1. (6R)-5,6,7,8-Tetrahydro-L-biopterin
2. (6R)-5,6,7,8-Tetrahydrobiopterin
3. (6R)-L-erythro-5,6,7,8-Tetrahydrobiopterin
4. (6R)-L-erythro-Tetrahydrobiopterin
5. (6R)-Tetrahydrobiopterin
6. 6R-BH4
7. 6R-Tetrahydro-L-biopterin
8. 6b-5,6,7,8-Tetrahydro-L-biopterin
9. R-THBP
10. Sapropterin
11. [6R-[6R*(1R*,2S*)]]-2-amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(1H)-Pteridinone

• Cytoplasm (Predicted from LogP)

• Blood
• Cerebrospinal Fluid

1. Toda Y, Mori K, Hashimoto T, Miyazaki M, Nozaki S, Watanabe Y, Kuroda Y, Kagami S: Administration of secretin for autism alters dopamine metabolism in the central nervous system. Brain Dev. 2006 Mar;28(2):99-103. Epub 2005 Sep 15. [PubMed ]
2. Moens AL, Kass DA: Tetrahydrobiopterin and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2006 Nov;26(11):2439-44. Epub 2006 Aug 31. [PubMed ]
3. Komori H, Matsuishi T, Yamada S, Yamashita Y, Ohtaki E, Kato H: Cerebrospinal fluid biopterin and biogenic amine metabolites during oral R-THBP therapy for infantile autism. J Autism Dev Disord. 1995 Apr;25(2):183-93. [PubMed ]

1. Tyrosine 3-monooxygenase
2. Phenylalanine-4-hydroxylase
3. Sepiapterin reductase
4. Tryptophan 5-hydroxylase 1
5. Tryptophan 5-hydroxylase 2
6. Dihydropteridine reductase
7. Nitric oxide synthase, endothelial

1. Tyrosine 3-hydroxylase
2. TH

MPTPDATTPQAKGFRRAVSELDAKQAEAIMVRGQGAPGPSLTGSPWPGTAAPAASYTPTP
RSPRFIGRRQSLIEDARKEREAAVAAAAAAVPSEPGDPLEAVAFEEKEGKAVLNLLFSPR
ATKPSALSRAVKVFETFEAKIHHLETRPAQRPRAGGPHLEYFVRLEVRRGDLAALLSGVR
QVSEDVRSPAGPKVPWFPRKVSELDKCHHLVTKFDPDLDLDHPGFSDQVYRQRRKLIAEI
AFQYRHGDPIPRVEYTAEEIATWKEVYTTLKGLYATHACGEHLEAFALLERFSGYREDNI
PQLEDVSRFLKERTGFQLRPVAGLLSARDFLASLAFRVFQCTQYIRHASSPMHSPEPDCC
HELLGHVPMLADRTFAQFSQDIGLASLGASDEEIEKLSTLYWFTVEFGLCKQNGEVKAYG
AGLLSSYGELLHCLSEEPEIRAFDPEAAAVQPYQDQTYQSVYFVSESFSDAKDKLRSYAS
RIQRPFSVKFDPYTLAIDVLDSPQAVRRSLEGVQDELDTLAHALSAIG

• Tyrosine Metabolism (map00350 )

• L-tyrosine + tetrahydrobiopterin + O2 = 3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin [RN:R07212]

• Biopterin_H (PF00351 )
• TOH_N (PF12549 )

• None

• None

ATGCCCACCCCCGACGCCACCACGCCACAGGCCAAGGGCTTCCGCAGGGCCGTGTCTGAG
CTGGACGCCAAGCAGGCAGAGGCCATCATGGTAAGAGGGCAGGGCGCCCCGGGGCCCAGC
CTCACAGGCTCTCCGTGGCCTGGAACTGCAGCCCCAGCTGCATCCTACACCCCCACCCCA
AGGTCCCCGCGGTTCATTGGGCGCAGGCAGAGCCTCATCGAGGACGCCCGCAAGGAGCGG
GAGGCGGCGGTGGCAGCAGCGGCCGCTGCAGTCCCCTCGGAGCCCGGGGACCCCCTGGAG
GCTGTGGCCTTTGAGGAGAAGGAGGGGAAGGCCGTGCTAAACCTGCTCTTCTCCCCGAGG
GCCACCAAGCCCTCGGCGCTGTCCCGAGCTGTGAAGGTGTTTGAGACGTTTGAAGCCAAA
ATCCACCATCTAGAGACCCGGCCCGCCCAGAGGCCGCGAGCTGGGGGCCCCCACCTGGAG
TACTTCGTGCGCCTCGAGGTGCGCCGAGGGGACCTGGCCGCCCTGCTCAGTGGTGTGCGC
CAGGTGTCAGAGGACGTGCGCAGCCCCGCGGGGCCCAAGGTCCCCTGGTTCCCAAGAAAA
GTGTCAGAGCTGGACAAGTGTCATCACCTGGTCACCAAGTTCGACCCTGACCTGGACTTG
GACCACCCGGGCTTCTCGGACCAGGTGTACCGCCAGCGCAGGAAGCTGATTGCTGAGATC
GCCTTCCAGTACAGGCACGGCGACCCGATTCCCCGTGTGGAGTACACCGCCGAGGAGATT
GCCACCTGGAAGGAGGTCTACACCACGCTGAAGGGCCTCTACGCCACGCACGCCTGCGGG
GAGCACCTGGAGGCCTTTGCTTTGCTGGAGCGCTTCAGCGGCTACCGGGAAGACAATATC
CCCCAGCTGGAGGACGTCTCCCGCTTCCTGAAGGAGCGCACGGGCTTCCAGCTGCGGCCT
GTGGCCGGCCTGCTGTCCGCCCGGGACTTCCTGGCCAGCCTGGCCTTCCGCGTGTTCCAG
TGCACCCAGTATATCCGCCACGCGTCCTCGCCCATGCACTCCCCTGAGCCGGACTGCTGC
CACGAGCTGCTGGGGCACGTGCCCATGCTGGCCGACCGCACCTTCGCGCAGTTCTCGCAG
GACATTGGCCTGGCGTCCCTGGGGGCCTCGGATGAGGAAATTGAGAAGCTGTCCACGCTG
TCATGGTTCACGGTGGAGTTCGGGCTGTGTAAGCAGAACGGGGAGGTGAAGGCCTATGGT
GCCGGGCTGCTGTCCTCCTACGGGGAGCTCCTGCACTGCCTGTCTGAGGAGCCTGAGATT
CGGGCCTTCGACCCTGAGGCTGCGGCCGTGCAGCCCTACCAAGACCAGACGTACCAGTCA
GTCTACTTCGTGTCTGAGAGCTTCAGTGACGCCAAGGACAAGCTCAGGAGCTATGCCTCA
CGCATCCAGCGCCCCTTCTCCGTGAAGTTCGACCCGTACACGCTGGCCATCGACGTGCTG
GACAGCCCCCAGGCCGTGCGGCGCTCCCTGGAGGGTGTCCAGGATGAGCTGGACACCCTT
GCCCATGCGCTGAGTGCCATTGGCTAG

