GGT1_PIG
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 03-AUG-2022, entry version 133.
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 alpha-amino acid + an N-terminal (5-L-glutamyl)-[peptide] =
CC 5-L-glutamyl amino acid + 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=H2O + leukotriene C4 = L-glutamate + leukotriene D4;
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 STRING; 9823.ENSSSCP00000028318; -.
DR PaxDb; P20735; -.
DR PeptideAtlas; P20735; -.
DR PRIDE; P20735; -.
DR GeneID; 397095; -.
DR KEGG; ssc:397095; -.
DR CTD; 2678; -.
DR eggNOG; KOG2410; Eukaryota.
DR InParanoid; P20735; -.
DR UniPathway; UPA00204; -.
DR UniPathway; UPA00880; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0036374; F:glutathione hydrolase activity; ISS:UniProtKB.
DR GO; GO:0102953; F:hypoglycin A gamma-glutamyl transpeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0103068; F:leukotriene C4 gamma-glutamyl transferase activity; IEA:UniProtKB-EC.
DR GO; GO:0006536; P:glutamate metabolic process; ISS:UniProtKB.
DR GO; GO:0006750; P:glutathione biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006751; P:glutathione catabolic process; ISS:UniProtKB.
DR GO; GO:0031638; P:zymogen activation; ISS:UniProtKB.
DR Gene3D; 1.10.246.130; -; 1.
DR Gene3D; 3.60.20.40; -; 1.
DR InterPro; IPR043138; GGT_lsub_C.
DR InterPro; IPR000101; GGT_peptidase.
DR InterPro; IPR043137; GGT_ssub.
DR InterPro; IPR029055; Ntn_hydrolases_N.
DR PANTHER; PTHR11686; PTHR11686; 1.
DR SUPFAM; SSF56235; SSF56235; 1.
DR TIGRFAMs; TIGR00066; g_glut_trans; 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
