UniProtKB - Q9Z2A9 (GGT5_MOUSE)
Protein
Glutathione hydrolase 5 proenzyme
Gene
Ggt5
Organism
Mus musculus (Mouse)
Status
Functioni
Cleaves the gamma-glutamyl peptide bond of glutathione and glutathione-S-conjugate (By similarity). Converts leukotriene C4 (LTC4), a glutathione-S-conjugate, to leukotriene D4 (LTD4) (PubMed:9774450, PubMed:11463821, PubMed:12163373). Does not cleaves gamma-glutamyl compounds such as gamma-glutamyl leucine. May also catalyze a transpeptidation reaction in addition to the hydrolysis reaction, transferring the gamma-glutamyl moiety to an acceptor amino acid to form a new gamma-glutamyl compound. Acts as a negative regulator of geranylgeranyl glutathione bioactivity by cleaving off its gamma-glutamyl group, playing a role in adaptive immune responses (By similarity).By similarity3 Publications
Miscellaneous
A previous study reported that GSH and oxidized glutathione (GSSG) are not substrates for murine GGT5 (PubMed:9774450). However, this result contrasts with two studies reported that GSH is indeed a substrate for GGT5 (By similarity).By similarity1 Publication
Catalytic activityi
- an α-amino acid + an N-terminal (5-L-glutamyl)-[peptide] = 5-L-glutamyl amino acid + N-terminal L-α-aminoacyl-[peptide]By similarityEC:2.3.2.2By similarityThis reaction proceeds in the forwardBy similarity direction.
- EC:3.4.19.13By similarityThis reaction proceeds in the forwardBy similarity direction.
- EC:3.4.19.13By similarityThis reaction proceeds in the forwardBy similarity direction.
- EC:3.4.19.143 PublicationsThis reaction proceeds in the forward1 Publication direction.
- H2O + S-[(2E,6E,10E)-geranylgeranyl]-L-glutathione = L-glutamate + S-[(2E,6E,10E)-geranylgeranyl]-L-cysteinylglycineBy similarityThis reaction proceeds in the forwardBy similarity direction.
Activity regulationi
Inhibited by serine-borate.By similarity
: leukotriene D4 biosynthesis Pathwayi
This protein is involved in the pathway leukotriene D4 biosynthesis, which is part of Lipid metabolism.3 PublicationsView all proteins of this organism that are known to be involved in the pathway leukotriene D4 biosynthesis and in Lipid metabolism.
Pathwayi: glutathione metabolism
This protein is involved in the pathway glutathione metabolism, which is part of Sulfur metabolism.By similarityView all proteins of this organism that are known to be involved in the pathway glutathione metabolism and in Sulfur metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 110 | GlutamateBy similarity | 1 | |
Active sitei | 389 | NucleophileBy similarity | 1 | |
Binding sitei | 407 | GlutamateBy similarity | 1 | |
Binding sitei | 428 | GlutamateBy similarity | 1 |
GO - Molecular functioni
- glutathione hydrolase activity Source: MGI
- hypoglycin A gamma-glutamyl transpeptidase activity Source: UniProtKB-EC
- leukotriene-C(4) hydrolase Source: UniProtKB
- leukotriene C4 gamma-glutamyl transferase activity Source: UniProtKB-EC
- peptidyltransferase activity Source: MGI
GO - Biological processi
- cellular amino acid metabolic process Source: MGI
- fatty acid metabolic process Source: MGI
- glutathione biosynthetic process Source: UniProtKB-KW
- glutathione catabolic process Source: MGI
- inflammatory response Source: MGI
- leukotriene D4 biosynthetic process Source: MGI
- proteolysis Source: MGI
- response to estradiol Source: GO_Central
- response to lipopolysaccharide Source: GO_Central
- response to tumor necrosis factor Source: GO_Central
- spermatogenesis Source: GO_Central
Keywordsi
Molecular function | Acyltransferase, Hydrolase, Protease, Transferase |
Biological process | Glutathione biosynthesis, Leukotriene biosynthesis |
Enzyme and pathway databases
BRENDAi | 3.4.19.14, 3474 |
Reactomei | R-MMU-174403, Glutathione synthesis and recycling R-MMU-5423646, Aflatoxin activation and detoxification |
SABIO-RKi | Q9Z2A9 |
UniPathwayi | UPA00204 UPA00880 |
Protein family/group databases
MEROPSi | T03.002 |
Names & Taxonomyi
Protein namesi | Recommended name: Glutathione hydrolase 5 proenzyme (EC:3.4.19.13By similarity)Alternative name(s): Gamma-glutamyl leukotrienase1 Publication Short name: GGL1 Publication Gamma-glutamyltransferase-like activity 1 Gamma-glutamyltranspeptidase 5 Leukotriene-C4 hydrolase (EC:3.4.19.143 Publications) Cleaved into the following 2 chains: |
