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Protein

GTP cyclohydrolase 1

Gene

GCH1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Enzyme 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

  1. 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 Publications
    Proteins known to be involved in this subpathway in this organism are:
    1. GTP cyclohydrolase 1 (GCH1)
    This subpathway is part of the pathway 7,8-dihydroneopterin triphosphate biosynthesis, which is itself part of Cofactor biosynthesis.
    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 keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi141 – 1411Zinc1 Publication
    Metal bindingi144 – 1441Zinc1 Publication
    Metal bindingi212 – 2121Zinc1 Publication

    GO - Molecular functioni

    • calcium ion binding Source: Ensembl
    • coenzyme binding Source: Ensembl
    • GTP binding Source: UniProtKB
    • GTP cyclohydrolase I activity Source: UniProtKB
    • protein homodimerization activity Source: UniProtKB
    • zinc ion binding Source: UniProtKB

    GO - Biological processi

    • 7,8-dihydroneopterin 3'-triphosphate biosynthetic process Source: UniProtKB-UniPathway
    • 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 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 nitric-oxide synthase activity Source: Reactome
    • 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
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Tetrahydrobiopterin biosynthesis

    Keywords - Ligandi

    GTP-binding, Metal-binding, Nucleotide-binding, Zinc

    Enzyme and pathway databases

    BioCyciMetaCyc:HS05586-MONOMER.
    BRENDAi3.5.4.16. 2681.
    ReactomeiR-HSA-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
    SABIO-RKP30793.
    UniPathwayiUPA00848; 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
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:4193. GCH1.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: UniProtKB
    • cytoplasmic vesicle Source: UniProtKB
    • cytosol Source: UniProtKB
    • nuclear membrane Source: HPA
    • nucleoplasm Source: HPA
    • nucleus Source: UniProtKB
    • protein complex Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    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 keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti108 – 1081G → D in HPABH4B; intermediate phenotype presenting with dystonia and motor delay. 1 Publication
    Corresponds to variant rs104894435 [ dbSNP | Ensembl ].
    VAR_016894
    Natural varianti184 – 1841R → H in HPABH4B; severe hyperphenylalaninemia. 1 Publication
    Corresponds to variant rs104894445 [ dbSNP | Ensembl ].
    VAR_002643
    Natural varianti211 – 2111M → I in HPABH4B; severe hyperphenylalaninemia. 1 Publication
    Corresponds to variant rs104894443 [ dbSNP | Ensembl ].
    VAR_002647
    Natural varianti221 – 2211M → T in HPABH4B; intermediate phenotype presenting with dystonia and motor delay; compound heterozygote for an additional deletion. 1 Publication
    Corresponds to variant rs104894434 [ dbSNP | Ensembl ].
    VAR_016905
    Natural varianti224 – 2241K → R in HPABH4B and DRD; phenotype presenting with dystonia and myoclonus. 3 Publications
    Corresponds to variant rs41298442 [ dbSNP | Ensembl ].
    VAR_002648
    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 keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti23 – 231P → L in DRD. 1 Publication
    Corresponds to variant rs41298432 [ dbSNP | Ensembl ].
    VAR_002633
    Natural varianti71 – 711L → Q in DRD. 1 Publication
    VAR_016888
    Natural varianti74 – 741A → V in DRD. 1 Publication
    VAR_016889
    Natural varianti75 – 751Y → C Found in patients with DRD; unknown pathological significance.
    VAR_072733
    Natural varianti79 – 791L → P in DRD. 1 Publication
    VAR_002634
    Natural varianti83 – 831G → A in DRD. 2 Publications
    VAR_016890
    Natural varianti88 – 892Missing in DRD. 1 Publication
    VAR_016891
    Natural varianti88 – 881R → P in DRD. 1 Publication
    VAR_002635
    Natural varianti88 – 881R → W in DRD. 1 Publication
    Corresponds to variant rs104894433 [ dbSNP | Ensembl ].
    VAR_002636
    Natural varianti90 – 901G → V in DRD. 1 Publication
    VAR_016892
    Natural varianti102 – 1021M → K in DRD. 1 Publication
    VAR_002637
    Natural varianti102 – 1021M → R in DRD. 1 Publication
    VAR_016893
    Natural varianti106 – 1061T → I in DRD. 1 Publication
    VAR_054112
    Natural varianti115 – 1151D → N in DRD. 1 Publication
    VAR_016895
    Natural varianti134 – 1341D → V in DRD. 1 Publication
    Corresponds to variant rs104894437 [ dbSNP | Ensembl ].
    VAR_002638
    Natural varianti135 – 1351I → K in DRD. 1 Publication
    Corresponds to variant rs104894441 [ dbSNP | Ensembl ].
    VAR_016896
    Natural varianti141 – 1411C → R in DRD. 1 Publication
    VAR_016897
    Natural varianti141 – 1411C → W in DRD. 1 Publication
    VAR_002639
    Natural varianti144 – 1441H → P in DRD. 1 Publication
    Corresponds to variant rs104894440 [ dbSNP | Ensembl ].
    VAR_002640
    Natural varianti153 – 1531H → P in DRD. 1 Publication
    VAR_002641
    Natural varianti163 – 1631L → R in DRD. 1 Publication
    VAR_016898
    Natural varianti176 – 1761S → T in DRD. 1 Publication
    VAR_016899
    Natural varianti178 – 1781R → S in DRD. 3 Publications
    VAR_002642
    Natural varianti180 – 1801Q → R in DRD. 1 Publication
    VAR_016900
    Natural varianti186 – 1861T → K in DRD. 1 Publication
    VAR_002644
    Natural varianti191 – 1911V → I in DRD. 1 Publication
    Corresponds to variant rs762208304 [ dbSNP | Ensembl ].
    VAR_016901
    Natural varianti199 – 1991P → L in DRD. 1 Publication
    VAR_016902
    Natural varianti201 – 2011G → E in DRD. 2 Publications
    Corresponds to variant rs104894438 [ dbSNP | Ensembl ].
    VAR_002645
    Natural varianti203 – 2031G → R in DRD. 1 Publication
    VAR_002646
    Natural varianti211 – 2111M → V in DRD. 1 Publication
    VAR_016903
    Natural varianti213 – 2131M → V in DRD. 1 Publication
    VAR_016904
    Natural varianti224 – 2241K → R in HPABH4B and DRD; phenotype presenting with dystonia and myoclonus. 3 Publications
    Corresponds to variant rs41298442 [ dbSNP | Ensembl ].
    VAR_002648
    Natural varianti234 – 2341F → S in DRD. 1 Publication
    VAR_002649
    Natural varianti241 – 2411R → W in DRD. 1 Publication
    VAR_016906
    Natural varianti249 – 2491R → S in DRD. 1 Publication
    Corresponds to variant rs104894442 [ dbSNP | Ensembl ].
    VAR_016907

