UniProtKB - Q92820 (GGH_HUMAN)
Protein
Gamma-glutamyl hydrolase
Gene
GGH
Organism
Homo sapiens (Human)
Status
Functioni
Hydrolyzes the polyglutamate sidechains of pteroylpolyglutamates. Progressively removes gamma-glutamyl residues from pteroylpoly-gamma-glutamate to yield pteroyl-alpha-glutamate (folic acid) and free glutamate. May play an important role in the bioavailability of dietary pteroylpolyglutamates and in the metabolism of pteroylpolyglutamates and antifolates.
Catalytic activityi
- (6S)-5,6,7,8-tetrahydrofolyl-(γ-L-Glu)n + (n-1) H2O = (6S)-5,6,7,8-tetrahydrofolate + (n-1) L-glutamateEC:3.4.19.9
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 134 | Nucleophile | 1 | |
Active sitei | 244 | Proton donor | 1 |
GO - Molecular functioni
- exopeptidase activity Source: ProtInc
- gamma-glutamyl-peptidase activity Source: UniProtKB
- omega peptidase activity Source: ProtInc
GO - Biological processi
- neutrophil degranulation Source: Reactome
- response to drug Source: Ensembl
- response to ethanol Source: Ensembl
- response to insulin Source: Ensembl
- response to zinc ion Source: Ensembl
- tetrahydrofolylpolyglutamate metabolic process Source: GO_Central
Keywordsi
Molecular function | Hydrolase |
Enzyme and pathway databases
BRENDAi | 3.4.19.9, 2681 |
PathwayCommonsi | Q92820 |
Reactomei | R-HSA-6798695, Neutrophil degranulation |
SIGNORi | Q92820 |
Protein family/group databases
MEROPSi | C26.001 |
Names & Taxonomyi
Protein namesi | Recommended name: Gamma-glutamyl hydrolase (EC:3.4.19.9)Alternative name(s): Conjugase GH Gamma-Glu-X carboxypeptidase |
Gene namesi | Name:GGH |
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:ENSG00000137563.11 |
HGNCi | HGNC:4248, GGH |
MIMi | 601509, gene |
neXtProti | NX_Q92820 |
Subcellular locationi
Lysosome
- Lysosome 1 Publication
Extracellular region or secreted
- extracellular space Curated
Other locations
- Melanosome 1 Publication
Note: While its intracellular location is primarily the lysosome, most of the enzyme activity is secreted. Identified by mass spectrometry in melanosome fractions from stage I to stage IV.1 Publication
Cytosol
- cytosol Source: Ensembl
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular region Source: Reactome
- extracellular space Source: UniProtKB
Lysosome
- azurophil granule lumen Source: Reactome
Nucleus
- nucleus Source: UniProtKB
Other locations
- melanosome Source: UniProtKB-SubCell
- specific granule lumen Source: Reactome
- tertiary granule lumen Source: Reactome
- vacuole Source: GO_Central
Keywords - Cellular componenti
Lysosome, SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 134 | C → A: Loss of activity. 2 Publications | 1 | |
Mutagenesisi | 195 | H → N: Reduces activity 250-fold. | 1 | |
Mutagenesisi | 244 | H → A: Loss of activity. 1 Publication | 1 | |
Mutagenesisi | 246 | E → A: Slightly reduced catalytic activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 8836 |
OpenTargetsi | ENSG00000137563 |
Orphaneti | 565785, Methotrexate dose selection |
PharmGKBi | PA432 |
Miscellaneous databases
Pharosi | Q92820, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2223 |
DrugBanki | DB00158, Folic acid DB00563, Methotrexate |
Polymorphism and mutation databases
BioMutai | GGH |
DMDMi | 6016127 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 24 | By similarityAdd BLAST | 24 | |
ChainiPRO_0000026539 | 25 – 318 | Gamma-glutamyl hydrolaseAdd BLAST | 294 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 116 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 163 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 203 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 307 | N-linked (GlcNAc...) asparagine; partial1 Publication | 1 |
Keywords - PTMi
GlycoproteinProteomic databases
EPDi | Q92820 |
jPOSTi | Q92820 |
MassIVEi | Q92820 |
MaxQBi | Q92820 |
PaxDbi | Q92820 |
PeptideAtlasi | Q92820 |
PRIDEi | Q92820 |
ProteomicsDBi | 75496 |
PTM databases
GlyConnecti | 1257, 26 N-Linked glycans (4 sites) |
GlyGeni | Q92820, 4 sites, 2 N-linked glycans (1 site) |
iPTMneti | Q92820 |
PhosphoSitePlusi | Q92820 |
SwissPalmi | Q92820 |
Expressioni
Gene expression databases
Bgeei | ENSG00000137563, Expressed in ventricular zone and 220 other tissues |
Genevisiblei | Q92820, HS |
Organism-specific databases
HPAi | ENSG00000137563, Tissue enhanced (kidney, liver) |
Interactioni
Subunit structurei
Homodimer.
