ID   GGT1_PIG                Reviewed;         568 AA.
AC   P20735; A5A784;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 1.
DT   04-NOV-2026, entry version 147.
DE   RecName: Full=Glutathione hydrolase 1 proenzyme;
DE            EC=3.4.19.13 {ECO:0000250|UniProtKB:P19440};
DE   AltName: Full=Gamma-glutamyltransferase 1;
DE   AltName: Full=Gamma-glutamyltranspeptidase 1;
DE            Short=GGT 1;
DE            EC=2.3.2.2 {ECO:0000250|UniProtKB:P19440};
DE   AltName: Full=Leukotriene-C4 hydrolase;
DE            EC=3.4.19.14 {ECO:0000250|UniProtKB:P07314};
DE   AltName: CD_antigen=CD224;
DE   Contains:
DE     RecName: Full=Glutathione hydrolase 1 heavy chain;
DE   Contains:
DE     RecName: Full=Glutathione hydrolase 1 light chain;
DE   Flags: Precursor;
GN   Name=GGT1; Synonyms=GGT;
OS   Sus scrofa (Pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX   NCBI_TaxID=9823;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-18.
RC   TISSUE=Brain capillary;
RX   PubMed=2476308; DOI=10.1111/j.1432-1033.1989.tb21100.x;
RA   Papandrikopoulou A., Frey A., Gassen H.G.;
RT   "Cloning and expression of gamma-glutamyl transpeptidase from isolated
RT   porcine brain capillaries.";
RL   Eur. J. Biochem. 183:693-698(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Okumura N., Matsumoto T., Hamasima N., Uenishi H., Ogawa T., Komatsuda A.,
RA   Fukudome N., Ide H., Suzuki A., Kojima C., Awata T.;
RT   "Sequences and genetic variations of fourty-four porcine coat color related
RT   genes.";
RL   Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   GENE ORGANIZATION, AND ALTERNATIVE PROMOTER USAGE.
RX   PubMed=10392451; DOI=10.1016/s0305-0491(99)00013-9;
RA   Chikhi N., Holic N., Guellaen G., Laperche Y.;
RT   "Gamma-glutamyl transpeptidase gene organization and expression: a
RT   comparative analysis in rat, mouse, pig and human species.";
RL   Comp. Biochem. Physiol. 122B:367-380(1999).
CC   -!- FUNCTION: Cleaves the gamma-glutamyl bond of extracellular glutathione
CC       (gamma-Glu-Cys-Gly), glutathione conjugates (such as maresin conjugate
CC       (13R)-S-glutathionyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)-
CC       docosahexaenoate, MCTR1) and other gamma-glutamyl compounds (such as
CC       leukotriene C4, LTC4). The metabolism of glutathione by GGT1 releases
CC       free glutamate and the dipeptide cysteinyl-glycine, which is hydrolyzed
CC       to cysteine and glycine by dipeptidases. In the presence of high
CC       concentrations of dipeptides and some amino acids, can also catalyze a
CC       transpeptidation reaction, transferring the gamma-glutamyl moiety to an
CC       acceptor amino acid to form a new gamma-glutamyl compound. Contributes
CC       to cysteine homeostasis, glutathione homeostasis and in the conversion
CC       of the leukotriene LTC4 to LTD4. {ECO:0000250|UniProtKB:P19440}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an N-terminal (5-L-glutamyl)-[peptide] + an alpha-amino acid =
CC         5-L-glutamyl amino acid + an N-terminal L-alpha-aminoacyl-[peptide];
CC         Xref=Rhea:RHEA:23904, Rhea:RHEA-COMP:9780, Rhea:RHEA-COMP:9795,
CC         ChEBI:CHEBI:77644, ChEBI:CHEBI:78597, ChEBI:CHEBI:78599,
CC         ChEBI:CHEBI:78608; EC=2.3.2.2;
CC         Evidence={ECO:0000250|UniProtKB:P19440};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23905;
CC         Evidence={ECO:0000250|UniProtKB:P19440};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:23906;
CC         Evidence={ECO:0000250|UniProtKB:P07314};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=glutathione + H2O = L-cysteinylglycine + L-glutamate;
CC         Xref=Rhea:RHEA:28807, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985,
CC         ChEBI:CHEBI:57925, ChEBI:CHEBI:61694; EC=3.4.19.13;
CC         Evidence={ECO:0000250|UniProtKB:P19440};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28808;
