1. 6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin
2. 6-pyruvoyl-5,6,7,8-tetrahydropterin
3. 6-pyruvoyl-tetrahydropterin
4. 6-pyruvoyltetrahydropterin
5. dyspropterin

• Cytoplasm (Predicted from LogP)
• nucleus

1. Niederwieser A, Curtius HC: Tetrahydrobiopterin biosynthetic pathway and deficiency. Enzyme. 1987;38(1-4):302-11. [PubMed ]
2. Dhondt JL, Hayte JM: [Screening of tetrahydrobiopterin deficiency among hyperphenylalaninemic patients] Ann Biol Clin (Paris). 2002 Mar-Apr;60(2):165-71. [PubMed ]
3. Bonafe L, Thony B, Leimbacher W, Kierat L, Blau N: Diagnosis of dopa-responsive dystonia and other tetrahydrobiopterin disorders by the study of biopterin metabolism in fibroblasts. Clin Chem. 2001 Mar;47(3):477-85. [PubMed ]
4. Iwanaga N, Yamamasu S, Tachibana D, Nishio J, Nakai Y, Shintaku H, Ishiko O: Activity of synthetic enzymes of tetrahydrobiopterin in the human placenta. Int J Mol Med. 2004 Jan;13(1):117-20. [PubMed ]

1. 6-pyruvoyl tetrahydrobiopterin synthase
2. Sepiapterin reductase
3. 6-pyruvoyl tetrahydrobiopterin synthase (6-pyruvoyltetrahydropterin synthase)

1. PTP synthase
2. PTPS

MSTEGGGRRCQAQVSRRISFSASHRLYSKFLSDEENLKLFGKCNNPNGHGHNYKVVVTVH
GEIDPATGMVMNLADLKKYMEEAIMQPLDHKNLDMDVPYFADVVSTTENVAVYIWDNLQK
VLPVGVLYKVKVYETDNNIVVYKGE

• Folate and Pterine Biosynthesis (map00790 )

• 7,8-dihydroneopterin 3'-triphosphate = 6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate [RN:R04286]

• PTPS (PF01242 )

• None

• None

ATGAGCACGGAAGGTGGTGGCCGTCGCTGCCAGGCACAAGTGTCCCGCCGCATCTCCTTC
AGCGCGAGCCACCGATTGTACAGTAAATTTCTAAGTGATGAAGAAAACTTGAAACTGTTT
GGGAAATGCAACAATCCAAATGGCCATGGGCACAATTATAAAGTTGTGGTGACAGTACAT
GGAGAGATTGACCCTGCTACGGGAATGGTTATGAATCTGGCTGATCTCAAAAAATATATG
GAGGAGGCGATTATGCAGCCCCTTGATCATAAGAATCTGGATATGGATGTGCCATACTTT
GCAGATGTGGTGAGCACGACTGAAAATGTAGCTGTTTATATCTGGGACAACCTCCAGAAA
GTTCTTCCTGTAGGAGTTCTTTATAAAGTAAAAGTATACGAAACTGACAATAATATTGTG
GTTTATAAAGGAGAATAG

1. 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 ]
2. 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 ]
3. 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 ]
4. 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 ]
5. 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 ]
6. 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. Epub 2008 Jul 31. [PubMed ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]

1. SPR

MEGGLGRAVCLLTGASRGFGRTLAPLLASLLSPGSVLVLSARNDEALRQLEAELGAERSG
LRVVRVPADLGAEAGLQQLLGALRELPRPKGLQRLLLINNAGSLGDVSKGFVDLSDSTQV
NNYWALNLTSMLCLTSSVLKAFPDSPGLNRTVVNISSLCALQPFKGWALYCAGKAARDML
FQVLALEEPNVRVLNYAPGPLDTDMQQLARETSVDPDMRKGLQELKAKGKLVDCKVSAQK
LLSLLEKDEFKSGAHVDFYDK

• Folate and Pterine Biosynthesis (map00790 )

• (1) 7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+ [RN:R02975]
• (2) tetrahydrobiopterin + 2 NADP+ = 6-pyruvoyl-5,6,7,8-tetrahydropterin + 2 NADPH + 2 H+ [RN:R08208]

• adh_short (PF00106 )

