GCH1_DICDI
ID GCH1_DICDI Reviewed; 232 AA.
AC Q94465; Q54IV6;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=GTP cyclohydrolase 1;
DE EC=3.5.4.16 {ECO:0000269|PubMed:8870645};
DE AltName: Full=GTP cyclohydrolase I {ECO:0000303|PubMed:8870645};
DE Short=GTP-CH {ECO:0000303|PubMed:8870645};
DE Short=GTP-CH-I;
GN Name=gchA; Synonyms=folE, gtoC; ORFNames=DDB_G0288481;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RC STRAIN=AX2;
RX PubMed=8870645; DOI=10.1042/bj3190027;
RA Witter K., Cahill D.J., Werner T., Ziegler I., Roedl W., Bacher A.,
RA Guetlich M.;
RT "Molecular cloning of a cDNA coding for GTP cyclohydrolase I from
RT Dictyostelium discoideum.";
RL Biochem. J. 319:27-32(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=AX2;
RX PubMed=16926386; DOI=10.1074/mcp.m600113-mcp200;
RA Gotthardt D., Blancheteau V., Bosserhoff A., Ruppert T., Delorenzi M.,
RA Soldati T.;
RT "Proteomics fingerprinting of phagosome maturation and evidence for the
RT role of a Galpha during uptake.";
RL Mol. Cell. Proteomics 5:2228-2243(2006).
CC -!- FUNCTION: First enzyme in the biosynthesis of tetrahydrobiopterin (BH4)
CC (PubMed:8870645). Catalyzes the conversion of GTP into dihydroneopterin
CC triphosphate (7,8-dihydroneopterin 3'-triphosphate), which is
CC subsequently catalyzed by 6-pyruvoyltetrahydropterin synthase (ptsA)
CC and sepiapterin reductase (sprA) (PubMed:8870645).
CC {ECO:0000269|PubMed:8870645}.
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:8870645};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17474;
CC Evidence={ECO:0000269|PubMed:8870645};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=50 uM for GTP {ECO:0000269|PubMed:8870645};
CC Temperature dependence:
CC Optimum temperature is 60 degrees Celsius.
CC {ECO:0000269|PubMed:8870645};
CC -!- PATHWAY: Cofactor biosynthesis; 7,8-dihydroneopterin triphosphate
CC biosynthesis; 7,8-dihydroneopterin triphosphate from GTP: step 1/1.
CC {ECO:0000305|PubMed:8870645}.
CC -!- SUBUNIT: Toroid-shaped homodecamer, composed of two pentamers of five
CC dimers. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the GTP cyclohydrolase I family. {ECO:0000305}.
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DR EMBL; Z49706; CAA89808.1; -; mRNA.
DR EMBL; AAFI02000112; EAL63189.1; -; Genomic_DNA.
DR PIR; S72439; S72439.
DR RefSeq; XP_636697.1; XM_631605.1.
DR AlphaFoldDB; Q94465; -.
DR SMR; Q94465; -.
DR STRING; 44689.DDB0191399; -.
DR PaxDb; Q94465; -.
DR EnsemblProtists; EAL63189; EAL63189; DDB_G0288481.
DR GeneID; 8626654; -.
DR KEGG; ddi:DDB_G0288481; -.
DR dictyBase; DDB_G0288481; gchA.
DR eggNOG; KOG2698; Eukaryota.
DR HOGENOM; CLU_049768_2_0_1; -.
DR InParanoid; Q94465; -.
DR OMA; CEHMCMS; -.
DR PhylomeDB; Q94465; -.
DR Reactome; R-DDI-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR UniPathway; UPA00848; UER00151.
DR PRO; PR:Q94465; -.
DR Proteomes; UP000002195; Chromosome 5.
DR GO; GO:0005737; C:cytoplasm; IDA:dictyBase.
DR GO; GO:0016020; C:membrane; IDA:dictyBase.
DR GO; GO:0045335; C:phagocytic vesicle; HDA:dictyBase.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0003934; F:GTP cyclohydrolase I activity; IDA:dictyBase.
DR GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR GO; GO:0035998; P:7,8-dihydroneopterin 3'-triphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IDA:dictyBase.
DR GO; GO:0140460; P:response to Gram-negative bacterium; HDA:dictyBase.
DR GO; GO:0006979; P:response to oxidative stress; IDA:dictyBase.
DR GO; GO:0006729; P:tetrahydrobiopterin biosynthetic process; IDA:dictyBase.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:InterPro.
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 Allosteric enzyme; GTP-binding; Hydrolase; Metal-binding;
KW Nucleotide-binding; Reference proteome; Tetrahydrobiopterin biosynthesis;
KW Zinc.
FT CHAIN 1..232
FT /note="GTP cyclohydrolase 1"
FT /id="PRO_0000119481"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 9..24
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 121
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 124
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 192
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT CONFLICT 187
FT /note="E -> D (in Ref. 1; CAA89808)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="V -> A (in Ref. 1; CAA89808)"
FT /evidence="ECO:0000305"
FT CONFLICT 216
FT /note="K -> E (in Ref. 1; CAA89808)"
FT /evidence="ECO:0000305"
FT CONFLICT 228..232
FT /note="IKSNK -> FNSTN (in Ref. 1; CAA89808)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 232 AA; 26277 MW; D36603D793EE5EA2 CRC64;
MSDNLKSYQD NHIENEDEEI YERSNGKGKE LVDFGKKREP LIHNHEVLNT MQSSVKTLLS
SLGEDPDREG LLKTPLRMSK ALLFFTQGYE QSVDEVIGEA IFNENHHEMV VVRDIDIFSL
CEHHMVPFHG KCHIGYIPDQ KVLGLSKLAR VAEIFARRLQ VQERLTRQIA QAIQAHLNPM
GVAVVIEASH MCMVMRGVQK PGASTVTSSV CGIFEKDSRT RAEFFSLIKS NK
