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Protein

6-pyruvoyl tetrahydrobiopterin synthase

Gene

PTS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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 (PTS)
  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
  • regulation of nitric-oxide synthase activity Source: Reactome
  • tetrahydrobiopterin biosynthetic process Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

Tetrahydrobiopterin biosynthesis

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:HS07692-MONOMER.
ZFISH:HS07692-MONOMER.
BRENDAi4.2.3.12. 2681.
ReactomeiR-HSA-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
SABIO-RKQ03393.
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

HGNCiHGNC:9689. PTS.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Hyperphenylalaninemia, BH4-deficient, A (HPABH4A)10 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 rs104894274dbSNPEnsembl.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 rs104894273dbSNPEnsembl.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 rs104894278dbSNPEnsembl.1
Natural variantiVAR_00682152N → S in HPABH4A; severe form; common in Chinese population. 2 PublicationsCorresponds to variant rs104894275dbSNPEnsembl.1
Natural variantiVAR_00682256V → M in HPABH4A; mild form. 1 PublicationCorresponds to variant rs104894277dbSNPEnsembl.1
Natural variantiVAR_00682357Missing in HPABH4A. 3 Publications1
Natural variantiVAR_00682467T → M in HPABH4A. 2 PublicationsCorresponds to variant rs370340361dbSNPEnsembl.1
Natural variantiVAR_00682570V → D in HPABH4A. 1 Publication1
Natural variantiVAR_00682687P → L in HPABH4A. 2 PublicationsCorresponds to variant rs765406631dbSNPEnsembl.1
Natural variantiVAR_00682787P → S in HPABH4A; severe form; common in Chinese population. 2 PublicationsCorresponds to variant rs104894276dbSNPEnsembl.1
Natural variantiVAR_00682896D → N in HPABH4A; severe form. 1 PublicationCorresponds to variant rs104894280dbSNPEnsembl.1
Natural variantiVAR_05826697V → M in HPABH4A. 1 PublicationCorresponds to variant rs750455879dbSNPEnsembl.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 rs200712908dbSNPEnsembl.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 rs104894279dbSNPEnsembl.1
Natural variantiVAR_058268124V → L in HPABH4A. 1 PublicationCorresponds to variant rs150726932dbSNPEnsembl.1
Natural variantiVAR_006832129K → E in HPABH4A. 1 Publication1
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.

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.
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

WithEntry#Exp.IntActNotes
itself9EBI-712344,EBI-712344
COILP384323EBI-712344,EBI-945751
LNX1Q8TBB13EBI-712344,EBI-739832
SDCBPO005603EBI-712344,EBI-727004
THAP10Q9P2Z03EBI-712344,EBI-745404

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi111769. 17 interactors.
IntActiQ03393. 8 interactors.
MINTiMINT-1419639.
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.
OMAiHGHNYVW.
OrthoDBiEOG091G0TKH.
PhylomeDBiQ03393.
TreeFamiTF105796.

Family and domain databases

InterProiIPR007115. 6-PTP_synth/QueD.
IPR022470. PTPS_Cys_AS.
IPR022469. PTPS_His_AS.
[Graphical view]
PANTHERiPTHR12589. PTHR12589. 1 hit.
PfamiPF01242. PTPS. 1 hit.
[Graphical view]
PIRSFiPIRSF006113. PTP_synth. 1 hit.
TIGRFAMsiTIGR00039. 6PTHBS. 1 hit.
PROSITEiPS00987. PTPS_1. 1 hit.
PS00988. PTPS_2. 1 hit.
[Graphical view]

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 rs104894274dbSNPEnsembl.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 rs104894273dbSNPEnsembl.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 rs104894278dbSNPEnsembl.1
Natural variantiVAR_00682152N → S in HPABH4A; severe form; common in Chinese population. 2 PublicationsCorresponds to variant rs104894275dbSNPEnsembl.1
Natural variantiVAR_00682256V → M in HPABH4A; mild form. 1 PublicationCorresponds to variant rs104894277dbSNPEnsembl.1
Natural variantiVAR_00682357Missing in HPABH4A. 3 Publications1
Natural variantiVAR_00682467T → M in HPABH4A. 2 PublicationsCorresponds to variant rs370340361dbSNPEnsembl.1
Natural variantiVAR_00682570V → D in HPABH4A. 1 Publication1
Natural variantiVAR_00682687P → L in HPABH4A. 2 PublicationsCorresponds to variant rs765406631dbSNPEnsembl.1
Natural variantiVAR_00682787P → S in HPABH4A; severe form; common in Chinese population. 2 PublicationsCorresponds to variant rs104894276dbSNPEnsembl.1
Natural variantiVAR_00682896D → N in HPABH4A; severe form. 1 PublicationCorresponds to variant rs104894280dbSNPEnsembl.1
Natural variantiVAR_05826697V → M in HPABH4A. 1 PublicationCorresponds to variant rs750455879dbSNPEnsembl.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 rs200712908dbSNPEnsembl.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 rs104894279dbSNPEnsembl.1
Natural variantiVAR_058268124V → L in HPABH4A. 1 PublicationCorresponds to variant rs150726932dbSNPEnsembl.1
Natural variantiVAR_006832129K → E in HPABH4A. 1 Publication1
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.

Cross-referencesi

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.

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...

Protein-protein interaction databases

BioGridi111769. 17 interactors.
IntActiQ03393. 8 interactors.
MINTiMINT-1419639.
STRINGi9606.ENSP00000280362.

PTM databases

iPTMnetiQ03393.
PhosphoSitePlusiQ03393.

Polymorphism and mutation databases

BioMutaiPTS.

Proteomic databases

EPDiQ03393.
MaxQBiQ03393.
PaxDbiQ03393.
PeptideAtlasiQ03393.
PRIDEiQ03393.
TopDownProteomicsiQ03393.

Protocols and materials databases

DNASUi5805.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5805.
DisGeNETi5805.
GeneCardsiPTS.
HGNCiHGNC:9689. PTS.
HPAiHPA001481.
MalaCardsiPTS.
MIMi261640. phenotype.
612719. gene.
neXtProtiNX_Q03393.
OpenTargetsiENSG00000150787.
Orphaneti13. 6-pyruvoyl-tetrahydropterin synthase deficiency.
PharmGKBiPA34032.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayiUPA00849; UER00819.
BioCyciMetaCyc:HS07692-MONOMER.
ZFISH:HS07692-MONOMER.
BRENDAi4.2.3.12. 2681.
ReactomeiR-HSA-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
SABIO-RKQ03393.
SIGNORiQ03393.

Miscellaneous databases

EvolutionaryTraceiQ03393.
GeneWikiiPTS_(gene).
GenomeRNAii5805.
PROiQ03393.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000150787.
CleanExiHS_PTS.
ExpressionAtlasiQ03393. baseline and differential.
GenevisibleiQ03393. HS.

Family and domain databases

InterProiIPR007115. 6-PTP_synth/QueD.
IPR022470. PTPS_Cys_AS.
IPR022469. PTPS_His_AS.
[Graphical view]
PANTHERiPTHR12589. PTHR12589. 1 hit.
PfamiPF01242. PTPS. 1 hit.
[Graphical view]
PIRSFiPIRSF006113. PTP_synth. 1 hit.
TIGRFAMsiTIGR00039. 6PTHBS. 1 hit.
PROSITEiPS00987. PTPS_1. 1 hit.
PS00988. PTPS_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPTPS_HUMAN
AccessioniPrimary (citable) accession number: Q03393
Secondary accession number(s): B0YJ87, Q8WVG8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: November 30, 2016
This is version 173 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

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.

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.