GCH1_RAT
ID GCH1_RAT Reviewed; 241 AA.
AC P22288;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=GTP cyclohydrolase 1;
DE EC=3.5.4.16 {ECO:0000269|PubMed:2557335};
DE AltName: Full=GTP cyclohydrolase I;
DE Short=GTP-CH-I;
DE Flags: Precursor;
GN Name=Gch1; Synonyms=Gch;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=1985963; DOI=10.1016/s0021-9258(17)35238-9;
RA Hatakeyama K., Inoue Y., Harada T., Kagamiyama H.;
RT "Cloning and sequencing of cDNA encoding rat GTP cyclohydrolase I. The
RT first enzyme of the tetrahydrobiopterin biosynthetic pathway.";
RL J. Biol. Chem. 266:765-769(1991).
RN [2]
RP PROTEIN SEQUENCE OF 37-46 AND 99-116.
RX PubMed=7802677; DOI=10.1006/bbrc.1994.2822;
RA Imazumi K., Sasaki T., Takahashi K., Takai Y.;
RT "Identification of a rabphilin-3A-interacting protein as GTP cyclohydrolase
RT I in PC12 cells.";
RL Biochem. Biophys. Res. Commun. 205:1409-1416(1994).
RN [3]
RP PARTIAL PROTEIN SEQUENCE, CATALYTIC ACTIVITY, PATHWAY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=2557335; DOI=10.1016/s0021-9258(20)88236-2;
RA Hatakeyama K., Harada T., Suzuki S., Watanabe Y., Kagamiyama H.;
RT "Purification and characterization of rat liver GTP cyclohydrolase I.
RT Cooperative binding of GTP to the enzyme.";
RL J. Biol. Chem. 264:21660-21664(1989).
RN [4]
RP FUNCTION.
RX PubMed=17057711; DOI=10.1038/nm1490;
RA Tegeder I., Costigan M., Griffin R.S., Abele A., Belfer I., Schmidt H.,
RA Ehnert C., Nejim J., Marian C., Scholz J., Wu T., Allchorne A.,
RA Diatchenko L., Binshtok A.M., Goldman D., Adolph J., Sama S., Atlas S.J.,
RA Carlezon W.A., Parsegian A., Loetsch J., Fillingim R.B., Maixner W.,
RA Geisslinger G., Max M.B., Woolf C.J.;
RT "GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and
RT persistence.";
RL Nat. Med. 12:1269-1277(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 12-241 IN COMPLEX WITH GCHFR, AND
RP SUBUNIT.
RX PubMed=11818540; DOI=10.1073/pnas.022646999;
RA Maita N., Okada K., Hatakeyama K., Hakoshima T.;
RT "Crystal structure of the stimulatory complex of GTP cyclohydrolase I and
RT its feedback regulatory protein GFRP.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:1212-1217(2002).
CC -!- FUNCTION: May positively regulate nitric oxide synthesis in endothelial
CC cells. May be involved in dopamine synthesis (By similarity). May
CC modify pain sensitivity and persistence. {ECO:0000250|UniProtKB:P30793,
CC ECO:0000269|PubMed:17057711}.
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:0000269|PubMed:2557335};
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+). {ECO:0000269|PubMed:2557335}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Vmax=2.7 umol/h/mg enzyme (at pH 7.5 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:2557335};
CC -!- PATHWAY: Cofactor biosynthesis; 7,8-dihydroneopterin triphosphate
CC biosynthesis; 7,8-dihydroneopterin triphosphate from GTP: step 1/1.
CC {ECO:0000305|PubMed:2557335}.
CC -!- SUBUNIT: Toroid-shaped homodecamer, composed of two pentamers of five
CC dimers. Interacts with AHSA1 and GCHFR/GFRP.
CC {ECO:0000269|PubMed:11818540}.
