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2.A.58 The Phosphate:Na+ Symporter (PNaS) Family

The PNaS family includes several closely related, functionally characterized, sodium-dependent, inorganic phosphate (Pi) transporter (NPT2) proteins from mammals. Other animals, including fish and the worm, C. elegans, possess functionally uncharacterized homologues. 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) than to any other bacterial homologue, and it may therefore have been obtained by lateral transfer from a eukaryotic source. Distantly related bacterial proteins are found in many bacteria including E. coli(543 aas; spP32683; 8 putative TMSs) and Bacillus subtilis(310 aas; spP54463; 8 putative TMSs). The bacterial homologue, NptA of V. cholerae has 10 putative TMSs. 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 are in the cytoplasm, and a large hydrophilic loop is localized between TMSs 3 and 4. While IIa isoforms are pH-dependent, IIb isoforms are pH-independent (de la Horra et al., 2000).

Mammalian porters of the PNaS family may catalyze cotransport of 3 Na+ with inorganic phosphate. In response to parathyroid hormone and dietary inorganic phosphate, the renal cotransporter is rapidly inserted into and retrieved from the renal brush border membrane in a fashion similar to that by which the glucose transporter (Glut4) (2.A.1.1) is regulated by insulin and aquaporins 1 and 2 (1.A.8.1) are regulated by vasopressin (Levi et al., 1999). The renal type IIa PNaS member is a functional monomer (Kohler et al., 2001), but it interacts with PDZ proteins which probably mediate apical sorting, parathyroid hormone-controlled endocytosis and/or lysosomal sorting of internalized transporter (Gisler et al., 2001). 


A single organism may have multiple paralogues of the PNaS family. All of these proteins exhibit an internal repeat that probably arose by a tandem intragenic duplication event.

The transport reaction catalyzed by the mammalian proteins is:



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



References associated with 2.A.58 family:

Bakouh, N., B. Chérif-Zahar, P. Hulin, D. Prié, G. Friedlander, A. Edelman, and G. Planelles. (2012). Functional Interaction between CFTR and the Sodium-Phosphate Co-Transport Type 2a in Xenopus laevis Oocytes. PLoS One 7: e34879. 22514683
Chen, P., Q. Tang, and C. Wang. (2016). Characterizing and evaluating the expression of the type IIb sodium-dependent phosphate cotransporter (slc34a2) gene and its potential influence on phosphorus utilization efficiency in yellow catfish (Pelteobagrus fulvidraco). Fish Physiol Biochem 42: 51-64. 26298316
Collins, J.F. and F.K. Ghishan. (1994). Molecular cloning, functional expression, tissue distribution, and in situ hybridization of the renal sodium phosphate (Na+/Pi) transporter in the control and hypophosphatemic mouse. FASEB J. 8: 862-868. 8070635
De la Horra, C., N. Hernando, G. Lambert, I. Forster, J. Biber, and H. Murer. (2000). Molecular determinants of pH sensitivity of the type IIa Na/P(i) cotransporter. J. Biol. Chem. 275: 6284-6287. 10692425
Ebert, M., S. Laaß, M. Burghartz, J. Petersen, S. Koßmehl, L. Wöhlbrand, R. Rabus, C. Wittmann, P. Tielen, and D. Jahn. (2013). Transposon mutagenesis identified chromosomal and plasmid genes essential for adaptation of the marine bacterium Dinoroseobacter shibae to anaerobic conditions. J. Bacteriol. 195: 4769-4777. 23974024
Fenollar-Ferrer, C., I.C. Forster, M. Patti, T. Knoepfel, A. Werner, and L.R. Forrest. (2015). Identification of the First Sodium Binding Site of the Phosphate Cotransporter NaPi-IIa (SLC34A1). Biophys. J. 108: 2465-2480. 25992725
Ghezzi C., Murer H. and Forster IC. (2009). Substrate interactions of the electroneutral Na+-coupled inorganic phosphate cotransporter (NaPi-IIc). J Physiol. 587(Pt 17):4293-307. 19596895
Gisler, S.M., I. Stagljar, M. Traebert, D. Bacic, J. Biber, and H. Murer. (2001). Interaction of the type IIa Na/Pi cotransporter with PDZ proteins. J. Biol. Chem. 276: 9206-9213. 11099500
Kohler, K., I.C. Forster, G. Lambert, J. Biber, and H. Murer. (2001). The functional unit of the renal type IIa Na+/Pi cotransporter is a monomer. J. Biol. Chem 275: 26113-26120. 10859311
Lebens, M., P. Lundquist, L. Söderlund, M. Todorovic, and N.I. Carlin. (2002). The nptA gene of Vibrio cholerae encodes a functional sodium-dependent phosphate cotransporter homologous to the type II cotransporters of eukaryotes. J. Bacteriol. 184: 4466-4474. 12142417
Levi, M., S.A. Kempson, M. Lötscher, J. Biber, and H. Murer. (1996). Molecular regulation of renal phosphate transport. J. Memb. Biol. 154: 1-9. 8881022
Magagnin, S., A. Werner, D. Markovich, V. Sorribas, G. Stange, J. Biber, and H. Murer. (1993). Expression cloning of human and rat renal cortex sodium-phosphorus cotransport. Proc. Natl. Acad. Sci. USA 90: 5979-5983. 8327470
Mamonova, T., Q. Zhang, J.A. Khajeh, Z. Bu, A. Bisello, and P.A. Friedman. (2015). Canonical and Noncanonical Sites Determine NPT2A Binding Selectivity to NHERF1 PDZ1. PLoS One 10: e0129554. 26070212
Motomura, K., R. Hirota, N. Ohnaka, M. Okada, T. Ikeda, T. Morohoshi, H. Ohtake, and A. Kuroda. (2011). Overproduction of YjbB reduces the level of polyphosphate in Escherichia coli: a hypothetical role of YjbB in phosphate export and polyphosphate accumulation. FEMS Microbiol. Lett. 320: 25-32. 21488939
Murer, H., N. Hernando, I. Forster, and J. Biber. (2000). Proximal tubular phosphate reabsorption: molecular mechanisms. Physiol. Rev. 80: 1373-1409. 11015617
Patti, M., C. Fenollar-Ferrer, A. Werner, L.R. Forrest, and I.C. Forster. (2016). Cation Interactions and Membrane Potential Induce Conformational Changes in NaPi-IIb. Biophys. J. 111: 973-988. 27602725
Segawa, H., I. Kaneko, A. Takahashi, M. Kuwahata, M. Ito, I. Ohkido, S. Tatsumi, and K. Miyamoto. (2002). Growth-related renal type II NaPi cotransporter. J. Biol. chem. 277: 19665-19672. 11880379
Stechman, M.J., N.Y. Loh, and R.V. Thakker. (2007). Genetics of hypercalciuric nephrolithiasis: renal stone disease. Ann. N.Y. Acad. Sci. 1116: 461-484. 17872384
Verri, T., D. Markovich, C. Perego, F. Norbis, G. Stange, V. Sorribas, J. Biber, and H. Murer. (1995). Cloning of a rabbit renal Na+-Pi cotransporter, which is regulated by dietary phosphate. Am. J. Physiol. 268: F626-F633. 7733319
Zhifeng, X., F. Rejun, H. Longchang, and S. Wenqing. (2012). Molecular cloning and functional characterization of swine sodium dependent phosphate cotransporter type II b (NaPi-IIb) gene. Mol Biol Rep 39: 10557-10564. 23065201