This gene catalyzes the hydrolysis of folylpoly-gamma-glutamates and antifolylpoly-gamma-glutamates by the removal of gamma-linked polyglutamates and glutamate. [provided by RefSeq, Jul 2008] See more...

Aliases for GGH Gene

Aliases for GGH Gene

  • Gamma-Glutamyl Hydrolase 2 3 4 5
  • Gamma-Glu-X Carboxypeptidase 3 4
  • Conjugase 2 4
  • GH 3 4
  • Gamma-Glutamyl Hydrolase (Conjugase, Folylpolygammaglutamyl Hydrolase) 3
  • Folylpolygammaglutamyl Hydrolase 2
  • EC 3.4.19.9 4
  • GGH 5

External Ids for GGH Gene

Previous GeneCards Identifiers for GGH Gene

  • GC08M063291
  • GC08M063867
  • GC08M063650
  • GC08M063977
  • GC08M064090
  • GC08M059415
  • GC08M063928

Summaries for GGH Gene

Entrez Gene Summary for GGH Gene

  • This gene catalyzes the hydrolysis of folylpoly-gamma-glutamates and antifolylpoly-gamma-glutamates by the removal of gamma-linked polyglutamates and glutamate. [provided by RefSeq, Jul 2008]

GeneCards Summary for GGH Gene

GGH (Gamma-Glutamyl Hydrolase) is a Protein Coding gene. Diseases associated with GGH include Tropical Sprue and Pulmonary Neuroendocrine Tumor. Among its related pathways are Glutathione metabolism and Innate Immune System. Gene Ontology (GO) annotations related to this gene include hydrolase activity and exopeptidase activity.

UniProtKB/Swiss-Prot Summary for GGH Gene

  • 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.

Gene Wiki entry for GGH Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GGH Gene

Genomics for GGH Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for GGH Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH08J063038 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 620.3 +0.0 5 2.8 ARHGAP35 SP1 HNRNPL CREB1 PRDM10 ZNF512 SIX5 IKZF1 POLR2A BACH1 GGH lnc-TTPA-3 lnc-NKAIN3-9 TTPA lnc-TTPA-4 RF00017-7078 NKAIN3
GH08J063007 Enhancer 0.9 ENCODE 53.8 +29.2 29224 3.9 GATAD2A REST FOXA1 RXRB SP1 POLR2A CEBPA SOX13 ARID3A RUNX3 LOC107986946 GGH ENSG00000240915 RF00017-7078 NKAIN3
GH08J063032 Enhancer 0.9 FANTOM5 Ensembl ENCODE 42.3 +6.1 6105 1.4 NFE2 MAFG NFE2L2 MAFK GGH YTHDF3 TTPA lnc-TTPA-4 lnc-TTPA-3 RF00017-7078 NKAIN3
GH08J063012 Enhancer 0.7 Ensembl ENCODE 42.2 +26.7 26706 0.2 CTCF RAD21 ZNF316 MAFF SMC3 MAFK YY1 EMSY ENSG00000240915 GGH LOC107986946 lnc-TTPA-5 RF00017-7078 NKAIN3
GH08J063085 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE CraniofacialAtlas 14.8 -47.0 -46995 2 HNRNPL REST RBFOX2 EZH2 ZFX KMT2B ZBTB20 USF1 KAT7 ZBTB48 TTPA lnc-TTPA-2 GGH RF00017-7078 L13713-227
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GGH on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GGH

Top Transcription factor binding sites by QIAGEN in the GGH gene promoter:
  • ATF-2
  • c-Jun
  • Chx10
  • CUTL1
  • Evi-1
  • HFH-3
  • LCR-F1
  • Nkx6-1
  • POU3F2
  • Sox5

Genomic Locations for GGH Gene

Genomic Locations for GGH Gene
chr8:63,015,079-63,038,806
(GRCh38/hg38)
Size:
23,728 bases
Orientation:
Minus strand
chr8:63,927,638-63,951,730
(GRCh37/hg19)
Size:
24,093 bases
Orientation:
Minus strand

Genomic View for GGH Gene

Genes around GGH on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GGH Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GGH Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GGH Gene

Proteins for GGH Gene

  • Protein details for GGH Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q92820-GGH_HUMAN
    Recommended name:
    Gamma-glutamyl hydrolase
    Protein Accession:
    Q92820

    Protein attributes for GGH Gene

    Size:
    318 amino acids
    Molecular mass:
    35964 Da
    Quaternary structure:
    • Homodimer.