1. Kaneda N, Kobayashi K, Ichinose H, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T: Isolation of a novel cDNA clone for human tyrosine hydroxylase: alternative RNA splicing produces four kinds of mRNA from a single gene. Biochem Biophys Res Commun. 1987 Aug 14;146(3):971-5. [PubMed ]
2. Grima B, Lamouroux A, Boni C, Julien JF, Javoy-Agid F, Mallet J: A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics. Nature. 1987 Apr 16-22;326(6114):707-11. [PubMed ]
3. Kobayashi K, Kaneda N, Ichinose H, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T: Isolation of a full-length cDNA clone encoding human tyrosine hydroxylase type 3. Nucleic Acids Res. 1987 Aug 25;15(16):6733. [PubMed ]
4. Kobayashi K, Kaneda N, Ichinose H, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T: Structure of the human tyrosine hydroxylase gene: alternative splicing from a single gene accounts for generation of four mRNA types. J Biochem (Tokyo). 1988 Jun;103(6):907-12. [PubMed ]
5. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [PubMed ]
6. 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 ]
7. Le Bourdelles B, Boularand S, Boni C, Horellou P, Dumas S, Grima B, Mallet J: Analysis of the 5' region of the human tyrosine hydroxylase gene: combinatorial patterns of exon splicing generate multiple regulated tyrosine hydroxylase isoforms. J Neurochem. 1988 Mar;50(3):988-91. [PubMed ]
8. Ginns EI, Rehavi M, Martin BM, Weller M, O'Malley KL, LaMarca ME, McAllister CG, Paul SM: Expression of human tyrosine hydroxylase cDNA in invertebrate cells using a baculovirus vector. J Biol Chem. 1988 May 25;263(15):7406-10. [PubMed ]
9. Ludecke B, Dworniczak B, Bartholome K: A point mutation in the tyrosine hydroxylase gene associated with Segawa's syndrome. Hum Genet. 1995 Jan;95(1):123-5. [PubMed ]
10. Ludecke B, Bartholome K: Frequent sequence variant in the human tyrosine hydroxylase gene. Hum Genet. 1995 Jun;95(6):716. [PubMed ]
11. Knappskog PM, Flatmark T, Mallet J, Ludecke B, Bartholome K: Recessively inherited L-DOPA-responsive dystonia caused by a point mutation (Q381K) in the tyrosine hydroxylase gene. Hum Mol Genet. 1995 Jul;4(7):1209-12. [PubMed ]
12. Ludecke B, Knappskog PM, Clayton PT, Surtees RA, Clelland JD, Heales SJ, Brand MP, Bartholome K, Flatmark T: Recessively inherited L-DOPA-responsive parkinsonism in infancy caused by a point mutation (L205P) in the tyrosine hydroxylase gene. Hum Mol Genet. 1996 Jul;5(7):1023-8. [PubMed ]
13. Kunugi H, Kawada Y, Hattori M, Ueki A, Otsuka M, Nanko S: Association study of structural mutations of the tyrosine hydroxylase gene with schizophrenia and Parkinson's disease. Am J Med Genet. 1998 Mar 28;81(2):131-3. [PubMed ]
14. Ishiguro H, Arinami T, Saito T, Akazawa S, Enomoto M, Mitushio H, Fujishiro H, Tada K, Akimoto Y, Mifune H, Shiozuka S, Hamaguchi H, Toru M, Shibuya H: Systematic search for variations in the tyrosine hydroxylase gene and their associations with schizophrenia, affective disorders, and alcoholism. Am J Med Genet. 1998 Sep 7;81(5):388-96. [PubMed ]
15. van den Heuvel LP, Luiten B, Smeitink JA, de Rijk-van Andel JF, Hyland K, Steenbergen-Spanjers GC, Janssen RJ, Wevers RA: A common point mutation in the tyrosine hydroxylase gene in autosomal recessive L-DOPA-responsive dystonia in the Dutch population. Hum Genet. 1998 Jun;102(6):644-6. [PubMed ]
16. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed ]
17. Swaans RJ, Rondot P, Renier WO, Van Den Heuvel LP, Steenbergen-Spanjers GC, Wevers RA: Four novel mutations in the tyrosine hydroxylase gene in patients with infantile parkinsonism. Ann Hum Genet. 2000 Jan;64(Pt 1):25-31. [PubMed ]

1. PAH
2. Phe-4-monooxygenase

MSTAVLENPGLGRKLSDFGQETSYIEDNCNQNGAISLIFSLKEEVGALAKVLRLFEENDV
NLTHIESRPSRLKKDEYEFFTHLDKRSLPALTNIIKILRHDIGATVHELSRDKKKDTVPW
FPRTIQELDRFANQILSYGAELDADHPGFKDPVYRARRKQFADIAYNYRHGQPIPRVEYM
EEEKKTWGTVFKTLKSLYKTHACYEYNHIFPLLEKYCGFHEDNIPQLEDVSQFLQTCTGF
RLRPVAGLLSSRDFLGGLAFRVFHCTQYIRHGSKPMYTPEPDICHELLGHVPLFSDRSFA
QFSQEIGLASLGAPDEYIEKLATIYWFTVEFGLCKQGDSIKAYGAGLLSSFGELQYCLSE
KPKLLPLELEKTAIQNYTVTEFQPLYYVAESFNDAKEKVRNFAATIPRPFSVRYDPYTQR
IEVLDNTQQLKILADSINSEIGILCSALQKIK

• Phenylalanine and Tyrosine Metabolism (map00400 )

• L-phenylalanine + tetrahydrobiopterin + O2 = L-tyrosine + 4a-hydroxytetrahydrobiopterin [RN:R07211]

• ACT (PF01842 )
• Biopterin_H (PF00351 )

• None

• None

ATGTCCACTGCGGTCCTGGAAAACCCAGGCTTGGGCAGGAAACTCTCTGACTTTGGACAG
GAAACAAGCTATATTGAAGACAACTGCAATCAAAATGGTGCCATATCACTGATCTTCTCA
CTCAAAGAAGAAGTTGGTGCATTGGCCAAAGTATTGCGCTTATTTGAGGAGAATGATGTA
AACCTGACCCACATTGAATCTAGACCTTCTCGTTTAAAGAAAGATGAGTATGAATTTTTC
ACCCATTTGGATAAACGTAGCCTGCCTGCTCTGACAAACATCATCAAGATCTTGAGGCAT
GACATTGGTGCCACTGTCCATGAGCTTTCACGAGATAAGAAGAAAGACACAGTGCCCTGG
TTCCCAAGAACCATTCAAGAGCTGGACAGATTTGCCAATCAGATTCTCAGCTATGGAGCG
GAACTGGATGCTGACCACCCTGGTTTTAAAGATCCTGTGTACCGTGCAAGACGGAAGCAG
TTTGCTGACATTGCCTACAACTACCGCCATGGGCAGCCCATCCCTCGAGTGGAATACATG
GAGGAAGAAAAGAAAACATGGGGCACAGTGTTCAAGACTCTGAAGTCCTTGTATAAAACC
CATGCTTGCTATGAGTACAATCACATTTTTCCACTTCTTGAAAAGTACTGTGGCTTCCAT
GAAGATAACATTCCCCAGCTGGAAGACGTTTCTCAATTCCTGCAGACTTGCACTGGTTTC
CGCCTCCGACCTGTGGCTGGCCTGCTTTCCTCTCGGGATTTCTTGGGTGGCCTGGCCTTC
CGAGTCTTCCACTGCACACAGTACATCAGACATGGATCCAAGCCCATGTATACCCCCGAA
CCTGACATCTGCCATGAGCTGTTGGGACATGTGCCCTTGTTTTCAGATCGCAGCTTTGCC
CAGTTTTCCCAGGAAATTGGCCTTGCCTCTCTGGGTGCACCTGATGAATACATTGAAAAG
CTCGCCACAATTTACTGGTTTACTGTGGAGTTTGGGCTCTGCAAACAAGGAGACTCCATA
AAGGCATATGGTGCTGGGCTCCTGTCATCCTTTGGTGAATTACAGTACTGCTTATCAGAG
AAGCCAAAGCTTCTCCCCCTGGAGCTGGAGAAGACAGCCATCCAAAATTACACTGTCACG
GAGTTCCAGCCCCTGTATTACGTGGCAGAGAGTTTTAATGATGCCAAGGAGAAAGTAAGG
AACTTTGCTGCCACAATACCTCGGCCCTTCTCAGTTCGCTACGACCCATACACCCAAAGG
ATTGAGGTCTTGGACAATACCCAGCAGCTTAAGATTTTGGCTGATTCCATTAACAGTGAA
ATTGGAATCCTTTGCAGTGCCCTCCAGAAAATAAAGTAA

