SLC26A1, also known as solute carrier family 26 (sulfate transporter) member 1, solute carrier family 26 (anion exchanger) member 1, sulfate/anion transporter SAT-1 protein, sulfate anion transporter AT1, SAT1, CAON, or EDM4, is a 75 kDa transmembrane protein with 701 amino acids length. In humans, it is encoded by the SLC26A1 gene which is localized at the chromosome 4p16.3. SLC26A1 is a founding member in the highly conserved SLC26A gene family, which codes for multifunctional anion channels and anion exchangers with a wide range of substrates and consists of 11 genes (SLC26A1 to SLC26A11) in mammals. SLC26A1 is predominantly expressed in the liver, brain, and pancreas, and works as an anion exchanger and transports, including sulfate, bicarbonate, chloride, and oxalate in an electroneutral manner.
Basic Information of SLC26A1 | |
Protein Name | Sulfate anion transporter 1 |
Gene Name | SLC26A1 |
Aliases | SAT-1, Solute carrier family 26 member 1 |
Organism | Homo sapiens (Human) |
UniProt ID | Q9H2B4 |
Transmembrane Times | 12 |
Length (aa) | 701 |
Sequence | MDESPEPLQQGRGPVPVRRQRPAPRGLREMLKARLWCSCSCSVLCVRALVQDLLPATRWLRQYRPREYLAGDVMSGLVIGIILVPQAIAYSLLAGLQPIYSLYTSFFANLIYFLMGTSRHVSVGIFSLLCLMVGQVVDRELQLAGFDPSQDGLQPGANSSTLNGSAAMLDCGRDCYAIRVATALTLMTGLYQVLMGVLRLGFVSAYLSQPLLDGFAMGASVTILTSQLKHLLGVRIPRHQGPGMVVLTWLSLLRGAGQANVCDVVTSTVCLAVLLAAKELSDRYRHRLRVPLPTELLVIVVATLVSHFGQLHKRFGSSVAGDIPTGFMPPQVPEPRLMQRVALDAVALALVAAAFSISLAEMFARSHGYSVRANQELLAVGCCNVLPAFLHCFATSAALAKSLVKTATGCRTQLSSVVSATVVLLVLLALAPLFHDLQRSVLACVIVVSLRGALRKVWDLPRLWRMSPADALVWAGTAATCMLVSTEAGLLAGVILSLLSLAGRTQRPRTALLARIGDTAFYEDATEFEGLVPEPGVRVFRFGGPLYYANKDFFLQSLYSLTGLDAGCMAARRKEGGSETGVGEGGPAQGEDLGPVSTRAALVPAAAGFHTVVIDCAPLLFLDAAGVSTLQDLRRDYGALGISLLLACCSPPVRDILSRGGFLGEGPGDTAEEEQLFLSVHDAVQTARARHRELEATDAHL |
The human SLC26A1 is a 4,4'-diisothiocyanato-2,2'-stilbenedisulfonic acid (DIDS)-sensitive, electroneutral sodium-independent anion exchanger, responsible for transporting the sulfate, thiosulfate, bicarbonate, oxalate, and chloride. Human SLC26A1-mediated anion exchange is different from that of its rodent orthologs in its stimulation by alkaline pH, inhibition by acidic pH, and failure to transport glyoxylate. The transport of sulfate and oxalate modulated by SLC26A1 is highly dependent on the allosteric activation via extracellular chloride or non-substrate anions. Extracellular chloride motivates apparent Vmax of human SLC26A1-mediated sulfate uptake by allowing a two-log reduction in sensitivity to inhibition by extracellular protons, but not changing the transporter affinity for extracellular sulfate. Compared to SLC26A1-mediated sulfate transport, SLC26A1-related chloride transport is activated by acidic pH, which reveals decreased sensitivity to DIDS and exhibits a cation dependence for its DIDS-insensitive component. Furthermore, mutations in SLC26A1 result in multiple disorders, including hepatotoxicity, urolithiasis, distal renal tubular acidosis, and impaired gastric secretion, caused by the disruption of ion homeostasis.
Fig.1 Position of amino acid substitutions in the predicted secondary structure model of the human SLC26A1 protein. (Dawson, 2013)
RT-PCR analysis in this work reveals that the main and interlobular ducts express all members of SLC26A family except for Slc26a5 and Slc26a8. SLC26A1, SLC26A4, SLC26A6, and SLC26A10 are observed to be localized at the luminal membrane of guinea pig pancreatic ducts by immunohistochemistry.
Some members of Slc26 gene family (Slc26a1, Slc26a3, Slc26a4, Slc26a6, and Slc26a7) are previously studied to be implicated in maturation-stage amelogenesis, particularly in a key process of pH regulation. The data here indicate that the involvement of SLC26A1 and SLC26A7 can function as pivotal ion transporters in pH regulatory networks during the enamel maturation.
The availability of the first crystal structure of a bacterial member (SLC26Dg) in the solute carrier SLC26 family of anion transporters has assisted authors to create three-dimensional models of all ten human members (SLC26A1-A11, A10 being a pseudogene) by a Phyre2 bioinformatic tool.
Analysis in this report reveals that the variant protein mimicking p.Thr185Met has defects in protein folding or trafficking. Furthermore, all the identified mutations in SLC26A1 may lead to a decreased transporter activity by measuring anion exchange activity of SLC26A1. The data identifies SLC26A1 mutations as causes of recessive Mendelian form of nephrolithiasis.
Genetic deficiency of SLC26A1 anion exchanger in mice is associated with hyposulfatemia and hyperoxaluria with nephrolithiasis. This study exhibits that rare SLC26A1 polymorphic variants from a patient with nephrolithiasis/calcinosis and a patient with renal Fanconi Syndrome have no loss-of-function phenotypes consistent with disease pathogenesis.
To harvest a soluble and natural protein, we have already established accessible reconstitution forms and active formats for these membrane proteins. Our powerful Magic™ membrane protein production platform offers a number of flexible options for wide users, from which you can always pick a suitable approach to attain your goals. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-SLC26A1 antibody development services.
Noticeably, Creative Biolabs as a seasoned expert in the protein manufacture filed has gained great recognition from researchers all over the world for successfully achieved challenging projects. Nowadays, we would like to present available and effective one-step, customized membrane protein preparation services to satisfy clients’ all needs. Please feel free to contact us for more information.
Reference
All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.
USA:
Europe: Germany: |
|
Call us at: USA: UK: Germany: |
|
Fax:
|
|
Email: info@creative-biolabs.com |