CC         Evidence={ECO:0000250|UniProtKB:P19440};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an S-substituted glutathione + H2O = an S-substituted L-
CC         cysteinylglycine + L-glutamate; Xref=Rhea:RHEA:59468,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:29985, ChEBI:CHEBI:90779,
CC         ChEBI:CHEBI:143103; EC=3.4.19.13;
CC         Evidence={ECO:0000250|UniProtKB:P19440};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59469;
CC         Evidence={ECO:0000250|UniProtKB:P19440};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=leukotriene C4 + H2O = leukotriene D4 + L-glutamate;
CC         Xref=Rhea:RHEA:31563, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985,
CC         ChEBI:CHEBI:57973, ChEBI:CHEBI:63166; EC=3.4.19.14;
CC         Evidence={ECO:0000250|UniProtKB:P07314};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31564;
CC         Evidence={ECO:0000250|UniProtKB:P19440};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(13R)-S-glutathionyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)-
CC         docosahexaenoate + H2O = (13R)-S-cysteinylglycyl-(14S)-hydroxy-
CC         (4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate + L-glutamate;
CC         Xref=Rhea:RHEA:53512, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985,
CC         ChEBI:CHEBI:137407, ChEBI:CHEBI:137408;
CC         Evidence={ECO:0000250|UniProtKB:P19440};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53513;
CC         Evidence={ECO:0000250|UniProtKB:P19440};
CC   -!- ACTIVITY REGULATION: Activated by autocatalytic cleavage.
CC       {ECO:0000250|UniProtKB:P19440}.
CC   -!- PATHWAY: Sulfur metabolism; glutathione metabolism.
CC   -!- PATHWAY: Lipid metabolism; leukotriene D4 biosynthesis.
CC       {ECO:0000250|UniProtKB:P19440}.
CC   -!- SUBUNIT: Heterodimer composed of the light and heavy chains. The active
CC       site is located in the light chain. {ECO:0000250|UniProtKB:P19440}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P19440};
CC       Single-pass type II membrane protein {ECO:0000250|UniProtKB:P07314}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in kidney. Detected at lower
CC       levels in liver, lung, plexus choroideus and brain capillary
CC       endothelial cells.
CC   -!- PTM: N-glycosylated on both chains. {ECO:0000250|UniProtKB:P19440}.
CC   -!- PTM: Cleaved by autocatalysis into a large and a small subunit and the
CC       autocatalytic cleavage is essential to the functional activation of the
CC       enzyme. {ECO:0000250|UniProtKB:P19440}.
CC   -!- SIMILARITY: Belongs to the gamma-glutamyltransferase family.
CC       {ECO:0000305}.
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DR   EMBL; Z46922; CAA87031.1; -; mRNA.
DR   EMBL; X16533; CAA34536.1; -; Genomic_DNA.
DR   EMBL; AB271954; BAF62329.1; -; mRNA.
DR   PIR; S05532; S05532.
DR   RefSeq; NP_999195.1; NM_214030.1.
DR   AlphaFoldDB; P20735; -.
DR   SMR; P20735; -.
DR   FunCoup; P20735; 224.
DR   STRING; 9823.ENSSSCP00000030498; -.
DR   GlyCosmos; P20735; 8 sites, No reported glycans.
DR   GlyGen; P20735; 9 sites.
DR   PaxDb; 9823-ENSSSCP00000030498; -.
DR   PeptideAtlas; P20735; -.
DR   GeneID; 397095; -.
DR   KEGG; ssc:397095; -.
DR   CTD; 2678; -.
DR   eggNOG; KOG2410; Eukaryota.
DR   InParanoid; P20735; -.
DR   OMA; AADAKCC; -.
DR   OrthoDB; 1081007at2759; -.
DR   UniPathway; UPA00204; -.
DR   UniPathway; UPA00880; -.
DR   Proteomes; UP000008227; Unplaced.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0036374; F:glutathione gamma-glutamate hydrolase; ISS:UniProtKB.
DR   GO; GO:0002951; F:leukotriene-C(4) hydrolase activity; IEA:UniProtKB-EC.
DR   GO; GO:0006536; P:glutamate metabolic process; ISS:UniProtKB.
DR   GO; GO:0006751; P:glutathione catabolic process; ISS:UniProtKB.
DR   GO; GO:0031179; P:peptide modification; IBA:GO_Central.
DR   GO; GO:0002682; P:regulation of immune system process; IBA:GO_Central.
DR   GO; GO:0050727; P:regulation of inflammatory response; IBA:GO_Central.