2 PublicationsBinary interactionsi
Q92820
With | #Exp. | IntAct |
---|---|---|
SGTB [Q96EQ0] | 3 | EBI-3045534,EBI-744081 |
Protein-protein interaction databases
BioGRIDi | 114363, 32 interactors |
IntActi | Q92820, 23 interactors |
MINTi | Q92820 |
STRINGi | 9606.ENSP00000260118 |
Chemistry databases
BindingDBi | Q92820 |
Miscellaneous databases
RNActi | Q92820, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q92820 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q92820 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 25 – 318 | Gamma-glutamyl hydrolasePROSITE-ProRule annotationAdd BLAST | 294 |
Sequence similaritiesi
Belongs to the peptidase C26 family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG1559, Eukaryota |
GeneTreei | ENSGT00490000043388 |
HOGENOMi | CLU_058704_1_1_1 |
InParanoidi | Q92820 |
OMAi | KWSLSVK |
OrthoDBi | 877490at2759 |
PhylomeDBi | Q92820 |
TreeFami | TF323437 |
Family and domain databases
Gene3Di | 3.40.50.880, 1 hit |
InterProi | View protein in InterPro IPR029062, Class_I_gatase-like IPR015527, Pept_C26_g-glut_hydrolase IPR011697, Peptidase_C26 |
PANTHERi | PTHR11315, PTHR11315, 1 hit |
Pfami | View protein in Pfam PF07722, Peptidase_C26, 1 hit |
SUPFAMi | SSF52317, SSF52317, 1 hit |
PROSITEi | View protein in PROSITE PS51275, PEPTIDASE_C26_GGH, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
Q92820-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MASPGCLLCV LGLLLCGAAS LELSRPHGDT AKKPIIGILM QKCRNKVMKN
60 70 80 90 100
YGRYYIAASY VKYLESAGAR VVPVRLDLTE KDYEILFKSI NGILFPGGSV
110 120 130 140 150
DLRRSDYAKV AKIFYNLSIQ SFDDGDYFPV WGTCLGFEEL SLLISGECLL
160 170 180 190 200
TATDTVDVAM PLNFTGGQLH SRMFQNFPTE LLLSLAVEPL TANFHKWSLS
210 220 230 240 250
VKNFTMNEKL KKFFNVLTTN TDGKIEFIST MEGYKYPVYG VQWHPEKAPY
260 270 280 290 300
EWKNLDGISH APNAVKTAFY LAEFFVNEAR KNNHHFKSES EEEKALIYQF
310
SPIYTGNISS FQQCYIFD
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_014697 | 6 | C → R. Corresponds to variant dbSNP:rs1800909Ensembl. | 1 | |
Natural variantiVAR_029230 | 31 | A → T. Corresponds to variant dbSNP:rs11545077Ensembl. | 1 | |
Natural variantiVAR_029231 | 151 | T → I. Corresponds to variant dbSNP:rs11545078Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U55206 mRNA Translation: AAC05579.1 AF147083, AF147081, AF147082 Genomic DNA Translation: AAF03360.1 BC025025 mRNA Translation: AAH25025.1 |
CCDSi | CCDS6177.1 |
PIRi | JC6115 |
RefSeqi | NP_003869.1, NM_003878.2 |
Genome annotation databases
Ensembli | ENST00000260118; ENSP00000260118; ENSG00000137563 |
GeneIDi | 8836 |
KEGGi | hsa:8836 |
UCSCi | uc003xuw.4, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U55206 mRNA Translation: AAC05579.1 AF147083, AF147081, AF147082 Genomic DNA Translation: AAF03360.1 BC025025 mRNA Translation: AAH25025.1 |
CCDSi | CCDS6177.1 |
PIRi | JC6115 |
RefSeqi | NP_003869.1, NM_003878.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1L9X | X-ray | 1.60 | A/B/C/D | 25-318 | [»] | |
SMRi | Q92820 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114363, 32 interactors |
