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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)LengthDescriptionGraphical viewFeature identifierActions
    Sitei87 – 871Involved in pterin ring bindingBy similarity
    Sitei96 – 961Involved in pterin ring bindingBy similarity
    Metal bindingi132 – 1321ZincBy similarity
    Metal bindingi135 – 1351ZincBy similarity
    Metal bindingi203 – 2031ZincBy similarity

    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

    • cytoplasmic vesicle Source: Ensembl
    • cytosol Source: Ensembl
    • nuclear membrane Source: Ensembl
    • nucleoplasm Source: Ensembl
    • protein complex Source: RGD
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Propeptidei1 – 1111PRO_0000010720Add
    BLAST
    Chaini12 – 241230GTP cyclohydrolase 1PRO_0000010721Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei51 – 511PhosphoserineCombined sources
    Modified residuei72 – 721PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylated.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiP22288.
    PRIDEiP22288.

    PTM databases

    iPTMnetiP22288.
    PhosphoSiteiP22288.

    Expressioni

    Inductioni

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

    Gene expression databases

    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 interactions.
    IntActiP22288. 1 interaction.
    STRINGi10116.ENSRNOP00000014821.

    Structurei

    Secondary structure

    1
    241
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi52 – 7322Combined sources
    Turni80 – 845Combined sources
    Helixi85 – 9612Combined sources
    Helixi98 – 1014Combined sources
    Helixi105 – 1084Combined sources
    Beta strandi109 – 1113Combined sources
    Beta strandi112 – 1176Combined sources
    Beta strandi121 – 13212Combined sources
    Turni133 – 1353Combined sources
    Beta strandi138 – 14811Combined sources
    Beta strandi150 – 1545Combined sources
    Helixi156 – 16712Combined sources
    Beta strandi168 – 1714Combined sources
    Helixi173 – 18816Combined sources
    Beta strandi191 – 20111Combined sources
    Helixi202 – 2054Combined sources
    Beta strandi207 – 2104Combined sources
    Beta strandi215 – 2239Combined sources
    Helixi224 – 2274Combined sources
    Helixi229 – 23911Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    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. Positions 48-241.
    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.
    OMAiIATAMVQ.
    OrthoDBiEOG77DJ6T.
    PhylomeDBiP22288.

    Family and domain databases

    HAMAPiMF_00223. FolE.
    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
    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. Positions 48-241.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi247920. 2 interactions.
    IntActiP22288. 1 interaction.
    STRINGi10116.ENSRNOP00000014821.

    PTM databases

    iPTMnetiP22288.
    PhosphoSiteiP22288.

    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.
    OMAiIATAMVQ.
    OrthoDBiEOG77DJ6T.
    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.
    NextBioi608526.
    PROiP22288.

    Gene expression databases

    GenevisibleiP22288. RN.

    Family and domain databases

    HAMAPiMF_00223. FolE.
    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...

    Publicationsi

    « Hide 'large scale' publications
    1. "Cloning and sequencing of cDNA encoding rat GTP cyclohydrolase I. The first enzyme of the tetrahydrobiopterin biosynthetic pathway."
      Hatakeyama K., Inoue Y., Harada T., Kagamiyama H.
      J. Biol. Chem. 266:765-769(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
      Strain: Wistar.
      Tissue: Liver.
    2. "Identification of a rabphilin-3A-interacting protein as GTP cyclohydrolase I in PC12 cells."
      Imazumi K., Sasaki T., Takahashi K., Takai Y.
      Biochem. Biophys. Res. Commun. 205:1409-1416(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 37-46 AND 99-116.
    3. "Purification and characterization of rat liver GTP cyclohydrolase I. Cooperative binding of GTP to the enzyme."
      Hatakeyama K., Harada T., Suzuki S., Watanabe Y., Kagamiyama H.
      J. Biol. Chem. 264:21660-21664(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: PARTIAL PROTEIN SEQUENCE, CATALYTIC ACTIVITY, PATHWAY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
    4. Cited for: FUNCTION.
    5. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
      Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
      Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    6. "Crystal structure of the stimulatory complex of GTP cyclohydrolase I and its feedback regulatory protein GFRP."
      Maita N., Okada K., Hatakeyama K., Hakoshima T.
      Proc. Natl. Acad. Sci. U.S.A. 99:1212-1217(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 12-241 IN COMPLEX WITH GCHFR, SUBUNIT.

    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: May 11, 2016
    This is version 145 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.