UniProtKB - P30793 (GCH1_HUMAN)
Protein
GTP cyclohydrolase 1
Gene
GCH1
Organism
Homo sapiens (Human)
Status
Functioni
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.5 Publications
Catalytic activityi
GTP + H2O = formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate.3 Publications
Activity regulationi
GTP shows a positive allosteric effect, and tetrahydrobiopterin inhibits the enzyme activity. Zinc is required for catalytic activity. Inhibited by Mg2+.3 Publications
Kineticsi
- KM=116 µM for GTP1 Publication
pH dependencei
Optimum pH is 7.7 in phosphate buffer.1 Publication
Temperature dependencei
Relatively stable at high temperatures. Retains 50% of its activity after incubation at 70 degrees Celsius for 15 minutes.1 Publication
Pathwayi: 7,8-dihydroneopterin triphosphate biosynthesis
This protein is involved in step 1 of the subpathway that synthesizes 7,8-dihydroneopterin triphosphate from GTP.3 PublicationsProteins known to be involved in this subpathway in this organism are:
- GTP cyclohydrolase 1 (GCH1)
View all proteins of this organism that are known to be involved in the subpathway that synthesizes 7,8-dihydroneopterin triphosphate from GTP, the pathway 7,8-dihydroneopterin triphosphate biosynthesis and in Cofactor biosynthesis.
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Metal bindingi | 141 | Zinc1 Publication | 1 | |
| Metal bindingi | 144 | Zinc1 Publication | 1 | |
| Metal bindingi | 212 | Zinc1 Publication | 1 |
GO - Molecular functioni
- calcium ion binding Source: Ensembl
- coenzyme binding Source: Ensembl
- GTPase activity Source: UniProtKB
- GTP binding Source: UniProtKB
- GTP cyclohydrolase I activity Source: UniProtKB
- GTP-dependent protein binding Source: Ensembl
- mitogen-activated protein kinase binding Source: ParkinsonsUK-UCL
- protein homodimerization activity Source: UniProtKB
- translation initiation factor binding Source: Ensembl
- zinc ion binding Source: UniProtKB
GO - Biological processi
- 7,8-dihydroneopterin 3'-triphosphate biosynthetic process Source: UniProtKB-UniPathway
- cofactor metabolic process Source: Reactome
- dopamine biosynthetic process Source: UniProtKB
- negative regulation of blood pressure Source: Ensembl
- neuromuscular process controlling posture Source: MGI
- nitric oxide biosynthetic process Source: UniProtKB
- positive regulation of heart rate Source: Ensembl
- positive regulation of nitric-oxide synthase activity Source: UniProtKB
- protein heterooligomerization Source: Ensembl
- protein homooligomerization Source: UniProtKB
- pteridine-containing compound biosynthetic process Source: UniProtKB
- regulation of blood pressure Source: UniProtKB
- regulation of lung blood pressure Source: Ensembl
- regulation of removal of superoxide radicals Source: BHF-UCL
- response to interferon-gamma Source: UniProtKB
- response to lipopolysaccharide Source: UniProtKB
- response to pain Source: UniProtKB
- response to tumor necrosis factor Source: UniProtKB
- tetrahydrobiopterin biosynthetic process Source: UniProtKB
- tetrahydrofolate biosynthetic process Source: InterPro
- vasodilation Source: Ensembl
Keywordsi
| Molecular function | Allosteric enzyme, Hydrolase |
| Biological process | Tetrahydrobiopterin biosynthesis |
| Ligand | GTP-binding, Metal-binding, Nucleotide-binding, Zinc |
Enzyme and pathway databases
| BioCyci | MetaCyc:HS05586-MONOMER |
| BRENDAi | 3.5.4.16 2681 |
| Reactomei | R-HSA-1474151 Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation |
| SABIO-RKi | P30793 |
| SIGNORi | P30793 |
| UniPathwayi | UPA00848;UER00151 |
Names & Taxonomyi
| Protein namesi | Recommended name: GTP cyclohydrolase 1 (EC:3.5.4.163 Publications)Alternative name(s): GTP cyclohydrolase I Short name: GTP-CH-I |
| Gene namesi | Name:GCH1 Synonyms:DYT5, GCH |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| EuPathDBi | HostDB:ENSG00000131979.18 |
| HGNCi | HGNC:4193 GCH1 |
| MIMi | 600225 gene |
| neXtProti | NX_P30793 |
Pathology & Biotechi
Involvement in diseasei
Hyperphenylalaninemia, BH4-deficient, B (HPABH4B)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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 mental retardation and only minimal, if any, hyperphenylalaninemia.
