UniProtKB - P36269 (GGT5_HUMAN)
Protein
Glutathione hydrolase 5 proenzyme
Gene
GGT5
Organism
Homo sapiens (Human)
Status
Functioni
Cleaves the gamma-glutamyl peptide bond of glutathione and glutathione-S-conjugate such as leukotriene C4 (PubMed:21447318). Does not cleaves gamma-glutamyl compounds such as gamma-glutamyl leucine (PubMed:21447318). 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 (PubMed:21447318). Acts as a negative regulator of geranylgeranyl glutathione bioactivity by cleaving off its gamma-glutamyl group, playing a role in adaptive immune responses (PubMed:30842656).2 Publications
Miscellaneous
A previous study reported that GSH and oxidized glutathione (GSSG) are not substrates for murine GGT5 (By similarity). However, this result contrasts with two studies reported that GSH is indeed a substrate for GGT5 (PubMed:21447318, PubMed:1676842).By similarity2 Publications
Catalytic activityi
- an α-amino acid + an N-terminal (5-L-glutamyl)-[peptide] = 5-L-glutamyl amino acid + N-terminal L-α-aminoacyl-[peptide]1 PublicationEC:2.3.2.21 PublicationThis reaction proceeds in the forwardCurated direction.
- EC:3.4.19.132 PublicationsThis reaction proceeds in the forwardCurated direction.
- EC:3.4.19.141 PublicationThis reaction proceeds in the forward1 Publication direction.
- an S-substituted glutathione + H2O = an S-substituted L-cysteinylglycine + L-glutamate2 PublicationsEC:3.4.19.132 PublicationsThis reaction proceeds in the forwardCurated direction.
- H2O + S-[(2E,6E,10E)-geranylgeranyl]-L-glutathione = L-glutamate + S-[(2E,6E,10E)-geranylgeranyl]-L-cysteinylglycine1 PublicationThis reaction proceeds in the forward1 Publication direction.
Activity regulationi
Inhibited by serine-borate.1 Publication
Kineticsi
- KM=10.5 µM for glutathione1 Publication
- KM=10.2 µM for leukotriene C41 Publication
- KM=18.2 µM for S-methylglutathione1 Publication
- KM=14.8 µM for S-(4-nitro-benzyl)glutathione1 Publication
- KM=43 µM for oxidized glutathione1 Publication
: glutathione metabolism Pathwayi
This protein is involved in the pathway glutathione metabolism, which is part of Sulfur metabolism.1 PublicationView all proteins of this organism that are known to be involved in the pathway glutathione metabolism and in Sulfur metabolism.
Pathwayi: leukotriene D4 biosynthesis
This protein is involved in the pathway leukotriene D4 biosynthesis, which is part of Lipid metabolism.1 PublicationView all proteins of this organism that are known to be involved in the pathway leukotriene D4 biosynthesis and in Lipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 110 | GlutamateBy similarity | 1 | |
Active sitei | 388 | NucleophileBy similarity | 1 | |
Binding sitei | 406 | GlutamateBy similarity | 1 | |
Binding sitei | 427 | GlutamateBy similarity | 1 |
GO - Molecular functioni
- glutathione hydrolase activity Source: UniProtKB
- 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: BHF-UCL
GO - Biological processi
- cellular amino acid metabolic process Source: UniProtKB
- fatty acid metabolic process Source: BHF-UCL
- glutathione biosynthetic process Source: UniProtKB-KW
- glutathione catabolic process Source: UniProtKB
- inflammatory response Source: GO_Central
- leukotriene D4 biosynthetic process Source: UniProtKB
- leukotriene metabolic process Source: Reactome
- proteolysis Source: UniProtKB
- 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