    Keywords - Diseasei

    Disease mutation, Dystonia, Parkinsonism, Phenylketonuria

    Organism-specific databases

    MalaCardsiGCH1.
    MIMi128230. phenotype.
    233910. phenotype.
    Orphaneti98808. Autosomal dominant dopa-responsive dystonia.
    2102. GTP cyclohydrolase I deficiency.
    PharmGKBiPA28608.

    Chemistry

    DrugBankiDB02325. Isopropyl Alcohol.

    Polymorphism and mutation databases

    BioMutaiGCH1.
    DMDMi399536.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 250250GTP cyclohydrolase 1PRO_0000119478Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei60 – 601PhosphoserineCombined sources
    Modified residuei81 – 811Phosphoserine1 Publication

    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

    Phosphoprotein

    Proteomic databases

    EPDiP30793.
    MaxQBiP30793.
    PaxDbiP30793.
    PeptideAtlasiP30793.
    PRIDEiP30793.

    PTM databases

    iPTMnetiP30793.
    PhosphoSiteiP30793.

    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

    BgeeiENSG00000131979.
    CleanExiHS_GCH1.
    ExpressionAtlasiP30793. baseline and differential.
    GenevisibleiP30793. HS.

    Organism-specific databases

    HPAiHPA028612.

    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

    WithEntry#Exp.IntActNotes
    AHSA1O954333EBI-958183,EBI-448610
    YWHAZP631044EBI-958183,EBI-347088

    GO - Molecular functioni

    • protein homodimerization activity Source: UniProtKB

    Protein-protein interaction databases

    BioGridi108913. 30 interactions.
    IntActiP30793. 12 interactions.
    MINTiMINT-3011998.
    STRINGi9606.ENSP00000378890.

    Structurei

    Secondary structure

    1
    250
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi61 – 8121Combined sources
    Helixi91 – 933Combined sources
    Helixi94 – 1029Combined sources
    Turni103 – 1064Combined sources
    Helixi108 – 1103Combined sources
    Turni113 – 1153Combined sources
    Beta strandi130 – 14112Combined sources
    Turni142 – 1443Combined sources
    Beta strandi147 – 15610Combined sources
    Helixi165 – 17612Combined sources
    Beta strandi177 – 1804Combined sources
    Helixi182 – 19716Combined sources
    Beta strandi202 – 2109Combined sources
    Helixi211 – 2144Combined sources
    Turni215 – 2173Combined sources
    Beta strandi224 – 2307Combined sources
    Helixi233 – 2364Combined sources
    Helixi238 – 24811Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1FB1X-ray3.10A/B/C/D/E55-250[»]
    ProteinModelPortaliP30793.
    SMRiP30793. Positions 55-250.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP30793.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the GTP cyclohydrolase I family.Curated

    Phylogenomic databases

    eggNOGiKOG2698. Eukaryota.
    COG0302. LUCA.
    GeneTreeiENSGT00390000013481.
    HOGENOMiHOG000221222.
    HOVERGENiHBG003136.
    InParanoidiP30793.
    KOiK01495.
    OMAiMGKVHIG.
    OrthoDBiEOG091G0PCE.
    PhylomeDBiP30793.
    TreeFamiTF105616.

    Family and domain databases

    HAMAPiMF_00223. FolE. 1 hit.
    InterProiIPR001474. GTP_CycHdrlase_I.
    IPR018234. GTP_CycHdrlase_I_CS.
    IPR020602. GTP_CycHdrlase_I_dom.
    [Graphical view]
    PANTHERiPTHR11109. PTHR11109. 1 hit.
    PfamiPF01227. GTP_cyclohydroI. 1 hit.
    [Graphical view]
    TIGRFAMsiTIGR00063. folE. 1 hit.
    PROSITEiPS00859. GTP_CYCLOHYDROL_1_1. 1 hit.
    PS00860. GTP_CYCLOHYDROL_1_2. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 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.

    « Hide

            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
    Length:250
    Mass (Da):27,903
    Last modified:July 1, 1993 - v1
    Checksum:iB8A0CB344C598B9A
    GO
    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.

    Show »
    Length:213
    Mass (Da):23,516
    Checksum:i021D95DE6B33E02A
    GO
    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.

    Show »
    Length:209
    Mass (Da):23,131
    Checksum:i8B33E02A53DF1259
    GO
    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.