CC -!- INTERACTION:
CC P22288; P70552: Gchfr; NbExp=3; IntAct=EBI-1032708, EBI-1032715;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P30793}. Nucleus
CC {ECO:0000250|UniProtKB:P30793}.
CC -!- INDUCTION: By cytokines such as insulin, interferon-gamma, and
CC phytohemagglutinin in adrenal gland, macrophages, and T-cell
CC respectively.
CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:P30793}.
CC -!- SIMILARITY: Belongs to the GTP cyclohydrolase I family. {ECO:0000305}.
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DR EMBL; M58364; AAA41299.1; -; mRNA.
DR PIR; A39080; A39080.
DR RefSeq; NP_077332.1; NM_024356.1.
DR PDB; 1IS7; X-ray; 2.80 A; A/B/C/D/E/F/G/H/I/J=12-241.
DR PDB; 1IS8; X-ray; 2.70 A; A/B/C/D/E/F/G/H/I/J=12-241.
DR PDB; 1WPL; X-ray; 2.80 A; A/B/C/D/E/F/G/H/I/J=12-241.
DR PDBsum; 1IS7; -.
DR PDBsum; 1IS8; -.
DR PDBsum; 1WPL; -.
DR AlphaFoldDB; P22288; -.
DR SMR; P22288; -.
DR BioGRID; 247920; 2.
DR CORUM; P22288; -.
DR IntAct; P22288; 1.
DR STRING; 10116.ENSRNOP00000014821; -.
DR iPTMnet; P22288; -.
DR PhosphoSitePlus; P22288; -.
DR jPOST; P22288; -.
DR PaxDb; P22288; -.
DR Ensembl; ENSRNOT00000014821; ENSRNOP00000014821; ENSRNOG00000011039.
DR GeneID; 29244; -.
DR KEGG; rno:29244; -.
DR UCSC; RGD:61992; rat.
DR CTD; 2643; -.
DR RGD; 61992; Gch1.
DR eggNOG; KOG2698; Eukaryota.
DR GeneTree; ENSGT00390000013481; -.
DR HOGENOM; CLU_049768_1_3_1; -.
DR InParanoid; P22288; -.
DR OMA; CEHMCMS; -.
DR OrthoDB; 793457at2759; -.
DR PhylomeDB; P22288; -.
DR BRENDA; 3.5.4.16; 5301.
DR Reactome; R-RNO-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR SABIO-RK; P22288; -.
DR UniPathway; UPA00848; UER00151.
DR EvolutionaryTrace; P22288; -.
DR PRO; PR:P22288; -.
DR Proteomes; UP000002494; Chromosome 15.
DR Bgee; ENSRNOG00000011039; Expressed in duodenum and 17 other tissues.
DR Genevisible; P22288; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0031965; C:nuclear membrane; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0005509; F:calcium ion binding; IDA:RGD.
DR GO; GO:0005525; F:GTP binding; IDA:RGD.
DR GO; GO:0003934; F:GTP cyclohydrolase I activity; IDA:RGD.
DR GO; GO:0030742; F:GTP-dependent protein binding; IPI:RGD.
DR GO; GO:0003924; F:GTPase activity; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; IDA:RGD.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0031369; F:translation initiation factor binding; IPI:RGD.
DR GO; GO:0008270; F:zinc ion binding; IDA:RGD.
DR GO; GO:0035998; P:7,8-dihydroneopterin 3'-triphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0051066; P:dihydrobiopterin metabolic process; IDA:RGD.
DR GO; GO:0042416; P:dopamine biosynthetic process; ISO:RGD.
DR GO; GO:0045776; P:negative regulation of blood pressure; IMP:RGD.
DR GO; GO:0050884; P:neuromuscular process controlling posture; ISO:RGD.
DR GO; GO:0010460; P:positive regulation of heart rate; ISO:RGD.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; ISO:RGD.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:RGD.
DR GO; GO:0042559; P:pteridine-containing compound biosynthetic process; ISO:RGD.
