Reviewed, UniProtKB/Swiss-Prot P22288 (GCH1_RAT)

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

Gene names

Name:	Gch1
Synonyms:	Gch

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	241 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May positively regulate nitric oxide synthesis in endothelial cells. May be involved in dopamine synthesis By similarity. May modify pain sensitivity and persistence.
Catalytic activity	GTP + H2O = formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate.
Enzyme regulation	GTP shows a positive allosteric effect, and tetrahydrobiopterin inhibits the enzyme activity. Zinc is required for catalytic activity. Inhibited by Mg2+.
Pathway	Cofactor biosynthesis; dihydroneopterin triphosphate biosynthesis; 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate from GTP: step 1/1.
Subunit structure	Toroid-shaped homodecamer, composed of two pentamers of five dimers. Interacts with AHSA1 and GCHFR/GFRP. Ref.4
Subcellular location	Cytoplasm By similarity. Nucleus By similarity.
Induction	By cytokines such as insulin, interferon-gamma, and phytohemagglutinin in adrenal gland, macrophages, and T-cell respectively.
Post-translational modification	Phosphorylated By similarity.
Sequence similarities	Belongs to the GTP cyclohydrolase I family.

Ontologies

Keywords
Biological process	Tetrahydrobiopterin biosynthesis
Cellular component	Cytoplasm Nucleus
Ligand	GTP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure Allosteric enzyme Direct protein sequencing
Gene Ontology (GO)
Biological process	dihydrobiopterin metabolic process Inferred from direct assay. Source: RGD induction of apoptosis Inferred from expression pattern. Source: RGD negative regulation of blood pressure Inferred from mutant phenotype. Source: RGD protein heterooligomerization Ref.4 Inferred from direct assay. Source: RGD protein homooligomerization Inferred from direct assay. Source: RGD response to pain Ref.3 Inferred from direct assay. Source: UniProtKB tetrahydrobiopterin biosynthetic process Traceable author statement. Source: RGD tetrahydrofolate biosynthetic process Inferred from electronic annotation. Source: InterPro vasodilation Inferred from mutant phenotype. Source: RGD
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell protein complex Ref.4 Inferred from direct assay. Source: RGD soluble fraction Inferred from direct assay. Source: RGD
Molecular function	GTP binding Inferred from direct assay. Source: RGD GTP cyclohydrolase I activity Inferred from direct assay. Source: RGD GTP-dependent protein binding Inferred from physical interaction. Source: RGD calcium ion binding Inferred from direct assay. Source: RGD coenzyme binding Inferred from direct assay. Source: RGD zinc ion binding Ref.4 Inferred from direct assay. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Propeptide

1 – 11

11

PRO_0000010720

Chain

12 – 241

230

GTP cyclohydrolase 1

PRO_0000010721

Sites

Metal binding

132

1

Zinc By similarity

Metal binding

135

1

Zinc By similarity

Metal binding

203

1

Zinc By similarity

Site

87

1

Involved in pterin ring binding By similarity

Site

96

1

Involved in pterin ring binding By similarity

Amino acid modifications

Modified residue

72

1

Phosphoserine By similarity

Secondary structure

1

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241

Helix Strand Turn

Details...

