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Protein

Glutathione hydrolase 1 proenzyme

Gene

Ggt1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. Indirectly regulates multiple aspects of skeletal biology.1 Publication

Catalytic activityi

A (5-L-glutamyl)-peptide + an amino acid = a peptide + a 5-L-glutamyl amino acid.By similarity
Glutathione + H2O = L-cysteinylglycine + L-glutamate.By similarity
Leukotriene C4 + H2O = leukotriene D4 + L-glutamate.By similarity

Activity regulationi

Activated by autocatalytic cleavage.By similarity

Pathwayi: glutathione metabolism

This protein is involved in the pathway glutathione metabolism, which is part of Sulfur metabolism.
View all proteins of this organism that are known to be involved in the pathway glutathione metabolism and in Sulfur metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei106GlutamateBy similarity1
Active sitei380NucleophileBy similarity1
Binding sitei398GlutamateBy similarity1
Binding sitei419GlutamateBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionAcyltransferase, Hydrolase, Protease, Transferase
Biological processGlutathione biosynthesis

Enzyme and pathway databases

ReactomeiR-MMU-174403 Glutathione synthesis and recycling
R-MMU-2142691 Synthesis of Leukotrienes (LT) and Eoxins (EX)
R-MMU-5423646 Aflatoxin activation and detoxification
UniPathwayi
UPA00204

Names & Taxonomyi

Protein namesi
Recommended name:
Glutathione hydrolase 1 proenzyme (EC:3.4.19.13By similarity)
Alternative name(s):
Gamma-glutamyltransferase 1
Gamma-glutamyltranspeptidase 1 (EC:2.3.2.2By similarity)
Short name:
GGT 1
Leukotriene-C4 hydrolase (EC:3.4.19.14By similarity)
CD_antigen: CD224
Cleaved into the following 2 chains:
Gene namesi
Name:Ggt1
Synonyms:Ggt, Ggtp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:95706 Ggt1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 4CytoplasmicSequence analysis4
Transmembranei5 – 26Helical; Signal-anchor for type II membrane proteinCuratedAdd BLAST22
Topological domaini27 – 568ExtracellularSequence analysisAdd BLAST542

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Defects in Ggt1 are a cause of glutathionuria, severe growth failure, reduced life spans and infertility. Ggt1-deficient mice have multiple metabolic abnormalities and are dwarf. Some abnormalities can be ameliorated by N-acetylcysteine treatment.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000110601 – 379Glutathione hydrolase 1 heavy chainAdd BLAST379
ChainiPRO_0000011061380 – 568Glutathione hydrolase 1 light chainAdd BLAST189

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi49 ↔ 73By similarity
Glycosylationi94N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi114N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi119N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi191 ↔ 195By similarity
Glycosylationi229N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi343N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi510N-linked (GlcNAc...) asparagine1 Publication1

Post-translational modificationi

N-glycosylated on both chains.By similarity
Cleaved by autocatalysis into a large and a small subunit and the autocatalytic cleavage is essential to the functional activation of the enzyme.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

MaxQBiQ60928
PaxDbiQ60928
PRIDEiQ60928
TopDownProteomicsiQ60928

PTM databases

iPTMnetiQ60928
PhosphoSitePlusiQ60928

Expressioni

Gene expression databases

BgeeiENSMUSG00000006345 Expressed in 126 organ(s), highest expression level in jejunum
CleanExiMM_GGT1
ExpressionAtlasiQ60928 baseline and differential
GenevisibleiQ60928 MM

Interactioni

Subunit structurei

Heterodimer composed of the light and heavy chains. The active site is located in the light chain.By similarity

Protein-protein interaction databases

IntActiQ60928, 2 interactors
MINTiQ60928
STRINGi10090.ENSMUSP00000006508

Structurei

3D structure databases

ProteinModelPortaliQ60928
SMRiQ60928
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni450 – 451Glutamate bindingBy similarity2

Sequence similaritiesi

Belongs to the gamma-glutamyltransferase family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2410 Eukaryota
COG0405 LUCA
GeneTreeiENSGT00550000074591
HOGENOMiHOG000175620
HOVERGENiHBG005835
InParanoidiQ60928
KOiK18592
OMAiTKNMFLD
OrthoDBiEOG091G03Y3
PhylomeDBiQ60928
TreeFamiTF313608

Family and domain databases

InterProiView protein in InterPro
IPR000101 GGT_peptidase
IPR029055 Ntn_hydrolases_N
PANTHERiPTHR11686 PTHR11686, 1 hit
SUPFAMiSSF56235 SSF56235, 1 hit
TIGRFAMsiTIGR00066 g_glut_trans, 1 hit
PROSITEiView protein in PROSITE
PS00462 G_GLU_TRANSPEPTIDASE, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 13 potential isoforms that are computationally mapped.Show allAlign All