Gene namesi | Name:Ggt5 Synonyms:Ggtla1 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1346063, Ggt5 |
Subcellular locationi
Other locations
- Membrane 1 Publication; Single-pass type II membrane protein 1 Publication
Plasma Membrane
- intrinsic component of plasma membrane Source: MGI
- plasma membrane Source: MGI
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 8 | Cytoplasmic1 Publication | 8 | |
Transmembranei | 9 – 29 | Helical; Signal-anchor for type II membrane protein1 PublicationAdd BLAST | 21 | |
Topological domaini | 30 – 573 | Extracellular1 PublicationAdd BLAST | 544 |
Keywords - Cellular componenti
MembranePathology & Biotechi
Disruption phenotypei
Deficient mice shown no obvious phenotype but in most organs they have only 10% of the wild-type levels of gamma-glutamyl leukotrienase activity (PubMed:11463821). Mice deficient in GGT5 have significantly more airway hyper-reactivity in a model of experimental asthma (PubMed:12163373).2 Publications
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000011074 | 1 – 388 | Glutathione hydrolase 5 heavy chainBy similarityAdd BLAST | 388 | |
ChainiPRO_0000011075 | 389 – 573 | Glutathione hydrolase 5 light chainBy similarityAdd BLAST | 185 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 98 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 185 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 204 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 277 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 303 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 347 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 378 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Cleaved by autocatalysis into a large and a small subunit.By similarity
Glycosylated.1 Publication
Keywords - PTMi
Glycoprotein, ZymogenProteomic databases
jPOSTi | Q9Z2A9 |
PaxDbi | Q9Z2A9 |
PeptideAtlasi | Q9Z2A9 |
PRIDEi | Q9Z2A9 |
PTM databases
GlyConnecti | 2331, 1 N-Linked glycan (1 site) |
GlyGeni | Q9Z2A9, 7 sites |
iPTMneti | Q9Z2A9 |
PhosphoSitePlusi | Q9Z2A9 |
SwissPalmi | Q9Z2A9 |
Expressioni
Tissue specificityi
Very low level of expression. Detected in spleen lymphocytes, medullary and paracortical thymic lymphocytes, lung interstitial cells, bronchial epithelium, proximal tubules in kidney, crypt cells in small intestine, neurons in brain stem and cerebral cortex and in Purkinje cells.2 Publications
Very low expression.1 Publication
Gene expression databases
Bgeei | ENSMUSG00000006344, Expressed in granulocyte and 123 other tissues |
Genevisiblei | Q9Z2A9, MM |
Interactioni
Subunit structurei
Heterodimer composed of the light and heavy chains (PubMed:12163373). The active site is located in the light chain (By similarity).
By similarity1 PublicationProtein-protein interaction databases
STRINGi | 10090.ENSMUSP00000072074 |
Miscellaneous databases
RNActi | Q9Z2A9, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 454 – 455 | Glutamate bindingBy similarity | 2 |
Sequence similaritiesi
Belongs to the gamma-glutamyltransferase family.Curated
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2410, Eukaryota |
GeneTreei | ENSGT00940000155794 |
HOGENOMi | CLU_014813_4_1_1 |
InParanoidi | Q9Z2A9 |
OMAi | CGMGPPS |
OrthoDBi | 1419292at2759 |
TreeFami | TF313608 |
Family and domain databases
Gene3Di | 1.10.246.130, 1 hit 3.60.20.40, 1 hit |
InterProi | View protein in InterPro IPR043138, GGT_lsub_C IPR000101, GGT_peptidase IPR043137, GGT_ssub IPR029055, Ntn_hydrolases_N |
PANTHERi | PTHR11686, PTHR11686, 1 hit |
SUPFAMi | SSF56235, SSF56235, 1 hit |
PROSITEi | View protein in PROSITE PS00462, G_GLU_TRANSPEPTIDASE, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q9Z2A9-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAWGHRATVC LVLLGVGLGL VIVVLAAVLS PRQASCGPGA FTRAAVAADS
60 70 80 90 100
KICSDIGRAI LQQRGSPVDA AIAALVCTGV VNPQSMGLGG GVVFTIYNAS
110 120 130 140 150
TGKVEIINAR ETVPASYDQG LLNQCKNVLP LGTGAQWIGV PGELRGYAEA
160 170 180 190 200
HRRHGRLPWA QLFQPTIALL REGFRVPFIL SQFLNNSILR PHLSASTLRQ
210 220 230 240 250
LFFNGTETLR SQDPFPWPAL ANTLETVAKE GAEVLYTGRL GRMLVEDIAK
260 270 280 290 300
