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P22288 (GCH1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length241 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. Ref.3

Catalytic activity

GTP + H2O = formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate. HAMAP-Rule MF_00223

Enzyme regulation

GTP shows a positive allosteric effect, and tetrahydrobiopterin inhibits the enzyme activity. Zinc is required for catalytic activity. Inhibited by Mg2+. HAMAP-Rule MF_00223

Pathway

Cofactor biosynthesis; 7,8-dihydroneopterin triphosphate biosynthesis; 7,8-dihydroneopterin triphosphate from GTP: step 1/1. HAMAP-Rule MF_00223

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 HAMAP-Rule MF_00223.

Induction

By cytokines such as insulin, interferon-gamma, and phytohemagglutinin in adrenal gland, macrophages, and T-cell respectively. HAMAP-Rule MF_00223

Post-translational modification

Phosphorylated By similarity. HAMAP-Rule MF_00223

Sequence similarities

Belongs to the GTP cyclohydrolase I family.

Ontologies

Keywords
   Biological processTetrahydrobiopterin biosynthesis
   Cellular componentCytoplasm
Nucleus
   LigandGTP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionHydrolase
   PTMPhosphoprotein
   Technical term3D-structure
Allosteric enzyme
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_process7,8-dihydroneopterin 3'-triphosphate biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

GTP catabolic process

Inferred from electronic annotation. Source: Ensembl

dihydrobiopterin metabolic process

Inferred from direct assay PubMed 2557335PubMed 8486153PubMed 8702680. Source: RGD

dopamine biosynthetic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of blood pressure

Inferred from mutant phenotype PubMed 12855421. Source: RGD

neuromuscular process controlling posture

Inferred from electronic annotation. Source: Ensembl

positive regulation of nitric-oxide synthase activity

Inferred from electronic annotation. Source: Ensembl

protein complex assembly

Inferred from direct assay Ref.4PubMed 15448133PubMed 9685352. Source: RGD

protein heterooligomerization

Inferred from direct assay Ref.4PubMed 15448133PubMed 9685352. Source: RGD

protein homooligomerization

Inferred from direct assay PubMed 2557335PubMed 9636709. Source: RGD

regulation of lung blood pressure

Inferred from electronic annotation. Source: Ensembl

response to interferon-gamma

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to pain

Inferred from direct assay Ref.3. Source: UniProtKB

response to tumor necrosis factor

Inferred from electronic annotation. Source: Ensembl

tetrahydrobiopterin biosynthetic process

Traceable author statement PubMed 12051753. Source: RGD

tetrahydrofolate biosynthetic process

Inferred from electronic annotation. Source: InterPro

vasodilation

Inferred from mutant phenotype PubMed 12855421. Source: RGD

   Cellular_componentcytoplasmic vesicle

Inferred from electronic annotation. Source: Ensembl

cytosol

Inferred from electronic annotation. Source: Ensembl

nuclear membrane

Inferred from electronic annotation. Source: Ensembl

protein complex

Inferred from direct assay Ref.4PubMed 15448133PubMed 8702680. Source: RGD

   Molecular_functionGTP binding

Inferred from direct assay PubMed 2557335PubMed 8486153PubMed 8702680. Source: RGD

GTP cyclohydrolase I activity

Inferred from direct assay PubMed 12051753PubMed 15292175PubMed 2557335PubMed 8486153PubMed 8702680PubMed 9636709. Source: RGD

GTP-dependent protein binding

Inferred from physical interaction PubMed 9685352. Source: RGD

calcium ion binding

Inferred from direct assay PubMed 9636709. Source: RGD

coenzyme binding

Inferred from direct assay PubMed 15448133. Source: RGD

zinc ion binding

Inferred from direct assay Ref.4PubMed 15448133. Source: RGD

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GchfrP705523EBI-1032708,EBI-1032715

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – 1111 HAMAP-Rule MF_00223
PRO_0000010720
Chain12 – 241230GTP cyclohydrolase 1 HAMAP-Rule MF_00223
PRO_0000010721

Sites

Metal binding1321Zinc By similarity
Metal binding1351Zinc By similarity
Metal binding2031Zinc By similarity
Site871Involved in pterin ring binding By similarity
Site961Involved in pterin ring binding By similarity

Amino acid modifications

Modified residue511Phosphoserine By similarity
Modified residue721Phosphoserine By similarity

Secondary structure

.................................. 241
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P22288 [UniParc].

Last modified August 1, 1991. Version 1.
Checksum: 8226E3319816325B

FASTA24127,057
        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 

« Hide

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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 12-241 IN COMPLEX WITH GFRP, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M58364 mRNA. Translation: AAA41299.1.
PIRA39080.
RefSeqNP_077332.1. NM_024356.1.
UniGeneRn.28195.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IS7X-ray2.80A/B/C/D/E/F/G/H/I/J12-241[»]
1IS8X-ray2.70A/B/C/D/E/F/G/H/I/J12-241[»]
1WPLX-ray2.80A/B/C/D/E/F/G/H/I/J12-241[»]
ProteinModelPortalP22288.
SMRP22288. Positions 48-241.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid247920. 2 interactions.
IntActP22288. 1 interaction.
STRING10116.ENSRNOP00000014821.

PTM databases

PhosphoSiteP22288.

Proteomic databases

PRIDEP22288.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000014821; ENSRNOP00000014821; ENSRNOG00000011039.
GeneID29244.
KEGGrno:29244.
UCSCRGD:61992. rat.

Organism-specific databases

CTD2643.
RGD61992. Gch1.

Phylogenomic databases

eggNOGCOG0302.
GeneTreeENSGT00390000013481.
HOGENOMHOG000221222.
HOVERGENHBG003136.
InParanoidP22288.
KOK01495.
OMAVIVVTEC.
OrthoDBEOG77DJ6T.
PhylomeDBP22288.

Enzyme and pathway databases

UniPathwayUPA00848; UER00151.

Gene expression databases

ArrayExpressP22288.
GenevestigatorP22288.

Family and domain databases

HAMAPMF_00223. FolE.
InterProIPR001474. GTP_CycHdrlase_I.
IPR018234. GTP_CycHdrlase_I_CS.
IPR020602. GTP_CycHdrlase_I_dom.
[Graphical view]
PANTHERPTHR11109. PTHR11109. 1 hit.
PfamPF01227. GTP_cyclohydroI. 1 hit.
[Graphical view]
TIGRFAMsTIGR00063. folE. 1 hit.
PROSITEPS00859. GTP_CYCLOHYDROL_1_1. 1 hit.
PS00860. GTP_CYCLOHYDROL_1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP22288.
NextBio608526.
PROP22288.

Entry information

Entry nameGCH1_RAT
AccessionPrimary (citable) accession number: P22288
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: April 16, 2014
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways