ID GGT5_RAT Reviewed; 572 AA.
AC Q9QWE9; Q5PQV0;
DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 02-DEC-2020, sequence version 2.
DT 27-MAR-2024, entry version 115.
DE RecName: Full=Glutathione hydrolase 5 proenzyme;
DE EC=3.4.19.13 {ECO:0000250|UniProtKB:P19440};
DE AltName: Full=Gamma-glutamyl leukotrienase;
DE Short=GGL;
DE AltName: Full=Gamma-glutamyl transpeptidase-related enzyme;
DE Short=GGT-rel;
DE AltName: Full=Gamma-glutamyltransferase 5;
DE Short=GGT 5;
DE EC=2.3.2.2 {ECO:0000250|UniProtKB:P19440};
DE AltName: Full=Gamma-glutamyltransferase-like activity 1;
DE AltName: Full=Gamma-glutamyltranspeptidase 5;
DE AltName: Full=Leukotriene-C4 hydrolase;
DE EC=3.4.19.14 {ECO:0000250|UniProtKB:P19440};
DE Contains:
DE RecName: Full=Glutathione hydrolase 5 heavy chain;
DE Contains:
DE RecName: Full=Glutathione hydrolase 5 light chain;
DE Flags: Precursor;
GN Name=Ggt5; Synonyms=Ggtla1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Fischer 344/N; TISSUE=Trachea;
RX PubMed=9374738; DOI=10.1152/ajplung.1997.273.5.l1082;
RA Potdar P.D., Andrews K.L., Nettesheim P., Ostrowski L.E.;
RT "Expression and regulation of gamma-glutamyl transpeptidase-related enzyme
RT in tracheal cells.";
RL Am. J. Physiol. 273:L1082-L1089(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Cleaves the gamma-glutamyl peptide bond of glutathione and
CC glutathione-S-conjugate. Converts leukotriene C4 (LTC4), a glutathione-
CC S-conjugate, to leukotriene D4 (LTD4). Does not cleave gamma-glutamyl
CC compounds such as gamma-glutamyl leucine. May also catalyze a
CC transpeptidation reaction in addition to the hydrolysis reaction,
CC transferring the gamma-glutamyl moiety to an acceptor amino acid to
CC form a new gamma-glutamyl compound. Acts as a negative regulator of
CC geranylgeranyl glutathione bioactivity by cleaving off its gamma-
CC glutamyl group, playing a role in adaptive immune responses.
CC {ECO:0000250|UniProtKB:P36269}.
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:P36269};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23905;
CC Evidence={ECO:0000250|UniProtKB:P36269};
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:P36269};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28808;
CC Evidence={ECO:0000250|UniProtKB:P36269};
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:P36269};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59469;
CC Evidence={ECO:0000250|UniProtKB:P36269};
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:P36269};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31564;
CC Evidence={ECO:0000250|UniProtKB:P36269};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + S-[(2E,6E,10E)-geranylgeranyl]-L-glutathione = L-
CC glutamate + S-[(2E,6E,10E)-geranylgeranyl]-L-cysteinylglycine;
CC Xref=Rhea:RHEA:65120, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:156326, ChEBI:CHEBI:156330;
CC Evidence={ECO:0000250|UniProtKB:P36269};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65121;
CC Evidence={ECO:0000250|UniProtKB:P36269};
CC -!- ACTIVITY REGULATION: Inhibited by serine-borate.
CC {ECO:0000250|UniProtKB:P36269}.
CC -!- PATHWAY: Lipid metabolism; leukotriene D4 biosynthesis.
CC {ECO:0000250|UniProtKB:Q9Z2A9}.
CC -!- PATHWAY: Sulfur metabolism; glutathione metabolism.
CC {ECO:0000250|UniProtKB:P36269}.
CC -!- SUBUNIT: Heterodimer composed of the light and heavy chains. The active
CC site is located in the light chain. {ECO:0000250|UniProtKB:Q9Z2A9}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q9Z2A9}; Single-
CC pass type II membrane protein {ECO:0000250|UniProtKB:Q9Z2A9}.
CC -!- TISSUE SPECIFICITY: Widely expressed, but at low level, except in the
CC airway epithelial cells. Detected in brain, heart, kidney, liver, lung,
CC spleen, testis and trachea. {ECO:0000269|PubMed:9374738}.
CC -!- PTM: Cleaved by autocatalysis into a large and a small subunit.
CC {ECO:0000250|UniProtKB:P19440}.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:Q9Z2A9}.
CC -!- MISCELLANEOUS: A previous study reported that GSH and oxidized
CC glutathione (GSSG) are not substrates for murine GGT5 (By similarity).
CC However, this result contrasts with two studies reported that GSH is
CC indeed a substrate for GGT5 (By similarity).
CC {ECO:0000250|UniProtKB:P36269, ECO:0000250|UniProtKB:Q9Z2A9}.
CC -!- SIMILARITY: Belongs to the gamma-glutamyltransferase family.
CC {ECO:0000305}.
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DR EMBL; U76252; AAC23546.1; -; mRNA.
DR EMBL; BC087018; AAH87018.1; -; mRNA.
DR RefSeq; NP_062108.2; NM_019235.2.
DR AlphaFoldDB; Q9QWE9; -.
DR SMR; Q9QWE9; -.
DR STRING; 10116.ENSRNOP00000076289; -.
DR MEROPS; T03.002; -.
