P48596 (GCH1_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
GTP cyclohydrolase 1
EC=3.5.4.16

Alternative name(s):
GTP cyclohydrolase I
Short name=GTP-CH-I
Protein punch

Gene names

Name:	Pu
ORF Names:	CG9441

Organism

Drosophila melanogaster (Fruit fly) [Reference proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Mandibulata › Pancrustacea › Hexapoda › Insecta › Dicondylia › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Eremoneura › Cyclorrhapha › Schizophora › Acalyptratae › Ephydroidea › Drosophilidae › Drosophilinae › Drosophilini › Drosophilina › Drosophiliti › Drosophila › Sophophora › melanogaster group › melanogaster subgroup

Protein attributes

Sequence length	324 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Isoform B is required for eye pigment production, Isoform C may be required for normal embryonic development and segment pattern formation. Ref.1
Catalytic activity	GTP + H2O = formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate.
Pathway	Cofactor biosynthesis; 7,8-dihydroneopterin triphosphate biosynthesis; 7,8-dihydroneopterin triphosphate from GTP: step 1/1.
Subunit structure	Toroid-shaped homodecamer, composed of two pentamers of five dimers By similarity.
Tissue specificity	Isoform B is expressed almost exclusively in adult heads. Ref.1
Developmental stage	Isoform C is expressed in embryos, larvae and adults. Ref.1
Sequence similarities	Belongs to the GTP cyclohydrolase I family.
Sequence caution	The sequence AAC04308.1 differs from that shown. Reason: Frameshift at positions 27, 75, 266 and 271. The sequence AAC04309.1 differs from that shown. Reason: Frameshift at positions 27, 75, 266 and 271. The sequence AAD44334.1 differs from that shown. Reason: Frameshift at positions 27, 75, 266 and 271. The sequence AAR20857.2 differs from that shown. Reason: Frameshift at position 53.

Ontologies

Keywords
Biological process	Tetrahydrobiopterin biosynthesis
Coding sequence diversity	Alternative splicing
Ligand	GTP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Hydrolase
Technical term	Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	7,8-dihydroneopterin 3'-triphosphate biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway compound eye pigmentation Inferred from mutant phenotype PubMed 3136053. Source: FlyBase cuticle pigmentation Inferred from mutant phenotype PubMed 3115849. Source: FlyBase embryonic pattern specification Inferred from mutant phenotype PubMed 3115849. Source: FlyBase larval chitin-based cuticle development Inferred from mutant phenotype PubMed 3115849. Source: FlyBase preblastoderm mitotic cell cycle Inferred from mutant phenotype PubMed 7706401. Source: FlyBase pteridine biosynthetic process Inferred from mutant phenotype PubMed 7706401. Source: FlyBase regulation of GTP cyclohydrolase I activity Inferred from direct assay PubMed 16966327. Source: FlyBase regulation of epithelial cell migration, open tracheal system Inferred from mutant phenotype PubMed 17585895. Source: FlyBase tetrahydrobiopterin biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW tetrahydrofolate biosynthetic process Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from direct assay PubMed 7706401. Source: FlyBase
Molecular_function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTP cyclohydrolase I activity Inferred from direct assay PubMed 16966327PubMed 3080426PubMed 3136053. Source: FlyBase GTP cyclohydrolase I regulator activity Inferred from direct assay PubMed 16966327. Source: FlyBase metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: P48596-1)

Also known as: C;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform B (identifier: P48596-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-117: MSFTRQLSEM...PLTPRTSTTP → MKPQTSEQNG...LNLELASNGS

Isoform C (identifier: P48596-3)

