P07314 · GGT1_RAT
- ProteinGlutathione hydrolase 1 proenzyme
- GeneGgt1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids568 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Cleaves the gamma-glutamyl bond of extracellular glutathione (gamma-Glu-Cys-Gly), glutathione conjugates (such as maresin conjugate (13R)-S-glutathionyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate, MCTR1) and other gamma-glutamyl compounds (such as leukotriene C4, LTC4) (By similarity) (PubMed:6122208).
The metabolism of glutathione by GGT1 releases free glutamate and the dipeptide cysteinyl-glycine, which is hydrolyzed to cysteine and glycine by dipeptidases (PubMed:6122208).
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:6122208).
Contributes to cysteine homeostasis, glutathione homeostasis and in the conversion of the leukotriene LTC4 to LTD4 (PubMed:6122208).
The metabolism of glutathione by GGT1 releases free glutamate and the dipeptide cysteinyl-glycine, which is hydrolyzed to cysteine and glycine by dipeptidases (PubMed:6122208).
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:6122208).
Contributes to cysteine homeostasis, glutathione homeostasis and in the conversion of the leukotriene LTC4 to LTD4 (PubMed:6122208).
Catalytic activity
- an alpha-amino acid + an N-terminal (5-L-glutamyl)-[peptide] = 5-L-glutamyl amino acid + N-terminal L-alpha-aminoacyl-[peptide]This reaction proceeds in the forward and the backward directions.
- (13R)-S-glutathionyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate + H2O = (13R)-S-cysteinylglycyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate + L-glutamateThis reaction proceeds in the forward direction.
Activity regulation
Activated by autocatalytic cleavage.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
5.9 μM | leukotriene C4 | |||||
5.7 μM | glutathione | |||||
5.8 μM | gamma-glutamyl-p-anilide |
Pathway
Sulfur metabolism; glutathione metabolism.
Lipid metabolism; leukotriene D4 biosynthesis.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 106 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Active site | 380 | Nucleophile | ||||
Sequence: T | ||||||
Binding site | 398-400 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: TIN | ||||||
Binding site | 419 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 422 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 450-451 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: SS | ||||||
Binding site | 473 | L-glutamate (UniProtKB | ChEBI) | ||||
Sequence: G |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameGlutathione hydrolase 1 proenzyme
- EC number
- Alternative names
- Cleaved into 2 chains
- CD Antigen Name
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP07314
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type II membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-4 | Cytoplasmic | ||||
Sequence: MKNR | ||||||
Transmembrane | 5-26 | Helical; Signal-anchor for type II membrane protein | ||||
Sequence: FLVLGLVAVVLVFVIIGLCIWL | ||||||
Topological domain | 27-568 | Extracellular | ||||
Sequence: PTTSGKPDHVYSRAAVATDAKRCSEIGRDMLQEGGSVVDAAIASLLCMGLINAHSMGIGGGLFFTIYNSTTRKAEVINAREMAPRLANTSMFNNSKDSEEGGLSVAVPGEIRGYELAHQRHGRLPWARLFQPSIQLARHGFPVGKGLARALDKKRDIIEKTPALCEVFCRQGKVLQEGETVTMPKLADTLQILAQEGARAFYNGSLTAQIVKDIQEAGGIMTVEDLNNYRAEVIEHPMSIGLGDSTLYVPSAPLSGPVLILILNILKGYNFSPKSVATPEQKALTYHRIVEAFRFAYAKRTMLGDPKFVDVSQVIRNMSSEFYATQLRARITDETTHPTAYYEPEFYLPDDGGTAHLSVVSEDGSAVAATSTINLYFGSKVLSRVSGILFNDEMDDFSSPNFTNQFGVAPSPANFIKPGKQPLSSMCPSIIVDKDGKVRMVVGASGGTQITTSVALAIINSLWFGYDVKRAVEEPRLHNQLLPNTTTVEKNIDQVVTAGLKTRHHHTEVTPDFIAVVQAVVRTSGGWAAASDSRKGGEPAGY |
