The human renal sodium sulfate cotransporter (SLC13A1; hNaSi-1) cDNA and gene: organization, chromosomal localization, and functional characterization.
Sulfate plays an essential role during growth, development, bone/cartilage formation, and cellular metabolism. In this study, we have determined the structure of the human Na+-sulfate cotransporter (hNaSi-1) cDNA (Human Genome Nomenclature Committee-approved symbol SLC13A1) and gene (NAS1). hNaSi-1 encodes a protein of 595 amino acids with 13 putative transmembrane domains. hNaSi-1 mRNA expression was exclusive to the human kidney. Expression of hNaSi-1 protein in Xenopus oocytes demonstrated a high-affinity Na+-sulfate cotransporter that was inhibited by selenate, thiosulfate, molybdate, tungstate, citrate, and succinate. Antisense inhibition experiments suggest hNaSi-1 to represent the major Na+-sulfate cotransporter in the human kidney. NAS1 was localized on human chromosome 7, mapped to 7q31-q32, near the sulfate transporter genes, DRA and SUT-1. The NAS1 gene contains 15 exons, spanning over 83 kb in length. Knowledge of the structure, function, and chromosomal localization of hNaSi-1 will permit the screening of NAS1 mutations in humans with disorders in renal sulfate reabsorption and homeostasis.
Lee
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Department of Physiology and Pharmacology, University of Queensland, Brisbane, Queensland, 4072, Australia.
Beck
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Markovich
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D027682:Cation Transport Proteins; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D005091:Exons; D006801:Humans; D007438:Introns; D007668:Kidney / Q000378:metabolism*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D000077003:Sodium Sulfate Cotransporter; D027981:Symporters; D014981:Xenopus
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D000077003:Sodium Sulfate Cotransporter; D027981:Symporters