1. (1R,2S)-(2-Amino-3,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)-1,2-propandiol
2. 2-Amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydoro-4(1H)-5,6,7,8-Tetrahydro-2-amino-6-(1,2-dihydroxypropyl)-4(1H)-pteridinone
3. 2-amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(1H)-Pteridinone
4. 5,6,7,8-Tetrahydro-2-amino-6-(1,2-dihydroxypropyl)-4(1H)-pteridinone
5. 5,6,7,8-Tetrahydrobiopterin
6. 5,6,7,8-erythro-tetrahydrobiopterin
7. 5,6,7,8-tetra-H-biopterin
8. L-erythro-2-Amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(3H)-pteridinon
9. Tetrahydrobiopterin
10. tetra-H-biopterin
11. tetra-hydro-biopterin

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• Cytoplasm (Predicted from LogP)
• nucleus

• Blood
• Cerebrospinal Fluid

1. Galley HF, Le Cras AE, Yassen K, Grant IS, Webster NR: Circulating tetrahydrobiopterin concentrations in patients with septic shock. Br J Anaesth. 2001 Apr;86(4):578-80. [PubMed ]
2. Kuhn DM, Geddes TJ: Tetrahydrobiopterin prevents nitration of tyrosine hydroxylase by peroxynitrite and nitrogen dioxide. Mol Pharmacol. 2003 Oct;64(4):946-53. [PubMed ]
3. Takikawa S, Curtius HC, Redweik U, Leimbacher W, Ghisla S: Biosynthesis of tetrahydrobiopterin. Purification and characterization of 6-pyruvoyl-tetrahydropterin synthase from human liver. Eur J Biochem. 1986 Dec 1;161(2):295-302. [PubMed ]
4. Walter R, Kaufmann PA, Buck A, Berthold T, Wyss C, von Schulthess GK, Schaffner A, Schoedon G: Tetrahydrobiopterin increases myocardial blood flow in healthy volunteers: a double-blind, placebo-controlled study. Swiss Med Wkly. 2001 Feb 24;131(7-8):91-4. [PubMed ]
5. Hyland K, Gunasekara RS, Munk-Martin TL, Arnold LA, Engle T: The hph-1 mouse: a model for dominantly inherited GTP-cyclohydrolase deficiency. Ann Neurol. 2003;54 Suppl 6:S46-8. [PubMed ]
6. Leeming RJ, Blair JA, Melikian V, O'Gorman DJ: Biopterin derivatives in human body fluids and tissues. J Clin Pathol. 1976 May;29(5):444-51. [PubMed ]
7. Schallreuter KU, Moore J, Wood JM, Beazley WD, Peters EM, Marles LK, Behrens-Williams SC, Dummer R, Blau N, Thony B: Epidermal H(2)O(2) accumulation alters tetrahydrobiopterin (6BH4) recycling in vitiligo: identification of a general mechanism in regulation of all 6BH4-dependent processes? J Invest Dermatol. 2001 Jan;116(1):167-74. [PubMed ]
8. Dhondt JL, Cotton RG, Danks DM: Liver enzyme activities in hyperphenylalaninaemia due to a defective synthesis of tetrahydrobiopterin. J Inherit Metab Dis. 1985;8(2):47-8. [PubMed ]
9. Sawabe K, Suetake Y, Nakanishi N, Wakasugi KO, Hasegawa H: Cellular accumulation of tetrahydrobiopterin following its administration is mediated by two different processes; direct uptake and indirect uptake mediated by a methotrexate-sensitive process. Mol Genet Metab. 2005 Dec;86 Suppl 1:S133-8. Epub 2005 Sep 13. [PubMed ]
10. Koch R, Moseley KD, Moats R, Yano S, Matalon R, Guttler F: Danger of high-protein dietary supplements to persons with hyperphenylalaninaemia. J Inherit Metab Dis. 2003;26(4):339-42. [PubMed ]
11. Cady EB, Lorek A, Penrice J, Reynolds EO, Iles RA, Burns SP, Coutts GA, Cowan FM: Detection of propan-1,2-diol in neonatal brain by in vivo proton magnetic resonance spectroscopy. Magn Reson Med. 1994 Dec;32(6):764-7. [PubMed ]
12. Matter H, Kumar HS, Fedorov R, Frey A, Kotsonis P, Hartmann E, Frohlich LG, Reif A, Pfleiderer W, Scheurer P, Ghosh DK, Schlichting I, Schmidt HH: Structural analysis of isoform-specific inhibitors targeting the tetrahydrobiopterin binding site of human nitric oxide synthases. J Med Chem. 2005 Jul 28;48(15):4783-92. [PubMed ]
13. Curtius HC, Heintel D, Ghisla S, Kuster T, Leimbacher W, Niederwieser A: Tetrahydrobiopterin biosynthesis. Studies with specifically labeled (2H)NAD(P)H and 2H2O and of the enzymes involved. Eur J Biochem. 1985 May 2;148(3):413-9. [PubMed ]
14. Furukawa Y, Kish SJ, Bebin EM, Jacobson RD, Fryburg JS, Wilson WG, Shimadzu M, Hyland K, Trugman JM: Dystonia with motor delay in compound heterozygotes for GTP-cyclohydrolase I gene mutations. Ann Neurol. 1998 Jul;44(1):10-6. [PubMed ]
15. Kaufman S, Kapatos G, Rizzo WB, Schulman JD, Tamarkin L, Van Loon GR: Tetrahydropterin therapy for hyperphenylalaninemia caused by defective synthesis of tetrahydrobiopterin. Ann Neurol. 1983 Sep;14(3):308-15. [PubMed ]
16. Spaapen LJ, Bakker JA, Velter C, Loots W, Rubio-Gozalbo ME, Forget PP, Dorland L, De Koning TJ, Poll-The BT, Ploos van Amstel HK, Bekhof J, Blau N, Duran M: Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency in Dutch neonates. J Inherit Metab Dis. 2001 Jun;24(3):352-8. [PubMed ]
17. Wikipedia

1. Tyrosinase
2. Tyrosine 3-monooxygenase
3. Phenylalanine-4-hydroxylase
4. 6-pyruvoyl tetrahydrobiopterin synthase
5. Sepiapterin reductase
6. Tryptophan 5-hydroxylase 1
7. Tryptophan 5-hydroxylase 2
8. Dihydropteridine reductase
9. Nitric oxide synthase, inducible
10. Nitric oxide synthase, brain
11. Nitric oxide synthase, endothelial
12. GTP cyclohydrolase 1
13. GTP cyclohydrolase 1 feedback regulatory protein
14. Pterin-4-alpha-carbinolamine dehydratase
15. cDNA FLJ76220, highly similar to Homo sapiens quinoid dihydropteridine reductase (QDPR), mRNA (Quinoid dihydropteridine reductase, isoform CRA_d)
16. Nitric oxide synthase 2A (Inducible, hepatocytes)
17. Calcium-calmodulin independent nitric oxide synthase iNOS protein
18. Nitric oxide synthase, inducible

1. LB24-AB
2. Monophenol monooxygenase
3. SK29-AB
4. Tumor rejection antigen AB

MLLAVLYCLLWSFQTSAGHFPRACVSSKNLMEKECCPPWSGDRSPCGQLSGRGSCQNILL
SNAPLGPQFPFTGVDDRESWPSVFYNRTCQCSGNFMGFNCGNCKFGFWGPNCTERRLLVR
RNIFDLSAPEKDKFFAYLTLAKHTISSDYVIPIGTYGQMKNGSTPMFNDINIYDLFVWMH
YYVSMDALLGGSEIWRDIDFAHEAPAFLPWHRLFLLRWEQEIQKLTGDENFTIPYWDWRD
AEKCDICTDEYMGGQHPTNPNLLSPASFFSSWQIVCSRLEEYNSHQSLCNGTPEGPLRRN
PGNHDKSRTPRLPSSADVEFCLSLTQYESGSMDKAANFSFRNTLEGFASPLTGIADASQS
SMHNALHIYMNGTMSQVQGSANDPIFLLHHAFVDSIFEQWLRRHRPLQEVYPEANAPIGH
NRESYMVPFIPLYRNGDFFISSKDLGYDYSYLQDSDPDSFQDYIKSYLEQASRIWSWLLG
AAMVGAVLTALLAGLVSLLCRHKRKQLPEEKQPLLMEKEDYHSLYQSHL

• Riboflavin Metabolism (map00740 )
• Stilbene, coumarine and lignin biosynthesis (map00940 )
• Tyrosine Metabolism (map00350 )

• L-tyrosine + L-dopa + O2 = L-dopa + dopaquinone + H2O [RN:R02078]

• Tyrosinase (PF00264 )

• 1-18

• 477-497

ATGCTCCTGGCTGTTTTGTACTGCCTGCTGTGGAGTTTCCAGACCTCCGCTGGCCATTTC
CCTAGAGCCTGTGTCTCCTCTAAGAACCTGATGGAGAAGGAATGCTGTCCACCGTGGAGC
GGGGACAGGAGTCCCTGTGGCCAGCTTTCAGGCAGAGGTTCCTGTCAGAATATCCTTCTG
TCCAATGCACCACTTGGGCCTCAATTTCCCTTCACAGGGGTGGATGACCGGGAGTCGTGG
CCTTCCGTCTTTTATAATAGGACCTGCCAGTGCTCTGGCAACTTCATGGGATTCAACTGT
GGAAACTGCAAGTTTGGCTTTTGGGGACCAAACTGCACAGAGAGACGACTCTTGGTGAGA
AGAAACATCTTCGATTTGAGTGCCCCAGAGAAGGACAAATTTTTTGCCTACCTCACTTTA
GCAAAGCATACCATCAGCTCAGACTATGTCATCCCCATAGGGACCTATGGCCAAATGAAA
AATGGATCAACACCCATGTTTAACGACATCAATATTTATGACCTCTTTGTCTGGATGCAT
TATTATGTGTCAATGGATGCACTGCTTGGGGGATCTGAAATCTGGAGAGACATTGATTTT
GCCCATGAAGCACCAGCTTTTCTGCCTTGGCATAGACTCTTCTTGTTGCGGTGGGAACAA
GAAATCCAGAAGCTGACAGGAGATGAAAACTTCACTATTCCATATTGGGACTGGCGGGAT
GCAGAAAAGTGTGACATTTGCACAGATGAGTACATGGGAGGTCAGCACCCCACAAATCCT
AACTTACTCAGCCCAGCATCATTCTTCTCCTCTTGGCAGATTGTCTGTAGCCGATTGGAG
GAGTACAACAGCCATCAGTCTTTATGCAATGGAACGCCCGAGGGACCTTTACGGCGTAAT
CCTGGAAACCATGACAAATCCAGAACCCCAAGGCTCCCCTCTTCAGCTGATGTAGAATTT
TGCCTGAGTTTGACCCAATATGAATCTGGTTCCATGGATAAAGCTGCCAATTTCAGCTTT
AGAAATACACTGGAAGGATTTGCTAGTCCACTTACTGGGATAGCGGATGCCTCTCAAAGC
AGCATGCACAATGCCTTGCACATCTATATGAATGGAACAATGTCCCAGGTACAGGGATCT
GCCAACGATCCTATCTTCCTTCTTCACCATGCATTTGTTGACAGTATTTTTGAGCAGTGG
CTCCGAAGGCACCGTCCTCTTCAAGAAGTTTATCCAGAAGCCAATGCACCCATTGGACAT
AACCGGGAATCCTACATGGTTCCTTTTATACCACTGTACAGAAATGGTGATTTCTTTATT
TCATCCAAAGATCTGGGCTATGACTATAGCTATCTACAAGATTCAGACCCAGACTCTTTT
CAAGACTACATTAAGTCCTATTTGGAACAAGCGAGTCGGATCTGGTCATGGCTCCTTGGG
GCGGCGATGGTAGGGGCCGTCCTCACTGCCCTGCTGGCAGGGCTTGTGAGCTTGCTGTGT
CGTCACAAGAGAAAGCAGCTTCCTGAAGAAAAGCAGCCACTCCTCATGGAGAAAGAGGAT
TACCACAGCTTGTATCAGAGCCATTTATAA

