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SLC13A4 Membrane Protein Introduction

Introduction of SLC13A4

Solute carrier family 13 member 4 (SLC13A4) is a member of SLC13 family with 12 transmembrane structures. Recent researches show that SLC13A4 may cooperate with SLC13A1 in structure, organization and tissue expression. It also influences fetal development. The loss of the sulfate transporter SLC13A4 in the placenta may cause severe fetal abnormalities and death in mice, as well as severe developmental defects and embryonic lethality. Besides, SLC13A4 is also responsible for skeletal development in mice.

Basic Information of SLC13A4
Protein Name Solute carrier family 13 member 4
Gene Name SLC13A4
Aliases Na(+)/sulfate cotransporter SUT-1(NaS2)
Organism Homo sapiens (Human)
UniProt ID Q9UKG4
Transmembrane Times 12
Length (aa) 626
Sequence MGLLQGLLRVRKLLLVVCVPLLLLPLPVLHPSSEASCAYVLIVTAVYWVSEAVPLGAAALVPAFLYPFFGVLRSNEVAAEYFKNTTLLLVGVICVAAAVEKWNLHKRIALRMVLMAGAKPGMLLLCFMCCTTLLSMWLSNTSTTAMVMPIVEAVLQELVSAEDEQLVAGNSNTEEAEPISLDVKNSQPSLELIFVNEESNADLTTLMHNENLNGVPSITNPIKTANQHQGKKQHPSQEKPQVLTPSPRKQKLNRKYRSHHDQMICKCLSLSISYSATIGGLTTIIGTSTSLIFLEHFNNQYPAAEVVNFGTWFLFSFPISLIMLVVSWFWMHWLFLGCNFKETCSLSKKKKTKREQLSEKRIQEEYEKLGDISYPEMVTGFFFILMTVLWFTREPGFVPGWDSFFEKKGYRTDATVSVFLGFLLFLIPAKKPCFGKKNDGENQEHSLGTEPIITWKDFQKTMPWEIVILVGGGYALASGSKSSGLSTWIGNQMLSLSSLPPWAVTLLACILVSIVTEFVSNPATITIFLPILCSLSETLHINPLYTLIPVTMCISFAVMLPVGNPPNAIVFSYGHCQIKDMVKAGLGVNVIGLVIVMVAINTWGVSLFHLDTYPAWARVSNITDQA

Function of SLC13A4 Membrane Protein

SLC13A4 is closely related to sodium/sulfate cotransporter in human, which mediates sulfate reabsorption in the high endothelial venules (HEV). Studies have shown that the transporting function of SLC13A4 can be inhibited by many factors, like thiosulfate, phosphate, molybdate, selenate and tungstate. While, this protein cannot be inhibited by oxalate, citrate, succinate, phenol red or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). The main function of SLC13A4 is sulfate symporter activity, as well as anion transmembrane transport and sulfate transport.

Predicted topology of the human SLC13A4 protein depicting the location of validated missense variants. Fig.1 Predicted topology of the human SLC13A4 protein depicting the location of validated missense variants. (Zhang, 2017)

Application of SLC13A4 Membrane Protein in Literature

  1. Markovich D., et al. Functional characterization and genomic organization of the human Na(+)-sulfate cotransporter hNaS2 gene (SLC13A4). Biochem Biophys Res Commun. 2005, 326(4):729-34. PubMed ID: 15607730

    The authors find the SLC13A4 gene contains 16 exons, spanning over 47kb in length. Its 5'-flanking region contains CAAT- and GC-box motifs, and a number of putative transcription factor binding sites, including GATA-1, AP-1, and AP-2 consensus sequences.

  2. Dawson P.A., et al. The rat Na+-sulfate cotransporter rNaS2: functional characterization, tissue distribution, and gene (slc13a4) structure. Pflugers Arch. 2005, 450(4):262-8. PubMed ID: 15889308

    This article is the first study to characterize rNaS2 transport kinetics, define its tissue distribution, and resolve its gene (slc13a4) structure and 5' flanking region.

  3. Dawson P.A., et al. Molecular cloning and characterization of the mouse Na+ sulfate cotransporter gene (Slc13a4): structure and expression. Genes Genet Syst. 2006, 81(4):265-72. PubMed ID: 17038798

    In this article, authors define the tissue distribution of mNaS2 and resolve its cDNA and gene structures, which will help to investigate mNaS2 gene expression in vivo and determine its role in mammalian physiology.

  4. Simmons D.G., et al. Human placental sulfate transporter mRNA profiling from term pregnancies identifies abundant SLC13A4 in syncytiotrophoblasts and SLC26A2 in cytotrophoblasts. Placenta. 2013, 34(4):381-4. PubMed ID: 23453247

    This article suggests SLC13A4 and SLC26A2 are the most abundant sulfate transporter mRNAs, which localizes to syncytiotrophoblast and cytotrophoblast cells, respectively. It indicates important physiological roles of SLC13A4 and SLC26A2 in human placental sulfate transport.

  5. Jefferis J., et al. Molecular analysis of the human SLC13A4 sulfate transporter gene promoter. Biochem Biophys Res Commun. 2013, 433(1):79-83. PubMed ID: 23485456

    The results show that the conserved NFY, SP1, KLF7, ZIC2 and HEN1 motifs in the SLC13A4 promoter of placental species but not in non-placental species may play a potential role for these putative transcriptional factors binding motifs in the physiological control of SLC13A4 mRNA expression.

SLC13A4 Preparation Options

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Reference

  1. Zhang Z, et al. (2017). Molecular analysis of sequence and splice variants of the human SLC13A4 sulfate transporter. Molecular Genetics and Metabolism. 121(1), 35-42.

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