HGNC Approved Gene Symbol:SLC13A2
Cytogenetic location:17q11.2 Genomic coordinates(GRCh38) :17:28,473,644-28,497,781 (from NCBI)
The sodium-dicarboxylate cotransporter (NADC) of the renal proximal tubule reabsorbs Krebs cycle intermediates, including succinate and citrate, from the tubular filtrate. Sodium-dicarboxylate cotransport is an electrogenic process, coupling 3 sodium ions to the transport of each divalent anion substrate. The NADC may play a role in the development of kidney stones in humans by determining citrate concentrations in the urine. Urinary citrate inhibits calcium stone formation, and hypocitraturia is associated with a tendency to form kidney stones. By screening a human kidney cDNA library with a rabbit kidney NADC1 cDNA,Pajor (1996) isolated cDNAs encoding human SLC13A2, which they called NADC1. The composite human NADC1 cDNA sequence predicts a 593-amino acid protein containing at least 8 transmembrane domains, 2 potential N-glycosylation sites, and 2 potential protein kinase C (e.g.,600448) phosphorylation sites. The deduced amino acid sequence of human NADC1 is 78% identical to that of rabbit NADC1 and 47% identical to that of the rat kidney sodium-sulfate transporter NaSi1 (606193). In vitro translation of human NADC1 produced an approximately 48-kD protein; its mass increased to approximately 59 kD in the presence of pancreatic microsomes, indicating that core glycosylation had occurred. Recombinant human NADC1 expressed in Xenopus oocytes transported both succinate and citrate. It was a low-affinity, sodium-dependent, and pH-insensitive transporter of succinate. NADC1 transport of citrate was stimulated by acidic pH. Northern blot analysis detected an approximately 2.8-kb NADC1 transcript in human kidney and intestine but not in liver.Pajor (1996) stated that the properties of human NADC1 resemble those of the low-affinity NADC found on the apical membrane of the rabbit renal proximal tubule.
In a study of longevity in the adult fruit fly,Rogina et al. (2000) found that 5 independent P-element insertional mutations in a single gene, called Indy (for 'I'm not dead yet'), which is 50% similar to human and rat renal sodium dicarboxylate cotransporters, resulted in a near doubling of the average adult life span without a decline in fertility or physical activity. Indy was most abundantly expressed in the fat body, midgut, and oenocytes, the principal sites of intermediary metabolism in the fly. Excision of the P element resulted in a reversion to normal life span.
Pajor (1996) mapped the SLC13A2 gene to chromosome 17 by analysis of somatic cell hybrids. By FISH and radiation hybrid mapping,Mann et al. (1999) localized the SLC13A2 gene to chromosome 17p11.1-q11.1, between markers D17S2123 and D17S841.
Mann, S. S., Hart, T. C., Pettenati, M. J., von Kap-herr, C., Holmes, R. P.Assignment of the sodium-dependent dicarboxylate transporter gene (SLC13A2 alias NaDC-1) to human chromosome region 17p11.1-q11.1 by radiation hybrid mapping and fluorescence in situ hybridization. Cytogenet. Cell Genet. 84: 89-90, 1999. [PubMed:10343111,related citations] [Full Text]
Pajor, A. M.Molecular cloning and functional expression of a sodium-dicarboxylate cotransporter from human kidney. Am. J. Physiol. 270: F642-F648, 1996. [PubMed:8967342,related citations] [Full Text]
Rogina, B., Reenan, R. A., Nilsen, S. P., Helfand, S. L.Extended life-span conferred by cotransporter gene mutations in Drosophila. Science 290: 2137-2140, 2000. [PubMed:11118146,related citations] [Full Text]
Alternative titles; symbols
HGNC Approved Gene Symbol: SLC13A2
Cytogenetic location: 17q11.2 Genomic coordinates(GRCh38) : 17:28,473,644-28,497,781(from NCBI)
The sodium-dicarboxylate cotransporter (NADC) of the renal proximal tubule reabsorbs Krebs cycle intermediates, including succinate and citrate, from the tubular filtrate. Sodium-dicarboxylate cotransport is an electrogenic process, coupling 3 sodium ions to the transport of each divalent anion substrate. The NADC may play a role in the development of kidney stones in humans by determining citrate concentrations in the urine. Urinary citrate inhibits calcium stone formation, and hypocitraturia is associated with a tendency to form kidney stones. By screening a human kidney cDNA library with a rabbit kidney NADC1 cDNA, Pajor (1996) isolated cDNAs encoding human SLC13A2, which they called NADC1. The composite human NADC1 cDNA sequence predicts a 593-amino acid protein containing at least 8 transmembrane domains, 2 potential N-glycosylation sites, and 2 potential protein kinase C (e.g., 600448) phosphorylation sites. The deduced amino acid sequence of human NADC1 is 78% identical to that of rabbit NADC1 and 47% identical to that of the rat kidney sodium-sulfate transporter NaSi1 (606193). In vitro translation of human NADC1 produced an approximately 48-kD protein; its mass increased to approximately 59 kD in the presence of pancreatic microsomes, indicating that core glycosylation had occurred. Recombinant human NADC1 expressed in Xenopus oocytes transported both succinate and citrate. It was a low-affinity, sodium-dependent, and pH-insensitive transporter of succinate. NADC1 transport of citrate was stimulated by acidic pH. Northern blot analysis detected an approximately 2.8-kb NADC1 transcript in human kidney and intestine but not in liver. Pajor (1996) stated that the properties of human NADC1 resemble those of the low-affinity NADC found on the apical membrane of the rabbit renal proximal tubule.
In a study of longevity in the adult fruit fly, Rogina et al. (2000) found that 5 independent P-element insertional mutations in a single gene, called Indy (for 'I'm not dead yet'), which is 50% similar to human and rat renal sodium dicarboxylate cotransporters, resulted in a near doubling of the average adult life span without a decline in fertility or physical activity. Indy was most abundantly expressed in the fat body, midgut, and oenocytes, the principal sites of intermediary metabolism in the fly. Excision of the P element resulted in a reversion to normal life span.
Pajor (1996) mapped the SLC13A2 gene to chromosome 17 by analysis of somatic cell hybrids. By FISH and radiation hybrid mapping, Mann et al. (1999) localized the SLC13A2 gene to chromosome 17p11.1-q11.1, between markers D17S2123 and D17S841.
Mann, S. S., Hart, T. C., Pettenati, M. J., von Kap-herr, C., Holmes, R. P.Assignment of the sodium-dependent dicarboxylate transporter gene (SLC13A2 alias NaDC-1) to human chromosome region 17p11.1-q11.1 by radiation hybrid mapping and fluorescence in situ hybridization. Cytogenet. Cell Genet. 84: 89-90, 1999. [PubMed: 10343111] [Full Text: https://doi.org/10.1159/000015222]
Pajor, A. M.Molecular cloning and functional expression of a sodium-dicarboxylate cotransporter from human kidney. Am. J. Physiol. 270: F642-F648, 1996. [PubMed: 8967342] [Full Text: https://doi.org/10.1152/ajprenal.1996.270.4.F642]
Rogina, B., Reenan, R. A., Nilsen, S. P., Helfand, S. L.Extended life-span conferred by cotransporter gene mutations in Drosophila. Science 290: 2137-2140, 2000. [PubMed: 11118146] [Full Text: https://doi.org/10.1126/science.290.5499.2137]
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