1. Giebel LB, Strunk KM, Spritz RA: Organization and nucleotide sequences of the human tyrosinase gene and a truncated tyrosinase-related segment. Genomics. 1991 Mar;9(3):435-45. [PubMed ]
2. Kwon BS, Haq AK, Pomerantz SH, Halaban R: Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7473-7. [PubMed ]
3. Bouchard B, Fuller BB, Vijayasaradhi S, Houghton AN: Induction of pigmentation in mouse fibroblasts by expression of human tyrosinase cDNA. J Exp Med. 1989 Jun 1;169(6):2029-42. [PubMed ]
4. Chintamaneni CD, Halaban R, Kobayashi Y, Witkop CJ Jr, Kwon BS: A single base insertion in the putative transmembrane domain of the tyrosinase gene as a cause for tyrosinase-negative oculocutaneous albinism. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5272-6. [PubMed ]
5. Brichard V, Van Pel A, Wolfel T, Wolfel C, De Plaen E, Lethe B, Coulie P, Boon T: The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med. 1993 Aug 1;178(2):489-95. [PubMed ]
6. Martinez-Arias R, Comas D, Andres A, Abello MT, Domingo-Roura X, Bertranpetit J: The tyrosinase gene in gorillas and the albinism of 'Snowflake'. Pigment Cell Res. 2000 Dec;13(6):467-70. [PubMed ]
7. 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 ]
8. Kikuchi H, Miura H, Yamamoto H, Takeuchi T, Dei T, Watanabe M: Characteristic sequences in the upstream region of the human tyrosinase gene. Biochim Biophys Acta. 1989 Dec 22;1009(3):283-6. [PubMed ]
9. Takeda A, Tomita Y, Okinaga S, Tagami H, Shibahara S: Functional analysis of the cDNA encoding human tyrosinase precursor. Biochem Biophys Res Commun. 1989 Aug 15;162(3):984-90. [PubMed ]
10. Murphy WJ, Eizirik E, Johnson WE, Zhang YP, Ryder OA, O'Brien SJ: Molecular phylogenetics and the origins of placental mammals. Nature. 2001 Feb 1;409(6820):614-8. [PubMed ]
11. Oetting WS, King RA: Molecular basis of type I (tyrosinase-related) oculocutaneous albinism: mutations and polymorphisms of the human tyrosinase gene. Hum Mutat. 1993;2(1):1-6. [PubMed ]
12. Oetting WS, King RA: Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. Hum Mutat. 1999;13(2):99-115. [PubMed ]
13. Basrur V, Yang F, Kushimoto T, Higashimoto Y, Yasumoto K, Valencia J, Muller J, Vieira WD, Watabe H, Shabanowitz J, Hearing VJ, Hunt DF, Appella E: Proteomic analysis of early melanosomes: identification of novel melanosomal proteins. J Proteome Res. 2003 Jan-Feb;2(1):69-79. [PubMed ]
14. Chi A, Valencia JC, Hu ZZ, Watabe H, Yamaguchi H, Mangini NJ, Huang H, Canfield VA, Cheng KC, Yang F, Abe R, Yamagishi S, Shabanowitz J, Hearing VJ, Wu C, Appella E, Hunt DF: Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. J Proteome Res. 2006 Nov;5(11):3135-44. [PubMed ]
15. Spritz RA, Strunk KM, Giebel LB, King RA: Detection of mutations in the tyrosinase gene in a patient with type IA oculocutaneous albinism. N Engl J Med. 1990 Jun 14;322(24):1724-8. [PubMed ]
16. Giebel LB, Strunk KM, King RA, Hanifin JM, Spritz RA: A frequent tyrosinase gene mutation in classic, tyrosinase-negative (type IA) oculocutaneous albinism. Proc Natl Acad Sci U S A. 1990 May;87(9):3255-8. [PubMed ]
17. Giebel LB, Tripathi RK, Strunk KM, Hanifin JM, Jackson CE, King RA, Spritz RA: Tyrosinase gene mutations associated with type IB ("yellow") oculocutaneous albinism. Am J Hum Genet. 1991 Jun;48(6):1159-67. [PubMed ]
18. Tripathi RK, Strunk KM, Giebel LB, Weleber RG, Spritz RA: Tyrosinase gene mutations in type I (tyrosinase-deficient) oculocutaneous albinism define two clusters of missense substitutions. Am J Med Genet. 1992 Jul 15;43(5):865-71. [PubMed ]
19. Spritz RA, Strunk KM, Hsieh CL, Sekhon GS, Francke U: Homozygous tyrosinase gene mutation in an American black with tyrosinase-negative (type IA) oculocutaneous albinism. Am J Hum Genet. 1991 Feb;48(2):318-24. [PubMed ]
20. Giebel LB, Tripathi RK, King RA, Spritz RA: A tyrosinase gene missense mutation in temperature-sensitive type I oculocutaneous albinism. A human homologue to the Siamese cat and the Himalayan mouse. J Clin Invest. 1991 Mar;87(3):1119-22. [PubMed ]
21. King RA, Mentink MM, Oetting WS: Non-random distribution of missense mutations within the human tyrosinase gene in type I (tyrosinase-related) oculocutaneous albinism. Mol Biol Med. 1991 Feb;8(1):19-29. [PubMed ]
22. Oetting WS, King RA: Molecular analysis of type I-A (tyrosinase negative) oculocutaneous albinism. Hum Genet. 1992 Nov;90(3):258-62. [PubMed ]
23. Tripathi RK, Bundey S, Musarella MA, Droetto S, Strunk KM, Holmes SA, Spritz RA: Mutations of the tyrosinase gene in Indo-Pakistani patients with type I (tyrosinase-deficient) oculocutaneous albinism (OCA). Am J Hum Genet. 1993 Dec;53(6):1173-9. [PubMed ]
24. Gershoni-Baruch R, Rosenmann A, Droetto S, Holmes S, Tripathi RK, Spritz RA: Mutations of the tyrosinase gene in patients with oculocutaneous albinism from various ethnic groups in Israel. Am J Hum Genet. 1994 Apr;54(4):586-94. [PubMed ]
25. Breimer LH, Winder AF, Jay B, Jay M: Initiation codon mutation of the tyrosinase gene as a cause of human albinism. Clin Chim Acta. 1994 Jun;227(1-2):17-22. [PubMed ]
26. Summers CG, Oetting WS, King RA: Diagnosis of oculocutaneous albinism with molecular analysis. Am J Ophthalmol. 1996 Jun;121(6):724-6. [PubMed ]
27. Morell R, Spritz RA, Ho L, Pierpont J, Guo W, Friedman TB, Asher JH Jr: Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and autosomal recessive ocular albinism (AROA). Hum Mol Genet. 1997 May;6(5):659-64. [PubMed ]
28. Spritz RA, Oh J, Fukai K, Holmes SA, Ho L, Chitayat D, France TD, Musarella MA, Orlow SJ, Schnur RE, Weleber RG, Levin AV: Novel mutations of the tyrosinase (TYR) gene in type I oculocutaneous albinism (OCA1). Hum Mutat. 1997;10(2):171-4. [PubMed ]
29. Oetting WS, Fryer JP, King RA: Mutations of the human tyrosinase gene associated with tyrosinase related oculocutaneous albinism (OCA1). Mutations in brief no. 204. Online. Hum Mutat. 1998;12(6):433-4. [PubMed ]
30. Passmore LA, Kaesmann-Kellner B, Weber BH: Novel and recurrent mutations in the tyrosinase gene and the P gene in the German albino population. Hum Genet. 1999 Sep;105(3):200-10. [PubMed ]
31. Tsai CH, Tsai FJ, Wu JY, Lin SP, Chang JG, Yang CF, Lee CC: Insertion/deletion mutations of type I oculocutaneous albinism in chinese patients from Taiwan. Hum Mutat. 1999 Dec;14(6):542. [PubMed ]
32. Camand O, Marchant D, Boutboul S, Pequignot M, Odent S, Dollfus H, Sutherland J, Levin A, Menasche M, Marsac C, Dufier JL, Heon E, Abitbol M: Mutation analysis of the tyrosinase gene in oculocutaneous albinism. Hum Mutat. 2001 Apr;17(4):352. [PubMed ]
33. Nakamura E, Miyamura Y, Matsunaga J, Kano Y, Dakeishi-Hara M, Tanita M, Kono M, Tomita Y: A novel mutation of the tyrosinase gene causing oculocutaneous albinism type 1 (OCA1). J Dermatol Sci. 2002 Feb;28(2):102-5. [PubMed ]
34. Opitz S, Kasmann-Kellner B, Kaufmann M, Schwinger E, Zuhlke C: Detection of 53 novel DNA variations within the tyrosinase gene and accumulation of mutations in 17 patients with albinism. Hum Mutat. 2004 Jun;23(6):630-1. [PubMed ]
35. Stokowski RP, Pant PV, Dadd T, Fereday A, Hinds DA, Jarman C, Filsell W, Ginger RS, Green MR, van der Ouderaa FJ, Cox DR: A genomewide association study of skin pigmentation in a South Asian population. Am J Hum Genet. 2007 Dec;81(6):1119-32. Epub 2007 Oct 15. [PubMed ]
36. Sulem P, Gudbjartsson DF, Stacey SN, Helgason A, Rafnar T, Magnusson KP, Manolescu A, Karason A, Palsson A, Thorleifsson G, Jakobsdottir M, Steinberg S, Palsson S, Jonasson F, Sigurgeirsson B, Thorisdottir K, Ragnarsson R, Benediktsdottir KR, Aben KK, Kiemeney LA, Olafsson JH, Gulcher J, Kong A, Thorsteinsdottir U, Stefansson K: Genetic determinants of hair, eye and skin pigmentation in Europeans. Nat Genet. 2007 Dec;39(12):1443-52. Epub 2007 Oct 21. [PubMed ]

1. Wood JM, Schallreuter-Wood KU, Lindsey NJ, Callaghan S, Gardner ML: A specific tetrahydrobiopterin binding domain on tyrosinase controls melanogenesis. Biochem Biophys Res Commun. 1995 Jan 17;206(2):480-5. [PubMed ]

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. Madsen JT, Jansen P, Hesslinger C, Meyer M, Zimmer J, Gramsbergen JB: Tetrahydrobiopterin precursor sepiapterin provides protection against neurotoxicity of 1-methyl-4-phenylpyridinium in nigral slice cultures. J Neurochem. 2003 Apr;85(1):214-23. [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 ]
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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. 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 ]

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. 9165069;16920111

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. Auerbach G, Nar H: The pathway from GTP to tetrahydrobiopterin: three-dimensional structures of GTP cyclohydrolase I and 6-pyruvoyl tetrahydropterin synthase. Biol Chem. 1997 Mar-Apr;378(3-4):185-92. [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. Sumi-Ichinose C, Urano F, Kuroda R, Ohye T, Kojima M, Tazawa M, Shiraishi H, Hagino Y, Nagatsu T, Nomura T, Ichinose H: Catecholamines and serotonin are differently regulated by tetrahydrobiopterin. A study from 6-pyruvoyltetrahydropterin synthase knockout mice. J Biol Chem. 2001 Nov 2;276(44):41150-60. Epub 2001 Aug 21. [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. Shen RS: Inhibition of dopamine autoxidation by tetrahydrobiopterin and NADH in the presence of dihydropteridine reductase. Neurotoxicology. 1991 Summer;12(2):201-8. [PubMed ]

