1. (protoporphyrinato)iron
2. Ferroheme
3. Ferroheme b
4. Ferroprotoheme
5. Ferroprotoporphyrin
6. Ferroprotoporphyrin IX
7. Ferrous protoheme
8. Ferrous protoheme IX
9. Haem
10. Hem
11. Heme
12. Iron protoporphyrin
13. Iron protoporphyrin IX
14. Iron(II) protoporphyrin IX
15. Protoferroheme
16. Protohaem
17. Protoheme
18. Protoheme IX
19. Reduced hematin

• Cytoplasm
• Extracellular
• mitochondria

1. Ono F, Sharma BK, Smith CC, Burnett JW, Aurelian L: CD34+ cells in the peripheral blood transport herpes simplex virus DNA fragments to the skin of patients with erythema multiforme (HAEM). J Invest Dermatol. 2005 Jun;124(6):1215-24. [PubMed ]
2. Allhorn M, Lundqvist K, Schmidtchen A, Akerstrom B: Heme-scavenging role of alpha1-microglobulin in chronic ulcers. J Invest Dermatol. 2003 Sep;121(3):640-6. [PubMed ]
3. Walczyk T, von Blanckenburg F: Natural iron isotope variations in human blood. Science. 2002 Mar 15;295(5562):2065-6. [PubMed ]
4. Kuhnel A, Gross U, Doss MO: Hereditary coproporphyria in Germany: clinical-biochemical studies in 53 patients. Clin Biochem. 2000 Aug;33(6):465-73. [PubMed ]
5. Zhang JP, Normark S: Induction of gene expression in Escherichia coli after pilus-mediated adherence. Science. 1996 Aug 30;273(5279):1234-6. [PubMed ]
6. Taylor TD, Litt M, Kramer P, Pandolfo M, Angelini L, Nardocci N, Davis S, Pineda M, Hattori H, Flett PJ, Cilio MR, Bertini E, Hayflick SJ: Homozygosity mapping of Hallervorden-Spatz syndrome to chromosome 20p12.3-p13. Nat Genet. 1996 Dec;14(4):479-81. [PubMed ]
7. Park KK, Park JH, Jung YJ, Chung WY: Inhibitory effects of chlorophyllin, hemin and tetrakis(4-benzoic acid)porphyrin on oxidative DNA damage and mouse skin inflammation induced by 12-O-tetradecanoylphorbol-13-acetate as a possible anti-tumor promoting mechanism. Mutat Res. 2003 Dec 9;542(1-2):89-97. [PubMed ]
8. Wikipedia

1. 5-aminolevulinate synthase, erythroid-specific, mitochondrial precursor
2. 5-aminolevulinate synthase, nonspecific, mitochondrial precursor
3. Succinate dehydrogenase cytochrome b560 subunit, mitochondrial precursor
4. Aldehyde oxidase
5. Heme oxygenase 2
6. Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial precursor
7. NADPH--cytochrome P450 reductase
8. Heme oxygenase 1
9. Uroporphyrinogen decarboxylase
10. Coproporphyrinogen III oxidase, mitochondrial precursor
11. Cytochrome P450 51A1
12. Thyroid peroxidase precursor
13. Lactoperoxidase precursor
14. Myeloperoxidase precursor
15. Eosinophil peroxidase precursor
16. Uroporphyrinogen-III synthase
17. Porphobilinogen deaminase
18. Cytochrome P450 4A11 precursor
19. Indoleamine 2,3-dioxygenase
20. Tryptophan 2,3-dioxygenase
21. Cytochrome P450 11B1, mitochondrial precursor
22. Cytochrome P450 7A1
23. Cytochrome P450 11B2, mitochondrial precursor
24. Cytochrome P450 21
25. Biliverdin reductase A precursor
26. Flavin reductase
27. Cytochrome P450 11A1, mitochondrial precursor
28. Cystathionine beta-synthase
29. Nitric oxide synthase, inducible
30. Nitric-oxide synthase, brain
31. Nitric-oxide synthase, endothelial
32. Succinyl-CoA ligase [ADP-forming] beta-chain, mitochondrial precursor
33. Prostaglandin G/H synthase 2 precursor
34. Prostaglandin G/H synthase 1 precursor
35. Ubiquinol-cytochrome c reductase complex 7.2 kDa protein
36. Cytochrome b
37. Cytochrome c1 heme protein, mitochondrial precursor
38. Ubiquinol-cytochrome c reductase complex 11 kDa protein, mitochondrial precursor
39. Cytochrome P450 4F2
40. Cytochrome P450 4F3
41. Cytochrome P450 3A4
42. Protoporphyrinogen oxidase
43. Cytochrome P450 2C9
44. Cytochrome P450 27, mitochondrial precursor
45. Cytochrome P450 2C19
46. 25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial precursor
47. Cytochrome P450 17A1
48. Sulfite oxidase, mitochondrial precursor
49. Ferrochelatase, mitochondrial precursor
50. Delta-aminolevulinic acid dehydratase
51. Guanylate cyclase soluble subunit beta-1
52. Guanylate cyclase soluble subunit beta-2
53. Prostacyclin synthase
54. Cytochrome P450 2E1
55. Cytochrome P450 4F11
56. Cytochrome P450 3A43
57. Cytochrome P450 1B1
58. Cytochrome P450 2D6
59. Cytochrome P450 2C18
60. Cytochrome P450 4F12
61. Cytochrome P450 2F1
62. Cytochrome P450 4X1
63. Cytochrome P450 2B6
64. Cytochrome P450 3A5
65. Cytochrome P450 1A1
66. Cytochrome P450 2A13
67. Cytochrome P450 3A7
68. Cytochrome P450 4B1
69. Cytochrome P450 4Z1
70. Cytochrome P450 1A2
71. Cytochrome P450 19A1
72. Cytochrome P450 2C8
73. Cytochrome P450 2S1
74. Cytochrome P450 4F8
75. Cytochrome P450 2J2
76. Cytochrome P450 2A7
77. Cytochrome P450 2A6
78. Catalase
79. Thromboxane-A synthase
80. Hemoglobin subunit beta
81. Hemoglobin subunit alpha
82. Hemoglobin subunit gamma-1
83. Hemopexin precursor
84. Cytochrome P450 7B1
85. Cytochrome c oxidase subunit 1
86. Protoheme IX farnesyltransferase, mitochondrial precursor
87. Hereditary hemochromatosis protein precursor
88. AMBP protein precursor [Contains: Alpha-1-microglobulin
89. Calcium-activated potassium channel subunit alpha 1
90. Cytochrome b561 domain-containing protein 2
91. Cytochrome b561
92. Cytochrome c
93. Cytochrome b-245 heavy chain
94. Cytochrome c-type heme lyase
95. Cytochrome P450 24A1, mitochondrial precursor
96. PR domain zinc finger protein 2
97. Cytochrome P450 26A1
98. Serotransferrin precursor
99. Feline leukemia virus subgroup C receptor-related protein 1
100. Myoglobin
101. Transcription factor NF-E2 45 kDa subunit
102. Cytochrome b-245 light chain
103. BC269730_2
104. Cytochrome P450 2R1
105. Translocator protein
106. Histidine-rich glycoprotein precursor
107. Hemoglobin subunit gamma-2
108. Cytochrome b5
109. Frataxin, mitochondrial precursor
110. Heme carrier protein 1
111. Hypothetical protein CYBRD1
112. Cytochrome c oxidase subunit 5A, mitochondrial precursor
113. Delta-6 fatty acid desaturase
114. Cytochrome P450 46A1
115. Cytochrome P450 39A1
116. Cytochrome P450 8B1
117. Cytochrome b5 reductase 4
118. Cytochrome P450 4A22 [Precursor]
119. cDNA FLJ76435, highly similar to Homo sapiens cytochrome P450, family 11, subfamily A, polypeptide 1
120. cDNA FLJ76483, highly similar to Homo sapiens ferrochelatase
121. Indoleamine 2,3-dioxygenase-like protein 1
122. Cytochrome P450, family 1, subfamily A, polypeptide 1
123. cDNA FLJ75236, highly similar to Human tryptophan oxygenase
124. Scavenger receptor cysteine-rich type 1 protein M130 precursor
125. NADPH oxidase 5
126. Peroxidasin homolog
127. Cardiac peroxidase
128. Metalloreductase STEAP3
129. NADPH oxidase homolog 1
130. NADPH oxidase 4
131. Metalloreductase STEAP1
132. Metalloreductase STEAP2
133. Metalloreductase STEAP4
134. Mitochondrial ATP-binding cassette sub-family B member 6
135. ATP-binding cassette sub-family B member 7, mitochondrial precursor
136. ATP-binding cassette sub-family B member 10, mitochondrial precursor
137. Cytochrome P450 27C1
138. CDNA FLJ45208 fis, clone BRCAN2015402, highly similar to Cytochrome P450 2G1
139. Cytochrome b561 domain-containing protein 1
140. Cytochrome b5 domain-containing protein 1
141. Cytochrome b5 domain-containing protein 2
142. Hsp90 co-chaperone Cdc37
143. Cytochrome c oxidase assembly protein COX15 homolog
144. Cytochrome P450 20A1
145. Cytochrome P450 26B1
146. Cytochrome P450 26C1
147. Cytochrome P450 2U1
148. Cytochrome P450 2W1
149. Cytochrome P450 4F22
150. Cytochrome P450 4V2
151. CDNA FLJ40054 fis, clone TBAES2000315, weakly similar to CYTOCHROME P450 4A1
152. CDNA PSEC0259 fis, clone NT2RP3003789, weakly similar to CYTOCHROME B561
153. Cytochrome b5 type B precursor
154. Uncharacterized protein ENSP00000382267
155. Cytoglobin
156. Eukaryotic translation initiation factor 2-alpha kinase 1
157. Fatty acid 2-hydroxylase
158. Uncharacterized protein ENSP00000382110
159. Fatty acid desaturase 3
160. Ferric-chelate reductase 1
161. Hemoglobin subunit theta-1
162. Hemoglobin subunit zeta
163. Hemoglobin subunit delta
164. Hemoglobin subunit epsilon
165. Hemoglobin subunit mu
166. Heme-binding protein 1
167. Heme-binding protein 2
168. Probable E3 ubiquitin-protein ligase HERC2
169. FLJ20489 protein
170. Mitoferrin-1
171. Mitoferrin-2
172. Neudesin precursor
173. Nuclear factor erythroid 2-related factor 1
174. Neuroglobin
175. Nuclear respiratory factor 1
176. Membrane-associated progesterone receptor component 1
177. Membrane-associated progesterone receptor component 2
178. Radical S-adenosyl methionine domain-containing protein 2
179. Cytochrome P450, family 21, subfamily A, polypeptide 2
180. Cytochrome P450, family 3, subfamily A, polypeptide 7
181. Cytochrome P450, family 2, subfamily D, polypeptide 6 (Cytochrome P450 2D6)
182. Cytochrome P450, family 3, subfamily A, polypeptide 5 (Cytochrome P450, family 3, subfamily A, polypeptide 5, isoform CRA_a)
183. Cytochrome P450, family 4, subfamily X, polypeptide 1 (Cytochrome P450, family 4, subfamily X, polypeptide 1, isoform CRA_b) (Cytochrome P450)
184. Putative uncharacterized protein CYP3A43 (Cytochrome P450, family 3, subfamily A, polypeptide 43, isoform CRA_e)
185. Myeloperoxidase (Myeloperoxidase, isoform CRA_a)
186. cDNA FLJ76595, highly similar to Homo sapiens peroxiredoxin 6 (PRDX6), mRNA (Peroxiredoxin 6, isoform CRA_a)
187. Uncharacterized protein ZNF554 (Zinc finger protein 554, isoform CRA_c)
188. Mitochondrial cytochrome P450, family 11, subfamily B, polypeptide 2 (Cytochrome P450, family 11, subfamily B, polypeptide 2)
189. cDNA, FLJ93424, highly similar to Homo sapiens cytochrome P450, family 2, subfamily A, polypeptide 6 (CYP2A6), mRNA (Cytochrome P450, family 2, subfamily A, polypeptide 6)
190. cDNA, FLJ93938, Homo sapiens cytochrome P450, family 2, subfamily C, polypeptide 18(CYP2C18), mRNA (HCG39167, isoform CRA_b)
191. cDNA FLJ40496 fis, clone TESTI2044788, highly similar to CYTOCHROME C-TYPE HEME LYASE (EC 4.4.1.17)

1. 5-aminolevulinic acid synthase
2. Delta- aminolevulinate synthase
3. Delta-ALA synthetase
4. ALAS-E

MVTAAMLLQCCPVLARGPTSLLGKVVKTHQFLFGIGRCPILATQGPNCSQIHLKATKAGG
DSPSWAKGHCPFMLSELQDGKSKIVQKAAPEVQEDVKAFKTDLPSSLVSVSLRKPFSGPQ
EQEQISGKVTHLIQNNMPGNYVFSYDQFFRDKIMEKKQDHTYRVFKTVNRWADAYPFAQH
FSEASVASKDVSVWCSNDYLGMSRHPQVLQATQETLQRHGAGAGGTRNISGTSKFHVELE
QELAELHQKDSALLFSSCFVANDSTLFTLAKILPGCEIYSDAGNHASMIQGIRNSGAAKF
VFRHNDPDHLKKLLEKSNPKIPKIVAFETVHSMDGAICPLEELCDVSHQYGALTFVDEVH
AVGLYGSRGAGIGERDGIMHKIDIISGTLGKAFGCVGGYIASTRDLVDMVRSYAAGFIFT
TSLPPMVLSGALESVRLLKGEEGQALRRAHQRNVKHMRQLLMDRGLPVIPCPSHIIPIRV
GNAALNSKLCDLLLSKHGIYVQAINYPTVPRGEELLRLAPSPHHSPQMMEDFVEKLLLAW
TAVGLPLQDVSVAACNFCRRPVHFELMSEWERSYFGNMGPQYVTTYA

• Glycine, Serine and Threonine Metabolism (map00260 )

• succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2

• Aminotran_1_2 (PF00155 )
• Preseq_ALAS (PF09029 )

• 1-15

ATGCTGCTACAGTGCTGCCCAGTGCTTGCCCGGGGCCCCACAAGCCTCCTAGGCAAGGTG
GTTAAGACTCACCAGTTCCTGTTTGGTATTGGACGCTGTCCCATCCTGGCTACCCAAGGA
CCAAACTGTTCTCAAATCCACCTTAAGGCAACAAAGGCTGGAGGAGATTCTCCATCTTGG
GCGAAGGGCCACTGTCCCTTCATGCTGTCGGAACTCCAGGATGGGAAGAGCAAGATTGTG
CAGAAGGCAGCCCCAGAAGTCCAGGAAGATGTGAAGGCTTTCAAGACAGATCTGCCTAGC
TCCCTGGTCTCAGTCAGCCTAAGGAAGCCATTTTCCGGTCCCCAGGAGCAGGAGCAGATC
TCTGGGAAGGTCACACACCTGATTCAGAACAATATGCCTGGAAACTATGTCTTCAGTTAT
GACCAGTTTTTCAGGGACAAGATCATGGAGAAGAAACAGGATCACACCTACCGTGTGTTC
AAGACTGTGAACCGCTGGGCTGATGCATATCCCTTTGCCCAACATTTCTTTGAGGCATCT
GTGGCCTCAAAGGATGTGTCCGTCTGGTGTAGTAATGATTACCTGGGCATGAGCCGACAC
CCTCAGGTCTTGCAAGCCACACAGGAGACCCTGCAGCGTCATGGTGCTGGAGCTGGTGGC
ACCCGCAACATCTCAGGCACCAGTAAGTTTCATGTGGAGCTTGAGCAGGAGCTGGCTGAG
CTGCACCAGAAGGACTCAGCCCTGCTCTTCTCCTCCTGCTTTGTTGCCAATGACTCTACT
CTCTTCACCTTGGCCAAGATCCTGCCAGGGTGCGAGATTTACTCAGACGCAGGCAACCAT
GCTTCCATGATCCAAGGTATCCGTAACAGTGGAGCAGCCAAGTTTGTCTTCAGGCACAAT
GACCCTGACCACCTAAAGAAACTTCTAGAGAAGTCTAACCCTAAGATACCCAAAATTGTG
GCCTTTGAGACTGTCCACTCCATGGATGGTGCCATCTGTCCCCTCGAGGAGTTGTGTGAT
GTGTCCCACCAGTATGGGGCCCTGACCTTCGTGGATGAGGTCCATGCTGTAGGACTGTAT
GGGTCCCGGGGCGCTGGGATTGGGGAGCGTGATGGAATTATGCATAAGATTGACATCATC
TCTGGAACTCTTGGCAAGGCCTTTGGCTGTGTGGGCGGCTACATTGCCAGCACCCGTGAC
TTGGTGGACATGGTGCGCTCCTATGCTGCAGGCTTCATCTTTACCACTTCTCTGCCCCCC
ATGGTGCTCTCTGGAGCTCTAGAATCTGTGCGGCTGCTCAAGGGAGAGGAGGGCCAAGCC
CTGAGGCGAGCCCACCAGCGCAATGTCAAGCACATGCGCCAGCTACTCATGGACAGGGGC
CTTCCTGTCATCCCCTGCCCCAGCCACATCATCCCCATCCGGGTGGGCAATGCAGCACTC
AACAGCAAGCTCTGTGATCTCCTGCTCTCCAAGCATGGCATCTATGTGCAGGCCATCAAC
TACCCAACTGTCCCCCGGGGTGAAGAGCTCCTGCGCTTGGCACCCTCCCCCCACCACAGC
CCTCAGATGATGGAAGATTTTGTGGAGAAGCTGCTGCTGGCTTGGACTGCGGTGGGGCTG
CCCCTCCAGGATGTGTCTGTGGCTGCCTGCAATTTCTGTCGCCGTCCTGTACACTTTGAG
CTCATGAGTGAGTGGGAACGTTCCTACTTCGGGAACATGGGGCCCCAGTATGTCACCACC
TATGCCTGA

1. Bishop DF: Two different genes encode delta-aminolevulinate synthase in humans: nucleotide sequences of cDNAs for the housekeeping and erythroid genes. Nucleic Acids Res. 1990 Dec 11;18(23):7187-8. [PubMed ]
2. Cox TC, Bawden MJ, Martin A, May BK: Human erythroid 5-aminolevulinate synthase: promoter analysis and identification of an iron-responsive element in the mRNA. EMBO J. 1991 Jul;10(7):1891-902. [PubMed ]
3. Surinya KH, Cox TC, May BK: Identification and characterization of a conserved erythroid-specific enhancer located in intron 8 of the human 5-aminolevulinate synthase 2 gene. J Biol Chem. 1998 Jul 3;273(27):16798-809. [PubMed ]
4. Cox TC, Bottomley SS, Wiley JS, Bawden MJ, Matthews CS, May BK: X-linked pyridoxine-responsive sideroblastic anemia due to a Thr388-to-Ser substitution in erythroid 5-aminolevulinate synthase. N Engl J Med. 1994 Mar 10;330(10):675-9. [PubMed ]
5. Cotter PD, Baumann M, Bishop DF: Enzymatic defect in "X-linked" sideroblastic anemia: molecular evidence for erythroid delta-aminolevulinate synthase deficiency. Proc Natl Acad Sci U S A. 1992 May 1;89(9):4028-32. [PubMed ]
6. Furuyama K, Uno R, Urabe A, Hayashi N, Fujita H, Kondo M, Sassa S, Yamamoto M: R411C mutation of the ALAS2 gene encodes a pyridoxine-responsive enzyme with low activity. Br J Haematol. 1998 Dec;103(3):839-41. [PubMed ]
7. Harigae H, Furuyama K, Kudo K, Hayashi N, Yamamoto M, Sassa S, Sasaki T: A novel mutation of the erythroid-specific gamma-Aminolevulinate synthase gene in a patient with non-inherited pyridoxine-responsive sideroblastic anemia. Am J Hematol. 1999 Oct;62(2):112-4. [PubMed ]
8. Cotter PD, May A, Li L, Al-Sabah AI, Fitzsimons EJ, Cazzola M, Bishop DF: Four new mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causing X-linked sideroblastic anemia: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis. Blood. 1999 Mar 1;93(5):1757-69. [PubMed ]

1. 5-aminolevulinic acid synthase
2. Delta-aminolevulinate synthase
3. Delta-ALA synthetase
4. ALAS-H

MESVVRRCPFLSRVPQAFLQKAGKSLLFYAQNCPKMMEVGAKPAPRALSTAAVHYQQIKE
TPPASEKDKTAKAKVQQTPDGSQQSPDGTQLPSGHPLPATSQGTASKCPFLAAQMNQRGS
SVFCKASLELQEDVQEMNAVRKEVAETSAGPSVVSVKTDGGDPSGLLKNFQDIMQKQRPE
RVSHLLQDNLPKSVSTFQYDRFFEKKIDEKKNDHTYRVFKTVNRRAHIFPMADDYSDSLI
TKKQVSVWCSNDYLGMSRHPRVCGAVMDTLKQHGAGAGGTRNISGTSKFHVDLERELADL
HGKDAALLFSSCFVANDSTLFTLAKMMPGCEIYSDSGNHASMIQGIRNSRVPKYIFRHND
VSHLRELLQRSDPSVPKIVAFETVHSMDGAVCPLEELCDVAHEFGAITFVDEVHAVGLYG
ARGGGIGDRDGVMPKMDIISGTLGKAFGCVGGYIASTSSLIDTVRSYAAGFIFTTSLPPM
LLAGALESVRILKSAEGRVLRRQHQRNVKLMRQMLMDAGLPVVHCPSHIIPVRVADAAKN
TEVCDELMSRHNIYVQAINYPTVPRGEELLRIAPTPHHTPQMMNYFLENLLVTWKQVGLE
LKPHSSAECNFCRRPLHFEVMSEREKSYFSGLSKLVSAQA

• Glycine, Serine and Threonine Metabolism (map00260 )

• succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2

• Aminotran_1_2 (PF00155 )

• None

• None

ATGGAGAGTGTTGTTCGCCGCTGCCCATTCTTATCCCGAGTCCCCCAGGCCTTTCTGCAG
AAAGCAGGCAAATCTCTGTTGTTCTATGCCCAAAACTGCCCCAAGATGATGGAAGTTGGG
GCCAAGCCAGCCCCTCGGGCATTGTCCACTGCAGCAGTACACTACCAACAGATCAAAGAA
ACCCCTCCGGCCAGTGAGAAAGACAAAACTGCTAAGGCCAAGGTCCAACAGACTCCTGAT
GGATCCCAGCAGAGTCCAGATGGCACACAGCTTCCGTCTGGACACCCCTTGCCTGCCACA
AGCCAGGGCACTGCAAGCAAATGCCCTTTCCTGGCAGCACAGATGAATCAGAGAGGCAGC
AGTGTCTTCTGCAAAGCCAGTCTTGAGCTTCAGGAGGATGTGCAGGAAATGAATGCCGTG
AGGAAAGAGGTTGCTGAAACCTCAGCAGGCCCCAGTGTGGTTAGTGTGAAAACCGATGGA
GGGGATCCCAGTGGACTGCTGAAGAACTTCCAGGACATTATGCAAAAGCAAAGACCAGAA
AGAGTGTCTCATCTTCTTCAAGATAACTTGCCAAAATCTGTTTCCACTTTTCAGTATGAT
CGTTTCTTTGAGAAAAAAATTGATGAGAAAAAGAATGACCACACCTATCGAGTTTTTAAA
ACTGTGAACCGGCGAGCACACATCTTCCCCATGGCAGATGACTATTCAGACTCCCTCATC
ACCAAAAAGCAAGTGTCAGTCTGGTGCAGTAATGACTACCTAGGAATGAGTCGCCACCCA
CGGGTGTGTGGGGCAGTTATGGACACTTTGAAACAACATGGTGCTGGGGCAGGTGGTACT
AGAAATATTTCTGGAACTAGTAAATTCCATGTGGACTTAGAGCGGGAGCTGGCAGACCTC
CATGGGAAAGATGCCGCACTCTTGTTTTCCTCGTGCTTTGTGGCCAATGACTCAACCCTC
TTCACCCTGGCTAAGATGATGCCAGGCTGTGAGATTTACTCTGATTCTGGGAACCATGCC
TCCATGATCCAAGGGATTCGAAACAGCCGAGTGCCAAAGTACATCTTCCGCCACAATGAT
GTCAGCCACCTCAGAGAACTGCTGCAAAGATCTGACCCCTCAGTCCCCAAGATTGTGGCA
TTTGAAACTGTCCATTCAATGGATGGGGCGGTGTGCCCACTGGAAGAGCTGTGTGATGTG
GCCCATGAGTTTGGAGCAATCACCTTCGTGGATGAGGTCCACGCAGTGGGGCTTTATGGG
GCTCGAGGCGGAGGGATTGGGGATCGGGATGGAGTCATGCCAAAAATGGACATCATTTCT
GGAACACTTGGCAAAGCCTTTGGTTGTGTTGGAGGGTACATCGCCAGCACGAGTTCTCTG
ATTGACACCGTACGGTCCTATGCTGCTGGCTTCATCTTCACCACCTCTCTGCCACCCATG
CTGCTGGCTGGAGCCCTGGAGTCTGTGCGGATCCTGAAGAGCGCTGAGGGACGGGTGCTT
CGCCGCCAGCACCAGCGCAACGTCAAACTCATGAGACAGATGCTAATGGATGCCGGCCTC
CCTGTTGTCCACTGCCCCAGCCACATCATCCCTGTGCGGGTTGCAGATGCTGCTAAAAAC
ACAGAAGTCTGTGATGAACTAATGAGCAGACATAACATCTACGTGCAAGCAATCAATTAC
CCTACGGTGCCCCGGGGAGAAGAGCTCCTACGGATTGCCCCCACCCCTCACCACACACCC
CAGATGATGAACTACTTCCTTGAGAATCTGCTAGTCACATGGAAGCAAGTGGGGCTGGAA
CTGAAGCCTCATTCCTCAGCTGAGTGCAACTTCTGCAGGAGGCCACTGCATTTTGAAGTG
ATGAGTGAAAGAGAGAAGTCCTATTTCTCAGGCTTGAGCAAGTTGGTATCTGCTCAGGCC
TGA

1. Bishop DF: Two different genes encode delta-aminolevulinate synthase in humans: nucleotide sequences of cDNAs for the housekeeping and erythroid genes. Nucleic Acids Res. 1990 Dec 11;18(23):7187-8. [PubMed ]
2. Bawden MJ, Borthwick IA, Healy HM, Morris CP, May BK, Elliott WH: Sequence of human 5-aminolevulinate synthase cDNA. Nucleic Acids Res. 1987 Oct 26;15(20):8563. [PubMed ]

1. Integral membrane protein CII-3
2. QPs1
3. QPs-1
4. Succinate dehydrogenase complex subunit C
5. Succinate-ubiquinone oxidoreductase cytochrome B large subunit
6. CYBL

MAALLLRHVGRHCLRAHFSPQLCIRNAVPLGTTAKEEMERFWNKNIGSNRPLSPHITIYS
WSLPMAMSICHRGTGIALSAGVSLFGMSALLLPGNFESYLELVKSLCLGPALIHTAKFAL
VFPLMYHTWNGIRHLMWDLGKGLKIPQLYQSGVVVLVLTVLSSMGLAAM

• Sdh_cyt (PF01127 )

• 1-16

• 71-93 105-127 147-168

ATGGCTGCGCTGTTGCTGAGACACGTTGGTCGTCATTGCCTCCGAGCCCACTTTAGCCCT
CAGCTCTGTATCAGAAATGCTGTTCCTTTGGGAACCACGGCCAAAGAAGAGATGGAGCGG
TTCTGGAATAAGAATATAGGTTCAAACCGTCCTCTGTCTCCCCACATTACTATCTACAGT
TGGTCTCTTCCCATGGCGATGTCCATCTGCCACCGTGGCACTGGTATTGCTTTGAGTGCA
GGGGTCTCTCTTTTTGGCATGTCGGCCCTGTTACTCCCTGGGAACTTTGAGTCTTATTTG
GAACTTGTGAAGTCCCTGTGTCTGGGGCCAGCACTGATCCACACAGCTAAGTTTGCACTT
GTCTTCCCTCTCATGTATCATACCTGGAATGGGATCCGACACTTGATGTGGGACCTAGGA
AAAGGCCTGAAGATTCCCCAGCTATACCAGTCTGGAGTGGTTGTCCTGGTTCTTACTGTG
TTGTCCTCTATGGGGCTGGCAGCCATGTGA

1. Hirawake H, Taniwaki M, Tamura A, Kojima S, Kita K: Cytochrome b in human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the components in liver mitochondria and chromosome assignment of the genes for the large (SDHC) and small (SDHD) subunits to 1q21 and 11q23. Cytogenet Cell Genet. 1997;79(1-2):132-8. [PubMed ]
2. Elbehti-Green A, Au HC, Mascarello JT, Ream-Robinson D, Scheffler IE: Characterization of the human SDHC gene encoding of the integral membrane proteins of succinate-quinone oxidoreductase in mitochondria. Gene. 1998 Jun 15;213(1-2):133-40. [PubMed ]
3. Niemann S, Muller U: Mutations in SDHC cause autosomal dominant paraganglioma, type 3. Nat Genet. 2000 Nov;26(3):268-70. [PubMed ]

