ID   GCH1_MOUSE              Reviewed;         241 AA.
AC   Q05915;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1994, sequence version 1.
DT   27-MAR-2024, entry version 186.
DE   RecName: Full=GTP cyclohydrolase 1;
DE            EC=3.5.4.16 {ECO:0000250|UniProtKB:P30793};
DE   AltName: Full=GTP cyclohydrolase I;
DE            Short=GTP-CH-I;
DE   Flags: Precursor;
GN   Name=Gch1; Synonyms=Gch;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=ICR; TISSUE=Brain;
RX   PubMed=8461009; DOI=10.1006/bbrc.1993.1249;
RA   Nomura T., Ichinose H., Sumi-Ichinose C., Nomura H., Hagino Y., Fujita K.,
RA   Nagatsu T.;
RT   "Cloning and sequencing of cDNA encoding mouse GTP cyclohydrolase I.";
RL   Biochem. Biophys. Res. Commun. 191:523-527(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Colon, and Mammary gland;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 51-241.
RX   PubMed=8304101; DOI=10.1007/978-1-4615-2960-6_32;
RA   Gutlich M., Schott K., Werner T., Bacher A., Ziegler I.;
RT   "Detection and quantification of GTP cyclohydrolase I mRNA.";
RL   Adv. Exp. Med. Biol. 338:167-170(1993).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA   Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of mouse liver.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Liver, and Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: May positively regulate nitric oxide synthesis in endothelial
CC       cells. May be involved in dopamine synthesis. May modify pain
CC       sensitivity and persistence. {ECO:0000250|UniProtKB:P30793}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=GTP + H2O = 7,8-dihydroneopterin 3'-triphosphate + formate +
CC         H(+); Xref=Rhea:RHEA:17473, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15740, ChEBI:CHEBI:37565, ChEBI:CHEBI:58462; EC=3.5.4.16;
CC         Evidence={ECO:0000250|UniProtKB:P30793};
CC   -!- ACTIVITY REGULATION: GTP shows a positive allosteric effect, and
CC       tetrahydrobiopterin inhibits the enzyme activity. Zinc is required for
CC       catalytic activity. Inhibited by Mg(2+).
CC       {ECO:0000250|UniProtKB:P30793}.
CC   -!- PATHWAY: Cofactor biosynthesis; 7,8-dihydroneopterin triphosphate
CC       biosynthesis; 7,8-dihydroneopterin triphosphate from GTP: step 1/1.
CC       {ECO:0000250|UniProtKB:P30793}.
CC   -!- SUBUNIT: Toroid-shaped homodecamer, composed of two pentamers of five
CC       dimers. Interacts with AHSA1 and GCHFR/GFRP.
CC       {ECO:0000250|UniProtKB:P30793}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P30793}. Nucleus
CC       {ECO:0000250|UniProtKB:P30793}.
CC   -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:P30793}.
CC   -!- SIMILARITY: Belongs to the GTP cyclohydrolase I family. {ECO:0000305}.
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DR   EMBL; L09737; AAA37757.1; -; mRNA.
DR   EMBL; BC005643; AAH05643.1; -; mRNA.
DR   EMBL; BC069921; AAH69921.1; -; mRNA.
DR   EMBL; S71373; AAC60677.2; -; mRNA.
DR   CCDS; CCDS26984.1; -.
DR   PIR; JQ1934; JQ1934.
DR   RefSeq; NP_032128.1; NM_008102.3.
DR   AlphaFoldDB; Q05915; -.
DR   SMR; Q05915; -.
DR   BioGRID; 199864; 2.
DR   STRING; 10090.ENSMUSP00000087405; -.
DR   iPTMnet; Q05915; -.
DR   PhosphoSitePlus; Q05915; -.
DR   jPOST; Q05915; -.
DR   PaxDb; 10090-ENSMUSP00000087405; -.
DR   PeptideAtlas; Q05915; -.
DR   ProteomicsDB; 268856; -.
DR   Antibodypedia; 23963; 407 antibodies from 35 providers.
DR   DNASU; 14528; -.
DR   Ensembl; ENSMUST00000089959.7; ENSMUSP00000087405.7; ENSMUSG00000037580.11.
DR   GeneID; 14528; -.
DR   KEGG; mmu:14528; -.
DR   UCSC; uc007tht.1; mouse.
DR   AGR; MGI:95675; -.
DR   CTD; 2643; -.
DR   MGI; MGI:95675; Gch1.
DR   VEuPathDB; HostDB:ENSMUSG00000037580; -.
DR   eggNOG; KOG2698; Eukaryota.
DR   GeneTree; ENSGT00390000013481; -.
DR   HOGENOM; CLU_049768_1_3_1; -.
DR   InParanoid; Q05915; -.
DR   OMA; CEHMCMS; -.
DR   OrthoDB; 1009at2759; -.
DR   PhylomeDB; Q05915; -.
DR   TreeFam; TF105616; -.
DR   BRENDA; 3.5.4.16; 3474.
DR   Reactome; R-MMU-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR   UniPathway; UPA00848; UER00151.
DR   BioGRID-ORCS; 14528; 5 hits in 78 CRISPR screens.
DR   ChiTaRS; Gch1; mouse.
DR   PRO; PR:Q05915; -.
DR   Proteomes; UP000000589; Chromosome 14.
DR   RNAct; Q05915; Protein.
DR   Bgee; ENSMUSG00000037580; Expressed in superior cervical ganglion and 190 other cell types or tissues.
