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Gene Review

CYB5R3  -  cytochrome b5 reductase 3

Homo sapiens

Synonyms: B5R, Cytochrome b5 reductase, DIA1, Diaphorase-1, NADH-cytochrome b5 reductase 3
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Disease relevance of CYB5R3


Psychiatry related information on CYB5R3


High impact information on CYB5R3


Chemical compound and disease context of CYB5R3


Biological context of CYB5R3


Anatomical context of CYB5R3


Associations of CYB5R3 with chemical compounds


Physical interactions of CYB5R3


Enzymatic interactions of CYB5R3

  • The deletion of the N-terminal region up to Thr36 of the native reductase (Mr 35,000) produced a truncated form (Mr about 31,000) which had full diaphorase activity but lost the capacity to catalyze the ferredoxin-dependent reaction [31].
  • The present study thus revealed that both dehydrogenase and diaphorase enzymes from the two Clostridium species catalyzed a hydride transfer to CL-20 and showed stereo-specificity for pro-R hydrogen of NAD(P)H [32].

Co-localisations of CYB5R3


Regulatory relationships of CYB5R3


Other interactions of CYB5R3


Analytical, diagnostic and therapeutic context of CYB5R3


  1. Exonic point mutations in NADH-cytochrome B5 reductase genes of homozygotes for hereditary methemoglobinemia, types I and III: putative mechanisms of tissue-dependent enzyme deficiency. Katsube, T., Sakamoto, N., Kobayashi, Y., Seki, R., Hirano, M., Tanishima, K., Tomoda, A., Takazakura, E., Yubisui, T., Takeshita, M. Am. J. Hum. Genet. (1991) [Pubmed]
  2. Molecular cloning of cDNAs of human liver and placenta NADH-cytochrome b5 reductase. Yubisui, T., Naitoh, Y., Zenno, S., Tamura, M., Takeshita, M., Sakaki, Y. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  3. Amino acid sequence of NADH-cytochrome b5 reductase of human erythrocytes. Yubisui, T., Miyata, T., Iwanaga, S., Tamura, M., Yoshida, S., Takeshita, M., Nakajima, H. J. Biochem. (1984) [Pubmed]
  4. Mitf regulation of Dia1 controls melanoma proliferation and invasiveness. Carreira, S., Goodall, J., Denat, L., Rodriguez, M., Nuciforo, P., Hoek, K.S., Testori, A., Larue, L., Goding, C.R. Genes Dev. (2006) [Pubmed]
  5. Nitroreduction of nitrated and C-9 oxidized fluorenes in vitro. Ritter, C.L., Malejka-Giganti, D. Chem. Res. Toxicol. (1998) [Pubmed]
  6. Selective sparing of a class of striatal neurons in Huntington's disease. Ferrante, R.J., Kowall, N.W., Beal, M.F., Richardson, E.P., Bird, E.D., Martin, J.B. Science (1985) [Pubmed]
  7. Analysis of mutant NADH-cytochrome b5 reductase: apparent "type III" methemoglobinemia can be explained as type I with an unstable reductase. Nagai, T., Shirabe, K., Yubisui, T., Takeshita, M. Blood (1993) [Pubmed]
  8. Alterations in nitrogen monoxide-synthesizing cortical neurons in amyotrophic lateral sclerosis with dementia. Kuljis, R.O., Schelper, R.L. J. Neuropathol. Exp. Neurol. (1996) [Pubmed]
  9. NADPH-diaphorase histochemistry reveals an autonomic-like innervation in the postnatal hamster cochlea. Morris, J.C., Phelps, P.E., Simmons, D.D. J. Comp. Neurol. (1999) [Pubmed]
  10. Neurogenic erectile dysfunction: the course of nicotinamide adenine dinucleotide phosphate diaphorase-positive nerve fibers on the surface of the prostate. Zvara, P., Spiess, P.E., Merlin, S.L., Bégin, L.R., Brock, G.B. Urology (1996) [Pubmed]
  11. Nitric oxide synthase activity in infantile hypertrophic pyloric stenosis. Vanderwinden, J.M., Mailleux, P., Schiffmann, S.N., Vanderhaeghen, J.J., De Laet, M.H. N. Engl. J. Med. (1992) [Pubmed]