Keywords
- Cellular component
Phenotypes & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 4 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000011064 | 1-379 | Glutathione hydrolase 1 heavy chain | |||
Sequence: MKNRFLVLGLVAVVLVFVIIGLCIWLPTTSGKPDHVYSRAAVATDAKRCSEIGRDMLQEGGSVVDAAIASLLCMGLINAHSMGIGGGLFFTIYNSTTRKAEVINAREMAPRLANTSMFNNSKDSEEGGLSVAVPGEIRGYELAHQRHGRLPWARLFQPSIQLARHGFPVGKGLARALDKKRDIIEKTPALCEVFCRQGKVLQEGETVTMPKLADTLQILAQEGARAFYNGSLTAQIVKDIQEAGGIMTVEDLNNYRAEVIEHPMSIGLGDSTLYVPSAPLSGPVLILILNILKGYNFSPKSVATPEQKALTYHRIVEAFRFAYAKRTMLGDPKFVDVSQVIRNMSSEFYATQLRARITDETTHPTAYYEPEFYLPDDGG | ||||||
Disulfide bond | 49↔73 | |||||
Sequence: CSEIGRDMLQEGGSVVDAAIASLLC | ||||||
Glycosylation | 94 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 114 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 119 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 191↔195 | |||||
Sequence: CEVFC | ||||||
Glycosylation | 229 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 343 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Chain | PRO_0000011065 | 380-568 | Glutathione hydrolase 1 light chain | |||
Sequence: TAHLSVVSEDGSAVAATSTINLYFGSKVLSRVSGILFNDEMDDFSSPNFTNQFGVAPSPANFIKPGKQPLSSMCPSIIVDKDGKVRMVVGASGGTQITTSVALAIINSLWFGYDVKRAVEEPRLHNQLLPNTTTVEKNIDQVVTAGLKTRHHHTEVTPDFIAVVQAVVRTSGGWAAASDSRKGGEPAGY | ||||||
Glycosylation | 427 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 510 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
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.
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.
Cleaved by autocatalysis into a large and a small subunit and the autocatalytic cleavage is essential to the functional activation of the enzyme.
Keywords
- PTM
PTM databases
Expression
Tissue specificity
Detected in adult kidney and mammary gland, and in fetal liver.
Structure
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length568
- Mass (Da)61,610
- Last updated2007-05-01 v4
- Checksum24DC62A1DEEEA38C
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
M0R8W8 | M0R8W8_RAT | Ggt1 | 447 |
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 9 | in Ref. 7; AAA41217 | ||||
Sequence: G → A | ||||||
Sequence conflict | 39 | in Ref. 2; AAA57295/AAB59698 | ||||
Sequence: R → K | ||||||
Sequence conflict | 111 | in Ref. 2; AAB59698 | ||||
Sequence: R → K | ||||||
Sequence conflict | 370 | in Ref. 2; AAA57295/AAB59698 and 8; CAA27224 | ||||
Sequence: P → A | ||||||
Sequence conflict | 397 | in Ref. 8; CAA27224 | ||||
Sequence: S → M | ||||||
Sequence conflict | 416 | in Ref. 8; CAA27224 | ||||
Sequence: F → V | ||||||
Sequence conflict | 444 | in Ref. 2; AAA57295/AAB59698 | ||||
Sequence: P → L |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X15443 EMBL· GenBank· DDBJ | CAA33483.1 EMBL· GenBank· DDBJ | mRNA | ||
M33821 EMBL· GenBank· DDBJ | AAA57295.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
M33822 EMBL· GenBank· DDBJ | AAB59698.1 EMBL· GenBank· DDBJ | mRNA | ||
BC078768 EMBL· GenBank· DDBJ | AAH78768.1 EMBL· GenBank· DDBJ | mRNA | ||
L29167 EMBL· GenBank· DDBJ | AAA41218.1 EMBL· GenBank· DDBJ | mRNA | ||
M57672 EMBL· GenBank· DDBJ | AAA41217.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X03518 EMBL· GenBank· DDBJ | CAA27224.1 EMBL· GenBank· DDBJ | mRNA | Frameshift |