Alternative titles; symbols
HGNC Approved Gene Symbol: FDX1
Cytogenetic location: 11q22.3 Genomic coordinates (GRCh38): 11:110,429,331-110,464,884 (from NCBI)
Ferredoxin is a small, acidic, iron-sulfur protein that functions as an electron transport intermediate for mitochondrial cytochromes P450 involved in steroid, vitamin D, and bile acid metabolism. Electrons are transferred from NADPH through a flavin-containing protein (ferredoxin oxidoreductase) and ferredoxin to the terminal cytochrome P450 for oxidation/reduction reactions (summary by Chang et al., 1990). Mitochondrial P450s and their ferredoxin are found mainly in the steroidogenic tissues, including adrenal, ovary, testis, and placenta (Jefcoate et al., 1986). Small amounts of them are also found in the liver and kidney for bile acid and vitamin D synthesis (summary by Chang et al., 1990).
Ferredoxin is synthesized as a precursor in which 60 amino acids of the signal peptide are later cleaved upon transport into the mitochondrial inner matrix to form a mature protein of 124 amino acids (Okamura et al., 1985).
Renal ferredoxin (renodoxin) has similar optic, renal, and immunochemical properties to adrenodoxin, although Maruya et al. (1983) suggested that the 2 have minor differences. Chashchin et al. (1986) found that adrenodoxin is identical in sequence to liver ferredoxin (hepatoredoxin). In almost all human tissues, Morel et al. (1987, 1988) found ADX mRNA in 3 sizes: 1.1, 1.4, and 1.65 kb. Cloning and sequencing of 3 ADX cDNAs showed that the mRNAs of various sizes resulted from alternate polyadenylation sites yielding 3-prime untranslated regions of 229, 530, and 790 bp, respectively. The 540-bp coding region and the 5-prime untranslated region were identical in all cases. Also see Picado-Leonard et al. (1988). Human adrenodoxin and placental ferredoxin cDNAs share an identical sequence, suggesting that they are the same (Mittal et al., 1988). By sequence analysis, Chang et al. (1990) found that the ferredoxin gene encodes only 1 protein product. They therefore suggested that there is no need to designate ferredoxin according to tissue origin.
Chang et al. (1988) found that the ADX gene spans more than 20 kb and contains 4 exons. The first exon encodes the 60-amino acid signal peptide, which directs transport of the protein into the inner mitochondrial matrix. The mature peptide of 124 amino acids is encoded by the other 3 exons. The third exon encodes the portion of the protein containing the iron-sulfur center and a domain that binds other components of the electron transport chain.
By means of Southern blot analysis of DNA from somatic cell hybrids using stringent conditions of hybridization, 2 chromosomal sites were identified for the ADX gene: chromosomes 11 and 20. One sequence was suspected to represent a processed, intronless pseudogene. Because of the restriction pattern, Morel et al. (1987) suggested that the sequence on chromosome 20 is a pseudogene.
By analysis of somatic cell hybrids, Morel et al. (1988) and Chang et al. (1990) assigned the ADX gene to 11q13-qter. Chang et al. (1990) identified pseudogenes on both chromosome 20 and chromosome 21. The pseudogenes lacked introns and contained numerous mutations, including an insertion, deletion, and substitution, which rendered them inactive. They concluded that there are 2 expressed genes, but only 1 gene product and that both expressed genes are located on chromosome 11.
By in situ hybridization, Sparkes et al. (1991) refined the assignment of ADX to 11q22 and demonstrated pseudogenes on 20q11-q12.
Chang, C.-Y., Wu, D.-A., Lai, C.-C., Miller, W. L., Chung, B.-C. Cloning and structure of the human adrenodoxin gene. DNA 7: 609-615, 1988. [PubMed: 3229285] [Full Text: https://doi.org/10.1089/dna.1988.7.609]
Chang, C.-Y., Wu, D.-A., Mohandas, T. K., Chung, B.-C. Structure, sequence, chromosomal location, and evolution of the human ferredoxin gene family. DNA Cell Biol. 9: 205-212, 1990. [PubMed: 2340092] [Full Text: https://doi.org/10.1089/dna.1990.9.205]
Chashchin, V. L., Lapko, V. N., Adamovich, T. B., Kirillova, N. M., Lapko, A. G., Akhrem, A. A. The primary structure of hepatoredoxin from bovine liver mitochondria. Bioorg. Khim. 12: 1286-1289, 1986. [PubMed: 3778538]
Jefcoate, C. R., McNamara, B. C., DiBartolomeis, M. J. Control of steroid synthesis in adrenal fasciculata cells. Endocr. Res. 12: 315-350, 1986. [PubMed: 3030718] [Full Text: https://doi.org/10.3109/07435808609035444]
Maruya, N., Hiwatashi, A., Ichikawa, Y., Yamano, T. Purification and characterization of renal ferredoxin from bovine renal mitochondria. J. Biochem. 93: 1239-1247, 1983. [PubMed: 6309754] [Full Text: https://doi.org/10.1093/oxfordjournals.jbchem.a134258]
Mittal, S., Zhu, Y. Z., Vickery, L. E. Molecular cloning and sequence analysis of human placental ferredoxin. Arch. Biochem. Biophys. 264: 383-391, 1988. [PubMed: 2969697] [Full Text: https://doi.org/10.1016/0003-9861(88)90303-7]
Morel, Y., Picado-Leonard, J., Mohandas, T. K., Miller, W. L. Two highly homologous genes for adrenodoxin lie on human chromosomes 11 and 20. (Abstract) Am. J. Hum. Genet. 41: A178 only, 1987.
Morel, Y., Picado-Leonard, J., Wu, D.-A., Chang, C.-Y., Mohandas, T. K., Chung, B.-C., Miller, W. L. Assignment of the functional gene for human adrenodoxin to chromosome 11q13-qter and of adrenodoxin pseudogenes to chromosome 20cen-q13.1. Am. J. Hum. Genet. 43: 52-59, 1988. [PubMed: 2837084]
Okamura, T., John, M. E., Zuber, M. X., Simpson, E. R., Waterman, M. R. Molecular cloning and amino acid sequence of the precursor form of bovine adrenodoxin: evidence for a previously unidentified COOH-terminal peptide. Proc. Nat. Acad. Sci. 82: 5705-5709, 1985. [PubMed: 2994043] [Full Text: https://doi.org/10.1073/pnas.82.17.5705]
Picado-Leonard, J., Voutilainen, R., Kao, L.-C., Chung, B.-C., Strauss, J. F., III, Miller, W. L. Human adrenodoxin: cloning of three cDNAs and cycloheximide enhancement in JEG-3 cells. J. Biol. Chem. 263: 3240-3244, 1988. Note: Erratum: J. Biol. Chem. 263: 11016 only, 1998. [PubMed: 3343244]
Sparkes, R. S., Klisak, I., Miller, W. L. Regional mapping of genes encoding human steroidogenic enzymes: P450scc to 15q23-q24; adrenodoxin to 11q22; adrenodoxin reductase to 17q24-q25; and P450c17 to 10q24-q25. DNA Cell Biol. 10: 359-365, 1991. [PubMed: 1863359] [Full Text: https://doi.org/10.1089/dna.1991.10.359]