    Show »
    Length:233
    Mass (Da):25,775
    Checksum:i7100FBD83BFDB2C9
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti11 – 111E → G in AAD38866 (PubMed:11284739).Curated
    Sequence conflicti206 – 2061V → I in CAA78908 (PubMed:1482676).Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti15 – 151G → D in HGCH-3.
    VAR_002632
    Natural varianti23 – 231P → L in DRD. 1 Publication
    Corresponds to variant rs41298432 [ dbSNP | Ensembl ].
    VAR_002633
    Natural varianti71 – 711L → Q in DRD. 1 Publication
    VAR_016888
    Natural varianti74 – 741A → V in DRD. 1 Publication
    VAR_016889
    Natural varianti75 – 751Y → C Found in patients with DRD; unknown pathological significance.
    VAR_072733
    Natural varianti79 – 791L → P in DRD. 1 Publication
    VAR_002634
    Natural varianti83 – 831G → A in DRD. 2 Publications
    VAR_016890
    Natural varianti88 – 892Missing in DRD. 1 Publication
    VAR_016891
    Natural varianti88 – 881R → P in DRD. 1 Publication
    VAR_002635
    Natural varianti88 – 881R → W in DRD. 1 Publication
    Corresponds to variant rs104894433 [ dbSNP | Ensembl ].
    VAR_002636
    Natural varianti90 – 901G → V in DRD. 1 Publication
    VAR_016892
    Natural varianti98 – 981A → V.
    VAR_072734
    Natural varianti102 – 1021M → K in DRD. 1 Publication
    VAR_002637
    Natural varianti102 – 1021M → R in DRD. 1 Publication
    VAR_016893
    Natural varianti106 – 1061T → I in DRD. 1 Publication
    VAR_054112
    Natural varianti108 – 1081G → D in HPABH4B; intermediate phenotype presenting with dystonia and motor delay. 1 Publication
    Corresponds to variant rs104894435 [ dbSNP | Ensembl ].
    VAR_016894
    Natural varianti115 – 1151D → N in DRD. 1 Publication
    VAR_016895
    Natural varianti134 – 1341D → V in DRD. 1 Publication
    Corresponds to variant rs104894437 [ dbSNP | Ensembl ].
    VAR_002638
    Natural varianti135 – 1351I → K in DRD. 1 Publication
    Corresponds to variant rs104894441 [ dbSNP | Ensembl ].
    VAR_016896
    Natural varianti135 – 1351I → T.
    VAR_072735
    Natural varianti141 – 1411C → R in DRD. 1 Publication
    VAR_016897
    Natural varianti141 – 1411C → W in DRD. 1 Publication
    VAR_002639
    Natural varianti144 – 1441H → P in DRD. 1 Publication
    Corresponds to variant rs104894440 [ dbSNP | Ensembl ].
    VAR_002640
    Natural varianti153 – 1531H → P in DRD. 1 Publication
    VAR_002641
    Natural varianti163 – 1631L → R in DRD. 1 Publication
    VAR_016898
    Natural varianti176 – 1761S → T in DRD. 1 Publication
    VAR_016899
    Natural varianti178 – 1781R → S in DRD. 3 Publications
    VAR_002642
    Natural varianti180 – 1801Q → R in DRD. 1 Publication
    VAR_016900
    Natural varianti184 – 1841R → H in HPABH4B; severe hyperphenylalaninemia. 1 Publication
    Corresponds to variant rs104894445 [ dbSNP | Ensembl ].
    VAR_002643
    Natural varianti186 – 1861T → K in DRD. 1 Publication
    VAR_002644
    Natural varianti191 – 1911V → I in DRD. 1 Publication
    Corresponds to variant rs762208304 [ dbSNP | Ensembl ].
    VAR_016901
    Natural varianti199 – 1991P → L in DRD. 1 Publication
    VAR_016902
    Natural varianti201 – 2011G → E in DRD. 2 Publications
    Corresponds to variant rs104894438 [ dbSNP | Ensembl ].
    VAR_002645
    Natural varianti203 – 2031G → R in DRD. 1 Publication
    VAR_002646
    Natural varianti211 – 2111M → I in HPABH4B; severe hyperphenylalaninemia. 1 Publication
    Corresponds to variant rs104894443 [ dbSNP | Ensembl ].
    VAR_002647
    Natural varianti211 – 2111M → V in DRD. 1 Publication
    VAR_016903
    Natural varianti213 – 2131M → V in DRD. 1 Publication
    VAR_016904
    Natural varianti221 – 2211M → T in HPABH4B; intermediate phenotype presenting with dystonia and motor delay; compound heterozygote for an additional deletion. 1 Publication
    Corresponds to variant rs104894434 [ dbSNP | Ensembl ].
    VAR_016905
    Natural varianti224 – 2241K → R in HPABH4B and DRD; phenotype presenting with dystonia and myoclonus. 3 Publications
    Corresponds to variant rs41298442 [ dbSNP | Ensembl ].
    VAR_002648
    Natural varianti234 – 2341F → S in DRD. 1 Publication
    VAR_002649
    Natural varianti241 – 2411R → W in DRD. 1 Publication
    VAR_016906
    Natural varianti249 – 2491R → S in DRD. 1 Publication
    Corresponds to variant rs104894442 [ dbSNP | Ensembl ].
    VAR_016907

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei210 – 25041Missing in isoform GCH-3. 1 PublicationVSP_001610Add
    BLAST
    Alternative sequencei210 – 23324HMCMV…TMLGV → KSNKYNKGLSPLLSSCHLFV AILK in isoform GCH-4. 1 PublicationVSP_001611Add
    BLAST
    Alternative sequencei210 – 2134HMCM → SAEP in isoform GCH-2. 2 PublicationsVSP_001612
    Alternative sequencei214 – 25037Missing in isoform GCH-2. 2 PublicationsVSP_001613Add
    BLAST
    Alternative sequencei234 – 25017Missing in isoform GCH-4. 1 PublicationVSP_001614Add
    BLAST

    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
    , U19256, U19257, U19258 Genomic DNA. Translation: AAB60633.1.
    CCDSiCCDS41954.1. [P30793-4]
    CCDS45110.1. [P30793-2]
    CCDS9720.1. [P30793-1]
    PIRiG01630. PC1117.
    JC1225.
    RefSeqiNP_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]
    UniGeneiHs.86724.