See also OMIM:233910| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_016894 | 108 | G → D in HPABH4B; intermediate phenotype presenting with dystonia and motor delay. 1 PublicationCorresponds to variant dbSNP:rs104894435EnsemblClinVar. | 1 | |
| Natural variantiVAR_002643 | 184 | R → H in HPABH4B; severe hyperphenylalaninemia. 1 PublicationCorresponds to variant dbSNP:rs104894445EnsemblClinVar. | 1 | |
| Natural variantiVAR_002647 | 211 | M → I in HPABH4B; severe hyperphenylalaninemia. 1 PublicationCorresponds to variant dbSNP:rs104894443EnsemblClinVar. | 1 | |
| Natural variantiVAR_016905 | 221 | M → T in HPABH4B; intermediate phenotype presenting with dystonia and motor delay; compound heterozygote for an additional deletion. 1 PublicationCorresponds to variant dbSNP:rs104894434EnsemblClinVar. | 1 |
Dystonia, dopa-responsive (DRD)15 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:128230| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_002633 | 23 | P → L in DRD. 1 PublicationCorresponds to variant dbSNP:rs41298432EnsemblClinVar. | 1 | |
| Natural variantiVAR_016888 | 71 | L → Q in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016889 | 74 | A → V in DRD. 1 Publication | 1 | |
| Natural variantiVAR_002634 | 79 | L → P in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016890 | 83 | G → A in DRD. 2 Publications | 1 | |
| Natural variantiVAR_016891 | 88 – 89 | Missing in DRD. 1 Publication | 2 | |
| Natural variantiVAR_002635 | 88 | R → P in DRD. 1 Publication | 1 | |
| Natural variantiVAR_002636 | 88 | R → W in DRD. 1 PublicationCorresponds to variant dbSNP:rs104894433EnsemblClinVar. | 1 | |
| Natural variantiVAR_016892 | 90 | G → V in DRD. 1 Publication | 1 | |
| Natural variantiVAR_002637 | 102 | M → K in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016893 | 102 | M → R in DRD. 1 Publication | 1 | |
| Natural variantiVAR_054112 | 106 | T → I in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016895 | 115 | D → N in DRD. 1 Publication | 1 | |
| Natural variantiVAR_002638 | 134 | D → V in DRD. 1 PublicationCorresponds to variant dbSNP:rs104894437EnsemblClinVar. | 1 | |
| Natural variantiVAR_016896 | 135 | I → K in DRD. 1 PublicationCorresponds to variant dbSNP:rs104894441EnsemblClinVar. | 1 | |
| Natural variantiVAR_016897 | 141 | C → R in DRD. 1 Publication | 1 | |
| Natural variantiVAR_002639 | 141 | C → W in DRD. 1 Publication | 1 | |
| Natural variantiVAR_002640 | 144 | H → P in DRD. 1 PublicationCorresponds to variant dbSNP:rs104894440EnsemblClinVar. | 1 | |
| Natural variantiVAR_002641 | 153 | H → P in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016898 | 163 | L → R in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016899 | 176 | S → T in DRD. 1 Publication | 1 | |
| Natural variantiVAR_002642 | 178 | R → S in DRD. 3 Publications | 1 | |
| Natural variantiVAR_016900 | 180 | Q → R in DRD. 1 Publication | 1 | |
| Natural variantiVAR_002644 | 186 | T → K in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016901 | 191 | V → I in DRD. 1 PublicationCorresponds to variant dbSNP:rs762208304Ensembl. | 1 | |
| Natural variantiVAR_016902 | 199 | P → L in DRD. 1 Publication | 1 | |
| Natural variantiVAR_002645 | 201 | G → E in DRD. 2 PublicationsCorresponds to variant dbSNP:rs104894438EnsemblClinVar. | 1 | |
| Natural variantiVAR_002646 | 203 | G → R in DRD. 1 PublicationCorresponds to variant dbSNP:rs988395114EnsemblClinVar. | 1 | |
| Natural variantiVAR_016903 | 211 | M → V in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016904 | 213 | M → V in DRD. 1 Publication | 1 | |
| Natural variantiVAR_002649 | 234 | F → S in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016906 | 241 | R → W in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016907 | 249 | R → S in DRD. 1 PublicationCorresponds to variant dbSNP:rs104894442EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease mutation, Dystonia, Parkinsonism, PhenylketonuriaOrganism-specific databases
| DisGeNETi | 2643 |
| GeneReviewsi | GCH1 |