BioCyci | MetaCyc:HS01949-MONOMER |
BRENDAi | 2.3.2.2, 2681 3.4.19.13, 2681 |
PathwayCommonsi | P36269 |
Reactomei | R-HSA-174403, Glutathione synthesis and recycling R-HSA-2142691, Synthesis of Leukotrienes (LT) and Eoxins (EX) R-HSA-5423646, Aflatoxin activation and detoxification R-HSA-9664535, LTC4-CYSLTR mediated IL4 production |
UniPathwayi | UPA00204 UPA00880 |
Protein family/group databases
MEROPSi | T03.002 |
Chemistry databases
SwissLipidsi | SLP:000001455 |
Names & Taxonomyi
Protein namesi | Recommended name: Glutathione hydrolase 5 proenzyme (EC:3.4.19.133 Publications)Alternative name(s): Gamma-glutamyl transpeptidase-related enzyme1 Publication Short name: GGT-rel1 Publication Gamma-glutamyltransferase-like activity 11 Publication Gamma-glutamyltranspeptidase 5 Leukotriene-C4 hydrolase (EC:3.4.19.141 Publication) Cleaved into the following 2 chains: |
Gene namesi | Name:GGT5 Synonyms:GGTLA1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000099998.17 |
HGNCi | HGNC:4260, GGT5 |
MIMi | 137168, gene |
neXtProti | NX_P36269 |
Subcellular locationi
Other locations
- Membrane By similarity; Single-pass type II membrane protein By similarity
Plasma Membrane
- intrinsic component of plasma membrane Source: UniProtKB
- plasma membrane Source: GO_Central
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 8 | CytoplasmicBy similarity | 8 | |
Transmembranei | 9 – 29 | Helical; Signal-anchor for type II membrane proteinBy similarityAdd BLAST | 21 | |
Topological domaini | 30 – 586 | ExtracellularBy similarityAdd BLAST | 557 |
Keywords - Cellular componenti
MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 2687 |
OpenTargetsi | ENSG00000099998 |
PharmGKBi | PA162389442 |
Miscellaneous databases
Pharosi | P36269, Tbio |
Polymorphism and mutation databases
BioMutai | GGT5 |
DMDMi | 116242493 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000011072 | 1 – 387 | Glutathione hydrolase 5 heavy chainBy similarityAdd BLAST | 387 | |
ChainiPRO_0000011073 | 388 – 586 | Glutathione hydrolase 5 light chainBy similarityAdd BLAST | 199 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 98 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 204 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 303 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 347 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 535 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 550 | N-linked (GlcNAc...) asparagine1 Publication | 1 |
Post-translational modificationi
Cleaved by autocatalysis into a large and a small subunit.By similarity
Glycosylated.By similarity
Keywords - PTMi
Glycoprotein, ZymogenProteomic databases
EPDi | P36269 |
jPOSTi | P36269 |
MassIVEi | P36269 |
PaxDbi | P36269 |
PeptideAtlasi | P36269 |
PRIDEi | P36269 |
ProteomicsDBi | 55177 [P36269-1] 55178 [P36269-2] 55179 [P36269-3] |
PTM databases
GlyGeni | P36269, 8 sites, 4 O-linked glycans (2 sites) |
iPTMneti | P36269 |
PhosphoSitePlusi | P36269 |
Expressioni
Gene expression databases
Bgeei | ENSG00000099998, Expressed in endocervix and 172 other tissues |
ExpressionAtlasi | P36269, baseline and differential |
Genevisiblei | P36269, HS |
Organism-specific databases
HPAi | ENSG00000099998, Low tissue specificity |
Interactioni
Subunit structurei
Heterodimer composed of the light and heavy chains. The active site is located in the light chain.
