ID GCH1_YEAST Reviewed; 243 AA. AC P51601; D6VV45; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 04-NOV-2026, entry version 196. DE RecName: Full=GTP cyclohydrolase 1 {ECO:0000303|Ref.1}; DE EC=3.5.4.16 {ECO:0000305|Ref.1}; DE AltName: Full=GTP cyclohydrolase I {ECO:0000303|Ref.1}; DE Short=GTP-CH-I {ECO:0000303|Ref.1}; GN Name=FOL2 {ECO:0000303|Ref.1}; OrderedLocusNames=YGR267C; GN ORFNames=G9349; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; OC Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DISRUPTION PHENOTYPE. RC STRAIN=C836; RA Witter K., Guetlich M., Stucka R., Ziegler I., Bacher A.; RL Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 96604 / S288c / FY1679; RX PubMed=8573145; DOI=10.1006/bbrc.1996.0048; RA Nardese V., Gutlich M., Brambilla A., Agostoni Carbone M.L.; RT "Disruption of the GTP-cyclohydrolase I gene in Saccharomyces cerevisiae."; RL Biochem. Biophys. Res. Commun. 218:273-279(1996). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 96604 / S288c / FY1679; RX PubMed=9605509; RX DOI=10.1002/(sici)1097-0061(19980430)14:6<587::aid-yea268>3.0.co;2-i; RA Agostoni Carbone M.L., Lucchini G., Melchioretto P., Nardese V., Vanoni M., RA Panzeri L.; RT "A 9359 bp fragment from the right arm of Saccharomyces cerevisiae RT chromosome VII includes the FOL2 and YTA7 genes and three unknown open RT reading frames."; RL Yeast 14:587-591(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169869; DOI=10.1038/387s081; RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J., RA Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M., RA Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L., RA Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H., RA Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P., RA Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M., RA Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A., RA Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K., RA Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P., RA Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E., RA Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K., RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A., RA Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S., RA Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M., RA Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C., RA Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M., RA Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M., RA Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y., RA Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L., RA Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D., RA Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F., RA Zaccaria P., Zimmermann M., Zollner A., Kleine K.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII."; RL Nature 387:81-84(1997). RN [5] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now."; RL G3 (Bethesda) 4:389-398(2014). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=17322287; DOI=10.1101/gr.6037607; RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J., RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., RA LaBaer J.; RT "Approaching a complete repository of sequence-verified protein-encoding RT clones for Saccharomyces cerevisiae."; RL Genome Res. 17:536-543(2007). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 115-208. RC STRAIN=ATCC 204508 / S288c; RX PubMed=7542887; DOI=10.1006/bbrc.1995.2026; RA Maier J., Witter K., Guetlich M., Ziegler I., Werner T., Ninnemann H.; RT "Homology cloning of GTP-cyclohydrolase I from various unrelated eukaryotes RT by reverse-transcription polymerase chain reaction using a general set of RT degenerate primers."; RL Biochem. Biophys. Res. Commun. 212:705-711(1995). RN [8] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., RA O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-15 AND SER-23, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC STRAIN=ADR376; RX PubMed=17330950; DOI=10.1021/pr060559j; RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J., RA Elias J.E., Gygi S.P.; RT "Large-scale phosphorylation analysis of alpha-factor-arrested RT Saccharomyces cerevisiae."; RL J. Proteome Res. 6:1190-1197(2007). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-15, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200; RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.; RT "A multidimensional chromatography technology for in-depth phosphoproteome RT analysis."; RL Mol. Cell. Proteomics 7:1389-1396(2008). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-15 AND SER-23, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19779198; DOI=10.1126/science.1172867; RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.; RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights RT into evolution."; RL Science 325:1682-1686(2009). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). CC -!- FUNCTION: GTP cyclohydrolase 1 is the first enzyme in the biosynthetic CC pathway leading to folic acid. {ECO:0000269|Ref.1}. 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:0000305|Ref.1}; CC -!- PATHWAY: Cofactor biosynthesis; 7,8-dihydroneopterin triphosphate CC biosynthesis; 7,8-dihydroneopterin triphosphate from GTP: step 1/1. CC {ECO:0000305|Ref.1}. CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q8VYU3}. CC -!- DISRUPTION PHENOTYPE: Leads to folinic acid auxotrophy, and lacks any CC detectable specific enzymatic activity. {ECO:0000269|Ref.1}. CC -!- MISCELLANEOUS: Present with 2840 molecules/cell in log phase SD medium. CC {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the GTP cyclohydrolase I family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z47201; CAA87397.1; -; Genomic_DNA. DR EMBL; X94314; CAA63975.1; -; Genomic_DNA. DR EMBL; Y07893; CAA69198.1; -; Genomic_DNA. DR EMBL; Z73052; CAA97297.1; -; Genomic_DNA. DR EMBL; AY692993; AAT93012.1; -; Genomic_DNA. DR EMBL; Z49756; CAA89826.1; -; mRNA. DR EMBL; BK006941; DAA08356.1; -; Genomic_DNA. DR PIR; JC4585; JC4585. DR RefSeq; NP_011783.1; NM_001181396.1. DR AlphaFoldDB; P51601; -. DR SMR; P51601; -. DR BioGRID; 33517; 67. DR DIP; DIP-1318N; -. DR FunCoup; P51601; 485. DR IntAct; P51601; 18. DR STRING; 4932.YGR267C; -. DR GlyGen; P51601; 1 site. DR iPTMnet; P51601; -. DR PaxDb; 4932-YGR267C; -. DR PeptideAtlas; P51601; -. DR EnsemblFungi; YGR267C_mRNA; YGR267C; YGR267C. DR GeneID; 853183; -. DR KEGG; sce:YGR267C; -. DR AGR; SGD:S000003499; -. DR SGD; S000003499; FOL2. DR VEuPathDB; FungiDB:YGR267C; -. DR eggNOG; KOG2698; Eukaryota. DR HOGENOM; CLU_049768_1_3_1; -. DR InParanoid; P51601; -. DR OMA; AAHLCMV; -. DR OrthoDB; 4966at2759; -. DR BioCyc; YEAST:YGR267C-MONOMER; -. DR Reactome; R-SCE-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation. DR UniPathway; UPA00848; UER00151. DR BioGRID-ORCS; 853183; 7 hits in 10 CRISPR screens. DR PRO; PR:P51601; -. DR Proteomes; UP000002311; Chromosome VII. DR RNAct; P51601; protein. DR GO; GO:0005737; C:cytoplasm; HDA:SGD. DR GO; GO:0005634; C:nucleus; IDA:SGD. DR GO; GO:0003934; F:GTP cyclohydrolase I activity; IMP:SGD. DR GO; GO:0009396; P:folic acid-containing compound biosynthetic process; IMP:SGD. DR GO; GO:0006729; P:tetrahydrobiopterin biosynthetic process; IBA:GO_Central. DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:InterPro. DR CDD; cd00642; GTP_cyclohydro1; 1. DR FunFam; 1.10.286.10:FF:000003; GTP cyclohydrolase 1; 1. DR FunFam; 3.30.1130.10:FF:000012; GTP cyclohydrolase 1; 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; NF006825; folE; 1. DR NCBIfam; NF006826; folE; 1. DR NCBIfam; TIGR00063; folE; 1. DR PANTHER; PTHR11109:SF7; 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. PE 1: Evidence at protein level; KW Allosteric enzyme; Folate biosynthesis; GTP-binding; Hydrolase; KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome; KW Zinc. FT CHAIN 1..243 FT /note="GTP cyclohydrolase 1" FT /id="PRO_0000119489" FT REGION 18..55 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 MOD_RES 15 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17330950, FT ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198" FT MOD_RES 23 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17330950, FT ECO:0007744|PubMed:19779198" FT CONFLICT 159..160 FT /note="LA -> QG (in Ref. 7; CAA89826)" FT /evidence="ECO:0000305" FT CONFLICT 206 FT /note="S -> M (in Ref. 7; CAA89826)" FT /evidence="ECO:0000305" FT CONFLICT 217 FT /note="V -> A (in Ref. 1; CAA87397)" FT /evidence="ECO:0000305" SQ SEQUENCE 243 AA; 27769 MW; A71AB8750AECD3F6 CRC64; MHNIQLVQEI ERHETPLNIR PTSPYTLNPP VERDGFSWPS VGTRQRAEET EEEEKERIQR ISGAIKTILT ELGEDVNREG LLDTPQRYAK AMLYFTKGYQ TNIMDDVIKN AVFEEDHDEM VIVRDIEIYS LCEHHLVPFF GKVHIGYIPN KKVIGLSKLA RLAEMYARRL QVQERLTKQI AMALSDILKP LGVAVVMEAS HMCMVSRGIQ KTGSSTVTSC MLGGFRAHKT REEFLTLLGR RSI //