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Q03393 (PTPS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
6-pyruvoyl tetrahydrobiopterin synthase

Short name=PTP synthase
Short name=PTPS
EC=4.2.3.12
Gene names
Name:PTS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length145 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Catalytic activity

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

Cofactor

Binds 1 zinc ion per subunit By similarity.

Pathway

Cofactor biosynthesis; tetrahydrobiopterin biosynthesis; tetrahydrobiopterin from 7,8-dihydroneopterin triphosphate: step 1/3.

Subunit structure

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

Post-translational modification

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

Involvement in disease

Hyperphenylalaninemia, BH4-deficient, A (HPABH4A) [MIM:261640]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.12 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23

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.

Sequence similarities

Belongs to the PTPS family.

Biophysicochemical properties

Kinetic parameters:

KM=8.1 µM for 7,8-dihydroneopterin triphosphate Ref.12

Vmax=120 nmol/min/mg enzyme

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself4EBI-712344,EBI-712344

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 1451456-pyruvoyl tetrahydrobiopterin synthase
PRO_0000057914

Sites

Active site431Proton acceptor By similarity
Active site901Charge relay system By similarity
Active site1341Charge relay system By similarity
Metal binding241Zinc By similarity
Metal binding491Zinc By similarity
Metal binding511Zinc By similarity

Amino acid modifications

Modified residue191Phosphoserine; by PKG Ref.10 Ref.11 Ref.12

Natural variations

Natural variant161R → C in HPABH4A; severe decrease in activity; diminishes phosphorylation by PKG. Ref.12 Ref.14 Ref.15
VAR_006816
Natural variant251R → G in HPABH4A; severe form. Ref.19
VAR_006817
Natural variant251R → Q in HPABH4A; abolishes activity; no effect on phosphorylation by PKG. Ref.12 Ref.14 Ref.15
VAR_006818
Natural variant261L → F in HPABH4A. Ref.23
VAR_058265
Natural variant351E → G in HPABH4A.
VAR_006819
Natural variant361N → K in HPABH4A.
VAR_006820
Natural variant471N → D in HPABH4A; transient phenotype; due to partial PTS deficiency; total loss of activity. Ref.21
VAR_008040
Natural variant521N → S in HPABH4A; severe form; common in Chinese population. Ref.16 Ref.19
VAR_006821
Natural variant561V → M in HPABH4A; mild form. Ref.19
VAR_006822
Natural variant571Missing in HPABH4A. Ref.15 Ref.17 Ref.20
VAR_006823
Natural variant671T → M in HPABH4A. Ref.17 Ref.23
VAR_006824
Natural variant701V → D in HPABH4A. Ref.19
VAR_006825
Natural variant871P → L in HPABH4A. Ref.15 Ref.23
VAR_006826
Natural variant871P → S in HPABH4A; severe form; common in Chinese population. Ref.16 Ref.19
Corresponds to variant rs104894276 [ dbSNP | Ensembl ].
VAR_006827
Natural variant961D → N in HPABH4A; severe form. Ref.19
Corresponds to variant rs104894280 [ dbSNP | Ensembl ].
VAR_006828
Natural variant971V → M in HPABH4A. Ref.20
VAR_058266
Natural variant991Y → C in HPABH4A. Ref.22
VAR_058267
Natural variant1001F → V in HPABH4A.
VAR_006829
Natural variant1061T → M in HPABH4A. Ref.19
VAR_006830
Natural variant1141I → V in HPABH4A. Ref.3 Ref.18
VAR_006831
Natural variant1161D → G in HPABH4A; due to partial PTS deficiency; mild form. Ref.21
VAR_008041
Natural variant1241V → L in HPABH4A. Ref.23
VAR_058268
Natural variant1291K → E in HPABH4A. Ref.17
VAR_006832
Natural variant1361D → G in HPABH4A. Ref.23
VAR_058269
Natural variant1361D → V in HPABH4A. Ref.17 Ref.23
VAR_006833

Experimental info

Mutagenesis191S → A: Decrease in activity; abolishes phosphorylation by PKG. Ref.12
Sequence conflict1141I → M in AAH18029. Ref.9

Secondary structure

.......................... 145
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q03393 [UniParc].