Helix

52 – 73

22

Turn

80 – 82

3

Helix

85 – 95

11

Turn

96 – 101

6

Helix

104 – 107

4

Helix

108 – 111

4

Beta strand

112 – 117

6

Beta strand

121 – 132

12

Turn

133 – 135

3

Beta strand

138 – 148

11

Beta strand

150 – 154

5

Helix

156 – 167

12

Beta strand

168 – 171

4

Helix

173 – 186

14

Beta strand

191 – 201

11

Helix

202 – 205

4

Beta strand

207 – 210

4

Beta strand

215 – 223

9

Helix

224 – 227

4

Helix

229 – 240

12

Sequences

	Sequence		Length	Mass (Da)
	P22288-1 [UniParc]. Last modified August 1, 1991. Version 1. Checksum: 8226E3319816325B	FASTA	241	27,057
	10 20 30 40 50 60 MEKPRGVRCT NGFPERELPR PGASRPAEKS RPPEAKGAQP ADAWKAGRPR SEEDNELNLP 70 80 90 100 110 120 NLAAAYSSIL RSLGEDPQRQ GLLKTPWRAA TAMQFFTKGY QETISDVLND AIFDEDHDEM 130 140 150 160 170 180 VIVKDIDMFS MCEHHLVPFV GRVHIGYLPN KQVLGLSKLA RIVEIYSRRL QVQERLTKQI 190 200 210 220 230 240 AVAITEALQP AGVGVVIEAT HMCMVMRGVQ KMNSKTVTST MLGVFREDPK TREEFLTLIR S

References

[1]	"Cloning and sequencing of cDNA encoding rat GTP cyclohydrolase I. The first enzyme of the tetrahydrobiopterin biosynthetic pathway." Hatakeyama K., Inoue Y., Harada T., Kagamiyama H. J. Biol. Chem. 266:765-769(1991) [PubMed: 1985963] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Strain: Wistar. Tissue: Liver.
[2]	"Identification of a rabphilin-3A-interacting protein as GTP cyclohydrolase I in PC12 cells." Imazumi K., Sasaki T., Takahashi K., Takai Y. Biochem. Biophys. Res. Commun. 205:1409-1416(1994) [PubMed: 7802677] [Abstract] Cited for: PROTEIN SEQUENCE OF 37-46 AND 99-116.
[3]	"GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence." Tegeder I., Costigan M., Griffin R.S., Abele A., Belfer I., Schmidt H., Ehnert C., Nejim J., Marian C., Scholz J., Wu T., Allchorne A., Diatchenko L., Binshtok A.M., Goldman D., Adolph J., Sama S., Atlas S.J. , Carlezon W.A., Parsegian A., Loetsch J., Fillingim R.B., Maixner W., Geisslinger G., Max M.B., Woolf C.J. Nat. Med. 12:1269-1277(2006) [PubMed: 17057711] [Abstract] Cited for: FUNCTION.
[4]	"Crystal structure of the stimulatory complex of GTP cyclohydrolase I and its feedback regulatory protein GFRP." Maita N., Okada K., Hatakeyama K., Hakoshima T. Proc. Natl. Acad. Sci. U.S.A. 99:1212-1217(2002) [PubMed: 11818540] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 12-241 IN COMPLEX WITH GFRP, SUBUNIT.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M58364 mRNA. Translation: AAA41299.1.

IPI

IPI00205214.

PIR

A39080.

RefSeq

NP_077332.1.

UniGene

Rn.28195

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IS7	X-ray	2.80	A/B/C/D/E/F/G/H/I/J	12-241	[»]
1IS8	X-ray	2.70	A/B/C/D/E/F/G/H/I/J	12-241	[»]
1WPL	X-ray	2.80	A/B/C/D/E/F/G/H/I/J	12-241	[»]

ModBase

Search...

Genome annotation databases

Ensembl

ENSRNOG00000011039. Rattus norvegicus. [Contig view]

GeneID

29244.

KEGG

rno:29244.

Organism-specific databases

RGD

61992. Gch.

Phylogenomic databases

HOVERGEN

P22288.

Enzyme and pathway databases

BRENDA

3.5.4.16. 248.

Gene expression databases

ArrayExpress

P22288.

GermOnline

ENSRNOG00000011039. Rattus norvegicus.

Family and domain databases

InterPro

IPR001474. GTP_CycHdrlase_I.
IPR018234. GTP_CycHdrlase_I_CS.
[Graphical view]

PANTHER

PTHR11109. GTP_cyclohydro_I. 1 hit.

Pfam

PF01227. GTP_cyclohydroI. 1 hit.
[Graphical view]

ProDom

PD003330. GTP_cyclohydroI. 1 hit.
[Graphical view] [Entries sharing at least one domain]

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 Resources

NextBio

608526.

Entry information

Entry name

GCH1_RAT

Accession

Primary (citable) accession number: P22288

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	August 1, 1991
Last modified:	June 16, 2009
This is version 88 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)