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P30793

- GCH1_HUMAN

UniProt

P30793 - GCH1_HUMAN

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Protein

GTP cyclohydrolase 1

Gene

GCH1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Positively regulates nitric oxide synthesis in umbilical vein endothelial cells (HUVECs). May be involved in dopamine synthesis. May modify pain sensitivity and persistence. Isoform GCH-1 is the functional enzyme, the potential function of the enzymatically inactive isoforms remains unknown.5 Publications

Catalytic activityi

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

Enzyme regulationi

GTP shows a positive allosteric effect, and tetrahydrobiopterin inhibits the enzyme activity. Zinc is required for catalytic activity. Inhibited by Mg2+.3 Publications

Kineticsi

  1. KM=116 µM for GTP1 Publication

pH dependencei

Optimum pH is 7.7 in phosphate buffer.1 Publication

Temperature dependencei

Relatively stable at high temperatures. Retains 50% of its activity after incubation at 70 degrees Celsius for 15 minutes.1 Publication

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi141 – 1411Zinc
Metal bindingi144 – 1441Zinc
Metal bindingi212 – 2121Zinc

GO - Molecular functioni

  1. calcium ion binding Source: Ensembl
  2. coenzyme binding Source: Ensembl
  3. GTP binding Source: UniProtKB
  4. GTP cyclohydrolase I activity Source: UniProtKB
  5. protein homodimerization activity Source: UniProtKB
  6. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. 7,8-dihydroneopterin 3'-triphosphate biosynthetic process Source: UniProtKB-UniPathway
  2. dopamine biosynthetic process Source: UniProtKB
  3. GTP catabolic process Source: UniProtKB
  4. metabolic process Source: GOC
  5. negative regulation of blood pressure Source: Ensembl
  6. neuromuscular process controlling posture Source: MGI
  7. nitric oxide biosynthetic process Source: UniProtKB
  8. nitric oxide metabolic process Source: Reactome
  9. positive regulation of nitric-oxide synthase activity Source: UniProtKB
  10. protein heterooligomerization Source: Ensembl
  11. protein homooligomerization Source: UniProtKB
  12. pteridine-containing compound biosynthetic process Source: UniProtKB
  13. regulation of blood pressure Source: UniProtKB
  14. regulation of lung blood pressure Source: Ensembl
  15. regulation of nitric-oxide synthase activity Source: Reactome
  16. response to interferon-gamma Source: UniProtKB
  17. response to lipopolysaccharide Source: UniProtKB
  18. response to pain Source: UniProtKB
  19. response to tumor necrosis factor Source: UniProtKB
  20. small molecule metabolic process Source: Reactome
  21. tetrahydrobiopterin biosynthetic process Source: UniProtKB
  22. tetrahydrofolate biosynthetic process Source: InterPro
  23. vasodilation Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Tetrahydrobiopterin biosynthesis

Keywords - Ligandi

GTP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:HS05586-MONOMER.
ReactomeiREACT_111176. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
SABIO-RKP30793.
UniPathwayiUPA00848; UER00151.

Names & Taxonomyi

Protein namesi
Recommended name:
GTP cyclohydrolase 1 (EC:3.5.4.16)
Alternative name(s):
GTP cyclohydrolase I
Short name:
GTP-CH-I
Gene namesi
Name:GCH1
Synonyms:DYT5, GCH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 14

Organism-specific databases

HGNCiHGNC:4193. GCH1.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytoplasmic vesicle Source: UniProtKB
  3. cytosol Source: UniProtKB
  4. nuclear membrane Source: HPA
  5. nucleus Source: UniProtKB
  6. protein complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

