NAS1, SCL13A1, (7q31.32), NaSi-1, sulfaatin kuljettaja geeni
- Official Symbol
- SLC13A1
- Official Full Name
- solute carrier family 13 member 1
- Also known as
- NAS1; NaSi-1
- Summary
- The protein encoded by this gene is an apical membrane Na(+)-sulfate cotransporter involved in sulfate homeostasis in the kidney. Defects in this gene lead to many pathophysiologic problems. [provided by RefSeq, May 2016]
- Expression
- Biased expression in kidney (RPKM 26.2), small intestine (RPKM 5.7) and 1 other tissue See more
- Orthologs mouse all
- Preferred Names
- solute carrier family 13 member 1
- Names
- Na(+)/sulfate cotransporter
- renal sodium/sulfate cotransporter
- solute carrier family 13 (sodium/sulfate symporters), member 1
- solute carrier family 13 (sodium/sulphate symporters), member 1
- Mutagenesis of the N-glycosylation site of hNaSi-1 reduces transport activity. Li H, et al. Am J Physiol Cell Physiol, 2003 Nov. PMID 12867358
- Serines 260 and 288 are involved in sulfate transport by hNaSi-1. Li H, et al. J Biol Chem, 2003 Sep 26. PMID 12857732
- From Genotype to Phenotype: Nonsense Variants in SLC13A1 Are Associated with Decreased Serum Sulfate and Increased Serum Aminotransferases. Tise CG, et al. G3 (Bethesda), 2016 Sep 8. PMID 27412988, Free PMC Article
- The human renal sodium sulfate cotransporter (SLC13A1; hNaSi-1) cDNA and gene: organization, chromosomal localization, and functional characterization. Lee A, et al. Genomics, 2000 Dec 15. PMID 11161786
- Molecular properties of the SLC13 family of dicarboxylate and sulfate transporters. Pajor AM. Pflugers Arch, 2006 Feb. PMID 16211368, Free PMC Article
GeneRIFs: Gene References Into Functions
- Consistent with sulfate's role in xenobiotic detoxification and protection against acetaminophen-induced hepatotoxicity, SLC13A1 nonsense SNV carriers had higher aminotransferase levels compared to noncarriers.
- Observational study and genome-wide association study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
- Observational study of gene-disease association. (HuGE Navigator)
- Serines 260 and 288 are involved in sulfate transport by hNaSi-1.
- Amino acid residue Asn591, located in the carboxyl (COOH) terminus of NaSi-1, is used as the glycosylation site and is critical for transport activity in NaSi-1.
- NaS1 ja NaS2 kuljettavat sulfaattia, selenaattia ja tiosulfaattia.
- NaXD1, NaCD3 ja NACDT kuljettavat di- ja trikarboksylaatteja kuten meripihkahappoa, sitraattia ja alfa-ketoglutaraattia.
Pflugers Arch. 2006 Feb;451(5):597-605. Epub 2005 Oct 7.
Molecular properties of the SLC13 family of dicarboxylate and sulfate transporters.
Pajor AM1. Abstract
The
SLC13 gene family consists of five members in humans, with
corresponding orthologs from different vertebrate species. All five
genes code for sodium-coupled transporters that are found on the plasma
membrane. Two of the transporters, NaS1 and NaS2, carry substrates such
as sulfate, selenate and thiosulfate. The other members of the family
(NaDC1, NaDC3, and NaCT) are transporters for di- and tri-carboxylates
including succinate, citrate and alpha-ketoglutarate. The SLC13
transporters from vertebrates are electrogenic and they produce inward
currents in the presence of sodium and substrate.
Substrate-independent leak currents have also been described.
Structure-function studies have identified the carboxy terminal half of these proteins as the most important for determining function. Transmembrane helices 9 and 10 may form part of the substrate permeation pathway and participate in conformational changes during the transport cycle. This review also discusses new members of the SLC13 superfamily that exhibit both sodium-dependent and sodium-independent transport mechanisms. The Indy protein from Drosophila, involved in determining lifespan, and the plant vacuolar malate transporter are both sodium-independent dicarboxylate transporters, possibly acting as exchangers. The purpose of this review is to provide an update on new advances in this gene family, particularly on structure-function studies and new members of the family.
Substrate-independent leak currents have also been described.
Structure-function studies have identified the carboxy terminal half of these proteins as the most important for determining function. Transmembrane helices 9 and 10 may form part of the substrate permeation pathway and participate in conformational changes during the transport cycle. This review also discusses new members of the SLC13 superfamily that exhibit both sodium-dependent and sodium-independent transport mechanisms. The Indy protein from Drosophila, involved in determining lifespan, and the plant vacuolar malate transporter are both sodium-independent dicarboxylate transporters, possibly acting as exchangers. The purpose of this review is to provide an update on new advances in this gene family, particularly on structure-function studies and new members of the family.