| MalaCardsi | GCH1 |
| MIMi | 128230 phenotype 233910 phenotype |
| OpenTargetsi | ENSG00000131979 |
| Orphaneti | 98808 Autosomal dominant dopa-responsive dystonia 2102 GTP cyclohydrolase I deficiency |
| PharmGKBi | PA28608 |
Chemistry databases
| DrugBanki | DB02377 Guanine DB02325 Isopropyl Alcohol |
Polymorphism and mutation databases
| BioMutai | GCH1 |
| DMDMi | 399536 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000119478 | 1 – 250 | GTP cyclohydrolase 1Add BLAST | 250 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 60 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 81 | Phosphoserine1 Publication | 1 |
Post-translational modificationi
Phosphorylated by casein kinase II at Ser-81 in HAECs during oscillatory shear stress; phosphorylation at Ser-81 results in increased enzyme activity.1 Publication
Keywords - PTMi
PhosphoproteinProteomic databases
| EPDi | P30793 |
| MaxQBi | P30793 |
| PaxDbi | P30793 |
| PeptideAtlasi | P30793 |
| PRIDEi | P30793 |
| ProteomicsDBi | 54735 54736 [P30793-2] 54737 [P30793-3] 54738 [P30793-4] |
PTM databases
| iPTMneti | P30793 |
| PhosphoSitePlusi | P30793 |
Expressioni
Tissue specificityi
In epidermis, expressed predominantly in basal undifferentiated keratinocytes and in some but not all melanocytes (at protein level).1 Publication
Inductioni
Up-regulated by IFNG/IFN-gamma, TNF, IL1B/interleukin-1 beta, bacterial lipopolysaccharides (LPS) and phenylalanine, and down-regulated by dibutyryl-cAMP, iloprost and 8-bromo-cGMP in HUVEC cells. Up-regulation of GCH1 expression, in turn, stimulates production of tetrahydrobiopterin, with subsequent elevation of endothelial nitric oxide synthase activity. Cytokine-induced GCH1 up-regulation in HUVECs in response to TNF and IFNG/IFN-gamma involves cooperative activation of both the NF-kappa-B and JAK2/STAT pathways. Also up-regulated by hydrogen peroxide in human aorta endothelial cells (HAECs).7 Publications
Gene expression databases
| Bgeei | ENSG00000131979 Expressed in 203 organ(s), highest expression level in secondary oocyte |
| CleanExi | HS_GCH1 |
| ExpressionAtlasi | P30793 baseline and differential |
| Genevisiblei | P30793 HS |
Organism-specific databases
| HPAi | HPA028612 |
Interactioni
Subunit structurei
Toroid-shaped homodecamer, composed of a dimer of pentamers. The inactive isoforms also form decamers and may possibly be incorporated into GCH1 heterodecamers, decreasing enzyme stability and activity. Interacts with AHSA1 and GCHFR/GFRP.3 Publications
Binary interactionsi
GO - Molecular functioni
- GTP-dependent protein binding Source: Ensembl
- mitogen-activated protein kinase binding Source: ParkinsonsUK-UCL
- protein homodimerization activity Source: UniProtKB
- translation initiation factor binding Source: Ensembl
Protein-protein interaction databases
| BioGridi | 108913, 31 interactors |
| IntActi | P30793, 14 interactors |
| MINTi | P30793 |
| STRINGi | 9606.ENSP00000378890 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
| ProteinModelPortali | P30793 |
| SMRi | P30793 |
| ModBasei | Search... |
| MobiDBi | Search... |
Miscellaneous databases
| EvolutionaryTracei | P30793 |
Family & Domainsi
Sequence similaritiesi
Belongs to the GTP cyclohydrolase I family.Curated
Phylogenomic databases
| eggNOGi | KOG2698 Eukaryota COG0302 LUCA |
| GeneTreei | ENSGT00390000013481 |
| HOGENOMi | HOG000221222 |
| HOVERGENi | HBG003136 |
| InParanoidi | P30793 |
| KOi | K01495 |
| OMAi | PFMGKVH |
| OrthoDBi | EOG091G0PCE |
| PhylomeDBi | P30793 |
| TreeFami | TF105616 |
Family and domain databases
| HAMAPi | MF_00223 FolE, 1 hit |
| InterProi | View protein in InterPro IPR001474 GTP_CycHdrlase_I IPR018234 GTP_CycHdrlase_I_CS IPR020602 GTP_CycHdrlase_I_dom |
| PANTHERi | PTHR11109 PTHR11109, 1 hit |
| Pfami | View protein in Pfam PF01227 GTP_cyclohydroI, 1 hit |
| TIGRFAMsi | TIGR00063 folE, 1 hit |
| PROSITEi | View protein in PROSITE PS00859 GTP_CYCLOHYDROL_1_1, 1 hit PS00860 GTP_CYCLOHYDROL_1_2, 1 hit |
Sequences (4)i
Sequence statusi: Complete.
