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Protein

GTP cyclohydrolase 1

Gene

Gch1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May positively regulate nitric oxide synthesis in endothelial cells. May be involved in dopamine synthesis (By similarity). May modify pain sensitivity and persistence.By similarity1 Publication

Catalytic activityi

GTP + H2O = formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate.1 Publication

Enzyme regulationi

GTP shows a positive allosteric effect, and tetrahydrobiopterin inhibits the enzyme activity. Zinc is required for catalytic activity. Inhibited by Mg2+.1 Publication

Kineticsi

    1. Vmax=2.7 µmol/h/mg enzyme (at pH 7.5 and 37 degrees Celsius)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.1 Publication
    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)DescriptionActionsGraphical viewLength
    Sitei87Involved in pterin ring bindingBy similarity1
    Sitei96Involved in pterin ring bindingBy similarity1
    Metal bindingi132ZincBy similarity1
    Metal bindingi135ZincBy similarity1
    Metal bindingi203ZincBy similarity1

    GO - Molecular functioni

    • calcium ion binding Source: RGD
    • coenzyme binding Source: RGD
    • GTP binding Source: RGD
    • GTP cyclohydrolase I activity Source: RGD
    • GTP-dependent protein binding Source: RGD
    • translation initiation factor binding Source: RGD
    • zinc ion binding Source: RGD

    GO - Biological processi

    • 7,8-dihydroneopterin 3'-triphosphate biosynthetic process Source: UniProtKB-UniPathway
    • dihydrobiopterin metabolic process Source: RGD
    • dopamine biosynthetic process Source: Ensembl
    • negative regulation of blood pressure Source: RGD
    • neuromuscular process controlling posture Source: Ensembl
    • positive regulation of nitric-oxide synthase activity Source: Ensembl
    • protein complex assembly Source: RGD
    • protein heterooligomerization Source: RGD
    • protein homooligomerization Source: RGD
    • regulation of lung blood pressure Source: Ensembl
    • regulation of removal of superoxide radicals Source: Ensembl
    • response to interferon-gamma Source: Ensembl
    • response to lipopolysaccharide Source: Ensembl
    • response to pain Source: UniProtKB
    • response to tumor necrosis factor Source: Ensembl
    • tetrahydrobiopterin biosynthetic process Source: RGD
    • tetrahydrofolate biosynthetic process Source: InterPro
    • vasodilation Source: RGD
    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

    BRENDAi3.5.4.16. 5301.
    ReactomeiR-RNO-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
    UniPathwayiUPA00848; UER00151.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    GTP cyclohydrolase 1 (EC:3.5.4.161 Publication)
    Alternative name(s):
    GTP cyclohydrolase I
    Short name:
    GTP-CH-I
    Gene namesi
    Name:Gch1
    Synonyms:Gch
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    Proteomesi
    • UP000002494 Componenti: Chromosome 15

    Organism-specific databases

    RGDi61992. Gch1.

    Subcellular locationi

    • Cytoplasm By similarity
    • Nucleus By similarity

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    PropeptideiPRO_00000107201 – 11Add BLAST11
    ChainiPRO_000001072112 – 241GTP cyclohydrolase 1Add BLAST230

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei51PhosphoserineCombined sources1
    Modified residuei72PhosphoserineBy similarity1

    Post-translational modificationi

    Phosphorylated.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiP22288.
    PRIDEiP22288.

    PTM databases

    iPTMnetiP22288.
    PhosphoSitePlusiP22288.

    Expressioni

    Inductioni

    By cytokines such as insulin, interferon-gamma, and phytohemagglutinin in adrenal gland, macrophages, and T-cell respectively.

    Gene expression databases

    BgeeiENSRNOG00000011039.
    GenevisibleiP22288. RN.

    Interactioni

    Subunit structurei

    Toroid-shaped homodecamer, composed of two pentamers of five dimers. Interacts with AHSA1 and GCHFR/GFRP.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    GchfrP705523EBI-1032708,EBI-1032715

    GO - Molecular functioni

    • GTP-dependent protein binding Source: RGD
    • translation initiation factor binding Source: RGD

    Protein-protein interaction databases

    BioGridi247920. 2 interactors.
    IntActiP22288. 1 interactor.
    STRINGi10116.ENSRNOP00000014821.

    Structurei

    Secondary structure

    1241
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi52 – 73Combined sources22
    Turni80 – 84Combined sources5
    Helixi85 – 96Combined sources12
    Helixi98 – 101Combined sources4
    Helixi105 – 108Combined sources4
    Beta strandi109 – 111Combined sources3
    Beta strandi112 – 117Combined sources6
    Beta strandi121 – 132Combined sources12
    Turni133 – 135Combined sources3
    Beta strandi138 – 148Combined sources11
    Beta strandi150 – 154Combined sources5
    Helixi156 – 167Combined sources12
    Beta strandi168 – 171Combined sources4
    Helixi173 – 188Combined sources16
    Beta strandi191 – 201Combined sources11
    Helixi202 – 205Combined sources4
    Beta strandi207 – 210Combined sources4
    Beta strandi215 – 223Combined sources9
    Helixi224 – 227Combined sources4
    Helixi229 – 239Combined sources11

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1IS7X-ray2.80A/B/C/D/E/F/G/H/I/J12-241[»]
    1IS8X-ray2.70A/B/C/D/E/F/G/H/I/J12-241[»]
    1WPLX-ray2.80A/B/C/D/E/F/G/H/I/J12-241[»]
    ProteinModelPortaliP22288.
    SMRiP22288.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP22288.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the GTP cyclohydrolase I family.Curated

    Phylogenomic databases

    eggNOGiKOG2698. Eukaryota.
    COG0302. LUCA.
    GeneTreeiENSGT00390000013481.
    HOGENOMiHOG000221222.
    HOVERGENiHBG003136.
    InParanoidiP22288.
    KOiK01495.
    OMAiMGKVHIG.
    OrthoDBiEOG091G0PCE.
    PhylomeDBiP22288.

    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]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P22288-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MEKPRGVRCT NGFPERELPR PGASRPAEKS RPPEAKGAQP ADAWKAGRPR
    60 70 80 90 100
    SEEDNELNLP NLAAAYSSIL RSLGEDPQRQ GLLKTPWRAA TAMQFFTKGY
    110 120 130 140 150
    QETISDVLND AIFDEDHDEM VIVKDIDMFS MCEHHLVPFV GRVHIGYLPN
    160 170 180 190 200
    KQVLGLSKLA RIVEIYSRRL QVQERLTKQI AVAITEALQP AGVGVVIEAT
    210 220 230 240
    HMCMVMRGVQ KMNSKTVTST MLGVFREDPK TREEFLTLIR S
    Length:241
    Mass (Da):27,057
    Last modified:August 1, 1991 - v1
    Checksum:i8226E3319816325B
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M58364 mRNA. Translation: AAA41299.1.
    PIRiA39080.
    RefSeqiNP_077332.1. NM_024356.1.
    UniGeneiRn.28195.

    Genome annotation databases

    EnsembliENSRNOT00000014821; ENSRNOP00000014821; ENSRNOG00000011039.
    GeneIDi29244.
    KEGGirno:29244.
    UCSCiRGD:61992. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M58364 mRNA. Translation: AAA41299.1.
    PIRiA39080.
    RefSeqiNP_077332.1. NM_024356.1.
    UniGeneiRn.28195.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1IS7X-ray2.80A/B/C/D/E/F/G/H/I/J12-241[»]
    1IS8X-ray2.70A/B/C/D/E/F/G/H/I/J12-241[»]
    1WPLX-ray2.80A/B/C/D/E/F/G/H/I/J12-241[»]
    ProteinModelPortaliP22288.
    SMRiP22288.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi247920. 2 interactors.
    IntActiP22288. 1 interactor.
    STRINGi10116.ENSRNOP00000014821.

    PTM databases

    iPTMnetiP22288.
    PhosphoSitePlusiP22288.

    Proteomic databases

    PaxDbiP22288.
    PRIDEiP22288.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSRNOT00000014821; ENSRNOP00000014821; ENSRNOG00000011039.
    GeneIDi29244.
    KEGGirno:29244.
    UCSCiRGD:61992. rat.

    Organism-specific databases

    CTDi2643.
    RGDi61992. Gch1.

    Phylogenomic databases

    eggNOGiKOG2698. Eukaryota.
    COG0302. LUCA.
    GeneTreeiENSGT00390000013481.
    HOGENOMiHOG000221222.
    HOVERGENiHBG003136.
    InParanoidiP22288.
    KOiK01495.
    OMAiMGKVHIG.
    OrthoDBiEOG091G0PCE.
    PhylomeDBiP22288.

    Enzyme and pathway databases

    UniPathwayiUPA00848; UER00151.
    BRENDAi3.5.4.16. 5301.
    ReactomeiR-RNO-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.

    Miscellaneous databases

    EvolutionaryTraceiP22288.
    PROiP22288.

    Gene expression databases

    BgeeiENSRNOG00000011039.
    GenevisibleiP22288. RN.

    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_RAT
    AccessioniPrimary (citable) accession number: P22288
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1991
    Last sequence update: August 1, 1991
    Last modified: November 2, 2016
    This is version 150 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Allosteric enzyme, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. 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.