Gch1 GTP cyclohydrolase 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Gch1provided by MGI
Official Full Name: GTP cyclohydrolase 1provided by MGI
Primary source: MGI:MGI:95675
See related: Ensembl:ENSMUSG00000037580 AllianceGenome:MGI:95675
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Gch; GTPCH; GTP-CH; GTP-CH-I
Summary: Enables GTP cyclohydrolase I activity. Involved in positive regulation of heart rate. Acts upstream of or within regulation of lung blood pressure. Predicted to be located in cytoplasmic vesicle; cytosol; and nucleus. Predicted to be part of protein-containing complex. Predicted to be active in cytoplasm. Is expressed in several structures, including alimentary system; genitourinary system; nervous system; respiratory system; and sensory organ. Used to study BH4-deficient hyperphenylalaninemia B. Human ortholog(s) of this gene implicated in BH4-deficient hyperphenylalaninemia B; bipolar disorder; dystonia; and dystonia 5. Orthologous to human GCH1 (GTP cyclohydrolase 1). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in liver adult (RPKM 53.7), adrenal adult (RPKM 35.5) and 10 other tissues See more
Orthologs: human all
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Genomic context

Location:: 14 C1; 14 24.6 cM

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	14	NC_000080.7 (47391352..47426870, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	14	NC_000080.6 (47153895..47189413, complement)

Chromosome 14 - NC_000080.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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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?

SPY1 inhibits neuronal ferroptosis in amyotrophic lateral sclerosis by reducing lipid peroxidation through regulation of GCH1 and TFR1.
Title: SPY1 inhibits neuronal ferroptosis in amyotrophic lateral sclerosis by reducing lipid peroxidation through regulation of GCH1 and TFR1.
Nitrosative stress induced by homocysteine thiolactone drives vascular cognitive impairments via GTP cyclohydrolase 1 S-nitrosylation in vivo.
Title: Nitrosative stress induced by homocysteine thiolactone drives vascular cognitive impairments via GTP cyclohydrolase 1 S-nitrosylation in vivo.
GCH1-regulated miRNAs are potential targets for microglial activation in neuropathic pain.
Title: GCH1-regulated miRNAs are potential targets for microglial activation in neuropathic pain.
Endothelial GTPCH (GTP Cyclohydrolase 1) and Tetrahydrobiopterin Regulate Gestational Blood Pressure, Uteroplacental Remodeling, and Fetal Growth.
Title: Endothelial GTPCH (GTP Cyclohydrolase 1) and Tetrahydrobiopterin Regulate Gestational Blood Pressure, Uteroplacental Remodeling, and Fetal Growth.
CTRP13 preserves endothelial function in diabetic mice by regulating GCH1/BH4 axis-dependent eNOS coupling, suggesting the therapeutic potential of CTRP13 against diabetic vasculopathy.
Title: CTRP13 Preserves Endothelial Function by Targeting GTP Cyclohydrolase 1 in Diabetes.
GCH1 knockout reduced, and its overexpression increased the tetrahydrobiopterin-mediated itching in mice.
Title: Mast cell tetrahydrobiopterin contributes to itch in mice.
The GTPCH p.Leu117Arg missense mutation is deleterious and could cause tetrahydrobiopterin, phenylalanine and neurotransmitter metabolic disturbances and infancy-onset motor dysfunctions recessively. This is the first GTPCH deficiency mouse model which could be live-born and exhibits significant motor impairments.
Title: A novel GTPCH deficiency mouse model exhibiting tetrahydrobiopterin-related metabolic disturbance and infancy-onset motor impairments.
Suggest key roles for endothelial cell and leucocyte Gch1 and BH4 in the progression of atherosclerosis.
Title: Roles for endothelial cell and macrophage Gch1 and tetrahydrobiopterin in atherosclerosis progression.
GCH1-induced cardioprotection against DCM mainly involves the tetrahydrobiopterin/nNOS/sarcoplasmic reticulum Ca2+ handling proteins signaling pathway and depression of p38 Mitogen-Activated Protein Kinases in Diabetes Mellitus, Type 1.
Title: Cardiomyocyte GTP Cyclohydrolase 1 Protects the Heart Against Diabetic Cardiomyopathy.
Cardiomyocyte-specific overexpression of GTP cyclohydrolase I (mGCH) increases BH4 several-fold in the heart.
Title: Increasing tetrahydrobiopterin in cardiomyocytes adversely affects cardiac redox state and mitochondrial function independently of changes in NO production.

