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Protein

Glutathione hydrolase 1 proenzyme

Gene

Ggt1

Organism
Rattus norvegicus (Rat)
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.By similarity

Catalytic activityi

A (5-L-glutamyl)-peptide + an amino acid = a peptide + a 5-L-glutamyl amino acid.1 Publication
Glutathione + H2O = L-cysteinylglycine + L-glutamate.1 Publication
Leukotriene C4 + H2O = leukotriene D4 + L-glutamate.1 Publication

Enzyme regulationi

Activated by autocatalytic cleavage.By similarity

Kineticsi

  1. KM=5.9 µM for leukotriene C41 Publication
  2. KM=5.7 µM for glutathione1 Publication
  3. KM=5.8 µM for gamma-glutamyl-p-anilide1 Publication

    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

    • aging Source: RGD
    • cellular response to oxidative stress Source: RGD
    • glutamate metabolic process Source: UniProtKB
    • glutathione biosynthetic process Source: UniProtKB-KW
    • glutathione catabolic process Source: UniProtKB
    • peptide modification Source: RGD
    • response to estradiol Source: RGD
    • response to lipopolysaccharide Source: RGD
    • response to tumor necrosis factor Source: RGD
    • zymogen activation Source: UniProtKB

    Keywordsi

    Molecular functionAcyltransferase, Hydrolase, Protease, Transferase
    Biological processGlutathione biosynthesis
    LigandSialic acid

    Enzyme and pathway databases

    BRENDAi2.3.2.2 5301
    UniPathwayiUPA00204

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Glutathione hydrolase 1 proenzyme (EC:3.4.19.131 Publication)
    Alternative name(s):
    Gamma-glutamyltransferase 1
    Gamma-glutamyltranspeptidase 1 (EC:2.3.2.21 Publication)
    Short name:
    GGT 1
    Leukotriene-C4 hydrolase (EC:3.4.19.141 Publication)
    CD_antigen: CD224
    Cleaved into the following 2 chains:
    Gene namesi
    Name:Ggt1
    Synonyms:Ggt
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
    Proteomesi
    • UP000002494 Componenti: Unplaced

    Organism-specific databases

    RGDi2683 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

    Chemistry databases

    ChEMBLiCHEMBL2943

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000110641 – 379Glutathione hydrolase 1 heavy chainAdd BLAST379
    ChainiPRO_0000011065380 – 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...) asparagineSequence analysis1
    Glycosylationi119N-linked (GlcNAc...) asparagineSequence analysis1
    Disulfide bondi191 ↔ 195By similarity
    Glycosylationi229N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi343N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi427N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi510N-linked (GlcNAc...) asparagine; alternateSequence analysis1
    Glycosylationi510N-linked (HexNAc...) asparagine; alternateCombined sources1

    Post-translational modificationi

    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.1 Publication
    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.1 Publication
    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

    PRIDEiP07314

    PTM databases

    GlyConnecti170
    iPTMnetiP07314
    PhosphoSitePlusiP07314
    UniCarbKBiP07314

    Expressioni

    Tissue specificityi

    Detected in adult kidney and mammary gland, and in fetal liver.

    Interactioni

    Subunit structurei

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

    Chemistry databases

    BindingDBiP07314

    Structurei

    3D structure databases

    ProteinModelPortaliP07314
    SMRiP07314
    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

    HOVERGENiHBG005835
    InParanoidiP07314
    KOiK18592
    PhylomeDBiP07314

    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

    Sequencei

    Sequence statusi: Complete.

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

    P07314-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MKNRFLVLGL VAVVLVFVII GLCIWLPTTS GKPDHVYSRA AVATDAKRCS
    60 70 80 90 100
    EIGRDMLQEG GSVVDAAIAS LLCMGLINAH SMGIGGGLFF TIYNSTTRKA
    110 120 130 140 150
    EVINAREMAP RLANTSMFNN SKDSEEGGLS VAVPGEIRGY ELAHQRHGRL
    160 170 180 190 200
    PWARLFQPSI QLARHGFPVG KGLARALDKK RDIIEKTPAL CEVFCRQGKV
    210 220 230 240 250
    LQEGETVTMP KLADTLQILA QEGARAFYNG SLTAQIVKDI QEAGGIMTVE
    260 270 280 290 300
    DLNNYRAEVI EHPMSIGLGD STLYVPSAPL SGPVLILILN ILKGYNFSPK
    310 320 330 340 350
    SVATPEQKAL TYHRIVEAFR FAYAKRTMLG DPKFVDVSQV IRNMSSEFYA
    360 370 380 390 400
    TQLRARITDE TTHPTAYYEP EFYLPDDGGT AHLSVVSEDG SAVAATSTIN
    410 420 430 440 450
    LYFGSKVLSR VSGILFNDEM DDFSSPNFTN QFGVAPSPAN FIKPGKQPLS
    460 470 480 490 500
    SMCPSIIVDK DGKVRMVVGA SGGTQITTSV ALAIINSLWF GYDVKRAVEE
    510 520 530 540 550
    PRLHNQLLPN TTTVEKNIDQ VVTAGLKTRH HHTEVTPDFI AVVQAVVRTS
    560
    GGWAAASDSR KGGEPAGY
    Length:568
    Mass (Da):61,610
    Last modified:May 1, 2007 - v4
    Checksum:i24DC62A1DEEEA38C
    GO

    Sequence cautioni

    The sequence CAA27224 differs from that shown. Reason: Frameshift at positions 66 and 134.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti9G → A in AAA41217 (PubMed:1671556).Curated1
    Sequence conflicti39R → K in AAA57295 (PubMed:2869484).Curated1
    Sequence conflicti39R → K in AAB59698 (PubMed:2869484).Curated1
    Sequence conflicti111R → K in AAB59698 (PubMed:2869484).Curated1
    Sequence conflicti370P → A in AAA57295 (PubMed:2869484).Curated1
    Sequence conflicti370P → A in AAB59698 (PubMed:2869484).Curated1
    Sequence conflicti370P → A in CAA27224 (PubMed:2869471).Curated1
    Sequence conflicti397S → M in CAA27224 (PubMed:2869471).Curated1
    Sequence conflicti416F → V in CAA27224 (PubMed:2869471).Curated1
    Sequence conflicti444P → L in AAA57295 (PubMed:2869484).Curated1
    Sequence conflicti444P → L in AAB59698 (PubMed:2869484).Curated1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X15443 mRNA Translation: CAA33483.1
    M33821 mRNA Translation: AAA57295.1 Sequence problems.
    M33822 mRNA Translation: AAB59698.1
    BC078768 mRNA Translation: AAH78768.1
    L29167 mRNA Translation: AAA41218.1
    M57672 Genomic DNA Translation: AAA41217.1
    X03518 mRNA Translation: CAA27224.1 Frameshift.
    PIRiA05225
    RefSeqiNP_446292.2, NM_053840.2
    UniGeneiRn.10010

    Genome annotation databases

    GeneIDi116568
    KEGGirno:116568

    Similar proteinsi

    Entry informationi

    Entry nameiGGT1_RAT
    AccessioniPrimary (citable) accession number: P07314
    Secondary accession number(s): Q63217, Q63218, Q6AZ32
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1988
    Last sequence update: May 1, 2007
    Last modified: May 23, 2018
    This is version 148 of the entry and version 4 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. SIMILARITY comments
      Index of protein domains and families

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