    Three dimensional structures from OCA and Proteopedia for GGH Gene

neXtProt entry for GGH Gene

Post-translational modifications for GGH Gene

  • Glycosylation at Asn116, Asn163, Asn203, and Asn307
  • Ubiquitination at Lys212, Lys235, Lys253, and Lys287
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect

Other Protein References for GGH Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for GGH Gene

Domains & Families for GGH Gene

Gene Families for GGH Gene

Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for GGH Gene

InterPro:
Blocks:
  • Peptidase C26
ProtoNet:

Suggested Antigen Peptide Sequences for GGH Gene

GenScript: Design optimal peptide antigens:
  • Gamma-Glu-X carboxypeptidase (GGH_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q92820

UniProtKB/Swiss-Prot:

GGH_HUMAN :
  • Belongs to the peptidase C26 family.
Family:
  • Belongs to the peptidase C26 family.
genes like me logo Genes that share domains with GGH: view

Function for GGH Gene

Molecular function for GGH Gene

UniProtKB/Swiss-Prot Function:
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.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(6S)-5,6,7,8-tetrahydrofolyl-(gamma-L-Glu)n + (n-1) H2O = (6S)-5,6,7,8-tetrahydrofolate + (n-1) L-glutamate; Xref=Rhea:RHEA:56784, Rhea:RHEA-COMP:14738, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985, ChEBI:CHEBI:57453, ChEBI:CHEBI:141005; EC=3.4.19.9;.
GENATLAS Biochemistry:
gammaglutamyl hydrolase,involved in the metabolism of folic acid

Enzyme Numbers (IUBMB) for GGH Gene

Phenotypes From GWAS Catalog for GGH Gene

Gene Ontology (GO) - Molecular Function for GGH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0008238 exopeptidase activity TAS 8816764
GO:0008242 omega peptidase activity TAS 8816764
GO:0016787 hydrolase activity IEA --
GO:0034722 gamma-glutamyl-peptidase activity IBA,IDA 11005824
genes like me logo Genes that share ontologies with GGH: view
genes like me logo Genes that share phenotypes with GGH: view

Animal Model Products

CRISPR Products

miRNA for GGH Gene

miRTarBase miRNAs that target GGH

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GGH

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for GGH Gene

Localization for GGH Gene

Subcellular locations from UniProtKB/Swiss-Prot for GGH Gene

Secreted, extracellular space. Lysosome. Melanosome. 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. {ECO:0000269 PubMed:12643545}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GGH gene
Compartment Confidence
extracellular 5
lysosome 5
nucleus 4
cytosol 4
plasma membrane 2
mitochondrion 2
endoplasmic reticulum 2
cytoskeleton 1
peroxisome 1
endosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for GGH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IEA,IDA 25645918
GO:0005634 nucleus HDA 21630459
GO:0005764 lysosome IEA --
GO:0005773 vacuole IBA 21873635
genes like me logo Genes that share ontologies with GGH: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for GGH Gene

Pathways & Interactions for GGH Gene

genes like me logo Genes that share pathways with GGH: view

Gene Ontology (GO) - Biological Process for GGH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:0010043 response to zinc ion IEA --
GO:0032868 response to insulin IEA --
GO:0042493 response to drug IEA --
GO:0043312 neutrophil degranulation TAS --
genes like me logo Genes that share ontologies with GGH: view

No data available for SIGNOR curated interactions for GGH Gene

Drugs & Compounds for GGH Gene

(14) Drugs for GGH Gene - From: DrugBank, PharmGKB, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Methotrexate Approved Pharma Enzyme, substrate Folate antagonist,inhibits DFHR 1825
Folic acid Approved, Vet_approved Nutra Enzyme, substrate 4765
Bevacizumab Approved, Investigational Pharma VEGF antagonist, Therapeutic Antibodies, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 2368
Methylphenidate Approved, Investigational Pharma 431
Pemetrexed Approved, Investigational Pharma TS, DHFR,GARFT and AICARFT inhibitor, DHFR and Thymidylate synthase inhibitor, Anti-Folates 850

(11) Additional Compounds for GGH Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Tetrahydrofolyl-[Glu](2)
  • Tetrahydropteroyldiglutamate
  • (6S)-H4PteGlu2
  • Tetrahydropteroyldiglutamic acid
  • Tetrahydrofolyl-[glu](n+1)
  • Tetrahydropteroyl-[gamma-glu]N
Tetrahydrofolyl-[Glu](n)
  • Tetrahydrofolyl-[glu](n+1)
  • Tetrahydropteroyl-[gamma-glu]N
  • Tetrahydropteroyl-[gamma-glu]n+1
  • THF-L-Glutamic acid
  • THF-Polyglutamate
genes like me logo Genes that share compounds with GGH: view

Transcripts for GGH Gene

mRNA/cDNA for GGH Gene

1 REFSEQ mRNAs :
4 NCBI additional mRNA sequence :
8 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GGH

Alternative Splicing Database (ASD) splice patterns (SP) for GGH Gene

No ASD Table

Relevant External Links for GGH Gene

GeneLoc Exon Structure for
GGH

Expression for GGH Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GGH Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for GGH Gene

This gene is overexpressed in Liver (x9.7).

