Alternative titles; symbols
HGNC Approved Gene Symbol: NDUFA5
Cytogenetic location: 7q31.32 Genomic coordinates (GRCh38): 7:123,536,997-123,601,651 (from NCBI)
The multisubunit NADH:ubiquinone oxidoreductase (complex I) is the first enzyme complex in the electron transport chain of mitochondria. The iron-sulfur protein (IP) fraction of complex I is made up of 7 subunits, including B13. See NDUFS1 (157655). By a combination of EST database screening and PCR, Pata et al. (1997) isolated cDNAs encoding the human homolog of bovine B13. The deduced 116-amino acid human protein has a calculated molecular mass of approximately 13 kD. The human and bovine B13 proteins are 87% identical. Northern blot analysis revealed that the 1.6-kb B13 mRNA was expressed in all human tissues tested, with the highest levels in heart, skeletal muscle, and brain. Two additional smaller transcripts were also detected. Using Southern blot analysis, Pata et al. (1997) determined that B13 is part of a multigene family in humans.
Tensing et al. (1999) determined that the NDUFA5 gene spans approximately 14 kb of genomic DNA and contains 5 exons.
During the course of a physical mapping project on 11p15.5, Russell et al. (1997) identified sequence with a high degree of similarity to the bovine NADH:ubiquinone oxidoreductase subunit B13. Following up on this lead, they isolated a clone with nucleotide sequence 88% and 83% identical over the predicted open reading frame with bovine and rat B13 subunit genes, respectively. The position of the initiation and termination codons was conserved. To determine the chromosomal localization of the B13 subunit gene, they screened a monochromosome somatic cell hybrid panel and showed that only the hybrid containing human chromosome 7 was positive.
By fluorescence in situ hybridization (FISH), Russell et al. (1997) localized the B13 gene to 7q32. They also identified a FISH signal at 11p15.5. Extensive sequencing of the genomic DNA on 11p15.5 revealed that the sequence at that location was a pseudogene.
By FISH, Tensing et al. (1999) mapped the NDUFA5 gene to 7q31.3.
Peralta et al. (2014) found that knockout of the Ndufa5 gene in mice caused death around embryonic day-9 (E9). Peralta et al. (2014) created a line of mice in which knockout of Ndufa5 was driven by the CaM kinase II-alpha (CAMK2A; 114078) promoter, which is expressed by cortical and hippocampal neurons beginning at birth. Knockout of Ndufa5 in the central nervous system (CNS) had no apparent effect until mice reached 10 to 11 months of age, when they became lethargic, lost motor control, and had difficulty maintaining balance. Concomitant with locomotor defects, CNS knockout of Ndufa5 caused loss of other complex I subunits and reduced NADH-ubiquinone oxidoreductase activity. Ndufa5 CNS-knockout mice showed a possibly compensatory increase in fatty acid and ketone body metabolism, but the content and activity of other mitochondrial respiratory complexes appeared normal, as did the morphology of hippocampus and cerebellum. Peralta et al. (2014) concluded that NDUFA5 is required for the assembly and/or stability of mitochondrial complex I.
Pata, I., Tensing, K., Metspalu, A. A human cDNA encoding the homologue of NADH:ubiquinone oxidoreductase subunit B13. Biochim. Biophys. Acta 1350: 115-118, 1997. [PubMed: 9048877] [Full Text: https://doi.org/10.1016/s0167-4781(96)00208-4]
Peralta, S., Torraco, A., Wenz, T., Garcia, S., Diaz, F., Moraes, C. T. Partial complex I deficiency due to the CNS conditional ablation of Ndufa5 results in a mild chronic encephalopathy but no increase in oxidative damage. Hum. Molec. Genet. 23: 1399-1412, 2014. [PubMed: 24154540] [Full Text: https://doi.org/10.1093/hmg/ddt526]
Russell, M. W., du Manoir, S., Collins, F. S., Brody, L. C. Cloning of the human NADH:ubiquinone oxidoreductase subunit B13: localization to chromosome 7q32 and identification of a pseudogene on 11p15. Mammalian Genome 8: 60-61, 1997. [PubMed: 9021153] [Full Text: https://doi.org/10.1007/s003359900350]
Tensing, K., Pata, I., Wittig, I., Wehnert, M., Metspalu, A. Genomic organization of the human complex I 13-kDa subunit gene NDUFA5. Cytogenet. Cell Genet. 84: 125-127, 1999. [PubMed: 10343126] [Full Text: https://doi.org/10.1159/000015237]