By similarityProtein-protein interaction databases
BioGRIDi | 108954, 6 interactors |
IntActi | P36269, 5 interactors |
STRINGi | 9606.ENSP00000381340 |
Miscellaneous databases
RNActi | P36269, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 469 – 470 | 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 | P36269 |
OMAi | CGMGPPS |
OrthoDBi | 1419292at2759 |
PhylomeDBi | P36269 |
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 (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: P36269-1) [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
MARGYGATVS LVLLGLGLAL AVIVLAVVLS RHQAPCGPQA FAHAAVAADS
60 70 80 90 100
KVCSDIGRAI LQQQGSPVDA TIAALVCTSV VNPQSMGLGG GVIFTIYNVT
110 120 130 140 150
TGKVEVINAR ETVPASHAPS LLDQCAQALP LGTGAQWIGV PGELRGYAEA
160 170 180 190 200
HRRHGRLPWA QLFQPTIALL RGGHVVAPVL SRFLHNSILR PSLQASTLRQ
210 220 230 240 250
LFFNGTEPLR PQDPLPWPAL ATTLETVATE GVEVFYTGRL GQMLVEDIAK
260 270 280 290 300
EGSQLTLQDL AKFQPEVVDA LEVPLGDYTL YSPPPPAGGA ILSFILNVLR
310 320 330 340 350
GFNFSTESMA RPEGRVNVYH HLVETLKFAK GQRWRLGDPR SHPKLQNASR
360 370 380 390 400
DLLGETLAQL IRQQIDGRGD HQLSHYSLAE AWGHGTGTSH VSVLGEDGSA
410 420 430 440 450
VAATSTINTP FGAMVYSPRT GIILNNELLD LCERCPRGSG TTPSPVSGDR
460 470 480 490 500
VGGAPGRCWP PVPGERSPSS MVPSILINKA QGSKLVIGGA GGELIISAVA
510 520 530 540 550
QAIMSKLWLG FDLRAAIAAP ILHVNSKGCV EYEPNFSQEV QRGLQDRGQN
560 570 580
QTQRPFFLNV VQAVSQEGAC VYAVSDLRKS GEAAGY
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketC9JU68 | C9JU68_HUMAN | Glutathione hydrolase 5 proenzyme | GGT5 | 73 | Annotation score: | ||
H7C1X2 | H7C1X2_HUMAN | Glutathione hydrolase 5 proenzyme | GGT5 | 220 | Annotation score: |
Sequence cautioni
The sequence CAB55910 differs from that shown. Reason: Frameshift.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 408 | N → Y in CAB55910 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 437 | R → W in AAA58503 (PubMed:1676842).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_028006 | 11 | L → I. Corresponds to variant dbSNP:rs5760274Ensembl. | 1 | |
Natural variantiVAR_028007 | 330 | K → R2 PublicationsCorresponds to variant dbSNP:rs2275984Ensembl. | 1 | |
Natural variantiVAR_028008 | 332 | Q → H. Corresponds to variant dbSNP:rs6004105Ensembl. | 1 | |
Natural variantiVAR_024455 | 475 | I → V. Corresponds to variant dbSNP:rs7288201Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_008146 | 101 – 132 | Missing in isoform 2. 1 PublicationAdd BLAST | 32 | |
Alternative sequenceiVSP_043470 | 445 | P → PA in isoform 3. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M64099 mRNA Translation: AAA58503.1 AL117414 mRNA Translation: CAB55910.1 Frameshift. BT009808 mRNA Translation: AAP88810.1 CT841518 mRNA Translation: CAJ86448.1 AK292006 mRNA Translation: BAF84695.1 AP000353 Genomic DNA No translation available. AP000354 Genomic DNA No translation available. CH471095 Genomic DNA Translation: EAW59643.1 BC011362 mRNA Translation: AAH11362.1 BC073999 mRNA Translation: AAH73999.1 |
CCDSi | CCDS13825.1 [P36269-1] CCDS42989.1 [P36269-2] CCDS42990.1 [P36269-3] |
PIRi | A41125 T17220 |
RefSeqi | NP_001093251.1, NM_001099781.2 [P36269-3] NP_001093252.1, NM_001099782.2 [P36269-2] NP_001289393.1, NM_001302464.1 NP_001289394.1, NM_001302465.1 NP_004112.2, NM_004121.3 [P36269-1] |
Genome annotation databases
Ensembli | ENST00000263112; ENSP00000263112; ENSG00000099998 [P36269-2] ENST00000327365; ENSP00000330080; ENSG00000099998 [P36269-1] ENST00000398292; ENSP00000381340; ENSG00000099998 [P36269-3] |
GeneIDi | 2687 |
KEGGi | hsa:2687 |
