Ggt1 gamma-glutamyltransferase 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Ggt1provided by MGI
Official Full Name: gamma-glutamyltransferase 1provided by MGI
Primary source: MGI:MGI:95706
See related: Ensembl:ENSMUSG00000006345 AllianceGenome:MGI:95706
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: GGT; dwg; Ggtp; CD224; GGT 1; GGT-1
Summary: This gene encodes gamma-glutamyl transpeptidase, a plasmamembrane-associated enzyme that cleaves the peptide bond between gamma-glutamyl and cysteinyl glycine moieties of glutathione. The encoded protein is autocatalytically processed to generate an enzymatically active heterodimer comprised of heavy and light chains. Mice lacking the encoded protein grow slowly, develop cataracts and have elevated levels of glutathione in plasma and urine. Transgenic overexpression of the encoded protein in mice enhances osteoclastic bone resorption. The mutant alleles termed 'Dwarf grey' and 'Dwarf grey Bayer' in mice are associated with deletions in this gene. A gamma-glutamyl transpeptidase paralog is located adjacent to this gene. Alternative splicing results in multiple transcript variants. Additional transcripts using alternate promoters and differing in 5' UTRs have been described. [provided by RefSeq, Apr 2015]
Expression: Biased expression in kidney adult (RPKM 265.8), duodenum adult (RPKM 234.7) and 4 other tissues See more
Orthologs: human all
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Genomic context

Location:: 10 C1; 10 38.55 cM

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	10	NC_000076.7 (75396910..75422027)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	10	NC_000076.6 (75561076..75586193)

Chromosome 10 - NC_000076.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

GGsTop is a newly-discovered gamma-glutamyl transpeptidase (GGT) inhibitor...GGsTop treated Oral mucositis (OM) quickly and safely. GGsTop is highly valuable for use as a treatment for OM
Title: Therapeutic Effect of GGsTop, Selective Gamma-glutamyl Transpeptidase Inhibitor, on a Mouse Model of 5-Fluorouracil-induced Oral Mucositis.
These findings elucidate a novel mechanism of inflammation-associated osteoclastogenesis, which involves TLR4 recognition of gamma-glutamyltranspeptidase and subsequent activation of MyD88-dependent signaling.
Title: γ-Glutamyltranspeptidase is an endogenous activator of Toll-like receptor 4-mediated osteoclastogenesis.
the present study developed a liver-specific GGT-overexpressing mice model and found that GGT elevation in short term had no effects on glucose metabolism but could increase insulin sensitivity through enhancing the activity of insulin signaling pathway.
Title: Liver-Specific Overexpression of Gamma-Glutamyltransferase Ameliorates Insulin Sensitivity of Male C57BL/6 Mice.
Statins can significantly decrease the expression of GGT in aortic atherosclerotic plaques of ApoE-knockout mice.
Title: Effect of atorvastatin on the expression of gamma-glutamyl transferase in aortic atherosclerotic plaques of apolipoprotein E-knockout mice.
Gamma-glutamyltransferase levels are an independent predictor of worsening kidney function and mortality in acute heart failure patients.
Title: Cardio-reno-hepatic interactions in acute heart failure: the role of γ-glutamyl transferase.
Disruption of the Mrds1/Ofcc1 gene elicits asymptomatic hyper-gamma-glutamyl-transpeptidasemia in mice.
Title: Ablation of Mrds1/Ofcc1 induces hyper-γ-glutamyl transpeptidasemia without abnormal head development and schizophrenia-relevant behaviors in mice.
Mutations in the Ggt1 gene are responsible for the phenotypes of dwg/dwg and dwg(Bayer)/dwg(Bayer) mice.
Title: Characterization of the dwg mutations: dwg and dwg(Bayer) are new mutant alleles of the Ggt1 gene.
GGT stimulates RANKL expression
Title: Gamma-glutamyltranspeptidase stimulates receptor activator of nuclear factor-kappaB ligand expression independent of its enzymatic activity and serves as a pathological bone-resorbing factor.
Gamma-glutamyl transferase deficiency results in lung oxidant stress in normoxia
Title: Gamma-glutamyl transferase deficiency results in lung oxidant stress in normoxia.
GGT is implicated as being involved in diseases characterized by accelerated osteoclast development and bone destruction.
Title: Overexpression of gamma-glutamyltransferase in transgenic mice accelerates bone resorption and causes osteoporosis.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Phenotypes

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Associated conditions

Description	Tests
dwarf grey GeneReviews: Not available

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (1) 1 citation
Endonuclease-mediated (6) 1 citation
Spontaneous (1)
Targeted (3) 1 citation

General gene information

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Markers

U30509 (e-PCR)
- UniSTS:125717

AI746379 (e-PCR)
- UniSTS:180054

Ggt1 (e-PCR), detects polymorphism
- UniSTS:265710

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables aminoacyltransferase activity	ISO Inferred from Sequence Orthology more info
enables glutathione hydrolase activity	IBA Inferred from Biological aspect of Ancestor more info
enables glutathione hydrolase activity	ISO Inferred from Sequence Orthology more info
enables glutathione hydrolase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables leukotriene C4 gamma-glutamyl transferase activity	IEA Inferred from Electronic Annotation more info
enables leukotriene-C(4) hydrolase	IEA Inferred from Electronic Annotation more info
enables leukotriene-C(4) hydrolase	ISO Inferred from Sequence Orthology more info
enables peptidyltransferase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in cellular response to oxidative stress	IEA Inferred from Electronic Annotation more info
involved_in cysteine biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in glutamate metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in glutathione biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in glutathione catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in glutathione catabolic process	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within glutathione metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in hepatoblast differentiation	IEA Inferred from Electronic Annotation more info
involved_in hepatocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in liver regeneration	IEA Inferred from Electronic Annotation more info
involved_in peptide modification	IBA Inferred from Biological aspect of Ancestor more info
involved_in peptide modification	IEA Inferred from Electronic Annotation more info
involved_in peptide modification	ISO Inferred from Sequence Orthology more info
involved_in regulation of immune system process	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of immune system process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to alcohol	IEA Inferred from Electronic Annotation more info
involved_in response to estradiol	IEA Inferred from Electronic Annotation more info
involved_in response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in response to tumor necrosis factor	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within spermatogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in zymogen activation	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
located_in extracellular space	IEA Inferred from Electronic Annotation more info
located_in extracellular space	ISO Inferred from Sequence Orthology more info
located_in perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info	PubMed
located_in vesicle	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: glutathione hydrolase 1 proenzyme