QGSLLTVQDL AAFQPEVVEP LEMPLGNYTL YSPPPPAGGA ILSFILNVLK
310 320 330 340 350
GFNFSAETVA RPGGEVNMYH HLVETLKFAV GQRWRLWDPS SHPGIQNISR
360 370 380 390 400
DLLREDLAQR IRQQIDGRGD HHQLSHYNLT GVRGNRMGTS HVSVLGEDGS
410 420 430 440 450
AVAATSTINT PFGAMVYSPR TGILLNNELL DLCWRHMPTS PITPPPVPGE
460 470 480 490 500
RPPSSMVPSI LVNKGQGSKL VIGGAGGELI ISAVAQTIMN KLWLGFDLTE
510 520 530 540 550
AIASPILHVN SKGHVEYEPK FNQEVQKGLQ DRGQIQSQSQ RPVFLNAVQA
560 570
VFQEGPCVYA ASDLRKAGKA SGY
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A087WNR3 | A0A087WNR3_MOUSE | Glutathione hydrolase 5 proenzyme | Ggt5 | 71 | Annotation score: | ||
Q80WV0 | Q80WV0_MOUSE | Ggt5 protein | Ggt5 Ggtla1 | 230 | Annotation score: | ||
A0A087WSM3 | A0A087WSM3_MOUSE | Glutathione hydrolase 5 proenzyme | Ggt5 | 205 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 479 | L → P in AAC71001 (PubMed:9774450).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_008147 | 447 – 456 | VPGERPPSSM → DYHEQAVAWL in isoform 2. 1 Publication | 10 | |
Alternative sequenceiVSP_008148 | 457 – 573 | Missing in isoform 2. 1 PublicationAdd BLAST | 117 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF077765 mRNA Translation: AAC71001.1 AK052183 mRNA Translation: BAC34873.1 AK170326 mRNA Translation: BAE41720.1 AC087540 Genomic DNA No translation available. CH466553 Genomic DNA Translation: EDL31901.1 BC113775 mRNA Translation: AAI13776.1 |
CCDSi | CCDS23928.1 [Q9Z2A9-1] |
RefSeqi | NP_035950.2, NM_011820.4 [Q9Z2A9-1] |
Genome annotation databases
Ensembli | ENSMUST00000072217; ENSMUSP00000072074; ENSMUSG00000006344 [Q9Z2A9-1] |
GeneIDi | 23887 |
KEGGi | mmu:23887 |
UCSCi | uc007fqq.1, mouse [Q9Z2A9-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF077765 mRNA Translation: AAC71001.1 AK052183 mRNA Translation: BAC34873.1 AK170326 mRNA Translation: BAE41720.1 AC087540 Genomic DNA No translation available. CH466553 Genomic DNA Translation: EDL31901.1 BC113775 mRNA Translation: AAI13776.1 |
CCDSi | CCDS23928.1 [Q9Z2A9-1] |
RefSeqi | NP_035950.2, NM_011820.4 [Q9Z2A9-1] |
3D structure databases
SMRi | Q9Z2A9 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000072074 |
Protein family/group databases
MEROPSi | T03.002 |
PTM databases
GlyConnecti | 2331, 1 N-Linked glycan (1 site) |
GlyGeni | Q9Z2A9, 7 sites |
iPTMneti | Q9Z2A9 |
PhosphoSitePlusi | Q9Z2A9 |
SwissPalmi | Q9Z2A9 |
Proteomic databases
jPOSTi | Q9Z2A9 |
PaxDbi | Q9Z2A9 |
PeptideAtlasi | Q9Z2A9 |
PRIDEi | Q9Z2A9 |
Protocols and materials databases
Antibodypediai | 285, 122 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000072217; ENSMUSP00000072074; ENSMUSG00000006344 [Q9Z2A9-1] |
GeneIDi | 23887 |
KEGGi | mmu:23887 |
UCSCi | uc007fqq.1, mouse [Q9Z2A9-1] |
Organism-specific databases
CTDi | 2687 |
MGIi | MGI:1346063, Ggt5 |
Phylogenomic databases
eggNOGi | KOG2410, Eukaryota |
GeneTreei | ENSGT00940000155794 |
HOGENOMi | CLU_014813_4_1_1 |
InParanoidi | Q9Z2A9 |
OMAi | CGMGPPS |
OrthoDBi | 1419292at2759 |
TreeFami | TF313608 |
Enzyme and pathway databases
UniPathwayi | UPA00204 UPA00880 |
BRENDAi | 3.4.19.14, 3474 |
Reactomei | R-MMU-174403, Glutathione synthesis and recycling R-MMU-5423646, Aflatoxin activation and detoxification |
SABIO-RKi | Q9Z2A9 |
Miscellaneous databases
BioGRID-ORCSi | 23887, 2 hits in 17 CRISPR screens |
PROi | PR:Q9Z2A9 |
RNActi | Q9Z2A9, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000006344, Expressed in granulocyte and 123 other tissues |
Genevisiblei | Q9Z2A9, MM |
Family and domain databases
Gene3Di | 1.10.246.130, 1 hit 3.60.20.40, 1 hit |
InterProi | View protein in InterPro IPR043138, GGT_lsub_C IPR000101, GGT_peptidase IPR043137, GGT_ssub IPR029055, Ntn_hydrolases_N |
PANTHERi | PTHR11686, PTHR11686, 1 hit |
SUPFAMi | SSF56235, SSF56235, 1 hit |
PROSITEi | View protein in PROSITE PS00462, G_GLU_TRANSPEPTIDASE, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | GGT5_MOUSE | |
Accessioni | Q9Z2A9Primary (citable) accession number: Q9Z2A9 Secondary accession number(s): Q8C7B4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 29, 2003 |
Last sequence update: | September 18, 2013 | |
Last modified: | December 2, 2020 | |
This is version 154 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families