DR GO; GO:0008217; P:regulation of blood pressure; ISO:RGD.
DR GO; GO:0014916; P:regulation of lung blood pressure; ISO:RGD.
DR GO; GO:2000121; P:regulation of removal of superoxide radicals; ISO:RGD.
DR GO; GO:0034341; P:response to interferon-gamma; ISO:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0048265; P:response to pain; IDA:UniProtKB.
DR GO; GO:0034612; P:response to tumor necrosis factor; ISO:RGD.
DR GO; GO:0006729; P:tetrahydrobiopterin biosynthetic process; ISO:RGD.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:InterPro.
DR GO; GO:0042311; P:vasodilation; IMP:RGD.
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 PANTHER; PTHR11109; PTHR11109; 1.
DR Pfam; PF01227; GTP_cyclohydroI; 1.
DR TIGRFAMs; TIGR00063; folE; 1.
DR PROSITE; PS00859; GTP_CYCLOHYDROL_1_1; 1.
DR PROSITE; PS00860; GTP_CYCLOHYDROL_1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; Cytoplasm; Direct protein sequencing;
KW GTP-binding; Hydrolase; Metal-binding; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Tetrahydrobiopterin biosynthesis; Zinc.
FT PROPEP 1..11
FT /id="PRO_0000010720"
FT CHAIN 12..241
FT /note="GTP cyclohydrolase 1"
FT /id="PRO_0000010721"
FT REGION 1..58
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:22673903"
FT MOD_RES 72
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P30793"
FT HELIX 52..73
FT /evidence="ECO:0007829|PDB:1IS8"
FT TURN 80..84
FT /evidence="ECO:0007829|PDB:1IS8"
FT HELIX 85..96
FT /evidence="ECO:0007829|PDB:1IS8"
FT HELIX 98..101
FT /evidence="ECO:0007829|PDB:1IS8"
FT HELIX 105..108
FT /evidence="ECO:0007829|PDB:1IS8"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:1IS8"
FT STRAND 112..117
FT /evidence="ECO:0007829|PDB:1IS7"
FT STRAND 121..132
FT /evidence="ECO:0007829|PDB:1IS8"
FT TURN 133..135
FT /evidence="ECO:0007829|PDB:1IS8"
FT STRAND 138..148
FT /evidence="ECO:0007829|PDB:1IS8"
FT STRAND 150..154
FT /evidence="ECO:0007829|PDB:1IS7"
FT HELIX 156..167
FT /evidence="ECO:0007829|PDB:1IS8"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:1IS8"
FT HELIX 173..188
FT /evidence="ECO:0007829|PDB:1IS8"
FT STRAND 191..201
FT /evidence="ECO:0007829|PDB:1IS8"
FT HELIX 202..205
FT /evidence="ECO:0007829|PDB:1IS8"
FT STRAND 207..210
FT /evidence="ECO:0007829|PDB:1IS7"
FT STRAND 215..223
FT /evidence="ECO:0007829|PDB:1IS8"
FT HELIX 224..227
FT /evidence="ECO:0007829|PDB:1IS8"
FT HELIX 229..239
FT /evidence="ECO:0007829|PDB:1IS8"
SQ SEQUENCE 241 AA; 27057 MW; 8226E3319816325B CRC64;
MEKPRGVRCT NGFPERELPR PGASRPAEKS RPPEAKGAQP ADAWKAGRPR SEEDNELNLP
NLAAAYSSIL RSLGEDPQRQ GLLKTPWRAA TAMQFFTKGY QETISDVLND AIFDEDHDEM
VIVKDIDMFS MCEHHLVPFV GRVHIGYLPN KQVLGLSKLA RIVEIYSRRL QVQERLTKQI
AVAITEALQP AGVGVVIEAT HMCMVMRGVQ KMNSKTVTST MLGVFREDPK TREEFLTLIR
S
