Gch1 GTP cyclohydrolase 1 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Gch1provided by RGD
Official Full Name: GTP cyclohydrolase 1provided by RGD
Primary source: RGD:61992
See related: EnsemblRapid:ENSRNOG00000011039 AllianceGenome:RGD:61992
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Gch; GTPCH; GTPCH-1
Summary: Enables several functions, including GTP binding activity; GTP cyclohydrolase I activity; and metal ion binding activity. Involved in several processes, including dihydrobiopterin metabolic process; negative regulation of cellular senescence; and regulation of apoptotic process. Located in mitochondrion and nucleus. Part of intracellular protein-containing complex. Used to study Parkinsonism; cerebral infarction; hypertension; myocardial infarction; and transient cerebral ischemia. Biomarker of several diseases, including artery disease (multiple); liver disease (multiple); middle cerebral artery infarction; pulmonary fibrosis; and sciatic neuropathy. Human ortholog(s) of this gene implicated in several diseases, including BH4-deficient hyperphenylalaninemia B; diabetic angiopathy; movement disease (multiple); sickle cell anemia; and type 2 diabetes mellitus. Orthologous to human GCH1 (GTP cyclohydrolase 1). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Biased expression in Liver (RPKM 291.2), Spleen (RPKM 179.1) and 4 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 15p14

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	15	NC_086033.1 (22884006..22917412, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	15	NC_051350.1 (20404267..20437727, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	15	NC_005114.4 (23935011..23968971, complement)

Chromosome 15 - NC_086033.1 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: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Ninety-six-hour starved peripheral blood mononuclear cell supernatant inhibited LA7 breast cancer stem cells induced tumor via reduction in angiogenesis and alternations in Gch1 and Spr expressions.
Title: Ninety-six-hour starved peripheral blood mononuclear cell supernatant inhibited LA7 breast cancer stem cells induced tumor via reduction in angiogenesis and alternations in Gch1 and Spr expressions.
MiR-124 inhibits spinal neuronal apoptosis through binding to GCH1.
Title: MiR-124 inhibits spinal neuronal apoptosis through binding to GCH1.
Reduced GCH1 levels in hyperoxia were due, in part, to increased degradation by the ubiquitin-proteasome system
Title: Caffeine ameliorates hyperoxia-induced lung injury by protecting GCH1 function in neonatal rat pups.
Pretreatment with a Gch1 antagonist produced a substantial dose related inhibition of pain behaviors.
Title: Evidence of a role for GTP cyclohydrolase-1 in visceral pain.
GCH1 levels of nerve cells in spinal dorsal horn was elevated after chronic sciatic nerve injury.
Title: Changes of GTP cyclohydrolase I and neuronal apoptosis in rat spinal dorsal cord induced by sciatic nerve injury.
GCH1 interacts with proteins in an organ dependant manner and EIF3I might be a general regulator of GCH1.
Title: The protein partners of GTP cyclohydrolase I in rat organs.
The N-terminal peptide of mammalian GTP cyclohydrolase I is an autoinhibitory control element and contributes to binding the allosteric regulatory protein GFRP.
Title: The N-terminal peptide of mammalian GTP cyclohydrolase I is an autoinhibitory control element and contributes to binding the allosteric regulatory protein GFRP.
GCH-1 activity is regulated either positively by phosphorylation S51, S72, T85, T91, T103, and S130, or negatively at T231.
Title: Identification and functional characterization of phosphorylation sites on GTP cyclohydrolase I.
Sp1 and Sp3 are found associated with native proximal promoter of cyclic AMP (cAMP)-dependent GTP cyclohydrolase I in PC12 cells but are not recruited to the promoter during cAMP-dependent transcription.
Title: Specificity proteins Sp1 and Sp3 interact with the rat GTP cyclohydrolase I proximal promoter to regulate transcription.
Increased blood flow causes vascular upregulation of eNOS and GTPCH I. Induction of GTPCH I increases BH4 production, thereby optimizing generation of NO by eNOS and adaptive, vasorelaxant response required in sustaining increased blood flow.
Title: Increased blood flow causes coordinated upregulation of arterial eNOS and biosynthesis of tetrahydrobiopterin.

Submit: New GeneRIF Correction See all GeneRIFs (19)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables GTP binding	IBA Inferred from Biological aspect of Ancestor more info
enables GTP binding	IDA Inferred from Direct Assay more info	PubMed
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	IEA Inferred from Electronic Annotation more info
NOT enables GTP cyclohydrolase I activity	ISO Inferred from Sequence Orthology more info
enables GTP cyclohydrolase I activity	ISO Inferred from Sequence Orthology more info
enables GTP-dependent protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables GTPase activity	ISO Inferred from Sequence Orthology more info
enables calcium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables mitogen-activated protein kinase binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein-containing complex binding	IDA Inferred from Direct Assay more info	PubMed
enables protein-containing complex binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	IBA Inferred from Biological aspect of Ancestor more info
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in dihydrobiopterin metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in dopamine biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of blood pressure	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cardiac muscle cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cellular senescence	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within neuromuscular process controlling posture	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of heart rate	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of nitric-oxide synthase activity	IEA Inferred from Electronic Annotation 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	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein-containing complex assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in pteridine-containing compound biosynthetic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of blood pressure	ISO Inferred from Sequence Orthology more info
involved_in regulation of blood pressure	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of lung blood pressure	ISO Inferred from Sequence Orthology more info
involved_in regulation of removal of superoxide radicals	ISO Inferred from Sequence Orthology more info
NOT involved_in response to lipopolysaccharide	ISO Inferred from Sequence Orthology more info
involved_in response to lipopolysaccharide	ISO Inferred from Sequence Orthology more info
involved_in response to pain	IDA Inferred from Direct Assay more info	PubMed
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
involved_in tetrahydrobiopterin biosynthetic process	IEA Inferred from Electronic Annotation more info
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	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IEA Inferred from Electronic Annotation 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
part_of intracellular protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear membrane	IEA Inferred from Electronic Annotation more info
located_in nuclear membrane	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
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 cyclohydrase I; GTP cyclohydrolase I; GTP-CH-I

NP_077332.1

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_024356.1 → NP_077332.1 GTP cyclohydrolase 1 precursor

See identical proteins and their annotated locations for NP_077332.1

Status: PROVISIONAL

Source sequence(s)

M58364

UniProtKB/Swiss-Prot

P22288

UniProtKB/TrEMBL

A0A8I5ZYD9, A6KE40

Related

ENSRNOP00000014821.5, ENSRNOT00000014821.9

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 ...