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HMDB Protein ID HMDBP00938
Secondary Accession Numbers
  • 6226
  • HMDBP05047
Name GTP cyclohydrolase 1
  1. GTP cyclohydrolase I
  2. GTP-CH-I
Gene Name GCH1
Protein Type Unknown
Biological Properties
General Function Involved in GTP cyclohydrolase I activity
Specific 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.
  • 7,8-dihydroneopterin triphosphate biosynthesis
  • Dopa-responsive dystonia
  • Folate biosynthesis
  • Hyperphenylalaniemia due to guanosine triphosphate cyclohydrolase deficiency
  • Hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency (ptps)
  • Hyperphenylalaninemia due to dhpr-deficiency
  • Pterine Biosynthesis
  • Segawa syndrome
  • Sepiapterin reductase deficiency
Guanosine triphosphate + Water → Formic acid + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate details
Guanosine triphosphate + Water → Formamidopyrimidine nucleoside triphosphate details
Dihydroneopterin triphosphate + Water → 2,5-Diamino-6-(5'-triphosphoryl-3',4'-trihydroxy-2'-oxopentyl)-amino-4-oxopyrimidine details
Formamidopyrimidine nucleoside triphosphate + Water → 2,5-Diaminopyrimidine nucleoside triphosphate + Formic acid details
2,5-Diaminopyrimidine nucleoside triphosphate → 2,5-Diamino-6-(5'-triphosphoryl-3',4'-trihydroxy-2'-oxopentyl)-amino-4-oxopyrimidine details
GO Classification
Biological Process
response to pain
GTP catabolic process
dopamine biosynthetic process
response to lipopolysaccharide
negative regulation of blood pressure
induction of apoptosis
response to interferon-gamma
response to tumor necrosis factor
7,8-dihydroneopterin 3'-triphosphate biosynthetic process
neuromuscular process controlling posture
positive regulation of nitric-oxide synthase activity
protein heterooligomerization
regulation of lung blood pressure
protein homooligomerization
regulation of blood pressure
tetrahydrobiopterin biosynthetic process
nitric oxide biosynthetic process
tetrahydrofolate biosynthetic process
Cellular Component
nuclear membrane
cytoplasmic vesicle
protein complex
cell part
intracellular part
catalytic activity
hydrolase activity
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
cyclohydrolase activity
gtp cyclohydrolase activity
gtp cyclohydrolase i activity
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines
Molecular Function
zinc ion binding
GTP cyclohydrolase I activity
calcium ion binding
GTP binding
coenzyme binding
metabolic process
cellular aromatic compound metabolic process
folic acid and derivative metabolic process
tetrahydrofolate biosynthetic process
cellular metabolic process
folic acid and derivative biosynthetic process
Cellular Location
  1. Nucleus
  2. Cytoplasm
Gene Properties
Chromosome Location 14
Locus 14q22.1-q22.2
Gene Sequence
>753 bp
Protein Properties
Number of Residues 250
Molecular Weight 27902.855
Theoretical pI 8.556
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>GTP cyclohydrolase 1
GenBank ID Protein 19343964
UniProtKB/Swiss-Prot ID P30793
UniProtKB/Swiss-Prot Entry Name GCH1_HUMAN
GenBank Gene ID BC025415
GeneCard ID GCH1
GenAtlas ID GCH1
General References
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  7. Golderer G, Werner ER, Heufler C, Strohmaier W, Grobner P, Werner-Felmayer G: GTP cyclohydrolase I mRNA: novel splice variants in the slime mould Physarum polycephalum and in human monocytes (THP-1) indicate conservation of mRNA processing. Biochem J. 2001 Apr 15;355(Pt 2):499-507. [PubMed:11284739 ]
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  13. Schoedon G, Redweik U, Curtius HC: Purification of GTP cyclohydrolase I from human liver and production of specific monoclonal antibodies. Eur J Biochem. 1989 Jan 2;178(3):627-34. [PubMed:2463916 ]
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  16. Cai S, Alp NJ, McDonald D, Smith I, Kay J, Canevari L, Heales S, Channon KM: GTP cyclohydrolase I gene transfer augments intracellular tetrahydrobiopterin in human endothelial cells: effects on nitric oxide synthase activity, protein levels and dimerisation. Cardiovasc Res. 2002 Sep;55(4):838-49. [PubMed:12176133 ]
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  19. Shiraishi H, Kato T, Atsuta K, Sumi-Ichinose C, Ohtsuki M, Itoh M, Hishida H, Tada S, Udagawa Y, Nagatsu T, Hagino Y, Ichinose H, Nomura T: cGMP inhibits GTP cyclohydrolase I activity and biosynthesis of tetrahydrobiopterin in human umbilical vein endothelial cells. J Pharmacol Sci. 2003 Nov;93(3):265-71. [PubMed:14646243 ]
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  22. Huang A, Zhang YY, Chen K, Hatakeyama K, Keaney JF Jr: Cytokine-stimulated GTP cyclohydrolase I expression in endothelial cells requires coordinated activation of nuclear factor-kappaB and Stat1/Stat3. Circ Res. 2005 Feb 4;96(2):164-71. Epub 2004 Dec 16. [PubMed:15604419 ]
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  31. Ichinose H, Ohye T, Segawa M, Nomura Y, Endo K, Tanaka H, Tsuji S, Fujita K, Nagatsu T: GTP cyclohydrolase I gene in hereditary progressive dystonia with marked diurnal fluctuation. Neurosci Lett. 1995 Aug 18;196(1-2):5-8. [PubMed:7501255 ]
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