Q60928-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MKNRFLVLGL VAVVLVFVII GLCIWLPYTS GKPDHVYSRA AVATDAKRCS
60 70 80 90 100
EIGRDILQEG GSVVDAAIAS LLCMGLMNAH SMGIGGGLFF TIYNSTTGKV
110 120 130 140 150
EVINAREVAP RLANTTMFNN SKDSEEGGLS VAVPGEIRGY ELAHQRHGRL
160 170 180 190 200
PWARLFQPSI QLARHGFPVG KGLAIALDKK RDVIEKTPAL CEVFCRQGKV
210 220 230 240 250
LQEGETVTMP KLADTLQILA QEGAKAFYNG SLTAQIVKDI QEAGGIMTVE
260 270 280 290 300
DLNNYRAELI EHPMSIGLGD ATLYVPSAPL SGPVLILILN ILKGYNFSPK
310 320 330 340 350
SVATPEQKAL TYHRIVEAFR FAYAKRTMLG DPKFVDVSQV IRNMSSEFYA
360 370 380 390 400
TQLRARITDE TTHPAAYYEP EFYLQDDGGT AHLSAVSEDG SAVAATSTIN
410 420 430 440 450
LYFGSKVLSR VSGILFNDEM DDFSSPNFIN QFRVAPSPAN FIKPGKQPLS
460 470 480 490 500
SMCPSIILDK DGQVRMVVGA SGGTQITTSV ALAIINSLWF GYDVKRAVEE
510 520 530 540 550
PRLHNQLLPN TTTVEKDIDQ VVTAGLKIRH HHTEVTPTFI AVVQAVVRAS
560
GGWAAASDSR KGGEPAGY
Length:568
Mass (Da):61,563
Last modified:November 1, 1996 - v1
Checksum:i293C6E224FDC0766
GO

Computationally mapped potential isoform sequencesi

There are 13 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D3Z266D3Z266_MOUSE
Glutathione hydrolase 1 proenzyme
Ggt1
243Annotation score:
D3YVY4D3YVY4_MOUSE
Glutathione hydrolase 1 proenzyme
Ggt1
237Annotation score:
D3YWW2D3YWW2_MOUSE
Glutathione hydrolase 1 proenzyme
Ggt1
189Annotation score:
D3YWW4D3YWW4_MOUSE
Glutathione hydrolase 1 proenzyme
Ggt1
190Annotation score:
D3Z4Q6D3Z4Q6_MOUSE
Glutathione hydrolase 1 proenzyme
Ggt1
235Annotation score:
D3YVX1D3YVX1_MOUSE
Glutathione hydrolase 1 proenzyme
Ggt1
88Annotation score:
D3YY79D3YY79_MOUSE
Glutathione hydrolase 1 proenzyme
Ggt1
209Annotation score:
D3Z2C6D3Z2C6_MOUSE
Glutathione hydrolase 1 proenzyme
Ggt1
60Annotation score:
D3YXV6D3YXV6_MOUSE
Glutathione hydrolase 1 proenzyme
Ggt1
126Annotation score:
D3YYH6D3YYH6_MOUSE
Glutathione hydrolase 1 proenzyme
Ggt1
110Annotation score:
There are more potential isoformsShow all

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U30509 mRNA Translation: AAA97395.1
BC012969 mRNA Translation: AAH12969.1
CCDSiCCDS23927.1
PIRiJC4570
RefSeqiNP_001292921.1, NM_001305992.1
NP_032142.1, NM_008116.3
XP_006513293.1, XM_006513230.3
XP_006513294.1, XM_006513231.3
UniGeneiMm.4559
Mm.486584

Genome annotation databases

EnsembliENSMUST00000006508; ENSMUSP00000006508; ENSMUSG00000006345
ENSMUST00000134503; ENSMUSP00000121312; ENSMUSG00000006345
GeneIDi14598
KEGGimmu:14598
UCSCiuc007fqo.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U30509 mRNA Translation: AAA97395.1
BC012969 mRNA Translation: AAH12969.1
CCDSiCCDS23927.1
PIRiJC4570
RefSeqiNP_001292921.1, NM_001305992.1
NP_032142.1, NM_008116.3
XP_006513293.1, XM_006513230.3
XP_006513294.1, XM_006513231.3
UniGeneiMm.4559
Mm.486584

3D structure databases

ProteinModelPortaliQ60928
SMRiQ60928
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ60928, 2 interactors
MINTiQ60928
STRINGi10090.ENSMUSP00000006508

PTM databases

iPTMnetiQ60928
PhosphoSitePlusiQ60928

Proteomic databases

MaxQBiQ60928
PaxDbiQ60928
PRIDEiQ60928
TopDownProteomicsiQ60928

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000006508; ENSMUSP00000006508; ENSMUSG00000006345
ENSMUST00000134503; ENSMUSP00000121312; ENSMUSG00000006345
GeneIDi14598
KEGGimmu:14598
UCSCiuc007fqo.2 mouse

Organism-specific databases

CTDi2678
MGIiMGI:95706 Ggt1

Phylogenomic databases

eggNOGiKOG2410 Eukaryota
COG0405 LUCA
GeneTreeiENSGT00550000074591
HOGENOMiHOG000175620
HOVERGENiHBG005835
InParanoidiQ60928
KOiK18592
OMAiTKNMFLD
OrthoDBiEOG091G03Y3
PhylomeDBiQ60928
TreeFamiTF313608

Enzyme and pathway databases

UniPathwayi
UPA00204

ReactomeiR-MMU-174403 Glutathione synthesis and recycling
R-MMU-2142691 Synthesis of Leukotrienes (LT) and Eoxins (EX)
R-MMU-5423646 Aflatoxin activation and detoxification

Miscellaneous databases

ChiTaRSiGgt1 mouse
PROiPR:Q60928
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000006345 Expressed in 126 organ(s), highest expression level in jejunum
CleanExiMM_GGT1
ExpressionAtlasiQ60928 baseline and differential
GenevisibleiQ60928 MM

Family and domain databases

InterProiView protein in InterPro
IPR000101 GGT_peptidase
IPR029055 Ntn_hydrolases_N
PANTHERiPTHR11686 PTHR11686, 1 hit
SUPFAMiSSF56235 SSF56235, 1 hit
TIGRFAMsiTIGR00066 g_glut_trans, 1 hit
PROSITEiView protein in PROSITE
PS00462 G_GLU_TRANSPEPTIDASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGGT1_MOUSE
AccessioniPrimary (citable) accession number: Q60928
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: November 7, 2018
This is version 158 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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