Last modified October 1, 1993. Version 1.
Checksum: A1CD0DC2F83187E0

FASTA14516,386
        10         20         30         40         50         60 
MSTEGGGRRC QAQVSRRISF SASHRLYSKF LSDEENLKLF GKCNNPNGHG HNYKVVVTVH 

        70         80         90        100        110        120 
GEIDPATGMV MNLADLKKYM EEAIMQPLDH KNLDMDVPYF ADVVSTTENV AVYIWDNLQK 

       130        140 
VLPVGVLYKV KVYETDNNIV VYKGE 

« Hide

References

« Hide 'large scale' references
[1]"Human 6-pyruvoyltetrahydropterin synthase: cDNA cloning and heterologous expression of the recombinant enzyme."
Thoeny B., Leimbacher W., Buergisser D., Heizmann C.W.
Biochem. Biophys. Res. Commun. 189:1437-1443(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]"cDNA cloning, expression in Escherichia coli and purification of human 6-pyruvoyl-tetrahydropterin synthase."
Ashida A., Hatakeyama K., Kagamiyama H.
Biochem. Biophys. Res. Commun. 195:1386-1393(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"A missense mutation (A to G) of 6-pyruvoyltetrahydropterin synthase in tetrahydrobiopterin-deficient form of hyperphenylalaninemia."
Ashida A., Owada M., Hatakeyama K.
Genomics 24:408-410(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HPABH4A VAL-114.
[4]"Chromosomal localization, genomic structure and characterization of the human gene and a retropseudogene for 6-pyruvoyltetrahydropterin synthase."
Kluge C., Brecevic L., Heizmann C.W., Blau N., Thoeny B.
Eur. J. Biochem. 240:477-484(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Genomic structure of 6-pyruvoyl-tetrahydropterin synthase gene and a T/C polymorphism detected in Chinese."
Liu T.T., Lu S.F., Hsiao K.J.
J. Biomed. Lab. Sci. 10:39-47(1998)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"Isolation and sequencing of human 6-pyruvoyl-tetrahydropterin synthase gene containing BAC clone 321H15."
Hsiao K.-J., Liu T.-T., Chang Y.-H., Chiu Y.-H., Chiang S.-H., Chang H.-M., Chen C.-Y., Tsai S.-F.
Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]NHLBI resequencing and genotyping service (RS&G)
Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"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].
Tissue: Brain and Pancreas.
[10]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"Serine 19 of human 6-pyruvoyltetrahydropterin synthase is phosphorylated by cGMP protein kinase II."
Scherer-Oppliger T., Leimbacher W., Blau N., Thoeny B.
J. Biol. Chem. 274:31341-31348(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS HPABH4A CYS-16 AND GLN-25, KINETIC PARAMETERS, PHOSPHORYLATION AT SER-19, MUTAGENESIS OF SER-19.
[13]"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.
[14]"Hyperphenylalaninemia due to defects in tetrahydrobiopterin metabolism: molecular characterization of mutations in 6-pyruvoyl-tetrahydropterin synthase."
Thoeny B., Leimbacher W., Blau N., Harvie A., Heizmann C.W.
Am. J. Hum. Genet. 54:782-792(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPABH4A CYS-16 AND GLN-25.
[15]"Structural and functional consequences of mutations in 6-pyruvoyltetrahydropterin synthase causing hyperphenylalaninemia in humans. Phosphorylation is a requirement for in vivo activity."
Oppliger T., Thoeny B., Nar H., Buergisser D., Huber R., Heizmann C.W., Blau N.
J. Biol. Chem. 270:29498-29506(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS HPABH4A CYS-16; GLN-25; VAL-57 DEL AND LEU-87.
[16]"Identification of a common 6-pyruvoyl-tetrahydropterin synthase mutation at codon 87 in Chinese phenylketonuria caused by tetrahydrobiopterin synthesis deficiency."
Liu T.T., Hsiao K.J.
Hum. Genet. 98:313-316(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPABH4A SER-52 AND SER-87.
[17]"Identification of mutations causing 6-pyruvoyl-tetrahydropterin synthase deficiency in four Italian families."
Oppliger T., Thoeny B., Kluge C., Matasovic A., Heizmann C.W., Ponzone A., Spada M., Blau N.
Hum. Mutat. 10:25-35(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPABH4A VAL-57 DEL; MET-67; GLU-129 AND VAL-136.
[18]"6-pyruvoyl-tetrahydropterin synthase deficiency with generalized dystonia and diurnal fluctuation of symptoms: a clinical and molecular study."
Hanihara T., Inoue K., Kawanishi C., Sugiyama N., Miyakawa T., Onishi H., Yamada Y., Osaka H., Kosaka K., Iwabuchi K., Owada M.
Mov. Disord. 12:408-411(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HPABH4A VAL-114.
[19]"Mutation analysis of the 6-pyruvoyl-tetrahydropterin synthase gene in Chinese hyperphenylalaninemia caused by tetrahydrobiopterin synthesis deficiency."
Liu T.-T., Hsiao K.-J., Lu S.-F., Wu S.-J., Wu K.-F., Chiang S.-H., Liu X.-Q., Chen R.-G., Yu W.-M.
Hum. Mutat. 11:76-83(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPABH4A GLY-25; SER-52; MET-56; ASP-70; SER-87; ASN-96 AND MET-106.
[20]"Single-step mutation scanning of the 6-pyruvoyltetrahydropterin synthase gene in patients with hyperphenylalaninemia."
Romstad A., Guldberg P., Blau N., Guettler F.
Clin. Chem. 45:2102-2108(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPABH4A VAL-57 DEL AND MET-97.
[21]"Dominant negative allele (N47D) in a compound heterozygote for a variant of 6-pyruvoyltetrahydropterin synthase deficiency causing transient hyperphenylalaninemia."
Scherer-Oppliger T., Matasovic A., Laufs S., Levy H.L., Quackenbush E.J., Blau N., Thoeny B.
Hum. Mutat. 13:286-289(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPABH4A ASP-47 AND GLY-116.
[22]"Isolated central form of tetrahydrobiopterin deficiency associated with hemizygosity on chromosome 11q and a mutant allele of PTPS."
Blau N., Scherer-Oppliger T., Baumer A., Riegel M., Matasovic A., Schinzel A., Jaeken J., Thoeny B.
Hum. Mutat. 16:54-60(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HPABH4A CYS-99.
[23]"Molecular analysis and long-term follow-up of patients with different forms of 6-pyruvoyl-tetrahydropterin synthase deficiency."
Dudesek A., Roeschinger W., Muntau A.C., Seidel J., Leupold D., Thoeny B., Blau N.
Eur. J. Pediatr. 160:267-276(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPABH4A PHE-26; MET-67; LEU-87; LEU-124; GLY-136 AND VAL-136.
+Additional computationally mapped references.

Web resources

BIOMDB

Db of mutations causing tetrahydrobiopterin deficiencies

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M97655 mRNA. Translation: AAA51541.1.
D17400 mRNA. Translation: BAA04224.1.
D25234 Genomic DNA. Translation: BAA04959.1.
L76259 Genomic DNA. Translation: AAB64229.1.
U63383 expand/collapse EMBL AC list , 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.
PIRJC1405.
RefSeqNP_000308.1. NM_000317.2.
UniGeneHs.503860.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3I2BX-ray2.30A/B/C/D/E/F/G/H/I/J/K/L7-145[»]
ProteinModelPortalQ03393.
SMRQ03393. Positions 8-145.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111769. 10 interactions.
IntActQ03393. 3 interactions.
MINTMINT-1419639.
STRING9606.ENSP00000280362.

PTM databases

PhosphoSiteQ03393.

Proteomic databases

PaxDbQ03393.
PRIDEQ03393.

Protocols and materials databases

DNASU5805.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000280362; ENSP00000280362; ENSG00000150787.
GeneID5805.
KEGGhsa:5805.
UCSCuc001pnj.4. human.

Organism-specific databases

CTD5805.
GeneCardsGC11P112097.
HGNCHGNC:9689. PTS.
HPAHPA001481.
MIM261640. phenotype.
612719. gene.
neXtProtNX_Q03393.
Orphanet13. 6-pyruvoyl-tetrahydropterin synthase deficiency.
PharmGKBPA34032.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0720.
HOGENOMHOG000225069.
HOVERGENHBG004358.
InParanoidQ03393.
KOK01737.
OMACIEEVIM.
OrthoDBEOG7NSB3V.
PhylomeDBQ03393.
TreeFamTF105796.

Enzyme and pathway databases

BioCycMetaCyc:HS07692-MONOMER.
BRENDA4.2.3.12. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKQ03393.
UniPathwayUPA00849; UER00819.

Gene expression databases

ArrayExpressQ03393.
BgeeQ03393.
CleanExHS_PTS.
GenevestigatorQ03393.

Family and domain databases

InterProIPR007115. 6-PTP_synth/QueD.
IPR022470. PTPS_Cys_AS.
IPR022469. PTPS_His_AS.
[Graphical view]
PANTHERPTHR12589. PTHR12589. 1 hit.
PfamPF01242. PTPS. 1 hit.
[Graphical view]
PIRSFPIRSF006113. PTP_synth. 1 hit.
TIGRFAMsTIGR00039. 6PTHBS. 1 hit.
PROSITEPS00987. PTPS_1. 1 hit.
PS00988. PTPS_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ03393.
GeneWikiPTS_(gene).
GenomeRNAi5805.
NextBio22628.
PROQ03393.
SOURCESearch...

Entry information

Entry namePTPS_HUMAN
AccessionPrimary (citable) accession number: Q03393
Secondary accession number(s): B0YJ87, Q8WVG8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: April 16, 2014
This is version 147 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM