NADH-cytochrome b5 reductase 3

Details

Name
NADH-cytochrome b5 reductase 3
Synonyms
  • 1.6.2.2
  • B5R
  • DIA1
  • Diaphorase-1
Gene Name
CYB5R3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0036961|NADH-cytochrome b5 reductase 3
MGAQLSTLGHMVLFPVWFLYSLLMKLFQRSTPAITLESPDIKYPLRLIDREIISHDTRRF
RFALPSPQHILGLPVGQHIYLSARIDGNLVVRPYTPISSDDDKGFVDLVIKVYFKDTHPK
FPAGGKMSQYLESMQIGDTIEFRGPSGLLVYQGKGKFAIRPDKKSNPIIRTVKSVGMIAG
GTGITPMLQVIRAIMKDPDDHTVCHLLFANQTEKDILLRPELEELRNKHSARFKLWYTLD
RAPEAWDYGQGFVNEEMIRDHLPPPEEEPLVLMCGPPPMIQYACLPNLDHVGHPTERCFV
F
Number of residues
301
Molecular Weight
34234.55
Theoretical pI
7.68
GO Classification
Functions
ADP binding / AMP binding / cytochrome-b5 reductase activity, acting on NAD(P)H / FAD binding / flavin adenine dinucleotide binding / NAD binding
Processes
blood circulation / cholesterol biosynthetic process / L-ascorbic acid metabolic process / small molecule metabolic process / vitamin metabolic process / water-soluble vitamin metabolic process
Components
cytoplasm / endoplasmic reticulum / endoplasmic reticulum membrane / extracellular exosome / hemoglobin complex / lipid particle / membrane / mitochondrial inner membrane / mitochondrial outer membrane / mitochondrion
General Function
Nad binding
Specific Function
Desaturation and elongation of fatty acids, cholesterol biosynthesis, drug metabolism, and, in erythrocyte, methemoglobin reduction.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Endoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0016023|NADH-cytochrome b5 reductase 3 (CYB5R3)
ATGGGGGCCCAGCTCAGCACGTTGGGCCATATGGTGCTCTTCCCAGTCTGGTTCCTGTAC
AGTCTGCTCATGAAGCTGTTCCAGCGCTCCACGCCAGCCATCACCCTCGAGAGCCCGGAC
ATCAAGTACCCGCTGCGGCTCATCGACCGGGAGATCATCAGCCATGACACCCGGCGCTTC
CGCTTTGCCCTGCCGTCACCCCAGCACATCCTGGGCCTCCCTGTCGGCCAGCACATCTAC
CTCTCGGCTCGAATTGATGGAAACCTGGTCGTCCGGCCCTATACACCCATCTCCAGCGAT
GATGACAAGGGCTTCGTGGACCTGGTCATCAAGGTTTACTTCAAGGACACCCATCCCAAG
TTTCCCGCTGGAGGGAAGATGTCTCAGTACCTGGAGAGCATGCAGATTGGAGACACCATT
GAGTTCCGGGGCCCCAGTGGGCTGCTGGTCTACCAGGGCAAAGGGAAGTTCGCCATCCGA
CCTGACAAAAAGTCCAACCCTATCATCAGGACAGTGAAGTCTGTGGGCATGATCGCGGGA
GGGACAGGCATCACCCCGATGCTGCAGGTGATCCGCGCCATCATGAAGGACCCTGATGAC
CACACTGTGTGCCACCTGCTCTTTGCCAACCAGACCGAGAAGGACATCCTGCTGCGACCT
GAGCTGGAGGAACTCAGGAACAAACATTCTGCACGCTTCAAGCTCTGGTACACGCTGGAC
AGAGCCCCTGAAGCCTGGGACTACGGCCAGGGCTTCGTGAATGAGGAGATGATCCGGGAC
CACCTTCCACCCCCAGAGGAGGAGCCGCTGGTGCTGATGTGTGGCCCCCCACCCATGATC
CAGTACGCCTGCCTTCCCAACCTGGACCACGTGGGCCACCCCACGGAGCGCTGCTTCGTC
TTCTGA
Chromosome Location
22
Locus
22q13.31-qter|22q13.2-q13.31
External Identifiers
ResourceLink
UniProtKB IDP00387
UniProtKB Entry NameNB5R3_HUMAN
GenBank Protein ID553600
GenBank Gene IDM28713
GenAtlas IDCYB5R3
HGNC IDHGNC:2873
General References
  1. Tomatsu S, Kobayashi Y, Fukumaki Y, Yubisui T, Orii T, Sakaki Y: The organization and the complete nucleotide sequence of the human NADH-cytochrome b5 reductase gene. Gene. 1989 Aug 15;80(2):353-61. [PubMed:2479590]
  2. Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I: A genome annotation-driven approach to cloning the human ORFeome. Genome Biol. 2004;5(10):R84. Epub 2004 Sep 30. [PubMed:15461802]
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  6. Yubisui T, Naitoh Y, Zenno S, Tamura M, Takeshita M, Sakaki Y: Molecular cloning of cDNAs of human liver and placenta NADH-cytochrome b5 reductase. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3609-13. [PubMed:3035541]
  7. Murakami K, Yubisui T, Takeshita M, Miyata T: The NH2-terminal structures of human and rat liver microsomal NADH-cytochrome b5 reductases. J Biochem. 1989 Feb;105(2):312-7. [PubMed:2498303]
  8. Yubisui T, Miyata T, Iwanaga S, Tamura M, Takeshita M: Complete amino acid sequence of NADH-cytochrome b5 reductase purified from human erythrocytes. J Biochem. 1986 Feb;99(2):407-22. [PubMed:3700359]
  9. Yubisui T, Miyata T, Iwanaga S, Tamura M, Yoshida S, Takeshita M, Nakajima H: Amino acid sequence of NADH-cytochrome b5 reductase of human erythrocytes. J Biochem. 1984 Aug;96(2):579-82. [PubMed:6389526]
  10. Bulbarelli A, Valentini A, DeSilvestris M, Cappellini MD, Borgese N: An erythroid-specific transcript generates the soluble form of NADH-cytochrome b5 reductase in humans. Blood. 1998 Jul 1;92(1):310-9. [PubMed:9639531]