Free PMC Article
NAS2 , SLC13A4 (7q33), SUT-1, SUT1
https://www.ncbi.nlm.nih.gov/gene
NAS2 , SLC13A4 (7q33), SUT-1, SUT1
https://www.ncbi.nlm.nih.gov/gene
- Official Symbol SLC13A4
- Official Full Name solute carrier family 13 member 4
- Also known as NAS2; SUT1; SUT-1
- Expression;Biased expression in placenta (RPKM 28.4) and testis (RPKM 3.0) See more
- Molecular analysis of sequence and splice variants of the human SLC13A4 sulfate transporter. Zhang Z, et al. Mol Genet Metab, 2017 May. PMID 28385533
- Molecular analysis of the human SLC13A4 sulfate transporter gene promoter. Jefferis J, et al. Biochem Biophys Res Commun, 2013 Mar 29. PMID 23485456
- Functional characterization and genomic organization of the human Na(+)-sulfate cotransporter hNaS2 gene (SLC13A4). Markovich D, et al. Biochem Biophys Res Commun, 2005 Jan 28. PMID 15607730
-
Molecular cloning and functional analysis of SUT-1, a sulfate transporter from human high endothelial venules.
Girard JP, et al. Proc Natl Acad Sci U S A, 1999 Oct 26. PMID 10535998, Free PMC Article AbstractHigh endothelial venules (HEV) are specialized postcapillary venules found in lymphoid organs and chronically inflamed tissues that support high levels of lymphocyte extravasation from the blood. One of the major characteristics of HEV endothelial cells (HEVEC) is their capacity to incorporate large amounts of sulfate into sialomucin-type counter-receptors for the lymphocyte homing receptor L-selectin. Here, we show that HEVEC express two functional classes of sulfate transporters defined by their differential sensitivity to the anion-exchanger inhibitor 4,4'-diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS), and we report the molecular characterization of a DIDS-resistant sulfate transporter from human HEVEC, designated SUT-1. SUT-1 belongs to the family of Na(+)-coupled anion transporters and exhibits 40-50% amino acid identity with the rat renal Na(+)/sulfate cotransporter, NaSi-1, as well as with the human and rat Na(+)/dicarboxylate cotransporters, NaDC-1/SDCT1 and NaDC-3/SDCT2. Functional expression studies in cRNA-injected Xenopus laevis oocytes showed that SUT-1 mediates high levels of Na(+)-dependent sulfate transport, which is resistant to DIDS inhibition. The SUT-1 gene mapped to human chromosome 7q33. Northern blotting analysis revealed that SUT-1 exhibits a highly restricted tissue distribution, with abundant expression in placenta. Reverse transcription-PCR analysis indicated that SUT-1 and the diastrophic dysplasia sulfate transporter (DTD), one of the two known human DIDS-sensitive sulfate transporters, are coexpressed in HEVEC. SUT-1 and DTD could correspond, respectively, to the DIDS-resistant and DIDS-sensitive components of sulfate uptake in HEVEC. Together, these results demonstrate that SUT-1 is a distinct human Na(+)-coupled sulfate transporter, likely to play a major role in sulfate incorporation in HEV.
- Human placental sulfate transporter mRNA profiling from term pregnancies identifies abundant SLC13A4 in syncytiotrophoblasts and SLC26A2 in cytotrophoblasts. Simmons DG, et al. Placenta, 2013 Apr. PMID 23453247 Sulfate is an important nutrient for fetal growth and development. The fetus has no mechanism for producing its own sulfate and is therefore totally reliant on sulfate from the maternal circulation via placental sulfate transport. To build a model of directional sulfate transport in the placenta, we investigated the relative abundance of the 10 known sulfate transporter mRNAs in human placenta from uncomplicated term pregnancies. SLC13A4 and SLC26A2 were the most abundant sulfate transporter mRNAs, which localized to syncytiotrophoblast and cytotrophoblast cells, respectively. These findings indicate important physiological roles for SLC13A4(NAS1) and SLC26A2(SUT1) in human placental sulfate transport.
GeneRIFs: Gene References Into Functions
- Study found that despite differential expression of the two SLC13A4 transcripts, no detectable functional difference in the cellular sorting or sulfate transporting was found. However, some variants can influence both mechanism in specific cell membranes. This is like to have clinical implications based on the consequences of impaired sulfate transport during pregnancy in rodent models.
- SLC13A4 and SLC26A2 were the most abundant sulfate transporter mRNAs, which localized to syncytiotrophoblast and cytotrophoblast cells, respectively.
- To investigate the regulation of SLC13A4 gene expression, we analysed the transcriptional activity of the SLC13A4 5'-flanking region in the JEG-3 placental cell line using luciferase reporter assays.
- Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
- Here, we characterized the functional properties of the human Na(+)-sulfate cotransporter (hNaS2), determined its tissue distribution, and identified its gene (SLC13A4) structure.
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