DR GlyCosmos; Q9QWE9; 8 sites, No reported glycans.
DR GlyGen; Q9QWE9; 8 sites.
DR PhosphoSitePlus; Q9QWE9; -.
DR SwissPalm; Q9QWE9; -.
DR Ensembl; ENSRNOT00000093720.2; ENSRNOP00000076334.2; ENSRNOG00000062276.2.
DR Ensembl; ENSRNOT00055036313; ENSRNOP00055029505; ENSRNOG00055021257.
DR Ensembl; ENSRNOT00060030408; ENSRNOP00060024565; ENSRNOG00060017767.
DR Ensembl; ENSRNOT00065046033; ENSRNOP00065037769; ENSRNOG00065026665.
DR GeneID; 29566; -.
DR KEGG; rno:29566; -.
DR AGR; RGD:2684; -.
DR CTD; 2687; -.
DR RGD; 2684; Ggt5.
DR GeneTree; ENSGT00940000155794; -.
DR InParanoid; Q9QWE9; -.
DR OMA; EGPCVYA; -.
DR OrthoDB; 2910309at2759; -.
DR PhylomeDB; Q9QWE9; -.
DR Reactome; R-RNO-174403; Glutathione synthesis and recycling.
DR Reactome; R-RNO-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-RNO-5423646; Aflatoxin activation and detoxification.
DR Reactome; R-RNO-9753281; Paracetamol ADME.
DR UniPathway; UPA00204; -.
DR UniPathway; UPA00880; -.
DR PRO; PR:Q9QWE9; -.
DR Proteomes; UP000002494; Chromosome 20.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0036374; F:glutathione hydrolase activity; ISO:RGD.
DR GO; GO:0103068; F:leukotriene C4 gamma-glutamyl transferase activity; IEA:UniProtKB-EC.
DR GO; GO:0002951; F:leukotriene-C(4) hydrolase; ISS:UniProtKB.
DR GO; GO:0000048; F:peptidyltransferase activity; ISS:UniProtKB.
DR GO; GO:0006520; P:amino acid metabolic process; ISO:RGD.
DR GO; GO:0006631; P:fatty acid metabolic process; ISO:RGD.
DR GO; GO:0006750; P:glutathione biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006751; P:glutathione catabolic process; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; ISO:RGD.
DR GO; GO:1901750; P:leukotriene D4 biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; ISO:RGD.
DR GO; GO:0010243; P:response to organonitrogen compound; IEP:RGD.
DR GO; GO:0006979; P:response to oxidative stress; TAS:RGD.
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; GAMMA GLUTAMYL TRANSPEPTIDASE; 1.
DR PANTHER; PTHR11686:SF19; GLUTATHIONE HYDROLASE 5 PROENZYME; 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; Glutathione biosynthesis; Glycoprotein; Hydrolase;
KW Leukotriene biosynthesis; Membrane; Protease; Reference proteome;
KW Signal-anchor; Transferase; Transmembrane; Transmembrane helix; Zymogen.
FT CHAIN 1..387
FT /note="Glutathione hydrolase 5 heavy chain"
FT /evidence="ECO:0000250|UniProtKB:P19440"
FT /id="PRO_0000011076"
FT CHAIN 388..572
FT /note="Glutathione hydrolase 5 light chain"
FT /evidence="ECO:0000250|UniProtKB:P19440"
FT /id="PRO_0000011077"
FT TOPO_DOM 1..6
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2A9"
FT TRANSMEM 7..29
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2A9"
FT TOPO_DOM 30..572
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2A9"
FT ACT_SITE 388
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P19440"
FT BINDING 110
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:P19440"
FT BINDING 406
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:P19440"
FT BINDING 427
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:P19440"
FT BINDING 453..454
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:P19440"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 194
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 277
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 303
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 347
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 377
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 200
FT /note="Q -> H (in Ref. 1; AAC23546)"
FT CONFLICT 325
FT /note="A -> T (in Ref. 1; AAC23546)"
SQ SEQUENCE 572 AA; 61569 MW; 72CE9CCEB1FEB645 CRC64;
MAWGHRTTVC LVLLGVSLGL AIIVLAVVLP HHQASCRPDA FTRAAVAADS KICSDIGRVI
LQQQGSPVDA AIAALICTGV VNPQSMGLGG GVVFTIYNAS TGKVEVINAR ETVPASHDQR
LLDQCTNALP LCTGAQWIGV PGELRGYAEA HRRYGRLPWA QLFQPTIALL REGFRVPPIL
SQFLNTSFLQ PCLNSSTLRQ LFFNGTETLR SQDPLPWPAL ANTLETVAKE GAEVLYTGKL
GQTLVEDIAW QGSQLTVQDL AAFRPKVVEP LEMALGNYTL YSPPPPAGGA ILSFILNVLK
GFNFSAETVA GPEGKVNMYH HLVEALKFAV GQRWRLWDPY SHPGIQNISQ DLLRETLAQH
IRQQIDGRGD HQLSHYNLSG VRGNSMGTSH VSVLGEDGSA VAATSTINTP FGAMVYSPRT
GILLNNELLD LCWRHKPGST VTPPPVPGEQ PPSSMVPSIL INEVQGSKLV IGGAGGELII
SAVTQAIVNK LWLGFSLTDA IAAPILHVNS KGHVEYEPKF NQEVRKGLQD RGQSQSQSQR
PVFLNSVQAV FQEGPCVYAA SDLRKAGKAS GY
//