IntActi | Q92820, 23 interactors |
MINTi | Q92820 |
STRINGi | 9606.ENSP00000260118 |
Chemistry databases
BindingDBi | Q92820 |
ChEMBLi | CHEMBL2223 |
DrugBanki | DB00158, Folic acid DB00563, Methotrexate |
Protein family/group databases
MEROPSi | C26.001 |
PTM databases
GlyConnecti | 1257, 26 N-Linked glycans (4 sites) |
GlyGeni | Q92820, 4 sites, 2 N-linked glycans (1 site) |
iPTMneti | Q92820 |
PhosphoSitePlusi | Q92820 |
SwissPalmi | Q92820 |
Polymorphism and mutation databases
BioMutai | GGH |
DMDMi | 6016127 |
Proteomic databases
EPDi | Q92820 |
jPOSTi | Q92820 |
MassIVEi | Q92820 |
MaxQBi | Q92820 |
PaxDbi | Q92820 |
PeptideAtlasi | Q92820 |
PRIDEi | Q92820 |
ProteomicsDBi | 75496 |
Protocols and materials databases
Antibodypediai | 4517, 309 antibodies |
DNASUi | 8836 |
Genome annotation databases
Ensembli | ENST00000260118; ENSP00000260118; ENSG00000137563 |
GeneIDi | 8836 |
KEGGi | hsa:8836 |
UCSCi | uc003xuw.4, human |
Organism-specific databases
CTDi | 8836 |
DisGeNETi | 8836 |
EuPathDBi | HostDB:ENSG00000137563.11 |
GeneCardsi | GGH |
HGNCi | HGNC:4248, GGH |
HPAi | ENSG00000137563, Tissue enhanced (kidney, liver) |
MIMi | 601509, gene |
neXtProti | NX_Q92820 |
OpenTargetsi | ENSG00000137563 |
Orphaneti | 565785, Methotrexate dose selection |
PharmGKBi | PA432 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1559, Eukaryota |
GeneTreei | ENSGT00490000043388 |
HOGENOMi | CLU_058704_1_1_1 |
InParanoidi | Q92820 |
OMAi | KWSLSVK |
OrthoDBi | 877490at2759 |
PhylomeDBi | Q92820 |
TreeFami | TF323437 |
Enzyme and pathway databases
BRENDAi | 3.4.19.9, 2681 |
PathwayCommonsi | Q92820 |
Reactomei | R-HSA-6798695, Neutrophil degranulation |
SIGNORi | Q92820 |
Miscellaneous databases
BioGRID-ORCSi | 8836, 7 hits in 844 CRISPR screens |
ChiTaRSi | GGH, human |
EvolutionaryTracei | Q92820 |
GeneWikii | GGH_(gene) |
GenomeRNAii | 8836 |
Pharosi | Q92820, Tchem |
PROi | PR:Q92820 |
RNActi | Q92820, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000137563, Expressed in ventricular zone and 220 other tissues |
Genevisiblei | Q92820, HS |
Family and domain databases
Gene3Di | 3.40.50.880, 1 hit |
InterProi | View protein in InterPro IPR029062, Class_I_gatase-like IPR015527, Pept_C26_g-glut_hydrolase IPR011697, Peptidase_C26 |
PANTHERi | PTHR11315, PTHR11315, 1 hit |
Pfami | View protein in Pfam PF07722, Peptidase_C26, 1 hit |
SUPFAMi | SSF52317, SSF52317, 1 hit |
PROSITEi | View protein in PROSITE PS51275, PEPTIDASE_C26_GGH, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | GGH_HUMAN | |
Accessioni | Q92820Primary (citable) accession number: Q92820 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1999 |
Last sequence update: | August 1, 1998 | |
Last modified: | December 2, 2020 | |
This is version 177 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
3D-structure, 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 - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 8
Human chromosome 8: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Peptidase families
Classification of peptidase families and list of entries