GCH1_DROME
ID GCH1_DROME Reviewed; 324 AA.
AC P48596; Q6TY66; Q6TY71; Q6TY73; Q6TY74; Q6TY78; Q960S4; Q9W2J9; Q9W2K1;
AC Q9Y0C8;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 27-JAN-2003, sequence version 3.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=GTP cyclohydrolase 1;
DE EC=3.5.4.16 {ECO:0000269|PubMed:3080426};
DE AltName: Full=GTP cyclohydrolase I;
DE Short=GTP-CH-I;
DE AltName: Full=Protein punch;
GN Name=Pu; ORFNames=CG9441;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND C), FUNCTION, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Head;
RX PubMed=8262960; DOI=10.1016/s0021-9258(19)74237-9;
RA McLean J.R., Krishnakumar S., O'Donnell J.M.;
RT "Multiple mRNAs from the Punch locus of Drosophila melanogaster encode
RT isoforms of GTP cyclohydrolase I with distinct N-terminal domains.";
RL J. Biol. Chem. 268:27191-27197(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RC TISSUE=Embryo;
RA Xu D., Neckameyer W., O'Donnell J.;
RT "Differential regulation of Drosophila GTP cyclohydrolase I isoforms and
RT their interaction with tyrosine hydroxylase.";
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-58; PRO-61; VAL-77 AND
RP SER-84.
RC STRAIN=Raleigh Inbred 1, Raleigh Inbred 11, Raleigh Inbred 24,
RC Raleigh Inbred 27, Raleigh Inbred 30, Raleigh Inbred 33, Raleigh Inbred 6,
RC and Raleigh Inbred 9;
RA Geiger-Thornsberry G.L., Harbison S.T., Lyman R.F., Mackay T.F.C.;
RT "Punch affects life history traits in Drosophila melanogaster.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [5]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [7]
RP CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=3080426; DOI=10.1016/s0021-9258(17)36114-8;
RA Weisberg E.P., O'Donnell J.M.;
RT "Purification and characterization of GTP cyclohydrolase I from Drosophila
RT melanogaster.";
RL J. Biol. Chem. 261:1453-1458(1986).
CC -!- FUNCTION: Isoform B is required for eye pigment production, Isoform C
CC may be required for normal embryonic development and segment pattern
CC formation. {ECO:0000269|PubMed:8262960}.
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:3080426};
CC -!- PATHWAY: Cofactor biosynthesis; 7,8-dihydroneopterin triphosphate
CC biosynthesis; 7,8-dihydroneopterin triphosphate from GTP: step 1/1.
CC {ECO:0000305|PubMed:3080426}.
CC -!- SUBUNIT: Toroid-shaped homodecamer, composed of two pentamers of five
CC dimers. {ECO:0000250|UniProtKB:P30793}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=A; Synonyms=C;
CC IsoId=P48596-1; Sequence=Displayed;
CC Name=B;
CC IsoId=P48596-2; Sequence=VSP_001616;
CC Name=C;
CC IsoId=P48596-3; Sequence=VSP_001615;
CC -!- TISSUE SPECIFICITY: Isoform B is expressed almost exclusively in adult
CC heads. {ECO:0000269|PubMed:8262960}.
CC -!- DEVELOPMENTAL STAGE: Isoform C is expressed in embryos, larvae and
CC adults. {ECO:0000269|PubMed:8262960}.
CC -!- SIMILARITY: Belongs to the GTP cyclohydrolase I family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC04308.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAC04309.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAD44334.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAR20857.2; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U01118; AAC04308.1; ALT_FRAME; mRNA.
DR EMBL; U01119; AAC04309.1; ALT_FRAME; mRNA.
DR EMBL; AF159422; AAD44334.1; ALT_FRAME; mRNA.
DR EMBL; AY382619; AAR20848.1; -; Genomic_DNA.
DR EMBL; AY382620; AAR20850.1; -; Genomic_DNA.
DR EMBL; AY382622; AAR20852.1; -; Genomic_DNA.
DR EMBL; AY382623; AAR20854.1; -; Genomic_DNA.
DR EMBL; AY382624; AAR20855.1; -; Genomic_DNA.
DR EMBL; AY382625; AAR20857.2; ALT_FRAME; Genomic_DNA.
DR EMBL; AY382626; AAR20859.1; -; Genomic_DNA.
DR EMBL; AY382628; AAR20862.1; -; Genomic_DNA.
DR EMBL; AE013599; AAF46690.1; -; Genomic_DNA.
DR EMBL; AE013599; AAF46692.1; -; Genomic_DNA.
DR EMBL; AE013599; AAM70858.1; -; Genomic_DNA.
DR EMBL; AY051890; AAK93314.1; -; mRNA.
DR PIR; A49302; A49302.
DR PIR; B49302; B49302.
DR RefSeq; NP_523801.2; NM_079077.4. [P48596-3]
DR RefSeq; NP_726037.1; NM_166430.3. [P48596-2]
DR RefSeq; NP_726038.1; NM_166431.4. [P48596-1]
DR AlphaFoldDB; P48596; -.
DR SMR; P48596; -.
DR BioGRID; 63049; 10.
DR DIP; DIP-24104N; -.
DR IntAct; P48596; 14.
DR STRING; 7227.FBpp0071507; -.
DR PaxDb; P48596; -.
DR DNASU; 37415; -.