MDRASELLFYVNGRKVIEKNVDPETMLLPYLRKKLRLTGTPYGCGGGGCGACTVMISRYN
PITKRIRHHPANACLIPICSLYGAAVTTVEGIGSTHTRIHPVQERIAKCHGTQCGFCTPG
MVMSIYPLLRNHPEPTLDQLTDALGGNLCRCHGYRPIIDACKTFCKTSGCCQSKENGVCC
LDQGINGLPEFEEGSKTSPKLFAEEEFLPLDPTQELIFPPELMIMADKQSQRTRVFGSER
MMWFSPVTLKDLLEFKFKYPQAPVIMGNTSVGPEVKFKGVFHPGYNSPDRIEEPECCKPC
IYGLTLGAGLSLAQVKDILADVVQKLPEEKTQMYHALLKHLGTLAGSQIRNMASLGGHII
SRHPDSDLNPILAVGNCTLNLLSKEGKRQIPLNEQFLSKCPNADLKPQEILVSVNIPISR
KWEFVSAFRQAQRQENALAIVNSGMRVFFGEGDGIIRELCISYGGVGPATICAKNSCQKL
IGRHWNEQMLDIACRLILNEVSLLGSAPGGKVEFKRTLIISFLFKFYLEVSQILKKMDPV
HYPSLADKYESALEDLHSKHHCSTLKYQNIGPKQHPEDPIGHPIMHLSGVKHATGEAIYC
DDMPLVDQELFLTFVTSSRAHAKIVSIDLSEALSMPGVVDIMTAEHLSDVNSFCFFTEAE
KFLATDKVFCVGQLVCAVLADSEVQAKRAAKRVKIVYQDLEPLILTIEESIQHNSSFKPE
RKLEYGNVDEAFKVVDQILEGEIHMGGQEHFYMETQSMLVVPKGEDQEMDVYVSTQFPKY
IQDIVASTLKLPANKVMCHVRRVGGAFGGKVLKTGIIAAVTAFAANKHGRAVRCVLERGE
DMLITGGRHPYLGKYKAGFMNDGRILALDMEHYSNAGASLDESLFVIEMGLLKMDNAYKF
PNLRCRGWACRTNLPSNTAFRGFGFPQAVLITESCITEVAAKCGLSPEKVRIINMYKEID
QTPYKQEINAKNLIQCWRECMAMSSYSLRKVAVEKFNAENYWKKKGLAMVPLKFPVGLAS
RAAGQAAALVHIYLDGSVLVTHGGIEMGQGVHTKMIQVVSRELRMPMSNVHLRGTSTETV
PNANISGGSVVADLNGLAVKDACQTLLKRLEPIISKNPKGTWKDWAQTAFDESINLSAVG
YFRGYESDMNWEKGEGQPFEYFVYGAACSEVEIDCLTGDHKNIRTDIVMDVGCSINPAID
IGQIEGAFIQGMGLYTIEELNYSPQGILHTRGPDQYKIPAICDMPTELHIALLPPSQNSN
TLYSSKGLGESGVFLGCSVFFAIHDAVSAARQERGLHGPLTLNSPLTPEKIRMACEDKFT
KMIPRDEPGSYVPWNVPI

• Nicotinate and Nicotinamide Metabolism (map00760 )
• Tryptophan Metabolism (map00380 )
• Tyrosine Metabolism (map00350 )
• Valine, Leucine and Isoleucine Degradation (map00280 )
• Vitamin B6 Metabolism (map00750 )

• an aldehyde + H2O + O2 = a carboxylic acid + H2O2

• Ald_Xan_dh_C (PF01315 )
• Ald_Xan_dh_C2 (PF02738 )
• CO_deh_flav_C (PF03450 )
• FAD_binding_5 (PF00941 )
• Fer2 (PF00111 )
• Fer2_2 (PF01799 )

• None

• None

ATGGACCGGGCGTCCGAGCTGCTCTTCTACGTGAACGGCCGCAAGGTGATAGAAAAAAAT
GTCGATCCTGAAACAATGCTGTTGCCTTATTTGAGGAAGAAGCTTCGACTCACAGGAACT
CCGTATGGCTGTGGAGGAGGAGGCTGTGGTGCTTGTACAGTGATGATATCACGATACAAC
CCCATCACCAAGAGGATAAGGCATCACCCAGCCAATGCCTGTCTGATTCCCATCTGTTCT
CTGTATGGTGCTGCCGTCACCACAGTAGAAGGCATAGGAAGCACCCACACCAGAATTCAT
CCTGTTCAGGAGAGGATTGCCAAGTGTCATGGCACCCAGTGTGGCTTCTGCACACCTGGG
ATGGTGATGTCCATCTACCCCCTGCTCAGGAACCACCCAGAGCCCACTCTGGATCAGTTA
ACTGATGCCCTTGGTGGTAACCTGTGCCGTTGCCATGGATACAGGCCCATAATTGATGCA
TGCAAGACTTTCTGTAAAACTTCGGGCTGCTGTCAAAGTAAAGAAAATGGGGTTTGCTGT
TTGGATCAAGGAATCAATGGATTGCCAGAATTTGAGGAAGGAAGTAAGACAAGTCCAAAA
CTCTTCGCAGAAGAGGAGTTTCTGCCATTGGATCCAACCCAGGAACTGATATTTCCTCCT
GAGCTAATGATAATGGCTGATAAACAGTCGCAAAGGACCAGGGTGTTTGGCAGTGAGAGA
ATGATGTGGTTTTCCCCCGTGACCCTGAAGGACCTGCTGGAATTTAAATTCAAGTATCCC
CAGGCTCCTGTTATCATGGGAAACACCTCTGTGGGGCCTGAAGTGAAATTTAAAGGCGTC
TTTCACCCAGGTTATAATTCTCCTGATAGAATTGAAGAACCTGAGTGTTGTAAACCATGC
ATATATGGACTCACCCTTGGTGCTGGTCTCAGCCTAGCCCAGGTGAAGGACATTTTGGCT
GATGTAGTCCAGAAGCTTCCAGAGGAGAAGACACAGATGTACCATGCTCTCCTGAAGCAT
TTGGGAACTCTGGCTGGGTCCCAGATCAGGAACATGGCTTCTTTAGGGGGACACATCATT
AGCAGGCATCCAGATTCAGATCTGAATCCCATCCTGGCTGTGGGTAACTGTACCCTCAAC
TTGCTATCAAAAGAAGGAAAACGACAGATTCCTTTAAATGAGCAATTCCTCAGCAAGTGC
CCTAATGCAGATCTTAAGCCTCAAGAAATCTTGGTCTCAGTGAACATCCCCATCTCAAGG
AAGTGGGAATTTGTGTCAGCCTTCCGACAAGCCCAGCGACAGGAGAATGCGCTAGCGATA
GTCAATTCAGGAATGAGAGTCTTTTTTGGAGAAGGGGATGGCATTATTAGAGAGTTATGC
ATCTCATATGGAGGCGTTGGTCCAGCCACCATCTGTGCCAAGAATTCCTGCCAGAAACTC
ATTGGAAGGCACTGGAACGAACAGATGCTGGATATAGCCTGCAGGCTTATTCTGAATGAA
GTCTCCCTTTTGGGCTCGGCGCCAGGTGGGAAAGTGGAGTTCAAGAGGACTCTCATCATC
AGCTTCCTCTTCAAGTTCTACCTGGAAGTGTCACAGATTTTGAAAAAGATGGATCCAGTT
CACTATCCTAGCCTTGCAGACAAGTATGAAAGTGCTTTAGAAGATCTTCATTCCAAACAT
CACTGCAGTACATTAAAGTACCAGAATATAGGCCCAAAGCAGCATCCTGAAGACCCAATT
GGCCACCCCATCATGCATCTGTCTGGTGTGAAGCATGCCACGGGGGAGGCCATCTACTGT
GATGACATGCCTCTGGTGGACCAGGAACTTTTCTTGACTTTTGTGACTAGTTCAAGAGCT
CATGCTAAGATTGTGTCTATTGATCTGTCAGAAGCTCTCAGCATGCCCGGTGTGGTGGAC
ATCATGACAGCAGAACATCTTAGTGACGTCAACTCCTTCTGCTTTTTTACTGAAGCTGAG
AAATTTCTGGCGACAGATAAGGTGTTCTGTGTGGGTCAGCTTGTCTGTGCTGTGCTTGCC
GATTCTGAGGTTCAGGCAAAGCGAGCTGCTAAGCGAGTGAAGATTGTCTATCAAGACTTG
GAGCCGCTGATACTAACAATTGAGGAAAGTATACAACACAACTCCTCCTTCAAGCCAGAA
AGGAAACTGGAATATGGAAATGTTGACGAAGCATTTAAAGTGGTTGATCAAATTCTTGAA
GGTGAAATACATATGGGAGGTCAAGAACATTTTTATATGGAAACCCAAAGCATGCTTGTC
GTTCCCAAGGGAGAGGATCAAGAAATGGATGTCTACGTGTCCACACAGTTTCCCAAATAT
ATACAGGACATTGTTGCCTCAACCTTGAAGCTCCCAGCTAACAAGGTCATGTGCCATGTA
AGGCGTGTTGGTGGAGCGTTTGGAGGGAAGGTGTTAAAAACCGGAATCATTGCAGCCGTC
ACTGCATTTGCCGCAAACAAACATGGCCGTGCAGTTCGCTGTGTTCTGGAACGAGGAGAA
GACATGTTAATAACTGGAGGCCGCCATCCTTACCTTGGAAAGTACAAAGCTGGATTCATG
AACGATGGCAGAATCTTGGCCCTGGACATGGAGCATTACAGCAATGCAGGCGCCTCCTTG
GATGAATCATTATTCGTGATAGAAATGGGACTTCTGAAAATGGACAATGCTTACAAGTTT
CCCAATCTCCGCTGCCGGGGTTGGGCATGCAGAACCAACCTTCCATCCAACACAGCTTTT
CGTGGGTTTGGCTTTCCTCAGGCAGTGCTGATCACCGAATCTTGTATCACGGAAGTTGCA
GCCAAATGTGGACTATCCCCTGAGAAGGTGCGAATCATAAACATGTACAAGGAAATTGAT
CAAACACCCTACAAACAAGAGATCAATGCCAAGAACCTAATCCAGTGTTGGAGAGAATGT
ATGGCCATGTCTTCCTACTCCTTGAGGAAAGTTGCTGTGGAAAAGTTCAATGCAGAGAAT
TATTGGAAGAAGAAAGGACTGGCCATGGTCCCCCTGAAGTTTCCTGTTGGCCTTGCGTCA
CGTGCTGCTGGTCAGGCTGCTGCCTTGGTTCACATTTATCTTGATGGCTCTGTGCTGGTC
ACTCACGGTGGAATTGAAATGGGGCAGGGGGTCCACACTAAAATGATTCAGGTGGTCAGC
CGTGAATTAAGAATGCCAATGTCGAATGTCCACCTGCGTGGAACAAGCACAGAAACTGTC
CCTAATGCAAATATCTCTGGAGGTTCTGTGGTGGCAGATCTCAACGGTTTGGCAGTAAAG
GATGCCTGTCAAACTCTTCTAAAACGCCTCGAACCCATCATCAGCAAGAATCCTAAAGGA
ACTTGGAAAGACTGGGCACAGACTGCTTTTGATGAAAGCATTAACCTTTCAGCTGTTGGA
TACTTCAGAGGTTATGAGTCAGACATGAACTGGGAGAAAGGCGAAGGCCAGCCCTTCGAA
TACTTTGTTTATGGAGCTGCCTGTTCCGAGGTTGAAATAGACTGCCTGACGGGGGATCAT
AAGAACATCAGAACAGACATTGTCATGGATGTTGGCTGCAGTATAAATCCAGCCATTGAC
ATAGGCCAGATTGAAGGTGCATTTATTCAAGGCATGGGACTTTATACAATAGAGGAACTG
AATTATTCTCCCCAGGGCATTCTGCACACTCGTGGTCCAGACCAATATAAAATCCCTGCC
ATCTGTGACATGCCCACGGAGTTGCACATTGCTTTGTTGCCTCCTTCTCAAAACTCAAAT
ACTCTTTATTCATCTAAGGGTCTGGGAGAGTCGGGGGTGTTCCTGGGGTGTTCCGTGTTT
TTCGCTATCCATGACGCAGTGAGTGCAGCACGACAGGAGAGAGGCCTGCATGGACCCTTG
ACCCTTAATAGTCCACTGACCCCGGAGAAGATTAGGATGGCCTGTGAAGACAAGTTCACA
AAAATGATTCCGAGAGATGAACCTGGATCCTACGTTCCTTGGAATGTACCCATCTGA

1. Wright RM, Vaitaitis GM, Wilson CM, Repine TB, Terada LS, Repine JE: cDNA cloning, characterization, and tissue-specific expression of human xanthine dehydrogenase/xanthine oxidase. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10690-4. [PubMed ]

1. HO-2

MSAEVETSEGVDESEKKNSGALEKENQMRMADLSELLKEGTKEAHDRAENTQFVKDFLKG
NIKKELFKLATTALYFTYSALEEEMERNKDHPAFAPLYFPMELHRKEALTKDMEYFFGEN
WEEQVQCPKAAQKYVERIHYIGQNEPELLVAHAYTRYMGDLSGGQVLKKVAQRALKLPST
GEGTQFYLFENVDNAQQFKQLYRARMNALDLNMKTKERIVEEANKAFEYNMQIFNELDQA
GSTLARETLEDGFPVHDGKGDMRKCPFYAAEQDKGALEGSSCPFRTAMAVLRKPSLQFIL
AAGVALAAGLLAWYYM

• Porphyrin Metabolism (map00860 )

• heme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O

• Heme_oxygenase (PF01126 )

• None

• 296-315

ATGTCAGCGGAAGTGGAAACCTCAGAGGGGGTAGACGAGTCAGAAAAAAAGAACTCTGGG
GCCCTAGAAAAGGAGAACCAAATGAGAATGGCTGACCTCTCGGAGCTCCTGAAGGAAGGG
ACCAAGGAAGCACACGACCGGGCAGAAAACACCCAGTTTGTCAAGGACTTCTTGAAAGGC
AACATTAAGAAGGAGCTGTTTAAGCTGGCCACCACGGCACTTTACTTCACATACTCAGCC
CTCGAGGAGGAAATGGAGCGCAACAAGGACCATCCAGCCTTTGCCCCTTTGTACTTCCCC
ATGGAGCTGCACCGGAAGGAGGCGCTGACCAAGGACATGGAGTATTTCTTTGGTGAAAAC
TGGGAGGAGCAGGTGCAGTGCCCCAAGGCTGCCCAGAAGTACGTGGAGCGGATCCACTAC
ATAGGGCAGAACGAGCCGGAGCTACTGGTGGCCCATGCATACACCCGCTACATGGGGGAT
CTCTCGGGGGGCCAGGTGCTGAAGAAGGTGGCCCAGCGAGCACTGAAACTCCCCAGCACA
GGGGAAGGGACCCAGTTCTACCTGTTTGAGAATGTGGACAATGCCCAGCAGTTCAAGCAG
CTCTACCGGGCCAGGATGAACGCCCTGGACCTGAACATGAAGACCAAAGAGAGGATCGTG
GAGGAGGCCAACAAGGCTTTTGAGTATAACATGCAGATATTCAATGAACTGGACCAGGCC
GGCTCCACACTGGCCAGAGAGACCTTGGAGGATGGGTTCCCTGTACACGATGGGAAAGGA
GACATGCGTAAATGCCCTTTCTACGCTGCTGAACAAGACAAAGGTGCCCTGGAGGGCAGC
AGCTGTCCCTTCCGAACAGCTATGGCTGTGCTGAGGAAGCCCAGCCTCCAGTTCATCCTG
GCCGCTGGTGTGGCCCTAGCTGCTGGACTCTTGGCCTGGTACTACATGTGA

1. Ishikawa K, Takeuchi N, Takahashi S, Matera KM, Sato M, Shibahara S, Rousseau DL, Ikeda-Saito M, Yoshida T: Heme oxygenase-2. Properties of the heme complex of the purified tryptic fragment of recombinant human heme oxygenase-2. J Biol Chem. 1995 Mar 17;270(11):6345-50. [PubMed ]
2. McCoubrey WK Jr, Ewing JF, Maines MD: Human heme oxygenase-2: characterization and expression of a full-length cDNA and evidence suggesting that the two HO-2 transcripts may differ by choice of polyadenylation signal. Arch Biochem Biophys. 1992 May 15;295(1):13-20. [PubMed ]

1. CybS
2. Succinate-ubiquinone reductase membrane anchor subunit
3. QPs3
4. CII-4
5. Succinate dehydrogenase complex subunit D
6. Succinate-ubiquinone oxidoreductase cytochrome b small subunit

MAVLWRLSAVCGALGGRALLLRTPVVRPAHISAFLQDRPIPEWCGVQHIHLSPSHHSGSK
AASLHWTSERVVSVLLLGLLPAAYLNPCSAMDYSLAAALTLHGHWGLGQVVTDYVHGDAL
QKAAKAGLLALSALTFAGLCYFNYHDVGICKAVAMLWKL

• CybS (PF05328 )

• 1-18

• 71-91 126-142

ATGGCGGTTCTCTGGAGGCTGAGTGCCGTTTGCGGTGCCCTAGGAGGCCGAGCTCTGTTG
CTTCGAACTCCAGTGGTCAGACCTGCTCATATCTCAGCATTTCTTCAGGACCGACCTATC
CCAGAATGGTGTGGAGTGCAGCACATACACTTGTCACCGAGCCACCATTCTGGCTCCAAG
GCTGCATCTCTCCACTGGACTAGCGAGAGGGTTGTCAGTGTTTTGCTCCTGGGTCTGCTT
CCGGCTGCTTATTTGAATCCTTGCTCTGCGATGGACTATTCCCTGGCTGCAGCCCTCACT
CTTCATGGTCACTGGGGCCTTGGACAAGTTGTTACTGACTATGTTCATGGGGATGCCTTG
CAGAAAGCTGCCAAGGCAGGGCTTTTGGCACTTTCAGCTTTAACCTTTGCTGGGCTTTGC
TATTTCAACTATCACGATGTGGGCATCTGCAAAGCTGTTGCCATGCTGTGGAAGCTCTGA

1. Hirawake H, Taniwaki M, Tamura A, Kojima S, Kita K: Cytochrome b in human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the components in liver mitochondria and chromosome assignment of the genes for the large (SDHC) and small (SDHD) subunits to 1q21 and 11q23. Cytogenet Cell Genet. 1997;79(1-2):132-8. [PubMed ]
2. Gimm O, Armanios M, Dziema H, Neumann HP, Eng C: Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma. Cancer Res. 2000 Dec 15;60(24):6822-5. [PubMed ]
3. Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A, van der Mey A, Taschner PE, Rubinstein WS, Myers EN, Richard CW 3rd, Cornelisse CJ, Devilee P, Devlin B: Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science. 2000 Feb 4;287(5454):848-51. [PubMed ]
4. Milunsky JM, Maher TA, Michels VV, Milunsky A: Novel mutations and the emergence of a common mutation in the SDHD gene causing familial paraganglioma. Am J Med Genet. 2001 May 15;100(4):311-4. [PubMed ]
5. Badenhop RF, Cherian S, Lord RS, Baysal BE, Taschner PE, Schofield PR: Novel mutations in the SDHD gene in pedigrees with familial carotid body paraganglioma and sensorineural hearing loss. Genes Chromosomes Cancer. 2001 Jul;31(3):255-63. [PubMed ]
6. Taschner PE, Jansen JC, Baysal BE, Bosch A, Rosenberg EH, Brocker-Vriends AH, van Der Mey AG, van Ommen GJ, Cornelisse CJ, Devilee P: Nearly all hereditary paragangliomas in the Netherlands are caused by two founder mutations in the SDHD gene. Genes Chromosomes Cancer. 2001 Jul;31(3):274-81. [PubMed ]
7. Masuoka J, Brandner S, Paulus W, Soffer D, Vital A, Chimelli L, Jouvet A, Yonekawa Y, Kleihues P, Ohgaki H: Germline SDHD mutation in paraganglioma of the spinal cord. Oncogene. 2001 Aug 16;20(36):5084-6. [PubMed ]
8. Kytola S, Nord B, Elder EE, Carling T, Kjellman M, Cedermark B, Juhlin C, Hoog A, Isola J, Larsson C: Alterations of the SDHD gene locus in midgut carcinoids, Merkel cell carcinomas, pheochromocytomas, and abdominal paragangliomas. Genes Chromosomes Cancer. 2002 Jul;34(3):325-32. [PubMed ]
9. Cascon A, Ruiz-Llorente S, Cebrian A, Leton R, Telleria D, Benitez J, Robledo M: G12S and H50R variations are polymorphisms in the SDHD gene. Genes Chromosomes Cancer. 2003 Jun;37(2):220-1. [PubMed ]

1. CPR
2. P450R

MGDSHVDTSSTVSEAVAEEVSLFSMTDMILFSLIVGLLTYWFLFRKKKEEVPEFTKIQTL
TSSVRESSFVEKMKKTGRNIIVFYGSQTGTAEEFANRLSKDAHRYGMRGMSADPEEYDLA
DLSSLPEIDNALVVFCMATYGEGDPTDNAQDFYDWLQETDVDLSGVKFAVFGLGNKTYEH
FNAMGKYVDKRLEQLGAQRIFELGLGDDDGNLEEDFITWREQFWPAVCEHFGVEATGEES
SIRQYELVVHTDIDAAKVYMGEMGRLKSYENQKPPFDAKNPFLAAVTTNRKLNQGTERHL
MHLELDISDSKIRYESGDHVAVYPANDSALVNQLGKILGADLDVVMSLNNLDEESNKKHP
FPCPTSYRTALTYYLDITNPPRTNVLYELAQYASEPSEQELLRKMASSSGEGKELYLSWV
VEARRHILAILQDCPSLRPPIDHLCELLPRLQARYYSIASSSKVHPNSVHICAVVVEYET
KAGRINKGVATNWLRAKEPAGENGGRALVPMFVRKSQFRLPFKATTPVIMVGPGTGVAPF
IGFIQERAWLRQQGKEVGETLLYYGCRRSDEDYLYREELAQFHRDGALTQLNVAFSREQS
HKVYVQHLLKQDREHLWKLIEGGAHIYVCGDARNMARDVQNTFYDIVAELGAMEHAQAVD
YIKKLMTKGRYSLDVWS

• NADPH + H+ + n oxidized hemoprotein = NADP+ + n reduced hemoprotein

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

• 1-39

GGAGACTCCCACGTGGACACCAGCTCCACCGTGTCCGAGGCGGTGGCCGAAGAAGTATCT
CTTTTCAGCATGACGGACATGATTCTGTTTTCGCTCATCGTGGGTCTCCTAACCTACTGG
TTCCTCTTCAGAAAGAAAAAAGAAGAAGTCCCCGAGTTCACCAAAATTCAGACATTGACC
TCCTCTGTCAGAGAGAGCAGCTTTGTGGAAAAGATGAAGAAAACGGGGAGGAACATCATC
GTGTTCTACGGCTCCCAGACGGGGACTGCAGAGGAGTTTGCCAACCGCCTGTCCAAGGAC
GCCCACCGCTACGGGATGCGAGGCATGTCAGCGGACCCTGAGGAGTATGACCTGGCCGAC
CTGAGCAGCCTGCCAGAGATCGACAACGCCCTGGTGGTTTTCTGCATGGCCACCTACGGT
GAGGGAGACCCCACCGACAATGCCCAGGACTTCTACGACTGGCTGCAGGAGACAGACGTG
GATCTCTCTGGGGTCAAGTTCGCGGTGTTTGGTCTTGGGAACAAGACCTACGAGCACTTC
AATGCCATGGGCAAGTACGTGGACAAGCGGCTGGAGCAGCTCGGCGCCCAGCGCATCTTT
GAGCTGGGGTTGGGCGACGACGATGGGAACTTGGAGGAGGACTTCATCACCTGGCGAGAG
CAGTTCTGGCCGGCCGTGTGTGAACACTTTGGGGTGGAAGCCACTGGCGAGGAGTCCAGC
ATTCGCCAGTACGAGCTTGTGGTCCACACCGACATAGATGCGGCCAAGGTGTACATGGGG
GAGATGGGCCGGCTGAAGAGCTACGAGAACCAGAAGCCCCCCTTTGATGCCAAGAATCCG
TTCCTGGCTGCAGTCACCACCAACCGGAAGCTGAACCAGGGAACCGAGCGCCACCTCATG
CACCTGGAATTGGACATCTCGGACTCCAAAATCAGGTATGAATCTGGGGACCACGTGGCT
GTGTACCCAGCCAACGACTCTGCTCTCGTCAACCAGCTGGGCAAAATCCTGGGTGCCGAC
CTGGACGTCGTCATGTCCCTGAACAACCTGGATGAGGAGTCCAACAAGAAGCACCCATTC
CCGTGCCCTACGTCCTACCGCACGGCCCTCACCTACTACCTGGACATCACCAACCCGCCG
CGTACCAACGTGCTGTACGAGCTGGCGCAGTACGCCTCGGAGCCCTCGGAGCAGGAGCTG
CTGCGCAAGATGGCCTCCTCCTCCGGCGAGGGCAAGGAGCTGTACCTGAGCTGGGTGGTG
GAGGCCCGGAGGCACATCCTGGCCATCCTGCAGGACTGCCCGTCCCTGCGGCCCCCCATC
GACCACCTGTGTGAGCTGCTGCCGCGCCTGCAGGCCCGCTACTACTCCATCGCCTCATCC
TCCAAGGTCCACCCCAACTCTGTGCACATCTGTGCGGTGGTTGTGGAGTACGAGACCAAG
GCCGGCCGCATCAACAAGGGCGTGGCCACCAACTGGCTGCGGGCCAAGGAGCCTGTCGGG
GAGAACGGCGGCCGTGCGCTGGTGCCCATGTTCGTGCGCAAGTCCCAGTTACGCCTGCCC
TTCAAGGCCACCACGCCTGTCATCATGGTGGGCCCCGGCACCGGGTGGCACCCTTTCATA
GGCTTCATCCAGGAGCGGGCCTGGCTGCGACAGCAGGGCAAGGAGGTGGGGGAGACGCTG
CTGTACTACGGCTGCCGCCGCTCGGATGAGGACTACCTGTACCGGGAGGAGCTGGCGCAG
TTCCACAGGGACGGTGCGCTCACCCAGCTCAACGTGGCCTTCTCCCGGGAGCAGTCCCAC
AAGGTCTACGTCCAGCACCTGCTAAAGCAAGACCGAGAGCACCTGTGGAAGTTGATCGAA
GGCGGTGCCCACATCTACGTCTGTGGGGATGCACGGAACATGGCCAGGGATGTGCAGAAC
ACCTTCTACGACATCGTGGCTGAGCTCGGGGCCATGGAGCACGCGCAGGCGGTGGACTAC
ATCAAGAAACTGATGACCAAGGGCCGCTACTCCCTGGACGTGTGGAGCTAG

1. Shephard EA, Palmer CN, Segall HJ, Phillips IR: Quantification of cytochrome P450 reductase gene expression in human tissues. Arch Biochem Biophys. 1992 Apr;294(1):168-72. [PubMed ]
2. Haniu M, McManus ME, Birkett DJ, Lee TD, Shively JE: Structural and functional analysis of NADPH-cytochrome P-450 reductase from human liver: complete sequence of human enzyme and NADPH-binding sites. Biochemistry. 1989 Oct 17;28(21):8639-45. [PubMed ]
3. Zhao Q, Modi S, Smith G, Paine M, McDonagh PD, Wolf CR, Tew D, Lian LY, Roberts GC, Driessen HP: Crystal structure of the FMN-binding domain of human cytochrome P450 reductase at 1.93 A resolution. Protein Sci. 1999 Feb;8(2):298-306. [PubMed ]

1. HO-1

MERPQPDSMPQDLSEALKEATKEVHTQAENAEFMRNFQKGQVTRDGFKLVMASLYHIYVA
LEEEIERNKESPVFAPVYFPEELHRKAALEQDLAFWYGPRWQEVIPYTPAMQRYVKRLHE
VGRTEPELLVAHAYTRYLGDLSGGQVLKKIAQKALDLPSSGEGLAFFTFPNIASATKFKQ
LYRSRMNSLEMTPAVRQRVIEEAKTAFLLNIQLFEELQELLTHDTKDQSPSRAPGLRQRA
SNKVQDSAPVETPRGKPPLNTRSQAPLLRWVLTLSFLVATVAVGLYAM

• Porphyrin Metabolism (map00860 )

• heme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O

• Heme_oxygenase (PF01126 )

• None

• 265-287

ATGGAGCGTCCGCAACCCGACAGCATGCCCCAGGATTTGTCAGAGGCCCTGAAGGAGGCC
ACCAAGGAGGTGCACACCCAGGCAGAGAATGCTGAGTTCATGAGGAACTTTCAGAAGGGC
CAGGTGACCCGAGACGGCTTCAAGCTGGTGATGGCCTCCCTGTACCACATCTATGTGGCC
CTGGAGGAGGAGATTGAGCGCAACAAGGAGAGCCCAGTCTTCGCCCCTGTCTACTTCCCA
GAAGAGCTGCACCGCAAGGCTGCCCTGGAGCAGGACCTGGCCTTCTGGTACGGGCCCCGC
TGGCAGGAGGTCATCCCCTACACACCAGCCATGCAGCGCTATGTGAAGCGGCTCCACGAG
GTGGGGCGCACAGAGCCCGAGCTGCTGGTGGCCCACGCCTACACCCGCTACCTGGGTGAC
CTGTCTGGGGGCCAGGTGCTCAAAAAGATTGCCCAGAAAGCCCTGGACCTGCCCAGCTCT
GGCGAGGGCCTGGCCTTCTTCACCTTCCCCAACATTGCCAGTGCCACCAAGTTCAAGCAG
CTCTACCGCTCCCGCATGAACTCCCTGGAGATGACTCCCGCAGTCAGGCAGAGGGTGATA
GAAGAGGCCAAGACTGCGTTCCTGCTCAACATCCAGCTCTTTGAGGAGTTGCAGGAGCTG
CTGACCCATGACACCAAGGACCAGAGCCCCTCACGGGCACCAGGGCTTCGCCAGCGGGCC
AGCAACAAAGTGCAAGATTCTGCCCCCGTGGAGACTCCCAGAGGGAAGCCCCCACTCAAC
ACCCGCTCCCAGGCTCCGCTTCTCCGATGGGTCCTTACACTCAGCTTTCTGGTGGCGACA
GTTGCTGTAGGGCTTTATGCCATGTGA

1. Yoshida T, Biro P, Cohen T, Muller RM, Shibahara S: Human heme oxygenase cDNA and induction of its mRNA by hemin. Eur J Biochem. 1988 Feb 1;171(3):457-61. [PubMed ]
2. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. [PubMed ]
3. Keyse SM, Tyrrell RM: Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. Proc Natl Acad Sci U S A. 1989 Jan;86(1):99-103. [PubMed ]
4. Shibahara S, Sato M, Muller RM, Yoshida T: Structural organization of the human heme oxygenase gene and the function of its promoter. Eur J Biochem. 1989 Feb 15;179(3):557-63. [PubMed ]
5. Schuller DJ, Wilks A, Ortiz de Montellano PR, Poulos TL: Crystal structure of human heme oxygenase-1. Nat Struct Biol. 1999 Sep;6(9):860-7. [PubMed ]