The sequence of this isoform differs from the canonical sequence as follows:
     102-117: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 324	324	GTP cyclohydrolase 1		PRO_0000119482
Sites
	Metal binding	214	1	Zinc By similarity
	Metal binding	217	1	Zinc By similarity
	Metal binding	285	1	Zinc By similarity
Natural variations
	Alternative sequence	1 – 117	117	MSFTR…TSTTP → MKPQTSEQNGSGQNGEGAAD AVAVATIPTGEASAASATSG TDLTVSKNSQQLKLEMLNLE LASNGS in isoform B.		VSP_001616
	Alternative sequence	102 – 117	16	Missing in isoform C.		VSP_001615
	Natural variant	58	1	A → T in strain: Raleigh Inbred 6, Raleigh Inbred 9, Raleigh Inbred 11, Raleigh Inbred 27 and Raleigh Inbred 33. Ref.3
	Natural variant	61	1	A → P in strain: Raleigh Inbred 6, Raleigh Inbred 9, Raleigh Inbred 11, Raleigh Inbred 27 and Raleigh Inbred 33. Ref.3
	Natural variant	77	1	A → V in strain: Raleigh Inbred 11. Ref.3
	Natural variant	84	1	N → S in strain: Raleigh Inbred 6, Raleigh Inbred 9, Raleigh Inbred 11 and Raleigh Inbred 33. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform A (C) [UniParc]. Last modified January 27, 2003. Version 3. Checksum: 712A0045F2C12D6A	FASTA	324	35,541
	10 20 30 40 50 60 MSFTRQLSEM SASELNDAID DTNFPQAHIL SRGRNNSVCS TSSTSGTSSL ADRQQNQAEE 70 80 90 100 110 120 ATAIAGTPVE EVAPAPALVP LAGNQRPRLI LKTNGSSPDS DGTQPKTPLT PRTSTTPGHE 130 140 150 160 170 180 KCTFHHDLEL DHKPPTREAL LPDMARSYRL LLGGLGENPD RQGLIKTPER AAKAMLYFTK 190 200 210 220 230 240 GYDQSLEDVL NGAVFDEDHD EMVVVKDIEM FSMCEHHLVP FYGKVSIGYL PCNKILGLSK 250 260 270 280 290 300 LARIVEIFSR RLQVQERLTK QIAVAVTQAV QPAGVAVVVE GVHMCMVMRG VQKINSKTVT 310 320 STMLGVFRDD PKTREEFLNL VNSK
	Isoform B [UniParc]. Checksum: 99B3DA99E8D4B2C2	FASTA	273	29,812
	10 20 30 40 50 60 MKPQTSEQNG SGQNGEGAAD AVAVATIPTG EASAASATSG TDLTVSKNSQ QLKLEMLNLE 70 80 90 100 110 120 LASNGSGHEK CTFHHDLELD HKPPTREALL PDMARSYRLL LGGLGENPDR QGLIKTPERA 130 140 150 160 170 180 AKAMLYFTKG YDQSLEDVLN GAVFDEDHDE MVVVKDIEMF SMCEHHLVPF YGKVSIGYLP 190 200 210 220 230 240 CNKILGLSKL ARIVEIFSRR LQVQERLTKQ IAVAVTQAVQ PAGVAVVVEG VHMCMVMRGV 250 260 270 QKINSKTVTS TMLGVFRDDP KTREEFLNLV NSK
	Isoform C [UniParc]. Checksum: A142F66EDE6D3969	FASTA	308	33,877
	10 20 30 40 50 60 MSFTRQLSEM SASELNDAID DTNFPQAHIL SRGRNNSVCS TSSTSGTSSL ADRQQNQAEE 70 80 90 100 110 120 ATAIAGTPVE EVAPAPALVP LAGNQRPRLI LKTNGSSPDS DGHEKCTFHH DLELDHKPPT 130 140 150 160 170 180 REALLPDMAR SYRLLLGGLG ENPDRQGLIK TPERAAKAML YFTKGYDQSL EDVLNGAVFD 190 200 210 220 230 240 EDHDEMVVVK DIEMFSMCEH HLVPFYGKVS IGYLPCNKIL GLSKLARIVE IFSRRLQVQE 250 260 270 280 290 300 RLTKQIAVAV TQAVQPAGVA VVVEGVHMCM VMRGVQKINS KTVTSTMLGV FRDDPKTREE FLNLVNSK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Multiple mRNAs from the Punch locus of Drosophila melanogaster encode isoforms of GTP cyclohydrolase I with distinct N-terminal domains." McLean J.R., Krishnakumar S., O'Donnell J.M. J. Biol. Chem. 268:27191-27197(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND C), FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Tissue: Head.
[2]	"Differential regulation of Drosophila GTP cyclohydrolase I isoforms and their interaction with tyrosine hydroxylase." Xu D., Neckameyer W., O'Donnell J. Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). Tissue: Embryo.