GTP cyclohydrolase 1 deficiency (GCH1D) [MIM:233910]: A cause of malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency. It is also responsible for defective neurotransmission due to depletion of the neurotransmitters dopamine and serotonin. The principal symptoms include: psychomotor retardation, tonicity disorders, convulsions, drowsiness, irritability, abnormal movements, hyperthermia, hypersalivation, and difficulty swallowing. Some patients may present a phenotype of intermediate severity between severe hyperphenylalaninemia and mild dystonia type 5 (dystonia-parkinsonism with diurnal fluctuation). In this intermediate phenotype, there is marked motor delay, but no mental retardation and only minimal, if any, hyperphenylalaninemia.2 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti108 – 1081G → D in GCH1D; phenotype presenting with dystonia and motor delay. 1 Publication
VAR_016894
Natural varianti184 – 1841R → H in GCH1D; severe hyperphenylalaninemia. 1 Publication
VAR_002643
Natural varianti211 – 2111M → I in GCH1D; severe hyperphenylalaninemia. 1 Publication
VAR_002647
Natural varianti221 – 2211M → T in GCH1D; a patient presenting with dystonia and motor delay; compound heterozygote for an additional deletion. 1 Publication
VAR_016905
Natural varianti224 – 2241K → R in GCH1D and DYT5; phenotype presenting with dystonia and myoclonus. 3 Publications
Corresponds to variant rs41298442 [ dbSNP | Ensembl ].
VAR_002648
Dystonia 5 (DYT5) [MIM:128230]: A DOPA-responsive dystonia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DYT5 typically presents in childhood with walking problems due to dystonia of the lower limbs and worsening of the dystonia towards the evening. It is characterized by postural and motor disturbances showing marked diurnal fluctuation. Torsion of the trunk is unusual. Symptoms are alleviated after sleep and aggravated by fatigue and exercise. There is a favorable response to L-DOPA without side effects.15 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti23 – 231P → L in DYT5. 1 Publication
Corresponds to variant rs41298432 [ dbSNP | Ensembl ].
VAR_002633
Natural varianti71 – 711L → Q in DYT5. 1 Publication
VAR_016888
Natural varianti74 – 741A → V in DYT5. 1 Publication
VAR_016889
Natural varianti79 – 791L → P in DYT5. 1 Publication
VAR_002634
Natural varianti83 – 831G → A in DYT5. 2 Publications
VAR_016890
Natural varianti88 – 892Missing in DYT5. 1 Publication
VAR_016891
Natural varianti88 – 881R → P in DYT5. 1 Publication
VAR_002635
Natural varianti88 – 881R → W in DYT5. 1 Publication
VAR_002636
Natural varianti90 – 901G → V in DYT5. 1 Publication
VAR_016892
Natural varianti102 – 1021M → K in DYT5. 1 Publication
VAR_002637
Natural varianti102 – 1021M → R in DYT5. 1 Publication
VAR_016893
Natural varianti106 – 1061T → I in DYT5. 1 Publication
VAR_054112
Natural varianti115 – 1151D → N in DYT5. 1 Publication
VAR_016895
Natural varianti134 – 1341D → V in DYT5. 1 Publication
VAR_002638
Natural varianti135 – 1351I → K in DYT5. 1 Publication
VAR_016896
Natural varianti141 – 1411C → R in DYT5. 1 Publication
VAR_016897
Natural varianti141 – 1411C → W in DYT5. 1 Publication
VAR_002639
Natural varianti144 – 1441H → P in DYT5. 1 Publication
VAR_002640
Natural varianti153 – 1531H → P in DYT5. 1 Publication
VAR_002641
Natural varianti163 – 1631L → R in DYT5. 1 Publication
VAR_016898
Natural varianti176 – 1761S → T in DYT5. 1 Publication
VAR_016899
Natural varianti178 – 1781R → S in DYT5. 3 Publications
VAR_002642
Natural varianti180 – 1801Q → R in DYT5. 1 Publication
VAR_016900
Natural varianti186 – 1861T → K in DYT5. 1 Publication
VAR_002644
Natural varianti191 – 1911V → I in DYT5. 1 Publication
VAR_016901
Natural varianti199 – 1991P → L in DYT5. 1 Publication
VAR_016902
Natural varianti201 – 2011G → E in DYT5. 2 Publications
VAR_002645
Natural varianti203 – 2031G → R in DYT5. 1 Publication
VAR_002646
Natural varianti211 – 2111M → V in DYT5. 1 Publication
VAR_016903
Natural varianti213 – 2131M → V in DYT5. 1 Publication
VAR_016904
Natural varianti224 – 2241K → R in GCH1D and DYT5; phenotype presenting with dystonia and myoclonus. 3 Publications
Corresponds to variant rs41298442 [ dbSNP | Ensembl ].
VAR_002648
Natural varianti234 – 2341F → S in DYT5. 1 Publication
VAR_002649
Natural varianti241 – 2411R → W in DYT5. 1 Publication
VAR_016906
Natural varianti249 – 2491R → S in DYT5. 1 Publication
VAR_016907

Keywords - Diseasei

Disease mutation, Dystonia, Parkinsonism, Phenylketonuria

Organism-specific databases

MIMi128230. phenotype.
233910. phenotype.
Orphaneti98808. Autosomal dominant dopa-responsive dystonia.
2102. GTP cyclohydrolase I deficiency.
PharmGKBiPA28608.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 250250GTP cyclohydrolase 1PRO_0000119478Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei60 – 601Phosphoserine1 Publication
Modified residuei81 – 811Phosphoserine1 Publication

Post-translational modificationi

Phosphorylated by casein kinase II at Ser-81 in HAECs during oscillatory shear stress; phosphorylation at Ser-81 results in increased enzyme activity.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP30793.
PaxDbiP30793.
PRIDEiP30793.

PTM databases

PhosphoSiteiP30793.

