InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: GCH1

Summary

InnateDB Protein

IDBP-600364.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

GCH1

Protein Name

GTP cyclohydrolase 1

Synonyms

DYT14; DYT5; DYT5a; GCH; GTP-CH-1; GTPCH1; HPABH4B;

Species

Homo sapiens

Ensembl Protein

ENSP00000445246

InnateDB Gene

IDBG-7150 (GCH1)

Protein Structure

UniProt Annotation

Function

Positively regulates nitric oxide synthesis in umbilical vein endothelial cells (HUVECs). May be involved in dopamine synthesis. May modify pain sensitivity and persistence. Isoform GCH-1 is the functional enzyme, the potential function of the enzymatically inactive isoforms remains unknown. {ECO:0000269PubMed:12176133, ECO:0000269PubMed:16338639, ECO:0000269PubMed:17057711, ECO:0000269PubMed:8068008, ECO:0000269PubMed:9445252}.

Subcellular Localization

Cytoplasm. Nucleus.

Disease Associations

GTP cyclohydrolase 1 deficiency (GCH1D) [MIM:233910]: A cause of malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency. It is also responsible for defective neurotransmission due to depletion of the neurotransmitters dopamine and serotonin. The principal symptoms include: psychomotor retardation, tonicity disorders, convulsions, drowsiness, irritability, abnormal movements, hyperthermia, hypersalivation, and difficulty swallowing. Some patients may present a phenotype of intermediate severity between severe hyperphenylalaninemia and mild dystonia type 5 (dystonia- parkinsonism with diurnal fluctuation). In this intermediate phenotype, there is marked motor delay, but no mental retardation and only minimal, if any, hyperphenylalaninemia. {ECO:0000269PubMed:7501255, ECO:0000269PubMed:9667588}. Note=The disease is caused by mutations affecting the gene represented in this entry.Dystonia 5 (DYT5) [MIM:128230]: A DOPA-responsive dystonia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DYT5 typically presents in childhood with walking problems due to dystonia of the lower limbs and worsening of the dystonia towards the evening. It is characterized by postural and motor disturbances showing marked diurnal fluctuation. Torsion of the trunk is unusual. Symptoms are alleviated after sleep and aggravated by fatigue and exercise. There is a favorable response to L-DOPA without side effects. {ECO:0000269PubMed:10076897, ECO:0000269PubMed:10208576, ECO:0000269PubMed:10582612, ECO:0000269PubMed:10825351, ECO:0000269PubMed:10987649, ECO:0000269PubMed:11113234, ECO:0000269PubMed:12391354, ECO:0000269PubMed:17101830, ECO:0000269PubMed:7501255, ECO:0000269PubMed:7874165, ECO:0000269PubMed:8852666, ECO:0000269PubMed:8957022, ECO:0000269PubMed:9120469, ECO:0000269PubMed:9328244, ECO:0000269PubMed:9778264}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

In epidermis, expressed predominantly in basal undifferentiated keratinocytes and in some but not all melanocytes (at protein level). {ECO:0000269PubMed:16778797}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 35 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	35 [view]
Protein-Protein	34 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003934	GTP cyclohydrolase I activity
GO:0005515	protein binding
GO:0005525	GTP binding
GO:0008270	zinc ion binding
GO:0042803	protein homodimerization activity

Biological Process

GO:0006184	GTP catabolic process
GO:0006729	tetrahydrobiopterin biosynthetic process
GO:0006809	nitric oxide biosynthetic process
GO:0008152	metabolic process
GO:0008217	regulation of blood pressure
GO:0032496	response to lipopolysaccharide
GO:0034341	response to interferon-gamma
GO:0034612	response to tumor necrosis factor
GO:0035998	7,8-dihydroneopterin 3'-triphosphate biosynthetic process
GO:0042416	dopamine biosynthetic process
GO:0042559	pteridine-containing compound biosynthetic process
GO:0044281	small molecule metabolic process
GO:0046209	nitric oxide metabolic process
GO:0046654	tetrahydrofolate biosynthetic process
GO:0048265	response to pain
GO:0050884	neuromuscular process controlling posture
GO:0050999	regulation of nitric-oxide synthase activity
GO:0051000	positive regulation of nitric-oxide synthase activity
GO:0051260	protein homooligomerization