1. Kwok SC, Ledley FD, DiLella AG, Robson KJ, Woo SL: Nucleotide sequence of a full-length complementary DNA clone and amino acid sequence of human phenylalanine hydroxylase. Biochemistry. 1985 Jan 29;24(3):556-61. [PubMed ]
2. 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 ]
3. Cotton RG, McAdam W, Jennings I, Morgan FJ: A monoclonal antibody to aromatic amino acid hydroxylases. Identification of the epitope. Biochem J. 1988 Oct 1;255(1):193-6. [PubMed ]
4. Siltberg-Liberles J, Steen IH, Svebak RM, Martinez A: The phylogeny of the aromatic amino acid hydroxylases revisited by characterizing phenylalanine hydroxylase from Dictyostelium discoideum. Gene. 2008 Dec 31;427(1-2):86-92. Epub 2008 Sep 16. [PubMed ]
5. Erlandsen H, Fusetti F, Martinez A, Hough E, Flatmark T, Stevens RC: Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria. Nat Struct Biol. 1997 Dec;4(12):995-1000. [PubMed ]
6. Erlandsen H, Flatmark T, Stevens RC, Hough E: Crystallographic analysis of the human phenylalanine hydroxylase catalytic domain with bound catechol inhibitors at 2.0 A resolution. Biochemistry. 1998 Nov 10;37(45):15638-46. [PubMed ]
7. Fusetti F, Erlandsen H, Flatmark T, Stevens RC: Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria. J Biol Chem. 1998 Jul 3;273(27):16962-7. [PubMed ]
8. Erlandsen H, Bjorgo E, Flatmark T, Stevens RC: Crystal structure and site-specific mutagenesis of pterin-bound human phenylalanine hydroxylase. Biochemistry. 2000 Mar 7;39(9):2208-17. [PubMed ]
9. Andersen OA, Flatmark T, Hough E: High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin. J Mol Biol. 2001 Nov 23;314(2):279-91. [PubMed ]
10. Konecki DS, Lichter-Konecki U: The phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations. Hum Genet. 1991 Aug;87(4):377-88. [PubMed ]
11. Cotton RG: Heterogeneity of phenylketonuria at the clinical, protein and DNA levels. J Inherit Metab Dis. 1990;13(5):739-50. [PubMed ]
12. Eisensmith RC, Woo SL: Molecular basis of phenylketonuria and related hyperphenylalaninemias: mutations and polymorphisms in the human phenylalanine hydroxylase gene. Hum Mutat. 1992;1(1):13-23. [PubMed ]
13. Hoang L, Byck S, Prevost L, Scriver CR: PAH Mutation Analysis Consortium Database: a database for disease-producing and other allelic variation at the human PAH locus. Nucleic Acids Res. 1996 Jan 1;24(1):127-31. [PubMed ]
14. Lichter-Konecki U, Konecki DS, DiLella AG, Brayton K, Marvit J, Hahn TM, Trefz FK, Woo SL: Phenylalanine hydroxylase deficiency caused by a single base substitution in an exon of the human phenylalanine hydroxylase gene. Biochemistry. 1988 Apr 19;27(8):2881-5. [PubMed ]
15. Lyonnet S, Caillaud C, Rey F, Berthelon M, Frezal J, Rey J, Munnich A: Molecular genetics of phenylketonuria in Mediterranean countries: a mutation associated with partial phenylalanine hydroxylase deficiency. Am J Hum Genet. 1989 Apr;44(4):511-7. [PubMed ]
16. Hofman KJ, Antonarakis SE, Missiou-Tsangaraki S, Boehm CD, Valle D: Phenylketonuria in the Greek population. Haplotype analysis of the phenylalanine hydroxylase gene and identification of a PKU mutation. Mol Biol Med. 1989 Jun;6(3):245-50. [PubMed ]
17. Svensson E, Andersson B, Hagenfeldt L: Two mutations within the coding sequence of the phenylalanine hydroxylase gene. Hum Genet. 1990 Aug;85(3):300-4. [PubMed ]
18. Dianzani I, Forrest SM, Camaschella C, Saglio G, Ponzone A, Cotton RG: Screening for mutations in the phenylalanine hydroxylase gene from Italian patients with phenylketonuria by using the chemical cleavage method: a new splice mutation. Am J Hum Genet. 1991 Mar;48(3):631-5. [PubMed ]
19. Hofman KJ, Steel G, Kazazian HH, Valle D: Phenylketonuria in U.S. blacks: molecular analysis of the phenylalanine hydroxylase gene. Am J Hum Genet. 1991 Apr;48(4):791-8. [PubMed ]
20. Okano Y, Wang T, Eisensmith RC, Longhi R, Riva E, Giovannini M, Cerone R, Romano C, Woo SL: Phenylketonuria missense mutations in the Mediterranean. Genomics. 1991 Jan;9(1):96-103. [PubMed ]
21. Dworniczak B, Grudda K, Stumper J, Bartholome K, Aulehla-Scholz C, Horst J: Phenylalanine hydroxylase gene: novel missense mutation in exon 7 causing severe phenylketonuria. Genomics. 1991 Jan;9(1):193-9. [PubMed ]
22. Konecki DS, Schlotter M, Trefz FK, Lichter-Konecki U: The identification of two mis-sense mutations at the PAH gene locus in a Turkish patient with phenylketonuria. Hum Genet. 1991 Aug;87(4):389-93. [PubMed ]
23. Caillaud C, Lyonnet S, Rey F, Melle D, Frebourg T, Berthelon M, Vilarinho L, Vaz Osorio R, Rey J, Munnich A: A 3-base pair in-frame deletion of the phenylalanine hydroxylase gene results in a kinetic variant of phenylketonuria. J Biol Chem. 1991 May 25;266(15):9351-4. [PubMed ]
24. Economou-Petersen E, Henriksen KF, Guldberg P, Guttler F: Molecular basis for nonphenylketonuria hyperphenylalaninemia. Genomics. 1992 Sep;14(1):1-5. [PubMed ]
25. Lin CH, Hsiao KJ, Tsai TF, Chao HK, Su TS: Identification of a missense phenylketonuria mutation at codon 408 in Chinese. Hum Genet. 1992 Aug;89(6):593-6. [PubMed ]
26. Jaruzelska J, Melle D, Matuszak R, Borski K, Munnich A: A new 15 bp deletion in exon 11 of the phenylalanine hydroxylase gene in phenylketonuria. Hum Mol Genet. 1992 Dec;1(9):763-4. [PubMed ]
27. Desviat LR, Perez B, Ugarte M: A new PKU mutation associated with haplotype 12. Hum Mol Genet. 1992 Dec;1(9):765-6. [PubMed ]
28. Guldberg P, Henriksen KF, Guttler F: Molecular analysis of phenylketonuria in Denmark: 99% of the mutations detected by denaturing gradient gel electrophoresis. Genomics. 1993 Jul;17(1):141-6. [PubMed ]
29. Abadie V, Jaruzelska J, Lyonnet S, Millasseau P, Berthelon M, Rey F, Munnich A, Rey J: Illegitimate transcription of the phenylalanine hydroxylase gene in lymphocytes for identification of mutations in phenylketonuria. Hum Mol Genet. 1993 Jan;2(1):31-4. [PubMed ]
30. Goebel-Schreiner B, Schreiner R: Identification of a new missense mutation in Japanese phenylketonuric patients. J Inherit Metab Dis. 1993;16(6):950-6. [PubMed ]
31. Guldberg P, Henriksen KF, Thony B, Blau N, Guttler F: Molecular heterogeneity of nonphenylketonuria hyperphenylalaninemia in 25 Danish patients. Genomics. 1994 May 15;21(2):453-5. [PubMed ]
32. Benit P, Rey F, Melle D, Munnich A, Rey J: Five novel missense mutations of the phenylalanine hydroxylase gene in phenylketonuria. Hum Mutat. 1994;4(3):229-31. [PubMed ]
33. Knappskog PM, Eiken HG, Martinez A, Bruland O, Apold J, Flatmark T: PKU mutation (D143G) associated with an apparent high residual enzyme activity: expression of a kinetic variant form of phenylalanine hydroxylase in three different systems. Hum Mutat. 1996;8(3):236-46. [PubMed ]
34. Guldberg P, Mallmann R, Henriksen KF, Guttler F: Phenylalanine hydroxylase deficiency in a population in Germany: mutational profile and nine novel mutations. Hum Mutat. 1996;8(3):276-9. [PubMed ]
35. Argiolas A, Bosco P, Cali F, Ceratto N, Anello G, Riva E, Biasucci G, Carducci C, Romano V: Two novel PAH gene mutations detected in Italian phenylketonuric patients. Hum Genet. 1997 Feb;99(2):275-8. [PubMed ]
36. Byck S, Tyfield L, Carter K, Scriver CR: Prediction of multiple hypermutable codons in the human PAH gene: codon 280 contains recurrent mutations in Quebec and other populations. Hum Mutat. 1997;9(4):316-21. [PubMed ]
37. Waters PJ, Parniak MA, Nowacki P, Scriver CR: In vitro expression analysis of mutations in phenylalanine hydroxylase: linking genotype to phenotype and structure to function. Hum Mutat. 1998;11(1):4-17. [PubMed ]
38. Bosco P, Cali F, Meli C, Mollica F, Zammarchi E, Cerone R, Vanni C, Palillo L, Greco D, Romano V: Eight new mutations of the phenylalanine hydroxylase gene in Italian patients with hyperphenylalaninemia. Hum Mutat. 1998;11(3):240-3. [PubMed ]
39. De Lucca M, Perez B, Desviat LR, Ugarte M: Molecular basis of phenylketonuria in Venezuela: presence of two novel null mutations. Hum Mutat. 1998;11(5):354-9. [PubMed ]
40. Mallolas J, Campistol J, Lambruschini N, Vilaseca MA, Cambra FJ, Estivill X, Mila M: Two novel mutations in exon 11 of the PAH gene (V1163del TG and P362T) associated with classic phenylketonuira and mild phenylketonuria. Mutations in brief no. 143. Online. Hum Mutat. 1998;11(6):482. [PubMed ]
41. Park YS, Seoung CS, Lee SW, Oh KH, Lee DH, Yim J: Identification of three novel mutations in Korean phenylketonuria patients: R53H, N207D, and Y325X. Hum Mutat. 1998;Suppl 1:S121-2. [PubMed ]
42. Michiels L, Francois B, Raus J, Vandevyver C: Identification of seven new mutations in the phenylalanine hydroxylase gene, associated with hyperphenylalaninemia in the Belgian population. Hum Mutat. 1998;Suppl 1:S123-4. [PubMed ]
43. Popescu T, Blazkova M, Kozak L, Jebeleanu G, Popescu A: Mutation spectrum and phenylalanine hydroxylase RFLP/VNTR background in 44 Romanian phenylketonuric alleles. Hum Mutat. 1998;12(5):314-9. [PubMed ]
44. Waters PJ, Parniak MA, Hewson AS, Scriver CR: Alterations in protein aggregation and degradation due to mild and severe missense mutations (A104D, R157N) in the human phenylalanine hydroxylase gene (PAH). Hum Mutat. 1998;12(5):344-54. [PubMed ]
45. Kibayashi M, Nagao M, Chiba S: Mutation analysis of the phenylalanine hydroxylase gene and its clinical implications in two Japanese patients with non-phenylketonuria hyperphenylalaninemia. J Hum Genet. 1998;43(4):231-6. [PubMed ]
46. Hennermann JB, Vetter B, Wolf C, Windt E, Buhrdel P, Seidel J, Monch E, Kulozik AE: Phenylketonuria and hyperphenylalaninemia in eastern Germany: a characteristic molecular profile and 15 novel mutations. Hum Mutat. 2000;15(3):254-60. [PubMed ]
47. Gjetting T, Petersen M, Guldberg P, Guttler F: Missense mutations in the N-terminal domain of human phenylalanine hydroxylase interfere with binding of regulatory phenylalanine. Am J Hum Genet. 2001 Jun;68(6):1353-60. Epub 2001 Apr 20. [PubMed ]
48. Acosta A, Silva W Jr, Carvalho T, Gomes M, Zago M: Mutations of the phenylalanine hydroxylase (PAH) gene in Brazilian patients with phenylketonuria. Hum Mutat. 2001 Feb;17(2):122-30. [PubMed ]
49. Yang Y, Drummond-Borg M, Garcia-Heras J: Molecular analysis of phenylketonuria (PKU) in newborns from Texas. Hum Mutat. 2001 Jun;17(6):523. [PubMed ]
50. Gjetting T, Romstad A, Haavik J, Knappskog PM, Acosta AX, Silva WA Jr, Zago MA, Guldberg P, Guttler F: A phenylalanine hydroxylase amino acid polymorphism with implications for molecular diagnostics. Mol Genet Metab. 2001 Jul;73(3):280-4. [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 ]