Expressioni

Tissue specificityi

In epidermis, expressed predominantly in basal undifferentiated keratinocytes and in some but not all melanocytes (at protein level).1 Publication

Inductioni

Up-regulated by IFNG/IFN-gamma, TNF, IL1B/interleukin-1 beta, bacterial lipopolysaccharides (LPS) and phenylalanine, and down-regulated by dibutyryl-cAMP, iloprost and 8-bromo-cGMP in HUVEC cells. Up-regulation of GCH1 expression, in turn, stimulates production of tetrahydrobiopterin, with subsequent elevation of endothelial nitric oxide synthase activity. Cytokine-induced GCH1 up-regulation in HUVECs in response to TNF and IFNG/IFN-gamma involves cooperative activation of both the NF-kappa-B and JAK2/STAT pathways. Also up-regulated by hydrogen peroxide in human aorta endothelial cells (HAECs).7 Publications

Gene expression databases

BgeeiP30793.
CleanExiHS_GCH1.
ExpressionAtlasiP30793. baseline and differential.
GenevestigatoriP30793.

Organism-specific databases

HPAiHPA028612.

Interactioni

Subunit structurei

Toroid-shaped homodecamer, composed of a dimer of pentamers. The inactive isoforms also form decamers and may possibly be incorporated into GCH1 heterodecamers, decreasing enzyme stability and activity. Interacts with AHSA1 and GCHFR/GFRP.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AHSA1O954333EBI-958183,EBI-448610
YWHAZP631044EBI-958183,EBI-347088

Protein-protein interaction databases

BioGridi108913. 30 interactions.
IntActiP30793. 12 interactions.
MINTiMINT-3011998.
STRINGi9606.ENSP00000378890.

Structurei

Secondary structure

1
250
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi61 – 8121
Helixi91 – 933
Helixi94 – 1029
Turni103 – 1064
Helixi108 – 1103
Turni113 – 1153
Beta strandi130 – 14112
Turni142 – 1443
Beta strandi147 – 15610
Helixi165 – 17612
Beta strandi177 – 1804
Helixi182 – 19716
Beta strandi202 – 2109
Helixi211 – 2144
Turni215 – 2173
Beta strandi224 – 2307
Helixi233 – 2364
Helixi238 – 24811

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1FB1X-ray3.10A/B/C/D/E55-250[»]
ProteinModelPortaliP30793.
SMRiP30793. Positions 55-250.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP30793.

Family & Domainsi

Sequence similaritiesi

Belongs to the GTP cyclohydrolase I family.Curated

Phylogenomic databases

eggNOGiCOG0302.
GeneTreeiENSGT00390000013481.
HOGENOMiHOG000221222.
HOVERGENiHBG003136.
InParanoidiP30793.
KOiK01495.
OMAiAHYKGEQ.
OrthoDBiEOG77DJ6T.
PhylomeDBiP30793.
TreeFamiTF105616.

Family and domain databases

HAMAPiMF_00223. FolE.
InterProiIPR001474. GTP_CycHdrlase_I.
IPR018234. GTP_CycHdrlase_I_CS.
IPR020602. GTP_CycHdrlase_I_dom.
[Graphical view]
PANTHERiPTHR11109. PTHR11109. 1 hit.
PfamiPF01227. GTP_cyclohydroI. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00063. folE. 1 hit.
PROSITEiPS00859. GTP_CYCLOHYDROL_1_1. 1 hit.
PS00860. GTP_CYCLOHYDROL_1_2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform GCH-1 (identifier: P30793-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MEKGPVRAPA EKPRGARCSN GFPERDPPRP GPSRPAEKPP RPEAKSAQPA
60 70 80 90 100
DGWKGERPRS EEDNELNLPN LAAAYSSILS SLGENPQRQG LLKTPWRAAS
110 120 130 140 150
AMQFFTKGYQ ETISDVLNDA IFDEDHDEMV IVKDIDMFSM CEHHLVPFVG
160 170 180 190 200
KVHIGYLPNK QVLGLSKLAR IVEIYSRRLQ VQERLTKQIA VAITEALRPA
210 220 230 240 250
GVGVVVEATH MCMVMRGVQK MNSKTVTSTM LGVFREDPKT REEFLTLIRS
Length:250
Mass (Da):27,903
Last modified:July 1, 1993 - v1
Checksum:iB8A0CB344C598B9A
GO
Isoform GCH-2 (identifier: P30793-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     210-213: HMCM → SAEP
     214-250: Missing.

Show »
Length:213
Mass (Da):23,516
Checksum:i021D95DE6B33E02A
GO
Isoform GCH-3 (identifier: P30793-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     210-250: Missing.

Show »
Length:209
Mass (Da):23,131
Checksum:i8B33E02A53DF1259
GO
Isoform GCH-4 (identifier: P30793-4) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     210-233: HMCMVMRGVQKMNSKTVTSTMLGV → KSNKYNKGLSPLLSSCHLFVAILK
     234-250: Missing.

