Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

6-pyruvoyl tetrahydrobiopterin synthase

Gene

PTS

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

Functioni

Involved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases. Catalyzes the transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin.1 Publication

Miscellaneous

The active site is at the interface between 2 subunits. The proton acceptor Cys is on one subunit, and the charge relay system is on the other subunit.

Catalytic activityi

7,8-dihydroneopterin 3'-triphosphate = 6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate.1 Publication

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Kineticsi

  1. KM=8.1 µM for 7,8-dihydroneopterin triphosphate1 Publication
  1. Vmax=120 nmol/min/mg enzyme1 Publication

Pathwayi: tetrahydrobiopterin biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes tetrahydrobiopterin from 7,8-dihydroneopterin triphosphate.
Proteins known to be involved in the 3 steps of the subpathway in this organism are:
  1. 6-pyruvoyl tetrahydrobiopterin synthase (BQ8482_130070), 6-pyruvoyl tetrahydrobiopterin synthase (BQ8482_290038), 6-pyruvoyl tetrahydrobiopterin synthase (BQ8482_220178), 6-pyruvoyl tetrahydrobiopterin synthase (PTS), 6-pyruvoyl tetrahydrobiopterin synthase (BQ8482_40019)
  2. no protein annotated in this organism
  3. no protein annotated in this organism
This subpathway is part of the pathway tetrahydrobiopterin biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes tetrahydrobiopterin from 7,8-dihydroneopterin triphosphate, the pathway tetrahydrobiopterin biosynthesis and in Cofactor biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi24ZincPROSITE-ProRule annotation1
Active sitei43Proton acceptorPROSITE-ProRule annotation1
Metal bindingi49ZincPROSITE-ProRule annotation1
Metal bindingi51ZincPROSITE-ProRule annotation1
Active sitei90Charge relay systemPROSITE-ProRule annotation1
Active sitei134Charge relay systemPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

  • cellular amino acid metabolic process Source: ProtInc
  • central nervous system development Source: ProtInc
  • cofactor metabolic process Source: Reactome
  • tetrahydrobiopterin biosynthetic process Source: ProtInc

Keywordsi

Molecular functionLyase
Biological processTetrahydrobiopterin biosynthesis
LigandMetal-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:HS07692-MONOMER
BRENDAi4.2.3.12 2681
ReactomeiR-HSA-1474151 Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
SABIO-RKiQ03393
SIGNORiQ03393
UniPathwayiUPA00849; UER00819

Names & Taxonomyi

Protein namesi
Recommended name:
6-pyruvoyl tetrahydrobiopterin synthase (EC:4.2.3.12)
Short name:
PTP synthase
Short name:
PTPS
Gene namesi
Name:PTS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000150787.7
HGNCiHGNC:9689 PTS
MIMi612719 gene
neXtProtiNX_Q03393

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Hyperphenylalaninemia, BH4-deficient, A (HPABH4A)12 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder characterized by hyperphenylalaninemia, depletion of the neurotransmitters dopamine and serotonin, and progressive cognitive and motor deficits. Neurological symptoms are unresponsive to the classic phenylalanine-low diet.
See also OMIM:261640
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00681616R → C in HPABH4A; severe decrease in activity; diminishes phosphorylation by PKG. 3 PublicationsCorresponds to variant dbSNP:rs104894274EnsemblClinVar.1
Natural variantiVAR_00681725R → G in HPABH4A; severe form. 1 Publication1
Natural variantiVAR_00681825R → Q in HPABH4A; abolishes activity; no effect on phosphorylation by PKG. 3 PublicationsCorresponds to variant dbSNP:rs104894273EnsemblClinVar.1
Natural variantiVAR_05826526L → F in HPABH4A. 1 Publication1
Natural variantiVAR_00681935E → G in HPABH4A. 1
Natural variantiVAR_00682036N → K in HPABH4A. 1
Natural variantiVAR_00804047N → D in HPABH4A; transient phenotype due to partial PTS deficiency; the patient is compound heterozygote for D-47 and G-116; total loss of activity. 1 PublicationCorresponds to variant dbSNP:rs104894278EnsemblClinVar.1
Natural variantiVAR_00682152N → S in HPABH4A; severe form; common in Chinese population. 2 PublicationsCorresponds to variant dbSNP:rs104894275EnsemblClinVar.1
Natural variantiVAR_00682256V → M in HPABH4A; mild form. 1 PublicationCorresponds to variant dbSNP:rs104894277EnsemblClinVar.1
Natural variantiVAR_00682357Missing in HPABH4A. 3 Publications1
Natural variantiVAR_00682467T → M in HPABH4A. 2 PublicationsCorresponds to variant dbSNP:rs370340361EnsemblClinVar.1
Natural variantiVAR_00682570V → D in HPABH4A. 1 Publication1
Natural variantiVAR_00682687P → L in HPABH4A. 2 PublicationsCorresponds to variant dbSNP:rs765406631Ensembl.1
Natural variantiVAR_00682787P → S in HPABH4A; severe form; common in Chinese population. 2 PublicationsCorresponds to variant dbSNP:rs104894276EnsemblClinVar.1
Natural variantiVAR_00682896D → N in HPABH4A; severe form. 1 PublicationCorresponds to variant dbSNP:rs104894280EnsemblClinVar.1
Natural variantiVAR_05826697V → M in HPABH4A. 1 PublicationCorresponds to variant dbSNP:rs750455879Ensembl.1
Natural variantiVAR_05826799Y → C in HPABH4A. 1 Publication1
Natural variantiVAR_006829100F → V in HPABH4A. 1
Natural variantiVAR_006830106T → M in HPABH4A. 1 PublicationCorresponds to variant dbSNP:rs200712908Ensembl.1
Natural variantiVAR_006831114I → V in HPABH4A. 2 Publications1
Natural variantiVAR_008041116D → G in HPABH4A; transient phenotype due to partial PTS deficiency; the patient is compound heterozygote for D-47 and G-116; mild decrease of activity. 1 PublicationCorresponds to variant dbSNP:rs104894279EnsemblClinVar.1
Natural variantiVAR_058268124V → L in HPABH4A. 1 PublicationCorresponds to variant dbSNP:rs150726932Ensembl.1
Natural variantiVAR_006832129K → E in HPABH4A. 1 PublicationCorresponds to variant dbSNP:rs1040441824Ensembl.1
Natural variantiVAR_058269136D → G in HPABH4A. 1 Publication1
Natural variantiVAR_006833136D → V in HPABH4A. 2 Publications1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi19S → A: Decrease in activity; abolishes phosphorylation by PKG. 1 Publication1

Keywords - Diseasei

Disease mutation, Phenylketonuria

Organism-specific databases

DisGeNETi5805
MalaCardsiPTS
MIMi261640 phenotype
OpenTargetsiENSG00000150787
Orphaneti13 6-pyruvoyl-tetrahydropterin synthase deficiency
PharmGKBiPA34032

Chemistry databases

DrugBankiDB03886 Biopterin

Polymorphism and mutation databases

BioMutaiPTS

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000579141 – 1456-pyruvoyl tetrahydrobiopterin synthaseAdd BLAST145

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19Phosphoserine; by PKGCombined sources1 Publication1
Modified residuei28PhosphoserineBy similarity1
Modified residuei128PhosphotyrosineCombined sources1

Post-translational modificationi

Phosphorylation of Ser-19 is required for maximal enzyme activity.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ03393
MaxQBiQ03393
PaxDbiQ03393
PeptideAtlasiQ03393
PRIDEiQ03393
ProteomicsDBi58205
TopDownProteomicsiQ03393

PTM databases

iPTMnetiQ03393
PhosphoSitePlusiQ03393

Expressioni

Gene expression databases

BgeeiENSG00000150787
CleanExiHS_PTS
ExpressionAtlasiQ03393 baseline and differential
GenevisibleiQ03393 HS

Organism-specific databases

HPAiHPA001481

Interactioni

Subunit structurei

Homohexamer formed of two homotrimers in a head to head fashion.

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111769, 24 interactors
IntActiQ03393, 10 interactors
MINTiQ03393
STRINGi9606.ENSP00000280362

Structurei

Secondary structure

1145
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi11 – 24Combined sources14
Beta strandi29 – 31Combined sources3
Helixi33 – 40Combined sources8
Helixi41 – 44Combined sources4
Beta strandi49 – 62Combined sources14
Turni65 – 67Combined sources3
Helixi73 – 83Combined sources11
Helixi85 – 88Combined sources4
Helixi93 – 96Combined sources4
Helixi98 – 101Combined sources4
Helixi107 – 119Combined sources13
Beta strandi127 – 135Combined sources9
Beta strandi138 – 142Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3I2BX-ray2.30A/B/C/D/E/F/G/H/I/J/K/L7-145[»]
ProteinModelPortaliQ03393
SMRiQ03393
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ03393

Family & Domainsi

Sequence similaritiesi

Belongs to the PTPS family.Curated

Phylogenomic databases

eggNOGiKOG4105 Eukaryota
COG0720 LUCA
GeneTreeiENSGT00390000002752
HOGENOMiHOG000225069
HOVERGENiHBG004358
InParanoidiQ03393
KOiK01737
OMAiNIAVVIW
OrthoDBiEOG091G0TKH
PhylomeDBiQ03393
TreeFamiTF105796

Family and domain databases

Gene3Di3.30.479.10, 1 hit
InterProiView protein in InterPro
IPR007115 6-PTP_synth/QueD
IPR038418 6-PTP_synth/QueD_sf
IPR022470 PTPS_Cys_AS
IPR022469 PTPS_His_AS
PANTHERiPTHR12589 PTHR12589, 1 hit
PfamiView protein in Pfam
PF01242 PTPS, 1 hit
PIRSFiPIRSF006113 PTP_synth, 1 hit
TIGRFAMsiTIGR00039 6PTHBS, 1 hit
PROSITEiView protein in PROSITE
PS00987 PTPS_1, 1 hit
PS00988 PTPS_2, 1 hit

Sequencei

Sequence statusi: Complete.

Q03393-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTEGGGRRC QAQVSRRISF SASHRLYSKF LSDEENLKLF GKCNNPNGHG
60 70 80 90 100
HNYKVVVTVH GEIDPATGMV MNLADLKKYM EEAIMQPLDH KNLDMDVPYF
110 120 130 140
ADVVSTTENV AVYIWDNLQK VLPVGVLYKV KVYETDNNIV VYKGE
Length:145
Mass (Da):16,386
Last modified:October 1, 1993 - v1
Checksum:iA1CD0DC2F83187E0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti114I → M in AAH18029 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00681616R → C in HPABH4A; severe decrease in activity; diminishes phosphorylation by PKG. 3 PublicationsCorresponds to variant dbSNP:rs104894274EnsemblClinVar.1
Natural variantiVAR_00681725R → G in HPABH4A; severe form. 1 Publication1
Natural variantiVAR_00681825R → Q in HPABH4A; abolishes activity; no effect on phosphorylation by PKG. 3 PublicationsCorresponds to variant dbSNP:rs104894273EnsemblClinVar.1
Natural variantiVAR_05826526L → F in HPABH4A. 1 Publication1
Natural variantiVAR_00681935E → G in HPABH4A. 1
Natural variantiVAR_00682036N → K in HPABH4A. 1
Natural variantiVAR_00804047N → D in HPABH4A; transient phenotype due to partial PTS deficiency; the patient is compound heterozygote for D-47 and G-116; total loss of activity. 1 PublicationCorresponds to variant dbSNP:rs104894278EnsemblClinVar.1
Natural variantiVAR_00682152N → S in HPABH4A; severe form; common in Chinese population. 2 PublicationsCorresponds to variant dbSNP:rs104894275EnsemblClinVar.1
Natural variantiVAR_00682256V → M in HPABH4A; mild form. 1 PublicationCorresponds to variant dbSNP:rs104894277EnsemblClinVar.1
Natural variantiVAR_00682357Missing in HPABH4A. 3 Publications1
Natural variantiVAR_00682467T → M in HPABH4A. 2 PublicationsCorresponds to variant dbSNP:rs370340361EnsemblClinVar.1
Natural variantiVAR_00682570V → D in HPABH4A. 1 Publication1
Natural variantiVAR_00682687P → L in HPABH4A. 2 PublicationsCorresponds to variant dbSNP:rs765406631Ensembl.1
Natural variantiVAR_00682787P → S in HPABH4A; severe form; common in Chinese population. 2 PublicationsCorresponds to variant dbSNP:rs104894276EnsemblClinVar.1
Natural variantiVAR_00682896D → N in HPABH4A; severe form. 1 PublicationCorresponds to variant dbSNP:rs104894280EnsemblClinVar.1
Natural variantiVAR_05826697V → M in HPABH4A. 1 PublicationCorresponds to variant dbSNP:rs750455879Ensembl.1
Natural variantiVAR_05826799Y → C in HPABH4A. 1 Publication1
Natural variantiVAR_006829100F → V in HPABH4A. 1
Natural variantiVAR_006830106T → M in HPABH4A. 1 PublicationCorresponds to variant dbSNP:rs200712908Ensembl.1
Natural variantiVAR_006831114I → V in HPABH4A. 2 Publications1
Natural variantiVAR_008041116D → G in HPABH4A; transient phenotype due to partial PTS deficiency; the patient is compound heterozygote for D-47 and G-116; mild decrease of activity. 1 PublicationCorresponds to variant dbSNP:rs104894279EnsemblClinVar.1
Natural variantiVAR_058268124V → L in HPABH4A. 1 PublicationCorresponds to variant dbSNP:rs150726932Ensembl.1
Natural variantiVAR_006832129K → E in HPABH4A. 1 PublicationCorresponds to variant dbSNP:rs1040441824Ensembl.1
Natural variantiVAR_058269136D → G in HPABH4A. 1 Publication1
Natural variantiVAR_006833136D → V in HPABH4A. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M97655 mRNA Translation: AAA51541.1
D17400 mRNA Translation: BAA04224.1
D25234 Genomic DNA Translation: BAA04959.1
L76259 Genomic DNA Translation: AAB64229.1
U63383
, U63380, U63381, U63382 Genomic DNA Translation: AAC16970.1
AB042297 Genomic DNA Translation: BAA95486.1
EF445018 Genomic DNA Translation: ACA06065.1
CH471065 Genomic DNA Translation: EAW67195.1
BC009686 mRNA Translation: AAH09686.1
BC018029 mRNA Translation: AAH18029.1
CCDSiCCDS8359.1
PIRiJC1405
RefSeqiNP_000308.1, NM_000317.2
UniGeneiHs.503860

Genome annotation databases

EnsembliENST00000280362; ENSP00000280362; ENSG00000150787
GeneIDi5805
KEGGihsa:5805
UCSCiuc001pnj.5 human

Similar proteinsi

Entry informationi

Entry nameiPTPS_HUMAN
AccessioniPrimary (citable) accession number: Q03393
Secondary accession number(s): B0YJ87, Q8WVG8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: June 20, 2018
This is version 185 of the entry and version 1 of the sequence. See 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, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: 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

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health