1. Tryptophan 5-monooxygenase 1

MIEDNKENKDHSLERGRASLIFSLKNEVGGLIKALKIFQEKHVNLLHIESRKSKRRNSEF
EIFVDCDINREQLNDIFHLLKSHTNVLSVNLPDNFTLKEDGMETVPWFPKKISDLDHCAN
RVLMYGSELDADHPGFKDNVYRKRRKYFADLAMNYKHGDPIPKVEFTEEEIKTWGTVFQE
LNKLYPTHACREYLKNLPLLSKYCGYREDNIPQLEDVSNFLKERTGFSIRPVAGYLSPRD
FLSGLAFRVFHCTQYVRHSSDPFYTPEPDTCHELLGHVPLLAEPSFAQFSQEIGLASLGA
SEEAVQKLATCYFFTVEFGLCKQDGQLRVFGAGLLSSISELKHALSGHAKVKPFDPKITC
KQECLITTFQDVYFVSESFEDAKEKMREFTKTIKRPFGVKYNPYTRSIQILKDTKSITSA
MNELQHDLDVVSDALAKVSRKPSI

• Tryptophan Metabolism (map00380 )

• L-tryptophan + tetrahydrobiopterin + O2 = 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin [RN:R07213]

• ACT (PF01842 )
• Biopterin_H (PF00351 )

• None

• None

ATGATTGAAGACAATAAGGAGAACAAAGACCATTCCTTAGAAAGGGGAAGAGCAAGTCTC
ATTTTTTCCTTAAAGAATGAAGTTGGAGGACTTATAAAAGCCCTGAAAATCTTTCAGGAG
AAGCATGTGAATCTGTTACATATCGAGTCCCGAAAATCAAAAAGAAGAAACTCAGAATTT
GAGATTTTTGTTGACTGTGACATCAACAGAGAACAATTGAATGATATTTTTCATCTGCTG
AAGTCTCATACCAATGTTCTCTCTGTGAATCTACCAGATAATTTTACTTTGAAGGAAGAT
GGTATGGAAACTGTTCCTTGGTTTCCAAAGAAGATTTCTGACCTGGACCATTGTGCCAAC
AGAGTTCTGATGTATGGATCTGAACTAGATGCAGACCATCCTGGCTTCAAAGACAATGTC
TACCGTAAACGTCGAAAGTATTTTGCGGACTTGGCTATGAACTATAAACATGGAGACCCC
ATTCCAAAGGTTGAATTCACTGAAGAGGAGATTAAGACCTGGGGAACCGTATTCCAAGAG
CTCAACAAACTCTACCCAACCCATGCTTGCAGAGAGTATCTCAAAAACTTACCTTTGCTT
TCTAAATATTGTGGATATCGGGAGGATAATATCCCACAATTGGAAGATGTCTCCAACTTT
TTAAAAGAGCGTACAGGTTTTTCCATCCGTCCTGTGGCTGGTTACTTATCACCAAGAGAT
TTCTTATCAGGTTTAGCCTTTCGAGTTTTTCACTGCACTCAATATGTGAGACACAGTTCA
GATCCCTTCTATACCCCAGAGCCAGATACCTGCCATGAACTCTTAGGTCATGTCCCGCTT
TTGGCTGAACCTAGTTTTGCCCAATTCTCCCAAGAAATTGGCTTGGCTTCTCTTGGCGCT
TCAGAGGAGGCTGTTCAAAAACTGGCAACGTGCTACTTTTTCACTGTGGAGTTTGGTCTA
TGTAAACAAGATGGACAGCTAAGAGTCTTTGGTGCTGGCTTACTTTCTTCTATCAGTGAA
CTCAAACATGCACTTTCTGGACATGCCAAAGTAAAGCCCTTTGATCCCAAGATTACCTGC
AAACAGGAATGTCTTATCACAACTTTTCAAGATGTCTACTTTGTATCTGAAAGTTTTGAA
GATGCAAAGGAGAAGATGAGAGAATTTACCAAAACAATTAAGCGTCCATTTGGAGTGAAG
TATAATCCATATACACGGAGTATTCAGATCCTGAAAGACACCAAGAGCATAACCAGTGCC
ATGAATGAGCTGCAGCATGATCTCGATGTTGTCAGTGATGCCCTTGCTAAGGTCAGCAGG
AAGCCGAGTATCTAA