1. Hepatocyte NOS
2. HEP-NOS
3. Inducible NO synthase
4. Inducible NOS
5. iNOS
6. NOS type II

MACPWKFLFKTKFHQYAMNGEKDINNNVEKAPCATSSPVTQDDLQYHNLSKQQNESPQPL
VETGKKSPESLVKLDATPLSSPRHVRIKNWGSGMTFQDTLHHKAKGILTCRSKSCLGSIM
TPKSLTRGPRDKPTPPDELLPQAIEFVNQYYGSFKEAKIEEHLARVEAVTKEIETTGTYQ
LTGDELIFATKQAWRNAPRCIGRIQWSNLQVFDARSCSTAREMFEHICRHVRYSTNNGNI
RSAITVFPQRSDGKHDFRVWNAQLIRYAGYQMPDGSIRGDPANVEFTQLCIDLGWKPKYG
RFDVVPLVLQANGRDPELFEIPPDLVLEVAMEHPKYEWFRELELKWYALPAVANMLLEVG
GLEFPGCPFNGWYMGTEIGVRDFCDVQRYNILEEVGRRMGLETHKLASLWKDQAVVEINI
AVLHSFQKQNVTIMDHHSAAESFMKYMQNEYRSRGGCPADWIWLVPPMSGSITPVFHQEM
LNYVLSPFYYYQVEAWKTHVWQDEKRRPKRREIPLKVLVKAVLFACMLMRKTMASRVRVT
ILFATETGKSEALAWDLGALFSCAFNPKVVCMDKYRLSCLEEERLLLVVTSTFGNGDCPG
NGEKLKKSLFMLKELNNKFRYAVFGLGSSMYPRFCAFAHDIDQKLSHLGASQLTPMGEGD
ELSGQEDAFRSWAVQTFKAACETFDVRGKQHIQIPKLYTSNVTWDPHHYRLVQDSQPLDL
SKALSSMHAKNVFTMRLKSRQNLQSPTSSRATILVELSCEDGQGLNYLPGEHLGVCPGNQ
PALVQGILERVVDGPTPHQTVRLEALDESGSYWVSDKRLPPCSLSQALTYFLDITTPPTQ
LLLQKLAQVATEEPERQRLEALCQPSEYSKWKFTNSPTFLEVLEEFPSLRVSAGFLLSQL
PILKPRFYSISSSRDHTPTEIHLTVAVVTYHTRDGQGPLHHGVCSTWLNSLKPQDPVPCF
VRNASGFHLPEDPSHPCILIGPGTGIAPFRSFWQQRLHDSQHKGVRGGRMTLVFGCRRPD
EDHIYQEEMLEMAQKGVLHAVHTAYSRLPGKPKVYVQDILRQQLASEVLRVLHKEPGHLY
VCGDVRMARDVAHTLKQLVAAKLKLNEEQVEDYFFQLKSQKRYHEDIFGAVFPYEAKKDR
VAVQPSSLEMSAL

• 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

ATGGCCTGTCCTTGGAAATTTCTGTTCAAGACCAAATTCCACCAGTATGCAATGAATGGG
GAAAAAGACATCAACAACAATGTGGAGAAAGCCCCCTGTGCCACCTCCAGTCCAGTGACA
CAGGATGACCTTCAGTATCACAACCTCAGCAAGCAGCAGAATGAGTCCCCGCAGCCCCTC
GTGGAGACGGGAAAGAAGTCTCCAGAATCTCTGGTCAAGCTGGATGCAACCCCATTGTCC
TCCCCACGGCATGTGAGGATCAAAAACTGGGGCAGCGGGATGACTTTCCAAGACACACTT
CACCATAAGGCCAAAGGGATTTTAACTTGCAGGTCCAAATCTTGCCTGGGGTCCATTATG
ACTCCCAAAAGTTTGACCAGAGGACCCAGGGACAAGCCTACCCCTCCAGATGAGCTTCTA
CCTCAAGCTATCGAATTTGTCAACCAATATTACGGCTCCTTCAAAGAGGCAAAAATAGAG
GAACATCTGGCCAGGGTGGAAGCGGTAACAAAGGAGATAGAAACAACAGGAACCTACCAA
CTGACGGGAGATGAGCTCATCTTCGCCACCAAGCAGGCCTGGCGCAATGCCCCACGCTGC
ATTGGGAGGATCCAGTGGTCCAACCTGCAGGTCTTCGATGCCCGCAGCTGTTCCACTGCC
CGGGAAATGTTTGAACACATCTGCAGACACGTGCGTTACTCCACCAACAATGGCAACATC
AGGTCGGCCATCACCGTGTTCCCCCAGCGGAGTGATGGCAAGCACGACTTCCGGGTGTGG
AATGCTCAGCTCATCCGCTATGCTGGCTACCAGATGCCAGATGGCAGCATCAGAGGGGAC
CCTGCCAACGTGGAATTCACTCAGCTGTGCATCGACCTGGGCTGGAAGCCCAAGTACGGC
CGCTTCGATGTGGTCCCCCTGGTCCTGCAGGCCAATGGCCGTGACCCTGAGCTCTTCGAA
ATCCCACCTGACCTTGTGCTTGAGGTGGCCATGGAACATCCCAAATACGAGTGGTTTCGG
GAACTGGAGCTAAAGTGGTACGCCCTGCCTGCAGTGGCCAACATGCTGCTTGAGGTGGGC
GGCCTGGAGTTCCCAGGGTGCCCCTTCAATGGCTGGTACATGGGCACAGAGATCGGAGTC
CGGGACTTCTGTGACGTCCAGCGCTACAACATCCTGGAGGAAGTGGGCAGGAGAATGGGC
CTGGAAACGCACAAGCTGGCCTCGCTCTGGAAAGACCAGGCTGTCGTTGAGATCAACATT
GCTGTGCTCCATAGTTTCCAGAAGCAGAATGTGACCATCATGGACCACCACTCGGCTGCA
GAATCCTTCATGAAGTACATGCAGAATGAATACCGGTCCCGTGGGGGCTGCCCGGCAGAC
TGGATTTGGCTGGTCCCTCCCATGTCTGGGAGCATCACCCCCGTGTTTCACCAGGAGATG
CTGAACTACGTCCTGTCCCCTTTCTACTACTATCAGGTAGAGGCCTGGAAAACCCATGTC
TGGCAGGACGAGAAGCGGAGACCCAAGAGAAGAGAGATTCCATTGAAAGTCTTGGTCAAA
GCTGTGCTCTTTGCCTGTATGCTGATGCGCAAGACAATGGCGTCCCGAGTCAGAGTCACC
ATCCTCTTTGCGACAGAGACAGGAAAATCAGAGGCGCTGGCCTGGGACCTGGGGGCCTTA
TTCAGCTGTGCCTTCAACCCCAAGGTTGTCTGCATGGATAAGTACAGGCTGAGCTGCCTG
GAGGAGGAACGGCTGCTGTTGGTGGTGACCAGTACGTTTGGCAATGGAGACTGCCCTGGC
AATGGAGAGAAACTGAAGAAATCGCTCTTCATGCTGAAAGAGCTCAACAACAAATTCAGG
TACGCTGTGTTTGGCCTCGGCTCCAGCATGTACCCTCGGTTCTGCGCCTTTGCTCATGAC
ATTGATCAGAAGCTGTCCCACCTGGGGGCCTCTCAGCTCACCCCGATGGGAGAAGGGGAT
GAGCTCAGTGGGCAGGAGGACGCCTTCCGCAGCTGGGCCGTGCAAACCTTCAAGGCAGCC
TGTGAGACGTTTGATGTCCGAGGCAAACAGCACATTCAGATCCCCAAGCTCTACACCTCC
AATGTGACCTGGGACCCGCACCACTACAGGCTCGTGCAGGACTCACAGCCTTTGGACCTC
AGCAAAGCCCTCAGCAGCATGCATGCCAAGAACGTGTTCACCATGAGGCTCAAATCTCGG
CAGAATCTACAAAGTCCGACATCCAGCCGTGCCACCATCCTGGTGGAACTCTCCTGTGAG
GATGGCCAAGGCCTGAACTACCTGCCGGGGGAGCACCTTGGGGTTTGCCCAGGCAACCAG
CCGGCCCTGGTCCAAGGCATCCTGGAGCGAGTGGTGGATGGCCCCACACCCCACCAGACA
GTGCGCCTGGAGGCCCTGGATGAGAGTGGCAGCTACTGGGTCAGTGACAAGAGGCTGCCC
CCCTGCTCACTCAGCCAGGCCCTCACCTACTTCCTGGACATCACCACACCCCCAACCCAG
CTGCTGCTCCAAAAGCTGGCCCAGGTGGCCACAGAAGAGCCTGAGAGACAGAGGCTGGAG
GCCCTGTGCCAGCCCTCAGAGTACAGCAAGTGGAAGTTCACCAACAGCCCCACATTCCTG
GAGGTGCTAGAGGAGTTCCCGTCCCTGCGGGTGTCTGCTGGCTTCCTGCTTTCCCAGCTC
CCCATTCTGAAGCCCAGGTTCTACTCCATCAGCTCCTCCCGGGATCACACGCCCACGGAG
ATCCACCTGACTGTGGCCGTGGTCACCTACCACACCCGAGATGGCCAGGGTCCCCTGCAC
CACGGCGTCTGCAGCACATGGCTCAACAGCCTGAAGCCCCAAGACCCAGTGCCCTGCTTT
GTGCGGAATGCCAGCGGCTTCCACCTCCCCGAGGATCCCTCCCATCCTTGCATCCTCATC
GGGCCTGGCACAGGCATCGCGCCCTTCCGCAGTTTCTGGCAGCAACGGCTCCATGACTCC
CAGCACAAGGGAGTGCGGGGAGGCCGCATGACCTTGGTGTTTGGGTGCCGCCGCCCAGAT
GAGGACCACATCTACCAGGAGGAGATGCTGGAGATGGCCCAGAAGGGGGTGCTGCATGCG
GTGCACACAGCCTATTCCCGCCTGCCTGGCAAGCCCAAGGTCTATGTTCAGGACATCCTG
CGGCAGCAGCTGGCCAGCGAGGTGCTCCGTGTGCTCCACAAGGAGCCAGGCCACCTCTAT
GTTTGCGGGGATGTGCGCATGGCCCGGGACGTGGCCCACACCCTGAAGCAGCTGGTGGCT
GCCAAGCTGAAATTGAATGAGGAGCAGGTCGAGGACTATTTCTTTCAGCTCAAGAGCCAG
AAGCGCTATCACGAAGATATCTTTGGTGCTGTATTTCCTTACGAGGCGAAGAAGGACAGG
GTGGCGGTGCAGCCCAGCAGCCTGGAGATGTCAGCGCTCTGA

1. Sherman PA, Laubach VE, Reep BR, Wood ER: Purification and cDNA sequence of an inducible nitric oxide synthase from a human tumor cell line. Biochemistry. 1993 Nov 2;32(43):11600-5. [PubMed ]
2. Geller DA, Lowenstein CJ, Shapiro RA, Nussler AK, Di Silvio M, Wang SC, Nakayama DK, Simmons RL, Snyder SH, Billiar TR: Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3491-5. [PubMed ]
3. Charles IG, Palmer RM, Hickery MS, Bayliss MT, Chubb AP, Hall VS, Moss DW, Moncada S: Cloning, characterization, and expression of a cDNA encoding an inducible nitric oxide synthase from the human chondrocyte. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11419-23. [PubMed ]
4. Maier R, Bilbe G, Rediske J, Lotz M: Inducible nitric oxide synthase from human articular chondrocytes: cDNA cloning and analysis of mRNA expression. Biochim Biophys Acta. 1994 Sep 21;1208(1):145-50. [PubMed ]
5. Park CS, Pardhasaradhi K, Gianotti C, Villegas E, Krishna G: Human retina expresses both constitutive and inducible isoforms of nitric oxide synthase mRNA. Biochem Biophys Res Commun. 1994 Nov 30;205(1):85-91. [PubMed ]
6. Hokari A, Zeniya M, Esumi H: Cloning and functional expression of human inducible nitric oxide synthase (NOS) cDNA from a glioblastoma cell line A-172. J Biochem (Tokyo). 1994 Sep;116(3):575-81. [PubMed ]
7. Guo FH, De Raeve HR, Rice TW, Stuehr DJ, Thunnissen FB, Erzurum SC: Continuous nitric oxide synthesis by inducible nitric oxide synthase in normal human airway epithelium in vivo. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7809-13. [PubMed ]
8. Luss H, Li RK, Shapiro RA, Tzeng E, McGowan FX, Yoneyama T, Hatakeyama K, Geller DA, Mickle DA, Simmons RL, Billiar TR: Dedifferentiated human ventricular cardiac myocytes express inducible nitric oxide synthase mRNA but not protein in response to IL-1, TNF, IFNgamma, and LPS. J Mol Cell Cardiol. 1997 Apr;29(4):1153-65. [PubMed ]
9. 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 ]
10. McLay JS, Chatterjee P, Nicolson AG, Jardine AG, McKay NG, Ralston SH, Grabowski P, Haites NE, MacLeod AM, Hawksworth GM: Nitric oxide production by human proximal tubular cells: a novel immunomodulatory mechanism? Kidney Int. 1994 Oct;46(4):1043-9. [PubMed ]
11. Fujisawa H, Ogura T, Hokari A, Weisz A, Yamashita J, Esumi H: Inducible nitric oxide synthase in a human glioblastoma cell line. J Neurochem. 1995 Jan;64(1):85-91. [PubMed ]
12. Bloch KD, Wolfram JR, Brown DM, Roberts JD Jr, Zapol DG, Lepore JJ, Filippov G, Thomas JE, Jacob HJ, Bloch DB: Three members of the nitric oxide synthase II gene family (NOS2A, NOS2B, and NOS2C) colocalize to human chromosome 17. Genomics. 1995 Jun 10;27(3):526-30. [PubMed ]
13. Taylor BS, Alarcon LH, Billiar TR: Inducible nitric oxide synthase in the liver: regulation and function. Biochemistry (Mosc). 1998 Jul;63(7):766-81. [PubMed ]
14. Glynne PA, Darling KE, Picot J, Evans TJ: Epithelial inducible nitric-oxide synthase is an apical EBP50-binding protein that directs vectorial nitric oxide output. J Biol Chem. 2002 Sep 6;277(36):33132-8. Epub 2002 Jun 21. [PubMed ]
15. Li H, Raman CS, Glaser CB, Blasko E, Young TA, Parkinson JF, Whitlow M, Poulos TL: Crystal structures of zinc-free and -bound heme domain of human inducible nitric-oxide synthase. Implications for dimer stability and comparison with endothelial nitric-oxide synthase. J Biol Chem. 1999 Jul 23;274(30):21276-84. [PubMed ]
16. Fischmann TO, Hruza A, Niu XD, Fossetta JD, Lunn CA, Dolphin E, Prongay AJ, Reichert P, Lundell DJ, Narula SK, Weber PC: Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation. Nat Struct Biol. 1999 Mar;6(3):233-42. [PubMed ]
17. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed ]