Names: gamma-glutamyltranspeptidase 1; leukotriene-C4 hydrolase

NP_001292921.1

EC 2.3.2.2

EC 3.4.19.13

EC 3.4.19.14

NP_001366466.1

EC 2.3.2.2

EC 3.4.19.13

EC 3.4.19.14

NP_001366467.1

EC 2.3.2.2

EC 3.4.19.13

EC 3.4.19.14

NP_001366468.1

EC 2.3.2.2

EC 3.4.19.13

EC 3.4.19.14

NP_001366469.1

EC 2.3.2.2

EC 3.4.19.13

EC 3.4.19.14

NP_001366470.1

EC 2.3.2.2

EC 3.4.19.13

EC 3.4.19.14

NP_032142.1

EC 2.3.2.2

EC 3.4.19.13

EC 3.4.19.14

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001305992.2 → NP_001292921.1 glutathione hydrolase 1 proenzyme precursor

See identical proteins and their annotated locations for NP_001292921.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and represents use of an alternate promoter, compared to variant 1. All ten variants encode the same protein.

Source sequence(s)

AC087540

Consensus CDS

CCDS23927.1

UniProtKB/Swiss-Prot

Q60928

UniProtKB/TrEMBL

Q4FK56

Related

ENSMUSP00000121312.2, ENSMUST00000134503.8

Conserved Domains (1) summary

pfam01019
Location:55 → 563

G_glu_transpept; Gamma-glutamyltranspeptidase
NM_001379537.1 → NP_001366466.1 glutathione hydrolase 1 proenzyme precursor

Status: REVIEWED

Source sequence(s)

AC087540

UniProtKB/Swiss-Prot

Q60928

UniProtKB/TrEMBL

Q4FK56

Conserved Domains (1) summary

pfam01019
Location:55 → 563

G_glu_transpept; Gamma-glutamyltranspeptidase
NM_001379538.1 → NP_001366467.1 glutathione hydrolase 1 proenzyme precursor

Status: REVIEWED

Source sequence(s)

AC087540

UniProtKB/Swiss-Prot

Q60928

UniProtKB/TrEMBL

Q4FK56

Conserved Domains (1) summary

pfam01019
Location:55 → 563

G_glu_transpept; Gamma-glutamyltranspeptidase
NM_001379539.1 → NP_001366468.1 glutathione hydrolase 1 proenzyme precursor

Status: REVIEWED

Source sequence(s)

AC087540

UniProtKB/Swiss-Prot

Q60928

UniProtKB/TrEMBL

Q4FK56

Conserved Domains (1) summary

pfam01019
Location:55 → 563

G_glu_transpept; Gamma-glutamyltranspeptidase
NM_001379540.1 → NP_001366469.1 glutathione hydrolase 1 proenzyme precursor

Status: REVIEWED

Source sequence(s)

AC087540

UniProtKB/Swiss-Prot

Q60928

UniProtKB/TrEMBL

Q4FK56

Conserved Domains (1) summary

pfam01019
Location:55 → 563

G_glu_transpept; Gamma-glutamyltranspeptidase
NM_001379541.1 → NP_001366470.1 glutathione hydrolase 1 proenzyme precursor

Status: REVIEWED

Source sequence(s)

AC087540

UniProtKB/Swiss-Prot

Q60928

UniProtKB/TrEMBL

Q4FK56

Conserved Domains (1) summary

pfam01019
Location:55 → 563

G_glu_transpept; Gamma-glutamyltranspeptidase
NM_001428490.1 → NP_001415419.1 glutathione hydrolase 1 proenzyme precursor

Status: REVIEWED

Source sequence(s)

AC087540

UniProtKB/Swiss-Prot

Q60928

UniProtKB/TrEMBL

Q4FK56
NM_001428491.1 → NP_001415420.1 glutathione hydrolase 1 proenzyme precursor

Status: REVIEWED

Source sequence(s)

AC087540

UniProtKB/Swiss-Prot

Q60928

UniProtKB/TrEMBL

Q4FK56
NM_001428492.1 → NP_001415421.1 glutathione hydrolase 1 proenzyme precursor

Status: REVIEWED

Source sequence(s)

AC087540

UniProtKB/Swiss-Prot

Q60928

UniProtKB/TrEMBL

Q4FK56
NM_008116.4 → NP_032142.1 glutathione hydrolase 1 proenzyme precursor

See identical proteins and their annotated locations for NP_032142.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes isoform 1. All ten variants encode the same protein.

Source sequence(s)

AC087540

Consensus CDS

CCDS23927.1

UniProtKB/Swiss-Prot

Q60928

UniProtKB/TrEMBL

Q4FK56

Related

ENSMUSP00000006508.4, ENSMUST00000006508.10

Conserved Domains (1) summary

pfam01019
Location:55 → 563

G_glu_transpept; Gamma-glutamyltranspeptidase