1. Boularand S, Darmon MC, Ganem Y, Launay JM, Mallet J: Complete coding sequence of human tryptophan hydroxylase. Nucleic Acids Res. 1990 Jul 25;18(14):4257. [PubMed ]
2. Tipper JP, Citron BA, Ribeiro P, Kaufman S: Cloning and expression of rabbit and human brain tryptophan hydroxylase cDNA in Escherichia coli. Arch Biochem Biophys. 1994 Dec;315(2):445-53. [PubMed ]
3. 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 ]
4. Wang GA, Coon SL, Kaufman S: Alternative splicing at the 3'-cDNA of human tryptophan hydroxylase. J Neurochem. 1998 Oct;71(4):1769-72. [PubMed ]
5. Wang L, Erlandsen H, Haavik J, Knappskog PM, Stevens RC: Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin. Biochemistry. 2002 Oct 22;41(42):12569-74. [PubMed ]

1. Neuronal tryptophan hydroxylase
2. Tryptophan 5-monooxygenase 2

MQPAMMMFSSKYWARRGFSLDSAVPEEHQLLGSSTLNKPNSGKNDDKGNKGSSKREAATE
SGKTAVVFSLKNEVGGLVKALRLFQEKRVNMVHIESRKSRRRSSEVEIFVDCECGKTEFN
ELIQLLKFQTTIVTLNPPENIWTEEEELEDVPWFPRKISELDKCSHRVLMYGSELDADHP
GFKDNVYRQRRKYFVDVAMGYKYGQPIPRVEYTEEETKTWGVVFRELSKLYPTHACREYL
KNFPLLTKYCGYREDNVPQLEDVSMFLKERSGFTVRPVAGYLSPRDFLAGLAYRVFHCTQ
YIRHGSDPLYTPEPDTCHELLGHVPLLADPKFAQFSQEIGLASLGASDEDVQKLATCYFF
TIEFGLCKQEGQLRAYGAGLLSSIGELKHALSDKACVKAFDPKTTCLQECLITTFQEAYF
VSESFEEAKEKMRDFAKSITRPFSVYFNPYTQSIEILKDTRSIENVVQDLRSDLNTVCDA
LNKMNQYLGI

• Tryptophan Metabolism (map00380 )

• L-tryptophan + tetrahydrobiopterin + O2 = 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin [RN:R07213]

• ACT (PF01842 )
• Biopterin_H (PF00351 )

• None

• None

ATGCAGCCAGCAATGATGATGTTTTCCAGTAAATACTGGGCACGGAGAGGGTTTTCCCTG
GATTCAGCAGTGCCCGAAGAGCATCAGCTACTTGGCAGCTCAACACTAAATAAACCTAAC
TCTGGCAAAAATGACGACAAAGGCAACAAGGGAAGCAGCAAACGTGAAGCTGCTACCGAA
AGTGGCAAGACAGCAGTTGTTTTCTCCTTGAAGAATGAAGTTGGTGGATTGGTAAAAGCA
CTGAGGCTCTTTCAGGAAAAACGTGTCAACATGGTTCATATTGAATCCAGGAAATCTCGG
CGAAGAAGTTCTGAGGTTGAAATCTTTGTGGACTGTGAGTGTGGGAAAACAGAATTCAAT
GAGCTCATTCAGTTGCTGAAATTTCAAACCACTATTGTGACGCTGAATCCTCCAGAGAAC
ATTTGGACAGAGGAAGAAGAGCTAGAGGATGTGCCCTGGTTCCCTCGGAAGATCTCTGAG
TTAGACAAATGCTCTCACAGAGTTCTCATGTATGGTTCTGAGCTTGATGCTGACCACCCA
GGATTTAAGGACAATGTCTATCGACAGAGAAGAAAGTATTTTGTGGATGTGGCCATGGGT
TATAAATATGGTCAGCCCATTCCCAGGGTGGAGTATACTGAAGAAGAAACTAAAACTTGG
GGTGTTGTATTCCGGGAGCTCTCCAAACTCTATCCCACTCATGCTTGCCGAGAGTATTTG
AAAAACTTCCCTCTGCTGACTAAATACTGTGGCTACAGAGAGGACAATGTGCCTCAACTC
GAAGATGTCTCCATGTTTCTGAAAGAAAGGTCTGGCTTCACGGTGAGGCCGGTGGCTGGA
TACCTGAGCCCACGAGACTTTCTGGCAGGACTGGCCTACAGAGTGTTCCACTGTACCCAG
TACATCCGGCATGGCTCAGATCCCCTCTACACCCCAGAACCAGACACATGCCATGAACTC
TTGGGACATGTTCCACTACTTGCGGATCCTAAGTTTGCTCAGTTTTCACAAGAAATAGGT
CTGGCGTCTCTGGGAGCATCAGATGAAGATGTTCAGAAACTAGCCACGTGCTATTTCTTC
ACAATCGAGTTTGGCCTTTGCAAGCAAGAAGGGCAACTGCGGGCATATGGAGCAGGACTC
CTTTCCTCCATTGGAGAATTAAAGCACGCCCTTTCTGACAAGGCATGTGTGAAAGCCTTT
GACCCAAAGACAACTTGCTTACAGGAATGCCTTATCACCACCTTCCAGGAAGCCTACTTT
GTTTCAGAAAGTTTTGAAGAAGCCAAAGAAAAGATGAGGGACTTTGCAAAGTCAATTACC
CGTCCCTTCTCAGTATACTTCAATCCCTACACACAGAGTATTGAAATTCTGAAAGACACC
AGAAGTATTGAAAATGTGGTGCAGGACCTTCGCAGCGACTTGAATACAGTGTGTGATGCT
TTAAACAAAATGAACCAATATCTGGGGATTTGA

