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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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi24 – 241ZincPROSITE-ProRule annotation
Active sitei43 – 431Proton acceptorPROSITE-ProRule annotation
Metal bindingi49 – 491ZincPROSITE-ProRule annotation
Metal bindingi51 – 511ZincPROSITE-ProRule annotation
Active sitei90 – 901Charge relay systemPROSITE-ProRule annotation
Active sitei134 – 1341Charge relay systemPROSITE-ProRule annotation

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.
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti16 – 161R → C in HPABH4A; severe decrease in activity; diminishes phosphorylation by PKG. 3 Publications
Corresponds to variant rs104894274 [ dbSNP | Ensembl ].
VAR_006816
Natural varianti25 – 251R → G in HPABH4A; severe form. 1 Publication
VAR_006817
Natural varianti25 – 251R → Q in HPABH4A; abolishes activity; no effect on phosphorylation by PKG. 3 Publications
Corresponds to variant rs104894273 [ dbSNP | Ensembl ].
VAR_006818
Natural varianti26 – 261L → F in HPABH4A. 1 Publication
VAR_058265
Natural varianti35 – 351E → G in HPABH4A.
VAR_006819
Natural varianti36 – 361N → K in HPABH4A.
VAR_006820
Natural varianti47 – 471N → 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 Publication
Corresponds to variant rs104894278 [ dbSNP | Ensembl ].
VAR_008040
Natural varianti52 – 521N → S in HPABH4A; severe form; common in Chinese population. 2 Publications
Corresponds to variant rs104894275 [ dbSNP | Ensembl ].
VAR_006821
Natural varianti56 – 561V → M in HPABH4A; mild form. 1 Publication
Corresponds to variant rs104894277 [ dbSNP | Ensembl ].
VAR_006822
Natural varianti57 – 571Missing in HPABH4A. 3 Publications
VAR_006823
Natural varianti67 – 671T → M in HPABH4A. 2 Publications
Corresponds to variant rs370340361 [ dbSNP | Ensembl ].
VAR_006824
Natural varianti70 – 701V → D in HPABH4A. 1 Publication
VAR_006825
Natural varianti87 – 871P → L in HPABH4A. 2 Publications
Corresponds to variant rs765406631 [ dbSNP | Ensembl ].
VAR_006826
Natural varianti87 – 871P → S in HPABH4A; severe form; common in Chinese population. 2 Publications
Corresponds to variant rs104894276 [ dbSNP | Ensembl ].
VAR_006827
Natural varianti96 – 961D → N in HPABH4A; severe form. 1 Publication
Corresponds to variant rs104894280 [ dbSNP | Ensembl ].
VAR_006828
Natural varianti97 – 971V → M in HPABH4A. 1 Publication
Corresponds to variant rs750455879 [ dbSNP | Ensembl ].
VAR_058266
Natural varianti99 – 991Y → C in HPABH4A. 1 Publication
VAR_058267
Natural varianti100 – 1001F → V in HPABH4A.
VAR_006829
Natural varianti106 – 1061T → M in HPABH4A. 1 Publication
Corresponds to variant rs200712908 [ dbSNP | Ensembl ].
VAR_006830
Natural varianti114 – 1141I → V in HPABH4A. 2 Publications
VAR_006831
Natural varianti116 – 1161D → 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 Publication
Corresponds to variant rs104894279 [ dbSNP | Ensembl ].
VAR_008041
Natural varianti124 – 1241V → L in HPABH4A. 1 Publication
Corresponds to variant rs150726932 [ dbSNP | Ensembl ].
VAR_058268
Natural varianti129 – 1291K → E in HPABH4A. 1 Publication
VAR_006832
Natural varianti136 – 1361D → G in HPABH4A. 1 Publication
VAR_058269
Natural varianti136 – 1361D → V in HPABH4A. 2 Publications
VAR_006833

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi19 – 191S → A: Decrease in activity; abolishes phosphorylation by PKG. 1 Publication

Keywords - Diseasei

Disease mutation, Phenylketonuria

Organism-specific databases

MalaCardsiPTS.
MIMi261640. phenotype.
Orphaneti13. 6-pyruvoyl-tetrahydropterin synthase deficiency.
PharmGKBiPA34032.

Polymorphism and mutation databases

BioMutaiPTS.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 1451456-pyruvoyl tetrahydrobiopterin synthasePRO_0000057914Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei19 – 191Phosphoserine; by PKGCombined sources1 Publication
Modified residuei28 – 281PhosphoserineBy similarity
Modified residuei128 – 1281PhosphotyrosineCombined sources

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.
PhosphoSiteiQ03393.

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
itself7EBI-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 interactions.
IntActiQ03393. 8 interactions.
MINTiMINT-1419639.
STRINGi9606.ENSP00000280362.