1. Constitutive NOS
2. NC-NOS
3. NOS type I
4. Neuronal NOS
5. N-NOS
6. nNOS
7. bNOS

MEDHMFGVQQIQPNVISVRLFKRKVGGLGFLVKERVSKPPVIISDLIRGGAAEQSGLIQA
GDIILAVNGRPLVDLSYDSALEVLRGIASETHVVLILRGPEGFTTHLETTFTGDGTPKTI
RVTQPLGPPTKAVDLSHQPPAGKEQPLAVDGASGPGNGPQHAYDDGQEAGSLPHANGLAP
RPPGQDPAKKATRVSLQGRGENNELLKEIEPVLSLLTSGSRGVKGGAPAKAEMKDMGIQV
DRDLDGKSHKPLPLGVENDRVFNDLWGKGNVPVVLNNPYSEKEQPPTSGKQSPTKNGSPS
KCPRFLKVKNWETEVVLTDTLHLKSTLETGCTEYICMGSIMHPSQHARRPEDVRTKGQLF
PLAKEFIDQYYSSIKRFGSKAHMERLEEVNKEIDTTSTYQLKDTELIYGAKHAWRNASRC
VGRIQWSKLQVFDARDCTTAHGMFNYICNHVKYATNKGNLRSAITIFPQRTDGKHDFRVW
NSQLIRYAGYKQPDGSTLGDPANVQFTEICIQQGWKPPRGRFDVLPLLLQANGNDPELFQ
IPPELVLEVPIRHPKFEWFKDLGLKWYGLPAVSNMLLEIGGLEFSACPFSGWYMGTEIGV
RDYCDNSRYNILEEVAKKMNLDMRKTSSLWKDQALVEINIAVLYSFQSDKVTIVDHHSAT
ESFIKHMENEYRCRGGCPADWVWIVPPMSGSITPVFHQEMLNYRLTPSFEYQPDPWNTHV
WKGTNGTPTKRRAIGFKKLAEAVKFSAKLMGQAMAKRVKATILYATETGKSQAYAKTLCE
IFKHAFDAKVMSMEEYDIVHLEHETLVLVVTSTFGNGDPPENGEKFGCALMEMRHPNSVQ
EERKSYKVRFNSVSSYSDSQKSSGDGPDLRDNFESAGPLANVRFSVFGLGSRAYPHFCAF
GHAVDTLLEELGGERILKMREGDELCGQEEAFRTWAKKVFKAACDVFCVGDDVNIEKANN
SLISNDRSWKRNKFRLTFVAEAPELTQGLSNVHKKRVSAARLLSRQNLQSPKSSRSTIFV
RLHTNGSQELQYQPGDHLGVFPGNHEDLVNALIERLEDAPPVNQMVKVELLEERNTALGV
ISNWTDELRLPPCTIFQAFKYYLDITTPPTPLQLQQFASLATSEKEKQRLLVLSKGLQEY
EEWKWGKNPTIVEVLEEFPSIQMPATLLLTQLSLLQPRYYSISSSPDMYPDEVHLTVAIV
SYRTRDGEGPIHHGVCSSWLNRIQADELVPCFVRGAPSFHLPRNPQVPCILVGPGTGIAP
FRSFWQQRQFDIQHKGMNPCPMVLVFGCRQSKIDHIYREETLQAKNKGVFRELYTAYSRE
PDKPKKYVQDILQEQLAESVYRALKEQGGHIYVCGDVTMAADVLKAIQRIMTQQGKLSAE
DAGVFISRMRDDNRYHEDIFGVTLRTYEVTNRLRSESIAFIEESKKDTDEVFSS

• 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 )
• PDZ (PF00595 )

• None

• None

ATGGAGGATCACATGTTCGGTGTTCAGCAAATCCAGCCCAATGTCATTTCTGTTCGTCTC
TTCAAGCGCAAAGTTGGGGGCCTGGGATTTCTGGTGAAGGAGCGGGTCAGTAAGCCGCCC
GTGATCATCTCTGACCTGATTCGTGGGGGCGCCGCAGAGCAGAGTGGCCTCATCCAGGCC
GGAGACATCATTCTTGCGGTCAACGGCCGGCCCTTGGTGGACCTGAGCTATGACAGCGCC
CTGGAGGTACTCAGAGGCATTGCCTCTGAGACCCACGTGGTCCTCATTCTGAGGGGCCCT
GAAGGTTTCACCACGCACCTGGAGACCACCTTTACAGGTGATGGGACCCCCAAGACCATC
CGGGTGACACAGCCCCTGGGTCCCCCCACCAAAGCCGTGGATCTGTCCCACCAGCCACCG
GCCGGCAAAGAACAGCCCCTGGCAGTGGATGGGGCCTCGGGTCCCGGGAATGGGCCTCAG
CATGCCTACGATGATGGGCAGGAGGCTGGCTCACTCCCCCATGCCAACGGCCTGGCCCCC
AGGCCCCCAGGCCAGGACCCCGCGAAGAAAGCAACCAGAGTCAGCCTCCAAGGCAGAGGG
GAGAACAATGAACTGCTCAAGGAGATAGAGCCTGTGCTGAGCCTTCTCACCAGTGGGAGC
AGAGGGGTCAAGGGAGGGGCACCTGCCAAGGCAGAGATGAAAGATATGGGAATCCAGGTG
GACAGAGATTTGGACGGCAAGTCACACAAACCTCTGCCCCTCGGCGTGGAGAACGACCGA
GTCTTCAATGACCTATGGGGGAAGGGCAATGTGCCTGTCGTCCTCAACAACCCATATTCA
GAGAAGGAGCAGCCCCCCACCTCAGGAAAACAGTCCCCCACAAAGAATGGCAGCCCCTCC
AAGTGTCCACGCTTCCTCAAGGTCAAGAACTGGGAGACTGAGGTGGTTCTCACTGACACC
CTCCACCTTAAGAGCACATTGGAAACGGGATGCACTGAGTACATCTGCATGGGCTCCATC
ATGCATCCTTCTCAGCATGCAAGGAGGCCTGAAGACGTCCGCACAAAAGGACAGCTCTTC
CCTCTCGCCAAAGAGTTTATTGATCAATACTATTCATCAATTAAAAGATTTGGCTCCAAA
GCCCACATGGAAAGGCTGGAAGAGGTGAACAAAGAGATCGACACCACTAGCACTTACCAG
CTCAAGGACACAGAGCTCATCTATGGGGCCAAGCACGCCTGGCGGAATGCCTCGCGCTGT
GTGGGCAGGATCCAGTGGTCCAAGCTGCAGGTATTCGATGCCCGTGACTGCACCACGGCC
CACGGGATGTTCAACTACATCTGTAACCATGTCAAGTATGCCACCAACAAAGGGAACCTC
AGGTCTGCCATCACCATATTCCCCCAGAGGACAGACGGCAAGCACGACTTCCGAGTCTGG
AACTCCCAGCTCATCCGCTACGCTGGCTACAAGCAGCCTGACGGCTCCACCCTGGGGGAC
CCAGCCAATGTGCAGTTCACAGAGATATGCATACAGCAGGGCTGGAAACCGCCTAGAGGC
CGCTTCGATGTCCTGCCGCTCCTGCTTCAGGCCAACGGCAATGACCCTGAGCTCTTCCAG
ATTCCTCCAGAGCTGGTGTTGGAAGTTCCCATCAGGCACCCCAAGTTTGAGTGGTTCAAG
GACCTGGGGCTGAAGTGGTACGGCCTCCCCGCCGTGTCCAACATGCTCCTAGAGATTGGC
GGCCTGGAGTTCAGCGCCTGTCCCTTCAGTGGCTGGTACATGGGCACAGAGATTGGTGTC
CGCGACTACTGTGACAACTCCCGCTACAATATCCTGGAGGAAGTGGCCAAGAAGATGAAC
TTAGACATGAGGAAGACGTCCTCCCTGTGGAAGGACCAGGCGCTGGTGGAGATCAATATC
GCGGTTCTCTATAGCTTCCAGAGTGACAAAGTGACCATTGTTGACCATCACTCCGCCACC
GAGTCCTTCATTAAGCACATGGAGAATGAGTACCGCTGCCGGGGGGGCTGCCCTGCCGAC
TGGGTGTGGATCGTGCCCCCCATGTCCGGAAGCATCACCCCTGTGTTCCACCAGGAGATG
CTCAACTACCGGCTCACCCCCTCCTTCGAATACCAGCCTGATCCCTGGAACACGCATGTC
TGGAAAGGCACCAACGGGACCCCCACAAAGCGGCGAGCCATCGGCTTCAAGAAGCTAGCA
GAAGCTGTCAAGTTCTCGGCCAAGCTGATGGGGCAGGCTATGGCCAAGAGGGTGAAAGCG
ACCATCCTCTATGCCACAGAGACAGGCAAATCGCAAGCTTATGCCAAGACCTTGTGTGAG
ATCTTCAAACACGCCTTTGATGCCAAGGTGATGTCCATGGAAGAATATGACATTGTGCAC
CTGGAACATGAAACTCTGGTCCTTGTGGTCACCAGCACCTTTGGCAATGGAGATCCCCCT
GAGAATGGGGAGAAATTCGGCTGTGCTTTGATGGAAATGAGGCACCCCAACTCTGTGCAG
GAAGAAAGGAAGAGCTACAAGGTCCGATTCAACAGCGTCTCCTCCTACTCTGACTCCCAA
AAATCATCAGGCGATGGGCCCGACCTCAGAGACAACTTTGAGAGTGCTGGACCCCTGGCC
AATGTGAGGTTCTCAGTTTTTGGCCTCGGCTCACGAGCATACCCTCACTTTTGCGCCTTC
GGACACGCTGTGGACACCCTCCTGGAAGAACTGGGAGGGGAGAGGATCCTGAAGATGAGG
GAAGGGGATGAGCTCTGTGGGCAGGAAGAGGCTTTCAGGACCTGGGCCAAGAAGGTCTTC
AAGGCAGCCTGTGATGTCTTCTGTGTGGGAGATGATGTCAACATTGAAAAGGCCAACAAT
TCCCTCATCAGCAATGATCGCAGCTGGAAGAGAAACAAGTTCCGCCTCACCTTTGTGGCC
GAAGCTCCAGAACTCACACAAGGTCTATCCAATGTCCACAAAAAGCGAGTCTCAGCTGCC
CGGCTCCTTAGCCGTCAAAACCTCCAGAGCCCTAAATCCAGTCGGTCAACTATCTTCGTG
CGTCTCCACACCAACGGGAGCCAGGAGCTGCAGTACCAGCCTGGGGACCACCTGGGTGTC
TTCCCTGGCAACCACGAGGACCTCGTGAATGCCCTGATCGAGCGGCTGGAGGACGCGCCG
CCTGTCAACCAGATGGTGAAAGTGGAACTGCTGGAGGAGCGGAACACGGCTTTAGGTGTC
ATCAGTAACTGGACAGACGAGCTCCGCCTCCCGCCCTGCACCATCTTCCAGGCCTTCAAG
TACTACCTGGACATCACCACGCCACCAACGCCTCTGCAGCTGCAGCAGTTTGCCTCCCTA
GCTACCAGCGAGAAGGAGAAGCAGCGTCTGCTGGTCCTCAGCAAGGGTTTGCAGGAGTAC
GAGGAATGGAAATGGGGCAAGAACCCCACCATCGTGGAGGTGCTGGAGGAGTTCCCATCT
ATCCAGATGCCGGCCACCCTGCTCCTGACCCAGCTGTCCCTGCTGCAGCCCCGCTACTAT
TCCATCAGCTCCTCCCCAGACATGTACCCTGATGAAGTGCACCTCACTGTGGCCATCGTT
TCCTACCGCACTCGAGATGGAGAAGGACCAATTCACCACGGCGTATGCTCCTCCTGGCTC
AACCGGATACAGGCTGACGAACTGGTCCCCTGTTTCGTGAGAGGAGCACCCAGCTTCCAC
CTGCCCCGGAACCCCCAAGTCCCCTGCATCCTCGTTGGACCAGGCACCGGCATTGCCCCT
TTCCGAAGCTTCTGGCAACAGCGGCAATTTGATATCCAACACAAAGGAATGAACCCCTGC
CCCATGGTCCTGGTCTTCGGGTGCCGGCAATCCAAGATAGATCATATCTACAGGGAAGAG
ACCCTGCAGGCCAAGAACAAGGGGGTCTTCAGAGAGCTGTACACGGCTTACTCCCGGGAG
CCAGACAAACCAAAGAAGTACGTGCAGGACATCCTGCAGGAGCAGCTGGCGGAGTCTGTG
TACCGAGCCCTGAAGGAGCAAGGGGGCCACATATACGTCTGTGGGGACGTCACCATGGCT
GCTGATGTCCTCAAAGCCATCCAGCGCATCATGACCCAGCAGGGGAAGCTCTCGGCAGAG
GACGCCGGCGTATTCATCAGCCGGATGAGGGATGACAACCGATACCATGAGGATATTTTT
GGAGTCACCCTGCGAACGTACGAAGTGACCAACCGCCTTAGATCTGAGTCCATTGCCTTC
ATTGAAGAGAGCAAAAAAGACACCGATGAGGTTTTCAGCTCCTAA