1. Walther DJ, Peter JU, Bashammakh S, Hortnagl H, Voits M, Fink H, Bader M: Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science. 2003 Jan 3;299(5603):76. [PubMed ]
2. Scherer SE, Muzny DM, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Montgomery KT, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Lovering RC, Wheeler DA, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clerc-Blankenburg KP, Davis C, Delgado O, Dinh HH, Draper H, Gonzalez-Garay ML, Havlak P, Jackson LR, Jacob LS, Kelly SH, Li L, Li Z, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Pasternak S, Perez LM, Plopper FJ, Santibanez J, Shen H, Tabor PE, Verduzco D, Waldron L, Wang Q, Williams GA, Zhang J, Zhou J, Allen CC, Amin AG, Anyalebechi V, Bailey M, Barbaria JA, Bimage KE, Bryant NP, Burch PE, Burkett CE, Burrell KL, Calderon E, Cardenas V, Carter K, Casias K, Cavazos I, Cavazos SR, Ceasar H, Chacko J, Chan SN, Chavez D, Christopoulos C, Chu J, Cockrell R, Cox CD, Dang M, Dathorne SR, David R, Davis CM, Davy-Carroll L, Deshazo DR, Donlin JE, D'Souza L, Eaves KA, Egan A, Emery-Cohen AJ, Escotto M, Flagg N, Forbes LD, Gabisi AM, Garza M, Hamilton C, Henderson N, Hernandez O, Hines S, Hogues ME, Huang M, Idlebird DG, Johnson R, Jolivet A, Jones S, Kagan R, King LM, Leal B, Lebow H, Lee S, LeVan JM, Lewis LC, London P, Lorensuhewa LM, Loulseged H, Lovett DA, Lucier A, Lucier RL, Ma J, Madu RC, Mapua P, Martindale AD, Martinez E, Massey E, Mawhiney S, Meador MG, Mendez S, Mercado C, Mercado IC, Merritt CE, Miner ZL, Minja E, Mitchell T, Mohabbat F, Mohabbat K, Montgomery B, Moore N, Morris S, Munidasa M, Ngo RN, Nguyen NB, Nickerson E, Nwaokelemeh OO, Nwokenkwo S, Obregon M, Oguh M, Oragunye N, Oviedo RJ, Parish BJ, Parker DN, Parrish J, Parks KL, Paul HA, Payton BA, Perez A, Perrin W, Pickens A, Primus EL, Pu LL, Puazo M, Quiles MM, Quiroz JB, Rabata D, Reeves K, Ruiz SJ, Shao H, Sisson I, Sonaike T, Sorelle RP, Sutton AE, Svatek AF, Svetz LA, Tamerisa KS, Taylor TR, Teague B, Thomas N, Thorn RD, Trejos ZY, Trevino BK, Ukegbu ON, Urban JB, Vasquez LI, Vera VA, Villasana DM, Wang L, Ward-Moore S, Warren JT, Wei X, White F, Williamson AL, Wleczyk R, Wooden HS, Wooden SH, Yen J, Yoon L, Yoon V, Zorrilla SE, Nelson D, Kucherlapati R, Weinstock G, Gibbs RA: The finished DNA sequence of human chromosome 12. Nature. 2006 Mar 16;440(7082):346-51. [PubMed ]
3. Molina H, Horn DM, Tang N, Mathivanan S, Pandey A: Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry. Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2199-204. Epub 2007 Feb 7. [PubMed ]
4. Cichon S, Winge I, Mattheisen M, Georgi A, Karpushova A, Freudenberg J, Freudenberg-Hua Y, Babadjanova G, Van Den Bogaert A, Abramova LI, Kapiletti S, Knappskog PM, McKinney J, Maier W, Jamra RA, Schulze TG, Schumacher J, Propping P, Rietschel M, Haavik J, Nothen MM: Brain-specific tryptophan hydroxylase 2 (TPH2): a functional Pro206Ser substitution and variation in the 5'-region are associated with bipolar affective disorder. Hum Mol Genet. 2008 Jan 1;17(1):87-97. Epub 2007 Sep 27. [PubMed ]
5. Zhang X, Gainetdinov RR, Beaulieu JM, Sotnikova TD, Burch LH, Williams RB, Schwartz DA, Krishnan KR, Caron MG: Loss-of-function mutation in tryptophan hydroxylase-2 identified in unipolar major depression. Neuron. 2005 Jan 6;45(1):11-6. [PubMed ]
6. McKinney J, Johansson S, Halmoy A, Dramsdahl M, Winge I, Knappskog PM, Haavik J: A loss-of-function mutation in tryptophan hydroxylase 2 segregating with attention-deficit/hyperactivity disorder. Mol Psychiatry. 2008 Apr;13(4):365-7. [PubMed ]
7. McKinney JA, Turel B, Winge I, Knappskog PM, Haavik J: Functional properties of missense variants of human tryptophan hydroxylase 2. Hum Mutat. 2009 May;30(5):787-94. [PubMed ]

1. HDHPR
2. Quinoid dihydropteridine reductase

MAAAAAAGEARRVLVYGGRGALGSRCVQAFRARNWWVASVDVVENEEASASIIVKMTDSF
TEQADQVTAEVGKLLGEEKVDAILCVAGGWAGGNAKSKSLFKNCDLMWKQSIWTSTISSH
LATKHLKEGGLLTLAGAKAALDGTPGMIGYGMAKGAVHQLCQSLAGKNSGMPPGAAAIAV
LPVTLDTPMNRKSMPEADFSSWTPLEFLVETFHDWITGKNRPSSGSLIQVVTTEGRTELT
PAYF

• Folate and Pterine Biosynthesis (map00790 )

• a 5,6,7,8-tetrahydropteridine + NAD(P)+ = a 6,7-dihydropteridine + NAD(P)H + H+ [RN:R07354 R07355]

• adh_short (PF00106 )

• None

• None

ATGGCGGCGGCGGCGGCTGCAGGCGAGGCGCGCCGGGTGCTGGTGTACGGCGGCAGGGGC
GCTCTGGGTTCTCGATGCGTGCAGGCTTTTCGGGCCCGCAACTGGTGGGTTGCCAGCGTT
GATGTGGTGGAGAATGAAGAGGCCAGCGCTACGATCATTGTTAAAATGACAGACTCGTTC
ACTGAGCAGGCTGACCAGGTGACTGCTGAGGTTGGAAAGCTCTTGGGTGAAGAGAAGGTG
GATGCAATTCTTTGCGTTGCTGGAGGATGGGCCGGGGGCAATGCCAAATCCAAGTCTCTC
TTTAAGAACTGTGACCTGATGTGGAAGCAGAGCATATGGACATCGACCATCTCCAGCCAT
CTGGCTACCAAGCATCTCAAGGAAGGAGGCCTCCTGACCTTGGCTGGCGCAAAGGCTGCC
CTGGATGGGACTCCTGGTATGATCGGGTACGGCATGGCCAAGGGTGCTGTTCACCAGCTC
TGCCAGAGCCTGGCTGGGAAGAACAGCGGCATGCCGCCCGGGGCAGCCGCCATCGCTGTG
CTCCCGGTTACCCTGGATACCCCGATGAACAGGAAATCAATGCCTGAGGCTGACTTCAGC
TCCTGGACACCCTTAGAATTCCTAGTTGAAACTTTCCATGACTGGATCACAGGGAAAAAC
CGACCGAGCTCAGGAAGCCTAATCCAGGTGGTAACCACAGAAGGAAGGACGGAACTCACC
CCAGCATATTTTTAG

1. Dahl HH, Hutchison W, McAdam W, Wake S, Morgan FJ, Cotton RG: Human dihydropteridine reductase: characterisation of a cDNA clone and its use in analysis of patients with dihydropteridine reductase deficiency. Nucleic Acids Res. 1987 Mar 11;15(5):1921-32. [PubMed ]
2. Lockyer J, Cook RG, Milstien S, Kaufman S, Woo SL, Ledley FD: Structure and expression of human dihydropteridine reductase. Proc Natl Acad Sci U S A. 1987 May;84(10):3329-33. [PubMed ]
3. Dianzani I, de Sanctis L, Smooker PM, Gough TJ, Alliaudi C, Brusco A, Spada M, Blau N, Dobos M, Zhang HP, Yang N, Ponzone A, Armarego WL, Cotton RG: Dihydropteridine reductase deficiency: physical structure of the QDPR gene, identification of two new mutations and genotype-phenotype correlations. Hum Mutat. 1998;12(4):267-73. [PubMed ]
4. 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 ]
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. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. [PubMed ]
7. Su Y, Varughese KI, Xuong NH, Bray TL, Roche DJ, Whiteley JM: The crystallographic structure of a human dihydropteridine reductase NADH binary complex expressed in Escherichia coli by a cDNA constructed from its rat homologue. J Biol Chem. 1993 Dec 25;268(36):26836-41. [PubMed ]
8. Smooker PM, Cotton RG: Molecular basis of dihydropteridine reductase deficiency. Hum Mutat. 1995;5(4):279-84. [PubMed ]
9. Dianzani I, Howells DW, Ponzone A, Saleeba JA, Smooker PM, Cotton RG: Two new mutations in the dihydropteridine reductase gene in patients with tetrahydrobiopterin deficiency. J Med Genet. 1993 Jun;30(6):465-9. [PubMed ]
10. Howells DW, Forrest SM, Dahl HH, Cotton RG: Insertion of an extra codon for threonine is a cause of dihydropteridine reductase deficiency. Am J Hum Genet. 1990 Aug;47(2):279-85. [PubMed ]
11. Smooker PM, Gough TJ, Cotton RG, Alliaudi C, de Sanctis L, Dianzani I: A series of mutations in the dihydropteridine reductase gene resulting in either abnormal RNA splicing or DHPR protein defects. Mutations in brief no. 244. Online. Hum Mutat. 1999;13(6):503-4. [PubMed ]
12. Romstad A, Kalkanoglu HS, Coskun T, Demirkol M, Tokatli A, Dursun A, Baykal T, Ozalp I, Guldberg P, Guttler F: Molecular analysis of 16 Turkish families with DHPR deficiency using denaturing gradient gel electrophoresis (DGGE). Hum Genet. 2000 Dec;107(6):546-53. [PubMed ]