Show »
Length:233
Mass (Da):25,775
Checksum:i7100FBD83BFDB2C9
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti11 – 111E → G in AAD38866. (PubMed:11284739)Curated
Sequence conflicti206 – 2061V → I in CAA78908. (PubMed:1482676)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti15 – 151G → D in HGCH-3.
VAR_002632
Natural varianti23 – 231P → L in DYT5. 1 Publication
Corresponds to variant rs41298432 [ dbSNP | Ensembl ].
VAR_002633
Natural varianti71 – 711L → Q in DYT5. 1 Publication
VAR_016888
Natural varianti74 – 741A → V in DYT5. 1 Publication
VAR_016889
Natural varianti79 – 791L → P in DYT5. 1 Publication
VAR_002634
Natural varianti83 – 831G → A in DYT5. 2 Publications
VAR_016890
Natural varianti88 – 892Missing in DYT5. 1 Publication
VAR_016891
Natural varianti88 – 881R → P in DYT5. 1 Publication
VAR_002635
Natural varianti88 – 881R → W in DYT5. 1 Publication
VAR_002636
Natural varianti90 – 901G → V in DYT5. 1 Publication
VAR_016892
Natural varianti102 – 1021M → K in DYT5. 1 Publication
VAR_002637
Natural varianti102 – 1021M → R in DYT5. 1 Publication
VAR_016893
Natural varianti106 – 1061T → I in DYT5. 1 Publication
VAR_054112
Natural varianti108 – 1081G → D in GCH1D; phenotype presenting with dystonia and motor delay. 1 Publication
VAR_016894
Natural varianti115 – 1151D → N in DYT5. 1 Publication
VAR_016895
Natural varianti134 – 1341D → V in DYT5. 1 Publication
VAR_002638
Natural varianti135 – 1351I → K in DYT5. 1 Publication
VAR_016896
Natural varianti141 – 1411C → R in DYT5. 1 Publication
VAR_016897
Natural varianti141 – 1411C → W in DYT5. 1 Publication
VAR_002639
Natural varianti144 – 1441H → P in DYT5. 1 Publication
VAR_002640
Natural varianti153 – 1531H → P in DYT5. 1 Publication
VAR_002641
Natural varianti163 – 1631L → R in DYT5. 1 Publication
VAR_016898
Natural varianti176 – 1761S → T in DYT5. 1 Publication
VAR_016899
Natural varianti178 – 1781R → S in DYT5. 3 Publications
VAR_002642
Natural varianti180 – 1801Q → R in DYT5. 1 Publication
VAR_016900
Natural varianti184 – 1841R → H in GCH1D; severe hyperphenylalaninemia. 1 Publication
VAR_002643
Natural varianti186 – 1861T → K in DYT5. 1 Publication
VAR_002644
Natural varianti191 – 1911V → I in DYT5. 1 Publication
VAR_016901
Natural varianti199 – 1991P → L in DYT5. 1 Publication
VAR_016902
Natural varianti201 – 2011G → E in DYT5. 2 Publications
VAR_002645
Natural varianti203 – 2031G → R in DYT5. 1 Publication
VAR_002646
Natural varianti211 – 2111M → I in GCH1D; severe hyperphenylalaninemia. 1 Publication
VAR_002647
Natural varianti211 – 2111M → V in DYT5. 1 Publication
VAR_016903
Natural varianti213 – 2131M → V in DYT5. 1 Publication
VAR_016904
Natural varianti221 – 2211M → T in GCH1D; a patient presenting with dystonia and motor delay; compound heterozygote for an additional deletion. 1 Publication
VAR_016905
Natural varianti224 – 2241K → R in GCH1D and DYT5; phenotype presenting with dystonia and myoclonus. 3 Publications
Corresponds to variant rs41298442 [ dbSNP | Ensembl ].
VAR_002648
Natural varianti234 – 2341F → S in DYT5. 1 Publication
VAR_002649
Natural varianti241 – 2411R → W in DYT5. 1 Publication
VAR_016906
Natural varianti249 – 2491R → S in DYT5. 1 Publication
VAR_016907

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei210 – 25041Missing in isoform GCH-3. 1 PublicationVSP_001610Add
BLAST
Alternative sequencei210 – 23324HMCMV…TMLGV → KSNKYNKGLSPLLSSCHLFV AILK in isoform GCH-4. 1 PublicationVSP_001611Add
BLAST
Alternative sequencei210 – 2134HMCM → SAEP in isoform GCH-2. 2 PublicationsVSP_001612
Alternative sequencei214 – 25037Missing in isoform GCH-2. 2 PublicationsVSP_001613Add
BLAST
Alternative sequencei234 – 25017Missing in isoform GCH-4. 1 PublicationVSP_001614Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
S44049 mRNA. Translation: AAB23164.1.
S44053 mRNA. Translation: AAB23165.1.
S43856 mRNA. Translation: AAB23166.1.
Z29433 mRNA. Translation: CAB77391.1.
Z29434 mRNA. Translation: CAB77392.1.
U19523 mRNA. Translation: AAB16861.1.
U66095 mRNA. Translation: AAD38866.1.
U66097 mRNA. Translation: AAD38868.1.
CR536551 mRNA. Translation: CAG38788.1.
CH471061 Genomic DNA. Translation: EAW80647.1.
BC025415 mRNA. Translation: AAH25415.1.
L29478 Genomic DNA. Translation: AAB42186.1.
Z30952 Genomic DNA. Translation: CAA83213.1.
Z16418 mRNA. Translation: CAA78908.1.
U19259
, U19256, U19257, U19258 Genomic DNA. Translation: AAB60633.1.
CCDSiCCDS41954.1. [P30793-4]
CCDS45110.1. [P30793-2]
CCDS9720.1. [P30793-1]
PIRiG01630. PC1117.
JC1225.
RefSeqiNP_000152.1. NM_000161.2. [P30793-1]
NP_001019195.1. NM_001024024.1. [P30793-1]
NP_001019241.1. NM_001024070.1. [P30793-4]
NP_001019242.1. NM_001024071.1. [P30793-2]
XP_005267587.1. XM_005267530.1. [P30793-4]
UniGeneiHs.86724.