This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basketIsoform GCH-1 (identifier: P30793-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MEKGPVRAPA EKPRGARCSN GFPERDPPRP GPSRPAEKPP RPEAKSAQPA
60 70 80 90 100
DGWKGERPRS EEDNELNLPN LAAAYSSILS SLGENPQRQG LLKTPWRAAS
110 120 130 140 150
AMQFFTKGYQ ETISDVLNDA IFDEDHDEMV IVKDIDMFSM CEHHLVPFVG
160 170 180 190 200
KVHIGYLPNK QVLGLSKLAR IVEIYSRRLQ VQERLTKQIA VAITEALRPA
210 220 230 240 250
GVGVVVEATH MCMVMRGVQK MNSKTVTSTM LGVFREDPKT REEFLTLIRS
Isoform GCH-2 (identifier: P30793-2) [UniParc]FASTAAdd to basket
The sequence of this isoform differs from the canonical sequence as follows:
210-213: HMCM → SAEP
214-250: Missing.
Isoform GCH-3 (identifier: P30793-3) [UniParc]FASTAAdd to basket
The sequence of this isoform differs from the canonical sequence as follows:
210-250: Missing.
Isoform GCH-4 (identifier: P30793-4) [UniParc]FASTAAdd to basket
The sequence of this isoform differs from the canonical sequence as follows:
210-233: HMCMVMRGVQKMNSKTVTSTMLGV → KSNKYNKGLSPLLSSCHLFVAILK
234-250: Missing.
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 11 | E → G in AAD38866 (PubMed:11284739).Curated | 1 | |
| Sequence conflicti | 206 | V → I in CAA78908 (PubMed:1482676).Curated | 1 |
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_002632 | 15 | G → D in HGCH-3. | 1 | |
| Natural variantiVAR_002633 | 23 | P → L in DRD. 1 PublicationCorresponds to variant dbSNP:rs41298432EnsemblClinVar. | 1 | |
| Natural variantiVAR_016888 | 71 | L → Q in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016889 | 74 | A → V in DRD. 1 Publication | 1 | |
| Natural variantiVAR_072733 | 75 | Y → C Found in patients with DRD; unknown pathological significance. | 1 | |
| Natural variantiVAR_002634 | 79 | L → P in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016890 | 83 | G → A in DRD. 2 Publications | 1 | |
| Natural variantiVAR_016891 | 88 – 89 | Missing in DRD. 1 Publication | 2 | |
| Natural variantiVAR_002635 | 88 | R → P in DRD. 1 Publication | 1 | |
| Natural variantiVAR_002636 | 88 | R → W in DRD. 1 PublicationCorresponds to variant dbSNP:rs104894433EnsemblClinVar. | 1 | |
| Natural variantiVAR_016892 | 90 | G → V in DRD. 1 Publication | 1 | |
| Natural variantiVAR_072734 | 98 | A → V. | 1 | |
| Natural variantiVAR_002637 | 102 | M → K in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016893 | 102 | M → R in DRD. 1 Publication | 1 | |
| Natural variantiVAR_054112 | 106 | T → I in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016894 | 108 | G → D in HPABH4B; intermediate phenotype presenting with dystonia and motor delay. 1 PublicationCorresponds to variant dbSNP:rs104894435EnsemblClinVar. | 1 | |
| Natural variantiVAR_016895 | 115 | D → N in DRD. 1 Publication | 1 | |
| Natural variantiVAR_002638 | 134 | D → V in DRD. 1 PublicationCorresponds to variant dbSNP:rs104894437EnsemblClinVar. | 1 | |
| Natural variantiVAR_016896 | 135 | I → K in DRD. 1 PublicationCorresponds to variant dbSNP:rs104894441EnsemblClinVar. | 1 | |