DR EnsemblMetazoa; FBtr0071578; FBpp0071505; FBgn0003162. [P48596-2]
DR EnsemblMetazoa; FBtr0071579; FBpp0071506; FBgn0003162. [P48596-3]
DR EnsemblMetazoa; FBtr0071580; FBpp0071507; FBgn0003162. [P48596-1]
DR GeneID; 37415; -.
DR KEGG; dme:Dmel_CG9441; -.
DR CTD; 37415; -.
DR FlyBase; FBgn0003162; Pu.
DR VEuPathDB; VectorBase:FBgn0003162; -.
DR eggNOG; KOG2698; Eukaryota.
DR GeneTree; ENSGT00390000013481; -.
DR InParanoid; P48596; -.
DR OMA; MVQAVRT; -.
DR PhylomeDB; P48596; -.
DR BioCyc; MetaCyc:MON-18450; -.
DR BRENDA; 3.5.4.16; 1994.
DR Reactome; R-DME-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR UniPathway; UPA00848; UER00151.
DR BioGRID-ORCS; 37415; 0 hits in 1 CRISPR screen.
DR ChiTaRS; Pu; fly.
DR GenomeRNAi; 37415; -.
DR PRO; PR:P48596; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0003162; Expressed in insect adult head and 12 other tissues.
DR ExpressionAtlas; P48596; baseline and differential.
DR Genevisible; P48596; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0003934; F:GTP cyclohydrolase I activity; IDA:FlyBase.
DR GO; GO:0060308; F:GTP cyclohydrolase I regulator activity; IDA:FlyBase.
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:0048072; P:compound eye pigmentation; IMP:FlyBase.
DR GO; GO:0048067; P:cuticle pigmentation; IMP:FlyBase.
DR GO; GO:0009880; P:embryonic pattern specification; IMP:FlyBase.
DR GO; GO:0008363; P:larval chitin-based cuticle development; IMP:FlyBase.
DR GO; GO:0035185; P:preblastoderm mitotic cell cycle; IMP:FlyBase.
DR GO; GO:0006728; P:pteridine biosynthetic process; IMP:FlyBase.
DR GO; GO:2000274; P:regulation of epithelial cell migration, open tracheal system; IMP:FlyBase.
DR GO; GO:0043095; P:regulation of GTP cyclohydrolase I activity; IDA:FlyBase.
DR GO; GO:0006729; P:tetrahydrobiopterin biosynthetic process; IDA:UniProtKB.
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; Alternative splicing; GTP-binding; Hydrolase;
KW Metal-binding; Nucleotide-binding; Reference proteome;
KW Tetrahydrobiopterin biosynthesis; Zinc.
FT CHAIN 1..324
FT /note="GTP cyclohydrolase 1"
FT /id="PRO_0000119482"
FT REGION 33..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 79..119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 89..118
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 214
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P30793"
FT BINDING 217
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P30793"
FT BINDING 285
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P30793"
FT VAR_SEQ 1..117
FT /note="MSFTRQLSEMSASELNDAIDDTNFPQAHILSRGRNNSVCSTSSTSGTSSLAD
FT RQQNQAEEATAIAGTPVEEVAPAPALVPLAGNQRPRLILKTNGSSPDSDGTQPKTPLTP
FT RTSTTP -> MKPQTSEQNGSGQNGEGAADAVAVATIPTGEASAASATSGTDLTVSKNS
FT QQLKLEMLNLELASNGS (in isoform B)"
FT /evidence="ECO:0000303|PubMed:8262960"
FT /id="VSP_001616"
FT VAR_SEQ 102..117
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000303|PubMed:8262960"
FT /id="VSP_001615"
FT VARIANT 58
FT /note="A -> T (in strain: Raleigh Inbred 6, Raleigh Inbred
FT 9, Raleigh Inbred 11, Raleigh Inbred 27 and Raleigh Inbred
FT 33)"
FT /evidence="ECO:0000269|Ref.3"
FT VARIANT 61
FT /note="A -> P (in strain: Raleigh Inbred 6, Raleigh Inbred
FT 9, Raleigh Inbred 11, Raleigh Inbred 27 and Raleigh Inbred
FT 33)"
FT /evidence="ECO:0000269|Ref.3"
FT VARIANT 77
FT /note="A -> V (in strain: Raleigh Inbred 11)"
FT /evidence="ECO:0000269|Ref.3"
FT VARIANT 84
FT /note="N -> S (in strain: Raleigh Inbred 6, Raleigh Inbred
FT 9, Raleigh Inbred 11 and Raleigh Inbred 33)"
FT /evidence="ECO:0000269|Ref.3"
SQ SEQUENCE 324 AA; 35541 MW; 712A0045F2C12D6A CRC64;
MSFTRQLSEM SASELNDAID DTNFPQAHIL SRGRNNSVCS TSSTSGTSSL ADRQQNQAEE
ATAIAGTPVE EVAPAPALVP LAGNQRPRLI LKTNGSSPDS DGTQPKTPLT PRTSTTPGHE
KCTFHHDLEL DHKPPTREAL LPDMARSYRL LLGGLGENPD RQGLIKTPER AAKAMLYFTK
GYDQSLEDVL NGAVFDEDHD EMVVVKDIEM FSMCEHHLVP FYGKVSIGYL PCNKILGLSK
LARIVEIFSR RLQVQERLTK QIAVAVTQAV QPAGVAVVVE GVHMCMVMRG VQKINSKTVT
STMLGVFRDD PKTREEFLNL VNSK
