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Identification
HMDB Protein ID HMDBP00435
Secondary Accession Numbers
  • 5672
Name 6-pyruvoyl tetrahydrobiopterin synthase
Synonyms
  1. PTP synthase
  2. PTPS
Gene Name PTS
Protein Type Unknown
Biological Properties
General Function Involved in 6-pyruvoyltetrahydropterin synthase activity
Specific 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.
Pathways
  • Dopa-responsive dystonia
  • Folate biosynthesis
  • Hyperphenylalaniemia due to guanosine triphosphate cyclohydrolase deficiency
  • Hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency (ptps)
  • Hyperphenylalaninemia due to dhpr-deficiency
  • Pterine Biosynthesis
  • Segawa syndrome
  • Sepiapterin reductase deficiency
  • tetrahydrobiopterin biosynthesis
Reactions
Dihydroneopterin triphosphate → Dyspropterin + Triphosphate details
Dihydroneopterin triphosphate → Dyspropterin + PPPi details
Dihydroneopterin triphosphate + Water → 6-Carboxy-5,6,7,8-tetrahydropterin + Acetaldehyde + PPPi details
GO Classification
Biological Process
cellular amino acid metabolic process
nitric oxide metabolic process
tetrahydrobiopterin biosynthetic process
regulation of nitric-oxide synthase activity
central nervous system development
Cellular Component
cytosol
mitochondrion
Function
ion binding
cation binding
metal ion binding
binding
catalytic activity
lyase activity
carbon-oxygen lyase activity
carbon-oxygen lyase activity, acting on phosphates
6-pyruvoyltetrahydropterin synthase activity
Molecular Function
metal ion binding
6-pyruvoyltetrahydropterin synthase activity
Process
metabolic process
biosynthetic process
cellular biosynthetic process
heterocycle biosynthetic process
pteridine and derivative biosynthetic process
tetrahydrobiopterin biosynthetic process
Cellular Location Not Available
Gene Properties
Chromosome Location 11
Locus 11q22.3
SNPs PTS
Gene Sequence
>438 bp
ATGAGCACGGAAGGTGGTGGCCGTCGCTGCCAGGCACAAGTGTCCCGCCGCATCTCCTTC
AGCGCGAGCCACCGATTGTACAGTAAATTTCTAAGTGATGAAGAAAACTTGAAACTGTTT
GGGAAATGCAACAATCCAAATGGCCATGGGCACAATTATAAAGTTGTGGTGACAGTACAT
GGAGAGATTGACCCTGCTACGGGAATGGTTATGAATCTGGCTGATCTCAAAAAATATATG
GAGGAGGCGATTATGCAGCCCCTTGATCATAAGAATCTGGATATGGATGTGCCATACTTT
GCAGATGTGGTGAGCACGACTGAAAATGTAGCTGTTTATATCTGGGACAACCTCCAGAAA
GTTCTTCCTGTAGGAGTTCTTTATAAAGTAAAAGTATACGAAACTGACAATAATATTGTG
GTTTATAAAGGAGAATAG
Protein Properties
Number of Residues 145
Molecular Weight 16385.63
Theoretical pI 6.68
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>6-pyruvoyl tetrahydrobiopterin synthase
MSTEGGGRRCQAQVSRRISFSASHRLYSKFLSDEENLKLFGKCNNPNGHGHNYKVVVTVH
GEIDPATGMVMNLADLKKYMEEAIMQPLDHKNLDMDVPYFADVVSTTENVAVYIWDNLQK
VLPVGVLYKVKVYETDNNIVVYKGE
GenBank ID Protein 7768658
UniProtKB/Swiss-Prot ID Q03393
UniProtKB/Swiss-Prot Entry Name PTPS_HUMAN
PDB IDs
GenBank Gene ID AB042297
GeneCard ID PTS
GenAtlas ID PTS
HGNC ID HGNC:9689
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  3. Thony B, Leimbacher W, Burgisser D, Heizmann CW: Human 6-pyruvoyltetrahydropterin synthase: cDNA cloning and heterologous expression of the recombinant enzyme. Biochem Biophys Res Commun. 1992 Dec 30;189(3):1437-43. [PubMed:1282802 ]
  4. Ashida A, Hatakeyama K, Kagamiyama H: cDNA cloning, expression in Escherichia coli and purification of human 6-pyruvoyl-tetrahydropterin synthase. Biochem Biophys Res Commun. 1993 Sep 30;195(3):1386-93. [PubMed:8216273 ]
  5. Ashida A, Owada M, Hatakeyama K: A missense mutation (A to G) of 6-pyruvoyltetrahydropterin synthase in tetrahydrobiopterin-deficient form of hyperphenylalaninemia. Genomics. 1994 Nov 15;24(2):408-10. [PubMed:7698774 ]
  6. Kluge C, Brecevic L, Heizmann CW, Blau N, Thony B: Chromosomal localization, genomic structure and characterization of the human gene and a retropseudogene for 6-pyruvoyltetrahydropterin synthase. Eur J Biochem. 1996 Sep 1;240(2):477-84. [PubMed:8841415 ]
  7. Scherer-Oppliger T, Leimbacher W, Blau N, Thony B: Serine 19 of human 6-pyruvoyltetrahydropterin synthase is phosphorylated by cGMP protein kinase II. J Biol Chem. 1999 Oct 29;274(44):31341-8. [PubMed:10531334 ]
  8. Thony B, Blau N: Mutations in the GTP cyclohydrolase I and 6-pyruvoyl-tetrahydropterin synthase genes. Hum Mutat. 1997;10(1):11-20. [PubMed:9222755 ]
  9. Thony B, Leimbacher W, Blau N, Harvie A, Heizmann CW: Hyperphenylalaninemia due to defects in tetrahydrobiopterin metabolism: molecular characterization of mutations in 6-pyruvoyl-tetrahydropterin synthase. Am J Hum Genet. 1994 May;54(5):782-92. [PubMed:8178819 ]
  10. Oppliger T, Thony B, Nar H, Burgisser D, Huber R, Heizmann CW, Blau N: Structural and functional consequences of mutations in 6-pyruvoyltetrahydropterin synthase causing hyperphenylalaninemia in humans. Phosphorylation is a requirement for in vivo activity. J Biol Chem. 1995 Dec 8;270(49):29498-506. [PubMed:7493990 ]
  11. Liu TT, Hsiao KJ: Identification of a common 6-pyruvoyl-tetrahydropterin synthase mutation at codon 87 in Chinese phenylketonuria caused by tetrahydrobiopterin synthesis deficiency. Hum Genet. 1996 Sep;98(3):313-6. [PubMed:8707300 ]
  12. Oppliger T, Thony B, Kluge C, Matasovic A, Heizmann CW, Ponzone A, Spada M, Blau N: Identification of mutations causing 6-pyruvoyl-tetrahydropterin synthase deficiency in four Italian families. Hum Mutat. 1997;10(1):25-35. [PubMed:9222757 ]
  13. Hanihara T, Inoue K, Kawanishi C, Sugiyama N, Miyakawa T, Onishi H, Yamada Y, Osaka H, Kosaka K, Iwabuchi K, Owada M: 6-Pyruvoyl-tetrahydropterin synthase deficiency with generalized dystonia and diurnal fluctuation of symptoms: a clinical and molecular study. Mov Disord. 1997 May;12(3):408-11. [PubMed:9159737 ]
  14. Liu TT, Hsiao KJ, Lu SF, Wu SJ, Wu KF, Chiang SH, Liu XQ, Chen RG, Yu WM: Mutation analysis of the 6-pyruvoyl-tetrahydropterin synthase gene in Chinese hyperphenylalaninemia caused by tetrahydrobiopterin synthesis deficiency. Hum Mutat. 1998;11(1):76-83. [PubMed:9450907 ]
  15. Romstad A, Guldberg P, Blau N, Guttler F: Single-step mutation scanning of the 6-pyruvoyltetrahydropterin synthase gene in patients with hyperphenylalaninemia. Clin Chem. 1999 Dec;45(12):2102-8. [PubMed:10585341 ]
  16. Scherer-Oppliger T, Matasovic A, Laufs S, Levy HL, Quackenbush EJ, Blau N, Thony B: Dominant negative allele (N47D) in a compound heterozygote for a variant of 6-pyruvoyltetrahydropterin synthase deficiency causing transient hyperphenylalaninemia. Hum Mutat. 1999;13(4):286-9. [PubMed:10220141 ]
  17. Blau N, Scherer-Oppliger T, Baumer A, Riegel M, Matasovic A, Schinzel A, Jaeken J, Thony B: Isolated central form of tetrahydrobiopterin deficiency associated with hemizygosity on chromosome 11q and a mutant allele of PTPS. Hum Mutat. 2000;16(1):54-60. [PubMed:10874306 ]
  18. Dudesek A, Roschinger W, Muntau AC, Seidel J, Leupold D, Thony B, Blau N: Molecular analysis and long-term follow-up of patients with different forms of 6-pyruvoyl-tetrahydropterin synthase deficiency. Eur J Pediatr. 2001 May;160(5):267-76. [PubMed:11388593 ]