| Natural variantiVAR_072735 | 135 | I → T. | 1 | |
| Natural variantiVAR_016897 | 141 | C → R in DRD. 1 Publication | 1 | |
| Natural variantiVAR_002639 | 141 | C → W in DRD. 1 Publication | 1 | |
| Natural variantiVAR_002640 | 144 | H → P in DRD. 1 PublicationCorresponds to variant dbSNP:rs104894440EnsemblClinVar. | 1 | |
| Natural variantiVAR_002641 | 153 | H → P in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016898 | 163 | L → R in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016899 | 176 | S → T in DRD. 1 Publication | 1 | |
| Natural variantiVAR_002642 | 178 | R → S in DRD. 3 Publications | 1 | |
| Natural variantiVAR_016900 | 180 | Q → R in DRD. 1 Publication | 1 | |
| Natural variantiVAR_002643 | 184 | R → H in HPABH4B; severe hyperphenylalaninemia. 1 PublicationCorresponds to variant dbSNP:rs104894445EnsemblClinVar. | 1 | |
| Natural variantiVAR_002644 | 186 | T → K in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016901 | 191 | V → I in DRD. 1 PublicationCorresponds to variant dbSNP:rs762208304Ensembl. | 1 | |
| Natural variantiVAR_016902 | 199 | P → L in DRD. 1 Publication | 1 | |
| Natural variantiVAR_002645 | 201 | G → E in DRD. 2 PublicationsCorresponds to variant dbSNP:rs104894438EnsemblClinVar. | 1 | |
| Natural variantiVAR_002646 | 203 | G → R in DRD. 1 PublicationCorresponds to variant dbSNP:rs988395114EnsemblClinVar. | 1 | |
| Natural variantiVAR_002647 | 211 | M → I in HPABH4B; severe hyperphenylalaninemia. 1 PublicationCorresponds to variant dbSNP:rs104894443EnsemblClinVar. | 1 | |
| Natural variantiVAR_016903 | 211 | M → V in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016904 | 213 | M → V in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016905 | 221 | M → T in HPABH4B; intermediate phenotype presenting with dystonia and motor delay; compound heterozygote for an additional deletion. 1 PublicationCorresponds to variant dbSNP:rs104894434EnsemblClinVar. | 1 | |
| Natural variantiVAR_002648 | 224 | K → R in HPABH4B and DRD; phenotype presenting with dystonia and myoclonus. 3 PublicationsCorresponds to variant dbSNP:rs41298442EnsemblClinVar. | 1 | |
| Natural variantiVAR_002649 | 234 | F → S in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016906 | 241 | R → W in DRD. 1 Publication | 1 | |
| Natural variantiVAR_016907 | 249 | R → S in DRD. 1 PublicationCorresponds to variant dbSNP:rs104894442EnsemblClinVar. | 1 |
Alternative sequence
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Alternative sequenceiVSP_001610 | 210 – 250 | Missing in isoform GCH-3. 1 PublicationAdd BLAST | 41 | |
| Alternative sequenceiVSP_001611 | 210 – 233 | HMCMV…TMLGV → KSNKYNKGLSPLLSSCHLFV AILK in isoform GCH-4. 1 PublicationAdd BLAST | 24 | |
| Alternative sequenceiVSP_001612 | 210 – 213 | HMCM → SAEP in isoform GCH-2. 2 Publications | 4 | |
| Alternative sequenceiVSP_001613 | 214 – 250 | Missing in isoform GCH-2. 2 PublicationsAdd BLAST | 37 | |
| Alternative sequenceiVSP_001614 | 234 – 250 | Missing in isoform GCH-4. 1 PublicationAdd BLAST | 17 |
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | S44049 mRNA Translation: AAB23164.1 S44053 mRNA Translation: AAB23165.1 S43856 mRNA Translation: AAB23166.1 Z29433 mRNA Translation: CAB77391.1 Z29434 mRNA Translation: CAB77392.1 U19523 mRNA Translation: AAB16861.1 U66095 mRNA Translation: AAD38866.1 U66097 mRNA Translation: AAD38868.1 CR536551 mRNA Translation: CAG38788.1 CH471061 Genomic DNA Translation: EAW80647.1 BC025415 mRNA Translation: AAH25415.1 L29478 Genomic DNA Translation: AAB42186.1 Z30952 Genomic DNA Translation: CAA83213.1 Z16418 mRNA Translation: CAA78908.1 U19259 U19258 Genomic DNA Translation: AAB60633.1 |
| CCDSi | CCDS41954.1 [P30793-4] CCDS45110.1 [P30793-2] CCDS9720.1 [P30793-1] |
| PIRi | G01630 PC1117 JC1225 |
| RefSeqi | NP_000152.1, NM_000161.2 [P30793-1] NP_001019195.1, NM_001024024.1 [P30793-1] NP_001019241.1, NM_001024070.1 [P30793-4] NP_001019242.1, NM_001024071.1 [P30793-2] |
| UniGenei | Hs.86724 |
Genome annotation databases
| Ensembli | ENST00000395514; ENSP00000378890; ENSG00000131979 [P30793-1] ENST00000491895; ENSP00000419045; ENSG00000131979 [P30793-1] ENST00000536224; ENSP00000445246; ENSG00000131979 [P30793-2] ENST00000543643; ENSP00000444011; ENSG00000131979 [P30793-4] ENST00000622544; ENSP00000477796; ENSG00000131979 [P30793-1] |
| GeneIDi | 2643 |
| KEGGi | hsa:2643 |
| UCSCi | uc001xbh.2 human [P30793-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | S44049 mRNA Translation: AAB23164.1 S44053 mRNA Translation: AAB23165.1 S43856 mRNA Translation: AAB23166.1 Z29433 mRNA Translation: CAB77391.1 Z29434 mRNA Translation: CAB77392.1 U19523 mRNA Translation: AAB16861.1 U66095 mRNA Translation: AAD38866.1 U66097 mRNA Translation: AAD38868.1 CR536551 mRNA Translation: CAG38788.1 CH471061 Genomic DNA Translation: EAW80647.1 BC025415 mRNA Translation: AAH25415.1 L29478 Genomic DNA Translation: AAB42186.1 Z30952 Genomic DNA Translation: CAA83213.1 Z16418 mRNA Translation: CAA78908.1 U19259 U19258 Genomic DNA Translation: AAB60633.1 |
| CCDSi | CCDS41954.1 [P30793-4] CCDS45110.1 [P30793-2] CCDS9720.1 [P30793-1] |
| PIRi | G01630 PC1117 JC1225 |
| RefSeqi | NP_000152.1, NM_000161.2 [P30793-1] NP_001019195.1, NM_001024024.1 [P30793-1] NP_001019241.1, NM_001024070.1 [P30793-4] NP_001019242.1, NM_001024071.1 [P30793-2] |
| UniGenei | Hs.86724 |
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 1FB1 | X-ray | 3.10 | A/B/C/D/E | 55-250 | [»] | |
| ProteinModelPortali | P30793 | |||||
| SMRi | P30793 | |||||
| ModBasei | Search... | |||||
| MobiDBi | Search... | |||||
Protein-protein interaction databases
| BioGridi | 108913, 31 interactors |
| IntActi | P30793, 14 interactors |
| MINTi | P30793 |
| STRINGi | 9606.ENSP00000378890 |
Chemistry databases
| DrugBanki | DB02377 Guanine DB02325 Isopropyl Alcohol |
PTM databases
| iPTMneti | P30793 |
| PhosphoSitePlusi | P30793 |
Polymorphism and mutation databases
| BioMutai | GCH1 |
| DMDMi | 399536 |
Proteomic databases
| EPDi | P30793 |
| MaxQBi | P30793 |
| PaxDbi | P30793 |
| PeptideAtlasi | P30793 |
| PRIDEi | P30793 |
| ProteomicsDBi | 54735 54736 [P30793-2] 54737 [P30793-3] 54738 [P30793-4] |
Protocols and materials databases
| DNASUi | 2643 |
| Structural Biology Knowledgebase | Search... |
Genome annotation databases
| Ensembli | ENST00000395514; ENSP00000378890; ENSG00000131979 [P30793-1] ENST00000491895; ENSP00000419045; ENSG00000131979 [P30793-1] ENST00000536224; ENSP00000445246; ENSG00000131979 [P30793-2] ENST00000543643; ENSP00000444011; ENSG00000131979 [P30793-4] ENST00000622544; ENSP00000477796; ENSG00000131979 [P30793-1] |
| GeneIDi | 2643 |
| KEGGi | hsa:2643 |
| UCSCi | uc001xbh.2 human [P30793-1] |
Organism-specific databases
| CTDi | 2643 |
| DisGeNETi | 2643 |
| EuPathDBi | HostDB:ENSG00000131979.18 |
| GeneCardsi | GCH1 |
| GeneReviewsi | GCH1 |
| HGNCi | HGNC:4193 GCH1 |
| HPAi | HPA028612 |
| MalaCardsi | GCH1 |
| MIMi | 128230 phenotype 233910 phenotype 600225 gene |
| neXtProti | NX_P30793 |
| OpenTargetsi | ENSG00000131979 |
| Orphaneti | 98808 Autosomal dominant dopa-responsive dystonia 2102 GTP cyclohydrolase I deficiency |
| PharmGKBi | PA28608 |
| GenAtlasi | Search... |
Phylogenomic databases
| eggNOGi | KOG2698 Eukaryota COG0302 LUCA |
| GeneTreei | ENSGT00390000013481 |
| HOGENOMi | HOG000221222 |
| HOVERGENi | HBG003136 |
| InParanoidi | P30793 |
| KOi | K01495 |
| OMAi | PFMGKVH |
| OrthoDBi | EOG091G0PCE |
| PhylomeDBi | P30793 |
| TreeFami | TF105616 |
Enzyme and pathway databases
| UniPathwayi | UPA00848;UER00151 |
| BioCyci | MetaCyc:HS05586-MONOMER |
| BRENDAi | 3.5.4.16 2681 |
| Reactomei | R-HSA-1474151 Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation |
| SABIO-RKi | P30793 |
| SIGNORi | P30793 |
Miscellaneous databases
| ChiTaRSi | GCH1 human |
| EvolutionaryTracei | P30793 |
| GeneWikii | GTP_cyclohydrolase_I |
| GenomeRNAii | 2643 |
| PROi | PR:P30793 |
| SOURCEi | Search... |
Gene expression databases
| Bgeei | ENSG00000131979 Expressed in 203 organ(s), highest expression level in secondary oocyte |
| CleanExi | HS_GCH1 |
| ExpressionAtlasi | P30793 baseline and differential |
| Genevisiblei | P30793 HS |
Family and domain databases
| HAMAPi | MF_00223 FolE, 1 hit |
| InterProi | View protein in InterPro IPR001474 GTP_CycHdrlase_I IPR018234 GTP_CycHdrlase_I_CS IPR020602 GTP_CycHdrlase_I_dom |
| PANTHERi | PTHR11109 PTHR11109, 1 hit |
| Pfami | View protein in Pfam PF01227 GTP_cyclohydroI, 1 hit |
| TIGRFAMsi | TIGR00063 folE, 1 hit |
| PROSITEi | View protein in PROSITE PS00859 GTP_CYCLOHYDROL_1_1, 1 hit PS00860 GTP_CYCLOHYDROL_1_2, 1 hit |
| ProtoNeti | Search... |
Entry informationi
| Entry namei | GCH1_HUMAN | |
| Accessioni | P30793Primary (citable) accession number: P30793 Secondary accession number(s): Q6FHY7, Q9Y4I8 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 1, 1993 |
| Last sequence update: | July 1, 1993 | |
| Last modified: | September 12, 2018 | |
| This is version 196 of the entry and version 1 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - Human chromosome 14
Human chromosome 14: entries, gene names and cross-references to MIM
