SLC34A1 Membrane Protein Introduction

Introduction of SLC34A1

Sodium-dependent phosphate transport protein 2A (Sodium-phosphate transport protein 2A), also known as Na(+)-dependent phosphate cotransporter 2A, Solute carrier family 34 member 1, Na(+)/Pi cotransporter 2A (NaPi-2a), is a protein that in humans is encoded by the SLC34A1 gene. The human NaPi-2a isoform consists of 639 amino acids. Human and rat NaPi-2a cDNAs were first isolated by expression cloning. NaPi-2a is predominantly expressed in the kidney and localizes to the apical brush border membrane of the proximal tubule. The expression is higher in early convoluted proximal tubules (S1 segments) and in juxtamedullary nephrons but spreads to the late proximal tubule (S2/S3 segments) and superficial nephrons during phosphate depletion. NaPi-2a mRNA has also been detected in brain and bone, but protein expression has not been confirmed.

Basic Information of SLC34A1
Protein Name	Sodium-dependent phosphate transport protein 2A
Gene Name	SLC34A1
Aliases	Sodium-phosphate transport protein 2A, Na(+)-dependent phosphate cotransporter 2A, NaPi-3, Sodium/phosphate cotransporter 2A, Na(+)/Pi cotransporter 2A, NaPi-2a, Solute carrier family 34 member 1, NPT2, SLC17A2
Organism	Homo sapiens (Human)
UniProt ID	Q06495
Transmembrane Times	8
Length (aa)	639
Sequence	MLSYGERLGSPAVSPLPVRGGHVMRGTAFAYVPSPQVLHRIPGTSAYAFPSLGPVALAEHTCPCGEVLERHEPLPAKLALEEEQKPESRLVPKLRQAGAMLLKVPLMLTFLYLFVCSLDMLSSAFQLAGGKVAGDIFKDNAILSNPVAGLVVGILVTVLVQSSSTSTSIIVSMVSSGLLEVSSAIPIIMGSNIGTSVTNTIVALMQAGDRTDFRRAFAGATVHDCFNWLSVLVLLPLEAATGYLHHITRLVVASFNIHGGRDAPDLLKIITEPFTKLIIQLDESVITSIATGDESLRNHSLIQIWCHPDSLQAPTSMSRAEANSSQTLGNATMEKCNHIFVDTGLPDLAVGLILLAGSLVLLCTCLILLVKMLNSLLKGQVAKVIQKVINTDFPAPFTWVTGYFAMVVGASMTFVVQSSSVFTSAITPLIGLGVISIERAYPLTLGSNIGTTTTAILAALASPREKLSSAFQIALCHFFFNISGILLWYPVPCTRLPIRMAKALGKRTAKYRWFAVLYLLVCFLLLPSLVFGISMAGWQVMVGVGTPFGALLAFVVLINVLQSRSPGHLPKWLQTWDFLPRWMHSLKPLDHLITRATLCCARPEPRSPPLPPRVFLEELPPATPSPRLALPAHHNATRL

Function of SLC34A1 Membrane Protein

In the case of SLC34A1, the regulation of SLC34 phosphate transporters has been best defined. Generally, regulation occurs primarily at the posttranscriptional level by changing the rate of synthesis and degradation and by altering the amount of NaPi-2a transporter molecules in the brush border membrane. There is little evidence that their activity in the brush border membrane to modulate the NaPi-2a transporter is altered by phosphorylation or other similar mechanisms. The biosynthetic pathways and mechanisms that control the insertion of NaPi-2a into the brush border membrane are little known. Activation of parathyroid hormone receptors downregulates NaPi-2a abundance at the brush border membrane in a few minutes by at least two different signaling pathways involving either PKA or PKC.

Fig.1 Localization of renal phosphate cotransporters in rodent kidney. (Wagner, 2014)

Application of SLC34A1 Membrane Protein in Literature

Rajagopal A., et al. Exome sequencing identifies a novel homozygous mutation in the phosphate transporter SLC34A1 in hypophosphatemia and nephrocalcinosis. J Clin Endocrinol Metab. 2014, 99(11): E2451-6. PubMed ID: 25050900

The article identifies a novel homozygous mutation in the phosphate transporter SLC34A1 in hypophosphatemia and nephrocalcinosis.
Wu H., et al. Assay development of inducible human renal phosphate transporter Npt2A (SLC34A1) in Flp-In-Trex-HEK293 cells. Eur J Pharmacol. 2013, 721(1-3): 332-40. PubMed ID: 24056120

Authors in this group found that the small molecule LC-1 can be used as a potent inhibitor of hNpt2A and it is possible to develop potent specific hNpt2A inhibitors to control phosphate overloading for hyperphosphatemia therapy.
Carlile M., et al. Strand selective generation of endo-siRNAs from the Na/phosphate transporter gene Slc34a1 in murine tissues. Nucleic Acids Res. 2009, 37(7): 2274-82. PubMed ID: 19237395

The article reports that Na/phosphate transporter gene Slc34a1 selectively generates endo-siRNAs in murine tissues.
Schlingmann K.P., et al. Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia. J Am Soc Nephrol. 2016, 27(2): 604-14. PubMed ID: 26047794

The article reveals that the early differentiation between SLC34A1 and CYP24A1 (24-hydroxylase) defects is critical for targeted therapy in patients with idiopathic infantile hypercalcemia.
Iwaki T., et al. A missense mutation in the sodium phosphate co-transporter Slc34a1 impairs phosphate homeostasis. J Am Soc Nephrol. 2008, 19(9): 1753-62. PubMed ID: 18550648

The article reports that a single amino acid substitution in Npt2a may lead to improper translocation of the protein to the cell membrane, disturbance of phosphate homeostasis, and renal calcification.

SLC34A1 Preparation Options

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Reference

Wagner C A, et al. (2014). The SLC34 family of sodium-dependent phosphate transporters. Pflugers Arch. 466(1): 139-53.

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