  11. Shirabe K, Yubisui T, Nishino T, Takeshita M: 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. J Biol Chem. 1991 Apr 25;266(12):7531-6. [PubMed:2019583]
  12. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648]
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  14. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  15. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
  16. Thinon E, Serwa RA, Broncel M, Brannigan JA, Brassat U, Wright MH, Heal WP, Wilkinson AJ, Mann DJ, Tate EW: Global profiling of co- and post-translationally N-myristoylated proteomes in human cells. Nat Commun. 2014 Sep 26;5:4919. doi: 10.1038/ncomms5919. [PubMed:25255805]
  17. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [PubMed:25944712]
  18. Bando S, Takano T, Yubisui T, Shirabe K, Takeshita M, Nakagawa A: Structure of human erythrocyte NADH-cytochrome b5 reductase. Acta Crystallogr D Biol Crystallogr. 2004 Nov;60(Pt 11):1929-34. Epub 2004 Oct 20. [PubMed:15502298]
  19. Yubisui T, Shirabe K, Takeshita M, Kobayashi Y, Fukumaki Y, Sakaki Y, Takano T: Structural role of serine 127 in the NADH-binding site of human NADH-cytochrome b5 reductase. J Biol Chem. 1991 Jan 5;266(1):66-70. [PubMed:1898726]
  20. Katsube T, Sakamoto N, Kobayashi Y, Seki R, Hirano M, Tanishima K, Tomoda A, Takazakura E, Yubisui T, Takeshita M, et al.: 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. Am J Hum Genet. 1991 Apr;48(4):799-808. [PubMed:1707593]
  21. Shirabe K, Yubisui T, Borgese N, Tang CY, Hultquist DE, Takeshita M: Enzymatic instability of NADH-cytochrome b5 reductase as a cause of hereditary methemoglobinemia type I (red cell type). J Biol Chem. 1992 Oct 5;267(28):20416-21. [PubMed:1400360]
  22. Shirabe K, Fujimoto Y, Yubisui T, Takeshita M: 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. J Biol Chem. 1994 Feb 25;269(8):5952-7. [PubMed:8119939]
  23. Vieira LM, Kaplan JC, Kahn A, Leroux A: Four new mutations in the NADH-cytochrome b5 reductase gene from patients with recessive congenital methemoglobinemia type II. Blood. 1995 Apr 15;85(8):2254-62. [PubMed:7718898]
  24. Jenkins MM, Prchal JT: A high-frequency polymorphism of NADH-cytochrome b5 reductase in African-Americans. Hum Genet. 1997 Feb;99(2):248-50. [PubMed:9048929]
  25. Wu YS, Huang CH, Wan Y, Huang QJ, Zhu ZY: Identification of a novel point mutation (Leu72Pro) in the NADH-cytochrome b5 reductase gene of a patient with hereditary methaemoglobinaemia type I. Br J Haematol. 1998 Jul;102(2):575-7. [PubMed:9695975]
  26. Higasa K, Manabe JI, Yubisui T, Sumimoto H, Pung-Amritt P, Tanphaichitr VS, Fukumaki Y: Molecular basis of hereditary methaemoglobinaemia, types I and II: two novel mutations in the NADH-cytochrome b5 reductase gene. Br J Haematol. 1998 Dec;103(4):922-30. [PubMed:9886302]
  27. Wang Y, Wu YS, Zheng PZ, Yang WX, Fang GA, Tang YC, Xie F, Lan FH, Zhu ZY: A novel mutation in the NADH-cytochrome b5 reductase gene of a Chinese patient with recessive congenital methemoglobinemia. Blood. 2000 May 15;95(10):3250-5. [PubMed:10807796]
  28. Huang C, Xie Y, Wang Y, Wu Y, Ye Y, Zhu Z: [Arginine-glutamine replacement at residue 57 of NADH-cytochrome b5 reductase in Chinese hereditary methemoglobinemia]. Zhonghua Xue Ye Xue Za Zhi. 1997 Apr;18(4):200-3. [PubMed:15622768]
  29. Percy MJ, Gillespie MJ, Savage G, Hughes AE, McMullin MF, Lappin TR: Familial idiopathic methemoglobinemia revisited: original cases reveal 2 novel mutations in NADH-cytochrome b5 reductase. Blood. 2002 Nov 15;100(10):3447-9. Epub 2002 Jul 5. [PubMed:12393396]
  30. Percy MJ, Crowley LJ, Davis CA, McMullin MF, Savage G, Hughes J, McMahon C, Quinn RJ, Smith O, Barber MJ, Lappin TR: Recessive congenital methaemoglobinaemia: functional characterization of the novel D239G mutation in the NADH-binding lobe of cytochrome b5 reductase. Br J Haematol. 2005 Jun;129(6):847-53. [PubMed:15953014]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00157NADHapproved, nutraceuticalunknownDetails
DB03147Flavin adenine dinucleotideapprovedunknownDetails
DB09130Copperapproved, investigationalunknownDetails