GCH1
entrez
2643
canonical
uniprot
P30793
canonical
ensembl
ENSG00000131979
resolver
ensp
ENSP00000378890
resolver
ensp
ENSP00000419045
resolver
ensp
ENSP00000444011
resolver
ensp
ENSP00000445246
resolver
ensp
ENSP00000779461
resolver
genesymbol
GCH1
resolver
genesymbol_syn
DYT5
resolver
genesymbol_syn
GCH
resolver
hgnc
HGNC:4193
resolver
uniprot
Q6FHY7
resolver
uniprot
Q8IZH9
resolver
uniprot
Q9Y4I8
resolver
uniprot_entry
GCH1_HUMAN
resolver
uniprot_entry
Q8IZH9_HUMAN
resolver
uniprot_sec
Q6FHY7
resolver
uniprot_sec
Q9Y4I8
resolver
activity_regulation
ACTIVITY REGULATION: GTP shows a positive allosteric effect, and tetrahydrobiopterin inhibits the enzyme activity. Zinc is required for catalytic activity. Inhibited by Mg(2+). {ECO:0000269|PubMed:14717702, ECO:0000269|PubMed:16778797, ECO:0000269|PubMed:3753653}.
uniprot
proteins
amino_acid_sequence
MEKGPVRAPAEKPRGARCSNGFPERDPPRPGPSRPAEKPPRPEAKSAQPADGWKGERPRSEEDNELNLPNLAAAYSSILSSLGENPQRQGLLKTPWRAASAMQFFTKGYQETISDVLNDAIFDEDHDEMVIVKDIDMFSMCEHHLVPFVGKVHIGYLPNKQVLGLSKLARIVEIYSRRLQVQERLTKQIAVAITEALRPAGVGVVVEATHMCMVMRGVQKMNSKTVTSTMLGVFREDPKTREEFLTLIRS
uniprot
proteins
disease_involvement
DISEASE: Hyperphenylalaninemia, BH4-deficient, B (HPABH4B) [MIM:233910]: A disease characterized by malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency, and 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. In this intermediate phenotype, there is marked motor delay, but no intellectual disability and only minimal, if any, hyperphenylalaninemia. {ECO:0000269|PubMed:7501255, ECO:0000269|PubMed:9667588}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Dystonia, dopa-responsive (DRD) [MIM:128230]: A form of dystonia that responds to L-DOPA treatment without side effects. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DRD 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. {ECO:0000269|PubMed:10076897, ECO:0000269|PubMed:10208576, ECO:0000269|PubMed:10582612, ECO:0000269|PubMed:10825351, ECO:0000269|PubMed:10987649, ECO:0000269|PubMed:11113234, ECO:0000269|PubMed:12391354, ECO:0000269|PubMed:17101830, ECO:0000269|PubMed:7501255, ECO:0000269|PubMed:7874165, ECO:0000269|PubMed:8852666, ECO:0000269|PubMed:8957022, ECO:0000269|PubMed:9120469, ECO:0000269|PubMed:9328244, ECO:0000269|PubMed:9778264}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.5.4.16
uniprot
proteins
function
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:0000269|PubMed:12176133, ECO:0000269|PubMed:16338639, ECO:0000269|PubMed:17057711, ECO:0000269|PubMed:8068008, ECO:0000269|PubMed:9445252}.
uniprot
proteins
mass_dalton
27903
uniprot
proteins
pathway_participation
PATHWAY: Cofactor biosynthesis; 7,8-dihydroneopterin triphosphate biosynthesis; 7,8-dihydroneopterin triphosphate from GTP: step 1/1. {ECO:0000305|PubMed:16778797, ECO:0000305|PubMed:2463916, ECO:0000305|PubMed:3753653}.
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by casein kinase II at Ser-81 in HAECs during oscillatory shear stress; phosphorylation at Ser-81 results in increased enzyme activity. {ECO:0000269|PubMed:17704208}.
uniprot
proteins
protein_family
GTP cyclohydrolase I family
uniprot
proteins
pubmed
10076897
uniprot
proteins
pubmed
10208576
uniprot
proteins
pubmed
10582612
uniprot
proteins
pubmed
10825351
uniprot
proteins
pubmed
10987649
uniprot
proteins
pubmed
11087827
uniprot
proteins
pubmed
11113234
uniprot
proteins
pubmed
11284739
uniprot
proteins
pubmed
12002810
uniprot
proteins
pubmed
12176133
uniprot
proteins
pubmed
12391354
uniprot
proteins
pubmed
12607127
uniprot
proteins
pubmed
14646243
uniprot
proteins
pubmed
14717702
uniprot
proteins
pubmed
1482676
uniprot
proteins
pubmed
1520321
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15604419
uniprot
proteins
pubmed
15649650
uniprot
proteins
pubmed
16338639
uniprot
proteins
pubmed
16696853
uniprot
proteins
pubmed
16778797
uniprot
proteins
pubmed
16848765
uniprot
proteins
pubmed
17057711
uniprot
proteins
pubmed
17101830
uniprot
proteins
pubmed
17704208
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
23762320
uniprot
proteins
pubmed
2463916
uniprot
proteins
pubmed
2500984
uniprot
proteins
pubmed
3753653
uniprot
proteins
pubmed
7501255
uniprot
proteins
pubmed
7678411
uniprot
proteins
pubmed
7730309
uniprot
proteins
pubmed
7874165
uniprot
proteins
pubmed
8068008
uniprot
proteins
pubmed
8666288
uniprot
proteins
pubmed
8695054
uniprot
proteins
pubmed
8852666
uniprot
proteins
pubmed
8957022
uniprot
proteins
pubmed
9120469
uniprot
proteins
pubmed
9222755
uniprot
proteins
pubmed
9328244
uniprot
proteins
pubmed
9445252
uniprot
proteins
pubmed
9667588
uniprot
proteins
pubmed
9778264
uniprot
proteins
sequence_length
250
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12176133, ECO:0000269|PubMed:16778797, ECO:0000269|PubMed:2463916}. Nucleus {ECO:0000269|PubMed:16778797}.
uniprot
proteins