Protein differential expression in normal tissues from HIPED for GGH Gene

This gene is overexpressed in Urine (24.9) and Serum (10.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for GGH Gene



Protein tissue co-expression partners for GGH Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GGH

SOURCE GeneReport for Unigene cluster for GGH Gene:

Hs.78619

Evidence on tissue expression from TISSUES for GGH Gene

  • Liver(4.6)
  • Skin(4.5)
  • Nervous system(3.3)
  • Kidney(2.9)
  • Intestine(2.6)
  • Blood(2.5)
  • Pancreas(2.3)
  • Bone marrow(2.1)
genes like me logo Genes that share expression patterns with GGH: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for GGH Gene

Orthologs for GGH Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for GGH Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia GGH 30 31
  • 99.58 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia GGH 30 31
  • 86.13 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia GGH 30 31
  • 82.29 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Ggh 30 17 31
  • 77.74 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Ggh 30
  • 76.81 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia GGH 31
  • 64 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia GGH 31
  • 59 (a)
OneToOne
Chicken
(Gallus gallus)
Aves GGH 30 31
  • 63.79 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia GGH 31
  • 58 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia ggh 30
  • 65.61 (n)
Str.11987 30
Zebrafish
(Danio rerio)
Actinopterygii ggh 30 31
  • 60 (n)
OneToOne
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.5979 30
Fruit Fly
(Drosophila melanogaster)
Insecta l(3)72Dp 30 31
  • 49.53 (n)
OneToMany
l(3)72Dr 31
  • 26 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP006670 30
  • 48.62 (n)
Thale Cress
(Arabidopsis thaliana)
eudicotyledons GGH3 30
  • 48.2 (n)
Rice
(Oryza sativa)
Liliopsida Os05g0517500 30
  • 46.26 (n)
Species where no ortholog for GGH was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for GGH Gene

ENSEMBL:
Gene Tree for GGH (if available)
TreeFam:
Gene Tree for GGH (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GGH: view image

Paralogs for GGH Gene

No data available for Paralogs for GGH Gene

Variants for GGH Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GGH Gene

SNP ID Clinical significance and condition Chr 08 pos Variation AA Info Type
718627 Benign: not provided 63,030,174(-) T/C MISSENSE_VARIANT
788273 Benign: not provided 63,035,706(-) C/T SYNONYMOUS_VARIANT
rs11545077 - p.Ala31Thr
rs11545078 - p.Thr151Ile
rs1800909 - p.Cys6Arg

Additional dbSNP identifiers (rs#s) for GGH Gene

Structural Variations from Database of Genomic Variants (DGV) for GGH Gene

Variant ID Type Subtype PubMed ID
nsv1018879 CNV gain 25217958
nsv611448 CNV loss 21841781
nsv6227 CNV deletion 18451855

Variation tolerance for GGH Gene

Residual Variation Intolerance Score: 68.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.74; 89.37% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GGH Gene

Human Gene Mutation Database (HGMD)
GGH
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GGH

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GGH Gene

Disorders for GGH Gene

MalaCards: The human disease database

(3) MalaCards diseases for GGH Gene - From: DISEASES and Novoseek

Disorder Aliases PubMed IDs
tropical sprue
  • sprue - tropical
pulmonary neuroendocrine tumor
  • neuroendocrine neoplasm of lung
leukemia, acute lymphoblastic
  • all
- elite association - COSMIC cancer census association via MalaCards
Search GGH in MalaCards View complete list of genes associated with diseases

Additional Disease Information for GGH

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with GGH: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GGH Gene

Publications for GGH Gene

  1. Characterization of Human gamma-glutamyl hydrolase in solution demonstrates that the enzyme is a non-dissociating homodimer. (PMID: 16945597) Eisele LE … Ryan TJ (Biochimica et biophysica acta 2006) 3 4 23 26
  2. Structural organization of the human gamma-glutamyl hydrolase gene. (PMID: 10570974) Yin D … Yao R (Gene 1999) 2 3 4 23
  3. Human gamma-glutamyl hydrolase: cloning and characterization of the enzyme expressed in vitro. (PMID: 8816764) Yao R … Galivan J (Proceedings of the National Academy of Sciences of the United States of America 1996) 2 3 4 23
  4. Phase II trial of pemetrexed plus bevacizumab for second-line therapy of patients with advanced non-small-cell lung cancer: NCCTG and SWOG study N0426. (PMID: 19841321) Adjei AA … Zinner RG (Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2010) 3 23 41
  5. Outcomes of methotrexate therapy for psoriasis and relationship to genetic polymorphisms. (PMID: 19016697) Warren RB … Griffiths CE (The British journal of dermatology 2009) 3 23 41

Products for GGH Gene

  • Signalway ELISA kits for GGH

Sources for GGH Gene