1. Hall AV, Antoniou H, Wang Y, Cheung AH, Arbus AM, Olson SL, Lu WC, Kau CL, Marsden PA: Structural organization of the human neuronal nitric oxide synthase gene (NOS1). J Biol Chem. 1994 Dec 30;269(52):33082-90. [PubMed ]
2. Fujisawa H, Ogura T, Kurashima Y, Yokoyama T, Yamashita J, Esumi H: Expression of two types of nitric oxide synthase mRNA in human neuroblastoma cell lines. J Neurochem. 1994 Jul;63(1):140-5. [PubMed ]
3. Nakane M, Schmidt HH, Pollock JS, Forstermann U, Murad F: Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle. FEBS Lett. 1993 Jan 25;316(2):175-80. [PubMed ]
4. Park CS, Gianotti C, Park R, Krishna G: Neuronal isoform of nitric oxide synthase is expressed at low levels in human retina. Cell Mol Neurobiol. 1996 Aug;16(4):499-515. [PubMed ]
5. Wang Y, Goligorsky MS, Lin M, Wilcox JN, Marsden PA: A novel, testis-specific mRNA transcript encoding an NH2-terminal truncated nitric-oxide synthase. J Biol Chem. 1997 Apr 25;272(17):11392-401. [PubMed ]

1. Kamada Y, Jenkins GJ, Lau M, Dunbar AY, Lowe ER, Osawa Y: Tetrahydrobiopterin depletion and ubiquitylation of neuronal nitric oxide synthase. Brain Res Mol Brain Res. 2005 Dec 7;142(1):19-27. Epub 2005 Oct 10. [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 ]
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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 ]
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21. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed ]

1. Shirodaria C, Antoniades C, Lee J, Jackson CE, Robson MD, Francis JM, Moat SJ, Ratnatunga C, Pillai R, Refsum H, Neubauer S, Channon KM: Global improvement of vascular function and redox state with low-dose folic acid: implications for folate therapy in patients with coronary artery disease. Circulation. 2007 May 1;115(17):2262-70. Epub 2007 Apr 9. [PubMed ]

1. GTP cyclohydrolase I
2. GTP-CH-I

MEKGPVRAPAEKPRGARCSNGFPERDPPRPGPSRPAEKPPRPEAKSAQPADGWKGERPRS
EEDNELNLPNLAAAYSSILSSLGENPQRQGLLKTPWRAASAMQFFTKGYQETISDVLNDA
IFDEDHDEMVIVKDIDMFSMCEHHLVPFVGKVHIGYLPNKQVLGLSKLARIVEIYSRRLQ
VQERLTKQIAVAITEALRPAGVGVVVEATHMCMVMRGVQKMNSKTVTSTMLGVFREDPKT
REEFLTLIRS

• Folate and Pterine Biosynthesis (map00790 )

• GTP + H2O = formate + 7,8-dihydroneopterin 3'-triphosphate [RN:R00424]

• GTP_cyclohydroI (PF01227 )

• None

• None

ATGGAGAAGGGCCCTGTGCGGGCACCGGCGGAGAAGCCGCGGGGCGCCAGGTGCAGCAAT
GGGTTCCCCGAGCGGGATCCGCCGCGGCCCGGGCCCAGCAGGCCGGCGGAGAAGCCCCCG
CGGCCCGAGGCCAAGAGCGCGCAGCCCGCGGACGGCTGGAAGGGCGAGCGGCCCCGCAGC
GAGGAGGATAACGAGCTGAACCTCCCTAACCTGGCAGCCGCCTACTCGTCCATCCTGAGC
TCGCTGGGCGAGAACCCCCAGCGGCAAGGGCTGCTCAAGACGCCCTGGAGGGCGGCCTCG
GCCATGCAGTTCTTCACCAAGGGCTACCAGGAGACCATCTCAGATGTCCTAAACGATGCT
ATATTTGATGAAGATCATGATGAGATGGTGATTGTGAAGGACATAGACATGTTTTCCATG
TGTGAGCATCACTTGGTTCCATTTGTTGGAAAGGTCCATATTGGTTATCTTCCTAACAAG
CAAGTCCTTGGCCTCAGCAAACTTGCGAGGATTGTAGAAATCTATAGTAGAAGACTACAA
GTTCAGGAGCGCCTTACAAAACAAATTGCTGTAGCAATCACGGAAGCCTTGCGGCCTGCT
GGAGTCGGGGTAGTGGTTGAAGCAACACACATGTGTATGGTAATGCGAGGTGTACAGAAA
ATGAACAGCAAAACTGTGACCAGCACAATGTTGGGTGTGTTCCGGGAGGATCCAAAGACT
CGGGAAGAGTTCCTGACTCTCATTAGGAGCTGA