Submit: New GeneRIF Correction See all GeneRIFs (37)

Variation

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Alleles

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

Endonuclease-mediated (4) 1 citation
Targeted (3) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Gch1 (e-PCR), detects polymorphism
- UniSTS:507410

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables GTP binding	IBA Inferred from Biological aspect of Ancestor more info
enables GTP binding	ISO Inferred from Sequence Orthology more info
enables GTP cyclohydrolase I activity	IBA Inferred from Biological aspect of Ancestor more info
enables GTP cyclohydrolase I activity	IDA Inferred from Direct Assay more info	PubMed
enables GTP cyclohydrolase I activity	ISO Inferred from Sequence Orthology more info
enables GTP-dependent protein binding	ISO Inferred from Sequence Orthology more info
enables GTPase activity	ISO Inferred from Sequence Orthology more info
enables calcium ion binding	ISO Inferred from Sequence Orthology more info
enables catalytic activity	IEA Inferred from Electronic Annotation more info
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables mitogen-activated protein kinase binding	ISO Inferred from Sequence Orthology more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info
enables zinc ion binding	IBA Inferred from Biological aspect of Ancestor more info
enables zinc ion binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in cellular response to lipopolysaccharide	TAS Traceable Author Statement more info	PubMed
involved_in dihydrobiopterin metabolic process	ISO Inferred from Sequence Orthology more info
involved_in dopamine biosynthetic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within metabolic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of blood pressure	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cardiac muscle cell apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cellular senescence	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within neuromuscular process controlling posture	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of heart rate	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of neuron apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of nitric-oxide synthase activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of telomere maintenance via telomerase	ISO Inferred from Sequence Orthology more info
involved_in protein-containing complex assembly	ISO Inferred from Sequence Orthology more info
involved_in pteridine-containing compound biosynthetic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of blood pressure	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of blood pressure	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of lung blood pressure	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of removal of superoxide radicals	ISO Inferred from Sequence Orthology more info
involved_in regulation of serotonin biosynthetic process	NAS Non-traceable Author Statement more info	PubMed
involved_in response to pain	ISO Inferred from Sequence Orthology more info
involved_in response to tumor necrosis factor	ISO Inferred from Sequence Orthology more info
involved_in response to type II interferon	ISO Inferred from Sequence Orthology more info
involved_in tetrahydrobiopterin biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within tetrahydrobiopterin biosynthetic process	IC Inferred by Curator more info	PubMed
involved_in tetrahydrobiopterin biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in tetrahydrofolate biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in vasodilation	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoplasmic vesicle	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in mitochondrion	ISO Inferred from Sequence Orthology more info
located_in nuclear membrane	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: GTP cyclohydrolase 1

Names: GTP cyclohydrolase I

NP_032128.1

EC 3.5.4.16

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_008102.4 → NP_032128.1 GTP cyclohydrolase 1

See identical proteins and their annotated locations for NP_032128.1

Status: VALIDATED

Source sequence(s)

AC154589, AC159006

Consensus CDS

CCDS26984.1

UniProtKB/Swiss-Prot

Q05915

UniProtKB/TrEMBL

Q3U7P6, Q3UC70

Related

ENSMUSP00000087405.7, ENSMUST00000089959.7

Conserved Domains (1) summary

cd00642
Location:57 → 241

GTP_cyclohydro1; GTP cyclohydrolase I (GTP-CH-I) catalyzes the conversion of GTP into dihydroneopterin triphosphate. The enzyme product is the precursor of tetrahydrofolate in eubacteria, fungi, and plants and of the folate analogs in methanogenic bacteria. In ...