contribute to stabilize the protein fold. |
| Miscellaneous | Cys-454 was thought to bind the gamma-glutamyl moiety, but mutagenesis of this residue had no effect on activity. |
| Pathway | Sulfur metabolism; glutathione metabolism. |
| Ptm | Cleaved by autocatalysis into a large and a small subunit and the autocatalytic cleavage is essential to the functional activation of the enzyme. |
| 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 |
| Sequence Caution | Sequence=AAA35899.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence= ; |
| Similarity | Belongs to the gamma-glutamyltransferase family. |
| Subcellular Location | Cell membrane {ECO |
| Subunit | Heterodimer composed of the light and heavy chains. The active site is located in the light chain. |
| Tissue Specificity | Detected in fetal and adult kidney and liver, adult pancreas, stomach, intestine, placenta and lung. Isoform 3 is lung-specific. There are several other tissue-specific forms that arise from alternative promoter usage but that produce the same protein. |
| Web Resource | Name=Wikipedia; Note=Gamma-glutamyl transpeptidase entry; URL="http://en.wikipedia.org/wiki/Gamma_glutamyl_transpeptidase"; |
Identical and Related Proteins
Unique RefSeq proteins for LMP001635 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 572152963 | RefSeq | NP_001275762 | 569 | gamma-glutamyltranspeptidase 1 precursor |
Identical Sequences to LMP001635 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:572152963 | DBBJ | BAI45314.1 | 569 | gamma-glutamyltransferase 1, partial [synthetic construct] |
| GI:572152963 | GenBank | AHD76691.1 | 569 | Sequence 20911 from patent US 8586006 |
| GI:572152963 | GenBank | AHD76692.1 | 569 | Sequence 20912 from patent US 8586006 |
| GI:572152963 | GenBank | AHD76693.1 | 569 | Sequence 20913 from patent US 8586006 |
| GI:572152963 | GenBank | AHD76694.1 | 569 | Sequence 20914 from patent US 8586006 |
| GI:572152963 | RefSeq | NP_038265.2 | 569 | gamma-glutamyltranspeptidase 1 precursor [Homo sapiens] |
Related Sequences to LMP001635 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:572152963 | EMBL | CAA42674.1 | 569 | gamma-glutamyltranspeptidase [Homo sapiens] |
| GI:572152963 | GenBank | AAA52546.1 | 569 | gamma-glutamyltransferase 1 (EC 2.3.2.2) [Homo sapiens] |
| GI:572152963 | GenBank | AAA52547.1 | 569 | gamma-glutamyl transpeptidase (EC 2.3.2.2) [Homo sapiens] |
| GI:572152963 | GenBank | AAX36095.1 | 570 | gamma-glutamyltransferase 1, partial [synthetic construct] |
| GI:572152963 | GenBank | ADT50493.1 | 569 | Sequence 2510 from patent US 7842467 |
| GI:572152963 | GenBank | AEN34568.1 | 569 | Sequence 496 from patent US 7998689 |