1. URO-D
2. UPD

MEANGLGPQGFPELKNDTFLRAAWGEETDYTPVWCMRQAGRYLPEFRETRAAQDFFSTCR
SPEACCELTLQPLRRFPLDAAIIFSDILVVPQALGMEVTMVPGKGPSFPEPLREEQDLER
LRDPEVVASELGYVFQAITLTRQRLAGRVPLIGFAGAPWTLMTYMVEGGGSSTMAQAKRW
LYQRPQASHQLLRILTDALVPYLVGQVVAGAQALQLFESHAGHLGPQLFNKFALPYIRDV
AKQVKARLREAGLAPVPMIIFAKDGHFALEELAQAGYEVVGLDWTVAPKKARECVGKTVT
LQGNLDPCALYASEEEIGQLVKQMLDDFGPHRYIANLGHGLYPDMDPEHVGAFVDAVHKH
SRLLRQN

• Porphyrin Metabolism (map00860 )

• uroporphyrinogen III = coproporphyrinogen + 4 CO2

• URO-D (PF01208 )

• None

• None

ATGGAAGCGAATGGGTTGGGACCTCAGGGTTTTCCGGAGCTGAAGAATGACACATTCCTG
CGAGCAGCTTGGGGAGAGGAAACAGACTACACTCCCGTTTGGTGCATGCGCCAGGCAGGC
CGTTACTTACCAGAGTTTAGGGAAACCCGGGCTGCCCAGGACTTTTTCAGCACGTGTCGC
TCTCCTGAGGCCTGCTGTGAACTGACTCTGCAGCCACTGCGTCGCTTCCCTCTGGATGCT
GCCATCATTTTCTCCGACATCCTTGTTGTACCCCAGGCACTGGGCATGGAGGTGACCATG
GTACCTAGCAAAGGACCCAGCTTCCCAGAGCCATTAAGAGAAGAGCAGGACCTAGAAGCG
CTACGGGATCCAGAAGTGGTAGCCTCTGAGCTAGGCTATGTGTTCCAAGCCATCACCCTT
ACCCGACAACGACTGGCTGGACGTGTGCCGCTGATTGGCTTTGCTGGTGCCCCATGGACC
CTGATGACATACATGGTTGAGGGTGGTGGCTCAAGCACCATGGCTCAGGCCAAGCGCTGG
CTCTATCAGAGACCTCAGGCTAGTCACCAGCTGCTTCGCATCCTCACTGATGCTCTGGTC
CCATATCTGGTAGGACAAGTGGTGGCTGGTGCCCAGGCATTGCAGCTGTTTGAGTCCCAT
GCAGGGCATCTTGGCCCACAGCTCTTCAACAAGTTTGCACTGCCTTACATCCGTGATGTG
GCCAAGCAAGTGAAGGCCAGGTTGCGGGAGGCAGGCCTGGCACCAGTGCCCATGATCATC
TTTGCTAAGGATGGGCATTTTGCCCTGGAGGAGCTGGCCCAAGCTGGCTATGAGGTGGTT
GGGCTTGACTGGACAGTGGCCCCAAAGAAAGCCCGGGAGTGTGTGGGGAAGACGGTGACA
TTGCAGGGCAACTTGGACCCCTGTGCCTTGTATGCATCTGAGGAGGAGATCGGGCAGTTG
GTGAAGCAGATGCTGGATGACTTTGGACCACATCGCTACATTGCCAACTTGGGCCATGGG
CTTTATCCTGACATGGACCCAGAACATGTGGGCGCCTTTGTGGATGCTGTGCATAAACAC
TCACGTCTGCTTCGACAGAACTGA

1. Romeo PH, Raich N, Dubart A, Beaupain D, Pryor M, Kushner J, Cohen-Solal M, Goossens M: Molecular cloning and nucleotide sequence of a complete human uroporphyrinogen decarboxylase cDNA. J Biol Chem. 1986 Jul 25;261(21):9825-31. [PubMed ]
2. Moran-Jimenez MJ, Ged C, Romana M, Enriquez De Salamanca R, Taieb A, Topi G, D'Alessandro L, de Verneuil H: Uroporphyrinogen decarboxylase: complete human gene sequence and molecular study of three families with hepatoerythropoietic porphyria. Am J Hum Genet. 1996 Apr;58(4):712-21. [PubMed ]
3. Romana M, Dubart A, Beaupain D, Chabret C, Goossens M, Romeo PH: Structure of the gene for human uroporphyrinogen decarboxylase. Nucleic Acids Res. 1987 Sep 25;15(18):7343-56. [PubMed ]
4. Garey JR, Harrison LM, Franklin KF, Metcalf KM, Radisky ES, Kushner JP: Uroporphyrinogen decarboxylase: a splice site mutation causes the deletion of exon 6 in multiple families with porphyria cutanea tarda. J Clin Invest. 1990 Nov;86(5):1416-22. [PubMed ]
5. Whitby FG, Phillips JD, Kushner JP, Hill CP: Crystal structure of human uroporphyrinogen decarboxylase. EMBO J. 1998 May 1;17(9):2463-71. [PubMed ]
6. Phillips JD, Parker TL, Schubert HL, Whitby FG, Hill CP, Kushner JP: Functional consequences of naturally occurring mutations in human uroporphyrinogen decarboxylase. Blood. 2001 Dec 1;98(12):3179-85. [PubMed ]
7. de Verneuil H, Grandchamp B, Beaumont C, Picat C, Nordmann Y: Uroporphyrinogen decarboxylase structural mutant (Gly281----Glu) in a case of porphyria. Science. 1986 Nov 7;234(4777):732-4. [PubMed ]
8. Garey JR, Hansen JL, Harrison LM, Kennedy JB, Kushner JP: A point mutation in the coding region of uroporphyrinogen decarboxylase associated with familial porphyria cutanea tarda. Blood. 1989 Mar;73(4):892-5. [PubMed ]
9. Romana M, Grandchamp B, Dubart A, Amselem S, Chabret C, Nordmann Y, Goossens M, Romeo PH: Identification of a new mutation responsible for hepatoerythropoietic porphyria. Eur J Clin Invest. 1991 Apr;21(2):225-9. [PubMed ]
10. de Verneuil H, Bourgeois F, de Rooij F, Siersema PD, Wilson JH, Grandchamp B, Nordmann Y: Characterization of a new mutation (R292G) and a deletion at the human uroporphyrinogen decarboxylase locus in two patients with hepatoerythropoietic porphyria. Hum Genet. 1992 Jul;89(5):548-52. [PubMed ]
11. Meguro K, Fujita H, Ishida N, Akagi R, Kurihara T, Galbraith RA, Kappas A, Zabriskie JB, Toback AC, Harber LC, et al.: Molecular defects of uroporphyrinogen decarboxylase in a patient with mild hepatoerythropoietic porphyria. J Invest Dermatol. 1994 May;102(5):681-5. [PubMed ]
12. Roberts AG, Elder GH, De Salamanca RE, Herrero C, Lecha M, Mascaro JM: A mutation (G281E) of the human uroporphyrinogen decarboxylase gene causes both hepatoerythropoietic porphyria and overt familial porphyria cutanea tarda: biochemical and genetic studies on Spanish patients. J Invest Dermatol. 1995 Apr;104(4):500-2. [PubMed ]
13. McManus JF, Begley CG, Sassa S, Ratnaike S: Five new mutations in the uroporphyrinogen decarboxylase gene identified in families with cutaneous porphyria. Blood. 1996 Nov 1;88(9):3589-600. [PubMed ]
14. Mendez M, Sorkin L, Rossetti MV, Astrin KH, del C Batlle AM, Parera VE, Aizencang G, Desnick RJ: Familial porphyria cutanea tarda: characterization of seven novel uroporphyrinogen decarboxylase mutations and frequency of common hemochromatosis alleles. Am J Hum Genet. 1998 Nov;63(5):1363-75. [PubMed ]
15. McManus JF, Begley CG, Sassa S, Ratnaike S: Three new mutations in the uroporphyrinogen decarboxylase gene in familial porphyria cutanea tarda. Mutation in brief no. 237. Online. Hum Mutat. 1999;13(5):412. [PubMed ]
16. Christiansen L, Ged C, Hombrados I, Brons-Poulsen J, Fontanellas A, de Verneuil H, Horder M, Petersen NE: Screening for mutations in the uroporphyrinogen decarboxylase gene using denaturing gradient gel electrophoresis. Identification and characterization of six novel mutations associated with familial PCT. Hum Mutat. 1999;14(3):222-32. [PubMed ]
17. Brady JJ, Jackson HA, Roberts AG, Morgan RR, Whatley SD, Rowlands GL, Darby C, Shudell E, Watson R, Paiker J, Worwood MW, Elder GH: Co-inheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates the onset of porphyria cutanea tarda. J Invest Dermatol. 2000 Nov;115(5):868-74. [PubMed ]
18. Cappellini MD, Martinez di Montemuros F, Tavazzi D, Fargion S, Pizzuti A, Comino A, Cainelli T, Fiorelli G: Seven novel point mutations in the uroporphyrinogen decarboxylase (UROD) gene in patients with familial porphyria cutanea tarda (f-PCT). Hum Mutat. 2001 Apr;17(4):350. [PubMed ]
19. Ged C, Ozalla D, Herrero C, Lecha M, Mendez M, de Verneuil H, Mascaro JM: Description of a new mutation in hepatoerythropoietic porphyria and prenatal exclusion of a homozygous fetus. Arch Dermatol. 2002 Jul;138(7):957-60. [PubMed ]

1. Coproporphyrinogenase
2. Coprogen oxidase
3. COX

MALQLGRLSSGPCWLVARGGCGGPRAWSQCGGGGLRAWSQRSAAGRVCRPPGPAGTEQSR
GLGHGSTSRGGPWVGTGLAAALAGLVGLATAAFGHVQRAEMLPKTSGTRATSLGRPEEEE
DELAHRCSSFMAPPVTDLGELRRRPGDMKTKMELLILETQAQVCQALAQVDGGANFSVDR
WERKEGGGGISCVLQDGCVFEKAGVSISVVHGNLSEEAAKQMRSRGKVLKTKDGKLPFCA
MGVSSVIHPKNPHAPTIHFNYRYFEVEEADGNKQWWFGGGCDLTPTYLNQEDAVHFHRTL
KEACDQHGPDLYPKFKKWCDDYFFIAHRGERRGIGGIFFDDLDSPSKEEVFRFVQSCARA
VVPSYIPLVKKHCDDSFTPQEKLWQQLRRGRYVEFNLLYDRGTKFGLFTPGSRIESILMS
LPLTARWEYMHSPSENSKEAEILEVLRHPRDWVR

• Porphyrin Metabolism (map00860 )

• coproporphyrinogen-III + O2 + 2 H+ = protoporphyrinogen-IX + 2 CO2 + 2 H2O

• Coprogen_oxidas (PF01218 )

• 1-15

ATGGCCTTGCAGCTGGGCAGGCTGAGCTCGGGCCCCTGCTGGCTCGTGGCGCGGGGCGGC
TGCGGAGGGCCCCGCGCCTGGTCCCAGTGCGGCGGCGGAGGGCTCCGAGCCTGGTCCCAG
CGCAGCGCAGCCGGACGCGTCTGCCGGCCCCCTGGCCCGGCTGGCACGGAGCAGAGCCGC
GGGCTGGGGCACGGCTCGACGTCGAGAGGCGGCCCCTGGGTGGGGACAGGGCTGGCCGCG
GCGCTGGCGGGGTTGGTGGGGCTGGCCACCGCCGCCTTCGGGCATGTGCAGCGGGCGGAG
ATGTTGCCTAAGACCTCGGGGACGCGGGCCACTTCGCTGGGGAGGCCGGAGGAGGAGGAG
GATGAGCTGGCCCACCGCTGCAGCAGCTTCATGGCCCCGCCTGTGACCGACCTGGGCGAG
CTGCGAAGGAGGCCGGGCGACATGAAGACCAAGATGGAGCTGCTGATTCTGGAGACCCAG
GCCCAGGTGTGCCAGGCTCTGGCACAGGTAGACGGGGGCGCCAACTTTTCTGTGGACCGG
TGGGAGAGGAAGGAAG

1. Delfau-Larue MH, Martasek P, Grandchamp B: Coproporphyrinogen oxidase: gene organization and description of a mutation leading to exon 6 skipping. Hum Mol Genet. 1994 Aug;3(8):1325-30. [PubMed ]
2. Taketani S, Kohno H, Furukawa T, Yoshinaga T, Tokunaga R: Molecular cloning, sequencing and expression of cDNA encoding human coproporphyrinogen oxidase. Biochim Biophys Acta. 1994 Jan 4;1183(3):547-9. [PubMed ]
3. Martasek P, Camadro JM, Delfau-Larue MH, Dumas JB, Montagne JJ, de Verneuil H, Labbe P, Grandchamp B: Molecular cloning, sequencing, and functional expression of a cDNA encoding human coproporphyrinogen oxidase. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3024-8. [PubMed ]
4. Martasek P, Nordmann Y, Grandchamp B: Homozygous hereditary coproporphyria caused by an arginine to tryptophane substitution in coproporphyrinogen oxidase and common intragenic polymorphisms. Hum Mol Genet. 1994 Mar;3(3):477-80. [PubMed ]
5. Fujita H, Kondo M, Taketani S, Nomura N, Furuyama K, Akagi R, Nagai T, Terajima M, Galbraith RA, Sassa S: Characterization and expression of cDNA encoding coproporphyrinogen oxidase from a patient with hereditary coproporphyria. Hum Mol Genet. 1994 Oct;3(10):1807-10. [PubMed ]
6. Lamoril J, Martasek P, Deybach JC, Da Silva V, Grandchamp B, Nordmann Y: A molecular defect in coproporphyrinogen oxidase gene causing harderoporphyria, a variant form of hereditary coproporphyria. Hum Mol Genet. 1995 Feb;4(2):275-8. [PubMed ]
7. Daimon M, Gojyou E, Sugawara M, Yamatani K, Tominaga M, Sasaki H: A novel missense mutation in exon 4 of the human coproporphyrinogen oxidase gene in two patients with hereditary coproporphyria. Hum Genet. 1997 Feb;99(2):199-201. [PubMed ]
8. Lamoril J, Deybach JC, Puy H, Grandchamp B, Nordmann Y: Three novel mutations in the coproporphyrinogen oxidase gene. Hum Mutat. 1997;9(1):78-80. [PubMed ]
9. Schreiber WE, Zhang X, Senz J, Jamani A: Hereditary coproporphyria: exon screening by heteroduplex analysis detects three novel mutations in the coproporphyrinogen oxidase gene. Hum Mutat. 1997;10(3):196-200. [PubMed ]
10. Rosipal R, Lamoril J, Puy H, Da Silva V, Gouya L, De Rooij FW, Te Velde K, Nordmann Y, Martasek P, Deybach JC: Systematic analysis of coproporphyrinogen oxidase gene defects in hereditary coproporphyria and mutation update. Hum Mutat. 1999;13(1):44-53. [PubMed ]

1. CYPLI
2. P450LI
3. Sterol 14-alpha demethylase
4. Lanosterol 14-alpha demethylase
5. LDM
6. P450-14DM
7. P45014DM

MLLLGLLQAGGSVLGQAMEKVTGGNLLSMLLIACAFTLSLVYLIRLAAGHLVQLPAGVKS
PPYIFSPIPFLGHAIAFGKSPIEFLENAYEKYGPVFSFTMVGKTFTYLLGSDAAALLFNS
KNEDLNAEDVYSRLTTPVFGKGVAYDVPNPVFLEQKKMLKSGLNIAHFKQHVSIIEKETK
EYFESWGESGEKNVFEALSELIILTASHCLHGKEIRSQLNEKVAQLYADLDGGFSHAAWL
LPGWLPLPSFRRRDRAHREIKDIFYKAIQKRRQSQEKIDDILQTLLDATYKDGRPLTDDE
VAGMLIGLLLAGQHTSSTTSAWMGFFLARDKTLQKKCYLEQKTVCGENLPPLTYDQLKDL
NLLDRCIKETLRLRPPIMIMMRMARTPQTVAGYTIPPGHQVCVSPTVNQRLKDSWVERLD
FNPDRYLQDNPASGEKFAYVPFGAGRHRCIGENFAYVQIKTIWSTMLRLYEFDLIDGYFP
TVNYTTMIHTPENPVIRYKRRSK

• obtusifoliol + 3 O2 + 3 NADPH + 3 H+ = 4alpha-methyl-5alpha-ergosta-8,14,24(28)-trien-3beta-ol + formate + 3 NADP+ + 3 H2O

• p450 (PF00067 )

• None

• 24-44

ATGGCGGCGGCGGCTGGGATGCTGCTGCTGGGCTTGCTGCAGGCGGGTGGGTCGGTGCTG
GGCCAGGCGATGGAGAAGGTGACAGGCGGCAACCTCTTGTCCATGCTGCTGATCGCCTGC
GCCTTCACCCTCAGCCTGGTCTACCTGATCCGTCTGGCCGCCGGCCACCTGGTCCAGCTG
CCCGCAGGGGTGAAAAGTCCTCCATACATTTTCTCCCCAATTCCATTCCTTGGGCATGCC
ATAGCATTTGGGAAAAGTCCAATTGAATTTCTAGAAAATGCATATGAGAAGTATGGACCT
GTATTTAGTTTTACCATGGTAGGCAAGACATTTACTTACCTTCTGGGGAGTGATGCTGCT
GCACTGCTTTTTAATAGTAAAAATGAAGACCTGAATGCAGAAGATGTCTACAGTCGCCTG
ACAACACCTGTGTTTGGGAAGGGAGTTGCATACGATGTGCCTAATCCAGTTTTCTTGGAG
CAGAAGAAAATGTTAAAAAGTGGCCTTAACATAGCCCACTTTAAACAGCATGTTTCTATA
ATTGAAAAAGAAACAAAGGAATACTTTGAGAGTTGGGGAGAAAGTGGAGAAAAAAATGTG
TTTGAAGCTCTTTCTGAGCTCATAATTTTAACAGCTAGCCATTGTTTGCATGGAAAGGAA
ATCAGAAGTCAACTCAATGAAAAGGTAGCACAGCTGTATGCAGATTTGGATGGAGGTTTC
AGCCATGCAGCCTGGCTCTTACCAGGTTGGCTGCCTTTGCCTAGTTTCAGACGCAGGGAC
AGAGCTCATCGGGAAATCAAGGATATTTTCTATAAGGCAATCCAGAAACGCAGACAGTCT
CAAGAAAAAATTGATGACATTCTCCAAACTTTACTAGATGCTACATACAAGGATGGGCGT
CCTTTGACTGATGATGAAGTAGCAGGGATGCTTATTGGATTACTCTTGGCAGGGCAGCAT
ACATCCTCAACTACTAGTGCTTGGATGGGCTTCTTTTTGGCCAGAGACAAAACACTTCAA
AAAAAATGTTATTTAGAACAGAAAACAGTCTGTGGAGAGAATCTGCCTCCTTTAACTTAT
GACCAGCTCAAGGATCTAAATTTACTTGATCGCTGTATAAAAGAAACATTAAGACTTAGA
CCTCCTATAATGATCATGATGAGAATGGCCAGAACTCCTCAGACTGTGGCAGGGTATACC
ATTCCTCCAGGACATCAGGTGTGTGTTTCTCCCACTGTCAATCAAAGACTTAAAGACTCA
TGGGTAGAACGCCTGGACTTTAATCCTGATCGCTACTTACAGGATAACCCAGCATCAGGG
GAAAAGTTTGCCTATGTGCCATTTGGAGCTGGGCGTCATCGTTGTATTGGGGAAAATTTT
GCCTATGTTCAAATTAAGACAATTTGGTCCACTATGCTTCGTTTATATGAATTTGATCTC
ATTGATGGATACTTTCCCACTGTGAATTATACAACTATGATTCACACCCCTGAGAACCCA
GTTATCCGTTACAAACGAAGATCAAAATGA

1. Stromstedt M, Rozman D, Waterman MR: The ubiquitously expressed human CYP51 encodes lanosterol 14 alpha-demethylase, a cytochrome P450 whose expression is regulated by oxysterols. Arch Biochem Biophys. 1996 May 1;329(1):73-81. [PubMed ]
2. Rozman D, Stromstedt M, Waterman MR: The three human cytochrome P450 lanosterol 14 alpha-demethylase (CYP51) genes reside on chromosomes 3, 7, and 13: structure of the two retrotransposed pseudogenes, association with a line-1 element, and evolution of the human CYP51 family. Arch Biochem Biophys. 1996 Sep 15;333(2):466-74. [PubMed ]
3. Rozman D, Stromstedt M, Tsui LC, Scherer SW, Waterman MR: Structure and mapping of the human lanosterol 14alpha-demethylase gene (CYP51) encoding the cytochrome P450 involved in cholesterol biosynthesis; comparison of exon/intron organization with other mammalian and fungal CYP genes. Genomics. 1996 Dec 15;38(3):371-81. [PubMed ]
4. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [PubMed ]

1. TPO

MRALAVLSVTLVMACTEAFFPFISRGKELLWGKPEESRVSSVLEESKRLVDTAMYATMQR
NLKKRGILSPAQLLSFSKLPEPTSGVIARAAEIMETSIQAMKRKVNLKTQQSQHPTDALS
EDLLSIIANMSGCLPYMLPPKCPNTCLANKYRPITGACNNRDHPRWGASNTALARWLPPV
YEDGFSQPRGWNPGFLYNGFPLPPVREVTRHVIQVSNEVVTDDDRYSDLLMAWGQYIDHD
IAFTPQSTSKAAFGGGADCQMTCENQNPCFPIQLPEEARPAAGTACLPFYRSSAACGTGD
QGALFGNLSTANPRQQMNGLTSFLDASTVYGSSPALERQLRNWTSAEGLLRVHARLRDSG
RAYLPFVPPRAPAACAPEPGIPGETRGPCFLAGDGRASEVPSLTALHTLWLREHNRLAAA
LKALNAHWSADAVYQEARKVVGALHQIITLRDYIPRILGPEAFQQYVGPYEGYDSTANPT
VSNVFSTAAFRFGHATIHPLVRRLDASFQEHPDLPGLWLHQAFFSPWTLLRGGGLDPLIR
GLLARPAKLQVQDQLMNEELTERLFVLSNSSTLDLASINLQRGRDHGLPGYNEWREFCGL
PRLETPADLSTAIASRSVADKILDLYKHPDNIDVWLGGLAENFLPRARTGPLFACLIGKQ
MKALRDGDWFWWENSHVFTDAQRRELEKHSLSRVICDNTGLTRVPMDAFQVGKFPEDFES
CDSIPGMNLEAWRETFPQDDKCGFPESVENGDFVHCEESGRRVLVYSCRHGYELQGREQL
TCTQEGWDFQPPLCKDVNECADGAHPPCHASARCRNTKGGFQCLCADPYELGDDGRTCVD
SGRLPRATWISMSLAALLIGGFAGLTSTVICRWTRTGTKSTLPISETGGGTPELRCGKHQ
AVGTSPQRAAAQDSEQESAGMEGRDTHRLPRAL

• Tyrosine Metabolism (map00350 )

• iodide + H2O2 = iodine + 2 H2O

• An_peroxidase (PF03098 )
• EGF_CA (PF07645 )
• Sushi (PF00084 )

• 1-14

• 847-871

ATGAGAGCGCTCGCTGTGCTGTCTGTCACGCTGGTTATGGCCTGCACAGAAGCCTTCTTC
CCCTTCATCTCGAGAGGGAAAGAACTCCTTTGGGGAAAGCCTGAGGAGTCTCGTGTCTCT
AGCGTCTTGGAGGAAAGCAAGCGCCTGGTGGACACCGCCATGTACGCCACGATGCAGAGA
AACCTCAAGAAAAGAGGAATCCTTTCTCCAGCTCAGCTTCTGTCTTTTTCCAAACTTCCT
GAGCCAACAAGCGGAGTGATTGCCCGAGCAGCAGAGATAATGGAAACATCAATACAAGCG
ATGAAAAGAAAAGTCAACCTGAAAACTCAACAATCACAGCATCCAACGGATGCTTTATCA
GAAGATCTGCTGAGCATCATTGCAAACATGTCTGGATGTCTCCCTTACATGCTGCCCCCA
AAATGCCCAAACACTTGCCTGGCGAACAAATACAGGCCCATCACAGGAGCTTGCAACAAC
AGAGACCACCCCAGATGGGGCGCCTCCAACACGGCCCTGGCACGATGGCTCCCTCCAGTC
TATGAGGACGGCTTCAGTCAGCCCCGAGGCTGGAACCCCGGCTTCTTGTACAACGGGTTC
CCACTGCCCCCGGTCCGGGAGGTGACAAGACATGTCATTCAAGTTTCAAATGAGGTTGTC
ACAGATGATGACCGCTATTCTGACCTCCTGATGGCATGGGGACAATACATCGACCACGAC
ATCGCGTTCACACCACAGAGCACCAGCAAAGCTGCCTTCGGGGGAGGGGCTGACTGCCAG
ATGACTTGTGAGAACCAAAACCCATGTTTTCCCATACAACTCCCGGAGGAGGCCCGGCCG
GCCGCGGGCACCGCCTGTCTGCCCTTCTACCGCTCTTCGGCCGCCTGCGGCACCGGGGAC
CAAGGCGCGCTCTTTGGGAACCTGTCCACGGCCAACCCGCGGCAGCAGATGAACGGGTTG
ACCTCGTTCCTGGACGCGTCCACCGTGTATGGCAGCTCCCCGGCCCTAGAGAGGCAGCTG
CGGAACTGGACCAGTGCCGAAGGGCTGCTCCGCGTCCACGCGCGCCTCCGGGACTCCGGC
CGCGCCTACCTGCCCTTCGTGCCGCCACGGCGGCCTGCGGCCTGTGCGCCCGAGCCCGGC
ATCCCCGGAGAGACCCGCGGGCCCTGCTTCCTGGCCGGAGACGGCCGCGCCAGCGAGGTC
CCCTCCCTGACGGCACTGCACACGCTGTGGCTGCGCGAGCACAACCGCCTGGCCGCGGCG
CTCAAGGCCCTCAATGCGCACTGGAGCGCGGACGCCGTGTACCAGGAGGCGCGCAAGGTC
GTGGGCGCTCTGCACCAGATCATCACCCTGAGGGATTACATCCCCAGGATCCTGGGACCC
GAGGCCTTCCAGCAGTACGTGGGTCCCTATGAAGGCTATGACTCCACCGCCAACCCCACT
GTGTCCAACGTGTTCTCCACAGCCGCCTTCCGCTTCGGCCATGCCACGATCCACCCGCTG
GTGAGGAGGCTGGACGCCAGCTTCCAGGAGCACCCCGACCTGCCCGGGCTGTGGCTGCAC
CAGGCTTTCTTCAGCCCATGGACATTACTCCGTGGAGGTGGTTTGGACCCACTAATACGA
GGCCTTCTTGCAAGACCAGCCAAACTGCAGGTGCAGGATCAGCTGATGAACGAGGAGCTG
ACGGAAAGGCTCTTTGTGCTGTCCAATTCCAGCACCTTGGATCTGGCGTCCATCAACCTG
CAGAGGGGCCGGGACCACGGGCTGCCAGGTTACAATGAGTGGAGGGAGTTCTGCGGCCTG
CCTCGCCTGGAGACCCCCGCTGACCTGAGCACAGCCATCGCCAGCAGGAGCGTGGCCGAC
AAGATCCTGGACTTGTACAAGCATCCTGACAACATCGATGTCTGGCTGGGAGGCTTAGCT
GAAAACTTCCTCCCCAGGGCTCGGACAGGGCCCCTGTTTGCCTGTCTCATTGGGAAGCAG
ATGAAGGCTCTGCGGGATGGTGACTGGTTTTGGTGGGAGAACAGCCACGTCTTCACGGAT
GCACAGAGGCGTGAGCTGGAGAAGCACTCCCTGTCTCGGGTCATCTGTGACAACACTGGC
CTCACCAGGGTGCCCATGGATGCCTTCCAAGTCGGCAAATTCCCTGAAGACTTTGAGTCT
TGTGACAGCATCCCTGGCATGAACCTGGAGGCCTGGAGGGAAACCTTTCCTCAAGACGAC
AAGTGTGGCTTCCCAGAGAGCGTGGAGAATGGGGACTTTGTGCACTGTGAGGAGTCTGGG
AGGCGCGTGCTGGTGTATTCCTGCCGGCACGGGTATGAGCTCCAAGGCCGGGAGCAGCTC
ACTTGCACCCAGGAAGGATGGGATTTCCAGCCTCCCCTCTGCAAAGATGTGAACGAGTGT
GCAGACGGTGCCCACCCCCCCTGCCACGCCTCTGCGAGGTGCAGAAACACCAAAGGCGGC
TTCCAGTGTCTCTGCGCGGACCCCTACGAGTTAGGAGACGATGGGAGAACCTGCGTAGAC
TCCGGGAGGCTCCCTCGGGCGACTTGGATCTCCATGTCGCTGGCTGCTCTGCTGATCGGA
GGCTTCGCAGGTCTCACCTCGACGGTGATTTGCAGGTGGACACGCACTGGCACTAAATCC
ACACTGCCCATCTCGGAGACAGGCGGAGGAACTCCCGAGCTGAGATGCGGAAAGCACCAG
GCCGTAGGGACCTCACCGCAGCGGGCCGCAGCTCAGGACTCGGAGCAGGAGAGTGCTGGG
ATGGAAGGCCGGGATACTCACAGGCTGCCGAGAGCCCTCTGA

1. Kimura S, Kotani T, McBride OW, Umeki K, Hirai K, Nakayama T, Ohtaki S: Human thyroid peroxidase: complete cDNA and protein sequence, chromosome mapping, and identification of two alternately spliced mRNAs. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5555-9. [PubMed ]
2. Libert F, Ruel J, Ludgate M, Swillens S, Alexander N, Vassart G, Dinsart C: Complete nucleotide sequence of the human thyroperoxidase-microsomal antigen cDNA. Nucleic Acids Res. 1987 Aug 25;15(16):6735. [PubMed ]
3. Kimura S, Hong YS, Kotani T, Ohtaki S, Kikkawa F: Structure of the human thyroid peroxidase gene: comparison and relationship to the human myeloperoxidase gene. Biochemistry. 1989 May 16;28(10):4481-9. [PubMed ]
4. Barnett PS, Banga JP, Watkins J, Huang GC, Gluckman DR, Page MJ, McGregor AM: Nucleotide sequence of the alternatively spliced human thyroid peroxidase cDNA, TPO-2. Nucleic Acids Res. 1990 Feb 11;18(3):670. [PubMed ]
5. Ferrand M, Le Fourn V, Franc JL: Increasing diversity of human thyroperoxidase generated by alternative splicing. Characterized by molecular cloning of new transcripts with single- and multispliced mRNAs. J Biol Chem. 2003 Feb 7;278(6):3793-800. Epub 2002 Nov 25. [PubMed ]
6. Seto P, Hirayu H, Magnusson RP, Gestautas J, Portmann L, DeGroot LJ, Rapoport B: Isolation of a complementary DNA clone for thyroid microsomal antigen. Homology with the gene for thyroid peroxidase. J Clin Invest. 1987 Oct;80(4):1205-8. [PubMed ]
7. Zanelli E, Henry M, Charvet B, Malthiery Y: Evidence for an alternate splicing in the thyroperoxidase messenger from patients with Graves' disease. Biochem Biophys Res Commun. 1990 Jul 31;170(2):735-41. [PubMed ]
8. Bikker H, Vulsma T, Baas F, de Vijlder JJ: Identification of five novel inactivating mutations in the human thyroid peroxidase gene by denaturing gradient gel electrophoresis. Hum Mutat. 1995;6(1):9-16. [PubMed ]
9. Bikker H, Baas F, De Vijlder JJ: Molecular analysis of mutated thyroid peroxidase detected in patients with total iodide organification defects. J Clin Endocrinol Metab. 1997 Feb;82(2):649-53. [PubMed ]
10. Santos CL, Bikker H, Rego KG, Nascimento AC, Tambascia M, De Vijlder JJ, Medeiros-Neto G: A novel mutation in the TPO gene in goitrous hypothyroid patients with iodide organification defect. Clin Endocrinol (Oxf). 1999 Aug;51(2):165-72. [PubMed ]
11. Pannain S, Weiss RE, Jackson CE, Dian D, Beck JC, Sheffield VC, Cox N, Refetoff S: Two different mutations in the thyroid peroxidase gene of a large inbred Amish kindred: power and limits of homozygosity mapping. J Clin Endocrinol Metab. 1999 Mar;84(3):1061-71. [PubMed ]
12. Kotani T, Umeki K, Yamamoto I, Maesaka H, Tachibana K, Ohtaki S: A novel mutation in the human thyroid peroxidase gene resulting in a total iodide organification defect. J Endocrinol. 1999 Feb;160(2):267-73. [PubMed ]
13. Bakker B, Bikker H, Vulsma T, de Randamie JS, Wiedijk BM, De Vijlder JJ: Two decades of screening for congenital hypothyroidism in The Netherlands: TPO gene mutations in total iodide organification defects (an update). J Clin Endocrinol Metab. 2000 Oct;85(10):3708-12. [PubMed ]
14. Ambrugger P, Stoeva I, Biebermann H, Torresani T, Leitner C, Gruters A: Novel mutations of the thyroid peroxidase gene in patients with permanent congenital hypothyroidism. Eur J Endocrinol. 2001 Jul;145(1):19-24. [PubMed ]
15. Umeki K, Kotani T, Kawano J, Suganuma T, Yamamoto I, Aratake Y, Furujo M, Ichiba Y: Two novel missense mutations in the thyroid peroxidase gene, R665W and G771R, result in a localization defect and cause congenital hypothyroidism. Eur J Endocrinol. 2002 Apr;146(4):491-8. [PubMed ]
16. Niu DM, Hwang B, Chu YK, Liao CJ, Wang PL, Lin CY: High prevalence of a novel mutation (2268 insT) of the thyroid peroxidase gene in Taiwanese patients with total iodide organification defect, and evidence for a founder effect. J Clin Endocrinol Metab. 2002 Sep;87(9):4208-12. [PubMed ]
17. Wu JY, Shu SG, Yang CF, Lee CC, Tsai FJ: Mutation analysis of thyroid peroxidase gene in Chinese patients with total iodide organification defect: identification of five novel mutations. J Endocrinol. 2002 Mar;172(3):627-35. [PubMed ]
18. Rivolta CM, Esperante SA, Gruneiro-Papendieck L, Chiesa A, Moya CM, Domene S, Varela V, Targovnik HM: Five novel inactivating mutations in the thyroid peroxidase gene responsible for congenital goiter and iodide organification defect. Hum Mutat. 2003 Sep;22(3):259. [PubMed ]

1. LPO
2. Salivary peroxidase
3. SPO

MRVLLHLPALLASLILLQAAASTTRAQTTRTSAISDTVSQAKVQVNKAFLDSRTRLKTAM
SSETPTSRQLSEYLKHAKGRTRTAIRNGQVWEESLKRLRQKASLTNVTDPSLDLTSLSLE
VGCGAPAPVVRCDPCSPYRTITGDCNNRRKPALGAANRALARWLPAEYEDGLSLPFGWTP
GKTRNGFPLPLAREVSNKIVGYLNEEGVLDQNRSLLFMQWGQIVDHDLDFAPDTELGSSE
YSKAQCDEYCIQGDNCFPIMFPPNDPKAGTQGKCMPFFRAGFVCPTPPYKSLAREQINAL
TSFLDASFVYSSEPSLASRLRNLSSPLGLMAVNQEVSDHGLPYLPYDSKKPSPCEFINTT
ARVPCFLAGDSRASEHILLATSHTLFLREHNRLARELKRLNPQWDGEKLYQEARKILGAF
VQIITFRDYLPILLGDHMQKWIPPYQGYSESVDPRISNVFTFAFRFGHLEVPSSMFRLDE
NYQPWGPEPELPLHTLFFNTWRMVKDGGIDPLVRGLLAKKSKLMKQNKMMTGELRNKLFQ
PTHRIHGFDLAAINTQRCRDHGQPGYNSWRAFCDLSQPQTLEELNTVLKSKMLAKKLLGL
YGTPDNIDIWIGAIAEPLVERGRVGPLLACLLGKQFQQIRDGDRFWWENPGVFTNEQKDS
LQKMSFSRLVCDNTRITKVPRDPFWANSYPYDFVDCSAIDKLDLSPWASVKN

• Arachidonic acid metabolism (map00590 )
• Methane metabolism (map00680 )
• Phenylalanine Metabolism (map00360 )
• Stilbene, coumarine and lignin biosynthesis (map00940 )

• donor + H2O2 = oxidized donor + 2 H2O

• An_peroxidase (PF03098 )

• 1-26

ATGAGGGTCCTTCTCCATCTCCCAGCCCTCCTGGCTTCCCTCATCTTGCTTCAGGCTGCA
GCATCTACCACAAGAGCGCAGACTACCAGAACCTCTGCCATCTCCGATACTGTGAGTCAG
GCCAAGGTCCAAGTCAACAAGGCCTTCCTGGACTCCCGAACCAGGCTGAAGACCGCCATG
AGCTCTGAGACTCCCACCAGCCGACAGCTCTCAGAATACCTCAAGCATGCCAAAGGCCGG
ACGCGCACAGCCATCCGCAATGGACAGGTGTGGGAGGAGTCTTTAAAGAGACTGAGGCAG
AAGGCATCCTTGACCAATGTCACAGATCCCAGCCTGGACTTGACTTCACTGTCTCTGGAG
GTGGGCTGTGGTGCTCCTGCTCCCGTGGTGAGATGCGACCCGTGCAGCCCTTACCGCACC
ATTACGGGAGACTGCAATAACAGGAGGAAGCCTGCGCTGGGCGCCGCCAACAGGGCTCTG
GCGCGCTGGCTGCCCGCGGAGTACGAGGACGGGCTCTCCCTGCCCTTCGGCTGGACGCCG
GGGAAGACGCGCAACGGCTTCCCTCTCCCGCTGGCCCGGGAGGTATCTAACAAGATTGTT
GGCTATCTGAATGAGGAGGGTGTTCTGGACCAAAACAGGTCCCTGCTCTTCATGCAGTGG
GGTCAGATTGTGGATCATGACCTGGACTTTGCCCCTGACACCGAGCTGGGGAGTAGCGAG
TACTCCAAAGCCCAGTGTGATGAGTACTGTATCCAGGGAGACAACTGCTTCCCCATCATG
TTCCCACCCAATGACCCCAAGGCGGGGACTCAAGGGAAATGCATGCCTTTCTTCCGAGCT
GGGTTCGTCTGCCCCACTCCACCCTACAAGTCCCTGGCCCGAGAGCAGATCAACGCTCTG
ACCTCCTTCCTGGATGCCAGCTTTGTGTACAGCTCCGAGCCAAGCCTGGCCAGCCGCCTC
CGCAACCTCAGCAGCCCCCTGGGCCTCATGGCTGTCAACCAGGAGGTCTCAGACCATGGA
CTACCCTACCTGCCCTATGACAGCAAGAAGCCAAGCCCCTGTGAGTTCATCAACACCACT
GCCCGTGTGCCCTGCTTCCTGGCAGGAGATTCTCGAGCCTCAGAGCATATTCTGCTGGCC
ACATCCCACACCCTCTTTCTCCGCGAGCATAACCGGCTGGCCAGAGAACTAAAGAGACTC
AACCCTCAGTGGGATGGAGAGAAGCTCTACCAGGAAGCCCGGAAAATCCTGGGAGCCTTC
GTGCAGATTATCACCTTTAGGGACTACCTACCCATTTTGCTAGGTGACCACATGCAGAAG
TGGATACCCCCATATCAAGGCTACAGTGAATCTGTGGATCCCAGAATTTCCAATGTCTTC
ACCTTCGCCTTCCGCTTTGGCCACTTGGAGGTCCCCTCTAGTATGTTCCGCCTGGATGAG
AATTATCAGCCATGGGGGCCAGAACCAGAACTCCCCCTCCACACCCTCTTCTTCAACACT
TGGAGGATGGTCAAAGATGGTGGAATTGATCCTCTGGTGCGGGGCCTGCTGGCCAAGAAA
TCCAAGCTGATGAAACAGAATAAAATGATGACTGGAGAGCTGCGCAACAAGCTTTTCCAG
CCAACTCACAGGATCCATGGCTTTGACCTGGCTGCCATCAACACACAGCGTTGCCGGGAC
CATGGGCAACCTGGGTACAATTCCTGGAGAGCCTTCTGTGACCTCTCACAGCCGCAGACA
CTAGAGGAGTTGAACACAGTGCTGAAGAGCAAGATGCTGGCCAAGAAGTTACTGGGTCTC
TACGGGACCCCTGACAACATCGACATCTGGATAGGGGCCATTGCTGAGCCGCTGGTGGAA
AGGGGTCGGGTGGGGCCTCTCCTGGCCTGCCTCTTGGGCAAGCAGTTCCAGCAGATCCGT
GATGGAGACAGGTTCTGGTGGGAAAACCCTGGGGTCTTCACGAACGAGCAGAAGGACTCT
CTACAGAAAATGTCCTTCTCACGCCTTGTCTGTGACAACACCCGCATCACCAAGGTCCCA
CGGGACCCATTCTGGGCCAACAGCTACCCCTATGACTTCGTGGATTGCTCAGCCATCGAC
AAGCTGGACCTGTCACCCTGGGCCTCAGTGAAGAATTAG

1. Kiser C, Caterina CK, Engler JA, Rahemtulla B, Rahemtulla F: Cloning and sequence analysis of the human salivary peroxidase-encoding cDNA. Gene. 1996 Sep 16;173(2):261-4. [PubMed ]
2. Dull TJ, Uyeda C, Strosberg AD, Nedwin G, Seilhamer JJ: Molecular cloning of cDNAs encoding bovine and human lactoperoxidase. DNA Cell Biol. 1990 Sep;9(7):499-509. [PubMed ]

1. MPO[Contains: 89 kDa myeloperoxidase
2. 84 kDa myeloperoxidase
3. Myeloperoxidase light chain
4. Myeloperoxidase heavy chain]

MGVPFFSSLRCMVDLGPCWAGGLTAEMKLLLALAGLLAILATPQPSEGAAPAVLGEVDTS
LVLSSMEEAKQLVDKAYKERRESIKQRLRSGSASPMELLSYFKQPVAATRTAVRAADYLH
VALDLLERKLRSLWRRPFNVTDVLTPAQLNVLSKSSGCAYQDVGVTCPEQDKYRTITGMC
NNRRSPTLGASNRAFVRWLPAEYEDGFSLPYGWTPGVKRNGFPVALARAVSNEIVRFPTD
QLTPDQERSLMFMQWGQLLDHDLDFTPEPAARASFVTGVNCETSCVQQPPCFPLKIPPND
PRIKNQADCIPFFRSCPACPGSNITIRNQINALTSFVDASMVYGSEEPLARNLRNMSNQL
GLLAVNQRFQDNGRALLPFDNLHDDPCLLTNRSARIPCFLAGDTRSSEMPELTSMHTLLL
REHNRLATELKSLNPRWDGERLYQEARKIVGAMVQIITYRDYLPLVLGPTAMRKYLPTYR
SYNDSVDPRIANVFTNAFRYGHTLIQPFMFRLDNRYQPMEPNPRVPLSRVFFASWRVVLE
GGIDPILRGLMATPAKLNRQNQIAVDEIRERLFEQVMRIGLDLPALNMQRSRDHGLPGYN
AWRRFCGLPQPETVGQLGTVLRNLKLARKLMEQYGTPNNIDIWMGGVSEPLKRKGRVGPL
LACIIGTQFRKLRDGDRFWWENEGVFSMQQRQALAQISLPRIICDNTGITTVSKNNIFMS
NSYPRDFVNCSTLPALNLASWREAS

• Arachidonic acid metabolism (map00590 )
• Methane metabolism (map00680 )
• Phenylalanine Metabolism (map00360 )
• Stilbene, coumarine and lignin biosynthesis (map00940 )

• donor + H2O2 = oxidized donor + 2 H2O

• An_peroxidase (PF03098 )

• None

• None

ATGGGGGTTCCCTTCTTCTCTTCTCTCAGATGCATGGTGGACTTAGGACCTTGCTGGGCT
GGGGGTCTCACTGCAGAGATGAAGCTGCTTCTGGCCCTAGCAGGGCTCCTGGCCATTCTG
GCCACGCCCCAGCCCTCTGAAGGTGCTGCTCCAGCTGTCCTGGGGGAGGTGGACACCTCG
TTGGTGCTGAGCTCCATGGAGGAGGCCAAGCAGCTGGTGGACAAGGCCTACAAGGAGCGG
CGGGAAAGCATCAAGCAGCGGCTTCGCAGCGGCTCAGCCAGCCCCATGGAACTCCTATCC
TACTTCAAGCAGCCGGTGGCAGCCACCAGGACGGCGGTGAGGGCCGCTGACTACCTGCAC
GTGGCTCTAGACCTGCTGGAGAGGAAGCTGCGGTCCCTGTGGCGAAGGCCATTCAATGTC
ACTGATGTGCTGACGCCCGCCCAGCTGAATGTGTTGTCCAAGTCAAGCGGCTGCGCCTAC
CAGGACGTGGGGGTGACTTGCCCGGAGCAGGACAAATACCGCACCATCACCGGGATGTGC
AACAACAGACGCAGCCCCACGCTGGGGGCCTCCAACCGTGCCTTTGTGCGCTGGCTGCCG
GCGGAGTATGAGGACGGCTTCTCTCTTCCCTACGGCTGGACGCCCGGGGTCAAGCGCAAC
GGCTTCCCGGTGGCTCTGGCTCGCGCGGTCTCCAACGAGATCGTGCGCTTCCCCACTGAT
CAGCTGACTCCGGACCAGGAGCGCTCACTCATGTTCATGCAATGGGGCCAGCTGTTGGAC
CACGACCTCGACTTCACCCCTGAGCCGGCCGCCCGGGCCTCCTTCGTCACTGGCGTCAAC
TGCGAGACCAGCTGCGTTCAGCAGCCGCCCTGCTTCCCGCTCAAGATCCCGCCCAATGAC
CCCCGCATCAAGAACCAAGCCGACTGCATCCCGTTCTTCCGCTCCTGCCCGGCTTGCCCC
GGGAGCAACATCACCATCCGCAACCAGATCAACGCGCTCACTTCCTTCGTGGACGCCAGC
ATGGTGTACGGCAGCGAGGAGCCCCTGGCCAGGAACCTGCGCAACATGTCCAACCAGCTG
GGGCTGCTGGCCGTCAACCAGCGCTTCCAAGACAACGGCCGGGCCCTGCTGCCCTTTGAC
AACCTGCACGATGACCCCTGTCTCCTCACCAACCGCTCAGCGCGCATCCCCTGCTTCCTG
GCAGGGGACACCCGTTCCAGTGAGATGCCCGAGCTCACCTCCATGCACACCCTCTTACTT
CGGGAGCACAACCGGCTGGCCACAGAGCTCAAGAGCCTGAACCCTAGGTGGGATGGGGAG
AGGCTCTACCAGGAAGCCCGGAAGATCGTGGGGGCCATGGTCCAGATCATCACTTACCGG
GACTACCTGCCCCTGGTGCTGGGGCCAACGGCCATGAGGAAGTACCTGCCCACGTACCGT
TCCTACAATGACTCAGTGGACCCACGCATCGCCAACGTCTTCACCAATGCCTTCCGCTAC
GGCCACACCCTCATCCAACCCTTCATGTTCCGCCTGGACAATCGGTACCAGCCCATGGAA
CCCAACCCCCGTGTCCCCCTCAGCAGGGTCTTTTTTGCCTCCTGGAGGGTCGTGCTGGAA
GGTGGCATTGACCCCATCCTCCGGGGCCTCATGGCCACCCCTGCCAAGCTGAATCGTCAG
AACCAAATTGCAGTGGATGAGATCCGGGAGCGATTGTTTGAGCAGGTCATGAGGATTGGG
CTGGACCTGCCTGCTCTGAACATGCAGCGCAGCAGGGACCACGGCCTCCCAGGATACAAT
GCCTGGAGGCGCTTCTGTGGGCTCCCGCAGCCTGAAACTGTGGGCCAGCTGGGCACGGTG
CTGAGGAACCTGAAATTGGCGAGGAAACTGATGGAGCAGTATGGCACGCCCAACAACATC
GACATCTGGATGGGCGGCGTGTCCGAGCCTCTGAAGCGCAAAGGCCGCGTGGGCCCACTC
CTCGCCTGCATCATCGGTACCCAGTTCAGGAAGCTCCGGGATGGTGATCGGTTTTGGTGG
GAGAACGAGGGTGTGTTCAGCATGCAGCAGCGACAGGCCCTGGCCCAGATCTCATTGCCC
CGGATCATCTGCGACAACACAGGCATCACCACCGTGTCTAAGAACAACATCTTCATGTCC
AACTCATATCCCCGGGACTTTGTCAACTGCAGTACACTTCCTGCATTGAACCTGGCTTCC
TGGAGGGAAGCCTCCTAG

1. Morishita K, Kubota N, Asano S, Kaziro Y, Nagata S: Molecular cloning and characterization of cDNA for human myeloperoxidase. J Biol Chem. 1987 Mar 15;262(8):3844-51. [PubMed ]
2. Morishita K, Tsuchiya M, Asano S, Kaziro Y, Nagata S: Chromosomal gene structure of human myeloperoxidase and regulation of its expression by granulocyte colony-stimulating factor. J Biol Chem. 1987 Nov 5;262(31):15208-13. [PubMed ]
3. Johnson KR, Nauseef WM, Care A, Wheelock MJ, Shane S, Hudson S, Koeffler HP, Selsted M, Miller C, Rovera G: Characterization of cDNA clones for human myeloperoxidase: predicted amino acid sequence and evidence for multiple mRNA species. Nucleic Acids Res. 1987 Mar 11;15(5):2013-28. [PubMed ]
4. Johnson K, Gemperlein I, Hudson S, Shane S, Rovera G: Complete nucleotide sequence of the human myeloperoxidase gene. Nucleic Acids Res. 1989 Oct 11;17(19):7985-6. [PubMed ]
5. Seto P, Hirayu H, Magnusson RP, Gestautas J, Portmann L, DeGroot LJ, Rapoport B: Isolation of a complementary DNA clone for thyroid microsomal antigen. Homology with the gene for thyroid peroxidase. J Clin Invest. 1987 Oct;80(4):1205-8. [PubMed ]
6. Hashinaka K, Nishio C, Hur SJ, Sakiyama F, Tsunasawa S, Yamada M: Multiple species of myeloperoxidase messenger RNAs produced by alternative splicing and differential polyadenylation. Biochemistry. 1988 Aug 9;27(16):5906-14. [PubMed ]
7. Hosokawa Y, Kawaguchi R, Hikiji K, Yamada M, Suzuki K, Nakagawa T, Yoshihara T, Yamaguchi K: Cloning and characterization of four types of cDNA encoding myeloperoxidase from human monocytic leukemia cell line, SKM-1. Leukemia. 1993 Mar;7(3):441-5. [PubMed ]
8. Yamada M, Yoshida M, Hashinaka K: Identification of transcriptional cis-elements in introns 7 and 9 of the myeloperoxidase gene. J Biol Chem. 1993 Jun 25;268(18):13479-85. [PubMed ]
9. Yamada M, Hur SJ, Hashinaka K, Tsuneoka K, Saeki T, Nishio C, Sakiyama F, Tsunasawa S: Isolation and characterization of a cDNA coding for human myeloperoxidase. Arch Biochem Biophys. 1987 May 15;255(1):147-55. [PubMed ]
10. Yamada M, Hur SJ, Toda H: Isolation and characterization of extracellular myeloperoxidase precursor in HL-60 cell cultures. Biochem Biophys Res Commun. 1990 Jan 30;166(2):852-9. [PubMed ]
11. Fiedler TJ, Davey CA, Fenna RE: X-ray crystal structure and characterization of halide-binding sites of human myeloperoxidase at 1.8 A resolution. J Biol Chem. 2000 Apr 21;275(16):11964-71. [PubMed ]
12. Fenna R, Zeng J, Davey C: Structure of the green heme in myeloperoxidase. Arch Biochem Biophys. 1995 Jan 10;316(1):653-6. [PubMed ]
13. Blair-Johnson M, Fiedler T, Fenna R: Human myeloperoxidase: structure of a cyanide complex and its interaction with bromide and thiocyanate substrates at 1.9 A resolution. Biochemistry. 2001 Nov 20;40(46):13990-7. [PubMed ]
14. Kizaki M, Miller CW, Selsted ME, Koeffler HP: Myeloperoxidase (MPO) gene mutation in hereditary MPO deficiency. Blood. 1994 Apr 1;83(7):1935-40. [PubMed ]
15. Nauseef WM, Brigham S, Cogley M: Hereditary myeloperoxidase deficiency due to a missense mutation of arginine 569 to tryptophan. J Biol Chem. 1994 Jan 14;269(2):1212-6. [PubMed ]
16. Nauseef WM, Cogley M, McCormick S: Effect of the R569W missense mutation on the biosynthesis of myeloperoxidase. J Biol Chem. 1996 Apr 19;271(16):9546-9. [PubMed ]
17. DeLeo FR, Goedken M, McCormick SJ, Nauseef WM: A novel form of hereditary myeloperoxidase deficiency linked to endoplasmic reticulum/proteasome degradation. J Clin Invest. 1998 Jun 15;101(12):2900-9. [PubMed ]
18. Romano M, Dri P, Dadalt L, Patriarca P, Baralle FE: Biochemical and molecular characterization of hereditary myeloperoxidase deficiency. Blood. 1997 Nov 15;90(10):4126-34. [PubMed ]

1. EPO[Contains: Eosinophil peroxidase light chain
2. Eosinophil peroxidase heavy chain]

MHLLPALAGVLATLVLAQPCEGTDPASPGAVETSVLRDCIAEAKLLVDAAYNWTQKSIKQ
RLRSGSASPMDLLSYFKQPVAATRTVVRAADYMHVALGLLEEKLQPQRSGPFNVTDVLTE
PQLRLLSQASGCALRDQAERCSDKYRTITGRCNNKRRPLLGASNQALARWLPAEYEDGLS
LPFGWTPSRRRNGFLLPLVRAVSNQIVRFPNERLTSDRGRALMFMQWGQFIDHDLDFSPE
SPARVAFTAGVDCERTCAQLPPCFPIKIPPNDPRIKNQRDCIPFFRSAPSCPQNKNRVRN
QINALTSFVDASMVYGSEVSLSLRLRNRTNYLGLLAINQRFQDNGRALLPFDNLHDDPCL
LTNRSARIPCFLAGDTRSTETPKLAAMHTLFMREHNRLATELRRLNPRWNGDKLYNEARK
IMGAMVQIITYRDFLPLVLGKARARRTLGHYRGYCSNVDPRVANVFTLAFRFGHTMLQPF
MFRLDSQYRASAPNSHVPLSSAFFASWRIVYEGGIDPILRGLMATPAKLNRQDAMLVDEL
RDRLFRQVRRIGLDLAALNMQRSRDHGLPGYNAWRRFCGLSQPRNLAQLSRVLKNQDLAR
KFLNLYGTPDNIDIWIGAIAEPLLPGARVGPLLACLFENQFRRARDGDRFWWQKRGVFTK
RQRKALSRISLSRIICDNTGITTVSRDIFRANIYPRGFVNCSRIPRLNLSAWRGT

• Arachidonic acid metabolism (map00590 )
• Methane metabolism (map00680 )
• Phenylalanine Metabolism (map00360 )
• Stilbene, coumarine and lignin biosynthesis (map00940 )

• donor + H2O2 = oxidized donor + 2 H2O

• An_peroxidase (PF03098 )

• 1-17

ATGCATCTGCTCCCAGCCCTGGCAGGGGTCCTGGCCACACTCGTCCTCGCCCAGCCCTGT
GAGGGCACTGACCCAGCCTCCCCTGGGGCAGTGGAGACCTCGGTCCTGCGAGACTGCATA
GCAGAGGCCAAGTTGCTGGTGGATGCTGCCTACAATTGGACCCAGAAGAGCATCAAGCAG
CGGCTTCGCAGCGGTTCAGCCAGCCCCATGGACCTCCTGTCCTACTTCAAACAACCGGTA
GCAGCCACCAGGACAGTTGTTCGGGCCGCAGATTATATGCATGTGGCTTTGGGGCTGCTT
GAAGAGAAGTTACAACCCCAGCGGTCCGGACCCTTCAATGTCACTGATGTGCTAACAGAA
CCACAGCTGCGGCTGCTGTCCCAGGCCAGTGGCTGTGCTCTCCGGGACCAGGCCGAGCGC
TGCAGCGACAAGTACCGCACCATCACTGGACGGTGCAACAACAAGAGGAGACCCTTGCTA
GGGGCCTCCAACCAGGCTCTGGCTCGCTGGCTGCCCGCCGAGTATGAGGATGGGCTGTCG
CTCCCCTTCGGCTGGACCCCCAGCAGGAGGCGCAATGGCTTCCTTCTCCCTCTTGTCCGG
GCTGTCTCCAACCAGATTGTGCGCTTCCCCAATGAGAGACTGACCTCCGACCGTGGCCGA
GCCCTCATGTTCATGCAGTGGGGCCAGTTCATTGACCATGACCTGGACTTCTCCCCGGAG
TCCCCGGCCAGAGTGGCCTTCACTGCAGGCGTTGACTGTGAGAGGACCTGCGCCCAGCTG
CCCCCCTGCTTTCCCATCAAGATCCCACCCAATGACCCCCGCATCAAGAACCAGCGTGAC
TGCATCCCTTTCTTCCGCTCGGCACCCTCATGCCCCCAAAACAAGAACAGAGTCCGCAAC
CAGATCAACGCGCTCACCTCCTTTGTGGACGCCAGCATGGTGTATGGCAGTGAGGTCTCC
CTCTCGCTGCGGCTCCGCAACCGGACCAACTACCTGGGGCTGCTGGCCATCAACCAGCGC
TTTCAAGACAACGGCCGGGCCCTGCTGCCCTTCGACAACCTGCACGATGACCCCTGTCTC
CTCACCAACCGCTCGGCGCGCATCCCCTGCTTCCTGGCAGGTGACACCCGATCAACGGAA
ACCCCCAAACTGGCAGCCATGCACACCCTCTTTATGCGAGAGCACAACCGGCTGGCCACC
GAGCTGAGACGCCTGAATCCCCGGTGGAATGGAGACAAACTGTACAATGAGGCTCGGAAG
ATCATGGGGGCCATGGTCCAGATCATCACCTACCGAGACTTTCTGCCCCTGGTTCTGGGC
AAGGCCCGGGCCAGGAGAACCCTGGGGCACTACAGGGGGTACTGCTCCAATGTGGACCCA
CGGGTGGCCAATGTCTTCACCCTGGCCTTCCGCTTTGGCCACACAATGCTCCAGCCCTTC
ATGTTCCGCTTGGACAGTCAGTACCGGGCCTCCGCACCCAACTCGCATGTCCCACTTAGC
TCTGCCTTCTTTGCCAGCTGGCGGATCGTGTATGAAGGGGGCATCGACCCCATCCTCCGG
GGCCTCATGGCCACCCCTGCCAAGCTGAACCGTCAGGATGCCATGTTAGTGGATGAGCTC
CGGGACCGGCTGTTTCGGCAAGTGAGGAGGATTGGGCTGGACCTGGCAGCTCTCAACATG
CAACGAAGCCGGGACCACGGCCTTCCAGGGTACAATGCTTGGAGGCGCTTCTGTGGGCTC
TCCCAGCCCCGGAATTTGGCACAGCTTAGCCGGGTGCTGAAAAACCAGGACTTGGCAAGG
AAGTTCCTGAATTTGTATGGAACACCTGACAACATTGACATCTGGATTGGGGCCATCGCT
GAGCCTCTTTTGCCGGGGGCTCGAGTGGGGCCTCTTCTGGCTTGTCTGTTCGAGAACCAG
TTCAGAAGAGCCCGAGACGGAGACAGGTTCTGGTGGCAGAAACGAGGTGTTTTCACCAAA
AGACAGCGCAAGGCCCTGAGCAGAATTTCCTTGTCTCGAATTATATGTGACAATACCGGT
ATCACCACGGTTTCAAGGGACATCTTCAGAGCCAACATCTACCCTCGGGGCTTTGTGAAC
TGCAGCCGTATCCCCAGGTTGAACCTATCAGCCTGGCGAGGGACATGA

1. Sakamaki K, Tomonaga M, Tsukui K, Nagata S: Molecular cloning and characterization of a chromosomal gene for human eosinophil peroxidase. J Biol Chem. 1989 Oct 5;264(28):16828-36. [PubMed ]
2. Ten RM, Pease LR, McKean DJ, Bell MP, Gleich GJ: Molecular cloning of the human eosinophil peroxidase. Evidence for the existence of a peroxidase multigene family. J Exp Med. 1989 May 1;169(5):1757-69. [PubMed ]
3. Oxvig C, Thomsen AR, Overgaard MT, Sorensen ES, Hojrup P, Bjerrum MJ, Gleich GJ, Sottrup-Jensen L: Biochemical evidence for heme linkage through esters with Asp-93 and Glu-241 in human eosinophil peroxidase. The ester with Asp-93 is only partially formed in vivo. J Biol Chem. 1999 Jun 11;274(24):16953-8. [PubMed ]
4. Romano M, Patriarca P, Melo C, Baralle FE, Dri P: Hereditary eosinophil peroxidase deficiency: immunochemical and spectroscopic studies and evidence for a compound heterozygosity of the defect. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12496-500. [PubMed ]

1. UROS
2. Uroporphyrinogen- III cosynthetase
3. Hydroxymethylbilane hydrolyase [cyclizing]
4. UROIIIS

MKVLLLKDAKEDDCGQDPYIRELGLYGLEATLIPVLSFEFLSLPSFSEKLSHPEDYGGLI
FTSPRAVEAAELCLEQNNKTEVWERSLKEKWNAKSVYVVGNATASLVSKIGLDTEGETCG
NAEKLAEYICSRESSALPLLFPCGNLKREILPKALKDKGIAMESITVYQTVAHPGIQGNL
NSYYSQQGVPASITFFSPSGLTYSLKHIQELSGDNIDQIKFAAIGPTTARALAAQGLPVS
CTAESPTPQALATGIRKALQPHGCC

• Porphyrin Metabolism (map00860 )

• hydroxymethylbilane = uroporphyrinogen III + H2O

• HEM4 (PF02602 )

• None

• None

ATGAAGGTTCTTTTACTGAAGGATGCGAAGGAAGATGACTGTGGCCAGGATCCGTATATC
AGGGAATTAGGATTATATGGACTTGAAGCCACTTTGATCCCTGTTTTATCGTTTGAGTTT
TTGTCTCTTCCCAGTTTCTCTGAGAAGCTTTCTCATCCTGAAGATTACGGGGGACTCATT
TTTACCAGCCCCAGAGCAGTGGAAGCAGCAGAGTTATGTTTGGAGCAAAACAATAAAACT
GAAGTCTGGGAAAGGTCTCTGAAAGAAAAATGGAATGCCAAGTCAGTGTATGTGGTTGGA
AATGCTACTGCTTCTCTAGTGAGTAAAATTGGCCTGGATACAGAAGGAGAAACCTGTGGA
AATGCAGAAAAGCTTGCAGAATATATTTGTTCCAGGGAGTCCTCAGCACTGCCTCTTCTA
TTTCCCTGTGGAAACCTCAAAAGAGAAATCCTGCCAAAAGCGCTCAAGGACAAAGGGATT
GCCATGGAAAGCATAACTGTGTATCAGACAGTTGCACACCCAGGAATCCAAGGGAACCTG
AACAGCTACTATTCCCAGCAGGGGGTTCCAGCCAGCATCACATTTTTTAGTCCCTCTGGC
CTCACATACAGTCTCAAGCACATTCAGGAGTTATCTGGTGACAATATCGATCAAATTAAG
TTTGCAGCCATCGGCCCCACTACGGCTCGCGCGCTGGCCGCCCAGGGCCTTCCTGTAAGC
TGCACTGCAGAGAGCCCCACGCCACAAGCCCTGGCCACTGGCATCAGGAAGGCTCTCCAG
CCCCATGGCTGCTGCTGA

1. Tsai SF, Bishop DF, Desnick RJ: Human uroporphyrinogen III synthase: molecular cloning, nucleotide sequence, and expression of a full-length cDNA. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7049-53. [PubMed ]
2. Xu W, Astrin KH, Desnick RJ: Molecular basis of congenital erythropoietic porphyria: mutations in the human uroporphyrinogen III synthase gene. Hum Mutat. 1996;7(3):187-92. [PubMed ]
3. Deybach JC, de Verneuil H, Boulechfar S, Grandchamp B, Nordmann Y: Point mutations in the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria (Gunther's disease). Blood. 1990 May 1;75(9):1763-5. [PubMed ]
4. Boulechfar S, Da Silva V, Deybach JC, Nordmann Y, Grandchamp B, de Verneuil H: Heterogeneity of mutations in the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria. Hum Genet. 1992 Jan;88(3):320-4. [PubMed ]
5. Warner CA, Yoo HW, Roberts AG, Desnick RJ: Congenital erythropoietic porphyria: identification and expression of exonic mutations in the uroporphyrinogen III synthase gene. J Clin Invest. 1992 Feb;89(2):693-700. [PubMed ]
6. Xu W, Warner CA, Desnick RJ: Congenital erythropoietic porphyria: identification and expression of 10 mutations in the uroporphyrinogen III synthase gene. J Clin Invest. 1995 Feb;95(2):905-12. [PubMed ]
7. Tanigawa K, Bensidhoum M, Takamura N, Namba H, Yamashita S, de Verneuil H, Ged C: A novel point mutation in congenital erythropoietic porphyria in two members of Japanese family. Hum Genet. 1996 May;97(5):557-60. [PubMed ]
8. Tezcan I, Xu W, Gurgey A, Tuncer M, Cetin M, Oner C, Yetgin S, Ersoy F, Aizencang G, Astrin KH, Desnick RJ: Congenital erythropoietic porphyria successfully treated by allogeneic bone marrow transplantation. Blood. 1998 Dec 1;92(11):4053-8. [PubMed ]
9. Frank J, Wang X, Lam HM, Aita VM, Jugert FK, Goerz G, Merk HF, Poh-Fitzpatrick MB, Christiano AM: C73R is a hotspot mutation in the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria. Ann Hum Genet. 1998 May;62(Pt 3):225-30. [PubMed ]
10. Rogounovitch T, Takamura N, Hombrados I, Morel C, Tanaka T, Kameyoshi Y, Shimizu-Yoshida Y, de Verneuil H, Yamashita S: Congenital erythropoietic porphyria: a novel homozygous mutation in a Japanese patient. J Invest Dermatol. 2000 Dec;115(6):1156. [PubMed ]
11. Shady AA, Colby BR, Cunha LF, Astrin KH, Bishop DF, Desnick RJ: Congenital erythropoietic porphyria: identification and expression of eight novel mutations in the uroporphyrinogen III synthase gene. Br J Haematol. 2002 Jun;117(4):980-7. [PubMed ]

1. Hydroxymethylbilane synthase
2. HMBS
3. Pre-uroporphyrinogen synthase
4. PBG-D

MSGNGNAAATAEENSPKMRVIRVGTRKSQLARIQTDSVVATLKASYPGLQFEIIAMSTTG
DKILDTALSKIGEKSLFTKELEHALEKNEVDLVVHSLKDLPTVLPPGFTIGAICKRENPH
DAVVFHPKFVGKTLETLPEKSVVGTSSLRRAAQLQRKFPHLEFRSIRGNLNTRLRKLDEQ
QEFSAIILATAGLQRMGWHNRVGQILHPEECMYAVGQGALGVEVRAKDQDILDLVGVLHD
PETLLRCIAERAFLRHLEGGCSVPVAVHTAMKDGQLYLTGGVWSLDGSDSIQETMQATIH
VPAQHEDGPEDDPQLVGITARNIPRGPQLAAQNLGISLANLLLSKGAKNILDVARQLNDA
H

• Porphyrin Metabolism (map00860 )

• 4 porphobilinogen + H2O = hydroxymethylbilane + 4 NH3

• Porphobil_deam (PF01379 )
• Porphobil_deamC (PF03900 )

• None

• None

ATGAGAGTGATTCGCGTGGGTACCCGCAAGAGCCAGCTTGCTCGCATACAGACGGACAGT
GTGGTGGCAACATTGAAAGCCTCGTACCCTGGCCTGCAGTTTGAAATCATTGCTATGTCC
ACCACAGGGGACAAGATTCTTGATACTGCACTCTCTAAGATTGGAGAGAAAAGCCTGTTT
ACCAAGGAGCTTGAACATGCCCTGGAGAAGAATGAAGTGGACCTGGTTGTTCACTCCTTG
AAGGACCTGCCCACTGTGCTTCCTCCTGGCTTCACCATCGGAGCCATCTGCAAGCGGGAA
AACCCTCATGATGCTGTTGTCTTTCACCCAAAATTTGTTGGGAAGACCCTAGAAACCCTG
CCAGAGAAGAGTGTGGTGGGAACCAGCTCCCTGCGAAGAGCAGCCCAGCTGCAGAGAAAG
TTCCCGCATCTGGAGTTCAGGAGTATTCGGGGAAACCTCAACACCCGGCTTCGGAAGCTG
GACGAGCAGCAGGAGTTCAGTGCCATCATCCTAGCAACAGCTGGCCTGCAGCGCATGGGC
TGGCACAACCGGGTTGGGCAGATCCTGCACCCTGAGGAATGCATGTATGCTGTGGGCCAG
GGGGCCTTGGGCGTGGAAGTGCGAGCCAAGGACCAGGACATCTTGGATCTGGTGGGTGTG
CTGCACGATCCCGAGACTCTGCTTCGCTGCATCGCTGAAAGGGCCTTCCTGAGGCACCTG
GAAGGAGGCTGCAGTGTGCCAGTAGCCGTGCATACAGCTATGAAGGATGGGCAACTGTAC
CTGACTGGAGGAGTCTGGAGTCTAGACGGCTCAGATAGCATACAAGAGACCATGCAGGCT
ACCATCCATGTCCCTGCCCAGCATGAAGATGGCCCTGAGGATGACCCACAGTTGGTAGGC
ATCACTGCTCGTAACATTCCACGAGGGCCCCAGTTGGCTGCCCAGAACTTGGGCATCAGC
CTGGCCAACTTGTTGCTGAGCAAAGGAGCCAAAACCATCCTGGATGTTGCACGGCAGCTT
AACGATGCCCATTAA

1. Raich N, Romeo PH, Dubart A, Beaupain D, Cohen-Solal M, Goossens M: Molecular cloning and complete primary sequence of human erythrocyte porphobilinogen deaminase. Nucleic Acids Res. 1986 Aug 11;14(15):5955-68. [PubMed ]
2. Grandchamp B, De Verneuil H, Beaumont C, Chretien S, Walter O, Nordmann Y: Tissue-specific expression of porphobilinogen deaminase. Two isoenzymes from a single gene. Eur J Biochem. 1987 Jan 2;162(1):105-10. [PubMed ]
3. Yoo HW, Warner CA, Chen CH, Desnick RJ: Hydroxymethylbilane synthase: complete genomic sequence and amplifiable polymorphisms in the human gene. Genomics. 1993 Jan;15(1):21-9. [PubMed ]
4. Chretien S, Dubart A, Beaupain D, Raich N, Grandchamp B, Rosa J, Goossens M, Romeo PH: Alternative transcription and splicing of the human porphobilinogen deaminase gene result either in tissue-specific or in housekeeping expression. Proc Natl Acad Sci U S A. 1988 Jan;85(1):6-10. [PubMed ]
5. Lannfelt L, Wetterberg L, Lilius L, Thunell S, Jornvall H, Pavlu B, Wielburski A, Gellerfors P: Porphobilinogen deaminase in human erythrocytes: purification of two forms with apparent molecular weights of 40 kDa and 42 kDa. Scand J Clin Lab Invest. 1989 Nov;49(7):677-84. [PubMed ]
6. Astrin KH, Desnick RJ: Molecular basis of acute intermittent porphyria: mutations and polymorphisms in the human hydroxymethylbilane synthase gene. Hum Mutat. 1994;4(4):243-52. [PubMed ]
7. Delfau MH, Picat C, de Rooij FW, Hamer K, Bogard M, Wilson JH, Deybach JC, Nordmann Y, Grandchamp B: Two different point G to A mutations in exon 10 of the porphobilinogen deaminase gene are responsible for acute intermittent porphyria. J Clin Invest. 1990 Nov;86(5):1511-6. [PubMed ]
8. Delfau MH, Picat C, De Rooij F, Voortman G, Deybach JC, Nordmann Y, Grandchamp B: Molecular heterogeneity of acute intermittent porphyria: identification of four additional mutations resulting in the CRIM-negative subtype of the disease. Am J Hum Genet. 1991 Aug;49(2):421-8. [PubMed ]
9. Gu XF, de Rooij F, Voortman G, Te Velde K, Nordmann Y, Grandchamp B: High frequency of mutations in exon 10 of the porphobilinogen deaminase gene in patients with a CRIM-positive subtype of acute intermittent porphyria. Am J Hum Genet. 1992 Sep;51(3):660-5. [PubMed ]
10. Mgone CS, Lanyon WG, Moore MR, Connor JM: Detection of seven point mutations in the porphobilinogen deaminase gene in patients with acute intermittent porphyria, by direct sequencing of in vitro amplified cDNA. Hum Genet. 1992 Sep-Oct;90(1-2):12-6. [PubMed ]
11. Kauppinen R, Peltonen L, Pihlaja H, Mustajoki P: CRIM-positive mutations of acute intermittent porphyria in Finland. Hum Mutat. 1992;1(5):392-6. [PubMed ]
12. Mgone CS, Lanyon WG, Moore MR, Louie GV, Connor JM: Detection of a high mutation frequency in exon 12 of the porphobilinogen deaminase gene in patients with acute intermittent porphyria. Hum Genet. 1993 Dec;92(6):619-22. [PubMed ]
13. Llewellyn DH, Whatley S, Elder GH: Acute intermittent porphyria caused by an arginine to histidine substitution (R26H) in the cofactor-binding cleft of porphobilinogen deaminase. Hum Mol Genet. 1993 Aug;2(8):1315-6. [PubMed ]
14. Gu XF, de Rooij F, de Baar E, Bruyland M, Lissens W, Nordmann Y, Grandchamp B: Two novel mutations of the porphobilinogen deaminase gene in acute intermittent porphyria. Hum Mol Genet. 1993 Oct;2(10):1735-6. [PubMed ]
15. Gu XF, de Rooij F, Voortman G, Te Velde K, Deybach JC, Nordmann Y, Grandchamp B: Detection of eleven mutations causing acute intermittent porphyria using denaturing gradient gel electrophoresis. Hum Genet. 1994 Jan;93(1):47-52. [PubMed ]
16. Lundin G, Wedell A, Thunell S, Anvret M: Two new mutations in the porphobilinogen deaminase gene and a screening method using PCR amplification of specific alleles. Hum Genet. 1994 Jan;93(1):59-62. [PubMed ]
17. Mgone CS, Lanyon WG, Moore MR, Louie GV, Connor JM: Identification of five novel mutations in the porphobilinogen deaminase gene. Hum Mol Genet. 1994 May;3(5):809-11. [PubMed ]
18. Chen CH, Astrin KH, Lee G, Anderson KE, Desnick RJ: Acute intermittent porphyria: identification and expression of exonic mutations in the hydroxymethylbilane synthase gene. An initiation codon missense mutation in the housekeeping transcript causes "variant acute intermittent porphyria" with normal expression of the erythroid-specific enzyme. J Clin Invest. 1994 Nov;94(5):1927-37. [PubMed ]
19. Kauppinen R, Mustajoki S, Pihlaja H, Peltonen L, Mustajoki P: Acute intermittent porphyria in Finland: 19 mutations in the porphobilinogen deaminase gene. Hum Mol Genet. 1995 Feb;4(2):215-22. [PubMed ]
20. Lundin G, Hashemi J, Floderus Y, Thunell S, Sagen E, Laegreid A, Wassif W, Peters T, Anvret M: Four mutations in the porphobilinogen deaminase gene in patients with acute intermittent porphyria. J Med Genet. 1995 Dec;32(12):979-81. [PubMed ]
21. Puy H, Deybach JC, Lamoril J, Robreau AM, Da Silva V, Gouya L, Grandchamp B, Nordmann Y: Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria. Am J Hum Genet. 1997 Jun;60(6):1373-83. [PubMed ]
22. Lundin G, Lee JS, Thunell S, Anvret M: Genetic investigation of the porphobilinogen deaminase gene in Swedish acute intermittent porphyria families. Hum Genet. 1997 Jul;100(1):63-6. [PubMed ]
23. Mustajoki S, Pihlaja H, Ahola H, Petersen NE, Mustajoki P, Kauppinen R: Three splicing defects, an insertion, and two missense mutations responsible for acute intermittent porphyria. Hum Genet. 1998 May;102(5):541-8. [PubMed ]
24. Ong PM, Lanyon WG, Hift RJ, Halkett J, Cramp CE, Moore MR, Connor JM: Identification of two novel mutations in the hydroxymethylbilane synthase gene in three patients from two unrelated families with acute intermittent porphyria. Hum Hered. 1998 Jan-Feb;48(1):24-9. [PubMed ]
25. De Siervi A, Rossetti MV, Parera VE, Astrin KH, Aizencang GI, Glass IA, Batlle AM, Desnick RJ: Identification and characterization of hydroxymethylbilane synthase mutations causing acute intermittent porphyria: evidence for an ancestral founder of the common G111R mutation. Am J Med Genet. 1999 Oct 8;86(4):366-75. [PubMed ]
26. Whatley SD, Woolf JR, Elder GH: Comparison of complementary and genomic DNA sequencing for the detection of mutations in the HMBS gene in British patients with acute intermittent porphyria: identification of 25 novel mutations. Hum Genet. 1999 Jun;104(6):505-10. [PubMed ]
27. De Siervi A, Mendez M, Parera VE, Varela L, Batlle AM, Rossetti MV: Acute intermittent porphyria: characterization of two novel mutations in the porphobilinogen deaminase gene, one amino acid deletion (453-455delAGC) and one splicing aceptor site mutation (IVS8-1G>T). Hum Mutat. 1999 Oct;14(4):355. [PubMed ]
28. Gross U, Puy H, Doss M, Robreau AM, Nordmann Y, Doss MO, Deybach JC: New mutations of the hydroxymethylbilane synthase gene in German patients with acute intermittent porphyria. Mol Cell Probes. 1999 Dec;13(6):443-7. [PubMed ]
29. Robreau-Fraolini AM, Puy H, Aquaron C, Bogard C, Traore M, Nordmann Y, Aquaron R, Deybach JC: Porphobilinogen deaminase gene in African and Afro-Caribbean ethnic groups: mutations causing acute intermittent porphyria and specific intragenic polymorphisms. Hum Genet. 2000 Aug;107(2):150-9. [PubMed ]
30. Schneider-Yin X, Bogard C, Rufenacht UB, Puy H, Nordmann Y, Minder EI, Deybach J: Identification of a prevalent nonsense mutation (W283X) and two novel mutations in the porphobilinogen deaminase gene of Swiss patients with acute intermittent porphyria. Hum Hered. 2000 Jul-Aug;50(4):247-50. [PubMed ]
31. De Siervi A, Weiss Cadiz DE, Parera VE, del C Batlle AM, Rossetti MV: Identification and characterization of two novel mutations that produce acute intermittent porphyria: A 3-base deletion (841-843delGGA) and a missense mutation (T35M). Hum Mutat. 2000 Oct;16(4):373. [PubMed ]

1. CYPIVA11
2. Fatty acid omega-hydroxylase
3. P-450 HK omega
4. Lauric acid omega-hydroxylase
5. CYP4AII
6. P450-HL-omega

MSVSVLSPSRLLGDVSGILQAASLLILLLLLIKAVQLYLHRQWLLKALQQFPCPPSHWLF
GHIQELQQDQELQRIQKWVETFPSACPHWLWGGKVRVQLYDPDYMKVILGRSDPKSHGSY
RFLAPWIGYGLLLLNGQTWFQHRRMLTPAFHYDILKPYVGLMADSVRVMLDKWEELLGQD
SPLEVFQHVSLMTLDTIMKCAFSHQGSIQVDRNSQSYIQAISDLNNLVFSRVRNAFHQND
TIYSLTSAGRWTHRACQLAHQHTDQVIQLRKAQLQKEGELEKIKRKRHLDFLDILLLAKM
ENGSILSDKDLRAEVDTFMFEGHDTTASGISWILYALATHPKHQERCREEIHSLLGDGAS
ITWNHLDQMPYTTMCIKEALRLYPPVPGIGRELSTPVTFPDGRSLPKGIMVLLSIYGLHH
NPKVWPNPEVFDPFRFAPGSAQHSHAFLPFSGGSRNCIGKQFAMNELKVATALTLLRFEL
LPDPTRIPIPIARLVLKSKNGIHLRLRRLPNPCEDKDQL

• Fatty Acid Metabolism (map00071 )

• octane + reduced rubredoxin + O2 = 1-octanol + oxidized rubredoxin + H2O

• p450 (PF00067 )

• 1-37

• 118-140

ATGAGTGTCTCTGTGCTGAGCCCCAGCAGACTCCTGGGTGATGTCTCTGGAATCCTCCAA
GCGGCCTCCCTGCTCATTCTGCTTCTGCTGCTGATCAAGGCAGTTCAGCTCTACCTGCAC
AGGCAGTGGCTGCTCAAAGCCCTCCAGCAGTTCCCGTGCCCTCCCTCCCACTGGCTCTTC
GGGCACATCCAGGAGCTCCAACAGGACCAGGAGCTACAACGGATTCAGAAATGGGTGGAG
ACATTCCCAAGTGCCTGTCCTCATTGGCTATGGGGAGGCAAAGTTCGTGTCCAGCTCTAT
GACCCTGACTATATGAAGGTGATTCTGGGGAGATCAGACCCGAAATCCCATGGTTCCTAC
AGATTCCTGGCTCCATGGATTGGGTACGGCTTGCTCCTGTTGAATGGGCAGACATGGTTC
CAGCATCGACGGATGCTGACCCCAGCCTTCCACTATGACATCCTGAAGCCCTATGTGGGG
CTCATGGCAGACTCTGTACGAGTGATGCTGGACAAATGGGAAGAGCTCCTTGGCCAGGAT
TCCCCTCTGGAGGTCTTTCAGCACGTCTCCTTGATGACCCTGGACACCATCATGAAGTGT
GCCTTCAGCCATCAGGGCAGCATCCAGGTGGACAGGAATTCTCAGTCCTACATACAGGCC
ATTAGTGACCTGAACAACCTGGTTTTTTCCCGTGTGAGGAATGCCTTTCACCAGAATGAC
ACCATCTACAGCCTGACCTCTGCTGGCCGCTGGACACACCGCGCCTGCCAGCTGGCCCAT
CAGCACACAGACCAAGTGATCCAACTGAGGAAGGCTCAACTACAGAAGGAGGGGGAGCTG
GAGAAGATCAAGAGGAAGAGGCATTTGGATTTTCTGGATATCCTCCTCTTGGCCAAAATG
GAGAATGGGAGCATCTTGTCAGACAAGGACCTCCGTGCTGAGGTGGACACGTTCATGTTT
GAGGGCCACGACACCACAGCCAGTGGGATCTCCTGGATCCTCTATGCTCTGGCCACACAC
CCCAAGCATCAGGAGAGGTGCCGGGAGGAGATCCACAGCCTCCTGGGTGATGGAGCCTCC
ATCACCTGGAACCACCTGGACCAGATGCCCTACACCACCATGTGCATTAAGGAGGCACTG
AGGCTCTACCCACCGGTGCCAGGCATTGGCAGAGAGCTCAGCACTCCCGTCACCTTCCCT
GATGGGCGCTCCTTGCCCAAAGGTATCATGGTCCTCCTCTCCATTTATGGCCTTCACCAC
AACCCAAAAGTGTGGCCCAACCCAGAGGTGTTTGACCCTTTCCGTTTTGCACCGGGTTCT
GCTCAACACAGCCACGCTTTCCTGCCCTTCTCAGGAGGATCAAGGAACTGCATTGGGAAA
CAATTTGCCATGAACGAGCTGAAGGTGGCCACGGCCCTGACCCTGCTCCGCTTTGAGCTG
CTGCCTGATCCCACCAGGATCCCCATCCCCATTGCACGACTTGTGTTGAAATCCAAAAAT
GGAATCCACCTGCGTCTCAGGAGGCTCCCTAACCCTTGTGAAGACAAGGACCAGCTTTGA

1. Palmer CN, Richardson TH, Griffin KJ, Hsu MH, Muerhoff AS, Clark JE, Johnson EF: Characterization of a cDNA encoding a human kidney, cytochrome P-450 4A fatty acid omega-hydroxylase and the cognate enzyme expressed in Escherichia coli. Biochim Biophys Acta. 1993 Feb 20;1172(1-2):161-6. [PubMed ]
2. Kawashima H, Kusunose E, Kikuta Y, Kinoshita H, Tanaka S, Yamamoto S, Kishimoto T, Kusunose M: Purification and cDNA cloning of human liver CYP4A fatty acid omega-hydroxylase. J Biochem (Tokyo). 1994 Jul;116(1):74-80. [PubMed ]
3. Imaoka S, Ogawa H, Kimura S, Gonzalez FJ: Complete cDNA sequence and cDNA-directed expression of CYP4A11, a fatty acid omega-hydroxylase expressed in human kidney. DNA Cell Biol. 1993 Dec;12(10):893-9. [PubMed ]
4. Bellamine A, Wang Y, Waterman MR, Gainer JV 3rd, Dawson EP, Brown NJ, Capdevila JH: Characterization of the CYP4A11 gene, a second CYP4A gene in humans. Arch Biochem Biophys. 2003 Jan 1;409(1):221-7. [PubMed ]
5. Kawashima H, Kusunose E, Kubota I, Maekawa M, Kusunose M: Purification and NH2-terminal amino acid sequences of human and rat kidney fatty acid omega-hydroxylases. Biochim Biophys Acta. 1992 Jan 24;1123(2):156-62. [PubMed ]
6. Bell DR, Plant NJ, Rider CG, Na L, Brown S, Ateitalla I, Acharya SK, Davies MH, Elias E, Jenkins NA, et al.: Species-specific induction of cytochrome P-450 4A RNAs: PCR cloning of partial guinea-pig, human and mouse CYP4A cDNAs. Biochem J. 1993 Aug 15;294 ( Pt 1):173-80. [PubMed ]
7. Hoch U, Ortiz De Montellano PR: Covalently linked heme in cytochrome p4504a fatty acid hydroxylases. J Biol Chem. 2001 Apr 6;276(14):11339-46. Epub 2001 Jan 3. [PubMed ]
8. LeBrun LA, Hoch U, Ortiz de Montellano PR: Autocatalytic mechanism and consequences of covalent heme attachment in the cytochrome P4504A family. J Biol Chem. 2002 Apr 12;277(15):12755-61. Epub 2002 Jan 30. [PubMed ]

1. IDO
2. Indoleamine-pyrrole 2,3-dioxygenase

MAHAMENSWTISKEYHIDEEVGFALPNPQENLPDFYNDWMFIAKHLPDLIESGQLRERVE
KLNMLSIDHLTDHKSQRLARLVLGCITMAYVWGKGHGDVRKVLPRNIAVPYCQLSKKLEL
PPILVYADCVLANWKKKDPNKPLTYENMDVLFSFRDGDCSKGFFLVSLLVEIAAASAIKV
IPTVFKAMQMQERDTLLKALLEIASCLEKALQVFHQIHDHVNPKAFFSVLRIYLSGWKGN
PQLSDGLVYEGFWEDPKEFAGGSAGQSSVFQCFDVLLGIQQTAGGGHAAQFLQDMRRYMP
PAHRNFLCSLESNPSVREFVLSKGDAGLREAYDACVKALVSLRSYHLQIVTKYILIPASQ
QPKENKTSEDPSKLEAKGTGGTDLMNFLKTVRSTTEKSLLKEG

• IDO (PF01231 )

• None

• None

ATGGCACACGCTATGGAAAACTCCTGGACAATCAGTAAAGAGTACCATATTGATGAAGAA
GTGGGCTTTGCTCTGCCAAATCCACAGGAAAATCTACCTGATTTTTATAATGACTGGATG
TTCATTGCTAAACATCTGCCTGATCTCATAGAGTCTGGCCAGCTTCGAGAAAGAGTTGAG
AAGTTAAACATGCTCAGCATTGATCATCTCACAGACCACAAGTCACAGCGCCTTGCACGT
CTAGTTCTGGGATGCATCACCATGGCATATGTGTGGGGCAAAGGTCATGGAGATGTCCGT
AAGGTCTTGCCAAGAAATATTGCTGTTCCTTACTGCCAACTCTCCAAGAAACTGGAACTG
CCTCCTATTTTGGTTTATGCAGACTGTGTCTTGGCAAACTGGAAGAAAAAGGATCCTAAT
AAGCCCCTGACTTATGAGAACATGGACGTTTTGTTCTCATTTCGTGATGGAGACTGCAGT
AAAGGATTCTTCCTGGTCTCTCTATTGGTGGAAATAGCAGCTGCTTCTGCAATCAAAGTA
ATTCCTACTGTATTCAAGGCAATGCAAATGCAAGAACGGGACACTTTGCTAAAGGCGCTG
TTGGAAATAGCTTCTTGCTTGGAGAAAGCCCTTCAAGTGTTTCACCAAATCCACGATCAT
GTGAACCCAAAAGCATTTTTCAGTGTTCTTCGCATATATTTGTCTGGCTGGAAAGGCAAC
CCCCAGCTATCAGACGGTCTGGTGTATGAAGGGTTCTGGGAAGACCCAAAGGAGTTTGCA
GGGGGCAGTGCAGGCCAAAGCAGCGTCTTTCAGTGCTTTGACGTCCTGCTGGGCATCCAG
CAGACTGCTGGTGGAGGACATGCTGCTCAGTTCCTCCAGGACATGAGAAGATATATGCCA
CCAGCTCACAGGAACTTCCTGTGCTCATTAGAGTCAAATCCCTCAGTCCGTGAGTTTGTC
CTTTCAAAAGGTGATGCTGGCCTGCGGGAAGCTTATGACGCCTGTGTGAAAGCTCTGGTC
TCCCTGAGGAGCTACCATCTGCAAATCGTGACTAAGTACATCCTGATTCCTGCAAGCCAG
CAGCCAAAGGAGAATAAGACCTCTGAAGACCCTTCAAAACTGGAAGCCAAAGGAACTGGA
GGCACTGATTTAATGAATTTCCTGAAGACTGTGAGAAGTACAACTGAGAAATCCCTTTTG
AAGGAAGGTTAA

1. Dai W, Gupta SL: Molecular cloning, sequencing and expression of human interferon-gamma-inducible indoleamine 2,3-dioxygenase cDNA. Biochem Biophys Res Commun. 1990 Apr 16;168(1):1-8. [PubMed ]
2. Tone S, Takikawa O, Habara-Ohkubo A, Kadoya A, Yoshida R, Kido R: Primary structure of human indoleamine 2,3-dioxygenase deduced from the nucleotide sequence of its cDNA. Nucleic Acids Res. 1990 Jan 25;18(2):367. [PubMed ]
3. Kadoya A, Tone S, Maeda H, Minatogawa Y, Kido R: Gene structure of human indoleamine 2,3-dioxygenase. Biochem Biophys Res Commun. 1992 Nov 30;189(1):530-6. [PubMed ]

1. TO
2. Tryptophan pyrrolase
3. Tryptophanase
4. Tryptophan oxygenase
5. Tryptamin 2,3-dioxygenase
6. TRPO

MSGCPFLGNNFGYTFKKLPVEGSEEDKSQTGVNRASKGGLIYGNYLHLEKVLNAQELQSE
TKGNKIHDEHLFIITHQAYELWFKQILWELDSVREIFQNGHVRDERNMLKVVSRMHRVSV
ILKLLVQQFSILETMTALDFNDFREYLSPASGFQSLQFRLLENKIGVLQNMRVPYNRRHY
RDNFKGEENELLLKSEQEKTLLELVEAWLERTPGLEPHGFNFWGKLEKNITRGLEEEFIR
IQAKEESEEKEEQVAEFQKQKEVLLSLFDEKRHEHLLSKGERRLSYRALQGALMIYFYRE
EPRFQVPFQLLTSLMDIDSLMTKWRYNHVCMVHRMLGSKAGTGGSSGYHYLRSTVSDRYK
VFVDLFNLSTYLIPRHWIPKMNPTIHKFLYTAEYCDSSYFSSDESD

• Tryptophan Metabolism (map00380 )

• L-tryptophan + O2 = L-formylkynurenine

• Trp_dioxygenase (PF03301 )

• None

• None

ATGAGTGGGTGCCCATTTTTAGGAAACAACTTTGGATATACTTTTAAAAAACTCCCCGTA
GAAGGCAGCGAAGAAGACAAATCACAAACTGGTGTGAATAGAGCCAGCAAAGGAGGTCTT
ATCTATGGGAACTACCTGCATTTGGAAAAAGTTTTGAATGCACAAGAACTGCAAAGTGAA
ACAAAAGGAAATAAAATCCATGATGAACATCTTTTTATCATAACTCATCAAGCTTATGAA
CTCTGGTTTAAGCAAATCCTCTGGGAGTTGGATTCTGTTCGAGAGATCTTTCAGAATGGC
CATGTCAGAGATGAAAGGAACATGCTTAAGGTTGTTTCTCGGATGCACCGAGTGTCAGTG
ATCCTGAAACTGCTGGTGCAGCAGTTTTCCATTCTGGAGACGATGACAGCCTTGGACTTC
AATGACTTCAGAGAGTACTTATCTCCAGCATCAGGCTTCCAGAGTTTGCAATTCCGACTA
TTAGAAAACAAGATAGGTGTTCTTCAGAACATGAGAGTCCCTTATAACAGAAGACATTAT
CGTGATAACTTCAAAGGAGAAGAAAATGAACTGCTACTTAAATCTGAGCAGGAAAAGACA
CTTCTGGAATTAGTGGAGGCATGGCTGGAAAGAACTCCAGGTTTAGAGCCACATGGATTT
AACTTCTGGGGAAAGCTTGAAAAAAATATCACCAGAGGCCTGGAAGAGGAATTCATAAGG
ATTCAGGCTAAAGAAGAGTCTGAAGAAAAAGAGGAACAGGTGGCTGAATTTCAGAAGCAA
AAAGAGGTGCTACTGTCCTTATTTGATGAGAAACGTCATGAACATCTCCTTAGTAAAGGT
GAAAGACGGCTGTCATACAGAGCACTTCAGGGAGCATTGATGATATATTTTTACAGGGAA
GAGCCTAGGTTCCAGGTGCCTTTTCAGTTGCTGACTTCTCTTATGGACATAGATTCACTG
ATGACCAAATGGAGATATAACCATGTGTGCATGGTGCACAGAATGCTGGGCAGCAAAGCT
GGCACCGGTGGTTCCTCAGGCTATCACTACCTGCGATCAACTGTGAGTGATAGGTACAAG
GTATTTGTAGATTTATTTAATCTTTCAACATACCTGATTCCCCGACACTGGATACCGAAG
ATGAACCCAACCATTCACAAATTTCTATATACAGCAGAATACTGTGATAGCTCCTACTTC
AGCAGTGATGAATCAGATTAA

1. Comings DE, Muhleman D, Dietz G, Sherman M, Forest GL: Sequence of human tryptophan 2,3-dioxygenase (TDO2): presence of a glucocorticoid response-like element composed of a GTT repeat and an intronic CCCCT repeat. Genomics. 1995 Sep 20;29(2):390-6. [PubMed ]

1. CYPXIB1
2. P450C11
3. P-450c11
4. Steroid 11-beta-hydroxylase

MALRAKAEVCMAVPWLSLQRAQALGTRAARVPRTVLPFEAMPQRPGNRWLRLLQIWREQG
YEDLHLEVHQTFQELGPIFRYDLGGAGMVCVMLPEDVEKLQQVDSLHPHRMSLEPWVAYR
QHRGHKCGVFLLNGPEWRFNRLRLNPEVLSPNAVQRFLPMVDAVARDFSQALKKKVLQNA
RGSLTLDVQPSIFHYTIEASNLALFGERLGLVGHSPSSASLNFLHALEVMFKSTVQLMFM
PRSLSRWTSPKVWKEHFEAWDCIFQYGDNCIQKIYQELAFSRPQQYTSIVAELLLNAELS
PDAIKANSMELTAGSVDTTVFPLLMTLFELARNPNVQQALRQESLAAAASISEHPQKATT
ELPLLRAALKETLRLYPVGLFLERVVSSDLVLQNYHIPAGTLVRVFLYSLGRNPALFPRP
ERYNPQRWLDIRGSGRNFYHVPFGFGMRQCLGRRLAEAEMLLLLHHVLKHLQVETLTQED
IKMVYSFILRPSMCPLLTFRAIN

• Androgen and Estrogen Metabolism (map00150 )
• C21 Steroid Hormone Metabolism (map00140 )

• a steroid + reduced adrenal ferredoxin + O2 = an 11beta-hydroxysteroid + oxidized adrenal ferredoxin + H2O

• p450 (PF00067 )

• 1-23

ATGGCACTCAGGGCAAAGGCAGAGGTGTGCATGGCAGTGCCCTGGCTGTCCCTGCAAAGG
GCACAGGCACTGGGCACGAGAGCCGCCCGGGTCCCCAGGACAGTGCTGCCCTTTGAAGCC
ATGCCCCGGCGTCCAGGCAACAGGTGGCTGAGGCTGCTGCAGATCTGGAGGGAGCAGGGT
TATGAGGACCTGCACCTGGAAGTACACCAGACCTTCCAGGAACTGGGGCCCATTTTCAGG
TACGATTTGGGAGGAGCAGGCATGGTGTGTGTGATGCTGCCGGAGGACGTGGAGAAGCTG
CAACAGGTGGACAGCCTGCATCCCCACAGGATGAGCCTGGAGCCCTGGGTGGCCTACAGA
CAACATCGTGGGCACAAATGTGGCGTGTTCTTGCTGAATGGGCCTGAATGGCGCTTCAAC
CGATTGCGGCTGAATCCAGAAGTGCTGTCGCCCAACGCTGTGCAGAGGTTCCTCCCGATG
GTGGATGCAGTGGCCAGGGACTTCTCCCAGGCCCTGAAGAAGAAGGTGCTGCAGAACGCC
CGGGGGAGCCTGACCCTGGACGTCCAGCCCAGCATCTTCCACTACACCATAGAAGCCAGC
AACTTGGCTCTTTTTGGAGAGCGGCTGGGCCTGGTTGGCCACAGCCCCAGTTCTGCCAGC
CTGAACTTCCTCCATGCCCTGGAGGTCATGTTCAAATCCACCGTCCAGCTCATGTTCATG
CCCAGGAGCCTGTCTCGCTGGACCAGCCCCAAGGTGTGGAAGGAGCACTTTGAGGCCTGG
GACTGCATCTTCCAGTACGGCGACAACTGTATCCAGAAAATCTATCAGGAACTGGCCTTC
AGCCGCCCTCAACAGTACACCAGCATCGTGGCGGAGCTCCTGTTGAATGCGGAACTGTCG
CCAGATGCCATCAAGGCCAACTCTATGGAACTCACTGCAGGGAGCGTGGACACGACGGTG
TTTCCCTTGCTGATGACGCTCTTTGAGCTGGCTCGGAACCCCAACGTGCAGCAGGCCCTG
CGCCAGGAGAGCCTGGCCGCCGCAGCCAGCATCAGTGAACATCCCCAGAAGGCAACCACC
GAGCTGCCCTTGCTGCGTGCGGCCCTCAAGGAGACCTTGCGGCTCTACCCTGTGGGTCTG
TTTCTGGAGCGAGTGGCGAGCTCAGACTTGGTGCTTCAGAACTACCACATCCCAGCTGGG
ACATTGGTGCGCGTGTTCCTCTACTCTCTGGGTCGCAACCCCGCCTTGTTCCCGAGGCCT
GAGCGCTATAACCCCCAGCGCTGGCTAGACATCAGGGGCTCCGGCAGGAACTTCTACCAC
GTGCCCTTTGGCTTTGGCATGCGCCAGTGCCTTGGGCGGCGCCTGGCAGAGGCAGAGATG
CTGCTGCTGCTGCACCATGTGCTGAAACACCTCCAGGTGGAGACACTAACCCAAGAGGAC
ATAAAGATGGTCTACAGCTTCATATTGAGGCCCAGCATGTGCCCCCTCCTCACCTTCAGA
GCCATCAACTAA

1. Mornet E, Dupont J, Vitek A, White PC: Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta). J Biol Chem. 1989 Dec 15;264(35):20961-7. [PubMed ]
2. Kawamoto T, Mitsuuchi Y, Toda K, Miyahara K, Yokoyama Y, Nakao K, Hosoda K, Yamamoto Y, Imura H, Shizuta Y: Cloning of cDNA and genomic DNA for human cytochrome P-45011 beta. FEBS Lett. 1990 Sep 3;269(2):345-9. [PubMed ]
3. Naiki Y, Kawamoto T, Mitsuuchi Y, Miyahara K, Toda K, Orii T, Imura H, Shizuta Y: A nonsense mutation (TGG [Trp116]-->TAG [Stop]) in CYP11B1 causes steroid 11 beta-hydroxylase deficiency. J Clin Endocrinol Metab. 1993 Dec;77(6):1677-82. [PubMed ]
4. Chua SC, Szabo P, Vitek A, Grzeschik KH, John M, White PC: Cloning of cDNA encoding steroid 11 beta-hydroxylase (P450c11). Proc Natl Acad Sci U S A. 1987 Oct;84(20):7193-7. [PubMed ]
5. Kawamoto T, Mitsuuchi Y, Toda K, Yokoyama Y, Miyahara K, Miura S, Ohnishi T, Ichikawa Y, Nakao K, Imura H, et al.: Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the biosynthesis of glucocorticoids and mineralocorticoids in humans. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1458-62. [PubMed ]
6. White PC, Dupont J, New MI, Leiberman E, Hochberg Z, Rosler A: A mutation in CYP11B1 (Arg-448----His) associated with steroid 11 beta-hydroxylase deficiency in Jews of Moroccan origin. J Clin Invest. 1991 May;87(5):1664-7. [PubMed ]
7. Joehrer K, Geley S, Strasser-Wozak EM, Azziz R, Wollmann HA, Schmitt K, Kofler R, White PC: CYP11B1 mutations causing non-classic adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Hum Mol Genet. 1997 Oct;6(11):1829-34. [PubMed ]
8. Loidi L, Quinteiro C, Barros F, Dominguez F, Barreiro J, Pombo M: The C494F variant in the CYP11B1 gene is a sequence polymorphism in the Spanish population. J Clin Endocrinol Metab. 1999 Dec;84(12):4749. [PubMed ]
9. 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 ]
10. Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A: Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nat Genet. 1999 Jul;22(3):239-47. [PubMed ]

1. Cholesterol 7-alpha-monooxygenase
2. CYPVII
3. Cholesterol 7-alpha-hydroxylase

MMTTSLIWGIAIAACCCLWLILGIRRRQTGEPPLENGLIPYLGCALQFGANPLEFLRANQ
RKHGHVFTCKLMGKYVHFITNPLSYHKVLCHGKYFDWKKFHFATSAKAFGHRSIDPMDGN
TTENINDTFIKTLQGHALNSLTESMMENLQRIMRPPVSSNSKTAAWVTEGMYSFCYRVMF
EAGYLTIFGRDLTRRDTQKAHILNNLDNFKQFDKVFPALVAGLPIHMFRTAHNAREKLAE
SLRHENLQKRESISELISLRMFLNDTLSTFDDLEKAKTHLVVLWASQANTIPATFWSLFQ
MIRNPEAMKAATEEVKRTLENAGQKVSLEGNPICLSQAELNDLPVLDSIIKESLRLSSAS
LNIRTAKEDFTLHLEDGSYNIRKDDIIALYPQLMHLDPEIYPDPLTFKYDRYLDENGKTK
TTFYCNGLKLKYYYMPFGSGATICPGRLFAIHEIKQFLILMLSYFELELIEGQAKCPPLD
QSRAGLGILPPLNDIEFKYKFKHL

• Bile Acid Biosynthesis (map00120 )

• cholesterol + NADPH + H+ + O2 = 7alpha-hydroxycholesterol + NADP+ + H2O

• p450 (PF00067 )

• 1-23

ATGATGACCACATCTTTGATTTGGGGGATTGCTATAGCAGCATGCTGTTGTCTATGGCTT
ATTCTTGGAATTAGGAGAAGGCAAACGGGTGAACCACCTCTAGAGAATGGATTAATTCCA
TACCTGGGCTGTGCTCTGCAATTTGGTGCCAATCCTCTTGAGTTCCTCAGAGCAAATCAA
AGGAAACATGGTCATGTTTTTACCTGCAAACTAATGGGAAAATATGTCCATTTCATCACA
AATCCCTTGTCATACCATAAGGTGTTGTGCCACGGAAAATATTTTGATTGGAAAAAATTT
CACTTTGCTACTTCTGCGAAGGCATTTGGGCACAGAAGCATTGACCCGATGGATGGAAAT
ACCACTGAAAACATAAACGACACTTTCATCAAAACCCTGCAGGGCCATGCCTTGAATTCC
CTCACGGAAAGCATGATGGAAAACCTCCAACGTATCATGAGACCTCCAGTCTCCTCTAAC
TCAAAGACCGCTGCCTGGGTGACAGAAGGGATGTATTCTTTCTGCTACCGAGTGATGTTT
GAAGCTGGGTATTTAACTATCTTTGGCAGAGATCTTACAAGGCGGGACACACAGAAAGCA
CATATTCTAAACAATCTTGACAACTTCAAGCAATTCGACAAAGTCTTTCCAGCCCTGGTA
GCAGGCCTCCCCATTCACATGTTCAGGACTGCGCACAATGCCCGGGAGAAACTGGCAGAG
AGCTTGAGGCACGAGAACCTCCAAAAGAGGGAAAGCATCTCAGAACTGATCAGCCTGCGC
ATGTTTCTCAATGACACTTTGTCCACCTTTGATGATCTGGAGAAGGCCAAGACACACCTC
GTGGTCCTCTGGGCATCGCAAGCAAACACCATTCCAGCGACTTTCTGGAGTTTATTTCAA
ATGATTAGGAACCCAGAAGCAATGAAAGCAGCTACTGAAGAAGTGAAAAGAACATTAGAG
AATGCTGGTCAAAAAGTCAGCTTGGAAGGCAATCCTATTTGTTTGAGTCAAGCAGAACTG
AATGACCTGCCAGTATTAAATAGTATAATCAAGGAATCGCTGAGGCTTTCCAGTGCCTCC
CTCAACATCCGGACAGCTAAGGAGGATTTCACTTTGCACCTTGAGGACGGTTCCTACAAC
ATCCGAAAAGATAGCATCATAGCTCTTTACCCACAGTTAATGCACTTAGATCCAGAAATC
TACCCAGACCCTTTGACTTTTAAATATGATAGGTATCTTGATGAAAACGGGAAGACAAAG
ACTACCTTCTATTGTAATGGACTCAAGTTAAAGTATTACTACATGCCCTTTGGATCGGGA
GCTACAATATGTCCTGGAAGATTGTTCGCTATCCACGAAATCAAGCAATTTTTGATTCTG
ATGCTTTCTTATTTTGAATTGGAGCTTATAGAGGGCCAAGCTAAATGTCCACCTTTGGAC
CAGTCCCGGGCAGGCTTGGGCATTTTGCCGCCATTGAATGATATTGAATTTAAATATAAA
TTCAAGCATTTGTGA

1. Nishimoto M, Noshiro M, Okuda K: Structure of the gene encoding human liver cholesterol 7 alpha-hydroxylase. Biochim Biophys Acta. 1993 Feb 20;1172(1-2):147-50. [PubMed ]
2. Noshiro M, Okuda K: Molecular cloning and sequence analysis of cDNA encoding human cholesterol 7 alpha-hydroxylase. FEBS Lett. 1990 Jul 30;268(1):137-40. [PubMed ]
3. Karam WG, Chiang JY: Polymorphisms of human cholesterol 7 alpha-hydroxylase. Biochem Biophys Res Commun. 1992 Jun 15;185(2):588-95. [PubMed ]
4. Wang DP, Chiang JY: Structure and nucleotide sequences of the human cholesterol 7 alpha-hydroxylase gene (CYP7). Genomics. 1994 Mar 15;20(2):320-3. [PubMed ]
5. Molowa DT, Chen WS, Cimis GM, Tan CP: Transcriptional regulation of the human cholesterol 7 alpha-hydroxylase gene. Biochemistry. 1992 Mar 10;31(9):2539-44. [PubMed ]
6. Saito S, Iida A, Sekine A, Kawauchi S, Higuchi S, Ogawa C, Nakamura Y: Catalog of 680 variations among eight cytochrome p450 ( CYP) genes, nine esterase genes, and two other genes in the Japanese population. J Hum Genet. 2003;48(5):249-70. Epub 2003 Apr 29. [PubMed ]

1. CYPXIB2
2. P-450Aldo
3. Aldosterone synthase
4. ALDOS
5. Aldosterone-synthesizing enzyme
6. Steroid 18-hydroxylase
7. P-450C18

MALRAKAEVCVAAPWLSLQRARALGTRAARAPRTVLPFEAMPQHPGNRWLRLLQIWREQG
YEHLHLEMHQTFQELGPIFRYNLGGPRMVCVMLPEDVEKLQQVDSLHPCRMILEPWVAYR
QHRGHKCGVFLLNGPEWRFNRLRLNPDVLSPKAVQRFLPMVDAVARDFSQALKKKVLQNA
RGSLTLDVQPSIFHYTIEASNLALFGERLGLVGHSPSSASLNFLHALEVMFKSTVQLMFM
PRSLSRWISPKVWKEHFEAWDCIFQYGDNCIQKIYQELAFNRPQHYTGIVAELLLKAELS
LEAIKANSMELTAGSVDTTAFPLLMTLFELARNPDVQQILRQESLAAAASISEHPQKATT
ELPLLRAALKETLRLYPVGLFLERVVSSDLVLQNYHIPAGTLVQVFLYSLGRNAALFPRP
ERYNPQRWLDIRGSGRNFHHVPFGFGMRQCLGRRLAEAEMLLLLHHVLKHFLVETLTQED
IKMVYSFILRPGTSPLLTFRAIN

• C21 Steroid Hormone Metabolism (map00140 )

• corticosterone + reduced adrenal ferredoxin + O2 = 18-hydroxycorticosterone + oxidized adrenal ferredoxin + H2O

• p450 (PF00067 )

• None

• None

ATGGCACTCAGGGCAAAGGCAGAGGTGTGCGTGGCAGCGCCCTGGCTGTGCCTGCAAAGG
GCACGGGCACTGGGCACTAGAGCCGCTCGGGCCCCTAGGACGGTGCTGCCGTTTGAAGCC
ATGCCCCAGCATCCAGGCAACAGGTGGCTGAGGCTGCTGCAGATGTGGAGGGAGCAGGGT
TATGAGCACCTGCACCTGGAGATGCACCAGACCTTCCAGGAGCTGGGGCCCATTTTCAGG
TACAACTTGGGAGGACCACGCATGGTGTGTGTGATGCTGCCGGAGGATGTGGAGAAGCTG
CAACAGGTGGACAGCCTGCATCCCTGCAGGATGATCCTGGAGCCCTGGGTGGCCATCAGA
CAACATCGTGGGCACAAATGTGGCGTGTTCTTGTTGAATGGGCCTGAATGGCGCTTCAAC
CGATTGCGGCTGAACCCAGATGTGCTGTCGCCCAAGGCCGTGCAGAGGTTCCTCCCGATG
GTGGATGCAGTGGCCAGGGACTTTTCCCAGGCCCTGAGGAAGAAGGTGCTGCAGAACGCC
CGGGGGAGCCTGACCCTGGACGTCCAGCCCAGCATCTTCCACTACACCATAGAAGCCAGC
AACTTAGCTCTTTTTGGAGAGCGGCTGGGCCTGGTTGGCCACAGCCCCAGTTCTGCCAGC
CTGAACTTCCTCCATGCCCTGGAGGTCATGTTCAAATCCACCGTCCAGCTCATGTTCATG
CCCAGGAGCCTGTCTCGCTGGATCAGCCCCAAGGTGTGGAAGGAGCACTTTGAGGCCTGG
GACTGCATCTTCCAGTACGGTGACAACTGTATCCAGAAAATCTACCAGGAACTGGCCTTC
AACCGCCCTCAACACTACACAGGCATCGTGGCAGAGCTCCTGTTGAAGGCGGAACTGTCA
CTAGAAGCCATCAAGGCCAACTCTATGGAACTCACTGCAGGGAGCGTGGACACGACAGCG
TTTCCGTTGCTGATGACGCTCTTTGAGCTGGCTCGGAACCCCGACGTGCAGCAGATCCTG
CGCAAGGAGAGCCTGGCCGCCGCAGCCAGCATCAGTGAACATCCCCAGAAGGCAACCACC
GAGCTGCCCTTGCTGCGGGCGGCCCTCAAGGAGACCTTGAGGCTCTACCCTGTGGGTCTG
TTTTTGGAGCGAGTGGTGAGCTCAGACTTGGTGCTTCAGAACTACCACATCCCAGCTGGG
ACATTGGTACAGGTTTTCCTCTACTCGCTGGGTCGCAATGCCGCCTTGTTCCCGAGGCCT
GAGCGGTATAATCCCCAGCGCTGGCTAGACATCAGGGGCTCCGGCAGGAACTTGCACCAC
GTGCCCTTTGGCTTTGGCATGCGCCAGTGCCTCGGGCGGCGCCTGGCAGAGGCAGAGATG
CTGCTGCTGCTGCACCACGTGCTGAAGCGCTTCCTGGTGGAGACACTAACTCAAGAGGAC
ATAAAGATGGTCTACAGCTTCATATTGAGGCCTGGCACGTCCCCCCTCCTCACTTTCAGA
GCGATTAACTAG

1. Mornet E, Dupont J, Vitek A, White PC: Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta). J Biol Chem. 1989 Dec 15;264(35):20961-7. [PubMed ]
2. Kawainoto T, Mitsuuchi Y, Ohnishi T, Ichikawa Y, Yokoyama Y, Sumimoto H, Toda K, Miyahara K, Kuribayashi I, Nakao K, et al.: Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism. Biochem Biophys Res Commun. 1990 Nov 30;173(1):309-16. [PubMed ]
3. Pascoe L, Curnow KM, Slutsker L, Rosler A, White PC: Mutations in the human CYP11B2 (aldosterone synthase) gene causing corticosterone methyloxidase II deficiency. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4996-5000. [PubMed ]
4. Mitsuuchi Y, Kawamoto T, Naiki Y, Miyahara K, Toda K, Kuribayashi I, Orii T, Yasuda K, Miura K, Nakao K, et al.: Congenitally defective aldosterone biosynthesis in humans: the involvement of point mutations of the P-450C18 gene (CYP11B2) in CMO II deficient patients. Biochem Biophys Res Commun. 1992 Jan 31;182(2):974-9. [PubMed ]
5. Mitsuuchi Y, Kawamoto T, Miyahara K, Ulick S, Morton DH, Naiki Y, Kuribayashi I, Toda K, Hara T, Orii T, et al.: Congenitally defective aldosterone biosynthesis in humans: inactivation of the P-450C18 gene (CYP11B2) due to nucleotide deletion in CMO I deficient patients. Biochem Biophys Res Commun. 1993 Feb 15;190(3):864-9. [PubMed ]
6. Nomoto S, Massa G, Mitani F, Ishimura Y, Miyahara K, Toda K, Nagano I, Yamashiro T, Ogoshi S, Fukata J, Onishi S, Hashimoto K, Doi Y, Imura H, Shizuta Y: CMO I deficiency caused by a point mutation in exon 8 of the human CYP11B2 gene encoding steroid 18-hydroxylase (P450C18). Biochem Biophys Res Commun. 1997 May 19;234(2):382-5. [PubMed ]
7. Peter M, Bunger K, Solyom J, Sippell WG: Mutation THR-185 ILE is associated with corticosterone methyl oxidase deficiency type II. Eur J Pediatr. 1998 May;157(5):378-81. [PubMed ]
8. Portrat-Doyen S, Tourniaire J, Richard O, Mulatero P, Aupetit-Faisant B, Curnow KM, Pascoe L, Morel Y: Isolated aldosterone synthase deficiency caused by simultaneous E198D and V386A mutations in the CYP11B2 gene. J Clin Endocrinol Metab. 1998 Nov;83(11):4156-61. [PubMed ]
9. Tamaki S, Iwai N, Tsujita Y, Kinoshita M: Genetic polymorphism of CYP11B2 gene and hypertension in Japanese. Hypertension. 1999 Jan;33(1 Pt 2):266-70. [PubMed ]
10. 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 ]
11. Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A: Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nat Genet. 1999 Jul;22(3):239-47. [PubMed ]
12. Kayes-Wandover KM, Schindler RE, Taylor HC, White PC: Type 1 aldosterone synthase deficiency presenting in a middle-aged man. J Clin Endocrinol Metab. 2001 Mar;86(3):1008-12. [PubMed ]
13. Dunlop FM, Crock PA, Montalto J, Funder JW, Curnow KM: A compound heterozygote case of type II aldosterone synthase deficiency. J Clin Endocrinol Metab. 2003 Jun;88(6):2518-26. [PubMed ]

1. Cytochrome P450 XXI
2. Steroid 21- hydroxylase
3. 21-OHase
4. P450-C21
5. P-450c21
6. P450-C21B

MLLLGLLLLPLLAGARLLWNWWKLRSLHLPPLAPGFLHLLQPDLPIYLLGLTQKFGPIYR
LHLGLQDVVVLNSKRTIEEAMVKKWADFAGRPEPLTYKLVSKNYPDLSLGDYSLLWKAHK
KLTRSALLLGIRDSMEPVVEQLTQEFCERMRAQPGTPVAIEEEFSLLTCSIICYLTFGDK
IKDDNLMPAYYKCIQEVLKTWSHWSIQIVDVIPFLRFFPNPGLRRLKQAIEKRDHIVEMQ
LRQHKESLVAGQWRDMMDYMLQGVAQPSMEEGSGQLLEGHVHMAAVDLLIGGTETTANTL
SWAVVFLLHHPEIQQRLQEELDHELGPGASSSRVPYKDRARLPLLNATIAEVLRLRPVVP
LALPHRTTRPSSISGYDIPEGTVIIPNLQGAHLDETVWERPHEFWPDRFLEPGKNSRALA
FGCGARVCLGEPLARLELFVVLTRLLQAFTLLPSGDALPSLQPLPHCSVILKMQPFQVRL
QPRGMGAHSPGQNQ

• C21 Steroid Hormone Metabolism (map00140 )

• a steroid + AH2 + O2 = a 21-hydroxysteroid + A + H2O

• p450 (PF00067 )

• 1-15

CGCATGAGAGCCCAGCCCGGCACCCCTGTGGCCATTGAGGAGGAATTCTCTCTCCTCACC
TGCAGCATCATCTGTTACCTCACCTTCGGAGACAAGATCAAG

1. White PC, New MI, Dupont B: Structure of human steroid 21-hydroxylase genes. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5111-5. [PubMed ]
2. Higashi Y, Yoshioka H, Yamane M, Gotoh O, Fujii-Kuriyama Y: Complete nucleotide sequence of two steroid 21-hydroxylase genes tandemly arranged in human chromosome: a pseudogene and a genuine gene. Proc Natl Acad Sci U S A. 1986 May;83(9):2841-5. [PubMed ]
3. Rodrigues NR, Dunham I, Yu CY, Carroll MC, Porter RR, Campbell RD: Molecular characterization of the HLA-linked steroid 21-hydroxylase B gene from an individual with congenital adrenal hyperplasia. EMBO J. 1987 Jun;6(6):1653-61. [PubMed ]
4. Helmberg A, Tusie-Luna MT, Tabarelli M, Kofler R, White PC: R339H and P453S: CYP21 mutations associated with nonclassic steroid 21-hydroxylase deficiency that are not apparent gene conversions. Mol Endocrinol. 1992 Aug;6(8):1318-22. [PubMed ]
5. Carroll MC, Campbell RD, Porter RR: Mapping of steroid 21-hydroxylase genes adjacent to complement component C4 genes in HLA, the major histocompatibility complex in man. Proc Natl Acad Sci U S A. 1985 Jan;82(2):521-5. [PubMed ]
6. Matteson KJ, Phillips JA 3rd, Miller WL, Chung BC, Orlando PJ, Frisch H, Ferrandez A, Burr IM: P450XXI (steroid 21-hydroxylase) gene deletions are not found in family studies of congenital adrenal hyperplasia. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5858-62. [PubMed ]
7. Wu DA, Chung BC: Mutations of P450c21 (steroid 21-hydroxylase) at Cys428, Val281, and Ser268 result in complete, partial, or no loss of enzymatic activity, respectively. J Clin Invest. 1991 Aug;88(2):519-23. [PubMed ]
8. White PC, Tusie-Luna MT, New MI, Speiser PW: Mutations in steroid 21-hydroxylase (CYP21). Hum Mutat. 1994;3(4):373-8. [PubMed ]
9. Amor M, Parker KL, Globerman H, New MI, White PC: Mutation in the CYP21B gene (Ile-172----Asn) causes steroid 21-hydroxylase deficiency. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1600-4. [PubMed ]
10. Chiou SH, Hu MC, Chung BC: A missense mutation at Ile172----Asn or Arg356----Trp causes steroid 21-hydroxylase deficiency. J Biol Chem. 1990 Feb 25;265(6):3549-52. [PubMed ]
11. Partanen J, Campbell RD: Substitution of Ile-172 to Asn in the steroid 21-hydroxylase B (P450c21B) gene in a Finnish patient with the simple virilizing form of congenital adrenal hyperplasia. Hum Genet. 1991 Oct;87(6):716-20. [PubMed ]
12. Tusie-Luna MT, Speiser PW, Dumic M, New MI, White PC: A mutation (Pro-30 to Leu) in CYP21 represents a potential nonclassic steroid 21-hydroxylase deficiency allele. Mol Endocrinol. 1991 May;5(5):685-92. [PubMed ]
13. Speiser PW, Dupont J, Zhu D, Serrat J, Buegeleisen M, Tusie-Luna MT, Lesser M, New MI, White PC: Disease expression and molecular genotype in congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Invest. 1992 Aug;90(2):584-95. [PubMed ]
14. Owerbach D, Sherman L, Ballard AL, Azziz R: Pro-453 to Ser mutation in CYP21 is associated with nonclassic steroid 21-hydroxylase deficiency. Mol Endocrinol. 1992 Aug;6(8):1211-5. [PubMed ]
15. Wedell A, Ritzen EM, Haglund-Stengler B, Luthman H: Steroid 21-hydroxylase deficiency: three additional mutated alleles and establishment of phenotype-genotype relationships of common mutations. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7232-6. [PubMed ]
16. Wedell A, Luthman H: Steroid 21-hydroxylase (P450c21): a new allele and spread of mutations through the pseudogene. Hum Genet. 1993 Apr;91(3):236-40. [PubMed ]
17. Barbat B, Bogyo A, Raux-Demay MC, Kuttenn F, Boue J, Simon-Bouy B, Serre JL, Mornet E: Screening of CYP21 gene mutations in 129 French patients affected by steroid 21-hydroxylase deficiency. Hum Mutat. 1995;5(2):126-30. [PubMed ]
18. Kirby-Keyser L, Porter CC, Donohoue PA: E380D: a novel point mutation of CYP21 in an HLA-homozygous patient with salt-losing congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Hum Mutat. 1997;9(2):181-2. [PubMed ]
19. Lajic S, Levo A, Nikoshkov A, Lundberg Y, Partanen J, Wedell A: A cluster of missense mutations at Arg356 of human steroid 21-hydroxylase may impair redox partner interaction. Hum Genet. 1997 Jun;99(6):704-9. [PubMed ]
20. Nikoshkov A, Lajic S, Holst M, Wedell A, Luthman H: Synergistic effect of partially inactivating mutations in steroid 21-hydroxylase deficiency. J Clin Endocrinol Metab. 1997 Jan;82(1):194-9. [PubMed ]
21. Ordonez-Sanchez ML, Ramirez-Jimenez S, Lopez-Gutierrez AU, Riba L, Gamboa-Cardiel S, Cerrillo-Hinojosa M, Altamirano-Bustamante N, Calzada-Leon R, Robles-Valdes C, Mendoza-Morfin F, Tusie-Luna MT: Molecular genetic analysis of patients carrying steroid 21-hydroxylase deficiency in the Mexican population: identification of possible new mutations and high prevalence of apparent germ-line mutations. Hum Genet. 1998 Feb;102(2):170-7. [PubMed ]
22. Nikoshkov A, Lajic S, Vlamis-Gardikas A, Tranebjaerg L, Holst M, Wedell A, Luthman H: Naturally occurring mutants of human steroid 21-hydroxylase (P450c21) pinpoint residues important for enzyme activity and stability. J Biol Chem. 1998 Mar 13;273(11):6163-5. [PubMed ]
23. Witchel SF, Smith R, Suda-Hartman M: Identification of CYP21 mutations, one novel, by single strand conformational polymorphism (SSCP) analysis. Mutations in brief no. 218. Online. Hum Mutat. 1999;13(2):172. [PubMed ]
24. Ohlsson G, Muller J, Skakkebaek NE, Schwartz M: Steroid 21-hydroxylase deficiency: mutational spectrum in Denmark, three novel mutations, and in vitro expression analysis. Hum Mutat. 1999;13(6):482-6. [PubMed ]
25. Kapelari K, Ghanaati Z, Wollmann H, Ventz M, Ranke MB, Kofler R, Peters H: A rapid screening for steroid 21-hydroxylase mutations in patients with congenital adrenal hyperplasia. Mutations in brief no. 247. Online. Hum Mutat. 1999;13(6):505. [PubMed ]
26. Lako M, Ramsden S, Campbell RD, Strachan T: Mutation screening in British 21-hydroxylase deficiency families and development of novel microsatellite based approaches to prenatal diagnosis. J Med Genet. 1999 Feb;36(2):119-24. [PubMed ]
27. 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 ]
28. Pinto G, Tardy V, Trivin C, Thalassinos C, Lortat-Jacob S, Nihoul-Fekete C, Morel Y, Brauner R: Follow-up of 68 children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: relevance of genotype for management. J Clin Endocrinol Metab. 2003 Jun;88(6):2624-33. [PubMed ]
29. Stikkelbroeck NM, Hoefsloot LH, de Wijs IJ, Otten BJ, Hermus AR, Sistermans EA: CYP21 gene mutation analysis in 198 patients with 21-hydroxylase deficiency in The Netherlands: six novel mutations and a specific cluster of four mutations. J Clin Endocrinol Metab. 2003 Aug;88(8):3852-9. [PubMed ]

1. Biliverdin-IX alpha- reductase
2. BVR A

MNAEPERKFGVVVVGVGRAGSVRMRDLRNPHPSSAFLNLIGFVSRRELGSIDGVQQISLE
DALSSQEVEVAYICSESSSHEDYIRQFLNAGKHVLVEYPMTLSLAAAQELWELAEQKGKV
LHEEHVELLMEEFAFLKKEVVGKDLLKGSLLFTAGPLEEERFGFPAFSGISRLTWLVSLF
GELSLVSATLEERKEDQYMKMTVCLETEKKSPLSWIEEKGPGLKRNRYLSFHFKSGSLEN
VPNVGVNKNIFLKDQNIFVQKLLGQFSEKELAAEKKRILHCLGLAEEIQKYCCSRK

• Porphyrin Metabolism (map00860 )

• bilirubin + NAD(P)+ = biliverdin + NAD(P)H + H+

• Biliv-reduc_cat (PF09166 )
• GFO_IDH_MocA (PF01408 )

• None

• None

ATGAATGCAGAGCCCGAGAGGAAGTTTGGCGTGGTGGTGGTTGGTGTTGGCCGAGCCGGC
TCCGTGCGGATGAGGGACTTGCGGAATCCACACCCTTCCTCAGCGTTCCTGAACCTGATT
GGCTTCGTGTCGAGAAGGGAGCTCGGGAGCATTGATGGAGTCCAGCAGATTTCTTTGGAG
GATGCTCTTTCCAGCCAAGAGGTGGAGGTCGCCTATATCTGCAGTGAGAGCTCCAGCCAT
GAGGACTACATCAGGCAGTTCCTTAATGCTGGCAAGCACGTCCTTGTGGAATACCCCATG
ACACTGTCATTGGCGGCCGCTCAGGAACTGTGGGAGCTGGCTGAGCAGAAAGGAAAAGTC
TTGCACGAGGAGCATGTTGAACTCTTGATGGAGGAATTCGCTTTCCTGAAAAAAGAAGTG
GTGGGGAAAGACCTGCTGAAAGGGTCGCTCCTCTTCACATCTGACCCGTTGGAAGAAGAC
CGGTTTGGCTTCCCTGCATTCAGCGGCATCTCTCGACTGACCTGGCTGGTCTCCCTCTTT
GGGGAGCTTTCTCTTGTGTCTGCCACTTTGGAAGAGCGAAAGGAAGATCAGTATATGAAA
ATGACAGTGTGTCTGGAGACAGAGAAGAAAAGTCCACTGTCATGGATTGAAGAAAAAGGA
CCTGGTCTAAAACGAAACAGATATTTAAGCTTCCATTTCAAGTCTGGGTCCTTGGAGAAT
GTGCCAAATGTAGGAGTGAATAAGAACATATTTCTGAAAGATCAAAATATATTTGTCCAG
AAACTCTTGGGCCAGTTCTCTGAGAAGGAACTGGCTGCTGAAAAGAAACGCATCCTGCAC
TGCCTGGGGCTTGCAGAAGAAATCCAGAAATATTGCTGTTCAAGGAAGTAA

1. Maines MD, Polevoda BV, Huang TJ, McCoubrey WK Jr: Human biliverdin IXalpha reductase is a zinc-metalloprotein. Characterization of purified and Escherichia coli expressed enzymes. Eur J Biochem. 1996 Jan 15;235(1-2):372-81. [PubMed ]
2. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [PubMed ]
3. Maines MD, Trakshel GM: Purification and characterization of human biliverdin reductase. Arch Biochem Biophys. 1993 Jan;300(1):320-6. [PubMed ]
4. Yamaguchi T, Komoda Y, Nakajima H: Biliverdin-IX alpha reductase and biliverdin-IX beta reductase from human liver. Purification and characterization. J Biol Chem. 1994 Sep 30;269(39):24343-8. [PubMed ]

1. FR
2. NADPH-dependent diaphorase
3. NADPH-flavin reductase
4. FLR
5. Biliverdin reductase B
6. BVR-B
7. Biliverdin-IX beta-reductase
8. Green heme-binding protein
9. GHBP

MAVKKIAIFGATGQTGLTTLAQAVQAGYEVTVLVRDSSRLPSEGPRPAHVVVGDVLQAAD
VDKTVAGQDAVIVLLGTRNDLSPTTVMSEGARNIVAAMKAHGVDKVVACTSAFLLWDPTK
VPPRLQAVTDDHIRMHKVLRESGLKYVAVMPPHIGDQPLTGAYTVTLDGRGPSRVISKHD
LGHFMLRCLTTDEYDGHSTYPSHQYQ

• Porphyrin Metabolism (map00860 )

• reduced riboflavin + NADP+ = riboflavin + NADPH + H+

• Epimerase (PF01370 )

• None

• None

ATGGCCGTCAAGAAGATCGCGATCTTCGGCGCCACTGGCCAGACCGGGCTCACCACCCTG
GCGCAGGCGGTGCAAGCAGGTTACGAAGTGACAGTGCTGGTGCGGGACTCCTCCAGGCTG
CCATCAGAGGGGCCCCGGCCGGCCCACGTGGTAGTGGGAGATGTTCTGCAGGCAGCCGAT
GTGGACAAGACCGTGGCTGGGCAGGACGCTGTCATCGTGCTGCTGGGCACCCGCAATGAC
CTCAGTCCCACGACAGTGATGTCCGAGGGCGCCCGGAACATTGTGGCAGCCATGAAGGCT
CATGGTGTGGACAAGGTCGTGGCCTGCACCTCGGCTTTCCTGCTCTGGGACCCTACCAAG
GTGCCCCCACGACTGCAGGCTGTGACTGATGACCACATCCGGATGCACAAGGTGCTGCGG
GAATCAGGCCTGAAGTACGTGGCTGTGATGCCGCCACACATAGGAGACCAGCCACTAACT
GGGGCGTACACAGTGACCCTGGATGGACGAGGGCCCTCAAGGGTCATCTCCAAACATGAC
CTGGGCCATTTCATGCTGCGCTGCCTCACCACCGATGAGTACGACGGACACAGCACCTAC
CCCTCCCACCAGTACCAGTAG

1. Chikuba K, Yubisui T, Shirabe K, Takeshita M: Cloning and nucleotide sequence of a cDNA of the human erythrocyte NADPH-flavin reductase. Biochem Biophys Res Commun. 1994 Feb 15;198(3):1170-6. [PubMed ]
2. Komuro A, Tobe T, Hashimoto K, Nakano Y, Yamaguchi T, Nakajima H, Tomita M: Molecular cloning and expression of human liver biliverdin-IX beta reductase. Biol Pharm Bull. 1996 Jun;19(6):796-804. [PubMed ]
3. Yamaguchi T, Komuro A, Nakano Y, Tomita M, Nakajima H: Complete amino acid sequence of biliverdin-IX beta reductase from human liver. Biochem Biophys Res Commun. 1993 Dec 30;197(3):1518-23. [PubMed ]
4. Yamaguchi T, Komoda Y, Nakajima H: Biliverdin-IX alpha reductase and biliverdin-IX beta reductase from human liver. Purification and characterization. J Biol Chem. 1994 Sep 30;269(39):24343-8. [PubMed ]
5. 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 ]
6. Golaz O, Hughes GJ, Frutiger S, Paquet N, Bairoch A, Pasquali C, Sanchez JC, Tissot JD, Appel RD, Walzer C, et al.: Plasma and red blood cell protein maps: update 1993. Electrophoresis. 1993 Nov;14(11):1223-31. [PubMed ]
7. Shalloe F, Elliott G, Ennis O, Mantle TJ: Evidence that biliverdin-IX beta reductase and flavin reductase are identical. Biochem J. 1996 Jun 1;316 ( Pt 2):385-7. [PubMed ]
8. Pereira PJ, Macedo-Ribeiro S, Parraga A, Perez-Luque R, Cunningham O, Darcy K, Mantle TJ, Coll M: Structure of human biliverdin IXbeta reductase, an early fetal bilirubin IXbeta producing enzyme. Nat Struct Biol. 2001 Mar;8(3):215-20. [PubMed ]

1. CYPXIA1
2. P450(scc
3. Cholesterol side-chain cleavage enzyme
4. Cholesterol desmolase

MLAKGLPPRSVLVKGCQTFLSAPREGLGRLRVPTGEGAGISTRSPRPFNEIPSPGDNGWL
NLYHFWRETGTHKVHLHHVQNFQKYGPIYREKLGNVESVYVIDPEDVALLFKSEGPNPER
FLIPPWVAYHQYYQRPIGVLLKKSAAWKKDRVALNQEVMAPEATKNFLPLLDAVSRDFVS
VLHRRIKKAGSGNYSGDISDDLFRFAFESITNVIFGERQGMLEEVVNPEAQRFIDAIYQM
FHTSVPMLNLPPDLFRLFRTKTWKDHVAAWDVIFSKADIYTQNFYWELRQKGSVHHDYRG
ILYRLLGDSKMSFEDIKANVTEMLAGGVDTTSMTLQWHLYEMARNLKVQDMLRAEVLAAR
HQAQGDMATMLQLVPLLKASIKETLRLHPISVTLQRYLVNDLVLRDYMIPAKTLVQVAIY
ALGREPTFFFDPENFDPTRWLSKDKNITYFRNLGFGWGVRQCLGRRIAELEMTIFLINML
ENFRVEIQHLSDVGTTFNLILMPEKPISFTFWPFNQEATQQ

• C21 Steroid Hormone Metabolism (map00140 )

• cholesterol + reduced adrenal ferredoxin + O2 = pregnenolone + 4-methylpentanal + oxidized adrenal ferredoxin + H2O

• None

• None

ATGCTGGCCAAGGGTCTTCCCCCACGCTCAGTCCTGGTCAAAGGCTACCAGACCTTTCTG
AGTGCCCCCAGGGAGGGGCTGGGGCGTCTCAGGGTGCCCACTGGCGAGGGAGCTGGCATC
TCCACCCGCAGTCCTCGCCCCTTCAATGAGATCCCCTCTCCTGGTGACAATGGCTGGCTA
AACCTGTACCATTTCTGGAGGGAGACGGGCACACACAAAGTCCACCTTCACCATGTCCAG
AATTTCCAGAAGTATGGCCCGATTTACAGGGAGAAGCTCGGCAACGTGGAGTCGGTTTAT
GTCATCGACCCTGAAGATGTGGCCCTTCTCTTTAAGTCCGAGGGCCCCAACCCAGAACGA
TTCCTCATCCCGCCCTGGGTCGCCTATCACCAGTATTACCAGAGACCCATAGGAGTCCTG
TTGAAGAAGTCGGCAGCCTGGAAGAAAGACCGGGTGGCCCTGAACCAGGAGGTGATGGCT
CCAGAGGCCACCAAGAACTTTTTGCCCCTGTTGGATGCAGTGTCTCGGGACTTCGTCAGT
GTCCTGCACAGGCGCATCAAGAAGGCGGGCTCCGGAAATTACTCGGGGGACATCAGTGAT
GACCTGTTCCGCTTTGCCTTTGAGTCCATCACTAACGTCATTTTTGGGGAGCGCCAGGGG
ATGCTGGAGGAAGTAGTGAACCCCGAGGCCCAGCGATTCATTGATGCCATCTACCAGATG
TTCCACACCAGCGTCCCCATGCTCAACCTTCCCCCAGACCTGTTCCGTCTGTTCAGGACC
AAGACCTGGAAGGACCATGTGGCTGCATGGGACGTGATTTTCAGTAAAGCTGACATATAC
ACCCAGAACTTCTACTGGGAATTGAGACAGAAAGGAAGTGTTCACCACGATTACCGTGGC
ATGCTCTACAGACTCCTGGGAGACAGCAAGATGTCCTTCGAGGACATCAAGGCCAACGTC
ACAGAGATGCTGGCAGGAGGGGTGGACACGACGTCCATGACCCTGCAGTGGCACTTGTAT
GAGATGGCACGCAACCTGAAGGTGCAGGATATGCTGCGGGCAGAGGTCTTGGCTGCGCGG
CACCAGGCCCAGGGAGACATGGCCACGATGCTACAGCTGGTCCCCCTCCTCAAAGCCAGC
ATCAAGGAGACACTAAGACTTCACCCCATCTCCGTGACCCTGCAGAGATATCTTGTAAAT
GACTTGGTTCTTCGAGATTACATGATTCCTGCCAAGACACTGGTGCAAGTGGCCATCTAT
GCTCTGGGCCGAGAGCCCACCTTCTTCTTCGACCCGGAAAATTTTGACCCAACCCGATGG
CTGAGCAAAGACAAGAACATCACCTACTTCCGGAACTTGGGCTTTGGCTGGGGTGTGCGG
CAGTGTCTGGGACGGCGGATCGCTGAGCTAGAGATGACCATCTTCCTCATCAATATGCTG
GAGAACTTCAGAGTTGAAATCCAACACCTCAGCGATGTGGGCACCACATTCAACCTCATT
CTGATGCCTGAAAAGCCCATCTCCTTCACCTTCTGGCCCTTTAACCAGGAAGCAACCCAG
CAGTGA

1. Chung BC, Matteson KJ, Voutilainen R, Mohandas TK, Miller WL: Human cholesterol side-chain cleavage enzyme, P450scc: cDNA cloning, assignment of the gene to chromosome 15, and expression in the placenta. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8962-6. [PubMed ]
2. Morohashi K, Sogawa K, Omura T, Fujii-Kuriyama Y: Gene structure of human cytochrome P-450(SCC), cholesterol desmolase. J Biochem (Tokyo). 1987 Apr;101(4):879-87. [PubMed ]
3. Hu MC, Guo IC, Lin JH, Chung BC: Regulated expression of cytochrome P-450scc (cholesterol-side-chain cleavage enzyme) in cultured cell lines detected by antibody against bacterially expressed human protein. Biochem J. 1991 Mar 15;274 ( Pt 3):813-7. [PubMed ]
4. Matteson KJ, Chung BC, Urdea MS, Miller WL: Study of cholesterol side-chain cleavage (20,22 desmolase) deficiency causing congenital lipoid adrenal hyperplasia using bovine-sequence P450scc oligodeoxyribonucleotide probes. Endocrinology. 1986 Apr;118(4):1296-305. [PubMed ]
5. 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 ]
6. Tajima T, Fujieda K, Kouda N, Nakae J, Miller WL: Heterozygous mutation in the cholesterol side chain cleavage enzyme (p450scc) gene in a patient with 46,XY sex reversal and adrenal insufficiency. J Clin Endocrinol Metab. 2001 Aug;86(8):3820-5. [PubMed ]
7. Katsumata N, Ohtake M, Hojo T, Ogawa E, Hara T, Sato N, Tanaka T: Compound heterozygous mutations in the cholesterol side-chain cleavage enzyme gene (CYP11A) cause congenital adrenal insufficiency in humans. J Clin Endocrinol Metab. 2002 Aug;87(8):3808-13. [PubMed ]

1. Serine sulfhydrase
2. Beta- thionase

MPSETPQAEVGPTGCPHRSGPHSAKGSLEKGSPEDKEAKEPLWIRPDAPSRCTWQLGRPA
SESPHHHTAPAKSPKILPDILKKIGDTPMVRINKIGKKFGLKCELLAKCEFFNAGGSVKD
RISLRMIEDAERDGTLKPGDTIIEPTSGNTGIGLALAAAVRGYRCIIVMPEKMSSEKVDV
LRALGAEIVRTPTNARFDSPESHVGVAWRLKNEIPNSHILDQYRNASNPLAHYDTTADEI
LQQCDGKLDMLVASVGTGGTITGIARKLKEKCPGCRIIGVDPEGSILAEPEELNQTEQTT
YEVEGIGYDFIPTVLDRTVVDKWFKSNDEEAFTFARMLIAQEGLLCGGSAGSTVAVAVKA
AQELQEGQRCVVILPDSVRNYMTKFLSDRWMLQKGFLKEEDLTEKKPWWWHLRVQELGLS
APLTVLPTITCGHTIEILREKGFDQAPVVDEAGVILGMVTLGNMLSSLLAGKVQPSDQVG
KVIYKQFKQIRLTDTLGRLSHILEMDHFALVVHEQIQYHSTGKSSQRQMVFGVVTAIDLL
NFVAAQERDQK

• Glycine, Serine and Threonine Metabolism (map00260 )
• Methionine Metabolism (map00271 )
• Selenoamino Acid Metabolism (map00450 )

• L-serine + L-homocysteine = cystathionine + H2O

• CBS (PF00571 )
• PALP (PF00291 )

• None

• None

ATGCCTTCTGAGACCCCCCAGGCAGAAGTGGGGCCCACAGGCTGCCCCCACCGCTCAGGG
CCACACTCGGCGAAGGGGAGCCTGGAGAAGGGGTCCCCAGAGGATAAGGAAGCCAAGGAG
CCCCTGTGGATCCGGCCCGATGCTCCGAGCAGGTGCACCTGGCAGCTGGGCCGGCCTGCC
TCCGAGTCCCCACATCACCACACTGCCCCGGCAAAATCTCCAAAAATCTTGCCAGATATT
CTGAAGAAAATCGGGGACACCCCTATGGTCAGAATCAACAAGATTGGGAAGAAGTTCGGC
CTGAAGTGTGAGCTCTTGGCCAAGTGTGAGTTCTTCAACGCGGGCGGGAGCGTGAAGGAC
CGCATCAGCCTGCGGATGATTGAGGATGCTGAGCGCGACGGGACGCTGAAGCCCGGGGAC
ACGATTATCGAGCCGACATCCGGGAACACCGGGATCGGGCTGGCCCTGGCTGCGGCAGTG
AGGGGCTATCGCTGCATCATCGTGATGCCAGAGAAGATGAGCTCCGAGAAGGTGGACGTG
CTGCGGGCACTGGGGGCTGAGATTGTGAGGACGCCCACCAATGCCAGGTTCGACTCCCCG
GAGTCACACGTGGGGGTGGCCTGGCGGCTGAAGAACGAAATCCCCAATTCTCACATCCTA
GACCAGTACCGCAACGCCAGCAACCCCCTGGCTCACTACGACACCACCGCTGATGAGATC
CTGCAGCAGTGTGATGGGAAGCTGGACATGCTGGTGGCTTCAGTGGGCACGGGCGGCACC
ATCACGGGCATTGCCAGGAAGCTGAAGGAGAAGTGTCCTGGATGCAGGATCATTGGGGTG
GATCCCGAAGGGTCCATCCTCGCAGAGCCGGAGGAGCTGAACCAGACGGAGCAGACAACC
TACGAGGTGGAAGGGATCGGCTACGACTTCATCCCCACGGTGCTGGACAGGACGGTGGTG
GACAAGTGGTTCAAGAGCAACGATGAGGAGGCGTTCACCTTTGCCCGCATGCTGATCGCG
CAAGAGGGGCTGCTGTGCGGTGGCAGTGCTGGCAGCACGGTGGCGGTGGCCGTGAAGGCT
GCGCAGGAGCTGCAGGAGGGCCAGCGCTGCGTGGTCATTCTGCCCGACTCAGTGCGGAAC
TACATGACCAAGTTCCTGAGCGACAGGTGGATGCTGCAGAAGGGCTTTCTGAAGGAGGAG
GACCTCACGGAGAAGAAGCCCTGGTGGTGGCACCTCCGTGTTCAGGAGCTGGGCCTGTCA
GCCCCGCTGACCGTGCTCCCGACCATCACCTGTGGGCACACCATCGAGATCCTCCGGGAG
AAGGGCTTCGACCAGGCGCCCGTGGTGGATGAGGCGGGGGTAATCCTGGGAATGGTGACG
CTTGGGAACATGCTCTCGTCCCTGCTTGCCGGGAAGGTGCAGCCGTCAGACCAAGTTGGC
AAAGTCATCTACAAGCAGTTCAAACAGATCCGCCTCACGGACACGCTGGGCAGGCTCTCG
CACATCCTGGAGATGGACCACTTCGCCCTGGTGGTGCACGAGCAGATCCAGTACCACAGC
ACCGGGAAGTCCAGTCAGCGGCAGATGGTGTTCGGGGTGGTCACCGCCATTGACTTGCTG
AACTTCGTGGCCGCCCAGGAGCGGGACCAGAAGTGA

1. Kraus JP, Le K, Swaroop M, Ohura T, Tahara T, Rosenberg LE, Roper MD, Kozich V: Human cystathionine beta-synthase cDNA: sequence, alternative splicing and expression in cultured cells. Hum Mol Genet. 1993 Oct;2(10):1633-8. [PubMed ]
2. Chasse JF, Paly E, Paris D, Paul V, Sinet PM, Kamoun P, London J: Genomic organization of the human cystathionine beta-synthase gene: evidence for various cDNAs. Biochem Biophys Res Commun. 1995 Jun 26;211(3):826-32. [PubMed ]
3. Kruger WD, Cox DR: A yeast system for expression of human cystathionine beta-synthase: structural and functional conservation of the human and yeast genes. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6614-8. [PubMed ]
4. Chasse JF, Paul V, Escanez R, Kamoun P, London J: Human cystathionine beta-synthase: gene organization and expression of different 5' alternative splicing. Mamm Genome. 1997 Dec;8(12):917-21. [PubMed ]
5. Kraus JP, Oliveriusova J, Sokolova J, Kraus E, Vlcek C, de Franchis R, Maclean KN, Bao L, Bukovsk, Patterson D, Paces V, Ansorge W, Kozich V: The human cystathionine beta-synthase (CBS) gene: complete sequence, alternative splicing, and polymorphisms. Genomics. 1998 Sep 15;52(3):312-24. [PubMed ]
6. Kraus J, Packman S, Fowler B, Rosenberg LE: Purification and properties of cystathionine beta-synthase from human liver. Evidence for identical subunits. J Biol Chem. 1978 Sep 25;253(18):6523-8. [PubMed ]
7. Meier M, Janosik M, Kery V, Kraus JP, Burkhard P: Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein. EMBO J. 2001 Aug 1;20(15):3910-6. [PubMed ]
8. Taoka S, Lepore BW, Kabil O, Ojha S, Ringe D, Banerjee R: Human cystathionine beta-synthase is a heme sensor protein. Evidence that the redox sensor is heme and not the vicinal cysteines in the CXXC motif seen in the crystal structure of the truncated enzyme. Biochemistry. 2002 Aug 20;41(33):10454-61. [PubMed ]
9. Kraus JP, Janosik M, Kozich V, Mandell R, Shih V, Sperandeo MP, Sebastio G, de Franchis R, Andria G, Kluijtmans LA, Blom H, Boers GH, Gordon RB, Kamoun P, Tsai MY, Kruger WD, Koch HG, Ohura T, Gaustadnes M: Cystathionine beta-synthase mutations in homocystinuria. Hum Mutat. 1999;13(5):362-75. [PubMed ]
10. Kozich V, Kraus JP: Screening for mutations by expressing patient cDNA segments in E. coli: homocystinuria due to cystathionine beta-synthase deficiency. Hum Mutat. 1992;1(2):113-23. [PubMed ]
11. Kozich V, de Franchis R, Kraus JP: Molecular defect in a patient with pyridoxine-responsive homocystinuria. Hum Mol Genet. 1993 Jun;2(6):815-6. [PubMed ]
12. Hu FL, Gu Z, Kozich V, Kraus JP, Ramesh V, Shih VE: Molecular basis of cystathionine beta-synthase deficiency in pyridoxine responsive and nonresponsive homocystinuria. Hum Mol Genet. 1993 Nov;2(11):1857-60. [PubMed ]
13. de Franchis R, Kozich V, McInnes RR, Kraus JP: Identical genotypes in siblings with different homocystinuric phenotypes: identification of three mutations in cystathionine beta-synthase using an improved bacterial expression system. Hum Mol Genet. 1994 Jul;3(7):1103-8. [PubMed ]
14. Marble M, Geraghty MT, de Franchis R, Kraus JP, Valle D: Characterization of a cystathionine beta-synthase allele with three mutations in cis in a patient with B6 nonresponsive homocystinuria. Hum Mol Genet. 1994 Oct;3(10):1883-6. [PubMed ]
15. Kraus JP: Komrower Lecture. Molecular basis of phenotype expression in homocystinuria. J Inherit Metab Dis. 1994;17(4):383-90. [PubMed ]
16. Shih VE, Fringer JM, Mandell R, Kraus JP, Berry GT, Heidenreich RA, Korson MS, Levy HL, Ramesh V: A missense mutation (I278T) in the cystathionine beta-synthase gene prevalent in pyridoxine-responsive homocystinuria and associated with mild clinical phenotype. Am J Hum Genet. 1995 Jul;57(1):34-9. [PubMed ]
17. Sebastio G, Sperandeo MP, Panico M, de Franchis R, Kraus JP, Andria G: The molecular basis of homocystinuria due to cystathionine beta-synthase deficiency in Italian families, and report of four novel mutations. Am J Hum Genet. 1995 Jun;56(6):1324-33. [PubMed ]
18. Kluijtmans LA, Blom HJ, Boers GH, van Oost BA, Trijbels FJ, van den Heuvel LP: Two novel missense mutations in the cystathionine beta-synthase gene in homocystinuric patients. Hum Genet. 1995 Aug;96(2):249-50. [PubMed ]
19. Kruger WD, Cox DR: A yeast assay for functional detection of mutations in the human cystathionine beta-synthase gene. Hum Mol Genet. 1995 Jul;4(7):1155-61. [PubMed ]
20. Sperandeo MP, Panico M, Pepe A, Candito M, de Franchis R, Kraus JP, Andria G, Sebastio G: Molecular analysis of patients affected by homocystinuria due to cystathionine beta-synthase deficiency: report of a new mutation in exon 8 and a deletion in intron 11. J Inherit Metab Dis. 1995;18(2):211-4. [PubMed ]
21. Kluijtmans LA, Boers GH, Stevens EM, Renier WO, Kraus JP, Trijbels FJ, van den Heuvel LP, Blom HJ: Defective cystathionine beta-synthase regulation by S-adenosylmethionine in a partially pyridoxine responsive homocystinuria patient. J Clin Invest. 1996 Jul 15;98(2):285-9. [PubMed ]
22. Sperandeo MP, Candito M, Sebastio G, Rolland MO, Turc-Carel C, Giudicelli H, Dellamonica P, Andria G: Homocysteine response to methionine challenge in four obligate heterozygotes for homocystinuria and relationship with cystathionine beta-synthase mutations. J Inherit Metab Dis. 1996;19(3):351-6. [PubMed ]
23. Dawson PA, Cox AJ, Emmerson BT, Dudman NP, Kraus JP, Gordon RB: Characterisation of five missense mutations in the cystathionine beta-synthase gene from three patients with B6-nonresponsive homocystinuria. Eur J Hum Genet. 1997 Jan-Feb;5(1):15-21. [PubMed ]
24. Kim CE, Gallagher PM, Guttormsen AB, Refsum H, Ueland PM, Ose L, Folling I, Whitehead AS, Tsai MY, Kruger WD: Functional modeling of vitamin responsiveness in yeast: a common pyridoxine-responsive cystathionine beta-synthase mutation in homocystinuria. Hum Mol Genet. 1997 Dec;6(13):2213-21. [PubMed ]
25. Aral B, Coude M, London J, Aupetit J, Chasse JF, Zabot MT, Chadefaux-Vekemans B, Kamoun P: Two novel mutations (K384E and L539S) in the C-terminal moiety of the cystathionine beta-synthase protein in two French pyridoxine-responsive homocystinuria patients. Hum Mutat. 1997;9(1):81-2. [PubMed ]
26. Kozich V, Janosik M, Sokolova J, Oliveriusova J, Orendac M, Kraus JP, Elleder D: Analysis of CBS alleles in Czech and Slovak patients with homocystinuria: report on three novel mutations E176K, W409X and 1223 + 37 del99. J Inherit Metab Dis. 1997 Jul;20(3):363-6. [PubMed ]
27. de Franchis R, Kraus E, Kozich V, Sebastio G, Kraus JP: Four novel mutations in the cystathionine beta-synthase gene: effect of a second linked mutation on the severity of the homocystinuric phenotype. Hum Mutat. 1999;13(6):453-7. [PubMed ]

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

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+

• 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
GCTGTGATCCATAGTTTTCAGAAGCAGAATGTGACCATCATGGACCACCACTCGGCTGCA
GAATCCTTCATGAAGTACATGCAGAATGAATACCGGTCCCGTGGGGGCTGCCCGGCAGAC
TGGATTTGGCTGGTCCCTCCCATGTCTGGGAGCATCACCCCCGTGTTTCACCAGGAGATG
CTGAACTACGTCCTGTCCCCTTTCTACTACTATCAGGTAGAGGCCTGGAAAACCCATGTC
TGGCAGGACGAGAAGCGGAGACCCAAGAGAAGAGAGATTCCATTGAAAGTCTTGGTCAAA
GCTGTGCTCTTTGCCTGTATGCTGATGCGCAAGACAATGGCGTCCCGAGTCAGAGTCACC
ATCCTCTTTGCGACAGAGACAGGAAAATCAGAGGCGCTGGCCTGGGACCTGGGGGCCTTA
TTCAGCTGTGCCTTCAACCCCAAGGTTGTCTGCATGGATAAGTACAGGCTGAGCTGCCTG
GAGGAGGAACGGCTGCTGTTGGTGGTGACCAGTACGTTTGGCAATGGAGACTGCCCTGGC
AATGGAGAGAAACTGAAGAAATCGCTCTTCATGCTGAAAGAGCTCAACAACAAATTCAGG
TACGCTGTGTTTGGCCTCGGCTCCAGCATGTACCCTCGGTTCTGCGCCTTTGCTCATGAC
ATTGATCAGAAGCTGTCCCACCTGGGGGCCTCTCAGCTCACCCCGATGGGAGAAGGGGAT
GAGCTCAGTGGGCAGGAGGACGCCTTCCGCAGCTGGGCCGTGCAAACCTTCAAGGCAGCC
TGTGAGACGTTTGATGTCCGAGGCAAACAGCACATTCAGATCCCCAAGCTCTACACCTCC
AATGTGACCTGGGACCCGCACCACTACAGGCTCGTGCAGGACTCACAGCCTTTGGACCTC
AGCAAAGCCCTCAGCAGCATGCATGCCAAGAACGTGTTCACCATGAGGCTCAAATCTCGG
CAGAATCTACAAAGTCCGACATCCAGCCGTGCCACCATCCTGGTGGAACTCTCCTGTGAG
GATGGCCAAGGCCTGAACTACCTGCCGGGGGAGCACCTTGGGGTTTGCCCAGGCAACCAG
CCGGCCCTGGTCCAAGGCATCCTGGAGCGAGTGGTGGATGGCCCCACACCCCACCAGACA
GTGCGCCTGGAGGACCTGGATGAGAGTGGCAGCTACTGGGTCAGTGACAAGAGGCTGCCC
CCCTGCTCACTCAGCCAGGCCCTCACCTACTCCCCGGACATCACCACACCCCCAACCCAG
CTGCTGCTCCAAAAGCTGGCCCAGGTGGCCACAGAAGAGCCTGAGAGACAGAGGCTGGAG
GCCCTGTGCCAGCCCTCAGAGTACAGCAAGTGGAAGTTCACCAACAGCCCCACATTCCTG
GAGGTGCTAGAGGAGTTCCCGTCCCTGCGGGTGTCTGCTGGCTTCCTGCTTTCCCAGCTC
CCCATTCTGAAGCCCAGGTTCTACTCCATCAGCTCCTCCCGGGATCACACGCCCACGGAG
ATCCACCTGACTGTGGCCGTGGTCACCTACCACACCGGAGATGGCCAGGGTCCCCTGCAC
CACGGTGTCTGCAGCACATGGCTCAACAGCCTGAAGCCCCAAGACCCAGTGCCCTGCTTT
GTGCGGAATGCCAGCGCCTTCCACCTCCCCGAGGATCCCTCCCATCCTTGCATCCTCATC
GGGCCTGGCACAGGCATCGTGCCCTTCCGCAGTTTCTGGCAGCAACGGCTCCATGACTCC
CAGCACAAGGGAGTGCGGGGAGGCCGCATGACCTTGGTGTTTGGGTGCCGCCGCCCAGAT
GAGGACCACATCTACCAGGAGGAGATGCTGGAGATGGCCCAGAAGGGGGTGCTGCATGCG
GTGCACACAGCCTATTCCCGCCTGCCTGGCAAGCCCAAGGTCTATGTTCAGGACATCCTG
CGGCAGCAGCTGGCCAGCGAGGTGCTCCGTGTGCTCCACAAGGAGCCAGGCCACCTCTAT
GTTTGCGGGGATGTGCGCATGGCCCGGGACGTGGCCCACACCCTGAAGCAGCTGGTGGCT
GCCAAGCTGAAATTGAATGAGGAGCAGGTCGAGGACTATTTCTTTCAGCTCAAGAGCCAG
AAGCGCTATCACGAAGATATCTTCGGTGCTGTATTTCCTTACGAGGCGAAGAAGGACAGG
GTGGCGGTGCAGCCCAGCAGCCTGGAGATGTCAGCGCTCTGA

1. 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 ]
2. 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 ]
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. 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 ]
10. 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 ]
11. 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 ]
12. 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 ]
13. 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 ]
14. 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 ]

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

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

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+

• 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. Robinson LJ, Weremowicz S, Morton CC, Michel T: Isolation and chromosomal localization of the human endothelial nitric oxide synthase (NOS3) gene. Genomics. 1994 Jan 15;19(2):350-7. [PubMed ]
7. Sase K, Michel T: Expression of constitutive endothelial nitric oxide synthase in human blood platelets. Life Sci. 1995;57(22):2049-55. [PubMed ]
8. 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 ]
9. Rosenfeld RJ, Garcin ED, Panda K, Andersson G, Aberg A, Wallace AV, Morris GM, Olson AJ, Stuehr DJ, Tainer JA, Getzoff ED: Conformational changes in nitric oxide synthases induced by chlorzoxazone and nitroindazoles: crystallographic and computational analyses of inhibitor potency. Biochemistry. 2002 Nov 26;41(47):13915-25. [PubMed ]
10. Yoshimura M, Yasue H, Nakayama M, Shimasaki Y, Sumida H, Sugiyama S, Kugiyama K, Ogawa H, Ogawa Y, Saito Y, Miyamoto Y, Nakao K: A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese. Hum Genet. 1998 Jul;103(1):65-9. [PubMed ]

1. Succinyl-CoA synthetase, betaA chain
2. SCS-betaA
3. ATP- specific succinyl-CoA synthetase subunit beta
4. Renal carcinoma antigen NY-REN-39

MAASMFYGRLVAVATLRNHRPRTAQRAAAQVLGSSGLFNNHGLQVQQQQQRNLSLHEYMS
MELLQEAGVSVPKGYVAKSPDEAYAIAKKLGSKDVVIKAQVLAGGRGKGTFESGLKGGVK
IVFSPEEAKAVSSQMIGKKLFTKQTGEKGRICNQVLVCERKYPRREYYFAITMERSFQGP
VLIGSSHGGVNIEDVAAESPEAIIKEPIDIEEGIKKEQALQLAQKMGFPPNIVESAAENM
VKLYSLFLKYDATMIEINPMVEDSDGAVLCMDAKINFDSNSAYRQKKIFDLQDWTQEDER
DKDAAKANLNYIGLDGNIGCLVNGAGLAMATMDIIKLHGGTPANFLDVGGGATVHQVTEA
FKLITSDKKVLAILVNIFGGIMRCDVIAQGIVMAVKDLEIKIPVVVRLQGTRVDDAKALI
ADSGLKILACDDLDEAARMVVKLSEIVTLAKQAHVDVKFQLPI

• C5-Branched Dibasic Acid Metabolism (map00660 )
• Citrate Cycle (map00020 )
• Propanoate Metabolism (map00640 )

• ATP + succinate + CoA = ADP + phosphate + succinyl-CoA

• ATP-grasp_2 (PF08442 )
• Ligase_CoA (PF00549 )

• None

• None

ATGGCGGCCTCCATGTTCTACGGCAGGCTAGTGGCCGTGGCCACCCTTCGGAACCACCGG
CCTCGGACGGCCCAGCGGGCTGCTGCTCAGGTTCTGGGAAGTTCTGGATTGTTTAATAAC
CATGGACTCCAAGTACAGCAGCAACAGCAAAGGAATCTCTCACTACATGAATACATGAGT
ATGGAATTATTGCAAGAAGCTGGTGTCTCCGTTCCCAAAGGATATGTGGCAAAGTCACCA
GATGAAGCTTATGCAATTGCCAAAAAATTAGGTTCAAAAGATGTCGTGATAAAGGCACAG
GTTTTAGCTGGTGGTAGAGGAAAAGGAACATTTGAAAGTGGCCTCAAAGGAGGAGTGAAG
ATAGTTTTCTCTCCAGAAGAAGCAAAAGCTGTTTCTTCACAAATGATTGGGAAAAAATTG
TTTACCAAGCAAACGGGAGAAAAGGGCAGAATATGCAATCAAGTATTGGTCTGTGAGCGA
AAATATCCCAGGAGAGAATACTACTTTGCAATAACAATGGAAAGGTCATTTCAAGGTCCT
GTATTAATAGGAAGTTCACATGGTGGTGTCAACATTGAAGATGTTGCTGCTGAGTCTCCT
GAAGCAATAATTAAAGAACCTATTGATATTGAAGAAGGCATCAAAAAGGAACAAGCTCTC
CAGCTTGCACAGAAGATGGGATTTCCACCTAATATTGTGGAATCAGCAGCAGAAAACATG
GTCAAGCTTTACAGCCTTTTTCTGAAATACGATGCAACCATGATAGAAATAAATCCAATG
GTGGAAGATTCAGATGGAGCTGTATTGTGTATGGATGCAAAGATCAATTTTGACTCTAAT
TCAGCCTATCGCCAAAAGAAAATCTTTGATCTACAGGACTGGACCCAGGAAGATGAAAGG
GACAAAGATGCTGCTAAGGCAAATCTCAACTACATTGGCCTCGATGGAAATATAGGCTGC
CTAGTAAATGGTGCTGGTTTGGCTATGGCCACAATGGATATAATAAAACTTCATGGAGGG
ACTCCAGCCAACTTCCTTGATGTTGGTGGTGGTGCTACAGTCCATCAAGTAACAGAAGCA
TTTAAGCTTATCACTTCAGATAAAAAGGTACTGGCTATTCTGGTCAACATTTTTGGAGGA
ATCATGCGCTGTGATGTTATTGCACAGGGTATAGTCATGGCAGTAAAAGACTTGGAAATT
AAAATACCTGTTGTGGTACGGTTACAAGGTACACGAGTCGATGATGCTAAGGCACTGATA
GCGGACAGTGGACTTAAAATACTTGCTTGTGATGACTTGGATGAAGCTGCTAGAATGGTT
GTAAAGCTCTCTGAAATAGTGACCTTAGCGAAGCAAGCACATGTGGATGTGAAATTTCAG
TTGCCAATATGA

1. Furuyama K, Sassa S: Interaction between succinyl CoA synthetase and the heme-biosynthetic enzyme ALAS-E is disrupted in sideroblastic anemia. J Clin Invest. 2000 Mar;105(6):757-64. [PubMed ]
2. Johnson JD, Mehus JG, Tews K, Milavetz BI, Lambeth DO: Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes. J Biol Chem. 1998 Oct 16;273(42):27580-6. [PubMed ]
3. Scanlan MJ, Gordan JD, Williamson B, Stockert E, Bander NH, Jongeneel V, Gure AO, Jager D, Jager E, Knuth A, Chen YT, Old LJ: Antigens recognized by autologous antibody in patients with renal-cell carcinoma. Int J Cancer. 1999 Nov 12;83(4):456-64. [PubMed ]

1. Cyclooxygenase- 2
2. COX-2
3. Prostaglandin-endoperoxide synthase 2
4. Prostaglandin H2 synthase 2
5. PGH synthase 2
6. PGHS-2
7. PHS II

MLARALLLCAVLALSHTANPCCSHPCQNRGVCMSVGFDQYKCDCTRTGFYGENCSTPEFL
TRIKLFLKPTPNTVHYILTHFKGFWNVVNNIPFLRNAIMSYVLTSRSHLIDSPPTYNADY
GYKSWEAFSNLSYYTRALPPVPDDCPTPLGVKGKKQLPDSNEIVEKLLLRRKFIPDPQGS
NMMFAFFAQHFTHQFFKTDHKRGPAFTNGLGHGVDLNHIYGETLARQRKLRLFKDGKMKY
QIIDGEMYPPTVKDTQAEMIYPPQVPEHLRFAVGQEVFGLVPGLMMYATIWLREHNRVCD
VLKQEHPEWGDEQLFQTSRLILIGETIKIVIEDYVQHLSGYHFKLKFDPELLFNKQFQYQ
NRIAAEFNTLYHWHPLLPDTFQIHDQKYNYQQFIYNNSILLEHGITQFVESFTRQIAGRV
AGGRNVPPAVQKVSQASIDQSRQMKYQSFNEYRKRFMLKPYESFEELTGEKEMSAELEAL
YGDIDAVELYPALLVEKPRPDAIFGETMVEVGAPFSLKGLMGNVICSPAYWKPSTFGGEV
GFQIINTASIQSLICNNVKGCPFTSFSVPDPELIKTVTINASSSRSGLDDINPTVLLKER
STEL

• Arachidonic acid metabolism (map00590 )

• arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O

• An_peroxidase (PF03098 )
• EGF (PF00008 )

• 1-17

ATGCTCGCCCGCGCCCTGCTGCTGTGCGCGGTCCTGGCGCTCAGCCATACAGCAAATCCT
TGCTGTTCCCACCCATGTCAAAACCGAGGTGTATGTATGAGTGTGGGATTTGACCAGTAT
AAGTGCGATTGTACCCGGACAGGATTCTATGGAGAAAACTGCTCAACACCGGAATTTTTG
ACAAGAATAAAATTATTTCTGAAACCCACTCCAAACACAGTGCACTACATACTTACCCAC
TTCAAGGGATTTTGGAACGTTGTGAATAACATTCCCTTCCTTCGAAATGCAATTATGAGT
TATGTGTTGACATCCAGATCACATTTGATTGACAGTCCACCAACTTACAATGCTGACTAT
GGCTACAAAAGCTGGGAAGCCTTCTCTAACCTCTCCTATTATACTAGAGCCCTTCCTCCT
GTGCCTGATGATTGCCCGACTCCCTTGGGTGTCAAAGGTAAAAAGCAGCTTCCTGATTCA
AATGAGATTGTGGAAAAATTGCTTCTAAGAAGAAAGTTCATCCCTGATCCCCAGGGCTCA
AACATGATGTTTGCATTCTTTGCCCAGCACTTCACGCATCAGTTTTTCAAGACAGATCAT
AAGCGAGGGCCAGCTTTCACCAACGGGCTGGGCCATGGGGTGGACTTAAATCATATTTAC
GGTGAAACTCTGGCTAGACAGCGTAAACTGCGCCTTTTCAAGGATGGAAAAATGAAATAT
CAGATAATTGATGGAGAGATGTATCCTCCCACAGTCAAAGATACTCAGGCAGAGATGATC
TACCCTCCTCAAGTCCCTGAGCATCTACGGTTTGCTGTGGGGCAGGAGGTCTTTGGTCTG
GTGCCTGGTCTGATGATGTATGCCACAATCTGGCTGCGGGAACACAACAGAGTATGCGAT
GTGCTTAAACAGGAGCATCCTGAATGGGGTGATGAGCAGTTGTTCCAGACAAGCAGGCTA
ATACTGATAGGAGAGACTATTAAGATTGTGATTGAAGATTATGTGCAACACTTGAGTGGC
TATCACTTCAAACTGAAATTTGACCCAGAACTACTTTTCAACAAACAATTCCAGTACCAA
AATCGTATTGCTGCTGAATTTAACACCCTCTATCACTGGCATCCCCTTCTGCCTGACACC
TTTCAAATTCATGACCAGAAATACAACTATCAACAGTTTATCTACAACAACTCTATATTG
CTGGAACATGGAATTACCCAGTTTGTTGAATCATTCACCAGGCAAATTGCTGGCAGGGTT
GCTGGTGGTAGGAATGTTCCACCCGCAGTACAGAAAGTATCACAGGCTTCCACTGACCAG
AGCAGGCAGATGAAATACCAGTCTTTTAATGAGTACCGCAAACGCTTTATGCTGAAGCCC
TATGAATCATTTGAAGAACTTACAGGAGAAAAGGAAATGTCTGCAGAGTTGGAAGCACTC
TATGGTGACATCGATGCTGTGGAGCTGTATCCTGCCCTTCTGGTAGAAAAGCCTCGGCCA
GATGCCATCTTTGGTGAAACCATGGTAGAAGTTGGAGCACCATTCTCCTTGAAAGGACTT
ATGGGTAATGTTATATGTTCTCCTGCCTACTGGAAGCCAAGCACTTTTGGTGGAGAAGTG
GGTTTTCAAATCATCAACACTGCCTCAATTCAGTCTCTCATCTGCAATAACGTGAAGGGC
TGTCCCTTTACTTCATTCAGTGTTCCAGATCCAGAGCTCATTAAAACAGTCACCATCAAT
GCAAGTTCTTCCCGCTCCGGACTAGATGATATCAATCCCACAGTACTACTAAAAGAACGT
TCGACTGAACTGTAG

1. Jones DA, Carlton DP, McIntyre TM, Zimmerman GA, Prescott SM: Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines. J Biol Chem. 1993 Apr 25;268(12):9049-54. [PubMed ]
2. Hla T, Neilson K: Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7384-8. [PubMed ]
3. Kosaka T, Miyata A, Ihara H, Hara S, Sugimoto T, Takeda O, Takahashi E, Tanabe T: Characterization of the human gene (PTGS2) encoding prostaglandin-endoperoxide synthase 2. Eur J Biochem. 1994 May 1;221(3):889-97. [PubMed ]
4. Appleby SB, Ristimaki A, Neilson K, Narko K, Hla T: Structure of the human cyclo-oxygenase-2 gene. Biochem J. 1994 Sep 15;302 ( Pt 3):723-7. [PubMed ]

1. Cyclooxygenase- 1
2. COX-1
3. Prostaglandin-endoperoxide synthase 1
4. Prostaglandin H2 synthase 1
5. PGH synthase 1
6. PGHS-1
7. PHS 1

MSRSLLLRFLLFLLLLPPLPVLLADPGAPTPVNPCCYYPCQHQGICVRFGLDRYQCDCTR
TGYSGPNCTIPGLWTWLRNSLRPSPSFTHFLLTHGRWFWEFVNATFIREMLMRLVLTVRS
NLIPSPPTYNSAHDYISWESFSNVSYYTRILPSVPKDCPTPMGTKGKKQLPDAQLLARRF
LLRRKFIPDPQGTNLMFAFFAQHFTHQFFKTSGKMGPGFTKALGHGVDLGHIYGDNLERQ
YQLRLFKDGKLKYQVLDGEMYPPSVEEAPVLMHYPRGIPPQSQMAVGQEVFGLLPGLMLY
ATLWLREHNRVCDLLKAEHPTWGDEQLFQTTRLILIGETIKIVIEEYVQQLSGYFLQLKF
DPELLFGVQFQYRNRIAMEFNHLYHWHPLMPDSFKVGSQEYSYEQFLFNTSMLVDYGVEA
LVDAFSRQIAGRIGGGRNMDHHILHVAVDVIRESREMRLQPFNEYRKRFGMKPYTSFQEL
VGEKEMAAELEELYGDIDALEFYPGLLLEKCHPNSIFGESMIEIGAPFSLKGLLGNPICS
PEYWKPSTFGGEVGFNIVKTATLKKLVCLNTKTCPYVSFRVPDASQDDGPAVERPSTEL

• Arachidonic acid metabolism (map00590 )

• arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O

• An_peroxidase (PF03098 )
• EGF (PF00008 )

• 1-23

ATGAGCCGGAGTCTCTTGCTCCGGTTCTTGCTGTTGCTGCTCCTGCTCCCGCCGCTCCCC
GTCCTGCTCGCGGACCCAGGGGCGCCCACGCCAGTGAATCCCTGTTGTTACTATCCATGC
CAGCACCAGGGCATCTGTGTCCGCTTCGGCCTTGACCGCTACCAGTGTGACTGCACCCGC
ACGGGCTATTCCGGCCCCAACTGCACCATCCCTGGCCTGTGGACCTGGCTCCGGAATTCA
CTGCGGCCCAGCCCCTCTTTCACCCACTTCCTGCTCACTCACGGGCGCTGGTTCTGGGAG
TTTGTCAATGCCACCTTCATCCGAGAGATGCTCATGCTCCTGGTACTCACAGTGCGCTCC
AACCTTATCCCCAGTCCCCCCACCTACAACTCTGCACATGACTACATCAGCTGGGAGTCT
TTCTCCAACGTGAGCTATTACACTCGTATTCTGCCCTCTGTGCCTAAAGATTGCCCCACA
CCCATGGGAACCAAAGGGAAGAAGCAGTTGCCAGATGCCCAGCTCCTGGCCCGCCGCTTC
CTGCTCAGGAGGAAGTTCATACCTGACCCCCAAGGCACCAACCTCATGTTTGCCTTCTTT
GCACAACACTTCACCCACCAGTTCTTCAAAACTTCTGGCAAGATGGGTCCTGGCTTCACC
AAGGCCTTGGGCCATGGGGTAGACCTCGGCCACATTTATGGAGACAATCTGGAGCGTCAG
TATCAACTGCGGCTCTTTAAGGATGGGAAACTCAAGTACCAGGTGCTGGATGGAGAAATG
TACCCGCCCTCGGTAGAAGAGGCGCCTGTGTTGATGCACTACCCCCGAGGCATCCCGCCC
CAGAGCCAGATGGCTGTGGGCCAGGAGGTGTTTGGGCTGCTTCCTGGGCTCATGCTGTAT
GCCACGCTCTGGCTACGTGAGCACAACCGTGTGTGTGACCTGCTGAAGGCTGAGCACCCC
ACCTGGGGCGATGAGCAGCTTTTCCAGACGACCCGCCTCATCCTCATAGGGGAGACCATC
AAGATTGTCATCGAGGAGTACGTGCAGCAGCTGAGTGGCTATTTCCTGCAGCTGAAATTT
GACCCAGAGCTGCTGTTCGGTGTCCAGTTCCAATACCGCAACCGCATTGCCACGGAGTTC
AACCATCTCTACCACTGGCACCCCCTCATGCCTGACTCCTTCAAGGTGGGCTCCCAGGAG
TACAGCTACGAGCAGTTCTTGTTCAACACCTCCATGTTGGTGGACTATGGGGTTGAGGCC
CTGGTGGATGCCTTCTCTCGCCAGATTGCTGGCCGGATCGGTGGGGGCAGGAACATGGAC
CACCACATCCTGCATGTGGCTGTGGATGTCATCAGGGAGTCTCGGGAGATGCGGCTGCAG
CCCTTCAATGAGTACCGCAAGAGGTTTGGCATGAAACCCTACACCTCCTTCCAGGAGCTC
GTAGGAGAGAAGGAGATGGCAGCAGAGTTGGAGGAATTGTATGGAGACATTGATGCGTTG
GAGTTCTACCCTGGACTGCTTCTTGAAAAGTGCCATCCAAACTCTATCTTTGGGGAGAGT
ATGATAGAGATTGGGGCTCCCTTTTCCCTCAAGGGTCTCCTAGGGAATCCCATCTGTTCT
CCGGAGTACTGGAAGCCGAGCACATTTGGCGGCGAGGTGGGCTTTAACATTGTCAAGACG
GCCACACTGAAGAAGCTGGTCTGCCTCAACACCAAGACCTGTCCCTACGTTTCCTTCCGT
GTGCCGGATGCCAGTCAGGATGATGGGCCTGCTGTGGAGCGACCATCCACAGAGCTCTGA

1. Yokoyama C, Tanabe T: Cloning of human gene encoding prostaglandin endoperoxide synthase and primary structure of the enzyme. Biochem Biophys Res Commun. 1989 Dec 15;165(2):888-94. [PubMed ]
2. Funk CD, Funk LB, Kennedy ME, Pong AS, Fitzgerald GA: Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment. FASEB J. 1991 Jun;5(9):2304-12. [PubMed ]
3. Takahashi Y, Ueda N, Yoshimoto T, Yamamoto S, Yokoyama C, Miyata A, Tanabe T, Fuse I, Hattori A, Shibata A: Immunoaffinity purification and cDNA cloning of human platelet prostaglandin endoperoxide synthase (cyclooxygenase). Biochem Biophys Res Commun. 1992 Jan 31;182(2):433-8. [PubMed ]
4. Diaz A, Reginato AM, Jimenez SA: Alternative splicing of human prostaglandin G/H synthase mRNA and evidence of differential regulation of the resulting transcripts by transforming growth factor beta 1, interleukin 1 beta, and tumor necrosis factor alpha. J Biol Chem. 1992 May 25;267(15):10816-22. [PubMed ]

1. Cytochrome c1 nonheme 7 kDa protein
2. Complex III subunit X
3. 7.2 kDa cytochrome c1-associated protein subunit

MAAATLTSKLYSLLFRRTSTFALTIIVGVMFFERAFDQGADAIYDHINEGKLWKHIKHKY
ENK

• Oxidative phosphorylation (map00190 )

• QH2 + 2 ferricytochrome c = Q + 2 ferrocytochrome c

• UCR_UQCRX_QCR9 (PF05365 )