1. Constitutive NOS
2. cNOS
3. EC-NOS
4. Endothelial NOS
5. eNOS
6. NOS type III
7. NOSIII

MGNLKSVAQEPGPPCGLGLGLGLGLCGKQGPATPAPEPSRAPASLLPPAPEHSPPSSPLT
QPPEGPKFPRVKNWEVGSITYDTLSAQAQQDGPCTPRRCLGSLVFPRKLQGRPSPGPPAP
EQLLSQARDFINQYYSSIKRSGSQAHEQRLQEVEAEVAATGTYQLRESELVFGAKQAWRN
APRCVGRIQWGKLQVFDARDCRSAQEMFTYICNHIKYATNRGNLRSAITVFPQRCPGRGD
FRIWNSQLVRYAGYRQQDGSVRGDPANVEITELCIQHGWTPGNGRFDVLPLLLQAPDEPP
ELFLLPPELVLEVPLEHPTLEWFAALGLRWYALPAVSNMLLEIGGLEFPAAPFSGWYMST
EIGTRNLCDPHRYNILEDVAVCMDLDTRTTSSLWKDKAAVEINVAVLHSYQLAKVTIVDH
HAATASFMKHLENEQKARGGCPADWAWIVPPISGSLTPVFHQEMVNYFLSPAFRYQPDPW
KGSAAKGTGITRKKTFKEVANAVKISASLMGTVMAKRVKATILYGSETGRAQSYAQQLGR
LFRKAFDPRVLCMDEYDVVSLEHETLVLVVTSTFGNGDPPENGESFAAALMEMSGPYNSS
PRPEQHKSYKIRFNSISCSDPLVSSWRRKRKESSNTDSAGALGTLRFCVFGLGSRAYPHF
CAFARAVDTRLEELGGERLLQLGQGDELCGQEEAFRGWAQAAFQAACETFCVGEDAKAAA
RDIFSPKRSWKRQRYRLSAQAEGLQLLPGLIHVHRRKMFQATIRSVENLQSSKSTRATIL
VRLDTGGQEGLQYQPGDHIGVCPPNRPGLVEALLSRVEDPPAPTEPVAVEQLEKGSPGGP
PPGWVRDPRLPPCTLRQALTFFLDITSPPSPQLLRLLSTLAEEPREQQELEALSQDPRRY
EEWKWFRCPTLLEVLEQFPSVALPAPLLLTQLPLLQPRYYSVSSAPSTHPGEIHLTVAVL
AYRTQDGLGPLHYGVCSTWLSQLKPGDPVPCFIRGAPSFRLPPDPSLPCILVGPGTGIAP
FRGFWQERLHDIESKGLQPTPMTLVFGCRCSQLDHLYRDEVQNAQQRGVFGRVLTAFSRE
PDNPKTYVQDILRTELAAEVHRVLCLERGHMFVCGDVTMATNVLQTVQRILATEGDMELD
EAGDVIGVLRDQQRYHEDIFGLTLRTQEVTSRIRTQSFSLQERQLRGAVPWAFDPPGSDT
NSP

• Arginine and Proline Metabolism (map00330 )

• L-arginine + n NADPH + n H+ + m O2 = citrulline + nitric oxide + n NADP+ [RN:R00557]

• FAD_binding_1 (PF00667 )
• Flavodoxin_1 (PF00258 )
• NAD_binding_1 (PF00175 )
• NO_synthase (PF02898 )

• None

• None

ATGGGCAACTTGAAGAGCGTGGCCCAGGAGCCTGGGCCACCCTGCGGCCTGGGGCTGGGG
CTGGGCCTTGGGCTGTGCGGCAAGCAGGGCCCAGCCACCCCGGCCCCTGAGCCCAGCCGG
GCCCCAGCATCCCTACTCCCACCAGCGCCAGAACACAGCCCCCCGAGCTCCCCGCTAACC
CAGCCCCCAGAGGGGCCCAAGTTCCCTCGTGTGAAGAACTGGGAGGTGGGGAGCATCACC
TATGACACCCTCAGCGCCCAGGCGCAGCAGGATGGGCCCTGCACCCCAAGACGCTGCCTG
GGCTCCCTGGTATTTCCACGGAAACTACAGGGCCGGCCCTCCCCCGGCCCCCCGGCCCCT
GAGCAGCTGCTGAGTCAGGCCCGGGACTTCATCAACCAGTACTACAGCTCCATTAAGAGG
AGCGGCTCCCAGGCCCACGAACAGCGGCTTCAAGAGGTGGAAGCCGAGGTGGCAGCCACA
GGCACCTACCAGCTTAGGGAGAGCGAGCTGGTGTTCGGGGCTAAGCAGGCCTGGCGCAAC
GCTCCCCGCTGCGTGGGCCGGATCCAGTGGGGGAAGCTGCAGGTGTTCGATGCCCGGGAC
TGCAGGTCTGCACAGGAAATGTTCACCTACATCTGCAACCACATCAAGTATGCCACCAAC
CGGGGCAACCTTCGCTCGGCCATCACAGTGTTCCCGCAGCGCTGCCCTGGCCGAGGAGAC
TTCCGAATCTGGAACAGCCAGCTGGTGCGCTACGCGGGCTACCGGCAGCAGGACGGCTCT
GTGCGGGGGGACCCAGCCAACGTGGAGATCACCGAGCTCTGCATTCAGCACGGCTGGACC
CCAGGAAACGGTCGCTTCGACGTGCTGCCCCTGCTGCTGCAGGCCCCAGATGAGCCCCCA
GAACTCTTCCTTCTGCCCCCCGAGCTGGTCCTTGAGGTGCCCCTGGAGCACCCCACGCTG
GAGTGGTTTGCAGCCCTGGGCCTGCGCTGGTACGCCCTCCCGGCAGTGTCCAACATGCTG
CTGGAAATTGGGGGCCTGGAGTTCCCCGCAGCCCCCTTCAGTGGCTGGTACATGAGCACT
GAGATCGGCACGAGGAACCTGTGTGACCCTCACCGCTACAACATCCTGGAGGATGTGGCT
GTCTGCATGGACCTGGATACCCGGACCACCTCGTCCCTGTGGAAAGACAAGGCAGCAGTG
GAAATCAACGTGGCCGTGCTGCACAGTTACCAGCTAGCCAAAGTCACCATCGTGGACCAC
CACGCCGCCACGGCCTCTTTCATGAAGCACCTGGAGAATGAGCAGAAGGCCAGGGGGGGC
TGCCCTGCAGACTGGGCCTGGATCGTGCCCCCCATCTCGGGCAGCCTCACTCCTGTTTTC
CATCAGGAGATGGTCAACTATTTCCTGTCCCCGGCCTTCCGCTACCAGCCAGACCCCTGG
AAGGGGAGTGCCGCCAAGGGCACCGGCATCACCAGGAAGAAGACCTTTAAAGAAGTGGCC
AACGCCGTGAAGATCTCCGCCTCGCTCATGGGCACGGTGATGGCGAAGCGAGTGAAGGCG
ACAATCCTGTATGGCTCCGAGACCGGCCGGGCCCAGAGCTACGCACAGCAGCTGGGGAGA
CTCTTCCGGAAGGCTTTTGATCCCCGGGTCCTGTGTATGGATGAGTATGACGTGGTGTCC
CTCGAACACGAGACGCTGGTGCTGGTGGTAACCAGCACATTTGGGAATGGGGATCCCCCG
GAGAATGGAGAGAGCTTTGCAGCTGCCCTGATGGAGATGTCCGGCCCCTACAACAGCTCC
CCTCGGCCGGAACAGCACAAGAGTTATAAGATCCGCTTCAACAGCATCTCCTGCTCAGAC
CCACTGGTGTCCTCTTGGCGGCGGAAGAGGAAGGAGTCCAGTAACACAGACAGTGCAGGG
GCCCTGGGCACCCTCAGGTTCTGTGTGTTCGGGCTCGGCTCCCGGGCATACCCCCACTTC
TGCGCCTTTGCTCGTGCCGTGGACACACGGCTGGAGGAACTGGGCGGGGAGCGGCTGCTG
CAGCTGGGCCAGGGCGACGAGCTGTGCGGCCAGGAGGAGGCCTTCCGAGGCTGGGCCCAG
GCTGCCTTCCAGGCCGCCTGTGAGACCTTCTGTGTGGGAGAGGATGCCAAGGCCGCCGCC
CGAGACATCTTCAGCCCCAAACGGAGCTGGAAGCGCCAGAGGTACCGGCTGAGCGCCCAG
GCCGAGGGCCTGCAGTTGCTGCCAGGTCTGATCCACGTGCACAGGCGGAAGATGTTCCAG
GCTACAATCCGCTCAGTGGAAAACCTGCAAAGCAGCAAGTCCACGAGGGCCACCATCCTG
GTGCGCCTGGACACCGGAGGCCAGGAGGGGCTGCAGTACCAGCCGGGGGACCACATAGGT
GTCTGCCCGCCCAACCGGCCCGGCCTTGTGGAGGCGCTGCTGAGCCGCGTGGAGGACCCG
CCGGCGCCCACTGAGCCCGTGGCAGTAGAGCAGCTGGAGAAGGGCAGCCCTGGTGGCCCT
CCCCCCGGCTGGGTGCGGGACCCCCGGCTGCCCCCGTGCACGCTGCGCCAGGCTCTCACC
TTCTTCCTGGACATCACCTCCCCACCCAGCCCTCAGCTCTTGCGGCTGCTCAGCACCTTG
GCAGAAGAGCCCAGGGAACAGCAGGAGCTGGAGGCCCTCAGCCAGGATCCCCGACGCTAC
GAGGAGTGGAAGTGGTTCCGCTGCCCCACGCTGCTGGAGGTGCTGGAGCAGTTCCCGTCG
GTGGCGCTGCCTGCCCCACTGCTCCTCACCCAGCTGCCTCTGCTCCAGCCCCGGTACTAC
TCAGTCAGCTCGGCACCCAGCACCCACCCAGGAGAGATCCACCTCACTGTAGCTGTGCTG
GCATACAGGACTCAGGATGGGCTGGGCCCCCTGCACTATGGAGTCTGCTCCACGTGGCTA
AGCCAGCTCAAGCCCGGAGACCCTGTGCCCTGCTTCATCCGGGGGGCTCCCTCCTTCCGG
CTGCCACCCGATCCCAGCTTGCCCTGCATCCTGGTGGGTCCAGGCACTGGCATTGCCCCC
TTCCGGGGATTCTGGCAGGAGCGGCTGCATGACATTGAGAGCAAAGGGCTGCAGCCCACT
CCCATGACTTTGGTGTTCGGCTGCCGATGCTCCCAACTTGACCATCTCTACCGCGACGAG
GTGCAGAACGCCCAGCAGCGCGGGGTGTTTGGCCGAGTCCTCACCGCCTTCTCCCGGGAA
CCTGACAACCCCAAGACCTACGTGCAGGACATCCTGAGGACGGAGCTGGCTGCGGAGGTG
CACCGCGTGCTGTGCCTCGAGCGGGGCCACATGTTTGTCTGCGGCGATGTTACCATGGCA
ACCAACGTCCTGCAGACCGTGCAGCGCATCCTGGCGACGGAGGGCGACATGGAGCTGGAC
GAGGCCGGCGACGTCATCGGCGTGCTGCGGGATCAGCAACGCTACCACGAAGACATTTTC
GGGCTCACGCTGCGCACCCAGGAGGTGACAAGCCGCATACGCACCCAGAGCTTTTCCTTG
CAGGAGCGTCAGTTGCGGGGCGCAGTGCCCTGGGCGTTCGACCCTCCCGGCTCAGACACC
AACAGCCCCTGA

1. Janssens SP, Shimouchi A, Quertermous T, Bloch DB, Bloch KD: Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase. J Biol Chem. 1992 Jul 25;267(21):14519-22. [PubMed ]
2. Marsden PA, Schappert KT, Chen HS, Flowers M, Sundell CL, Wilcox JN, Lamas S, Michel T: Molecular cloning and characterization of human endothelial nitric oxide synthase. FEBS Lett. 1992 Aug 3;307(3):287-93. [PubMed ]
3. Marsden PA, Heng HH, Scherer SW, Stewart RJ, Hall AV, Shi XM, Tsui LC, Schappert KT: Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem. 1993 Aug 15;268(23):17478-88. [PubMed ]
4. Nadaud S, Bonnardeaux A, Lathrop M, Soubrier F: Gene structure, polymorphism and mapping of the human endothelial nitric oxide synthase gene. Biochem Biophys Res Commun. 1994 Feb 15;198(3):1027-33. [PubMed ]
5. Miyahara K, Kawamoto T, Sase K, Yui Y, Toda K, Yang LX, Hattori R, Aoyama T, Yamamoto Y, Doi Y, et al.: Cloning and structural characterization of the human endothelial nitric-oxide-synthase gene. Eur J Biochem. 1994 Aug 1;223(3):719-26. [PubMed ]
6. 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 ]
7. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [PubMed ]
8. 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 ]
9. Robinson LJ, Weremowicz S, Morton CC, Michel T: Isolation and chromosomal localization of the human endothelial nitric oxide synthase (NOS3) gene. Genomics. 1994 Jan 15;19(2):350-7. [PubMed ]
10. Sase K, Michel T: Expression of constitutive endothelial nitric oxide synthase in human blood platelets. Life Sci. 1995;57(22):2049-55. [PubMed ]
11. Garvey EP, Tuttle JV, Covington K, Merrill BM, Wood ER, Baylis SA, Charles IG: Purification and characterization of the constitutive nitric oxide synthase from human placenta. Arch Biochem Biophys. 1994 Jun;311(2):235-41. [PubMed ]
12. Dedio J, Konig P, Wohlfart P, Schroeder C, Kummer W, Muller-Esterl W: NOSIP, a novel modulator of endothelial nitric oxide synthase activity. FASEB J. 2001 Jan;15(1):79-89. [PubMed ]
13. Zimmermann K, Opitz N, Dedio J, Renne C, Muller-Esterl W, Oess S: NOSTRIN: a protein modulating nitric oxide release and subcellular distribution of endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):17167-72. Epub 2002 Nov 21. [PubMed ]
14. Icking A, Matt S, Opitz N, Wiesenthal A, Muller-Esterl W, Schilling K: NOSTRIN functions as a homotrimeric adaptor protein facilitating internalization of eNOS. J Cell Sci. 2005 Nov 1;118(Pt 21):5059-69. Epub 2005 Oct 18. [PubMed ]
15. Schleicher M, Brundin F, Gross S, Muller-Esterl W, Oess S: Cell cycle-regulated inactivation of endothelial NO synthase through NOSIP-dependent targeting to the cytoskeleton. Mol Cell Biol. 2005 Sep;25(18):8251-8. [PubMed ]
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