Genome annotation databases

EnsembliENST00000395514; ENSP00000378890; ENSG00000131979. [P30793-1]
ENST00000491895; ENSP00000419045; ENSG00000131979. [P30793-1]
ENST00000536224; ENSP00000445246; ENSG00000131979. [P30793-2]
ENST00000543643; ENSP00000444011; ENSG00000131979. [P30793-4]
ENST00000622544; ENSP00000477796; ENSG00000131979. [P30793-1]
GeneIDi2643.
KEGGihsa:2643.
UCSCiuc001xbh.1. human. [P30793-1]
uc001xbj.1. human. [P30793-4]
uc001xbk.1. human. [P30793-2]

Polymorphism databases

DMDMi399536.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
S44049 mRNA. Translation: AAB23164.1 .
S44053 mRNA. Translation: AAB23165.1 .
S43856 mRNA. Translation: AAB23166.1 .
Z29433 mRNA. Translation: CAB77391.1 .
Z29434 mRNA. Translation: CAB77392.1 .
U19523 mRNA. Translation: AAB16861.1 .
U66095 mRNA. Translation: AAD38866.1 .
U66097 mRNA. Translation: AAD38868.1 .
CR536551 mRNA. Translation: CAG38788.1 .
CH471061 Genomic DNA. Translation: EAW80647.1 .
BC025415 mRNA. Translation: AAH25415.1 .
L29478 Genomic DNA. Translation: AAB42186.1 .
Z30952 Genomic DNA. Translation: CAA83213.1 .
Z16418 mRNA. Translation: CAA78908.1 .
U19259
, U19256 , U19257 , U19258 Genomic DNA. Translation: AAB60633.1 .
CCDSi CCDS41954.1. [P30793-4 ]
CCDS45110.1. [P30793-2 ]
CCDS9720.1. [P30793-1 ]
PIRi G01630. PC1117.
JC1225.
RefSeqi NP_000152.1. NM_000161.2. [P30793-1 ]
NP_001019195.1. NM_001024024.1. [P30793-1 ]
NP_001019241.1. NM_001024070.1. [P30793-4 ]
NP_001019242.1. NM_001024071.1. [P30793-2 ]
XP_005267587.1. XM_005267530.1. [P30793-4 ]
UniGenei Hs.86724.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1FB1 X-ray 3.10 A/B/C/D/E 55-250 [» ]
ProteinModelPortali P30793.
SMRi P30793. Positions 55-250.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108913. 30 interactions.
IntActi P30793. 12 interactions.
MINTi MINT-3011998.
STRINGi 9606.ENSP00000378890.

PTM databases

PhosphoSitei P30793.

Polymorphism databases

DMDMi 399536.

Proteomic databases

MaxQBi P30793.
PaxDbi P30793.
PRIDEi P30793.

Protocols and materials databases

DNASUi 2643.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000395514 ; ENSP00000378890 ; ENSG00000131979 . [P30793-1 ]
ENST00000491895 ; ENSP00000419045 ; ENSG00000131979 . [P30793-1 ]
ENST00000536224 ; ENSP00000445246 ; ENSG00000131979 . [P30793-2 ]
ENST00000543643 ; ENSP00000444011 ; ENSG00000131979 . [P30793-4 ]
ENST00000622544 ; ENSP00000477796 ; ENSG00000131979 . [P30793-1 ]
GeneIDi 2643.
KEGGi hsa:2643.
UCSCi uc001xbh.1. human. [P30793-1 ]
uc001xbj.1. human. [P30793-4 ]
uc001xbk.1. human. [P30793-2 ]

Organism-specific databases

CTDi 2643.
GeneCardsi GC14M055308.
GeneReviewsi GCH1.
HGNCi HGNC:4193. GCH1.
HPAi HPA028612.
MIMi 128230. phenotype.
233910. phenotype.
600225. gene.
neXtProti NX_P30793.
Orphaneti 98808. Autosomal dominant dopa-responsive dystonia.
2102. GTP cyclohydrolase I deficiency.
PharmGKBi PA28608.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0302.
GeneTreei ENSGT00390000013481.
HOGENOMi HOG000221222.
HOVERGENi HBG003136.
InParanoidi P30793.
KOi K01495.
OMAi AHYKGEQ.
OrthoDBi EOG77DJ6T.
PhylomeDBi P30793.
TreeFami TF105616.