DR   ExpressionAtlas; Q05915; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR   GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; ISO:MGI.
DR   GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR   GO; GO:0005509; F:calcium ion binding; ISO:MGI.
DR   GO; GO:0005525; F:GTP binding; ISO:MGI.
DR   GO; GO:0003934; F:GTP cyclohydrolase I activity; IDA:MGI.
DR   GO; GO:0030742; F:GTP-dependent protein binding; ISO:MGI.
DR   GO; GO:0003924; F:GTPase activity; ISO:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0051019; F:mitogen-activated protein kinase binding; ISO:MGI.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR   GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR   GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR   GO; GO:0035998; P:7,8-dihydroneopterin 3'-triphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; TAS:ParkinsonsUK-UCL.
DR   GO; GO:0051066; P:dihydrobiopterin metabolic process; ISO:MGI.
DR   GO; GO:0042416; P:dopamine biosynthetic process; ISO:MGI.
DR   GO; GO:0045776; P:negative regulation of blood pressure; ISO:MGI.
DR   GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; ISO:MGI.
DR   GO; GO:2000773; P:negative regulation of cellular senescence; ISO:MGI.
DR   GO; GO:0050884; P:neuromuscular process controlling posture; ISO:MGI.
DR   GO; GO:0010460; P:positive regulation of heart rate; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
DR   GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; ISO:MGI.
DR   GO; GO:0065003; P:protein-containing complex assembly; ISO:MGI.
DR   GO; GO:0042559; P:pteridine-containing compound biosynthetic process; ISO:MGI.
DR   GO; GO:0008217; P:regulation of blood pressure; IMP:MGI.
DR   GO; GO:0014916; P:regulation of lung blood pressure; IMP:MGI.
DR   GO; GO:2000121; P:regulation of removal of superoxide radicals; ISO:MGI.
DR   GO; GO:1905627; P:regulation of serotonin biosynthetic process; NAS:ParkinsonsUK-UCL.
DR   GO; GO:0048265; P:response to pain; ISS:UniProtKB.
DR   GO; GO:0034612; P:response to tumor necrosis factor; ISO:MGI.
DR   GO; GO:0034341; P:response to type II interferon; ISO:MGI.
DR   GO; GO:0006729; P:tetrahydrobiopterin biosynthetic process; ISO:MGI.
DR   GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:InterPro.
DR   GO; GO:0042311; P:vasodilation; ISO:MGI.
DR   CDD; cd00642; GTP_cyclohydro1; 1.
DR   Gene3D; 1.10.286.10; -; 1.
DR   Gene3D; 3.30.1130.10; -; 1.
DR   HAMAP; MF_00223; FolE; 1.
DR   InterPro; IPR043133; GTP-CH-I_C/QueF.
DR   InterPro; IPR043134; GTP-CH-I_N.
DR   InterPro; IPR001474; GTP_CycHdrlase_I.
DR   InterPro; IPR018234; GTP_CycHdrlase_I_CS.
DR   InterPro; IPR020602; GTP_CycHdrlase_I_dom.
DR   NCBIfam; TIGR00063; folE; 1.
DR   PANTHER; PTHR11109:SF11; GTP CYCLOHYDROLASE 1; 1.
DR   PANTHER; PTHR11109; GTP CYCLOHYDROLASE I; 1.
DR   Pfam; PF01227; GTP_cyclohydroI; 1.
DR   SUPFAM; SSF55620; Tetrahydrobiopterin biosynthesis enzymes-like; 1.
DR   PROSITE; PS00859; GTP_CYCLOHYDROL_1_1; 1.
DR   PROSITE; PS00860; GTP_CYCLOHYDROL_1_2; 1.
DR   Genevisible; Q05915; MM.
PE   1: Evidence at protein level;
KW   Allosteric enzyme; Cytoplasm; GTP-binding; Hydrolase; Metal-binding;
KW   Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW   Tetrahydrobiopterin biosynthesis; Zinc.
FT   PROPEP          1..11
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000010718"
FT   CHAIN           12..241
FT                   /note="GTP cyclohydrolase 1"
FT                   /id="PRO_0000010719"
FT   REGION          1..56
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         132
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P30793"
FT   BINDING         135
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P30793"
FT   BINDING         203
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P30793"
FT   SITE            87
FT                   /note="Involved in pterin ring binding"
FT                   /evidence="ECO:0000250"
FT   SITE            96
FT                   /note="Involved in pterin ring binding"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         51
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17242355,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         72
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P30793"
FT   CONFLICT        54
FT                   /note="E -> D (in Ref. 3; AAC60677)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        56
FT                   /note="Q -> E (in Ref. 3; AAC60677)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        235
FT                   /note="F -> S (in Ref. 3; AAC60677)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   241 AA;  27014 MW;  B4366F102B4A6FE6 CRC64;
     MEKPRGVRCT NGFSERELPR PGASPPAEKS RPPEAKGAQP ADAWKAGRHR SEEENQVNLP
     KLAAAYSSIL LSLGEDPQRQ GLLKTPWRAA TAMQYFTKGY QETISDVLND AIFDEDHDEM
     VIVKDIDMFS MCEHHLVPFV GRVHIGYLPN KQVLGLSKLA RIVEIYSRRL QVQERLTKQI
     AVAITEALQP AGVGVVIEAT HMCMVMRGVQ KMNSKTVTST MLGVFREDPK TREEFLTLIR
     S
//