SLC13A1 Membrane Protein Introduction

Introduction of SLC13A1

The apical membrane Na⁺-sulfate cotransporter NaS1 (SLC13A1) mediates sulfate (re)absorption across renal proximal tubule and small intestinal epithelia. NaS1 is a 595-amino acid (~66 kDa) protein with 13 putative transmembrane domains. Substrate preferences of NaS1 are sodium and sulfate, thiosulfate, and selenite. Its activity is inhibited by molybdate, selenate, tungstate, thiosulfate, succinate, and citrate. NaS1 is primarily expressed in the kidney and intestine. Its expression is down-regulated in the renal cortex by high sulfate diet, hypothyroidism, vitamin D depletion, glucocorticoids, hypokalemia, metabolic acidosis, and NSAIDs and up-regulated by low sulfate diet, thyroid hormone, vitamin D supplementation, growth hormone, chronic renal failure, and during post-natal growth.

Basic Information of SLC13A1
Protein Name	Solute carrier family 13 member 1
Gene Name	SLC13A1/NAS1
Aliases	Renal sodium/sulfate cotransporter, Na(+)/sulfate cotransporter, hNaSi-1
Organism	Homo sapiens (Human)
UniProt ID	Q9BZW2
Transmembrane Times	13
Length (aa)	595
Sequence	MKFFSYILVYRRFLFVVFTVLVLLPLPIVLHTKEAECAYTLFVVATFWLTEALPLSVTALLPSLMLPMFGIMPSKKVASAYFKDFHLLLIGVICLATSIEKWNLHKRIALKMVMMVGVNPAWLTLGFMSSTAFLSMWLSNTSTAAMVMPIAEAVVQQIINAEAEVEATQMTYFNGSTNHGLEIDESVNGHEINERKEKTKPVPGYNNDTGKISSKVELEKNSGMRTKYRTKKGHVTRKLTCLCIAYSSTIGGLTTITGTSTNLIFAEYFNTRYPDCRCLNFGSWFTFSFPAALIILLLSWIWLQWLFLGFNFKEMFKCGKTKTVQQKACAEVIKQEYQKLGPIRYQEIVTLVLFIIMALLWFSRDPGFVPGWSALFSEYPGFATDSTVALLIGLLFFLIPAKTLTKTTPTGEIVAFDYSPLITWKEFQSFMPWDIAILVGGGFALADGCEESGLSKWIGNKLSPLGSLPAWLIILISSLMVTSLTEVASNPATITLFLPILSPLAEAIHVNPLYILIPSTLCTSFAFLLPVANPPNAIVFSYGHLKVIDMVKAGLGVNIVGVAVVMLGICTWIVPMFDLYTYPSWAPAMSNETMP

Function of SLC13A1 Membrane Protein

SLC13A1/NaS1 is an important protein regulating sulfate reabsorption in the kidney in human. Disruption of this protein leads to hyposulfatemia and hypersulfaturia, as well as changes in metabolism, growth, fecundity, behavior, gut physiology, and liver detoxification. NaS1 is an important sulfate transporter and its disruption leads to perturbed sulfate homeostasis, which contributes to numerous pathophysiological conditions. It also takes part in sulfate symporter activity and sodium ion transmembrane transporting.

Fig.1 Sulfate transporters in the renal and small intestinal epithelial cell. (Tise, 2016)

Application of SLC13A1 Membrane Protein in Literature

Lee A., et al. The human renal sodium sulfate cotransporter (SLC13A1; hNaSi-1) cDNA and gene: organization, chromosomal localization, and functional characterization. Genomics. 2000, 70(3):354-63. PubMed ID: 11161786

This article identifies that NAS1 gene contains 15 exons, spanning over 83 kb in length. These findings will permit the screening of NAS1 mutations in humans with disorders in renal sulfate reabsorption and homeostasis.
Nakada T., et al. Roles of Slc13a1 and Slc26a1 sulfate transporters of eel kidney in sulfate homeostasis and osmoregulation in freshwater. Am J Physiol Regul Integr Comp Physiol. 2005, 289(2):R575-R585. PubMed ID: 15802556

Authors in this study reveal that the expression of these two proteins, Slc13a1 and Slc26a1, is dramatically reduced after the transfer of eels from freshwater to seawater.
Markovich D., Slc13a1 and Slc26a1 KO models reveal physiological roles of anion transporters. Physiology (Bethesda). 2012, 27(1):7-14. PubMed ID: 22311966

This article suggests that NaS1 (SLC13A1) and Sat1 (SLC26A1) mediate sulfate (re)absorption across renal proximal tubule and small intestinal epithelia, thereby regulating blood sulfate levels. Disruption of these two genes will lead to hyposulfatemia and hypersulfaturia.
Neff M.W., et al. Partial deletion of the sulfate transporter SLC13A1 is associated with an osteochondrodysplasia in the Miniature Poodle breed. PLoS One. 2012, 7(12):e51917. PubMed ID: 23300579

This article shows that disruption of SLC13A1 in the dog similarly causes undersulfation of proteoglycans in the extracellular matrix (ECM), which impacts the conversion of cartilage to bone.
Markovich D., Na⁺-sulfate cotransporter SLC13A1. Pflugers Arch. 2014, 466(1):131-7. PubMed ID: 24193406

This article suggests that NaS1 is an important sulfate transporter and its disruption leads to perturbed sulfate homeostasis, which contributes to numerous pathophysiological conditions.

SLC13A1 Preparation Options

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Reference

Tise C G, et al. (2016). From genotype to phenotype: Nonsense variants in SLC13A1 are associated with decreased serum sulfate and increased serum aminotransferases. GENES, GENOMES, GENETICS. 6(9), 2909-2918.

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