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2. Gutlich M, Jaeger E, Rucknagel KP, Werner T, Rodl W, Ziegler I, Bacher A: Human GTP cyclohydrolase I: only one out of three cDNA isoforms gives rise to the active enzyme. Biochem J. 1994 Aug 15;302 ( Pt 1):215-21. [PubMed ]
3. Nomura T, Ohtsuki M, Matsui S, Sumi-Ichinose C, Nomura H, Hagino Y, Iwase K, Ichinose H, Fujita K, Nagatsu T: Isolation of a full-length cDNA clone for human GTP cyclohydrolase I type 1 from pheochromocytoma. J Neural Transm Gen Sect. 1995;101(1-3):237-42. [PubMed ]
4. Golderer G, Werner ER, Heufler C, Strohmaier W, Grobner P, Werner-Felmayer G: GTP cyclohydrolase I mRNA: novel splice variants in the slime mould Physarum polycephalum and in human monocytes (THP-1) indicate conservation of mRNA processing. Biochem J. 2001 Apr 15;355(Pt 2):499-507. [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. Witter K, Werner T, Blusch JH, Schneider EM, Riess O, Ziegler I, Rodl W, Bacher A, Gutlich M: Cloning, sequencing and functional studies of the gene encoding human GTP cyclohydrolase I. Gene. 1996 Jun 1;171(2):285-90. [PubMed ]
7. Gutlich M, Schott K, Werner T, Bacher A, Ziegler I: Species and tissue specificity of mammalian GTP cyclohydrolase I messenger RNA. Biochim Biophys Acta. 1992 Dec 29;1171(2):133-40. [PubMed ]
8. Ichinose H, Ohye T, Matsuda Y, Hori T, Blau N, Burlina A, Rouse B, Matalon R, Fujita K, Nagatsu T: Characterization of mouse and human GTP cyclohydrolase I genes. Mutations in patients with GTP cyclohydrolase I deficiency. J Biol Chem. 1995 Apr 28;270(17):10062-71. [PubMed ]
9. Blau N, Niederwieser A: The application of 8-aminoguanosine triphosphate, a new inhibitor of GTP cyclohydrolase I, to the purification of the enzyme from human liver. Biochim Biophys Acta. 1986 Jan 15;880(1):26-31. [PubMed ]
10. Shen RS, Alam A, Zhang YX: Human liver GTP cyclohydrolase I: purification and some properties. Biochimie. 1989 Mar;71(3):343-9. [PubMed ]
11. Schoedon G, Redweik U, Curtius HC: Purification of GTP cyclohydrolase I from human liver and production of specific monoclonal antibodies. Eur J Biochem. 1989 Jan 2;178(3):627-34. [PubMed ]
12. Werner-Felmayer G, Werner ER, Fuchs D, Hausen A, Reibnegger G, Schmidt K, Weiss G, Wachter H: Pteridine biosynthesis in human endothelial cells. Impact on nitric oxide-mediated formation of cyclic GMP. J Biol Chem. 1993 Jan 25;268(3):1842-6. [PubMed ]
13. Thony B, Blau N: Mutations in the GTP cyclohydrolase I and 6-pyruvoyl-tetrahydropterin synthase genes. Hum Mutat. 1997;10(1):11-20. [PubMed ]
14. Katusic ZS, Stelter A, Milstien S: Cytokines stimulate GTP cyclohydrolase I gene expression in cultured human umbilical vein endothelial cells. Arterioscler Thromb Vasc Biol. 1998 Jan;18(1):27-32. [PubMed ]
15. Cai S, Alp NJ, McDonald D, Smith I, Kay J, Canevari L, Heales S, Channon KM: GTP cyclohydrolase I gene transfer augments intracellular tetrahydrobiopterin in human endothelial cells: effects on nitric oxide synthase activity, protein levels and dimerisation. Cardiovasc Res. 2002 Sep;55(4):838-49. [PubMed ]
16. Ohtsuki M, Shiraishi H, Kato T, Kuroda R, Tazawa M, Sumi-Ichinose C, Tada S, Udagawa Y, Itoh M, Hishida H, Ichinose H, Nagatsu T, Hagino Y, Nomura T: cAMP inhibits cytokine-induced biosynthesis of tetrahydrobiopterin in human umbilical vein endothelial cells. Life Sci. 2002 Mar 22;70(18):2187-98. [PubMed ]
17. Gesierich A, Niroomand F, Tiefenbacher CP: Role of human GTP cyclohydrolase I and its regulatory protein in tetrahydrobiopterin metabolism. Basic Res Cardiol. 2003 Mar;98(2):69-75. [PubMed ]
18. Shiraishi H, Kato T, Atsuta K, Sumi-Ichinose C, Ohtsuki M, Itoh M, Hishida H, Tada S, Udagawa Y, Nagatsu T, Hagino Y, Ichinose H, Nomura T: cGMP inhibits GTP cyclohydrolase I activity and biosynthesis of tetrahydrobiopterin in human umbilical vein endothelial cells. J Pharmacol Sci. 2003 Nov;93(3):265-71. [PubMed ]
19. Suzuki T, Kurita H, Ichinose H: GTP cyclohydrolase I utilizes metal-free GTP as its substrate. Eur J Biochem. 2004 Jan;271(2):349-55. [PubMed ]
20. Duan CL, Su Y, Zhao CL, Lu LL, Xu QY, Yang H: The assays of activities and function of TH, AADC, and GCH1 and their potential use in ex vivo gene therapy of PD. Brain Res Brain Res Protoc. 2005 Dec;16(1-3):37-43. [PubMed ]
21. Huang A, Zhang YY, Chen K, Hatakeyama K, Keaney JF Jr: Cytokine-stimulated GTP cyclohydrolase I expression in endothelial cells requires coordinated activation of nuclear factor-kappaB and Stat1/Stat3. Circ Res. 2005 Feb 4;96(2):164-71. Epub 2004 Dec 16. [PubMed ]
22. Kalivendi S, Hatakeyama K, Whitsett J, Konorev E, Kalyanaraman B, Vasquez-Vivar J: Changes in tetrahydrobiopterin levels in endothelial cells and adult cardiomyocytes induced by LPS and hydrogen peroxide--a role for GFRP? Free Radic Biol Med. 2005 Feb 15;38(4):481-91. [PubMed ]
23. Pandya MJ, Golderer G, Werner ER, Werner-Felmayer G: Interaction of human GTP cyclohydrolase I with its splice variants. Biochem J. 2006 Nov 15;400(1):75-80. [PubMed ]
24. Chavan B, Gillbro JM, Rokos H, Schallreuter KU: GTP cyclohydrolase feedback regulatory protein controls cofactor 6-tetrahydrobiopterin synthesis in the cytosol and in the nucleus of epidermal keratinocytes and melanocytes. J Invest Dermatol. 2006 Nov;126(11):2481-9. Epub 2006 Jun 15. [PubMed ]
25. Swick L, Kapatos G: A yeast 2-hybrid analysis of human GTP cyclohydrolase I protein interactions. J Neurochem. 2006 Jun;97(5):1447-55. [PubMed ]
26. Tegeder I, Costigan M, Griffin RS, Abele A, Belfer I, Schmidt H, Ehnert C, Nejim J, Marian C, Scholz J, Wu T, Allchorne A, Diatchenko L, Binshtok AM, Goldman D, Adolph J, Sama S, Atlas SJ, Carlezon WA, Parsegian A, Lotsch J, Fillingim RB, Maixner W, Geisslinger G, Max MB, Woolf CJ: GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med. 2006 Nov;12(11):1269-77. Epub 2006 Oct 22. [PubMed ]
27. Widder JD, Chen W, Li L, Dikalov S, Thony B, Hatakeyama K, Harrison DG: Regulation of tetrahydrobiopterin biosynthesis by shear stress. Circ Res. 2007 Oct 12;101(8):830-8. Epub 2007 Aug 17. [PubMed ]
28. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. [PubMed ]
29. Auerbach G, Herrmann A, Bracher A, Bader G, Gutlich M, Fischer M, Neukamm M, Garrido-Franco M, Richardson J, Nar H, Huber R, Bacher A: Zinc plays a key role in human and bacterial GTP cyclohydrolase I. Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13567-72. [PubMed ]
30. Ichinose H, Ohye T, Takahashi E, Seki N, Hori T, Segawa M, Nomura Y, Endo K, Tanaka H, Tsuji S, et al.: Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. Nat Genet. 1994 Nov;8(3):236-42. [PubMed ]
31. Ichinose H, Ohye T, Segawa M, Nomura Y, Endo K, Tanaka H, Tsuji S, Fujita K, Nagatsu T: GTP cyclohydrolase I gene in hereditary progressive dystonia with marked diurnal fluctuation. Neurosci Lett. 1995 Aug 18;196(1-2):5-8. [PubMed ]
32. Hirano M, Tamaru Y, Ito H, Matsumoto S, Imai T, Ueno S: Mutant GTP cyclohydrolase I mRNA levels contribute to dopa-responsive dystonia onset. Ann Neurol. 1996 Nov;40(5):796-8. [PubMed ]
33. Bandmann O, Nygaard TG, Surtees R, Marsden CD, Wood NW, Harding AE: Dopa-responsive dystonia in British patients: new mutations of the GTP-cyclohydrolase I gene and evidence for genetic heterogeneity. Hum Mol Genet. 1996 Mar;5(3):403-6. [PubMed ]
34. Beyer K, Lao-Villadoniga JI, Vecino-Bilbao B, Cacabelos R, De la Fuente-Fernandez R: A novel point mutation in the GTP cyclohydrolase I gene in a Spanish family with hereditary progressive and dopa responsive dystonia. J Neurol Neurosurg Psychiatry. 1997 Apr;62(4):420-1. [PubMed ]
35. Jarman PR, Bandmann O, Marsden CD, Wood NW: GTP cyclohydrolase I mutations in patients with dystonia responsive to anticholinergic drugs. J Neurol Neurosurg Psychiatry. 1997 Sep;63(3):304-8. [PubMed ]
36. Furukawa Y, Kish SJ, Bebin EM, Jacobson RD, Fryburg JS, Wilson WG, Shimadzu M, Hyland K, Trugman JM: Dystonia with motor delay in compound heterozygotes for GTP-cyclohydrolase I gene mutations. Ann Neurol. 1998 Jul;44(1):10-6. [PubMed ]
37. Bandmann O, Valente EM, Holmans P, Surtees RA, Walters JH, Wevers RA, Marsden CD, Wood NW: Dopa-responsive dystonia: a clinical and molecular genetic study. Ann Neurol. 1998 Oct;44(4):649-56. [PubMed ]
38. Hwu WL, Wang PJ, Hsiao KJ, Wang TR, Chiou YW, Lee YM: Dopa-responsive dystonia induced by a recessive GTP cyclohydrolase I mutation. Hum Genet. 1999 Sep;105(3):226-30. [PubMed ]
39. Suzuki T, Ohye T, Inagaki H, Nagatsu T, Ichinose H: Characterization of wild-type and mutants of recombinant human GTP cyclohydrolase I: relationship to etiology of dopa-responsive dystonia. J Neurochem. 1999 Dec;73(6):2510-6. [PubMed ]
40. Brique S, Destee A, Lambert JC, Mouroux V, Delacourte A, Amouyel P, Chartier-Harlin MC: A new GTP-cyclohydrolase I mutation in an unusual dopa-responsive dystonia, familial form. Neuroreport. 1999 Feb 25;10(3):487-91. [PubMed ]
41. Hirano M, Komure O, Ueno S: A novel missense mutant inactivates GTP cyclohydrolase I in dopa-responsive dystonia. Neurosci Lett. 1999 Feb 5;260(3):181-4. [PubMed ]
42. Tassin J, Durr A, Bonnet AM, Gil R, Vidailhet M, Lucking CB, Goas JY, Durif F, Abada M, Echenne B, Motte J, Lagueny A, Lacomblez L, Jedynak P, Bartholome B, Agid Y, Brice A: Levodopa-responsive dystonia. GTP cyclohydrolase I or parkin mutations? Brain. 2000 Jun;123 ( Pt 6):1112-21. [PubMed ]
43. Steinberger D, Korinthenberg R, Topka H, Berghauser M, Wedde R, Muller U: Dopa-responsive dystonia: mutation analysis of GCH1 and analysis of therapeutic doses of L-dopa. German Dystonia Study Group. Neurology. 2000 Dec 12;55(11):1735-7. [PubMed ]
44. Leuzzi V, Carducci C, Carducci C, Cardona F, Artiola C, Antonozzi I: Autosomal dominant GTP-CH deficiency presenting as a dopa-responsive myoclonus-dystonia syndrome. Neurology. 2002 Oct 22;59(8):1241-3. [PubMed ]
45. Ohta E, Funayama M, Ichinose H, Toyoshima I, Urano F, Matsuo M, Tomoko N, Yukihiko K, Yoshino S, Yokoyama H, Shimazu H, Maeda K, Hasegawa K, Obata F: Novel mutations in the guanosine triphosphate cyclohydrolase 1 gene associated with DYT5 dystonia. Arch Neurol. 2006 Nov;63(11):1605-10. [PubMed ]

1. Auerbach G, Nar H: The pathway from GTP to tetrahydrobiopterin: three-dimensional structures of GTP cyclohydrolase I and 6-pyruvoyl tetrahydropterin synthase. Biol Chem. 1997 Mar-Apr;378(3-4):185-92. [PubMed ]

1. GFRP
2. GTP cyclohydrolase I feedback regulatory protein
3. p35

MPYLLISTQIRMEVGPTMVGDEQSDPELMQHLGASKRRALGNNFYEYYVDDPPRIVLDKL
ERRGFRVLSMTGVGQTLVWCLHKE

• GFRP (PF06399 )

• None

• None

ATGCCCTACCTGCTCATCAGCACCCAGATCCGCATGGAGGTGGGCCCCACTATGGTGGGC
GATGAACAGTCGGATCCAGAGCTGATGCAGCATCTGGGGGCTTCAAAGAGAAGAGCCTTG
GGAAACAACTTTTATGAATACTACGTCGATGACCCTCCCCGCATAGTCCTGGACAAGCTG
GAACGCAGGGGCTTCCGTGTGCTGAGCATGACGGGGGTGGGCCAGACGCTGGTGTGGTGT
CTGCACAAGGAGTGA

1. 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 ]
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. Hochstrasser DF, Frutiger S, Paquet N, Bairoch A, Ravier F, Pasquali C, Sanchez JC, Tissot JD, Bjellqvist B, Vargas R, et al.: Human liver protein map: a reference database established by microsequencing and gel comparison. Electrophoresis. 1992 Dec;13(12):992-1001. [PubMed ]
4. Chavan B, Gillbro JM, Rokos H, Schallreuter KU: GTP cyclohydrolase feedback regulatory protein controls cofactor 6-tetrahydrobiopterin synthesis in the cytosol and in the nucleus of epidermal keratinocytes and melanocytes. J Invest Dermatol. 2006 Nov;126(11):2481-9. Epub 2006 Jun 15. [PubMed ]
5. Swick L, Kapatos G: A yeast 2-hybrid analysis of human GTP cyclohydrolase I protein interactions. J Neurochem. 2006 Jun;97(5):1447-55. [PubMed ]

1. Kapatos G, Hirayama K, Shimoji M, Milstien S: GTP cyclohydrolase I feedback regulatory protein is expressed in serotonin neurons and regulates tetrahydrobiopterin biosynthesis. J Neurochem. 1999 Feb;72(2):669-75. [PubMed ]

1. PHS
2. 4-alpha-hydroxy-tetrahydropterin dehydratase
3. Dimerization cofactor of hepatocyte nuclear factor 1-alpha
4. DCoH
5. Dimerization cofactor of HNF1
6. Phenylalanine hydroxylase-stimulating protein
7. Pterin carbinolamine dehydratase
8. PCD

MAGKAHRLSAEERDQLLPNLRAVGWNELEGRDAIFKQFHFKDFNRAFGFMTRVALQAEKL
DHHPEWFNVYNKVHITLSTHECAGLSERDINLASFIEQVAVSMT

• (6R)-6-(L-erythro-1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4a- hydroxypterin = (6R)-6-(L-erythro-1,2-dihydroxypropyl)-7,8-dihydro-6H-pterin + H2O [RN:R04734]

• Pterin_4a (PF01329 )

• None

• None

ATGGCTGGCAAAGCACACAGGCTGAGCGCTGAGGAGAGGGACCAGCTGCTGCCAAACCTG
AGGGCTGTGGGGTGGAATGAGCTGGAAGGCCGTGATGCCATCTTCAAGCAGTTTCATTTC
AAAGACTTCAACAGGGCCTTTGGGTTCATGACAAGAGTGGCCCTGCAGGCTGAGAAACTG
GACCACCATCCTGAATGGTTTAACGTGTACAACAAGGTCCACATCACGCTGAGCACCCAT
GAGTGTGCCGGCCTTTCAGAACGGGACATAAACCTGGCCAGCTTCATCGAACAAGTAGCA
GTGTCCATGACATAG

1. Mendel DB, Khavari PA, Conley PB, Graves MK, Hansen LP, Admon A, Crabtree GR: Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein. Science. 1991 Dec 20;254(5039):1762-7. [PubMed ]
2. Thony B, Neuheiser F, Blau N, Heizmann CW: Characterization of the human PCBD gene encoding the bifunctional protein pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor for the transcription factor HNF-1 alpha. Biochem Biophys Res Commun. 1995 May 25;210(3):966-73. [PubMed ]
3. Lei XD, Kaufman S: Characterization of expression of the gene for human pterin carbinolamine dehydratase/dimerization cofactor of HNF1. DNA Cell Biol. 1999 Mar;18(3):243-52. [PubMed ]
4. 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 ]
5. Hauer CR, Rebrin I, Thony B, Neuheiser F, Curtius HC, Hunziker P, Blau N, Ghisla S, Heizmann CW: Phenylalanine hydroxylase-stimulating protein/pterin-4 alpha-carbinolamine dehydratase from rat and human liver. Purification, characterization, and complete amino acid sequence. J Biol Chem. 1993 Mar 5;268(7):4828-31. [PubMed ]
6. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. Epub 2009 Jul 16. [PubMed ]
7. Citron BA, Kaufman S, Milstien S, Naylor EW, Greene CL, Davis MD: Mutation in the 4a-carbinolamine dehydratase gene leads to mild hyperphenylalaninemia with defective cofactor metabolism. Am J Hum Genet. 1993 Sep;53(3):768-74. [PubMed ]
8. Thony B, Neuheiser F, Kierat L, Rolland MO, Guibaud P, Schluter T, Germann R, Heidenreich RA, Duran M, de Klerk JB, Ayling JE, Blau N: Mutations in the pterin-4alpha-carbinolamine dehydratase (PCBD) gene cause a benign form of hyperphenylalaninemia. Hum Genet. 1998 Aug;103(2):162-7. [PubMed ]

1. Hirayama K, Kapatos G: Expression and regulation of rat 6-pyruvoyl tetrahydropterin synthase mRNA. Neurochem Int. 1995 Jun;26(6):601-6. [PubMed ]

MAAAAAAGEARRVLVYGGRGALGSRCVQAFRARNWWVASVDVVENEEASASIIVKMTDSF
TEQADQVTAEVGKLLGEEKVDAILCVAGGWAGGNAKSKSLFKNCDLMWKQSIWTSTISSH
LATKHLKEGGLLTLAGAKAALDGTPGMIGYGMAKGAVHQLCQSLAGKNSGMPPGAAAIAV
LPVTLDTPMNRKSMPEADFSSWTPLEFLVETFHDWITGKNRPSSGSLIQVVTTEGRTELT
PAYF

• None

• None

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

MACPWKFLFKTKFHQYAMNGEKDINNNVEKAPCATSSPVTQDDLQYHNLSKQQNESPQPL
VETGKKSPESLVKLDATPLSSPRHVRIKNWGSGMTFQDTLHHKAKGILTCRSKSCLGSIM
TPKSLTRGPRDKPTPPDELLPQAIEFVNQYYGSFKEAKIEEHLARVEAVTKEIETTGTYQ
LTGDELIFATKQAWRNAPRCIGRIQWSNLQVFDARSCSTAREMFEHICRHVRYSTNNGNI
RSAITVFPQRSDGKHDFRVWNAQLIRYAGYQMPDGSIRGDPANVEFTQLCIDLGWKPKYG
RFDVVPLVLQANGRDPELFEIPPDLVLEVAMEHPKYEWFRELELKWYALPAVANMLLEVG
GLEFPGCPFNGWYMGTEIGVRDFCDVQRYNILEEVGRRMGLETHKLASLWKDQAVVEINI
AVLHSFQKQNVTIMDHHSAAESFMKYMQNEYRSRGGCPADWIWLVPPMSGSITPVFHQEM
LNYVLSPFYYYQVEAWKTHVWQDEKRRPKRREIPLKVLVKAVLFACMLMRKTMASRVRVT
ILFATETGKSEALAWDLGALFSCAFNPKVVCMDKYRLSCLEEERLLLVVTSTFGNGDCPG
NGEKLKKSLFMLKELNNKFRYAVFGLGSSMYPRFCAFAHDIDQKLSHLGASQLTPMGEGD
ELSGQEDAFRSWAVQTFKAACETFDVRGKQHIQIPKLYTSNVTWDPHHYRLVQDSQPLDL
SKALSSMHAKNVFTMRLKSRQNLQSPTSSRATILVELSCEDGQGLNYLPGEHLGVCPGNQ
PALVQGILERVVDGPTPHQTVRLEALDESGSYWVSDKRLPPCSLSQALTYFLDITTPPTQ
LLLQKLAQVATEEPERQRLEALCQPSEYSKWKFTNSPTFLEVLEEFPSLRVSAGFLLSQL
PILKPRFYSISSSRDHTPTEIHLTVAVVTYHTRDGQGPLHHGVCSTWLNSLKPQDPVPCF
VRNASGFHLPEDPSHPCILIGPGTGIAPFRSFWQQRLHDSQHKGVRGGRMTLVFGCRRPD
EDHIYQEEMLEMAQKGVLHAVHTAYSRLPGKPKVYVQDILRQQLASEVLRVLHKEPGHLY
VCGDVRMARDVAHTLKQLVAAKLKLNEEQVEDYFFQLKSQKRYHEDIFGAVFPYEAKKDR
VAVQPSSLEMSAL

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

• None

• None

ATGGCCTGTCCTTGGAAATTTCTGTTCAAGACCAAATTCCACCAGTATGCAATGAATGGG
GAAAAAGACATCAACAACAATGTGGAGAAAGCCCCCTGTGCCACCTCCAGTCCAGTGACA
CAGGATGACCTTCAGTATCACAACCTCAGCAAGCAGCAGAATGAGTCCCCGCAGCCCCTC
GTGGAGACGGGAAAGAAGTCTCCAGAATCTCTGGTCAAGCTGGATGCAACCCCATTGTCC
TCCCCACGGCATGTGAGGATCAAAAACTGGGGCAGCGGGATGACTTTCCAAGACACACTT
CACCATAAGGCCAAAGGGATTTTAACTTGCAGGTCCAAATCTTGCCTGGGGTCCATTATG
ACTCCCAAAAGTTTGACCAGAGGACCCAGGGACAAGCCTACCCCTCCAGATGAGCTTCTA
CCTCAAGCTATCGAATTTGTCAACCAATATTACGGCTCCTTCAAAGAGGCAAAAATAGAG
GAACATCTGGCCAGGGTGGAAGCGGTAACAAAGGAGATAGAAACAACAGGAACCTACCAA
CTGACGGGAGATGAGCTCATCTTCGCCACCAAGCAGGCCTGGCGCAATGCCCCACGCTGC
ATTGGGAGGATCCAGTGGTCCAACCTGCAGGTCTTCGATGCCCGCAGCTGTTCCACTGCC
CGGGAAATGTTTGAACACATCTGCAGACACGTGCGTTACTCCACCAACAATGGCAACATC
AGGTCGGCCATCACCGTGTTCCCCCAGCGGAGTGATGGCAAGCACGACTTCCGGGTGTGG
AATGCTCAGCTCATCCGCTATGCTGGCTACCAGATGCCAGATGGCAGCATCAGAGGGGAC
CCTGCCAACGTGGAATTCACTCAGCTGTGCATCGACCTGGGCTGGAAGCCCAAGTACGGC
CGCTTCGATGTGGTCCCCCTGGTCCTGCAGGCCAATGGCCGTGACCCTGAGCTCTTCGAA
ATCCCACCTGACCTTGTGCTTGAGGTGGCCATGGAACATCCCAAATACGAGTGGTTTCGG
GAACTGGAGCTAAAGTGGTACGCCCTGCCTGCAGTGGCCAACATGCTGCTTGAGGTGGGC
GGCCTGGAGTTCCCAGGGTGCCCCTTCAATGGCTGGTACATGGGCACAGAGATCGGAGTC
CGGGACTTCTGTGACGTCCAGCGCTACAACATCCTGGAGGAAGTGGGCAGGAGAATGGGC
CTGGAAACGCACAAGCTGGCCTCGCTCTGGAAAGACCAGGCTGTCGTTGAGATCAACATT
GCTGTGCTCCATAGTTTCCAGAAGCAGAATGTGACCATCATGGACCACCACTCGGCTGCA
GAATCCTTCATGAAGTACATGCAGAATGAATACCGGTCCCGTGGGGGCTGCCCGGCAGAC
TGGATTTGGCTGGTCCCTCCCATGTCTGGGAGCATCACCCCCGTGTTTCACCAGGAGATG
CTGAACTACGTCCTGTCCCCTTTCTACTACTATCAGGTAGAGGCCTGGAAAACCCATGTC
TGGCAGGACGAGAAGCGGAGACCCAAGAGAAGAGAGATTCCATTGAAAGTCTTGGTCAAA
GCTGTGCTCTTTGCCTGTATGCTGATGCGCAAGACAATGGCGTCCCGAGTCAGAGTCACC
ATCCTCTTTGCGACAGAGACAGGAAAATCAGAGGCGCTGGCCTGGGACCTGGGGGCCTTA
TTCAGCTGTGCCTTCAACCCCAAGGTTGTCTGCATGGATAAGTACAGGCTGAGCTGCCTG
GAGGAGGAACGGCTGCTGTTGGTGGTGACCAGTACGTTTGGCAATGGAGACTGCCCTGGC
AATGGAGAGAAACTGAAGAAATCGCTCTTCATGCTGAAAGAGCTCAACAACAAATTCAGG
TACGCTGTGTTTGGCCTCGGCTCCAGCATGTACCCTCGGTTCTGCGCCTTTGCTCATGAC
ATTGATCAGAAGCTGTCCCACCTGGGGGCCTCTCAGCTCACCCCGATGGGAGAAGGGGAT
GAGCTCAGTGGGCAGGAGGACGCCTTCCGCAGCTGGGCCGTGCAAACCTTCAAGGCAGCC
TGTGAGACGTTTGATGTCCGAGGCAAACAGCACATTCAGATCCCCAAGCTCTACACCTCC
AATGTGACCTGGGACCCGCACCACTACAGGCTCGTGCAGGACTCACAGCCTTTGGACCTC
AGCAAAGCCCTCAGCAGCATGCATGCCAAGAACGTGTTCACCATGAGGCTCAAATCTCGG
CAGAATCTACAAAGTCCGACATCCAGCCGTGCCACCATCCTGGTGGAACTCTCCTGTGAG
GATGGCCAAGGCCTGAACTACCTGCCGGGGGAGCACCTTGGGGTTTGCCCAGGCAACCAG
CCGGCCCTGGTCCAAGGCATCCTGGAGCGAGTGGTGGATGGCCCCACACCCCACCAGACA
GTGCGCCTGGAGGCCCTGGATGAGAGTGGCAGCTACTGGGTCAGTGACAAGAGGCTGCCC
CCCTGCTCACTCAGCCAGGCCCTCACCTACTTCCTGGACATCACCACACCCCCAACCCAG
CTGCTGCTCCAAAAGCTGGCCCAGGTGGCCACAGAAGAGCCTGAGAGACAGAGGCTGGAG
GCCCTGTGCCAGCCCTCAGAGTACAGCAAGTGGAAGTTCACCAACAGCCCCACATTCCTG
GAGGTGCTAGAGGAGTTCCCGTCCCTGCGGGTGTCTGCTGGCTTCCTGCTTTCCCAGCTC
CCCATTCTGAAGCCCAGGTTCTACTCCATCAGCTCCTCCCGGGATCACACGCCCACGGAG
ATCCACCTGACTGTGGCCGTGGTCACCTACCACACCCGAGATGGCCAGGGTCCCCTGCAC
CACGGCGTCTGCAGCACATGGCTCAACAGCCTGAAGCCCCAAGACCCAGTGCCCTGCTTT
GTGCGGAATGCCAGCGGCTTCCACCTCCCCGAGGATCCCTCCCATCCTTGCATCCTCATC
GGGCCTGGCACAGGCATCGCGCCCTTCCGCAGTTTCTGGCAGCAACGGCTCCATGACTCC
CAGCACAAGGGAGTGCGGGGAGGCCGCATGACCTTGGTGTTTGGGTGCCGCCGCCCAGAT
GAGGACCACATCTACCAGGAGGAGATGCTGGAGATGGCCCAGAAGGGGGTGCTGCATGCG
GTGCACACAGCCTATTCCCGCCTGCCTGGCAAGCCCAAGGTCTATGTTCAGGACATCCTG
CGGCAGCAGCTGGCCAGCGAGGTGCTCCGTGTGCTCCACAAGGAGCCAGGCCACCTCTAT
GTTTGCGGGGATGTGCGCATGGCCCGGGACGTGGCCCACACCCTGAAGCAGCTGGTGGCT
GCCAAGCTGAAATTGAATGAGGAGCAGGTCGAGGACTATTTCTTTCAGCTCAAGAGCCAG
AAGCGCTATCACGAAGATATCTTTGGTGCTGTATTTCCTTACGAGGCGAAGAAGGACAGG
GTGGCGGTGCAGCCCAGCAGCCTGGAGATGTCAGCGCTCTGA

1. Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA: Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16899-903. Epub 2002 Dec 11. [PubMed ]

GILTCRSKSCLGSIMTPKSLTRGPRDKPTPPDELLPQAIEFVNQYYGSFKEAKIEEHLA

• NO_synthase (PF02898 )

• None

• None

AAGGGATTTTAACTTGCAGGTCCAAATCTTGCCTGGGGTCCATTATGACTCCCAAAAGTT
TGACCAGAGGACCCAGGGACAAGCCTACCCCTCCAGATGAGCTTCTACCTCAAGCTATCG
AATTTGTCAACCAATATTACGGCTCCTTCAAAGAGGCAAAAATAGAGGAACATCTGGCCA

1. Mannick JB, Asano K, Izumi K, Kieff E, Stamler JS: Nitric oxide produced by human B lymphocytes inhibits apoptosis and Epstein-Barr virus reactivation. Cell. 1994 Dec 30;79(7):1137-46. [PubMed ]

1. Hepatocyte NOS
2. HEP-NOS
3. Inducible NO synthase
4. Inducible NOS
5. iNOS
6. NOS type II

MACPWKFLFKTKFHQYAMNGEKDINNNVEKAPCATSSPVTQDDLQYHNLSKQQNESPQPL
VETGKKSPESLVKLDATPLSSPRHVRIKNWGSGMTFQDTLHHKAKGILTCRSKSCLGSIM
TPKSLTRGPRDKPTPPDELLPQAIEFVNQYYGSFKEAKIEEHLARVEAVTKEIETTGTYQ
LTGDELIFATKQAWRNAPRCIGRIQWSNLQVFDARSCSTAREMFEHICRHVRYSTNNGNI
RSAITVFPQRSDGKHDFRVWNAQLIRYAGYQMPDGSIRGDPANVEFTQLCIDLGWKPKYG
RFDVVPLVLQANGRDPELFEIPPDLVLEVAMEHPKYEWFRELELKWYALPAVANMLLEVG
GLEFPGCPFNGWYMGTEIGVRDFCDVQRYNILEEVGRRMGLETHKLASLWKDQAVVEINI
AVLHSFQKQNVTIMDHHSAAESFMKYMQNEYRSRGGCPADWIWLVPPMSGSITPVFHQEM
LNYVLSPFYYYQVEAWKTHVWQDEKRRPKRREIPLKVLVKAVLFACMLMRKTMASRVRVT
ILFATETGKSEALAWDLGALFSCAFNPKVVCMDKYRLSCLEEERLLLVVTSTFGNGDCPG
NGEKLKKSLFMLKELNNKFRYAVFGLGSSMYPRFCAFAHDIDQKLSHLGASQLTPMGEGD
ELSGQEDAFRSWAVQTFKAACETFDVRGKQHIQIPKLYTSNVTWDPHHYRLVQDSQPLDL
SKALSSMHAKNVFTMRLKSRQNLQSPTSSRATILVELSCEDGQGLNYLPGEHLGVCPGNQ
PALVQGILERVVDGPTPHQTVRLEALDESGSYWVSDKRLPPCSLSQALTYFLDITTPPTQ
LLLQKLAQVATEEPERQRLEALCQPSEYSKWKFTNSPTFLEVLEEFPSLRVSAGFLLSQL
PILKPRFYSISSSRDHTPTEIHLTVAVVTYHTRDGQGPLHHGVCSTWLNSLKPQDPVPCF
VRNASGFHLPEDPSHPCILIGPGTGIAPFRSFWQQRLHDSQHKGVRGGRMTLVFGCRRPD
EDHIYQEEMLEMAQKGVLHAVHTAYSRLPGKPKVYVQDILRQQLASEVLRVLHKEPGHLY
VCGDVRMARDVAHTLKQLVAAKLKLNEEQVEDYFFQLKSQKRYHEDIFGAVFPYEAKKDR
VAVQPSSLEMSAL

• 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

ATGGCCTGTCCTTGGAAATTTCTGTTCAAGACCAAATTCCACCAGTATGCAATGAATGGG
GAAAAAGACATCAACAACAATGTGGAGAAAGCCCCCTGTGCCACCTCCAGTCCAGTGACA
CAGGATGACCTTCAGTATCACAACCTCAGCAAGCAGCAGAATGAGTCCCCGCAGCCCCTC
GTGGAGACGGGAAAGAAGTCTCCAGAATCTCTGGTCAAGCTGGATGCAACCCCATTGTCC
TCCCCACGGCATGTGAGGATCAAAAACTGGGGCAGCGGGATGACTTTCCAAGACACACTT
CACCATAAGGCCAAAGGGATTTTAACTTGCAGGTCCAAATCTTGCCTGGGGTCCATTATG
ACTCCCAAAAGTTTGACCAGAGGACCCAGGGACAAGCCTACCCCTCCAGATGAGCTTCTA
CCTCAAGCTATCGAATTTGTCAACCAATATTACGGCTCCTTCAAAGAGGCAAAAATAGAG
GAACATCTGGCCAGGGTGGAAGCGGTAACAAAGGAGATAGAAACAACAGGAACCTACCAA
CTGACGGGAGATGAGCTCATCTTCGCCACCAAGCAGGCCTGGCGCAATGCCCCACGCTGC
ATTGGGAGGATCCAGTGGTCCAACCTGCAGGTCTTCGATGCCCGCAGCTGTTCCACTGCC
CGGGAAATGTTTGAACACATCTGCAGACACGTGCGTTACTCCACCAACAATGGCAACATC
AGGTCGGCCATCACCGTGTTCCCCCAGCGGAGTGATGGCAAGCACGACTTCCGGGTGTGG
AATGCTCAGCTCATCCGCTATGCTGGCTACCAGATGCCAGATGGCAGCATCAGAGGGGAC
CCTGCCAACGTGGAATTCACTCAGCTGTGCATCGACCTGGGCTGGAAGCCCAAGTACGGC
CGCTTCGATGTGGTCCCCCTGGTCCTGCAGGCCAATGGCCGTGACCCTGAGCTCTTCGAA
ATCCCACCTGACCTTGTGCTTGAGGTGGCCATGGAACATCCCAAATACGAGTGGTTTCGG
GAACTGGAGCTAAAGTGGTACGCCCTGCCTGCAGTGGCCAACATGCTGCTTGAGGTGGGC
GGCCTGGAGTTCCCAGGGTGCCCCTTCAATGGCTGGTACATGGGCACAGAGATCGGAGTC
CGGGACTTCTGTGACGTCCAGCGCTACAACATCCTGGAGGAAGTGGGCAGGAGAATGGGC
CTGGAAACGCACAAGCTGGCCTCGCTCTGGAAAGACCAGGCTGTCGTTGAGATCAACATT
GCTGTGCTCCATAGTTTCCAGAAGCAGAATGTGACCATCATGGACCACCACTCGGCTGCA
GAATCCTTCATGAAGTACATGCAGAATGAATACCGGTCCCGTGGGGGCTGCCCGGCAGAC
TGGATTTGGCTGGTCCCTCCCATGTCTGGGAGCATCACCCCCGTGTTTCACCAGGAGATG
CTGAACTACGTCCTGTCCCCTTTCTACTACTATCAGGTAGAGGCCTGGAAAACCCATGTC
TGGCAGGACGAGAAGCGGAGACCCAAGAGAAGAGAGATTCCATTGAAAGTCTTGGTCAAA
GCTGTGCTCTTTGCCTGTATGCTGATGCGCAAGACAATGGCGTCCCGAGTCAGAGTCACC
ATCCTCTTTGCGACAGAGACAGGAAAATCAGAGGCGCTGGCCTGGGACCTGGGGGCCTTA
TTCAGCTGTGCCTTCAACCCCAAGGTTGTCTGCATGGATAAGTACAGGCTGAGCTGCCTG
GAGGAGGAACGGCTGCTGTTGGTGGTGACCAGTACGTTTGGCAATGGAGACTGCCCTGGC
AATGGAGAGAAACTGAAGAAATCGCTCTTCATGCTGAAAGAGCTCAACAACAAATTCAGG
TACGCTGTGTTTGGCCTCGGCTCCAGCATGTACCCTCGGTTCTGCGCCTTTGCTCATGAC
ATTGATCAGAAGCTGTCCCACCTGGGGGCCTCTCAGCTCACCCCGATGGGAGAAGGGGAT
GAGCTCAGTGGGCAGGAGGACGCCTTCCGCAGCTGGGCCGTGCAAACCTTCAAGGCAGCC
TGTGAGACGTTTGATGTCCGAGGCAAACAGCACATTCAGATCCCCAAGCTCTACACCTCC
AATGTGACCTGGGACCCGCACCACTACAGGCTCGTGCAGGACTCACAGCCTTTGGACCTC
AGCAAAGCCCTCAGCAGCATGCATGCCAAGAACGTGTTCACCATGAGGCTCAAATCTCGG
CAGAATCTACAAAGTCCGACATCCAGCCGTGCCACCATCCTGGTGGAACTCTCCTGTGAG
GATGGCCAAGGCCTGAACTACCTGCCGGGGGAGCACCTTGGGGTTTGCCCAGGCAACCAG
CCGGCCCTGGTCCAAGGTATCCTGGAGCGAGTGGTGGATGGCCCCACACCCCACCAGACA
GTGCGCCTGGAGGCCCTGGATGAGAGTGGCAGCTACTGGGTCAGTGACAAGAGGCTGCCC
CCCTGCTCACTCAGCCAGGCCCTCACCTACTTCCTGGACATCACCACACCCCCAACCCAG
CTGCTGCTCCAAAAGCTGGCCCAGGTGGCCACAGAAGAGCCTGAGAGACAGAGGCTGGAG
GCCCTGTGCCAGCCCTCAGAGTACAGCAAGTGGAAGTTCACCAACAGCCCCACATTCCTG
GAGGTGCTAGAGGAGTTCCCGTCCCTGCGGGTGTCTGCTGGCTTCCTGCTTTCCCAGCTC
CCCATTCTGAAGCCCAGGTTCTACTCCATCAGCTCCTCCCGGGATCACACGCCCACAGAG
ATCCACCTGACTGTGGCCGTGGTCACCTACCACACCCGAGATGGCCAGGGTCCCCTGCAC
CACGGCGTCTGCAGCACATGGCTCAACAGCCTGAAGCCCCAAGACCCAGTGCCCTGCTTT
GTGCGGAATGCCAGCGGCTTCCACCTCCCCGAGGATCCCTCCCATCCTTGCATCCTCATC
GGGCCTGGCACAGGCATCGCGCCCTTCCGCAGTTTCTGGCAGCAACGGCTCCATGACTCC
CAGCACAAGGGAGTGCGGGGAGGCCGCATGACCTTGGTGTTTGGGTGCCGCCGCCCAGAT
GAGGACCACATCTACCAGGAGGAGATGCTGGAGATGGCCCAGAAGGGGGTGCTGCATGCG
GTGCACACAGCCTATTCCCGCCTGCCTGGCAAGCCCAAGGTCTATGTTCAGGACATCCTG
CGGCAGCAGCTGGCCAGCGAGGTGCTCCGTGTGCTCCACAAGGAGCCAGGCCACCTCTAT
GTTTGCGGGGATGTGCGCATGGCCCGGGACGTGGCCCACACCCTGAAGCAGCTGGTGGCT
GCCAAGCTGAAATTGAATGAGGAGCAGGTCGAGGACTATTTCTTTCAGCTCAAGAGCCAG
AAGCGCTATCACGAAGATATCTTTGGTGCTGTATTTCCTTACGAGGCGAAGAAGGACAGG
GTGGCGGTGCAGCCCAGCAGCCTGGAGATGTCAGCGCTCTGA

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