Enzyme and pathway databases

UniPathwayi UPA00848 ; UER00151 .
BioCyci MetaCyc:HS05586-MONOMER.
Reactomei REACT_111176. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
SABIO-RK P30793.

Miscellaneous databases

EvolutionaryTracei P30793.
GeneWikii GTP_cyclohydrolase_I.
GenomeRNAii 2643.
NextBioi 10420.
PROi P30793.
SOURCEi Search...

Gene expression databases

Bgeei P30793.
CleanExi HS_GCH1.
ExpressionAtlasi P30793. baseline and differential.
Genevestigatori P30793.

Family and domain databases

HAMAPi MF_00223. FolE.
InterProi IPR001474. GTP_CycHdrlase_I.
IPR018234. GTP_CycHdrlase_I_CS.
IPR020602. GTP_CycHdrlase_I_dom.
[Graphical view ]
PANTHERi PTHR11109. PTHR11109. 1 hit.
Pfami PF01227. GTP_cyclohydroI. 1 hit.
[Graphical view ]
TIGRFAMsi TIGR00063. folE. 1 hit.
PROSITEi PS00859. GTP_CYCLOHYDROL_1_1. 1 hit.
PS00860. GTP_CYCLOHYDROL_1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GCH-1; GCH-2 AND GCH-3).
    Tissue: Liver.
  2. "Human GTP cyclohydrolase I: only one out of three cDNA isoforms gives rise to the active enzyme."
    Guetlich M., Jaeger E., Rucknaegel K.P., Werner T., Roedl W., Ziegler I., Bacher A.
    Biochem. J. 302:215-221(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GCH-1 AND GCH-2), FUNCTION.
    Tissue: Liver.
  3. "Isolation of a full-length cDNA clone for human GTP cyclohydrolase I type 1 from pheochromocytoma."
    Nomura T., Ohtsuki M., Matsui S., Sumi-Ichinose C., Nomura H., Hagino Y., Iwase K., Ichinose H., Fujita K., Nagatsu T.
    J. Neural Transm. 101:237-242(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Pheochromocytoma.
  4. "GTP cyclohydrolase I mRNA: novel splice variants in the slime mould Physarum polycephalum and in human monocytes (THP-1) indicate conservation of mRNA processing."
    Golderer G., Werner E.R., Heufler C., Strohmaier W., Grobner P., Werner-Felmayer G.
    Biochem. J. 355:499-507(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GCH-1 AND GCH-4).
    Tissue: Myelomonocyte.
  5. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GCH-1).
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GCH-1).
    Tissue: Brain.
  8. "Cloning, sequencing and functional studies of the gene encoding human GTP cyclohydrolase I."
    Witter K., Werner T., Blusch J.H., Schneider E.-M., Riess O., Ziegler I., Roedl W., Bacher A., Guetlich M.
    Gene 171:285-290(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-114.
    Tissue: Granulocyte.
  9. "Species and tissue specificity of mammalian GTP cyclohydrolase I messenger RNA."
    Guetlich M., Schott K., Werner T., Bacher A., Ziegler I.
    Biochim. Biophys. Acta 1171:133-140(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 60-242.
  10. "Characterization of mouse and human GTP cyclohydrolase I genes. Mutations in patients with GTP cyclohydrolase I deficiency."
    Ichinose H., Ohye T., Matsuda Y., Hori T.A., Blau N., Burlina A., Rouse B., Matalon R., Fujita K., Nagatsu T.
    J. Biol. Chem. 270:10062-10071(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 116-209.
  11. "The application of 8-aminoguanosine triphosphate, a new inhibitor of GTP cyclohydrolase I, to the purification of the enzyme from human liver."
    Blau N., Niederwieser A.
    Biochim. Biophys. Acta 880:26-31(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME ACTIVITY, ENZYME REGULATION.
  12. "Human liver GTP cyclohydrolase I: purification and some properties."
    Shen R.-S., Alam A., Zhang Y.X.
    Biochimie 71:343-349(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
  13. "Purification of GTP cyclohydrolase I from human liver and production of specific monoclonal antibodies."
    Schoedon G., Redweik U., Curtius H.-C.
    Eur. J. Biochem. 178:627-634(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME ACTIVITY, SUBCELLULAR LOCATION.
  14. "Pteridine biosynthesis in human endothelial cells. Impact on nitric oxide-mediated formation of cyclic GMP."
    Werner-Felmayer G., Werner E.R., Fuchs D., Hausen A., Reibnegger G., Schmidt K., Weiss G., Wachter H.
    J. Biol. Chem. 268:1842-1846(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  15. "Mutations in the GTP cyclohydrolase I and 6-pyruvoyl-tetrahydropterin synthase genes."
    Thoeny B., Blau N.
    Hum. Mutat. 10:11-20(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON VARIANTS.
  16. "Cytokines stimulate GTP cyclohydrolase I gene expression in cultured human umbilical vein endothelial cells."