Structurei

Secondary structure

1
145
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi11 – 2414Combined sources
Beta strandi29 – 313Combined sources
Helixi33 – 408Combined sources
Helixi41 – 444Combined sources
Beta strandi49 – 6214Combined sources
Turni65 – 673Combined sources
Helixi73 – 8311Combined sources
Helixi85 – 884Combined sources
Helixi93 – 964Combined sources
Helixi98 – 1014Combined sources
Helixi107 – 11913Combined sources
Beta strandi127 – 1359Combined sources
Beta strandi138 – 1425Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3I2BX-ray2.30A/B/C/D/E/F/G/H/I/J/K/L7-145[»]
ProteinModelPortaliQ03393.
SMRiQ03393. Positions 8-145.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti114 – 1141I → M in AAH18029 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti16 – 161R → C in HPABH4A; severe decrease in activity; diminishes phosphorylation by PKG. 3 Publications
Corresponds to variant rs104894274 [ dbSNP | Ensembl ].
VAR_006816
Natural varianti25 – 251R → G in HPABH4A; severe form. 1 Publication
VAR_006817
Natural varianti25 – 251R → Q in HPABH4A; abolishes activity; no effect on phosphorylation by PKG. 3 Publications
Corresponds to variant rs104894273 [ dbSNP | Ensembl ].
VAR_006818
Natural varianti26 – 261L → F in HPABH4A. 1 Publication
VAR_058265
Natural varianti35 – 351E → G in HPABH4A.
VAR_006819
Natural varianti36 – 361N → K in HPABH4A.
VAR_006820
Natural varianti47 – 471N → 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 Publication
Corresponds to variant rs104894278 [ dbSNP | Ensembl ].
VAR_008040
Natural varianti52 – 521N → S in HPABH4A; severe form; common in Chinese population. 2 Publications
Corresponds to variant rs104894275 [ dbSNP | Ensembl ].
VAR_006821
Natural varianti56 – 561V → M in HPABH4A; mild form. 1 Publication
Corresponds to variant rs104894277 [ dbSNP | Ensembl ].
VAR_006822
Natural varianti57 – 571Missing in HPABH4A. 3 Publications
VAR_006823
Natural varianti67 – 671T → M in HPABH4A. 2 Publications
Corresponds to variant rs370340361 [ dbSNP | Ensembl ].
VAR_006824
Natural varianti70 – 701V → D in HPABH4A. 1 Publication
VAR_006825
Natural varianti87 – 871P → L in HPABH4A. 2 Publications
Corresponds to variant rs765406631 [ dbSNP | Ensembl ].
VAR_006826
Natural varianti87 – 871P → S in HPABH4A; severe form; common in Chinese population. 2 Publications
Corresponds to variant rs104894276 [ dbSNP | Ensembl ].
VAR_006827
Natural varianti96 – 961D → N in HPABH4A; severe form. 1 Publication
Corresponds to variant rs104894280 [ dbSNP | Ensembl ].
VAR_006828
Natural varianti97 – 971V → M in HPABH4A. 1 Publication
Corresponds to variant rs750455879 [ dbSNP | Ensembl ].
VAR_058266
Natural varianti99 – 991Y → C in HPABH4A. 1 Publication
VAR_058267
Natural varianti100 – 1001F → V in HPABH4A.
VAR_006829
Natural varianti106 – 1061T → M in HPABH4A. 1 Publication
Corresponds to variant rs200712908 [ dbSNP | Ensembl ].
VAR_006830
Natural varianti114 – 1141I → V in HPABH4A. 2 Publications
VAR_006831
Natural varianti116 – 1161D → 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 Publication
Corresponds to variant rs104894279 [ dbSNP | Ensembl ].
VAR_008041
Natural varianti124 – 1241V → L in HPABH4A. 1 Publication
Corresponds to variant rs150726932 [ dbSNP | Ensembl ].
VAR_058268
Natural varianti129 – 1291K → E in HPABH4A. 1 Publication
VAR_006832
Natural varianti136 – 1361D → G in HPABH4A. 1 Publication
VAR_058269
Natural varianti136 – 1361D → V in HPABH4A. 2 Publications
VAR_006833

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
EntryMethodResolution (Å)ChainPositionsPDBsum
3I2BX-ray2.30A/B/C/D/E/F/G/H/I/J/K/L7-145[»]
ProteinModelPortaliQ03393.
SMRiQ03393. Positions 8-145.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiQ03393.
PhosphoSiteiQ03393.

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.
GeneCardsiPTS.
HGNCiHGNC:9689. PTS.
HPAiHPA001481.
MalaCardsiPTS.
MIMi261640. phenotype.
612719. gene.
neXtProtiNX_Q03393.
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.
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: September 7, 2016
This is version 171 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.