DR   GO; GO:0031638; P:zymogen activation; ISS:UniProtKB.
DR   FunFam; 3.60.20.40:FF:000007; Glutathione hydrolase 1 proenzyme; 1.
DR   FunFam; 1.10.246.130:FF:000002; glutathione hydrolase 1 proenzyme; 1.
DR   Gene3D; 1.10.246.130; -; 1.
DR   Gene3D; 3.60.20.40; -; 1.
DR   InterPro; IPR055262; GGT_CS.
DR   InterPro; IPR043138; GGT_lsub.
DR   InterPro; IPR000101; GGT_peptidase.
DR   InterPro; IPR043137; GGT_ssub_C.
DR   InterPro; IPR029055; Ntn_hydrolases_N.
DR   NCBIfam; TIGR00066; g_glut_trans; 1.
DR   PANTHER; PTHR11686; GAMMA GLUTAMYL TRANSPEPTIDASE; 1.
DR   PANTHER; PTHR11686:SF56; GLUTATHIONE HYDROLASE 1 PROENZYME-RELATED; 1.
DR   Pfam; PF01019; G_glu_transpept; 1.
DR   PRINTS; PR01210; GGTRANSPTASE.
DR   SUPFAM; SSF56235; N-terminal nucleophile aminohydrolases (Ntn hydrolases); 1.
DR   PROSITE; PS00462; G_GLU_TRANSPEPTIDASE; 1.
PE   2: Evidence at transcript level;
KW   Acyltransferase; Cell membrane; Disulfide bond; Glutathione biosynthesis;
KW   Glycoprotein; Hydrolase; Membrane; Protease; Reference proteome;
KW   Signal-anchor; Transferase; Transmembrane; Transmembrane helix; Zymogen.
FT   CHAIN           1..379
FT                   /note="Glutathione hydrolase 1 heavy chain"
FT                   /id="PRO_0000011062"
FT   CHAIN           380..568
FT                   /note="Glutathione hydrolase 1 light chain"
FT                   /id="PRO_0000011063"
FT   TOPO_DOM        1..4
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P07314"
FT   TRANSMEM        5..26
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000250|UniProtKB:P07314"
FT   TOPO_DOM        27..568
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P07314"
FT   ACT_SITE        380
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:P19440"
FT   BINDING         106
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250|UniProtKB:P19440"
FT   BINDING         398..400
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250|UniProtKB:P19440"
FT   BINDING         419
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250|UniProtKB:P19440"
FT   BINDING         422
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250|UniProtKB:P19440"
FT   BINDING         450..451
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250|UniProtKB:P19440"
FT   BINDING         473
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250|UniProtKB:P19440"
FT   CARBOHYD        94
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        119
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        229
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        296
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        336
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        343
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        427
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        510
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        49..73
FT                   /evidence="ECO:0000250|UniProtKB:P19440"
FT   DISULFID        191..195
FT                   /evidence="ECO:0000250|UniProtKB:P19440"
SQ   SEQUENCE   568 AA;  61316 MW;  EB2D1896B1229487 CRC64;
     MKKRYLLLAL AAVALVLLIL GLCLWLPSNS KPHNHVYPRA AVAADALRCS EIGRDTLRDG
     GSAVDAAIAA LLCVGLMNAH SMGIGGGLFL TIYNSTTRKA EIINAREVAP RLASASMFNS
     SEQSEEGGLS VAVPGEIRGY ELAHQRHGRL PWARLFQPSI ELASQGFPVG KGLAAALERS
     QDAIKRHPAL CEVFCRNGNV LREGDLVTMP RLAKTYETLA VEGAQAFYNG SLTAQIVKDI
     QEAGGIVTAE DLNNYRAELI EQPLRISLGD AQLYAPNAPL SGPVLALILN ILKGYNFSRA
     SVETPEQKGL TYHRIVEAFR FAYAKRTLLG DPKFVNVTEV VRNMSSEFFA DQLRARISDT
     TTHPDSYYEP EFYTPDDAGT AHLSVVSDDG SAVSATSTIN LYFGSKVRSR ISGILFNDEM
     DDFSSPNITN QFGVRPSPAN FITPGKQPLS SMCPVIIVGE DGQVRMVVGA SGGTQITTST
     ALAIIHSLWF GYDVKRAVEE PRLHNQLLPN TTTLEKGIDQ AVAAALKTRH HYIQDASTFI
     GVVQAIVRTP SGWAAASDSR KGGEPAGY
//