UCSCi | uc002zzo.4, human [P36269-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M64099 mRNA Translation: AAA58503.1 AL117414 mRNA Translation: CAB55910.1 Frameshift. BT009808 mRNA Translation: AAP88810.1 CT841518 mRNA Translation: CAJ86448.1 AK292006 mRNA Translation: BAF84695.1 AP000353 Genomic DNA No translation available. AP000354 Genomic DNA No translation available. CH471095 Genomic DNA Translation: EAW59643.1 BC011362 mRNA Translation: AAH11362.1 BC073999 mRNA Translation: AAH73999.1 |
CCDSi | CCDS13825.1 [P36269-1] CCDS42989.1 [P36269-2] CCDS42990.1 [P36269-3] |
PIRi | A41125 T17220 |
RefSeqi | NP_001093251.1, NM_001099781.2 [P36269-3] NP_001093252.1, NM_001099782.2 [P36269-2] NP_001289393.1, NM_001302464.1 NP_001289394.1, NM_001302465.1 NP_004112.2, NM_004121.3 [P36269-1] |
3D structure databases
SMRi | P36269 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 108954, 6 interactors |
IntActi | P36269, 5 interactors |
STRINGi | 9606.ENSP00000381340 |
Chemistry databases
SwissLipidsi | SLP:000001455 |
Protein family/group databases
MEROPSi | T03.002 |
PTM databases
GlyGeni | P36269, 8 sites, 4 O-linked glycans (2 sites) |
iPTMneti | P36269 |
PhosphoSitePlusi | P36269 |
Polymorphism and mutation databases
BioMutai | GGT5 |
DMDMi | 116242493 |
Proteomic databases
EPDi | P36269 |
jPOSTi | P36269 |
MassIVEi | P36269 |
PaxDbi | P36269 |
PeptideAtlasi | P36269 |
PRIDEi | P36269 |
ProteomicsDBi | 55177 [P36269-1] 55178 [P36269-2] 55179 [P36269-3] |
Protocols and materials databases
Antibodypediai | 285, 122 antibodies |
DNASUi | 2687 |
Genome annotation databases
Ensembli | ENST00000263112; ENSP00000263112; ENSG00000099998 [P36269-2] ENST00000327365; ENSP00000330080; ENSG00000099998 [P36269-1] ENST00000398292; ENSP00000381340; ENSG00000099998 [P36269-3] |
GeneIDi | 2687 |
KEGGi | hsa:2687 |
UCSCi | uc002zzo.4, human [P36269-1] |
Organism-specific databases
CTDi | 2687 |
DisGeNETi | 2687 |
EuPathDBi | HostDB:ENSG00000099998.17 |
GeneCardsi | GGT5 |
HGNCi | HGNC:4260, GGT5 |
HPAi | ENSG00000099998, Low tissue specificity |
MIMi | 137168, gene |
neXtProti | NX_P36269 |
OpenTargetsi | ENSG00000099998 |
PharmGKBi | PA162389442 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2410, Eukaryota |
GeneTreei | ENSGT00940000155794 |
HOGENOMi | CLU_014813_4_1_1 |
InParanoidi | P36269 |
OMAi | CGMGPPS |
OrthoDBi | 1419292at2759 |
PhylomeDBi | P36269 |
TreeFami | TF313608 |
Enzyme and pathway databases
UniPathwayi | UPA00204 UPA00880 |
BioCyci | MetaCyc:HS01949-MONOMER |
BRENDAi | 2.3.2.2, 2681 3.4.19.13, 2681 |
PathwayCommonsi | P36269 |
Reactomei | R-HSA-174403, Glutathione synthesis and recycling R-HSA-2142691, Synthesis of Leukotrienes (LT) and Eoxins (EX) R-HSA-5423646, Aflatoxin activation and detoxification R-HSA-9664535, LTC4-CYSLTR mediated IL4 production |
Miscellaneous databases
BioGRID-ORCSi | 2687, 10 hits in 844 CRISPR screens |
ChiTaRSi | GGT5, human |
GeneWikii | GGTLA1 |
GenomeRNAii | 2687 |
Pharosi | P36269, Tbio |
PROi | PR:P36269 |
RNActi | P36269, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000099998, Expressed in endocervix and 172 other tissues |
ExpressionAtlasi | P36269, baseline and differential |
Genevisiblei | P36269, HS |
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_HUMAN | |
Accessioni | P36269Primary (citable) accession number: P36269 Secondary accession number(s): Q53XM9 Q9UFM5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 1, 1994 |
Last sequence update: | October 17, 2006 | |
Last modified: | December 2, 2020 | |
This is version 188 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families - Human chromosome 22
Human chromosome 22: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations