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Sodium/phosphate cotransporter

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The sodium/phosphate cotransporter is a member of the phosphate:Na+ symporter (PNaS) family under the TOG Superfamily of transport proteins as defined by the Transporter Classification Database.

Nomenclature

The sodium/phosphate cotransporter is also known as:

  • Na+-Pi cotransport protein (NaPi-2a),
  • Sodium-dependent phosphate transporter, or
  • Phosphate:Na+ symporter.

PNaS protein family

The Phosphate:Na+ Symporter (PNaS) family (TC# 2.A.58) includes several closely related, functionally characterized, sodium-dependent, inorganic phosphate (Pi) transporter (NPT2) proteins from mammals. Other organisms that possess NPT2 homologues are fish and the worm, C. elegans, although these homologues are functionally uncategorized. One closely related bacterial protein, NptA of Vibrio cholerae, resembles the animal proteins to a much greater degree (34% identity; 51% similarity to many mammalian Npt2 symporters [1]) than to any other bacterial homologue. This may be evidence that the gene was obtained through lateral transfer from a eukaryotic source. The well-characterized mammalian proteins are found in renal (IIa isoform) and intestinal (IIb isoform) brush border membranes and are about 640 amino acyl residues long with 8-12 putative TMSs. The N- and C-termini both reside in the cytoplasm, and a large hydrophilic loop is localized between trans-membrane segments (TMSs) 3 and 4. While IIa isoforms are pH-dependent, IIb isoforms are found to be pH-independent.[2] The IIa SodiumPphosphate Symporter isoform is a functional monomer,[3] but it interacts with PDZ proteins which probably mediate apical sorting, parathyroid hormone-controlled endocytosis and/or lysosomal sorting of internalized transporter.[1][4]

Transport reaction

The transport reaction catalyzed by the mammalian proteins is:[1]

Pi (out) + 3 Na+ (out) ⇌ Pi (in) + 3 Na+ (in).

Human PNaS proteins

There are several known sodium-dependent phosphate transporters found in humans. For example, the sodium-dependent phosphate transport protein 2A is a protein that in humans is encoded by the solute carrier family 34, member 1 (SLC34A1) gene.[5] and fascilitates uptake of phosphate for normal cellular functions including cellular metabolism, signal transduction, and nucleic acid and lipid synthesis.

Other known sodium-dependent phosphate transporters found in humans include (but are not limited to):

  • Sodium-Phosphate Cotransporter Proteins, Type I:
  • Sodium-Phosphate Cotransporter Proteins, Type II:
  • Sodium-Phosphate Cotransporter Proteins, Type III:

See also

References

  1. ^ a b c Saier, Milton. "Transporter Classification Database: 2.A.58 The Phosphate:Na+ Symporter (PNaS) Family". tcdb.org.
  2. ^ de la Horra C, Hernando N, Lambert G, Forster I, Biber J, Murer H (Mar 2000). "Molecular determinants of pH sensitivity of the type IIa Na/P(i) cotransporter". The Journal of Biological Chemistry. 275 (9): 6284–7. PMID 10692425.
  3. ^ Köhler K, Forster IC, Lambert G, Biber J, Murer H (Aug 2000). "The functional unit of the renal type IIa Na+/Pi cotransporter is a monomer". The Journal of Biological Chemistry. 275 (34): 26113–20. doi:10.1074/jbc.M003564200. PMID 10859311.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  4. ^ Gisler SM, Stagljar I, Traebert M, Bacic D, Biber J, Murer H (Mar 2001). "Interaction of the type IIa Na/Pi cotransporter with PDZ proteins". The Journal of Biological Chemistry. 276 (12): 9206–13. doi:10.1074/jbc.M008745200. PMID 11099500.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  5. ^ "Entrez Gene: Solute carrier family 34 (sodium phosphate), member 1".

Further reading

  • Tenenhouse HS (Feb 1999). "X-linked hypophosphataemia: a homologous disorder in humans and mice". Nephrology, Dialysis, Transplantation. 14 (2): 333–41. doi:10.1093/ndt/14.2.333. PMID 10069185.
  • Murer H, Hernando N, Forster I, Biber J (Oct 2000). "Proximal tubular phosphate reabsorption: molecular mechanisms". Physiological Reviews. 80 (4): 1373–409. PMID 11015617.
  • Fenollar-Ferrer C, Forster IC, Patti M, Knoepfel T, Werner A, Forrest LR (May 2015). "Identification of the first sodium binding site of the phosphate cotransporter NaPi-IIa (SLC34A1)". Biophysical Journal. 108 (10): 2465–80. doi:10.1016/j.bpj.2015.03.054. PMID 25992725.
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