ID   GCH1_NEUCR              Reviewed;         313 AA.
AC   P51599; Q7RV90; Q9C2R6;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   30-APR-2003, sequence version 2.
DT   04-NOV-2026, entry version 136.
DE   RecName: Full=GTP cyclohydrolase 1;
DE            EC=3.5.4.16;
DE   AltName: Full=GTP cyclohydrolase I;
DE            Short=GTP-CH-I;
GN   Name=gch-1; ORFNames=104H10.80, NCU07774;
OS   Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 /
OS   FGSC 987).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Sordariomycetidae; Sordariales; Sordariaceae; Neurospora.
OX   NCBI_TaxID=367110;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX   PubMed=12655011; DOI=10.1093/nar/gkg293;
RA   Mannhaupt G., Montrone C., Haase D., Mewes H.-W., Aign V., Hoheisel J.D.,
RA   Fartmann B., Nyakatura G., Kempken F., Maier J., Schulte U.;
RT   "What's in the genome of a filamentous fungus? Analysis of the Neurospora
RT   genome sequence.";
RL   Nucleic Acids Res. 31:1944-1954(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX   PubMed=12712197; DOI=10.1038/nature01554;
RA   Galagan J.E., Calvo S.E., Borkovich K.A., Selker E.U., Read N.D.,
RA   Jaffe D.B., FitzHugh W., Ma L.-J., Smirnov S., Purcell S., Rehman B.,
RA   Elkins T., Engels R., Wang S., Nielsen C.B., Butler J., Endrizzi M.,
RA   Qui D., Ianakiev P., Bell-Pedersen D., Nelson M.A., Werner-Washburne M.,
RA   Selitrennikoff C.P., Kinsey J.A., Braun E.L., Zelter A., Schulte U.,
RA   Kothe G.O., Jedd G., Mewes H.-W., Staben C., Marcotte E., Greenberg D.,
RA   Roy A., Foley K., Naylor J., Stange-Thomann N., Barrett R., Gnerre S.,
RA   Kamal M., Kamvysselis M., Mauceli E.W., Bielke C., Rudd S., Frishman D.,
RA   Krystofova S., Rasmussen C., Metzenberg R.L., Perkins D.D., Kroken S.,
RA   Cogoni C., Macino G., Catcheside D.E.A., Li W., Pratt R.J., Osmani S.A.,
RA   DeSouza C.P.C., Glass N.L., Orbach M.J., Berglund J.A., Voelker R.,
RA   Yarden O., Plamann M., Seiler S., Dunlap J.C., Radford A., Aramayo R.,
RA   Natvig D.O., Alex L.A., Mannhaupt G., Ebbole D.J., Freitag M., Paulsen I.,
RA   Sachs M.S., Lander E.S., Nusbaum C., Birren B.W.;
RT   "The genome sequence of the filamentous fungus Neurospora crassa.";
RL   Nature 422:859-868(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 185-278.
RC   STRAIN=BD AL-2;
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).
CC   -!- FUNCTION: GTP cyclohydrolase 1 is the first enzyme in the biosynthetic
CC       pathway leading to folic acid.
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   -!- ACTIVITY REGULATION: GTP shows a positive allosteric effect, and
CC       tetrahydrobiopterin inhibits the enzyme activity. {ECO:0000250}.
CC   -!- PATHWAY: Cofactor biosynthesis; 7,8-dihydroneopterin triphosphate
CC       biosynthesis; 7,8-dihydroneopterin triphosphate from GTP: step 1/1.
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; AL513410; CAC28574.1; -; Genomic_DNA.
DR   EMBL; CM002240; EAA29459.3; -; Genomic_DNA.
DR   EMBL; Z49758; CAA89828.1; -; mRNA.
DR   RefSeq; XP_958695.3; XM_953602.3.
DR   AlphaFoldDB; P51599; -.
DR   SMR; P51599; -.
DR   FunCoup; P51599; 350.
DR   STRING; 367110.P51599; -.
DR   PaxDb; 367110-P51599; -.
DR   EnsemblFungi; EAA29459; EAA29459; NCU07774.
DR   GeneID; 3874842; -.
DR   KEGG; ncr:NCU07774; -.
DR   VEuPathDB; FungiDB:NCU07774; -.
DR   HOGENOM; CLU_049768_3_4_1; -.
DR   InParanoid; P51599; -.
DR   OrthoDB; 4966at2759; -.
DR   UniPathway; UPA00848; UER00151.
DR   Proteomes; UP000001805; Chromosome 2, Linkage Group V.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0003934; F:GTP cyclohydrolase I activity; IBA:GO_Central.
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   2: Evidence at transcript level;
KW   Allosteric enzyme; Folate biosynthesis; GTP-binding; Hydrolase;
KW   Metal-binding; Nucleotide-binding; Reference proteome; Zinc.
FT   CHAIN           1..313
FT                   /note="GTP cyclohydrolase 1"
FT                   /id="PRO_0000119486"
FT   REGION          1..120
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..10
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        11..20
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        29..39
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        40..64
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        72..102
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         202
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   BINDING         205
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   BINDING         273
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        186..188
FT                   /note="GHN -> DHD (in Ref. 3; CAA89828)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   313 AA;  34471 MW;  C8535C0A7FF84114 CRC64;
     MAQETTRDGS DSPSGSVSPP IANGTNNKKD KKSSKKRAHS SGERRSSVSK PARDPSDKPE
     ESPSKKKKRK TTSSTAAAAV PSTITEEVSP STSVTRSPSP VIDFDGLSRP SRGTRERLEE
     TEAQKQERLD KMKGAVRTLL ECIGEDPDRE GLLATPERYA KAMLFLTKGY QENVRDIVNG
     AIFQEGHNEM VIVKDIEVFS MCEHHLVPFT GKMHIGYIPS NAVIGISKLP RIAELFARRL
     QIQERLTKEV ANAIMEILKP QGVAVVMESS HLCMVMRGVQ KTTSSTITSC VLGCFESREK
     TRLEFLSLIG VNR
//