[3]	"Punch affects life history traits in Drosophila melanogaster." Geiger-Thornsberry G.L., Harbison S.T., Lyman R.F., Mackay T.F.C. Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-58; PRO-61; VAL-77 AND SER-84. Strain: Raleigh Inbred 1, Raleigh Inbred 11, Raleigh Inbred 24, Raleigh Inbred 27, Raleigh Inbred 30, Raleigh Inbred 33, Raleigh Inbred 6 and Raleigh Inbred 9.
[4]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[5]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed] [Europe PMC] [Abstract] Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING. Strain: Berkeley.
[6]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). Strain: Berkeley. Tissue: Embryo.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U01118 mRNA. Translation: AAC04308.1. Frameshift. U01119 mRNA. Translation: AAC04309.1. Frameshift. AF159422 mRNA. Translation: AAD44334.1. Frameshift. AY382619 Genomic DNA. Translation: AAR20848.1. AY382620 Genomic DNA. Translation: AAR20850.1. AY382622 Genomic DNA. Translation: AAR20852.1. AY382623 Genomic DNA. Translation: AAR20854.1. AY382624 Genomic DNA. Translation: AAR20855.1. AY382625 Genomic DNA. Translation: AAR20857.2. Frameshift. AY382626 Genomic DNA. Translation: AAR20859.1. AY382628 Genomic DNA. Translation: AAR20862.1. AE013599 Genomic DNA. Translation: AAF46690.1. AE013599 Genomic DNA. Translation: AAF46692.1. AE013599 Genomic DNA. Translation: AAM70858.1. AY051890 mRNA. Translation: AAK93314.1.
PIR	A49302. B49302.
RefSeq	NP_523801.2. NM_079077.4. NP_726037.1. NM_166430.3. NP_726038.1. NM_166431.4.
UniGene	Dm.7417.
3D structure databases
ProteinModelPortal	P48596.
SMR	P48596. Positions 138-323.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-24104N.
MINT	MINT-937025.
Proteomic databases
PaxDb	P48596.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0071580; FBpp0071507; FBgn0003162.
GeneID	37415.
KEGG	dme:Dmel_CG9441.
Organism-specific databases
CTD	37415.
FlyBase	FBgn0003162. Pu.
Phylogenomic databases
eggNOG	COG0302.
GeneTree	ENSGT00390000013481.
InParanoid	P48596.
KO	K01495.
OMA	FSGHEKC.
OrthoDB	EOG405QH1.
PhylomeDB	P48596.
Enzyme and pathway databases
UniPathway	UPA00848; UER00151.
Gene expression databases
Bgee	P48596.
GermOnline	CG9441. Drosophila melanogaster.
Family and domain databases
InterPro	IPR001474. GTP_CycHdrlase_I. IPR020602. GTP_CycHdrlase_I/CN_OxRdtase. IPR018234. GTP_CycHdrlase_I_CS. [Graphical view]
PANTHER	PTHR11109. PTHR11109. 1 hit.
Pfam	PF01227. GTP_cyclohydroI. 1 hit. [Graphical view]
TIGRFAMs	TIGR00063. folE. 1 hit.
PROSITE	PS00859. GTP_CYCLOHYDROL_1_1. 1 hit. PS00860. GTP_CYCLOHYDROL_1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	Pu. drosophila.
GenomeRNAi	37415.
NextBio	803517.

Entry information

Entry name

GCH1_DROME

Accession

Primary (citable) accession number: P48596
Secondary accession number(s): Q6TY66 , Q6TY71, Q6TY73, Q6TY74, Q6TY78, Q960S4, Q9W2J9, Q9W2K1, Q9Y0C8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	January 27, 2003
Last modified:	April 3, 2013
This is version 117 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project