    Katusic Z.S., Stelter A., Milstien S.
    Arterioscler. Thromb. Vasc. Biol. 18:27-32(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION.
  17. "GTP cyclohydrolase I gene transfer augments intracellular tetrahydrobiopterin in human endothelial cells: effects on nitric oxide synthase activity, protein levels and dimerisation."
    Cai S., Alp N.J., McDonald D., Smith I., Kay J., Canevari L., Heales S., Channon K.M.
    Cardiovasc. Res. 55:838-849(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  18. "cAMP inhibits cytokine-induced biosynthesis of tetrahydrobiopterin in human umbilical vein endothelial cells."
    Ohtsuki M., Shiraishi H., Kato T., Kuroda R., Tazawa M., Sumi-Ichinose C., Tada S., Udagawa Y., Itoh M., Hishida H., Ichinose H., Nagatsu T., Hagino Y., Nomura T.
    Life Sci. 70:2187-2198(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  19. "Role of human GTP cyclohydrolase I and its regulatory protein in tetrahydrobiopterin metabolism."
    Gesierich A., Niroomand F., Tiefenbacher C.P.
    Basic Res. Cardiol. 98:69-75(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  20. "cGMP inhibits GTP cyclohydrolase I activity and biosynthesis of tetrahydrobiopterin in human umbilical vein endothelial cells."
    Shiraishi H., Kato T., Atsuta K., Sumi-Ichinose C., Ohtsuki M., Itoh M., Hishida H., Tada S., Udagawa Y., Nagatsu T., Hagino Y., Ichinose H., Nomura T.
    J. Pharmacol. Sci. 93:265-271(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  21. "GTP cyclohydrolase I utilizes metal-free GTP as its substrate."
    Suzuki T., Kurita H., Ichinose H.
    Eur. J. Biochem. 271:349-355(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME REGULATION.
  22. "The assays of activities and function of TH, AADC, and GCH1 and their potential use in ex vivo gene therapy of PD."
    Duan C.-L., Su Y., Zhao C.-L., Lu L.-L., Xu Q.-Y., Yang H.
    Brain Res. Brain Res. Protoc. 16:37-43(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  23. "Cytokine-stimulated GTP cyclohydrolase I expression in endothelial cells requires coordinated activation of nuclear factor-kappaB and Stat1/Stat3."
    Huang A., Zhang Y.-Y., Chen K., Hatakeyama K., Keaney J.F. Jr.
    Circ. Res. 96:164-171(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  24. "Changes in tetrahydrobiopterin levels in endothelial cells and adult cardiomyocytes induced by LPS and hydrogen peroxide -- a role for GFRP?"
    Kalivendi S., Hatakeyama K., Whitsett J., Konorev E., Kalyanaraman B., Vasquez-Vivar J.
    Free Radic. Biol. Med. 38:481-491(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  25. "Interaction of human GTP cyclohydrolase I with its splice variants."
    Pandya M.J., Golderer G., Werner E.R., Werner-Felmayer G.
    Biochem. J. 400:75-80(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  26. "GTP cyclohydrolase feedback regulatory protein controls cofactor 6-tetrahydrobiopterin synthesis in the cytosol and in the nucleus of epidermal keratinocytes and melanocytes."
    Chavan B., Gillbro J.M., Rokos H., Schallreuter K.U.
    J. Invest. Dermatol. 126:2481-2489(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME ACTIVITY, ENZYME REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  27. "A yeast 2-hybrid analysis of human GTP cyclohydrolase I protein interactions."
    Swick L., Kapatos G.
    J. Neurochem. 97:1447-1455(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH AHSA1 AND GCHFR.
  28. Cited for: FUNCTION.
  29. "Regulation of tetrahydrobiopterin biosynthesis by shear stress."
    Widder J.D., Chen W., Li L., Dikalov S., Thony B., Hatakeyama K., Harrison D.G.
    Circ. Res. 101:830-838(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-81.
  30. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  31. Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 55-250, SUBUNIT, ZINC-BINDING SITES.
  32. "Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene."
    Ichinose H., Ohye T., Takahashi E., Seki N., Hori T., Segawa M., Nomura Y., Endo K., Tanaka H., Tsuji S., Fujita K., Nagatsu T.
    Nat. Genet. 8:236-242(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS DYT5 TRP-88; VAL-134 AND GLU-201.
  33. "GTP cyclohydrolase I gene in hereditary progressive dystonia with marked diurnal fluctuation."
    Ichinose H., Ohye T., Segawa M., Nomura Y., Endo K., Tanaka H., Tsuji S., Fujita K., Nagatsu T.