• None

• None

ATGGAGGGCGGGCTGGGGCGTGCTGTGTGCTTGCTGACCGGGGCCTCCCGCGGCTTCGGC
CGGACGCTGGCCCCGCTCCTGGCCTCGCTGCTGTCGCCCGGCTCCGTGCTTGTCCTTAGC
GCCCGCAACGACGAGGCACTGCGCCAGCTGGAGGCCGAGCTGGGCGCCGAGCGGTCTGGC
CTGCGCGTGGTGCGGGTGCCCGCCGACCTGGGCGCCGAGGCCGGCTTGCAGCAGCTGCTC
GGCGCCCTGCGCGAGCTCCCCCGGCCCAAGGGGCTGCAGCGACTGCTGCTTATCAACAAC
GCGGGCTCTCTTGGGGATGTGTCCAAAGGCTTCGTGGACCTGAGTGACTCCACTCAAGTG
AACAACTACTGGGCACTGAACTTGACCTCCATGCTCTGCCTGACTTCCAGCGTCCTGAAG
GCCTTCCCGGACAGTCCTGGCCTCAACAGAACCGTGGTTAACATCTCGTCCCTCTGTGCC
CTGCAACCTTTCAAAGGCTGGGCGCTGTACTGTGCAGGAAAGGCTGCTCGTGATATGCTG
TTCCAGGTCCTGGCGCTGGAGGAACCTAATGTGAGGGTGCTGAACTATGCCCCAGGTCCT
CTGGACACAGACATGCAGCAGTTGGCCCGGGAGACCTCCGTGGACCCAGACATGCGAAAA
GGGCTGCAGGAGCTGAAGGCAAAGGGGAAGCTGGTGGATTGCAAGGTGTCAGCCCAGAAA
CTGCTGAGCTTACTGGAAAAGGACGAGTTCAAGTCTGGAGCCCACGTGGACTTCTATGAC
AAATAA

1. Ichinose H, Katoh S, Sueoka T, Titani K, Fujita K, Nagatsu T: Cloning and sequencing of cDNA encoding human sepiapterin reductase--an enzyme involved in tetrahydrobiopterin biosynthesis. Biochem Biophys Res Commun. 1991 Aug 30;179(1):183-9. [PubMed ]
2. Maier J, Schott K, Werner T, Bacher A, Ziegler I: Detection of a novel sepiapterin reductase mRNA: assay of mRNA in various cells and tissues of various species. Exp Cell Res. 1993 Feb;204(2):217-22. [PubMed ]
3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed ]
4. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [PubMed ]
5. 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 ]
6. Ohye T, Hori TA, Katoh S, Nagatsu T, Ichinose H: Genomic organization and chromosomal localization of the human sepiapterin reductase gene. Biochem Biophys Res Commun. 1998 Oct 20;251(2):597-602. [PubMed ]
7. Fujimoto K, Takahashi SY, Katoh S: Mutational analysis of sites in sepiapterin reductase phosphorylated by Ca2+/calmodulin-dependent protein kinase II. Biochim Biophys Acta. 2002 Jan 31;1594(1):191-8. [PubMed ]
8. Bonafe L, Thony B, Penzien JM, Czarnecki B, Blau N: Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia. Am J Hum Genet. 2001 Aug;69(2):269-77. Epub 2001 Jul 6. [PubMed ]
9. Abeling NG, Duran M, Bakker HD, Stroomer L, Thony B, Blau N, Booij J, Poll-The BT: Sepiapterin reductase deficiency an autosomal recessive DOPA-responsive dystonia. Mol Genet Metab. 2006 Sep-Oct;89(1-2):116-20. Epub 2006 May 2. [PubMed ]
10. Friedman J, Hyland K, Blau N, MacCollin M: Dopa-responsive hypersomnia and mixed movement disorder due to sepiapterin reductase deficiency. Neurology. 2006 Dec 12;67(11):2032-5. [PubMed ]

MSTEGGGRRCQAQVSRRISFSASHRLYSKFLSDEENLKLFGKCNNPNGHGHNYKVVVTVH
GEIDPATGMVMNLADLKKYMEEAIMQPLDHKNLDMDVPYFADVVSTTENVAVYIWDNLQK
VLPVGVLYKVKVYETDNNIVVYKGE

• PTPS (PF01242 )

• None

• None