  12. Atomic structure of ferredoxin-NADP+ reductase: prototype for a structurally novel flavoenzyme family. Karplus, P.A., Daniels, M.J., Herriott, J.R. Science (1991) [Pubmed]
  13. Sperm diaphorase: genetic polymorphism of a sperm-specific enzyme in man. Caldwell, K., Blake, E.T., Sensabaugh, G.F. Science (1976) [Pubmed]
  14. ROCK and Dia have opposing effects on adherens junctions downstream of Rho. Sahai, E., Marshall, C.J. Nat. Cell Biol. (2002) [Pubmed]
  15. A novel point mutation in a 3' splice site of the NADH-cytochrome b5 reductase gene results in immunologically undetectable enzyme and impaired NADH-dependent ascorbate regeneration in cultured fibroblasts of a patient with type II hereditary methemoglobinemia. Shirabe, K., Landi, M.T., Takeshita, M., Uziel, G., Fedrizzi, E., Borgese, N. Am. J. Hum. Genet. (1995) [Pubmed]
  16. Enzymatic instability of NADH-cytochrome b5 reductase as a cause of hereditary methemoglobinemia type I (red cell type). Shirabe, K., Yubisui, T., Borgese, N., Tang, C.Y., Hultquist, D.E., Takeshita, M. J. Biol. Chem. (1992) [Pubmed]
  17. NADH cytochrome b5 reductase and cytochrome b5 catalyze the microsomal reduction of xenobiotic hydroxylamines and amidoximes in humans. Kurian, J.R., Bajad, S.U., Miller, J.L., Chin, N.A., Trepanier, L.A. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  18. Vaccinia virus F13L protein with a conserved phospholipase catalytic motif induces colocalization of the B5R envelope glycoprotein in post-Golgi vesicles. Husain, M., Moss, B. J. Virol. (2001) [Pubmed]
  19. Characterization of a vaccinia virus-encoded 42-kilodalton class I membrane glycoprotein component of the extracellular virus envelope. Isaacs, S.N., Wolffe, E.J., Payne, L.G., Moss, B. J. Virol. (1992) [Pubmed]
  20. An erythroid-specific transcript generates the soluble form of NADH-cytochrome b5 reductase in humans. Bulbarelli, A., Valentini, A., DeSilvestris, M., Cappellini, M.D., Borgese, N. Blood (1998) [Pubmed]
  21. An in-frame deletion of codon 298 of the NADH-cytochrome b5 reductase gene results in hereditary methemoglobinemia type II (generalized type). A functional implication for the role of the COOH-terminal region of the enzyme. Shirabe, K., Fujimoto, Y., Yubisui, T., Takeshita, M. J. Biol. Chem. (1994) [Pubmed]
  22. Identification of alternative first exons of NADH-cytochrome b5 reductase gene expressed ubiquitously in human cells. Du, M., Shirabe, K., Takeshita, M. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  23. Complete amino acid sequence of NADH-cytochrome b5 reductase purified from human erythrocytes. Yubisui, T., Miyata, T., Iwanaga, S., Tamura, M., Takeshita, M. J. Biochem. (1986) [Pubmed]
  24. Prenatal development of nicotinamide adenine dinucleotide phosphate-diaphorase activity in the human hippocampal formation. Yan, X.X., Ribak, C.E. Hippocampus. (1997) [Pubmed]
  25. Diaphorase P: a new fetal isozyme identified in human placenta. Choury, D., Kaplan, J.C. Biochim. Biophys. Acta (1980) [Pubmed]
  26. Binding of cytochrome b5 to membranes of isolated subcellular organelles from rat liver. Remacle, J. J. Cell Biol. (1978) [Pubmed]
  27. Purification and characterization of the human neutrophil NADH-cytochrome b5 reductase. Tauber, A.I., Wright, J., Higson, F.K., Edelman, S.A., Waxman, D.J. Blood (1985) [Pubmed]
  28. Structural role of serine 127 in the NADH-binding site of human NADH-cytochrome b5 reductase. Yubisui, T., Shirabe, K., Takeshita, M., Kobayashi, Y., Fukumaki, Y., Sakaki, Y., Takano, T. J. Biol. Chem. (1991) [Pubmed]
  29. Role of cysteine residues in human NADH-cytochrome b5 reductase studied by site-directed mutagenesis. Cys-273 and Cys-283 are located close to the NADH-binding site but are not catalytically essential. Shirabe, K., Yubisui, T., Nishino, T., Takeshita, M. J. Biol. Chem. (1991) [Pubmed]
  30. Electrostatic properties deduced from refined structures of NADH-cytochrome b5 reductase and the other flavin-dependent reductases: pyridine nucleotide-binding and interaction with an electron-transfer partner. Nishida, H., Miki, K. Proteins (1996) [Pubmed]
  31. Structure-function relationship in spinach ferredoxin-NADP+ reductase as studied by limited proteolysis. Gadda, G., Aliverti, A., Ronchi, S., Zanetti, G. J. Biol. Chem. (1990) [Pubmed]
  32. Stereo-specificity for pro-(R) hydrogen of NAD(P)H during enzyme-catalyzed hydride transfer to CL-20. Bhushan, B., Halasz, A., Hawari, J. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  33. Nonvascular contractile cells in sclera and choroid of humans and monkeys. Poukens, V., Glasgow, B.J., Demer, J.L. Invest. Ophthalmol. Vis. Sci. (1998) [Pubmed]
  34. Essential requirement of cytosolic phospholipase A(2) for stimulation of NADPH oxidase-associated diaphorase activity in granulocyte-like cells. Pessach, I., Leto, T.L., Malech, H.L., Levy, R. J. Biol. Chem. (2001) [Pubmed]
  35. The human dioxin-inducible NAD(P)H: quinone oxidoreductase cDNA-encoded protein expressed in COS-1 cells is identical to diaphorase 4. Shaw, P.M., Reiss, A., Adesnik, M., Nebert, D.W., Schembri, J., Jaiswal, A.K. Eur. J. Biochem. (1991) [Pubmed]
  36. The genes for the highly homologous Ca(2+)-binding proteins oncomodulin and parvalbumin are not linked in the human genome. Ritzler, J.M., Sawhney, R., Geurts van Kessel, A.H., Grzeschik, K.H., Schinzel, A., Berchtold, M.W. Genomics (1992) [Pubmed]
  37. Compared mechanisms of tumor cytolysis by human natural killer cells and activated polymorphonuclear leukocytes. Abrams, S.I., Brahmi, Z. J. Immunol. (1984) [Pubmed]
  38. Regional assignment of arylsulfatase A, mitochondrial aconitase and NADH-cytochrome b5 reductase by somatic cell hybridization. Hors-Cayla, M.C., Junien, C., Heuertz, S., Mattei, J.F., Frézal, J. Hum. Genet. (1981) [Pubmed]
  39. Molecular heterogeneity of ferredoxin:NADP+ oxidoreductase from the cyanobacterium Anabaena cylindrica. Rowell, P., Diez, J., Apte, S.K., Stewart, W.D. Biochim. Biophys. Acta (1981) [Pubmed]
  40. Exponential decay of cytochrome b5 and cytochrome b5 reductase during senescence of erythrocytes: relation to the increased methemoglobin content. Takeshita, M., Tamura, M., Yubisui, T., Yoneyama, Y. J. Biochem. (1983) [Pubmed]
  41. The organization and the complete nucleotide sequence of the human NADH-cytochrome b5 reductase gene. Tomatsu, S., Kobayashi, Y., Fukumaki, Y., Yubisui, T., Orii, T., Sakaki, Y. Gene (1989) [Pubmed]
  42. Prenatal diagnosis of recessive congenital methaemoglobinaemia type II: novel mutation in the NADH-cytochrome b5 reductase gene leading to stop codon read-through. Leroux, A., Leturcq, F., Deburgrave, N., Szajnert, M.F. Eur. J. Haematol. (2005) [Pubmed]
  43. Affinity chromatography of microsomal enzymes on immobilized detergent-solubilized cytochrome b5. Kawata, S., Trzaskos, J.M., Gaylor, J.L. J. Biol. Chem. (1986) [Pubmed]
  44. Ecdysteroid coordinates optic lobe neurogenesis via a nitric oxide signaling pathway. Champlin, D.T., Truman, J.W. Development (2000) [Pubmed]
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