    Genome annotation databases

    EnsembliENST00000395514; ENSP00000378890; ENSG00000131979. [P30793-1]
    ENST00000491895; ENSP00000419045; ENSG00000131979. [P30793-1]
    ENST00000536224; ENSP00000445246; ENSG00000131979. [P30793-2]
    ENST00000543643; ENSP00000444011; ENSG00000131979. [P30793-4]
    ENST00000622544; ENSP00000477796; ENSG00000131979. [P30793-1]
    GeneIDi2643.
    KEGGihsa:2643.
    UCSCiuc001xbh.2. human. [P30793-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    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
    , U19256, U19257, U19258 Genomic DNA. Translation: AAB60633.1.
    CCDSiCCDS41954.1. [P30793-4]
    CCDS45110.1. [P30793-2]
    CCDS9720.1. [P30793-1]
    PIRiG01630. PC1117.
    JC1225.
    RefSeqiNP_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]
    UniGeneiHs.86724.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1FB1X-ray3.10A/B/C/D/E55-250[»]
    ProteinModelPortaliP30793.
    SMRiP30793. Positions 55-250.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi108913. 30 interactions.
    IntActiP30793. 12 interactions.
    MINTiMINT-3011998.
    STRINGi9606.ENSP00000378890.

    Chemistry

    DrugBankiDB02325. Isopropyl Alcohol.

    PTM databases

    iPTMnetiP30793.
    PhosphoSiteiP30793.

    Polymorphism and mutation databases

    BioMutaiGCH1.
    DMDMi399536.

    Proteomic databases

    EPDiP30793.
    MaxQBiP30793.
    PaxDbiP30793.
    PeptideAtlasiP30793.
    PRIDEiP30793.

    Protocols and materials databases

    DNASUi2643.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000395514; ENSP00000378890; ENSG00000131979. [P30793-1]
    ENST00000491895; ENSP00000419045; ENSG00000131979. [P30793-1]
    ENST00000536224; ENSP00000445246; ENSG00000131979. [P30793-2]
    ENST00000543643; ENSP00000444011; ENSG00000131979. [P30793-4]
    ENST00000622544; ENSP00000477796; ENSG00000131979. [P30793-1]
    GeneIDi2643.
    KEGGihsa:2643.
    UCSCiuc001xbh.2. human. [P30793-1]

    Organism-specific databases

    CTDi2643.
    GeneCardsiGCH1.
    GeneReviewsiGCH1.
    HGNCiHGNC:4193. GCH1.
    HPAiHPA028612.
    MalaCardsiGCH1.
    MIMi128230. phenotype.
    233910. phenotype.
    600225. gene.
    neXtProtiNX_P30793.
    Orphaneti98808. Autosomal dominant dopa-responsive dystonia.
    2102. GTP cyclohydrolase I deficiency.
    PharmGKBiPA28608.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2698. Eukaryota.
    COG0302. LUCA.
    GeneTreeiENSGT00390000013481.
    HOGENOMiHOG000221222.
    HOVERGENiHBG003136.
    InParanoidiP30793.
    KOiK01495.
    OMAiMGKVHIG.
    OrthoDBiEOG091G0PCE.
    PhylomeDBiP30793.
    TreeFamiTF105616.

    Enzyme and pathway databases

    UniPathwayiUPA00848; UER00151.
    BioCyciMetaCyc:HS05586-MONOMER.
    BRENDAi3.5.4.16. 2681.
    ReactomeiR-HSA-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
    SABIO-RKP30793.

    Miscellaneous databases

    ChiTaRSiGCH1. human.
    EvolutionaryTraceiP30793.
    GeneWikiiGTP_cyclohydrolase_I.
    GenomeRNAii2643.
    PROiP30793.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000131979.
    CleanExiHS_GCH1.
    ExpressionAtlasiP30793. baseline and differential.
    GenevisibleiP30793. HS.

    Family and domain databases

    HAMAPiMF_00223. FolE. 1 hit.
    InterProiIPR001474. GTP_CycHdrlase_I.
    IPR018234. GTP_CycHdrlase_I_CS.
    IPR020602. GTP_CycHdrlase_I_dom.
    [Graphical view]
    PANTHERiPTHR11109. PTHR11109. 1 hit.
    PfamiPF01227. GTP_cyclohydroI. 1 hit.
    [Graphical view]
    TIGRFAMsiTIGR00063. folE. 1 hit.
    PROSITEiPS00859. GTP_CYCLOHYDROL_1_1. 1 hit.
    PS00860. GTP_CYCLOHYDROL_1_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiGCH1_HUMAN
    AccessioniPrimary (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 7, 2016
    This is version 179 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny 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, Allosteric enzyme, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 14
      Human chromosome 14: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.