    Neurosci. Lett. 196:5-8(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT DYT5 PRO-79, VARIANTS GCH1D HIS-184 AND ILE-211.
  34. "Mutant GTP cyclohydrolase I mRNA levels contribute to dopa-responsive dystonia onset."
    Hirano M., Tamaru Y., Ito H., Matsumoto S., Imai T., Ueno S.
    Ann. Neurol. 40:796-798(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT DYT5 PRO-144.
  35. "Dopa-responsive dystonia in British patients: new mutations of the GTP-cyclohydrolase I gene and evidence for genetic heterogeneity."
    Bandmann O., Nygaard T.G., Surtess R., Mardsen C.D., Wood N.W., Harding A.E.
    Hum. Mol. Genet. 5:403-406(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS DYT5 PRO-88; PRO-153; ARG-203; ARG-224 AND SER-234.
  36. "A novel point mutation in the GTP cyclohydrolase I gene in a Spanish family with hereditary progressive and dopa responsive dystonia."
    Beyer K., Lao-Villadoniga J.I., Vecino-Bilbao B., Cacabelos R., de la Fuent-Fernandez R.
    J. Neurol. Neurosurg. Psych. 62:420-421(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT DYT5 SER-178.
  37. "GTP cyclohydrolase I mutations in patients with dystonia responsive to anticholinergic drugs."
    Jarman P.R., Bandmann O., Marsden C.D., Wood N.W.
    J. Neurol. Neurosurg. Psych. 63:304-308(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS DYT5 LEU-23 AND ASN-115.
  38. "Dystonia with motor delay in compound heterozygotes for GTP-cyclohydrolase I gene mutations."
    Furukawa Y., Kish S.J., Bebin E.M., Jacobson R.D., Fryburg J.S., Wilson W.G., Shimadzu M., Hyland K., Trugman J.M.
    Ann. Neurol. 44:10-16(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS GCH1D ASP-108; THR-221 AND ARG-224.
  39. Cited for: VARIANTS DYT5 GLN-71; VAL-74; ALA-83; ILE-191; VAL-211 AND TRP-241.
  40. "Dopa-responsive dystonia induced by a recessive GTP cyclohydrolase I mutation."
    Hwu W.-L., Wang P.-J., Hsiao K.-J., Wang T.-R., Chiou Y.-W., Lee Y.-M.
    Hum. Genet. 105:226-230(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT DYT5 SER-249.
  41. "Characterization of wild-type and mutants of recombinant human GTP cyclohydrolase I: relationship to etiology of dopa-responsive dystonia."
    Suzuki T., Ohye T., Inagaki H., Nagatsu T., Ichinose H.
    J. Neurochem. 73:2510-2516(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS DYT5 ARG-102; LYS-102; ARG-141; TRP-141; THR-176; SER-178 AND LYS-186.
  42. "A new GTP-cyclohydrolase I mutation in an unusual dopa-responsive dystonia, familial form."
    Brique S., Destee A., Lambert J.-C., Mouroux V., Delacourte A., Amouyel P., Chartier-Harlin M.-C.
    NeuroReport 10:487-491(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT DYT5 LYS-135.
  43. "A novel missense mutant inactivates GTP cyclohydrolase I in dopa-responsive dystonia."
    Hirano M., Komure O., Ueno S.
    Neurosci. Lett. 260:181-184(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT DYT5 VAL-90.
  44. Cited for: VARIANTS DYT5 ALA-83; 88-ARG-GLN-89 DEL; SER-178; ARG-180; LEU-199 AND GLU-201.
  45. "Dopa-responsive dystonia: mutation analysis of GCH1 and analysis of therapeutic doses of L-dopa. German Dystonia Study Group."
    Steinberger D., Korinthenberg R., Topka H., Berghaeuser M., Wedde R., Mueller U.
    Neurology 55:1735-1737(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS DYT5 ARG-163 AND VAL-213.
  46. "Autosomal dominant GTP-CH deficiency presenting as a dopa-responsive myoclonus-dystonia syndrome."
    Leuzzi V., Carducci C., Carducci C., Cardona F., Artiola C., Antonozzi I.
    Neurology 59:1241-1243(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT DYT5 ARG-224.
  47. "Novel mutations in the guanosine triphosphate cyclohydrolase 1 gene associated with DYT5 dystonia."
    Ohta E., Funayama M., Ichinose H., Toyoshima I., Urano F., Matsuo M., Tomoko N., Yukihiko K., Yoshino S., Yokoyama H., Shimazu H., Maeda K., Hasegawa K., Obata F.
    Arch. Neurol. 63:1605-1610(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT DYT5 ILE-106.

Entry informationi

Entry nameiGCH1_HUMAN
AccessioniPrimary (citable) accession number: P30793
Secondary accession number(s): Q6FHY7, Q9Y4I8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: October 29, 2014
This is version 161 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Allosteric enzyme, Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

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