Sodium/phosphate cotransporter

Last updated

The sodium/phosphate cotransporter is a member of the phosphate:Na+ symporter (PNaS) family within the TOG Superfamily of transport proteins as specified in the Transporter Classification Database (TCDB).

Contents

Nomenclature

Sodium/phosphate cotransporters are also known as:

PNaS family

The Phosphate:Na+ Symporter (PNaS) family (TC# 2.A.58 ) includes several closely related, functionally characterized, sodium-dependent, inorganic phosphate (Pi) transporter (NPT) proteins from mammals. Other organisms that possess PNaS family members include many in eukaryotic, bacterial and archaeal phyla. Bacterial sodium:phosphate symporters, NptA of Vibrio cholerae (TC#2.A.58.1.2) and YjbB of E. coli (TC# 2.A.58.2.1) have been functionally characterized. [1] [2]

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 pH-independent. [3] The IIa sodium phosphate symporter isoform is a functional monomer, [4] but it interacts with PDZ proteins which probably mediate apical sorting, parathyroid hormone-controlled endocytosis and/or lysosomal sorting of internalized transporters. [5] [6]

Transport reaction

The transport reaction catalyzed by the mammalian proteins is: [5]

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 protein 2A is encoded by the solute carrier family 34, member 1 (SLC34A1) gene [7] and facilitates uptake of phosphate for normal cellular functions including cellular metabolism, signal transduction, and nucleic acid and lipid synthesis. The PNaS family is also called the SLC34 family.

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

PNaS Proteins in Other Groups

Teleost Fish

Due to the Actinopterygian whole genome duplication event, slc34a1 and slc34a2 are present in a duplicated form in many teleost fish - slc34a1a and slc34a1b, slc34a2a and slc34a2b. [9] This is not uniform and slc341b is frequently lost in some Actinopterygian lineages. [9] slc34a3-type genes are not present. [9]

Antibody

Lifastuzumab vedotin is a monoclonal antibody for the sodium/phosphate cotransporter that is under development for the treatment of cancer.

See also

Related Research Articles

<span class="mw-page-title-main">Antiporter</span> Class of transmembrane transporter protein

An antiporter (also called exchanger or counter-transporter) is a cotransporter and integral membrane protein involved in secondary active transport of two or more different molecules or ions across a phospholipid membrane such as the plasma membrane in opposite directions, one into the cell and one out of the cell. Na+/H+ antiporters have been reviewed.

<span class="mw-page-title-main">Cotransporter</span> Type of membrane transport proteins

Cotransporters are a subcategory of membrane transport proteins (transporters) that couple the favorable movement of one molecule with its concentration gradient and unfavorable movement of another molecule against its concentration gradient. They enable coupled or cotransport and include antiporters and symporters. In general, cotransporters consist of two out of the three classes of integral membrane proteins known as transporters that move molecules and ions across biomembranes. Uniporters are also transporters but move only one type of molecule down its concentration gradient and are not classified as cotransporters.

The solute carrier (SLC) group of membrane transport proteins include over 400 members organized into 66 families. Most members of the SLC group are located in the cell membrane. The SLC gene nomenclature system was originally proposed by the HUGO Gene Nomenclature Committee (HGNC) and is the basis for the official HGNC names of the genes that encode these transporters. A more general transmembrane transporter classification can be found in TCDB database.

The Na–K–Cl cotransporter (NKCC) is a transport protein that aids in the secondary active transport of sodium, potassium, and chloride into cells. In humans there are two isoforms of this membrane transport protein, NKCC1 and NKCC2, encoded by two different genes. Two isoforms of the NKCC1/Slc12a2 gene result from keeping or skipping exon 21 in the final gene product.

A neurotransmitter sodium symporter (NSS) (TC# 2.A.22) is type of neurotransmitter transporter that catalyzes the uptake of a variety of neurotransmitters, amino acids, osmolytes and related nitrogenous substances by a solute:Na+ symport mechanism. The NSS family is a member of the APC superfamily. Its constituents have been found in bacteria, archaea and eukaryotes.

<span class="mw-page-title-main">SLC20A1</span> Protein-coding gene in the species Homo sapiens

Sodium-dependent phosphate transporter 1 is a protein that in humans is encoded by the SLC20A1 gene.

<span class="mw-page-title-main">Sodium/bile acid cotransporter</span> Protein-coding gene in the species Homo sapiens

Sodium/bile acid cotransporter also known as the Na+-taurocholate cotransporting polypeptide (NTCP) or liver bile acid transporter (LBAT) is a protein that in humans is encoded by the SLC10A1 (solute carrier family 10 member 1) gene.

An amino acid transporter is a membrane transport protein that transports amino acids. They are mainly of the solute carrier family.

<span class="mw-page-title-main">Sodium-dependent phosphate transport protein 2B</span> Protein-coding gene in the species Homo sapiens

Sodium-dependent phosphate transport protein 2B (NaPi2b) is a protein that in humans is encoded by the SLC34A2 gene.

<span class="mw-page-title-main">Vesicular glutamate transporter 1</span> Protein-coding gene in the species Homo sapiens

Vesicular glutamate transporter 1 (VGLUT1) is a protein that in humans is encoded by the SLC17A7 gene.

<span class="mw-page-title-main">Sodium-dependent phosphate transport protein 1</span> Protein-coding gene in the species Homo sapiens

Sodium-dependent phosphate transport protein 1 is a protein that in humans is encoded by the SLC17A1 gene.

<span class="mw-page-title-main">SLC20A2</span> Protein-coding gene in the species Homo sapiens

Sodium-dependent phosphate transporter 2 is a protein that in humans is encoded by the SLC20A2 gene.

<span class="mw-page-title-main">SLC13A3</span> Protein-coding gene in the species Homo sapiens

Solute carrier family 13 member 3 also called sodium-dependent dicarboxylate transporter (NaDC3) is a protein that in humans is encoded by the SLC13A3 gene.

<span class="mw-page-title-main">Sodium-dependent phosphate transport protein 2C</span> Protein-coding gene in the species Homo sapiens

Sodium-dependent phosphate transport protein 2C is a protein that in humans is encoded by the SLC34A3 gene.

<span class="mw-page-title-main">SLC5A4</span> Protein-coding gene in the species Homo sapiens

The low affinity sodium-glucose cotransporter also known as the sodium/glucose cotransporter 3 (SGLT3) or solute carrier family 5 member 4 (SLC5A4) is a protein that in humans is encoded by the SLC5A4 gene. It functions as a sugar sensor.

Sodium sulfate symporters are integral membrane proteins that mediate the intake of a wide variety of molecules with the concomitant uptake of sodium ions. These sodium symporters can be grouped, on the basis of sequence and functional similarities into a number of distinct families. One of these families, also known as SLC13 transporters, consists of the following proteins:

The lysosomal cystine transporter (LCT) family is part of the TOG Superfamily and includes secondary transport proteins that are derived from animals, plants, fungi and other eukaryotes. They exhibit 7 putative transmembrane α-helical spanners (TMSs) and vary in size between about 200 and 500 amino acyl residues, although most have between 300 and 400 residues.

<span class="mw-page-title-main">Sodium-dependent phosphate transport protein 2A</span> Protein-coding gene in the species Homo sapiens

Sodium-dependent phosphate transport protein 2A, also known as Na+-Pi cotransporter 2a (NaPi-2a), is a protein in humans that is encoded by the SLC34A1 gene. This gene encodes a member of the type II sodium-phosphate cotransporter family.

The cation-chloride cotransporter (CCC) family is part of the APC superfamily of secondary carriers. Members of the CCC family are found in animals, plants, fungi and bacteria. Most characterized CCC family proteins are from higher eukaryotes, but one has been partially characterized from Nicotiana tabacum, and homologous ORFs have been sequenced from Caenorhabditis elegans (worm), Saccharomyces cerevisiae (yeast) and Synechococcus sp.. The latter proteins are of unknown function. These proteins show sequence similarity to members of the APC family. CCC family proteins are usually large, and possess 12 putative transmembrane spanners (TMSs) flanked by large N-terminal and C-terminal hydrophilic domains.

Divalent anion:Na+ symporters were found in bacteria, archaea, plant chloroplasts and animals.

References

  1. Lebens, M; Lundquist, P; Söderlund, L; Todorovic, M; Carlin, NI (August 2002). "The nptA gene of Vibrio cholerae encodes a functional sodium-dependent phosphate cotransporter homologous to the type II cotransporters of eukaryotes". Journal of Bacteriology. 184 (16): 4466–74. doi:10.1128/jb.184.16.4466-4474.2002. PMC   135239 . PMID   12142417.
  2. Motomura, K; Hirota, R; Ohnaka, N; Okada, M; Ikeda, T; Morohoshi, T; Ohtake, H; Kuroda, A (2011). "Overproduction of YjbB reduces the level of polyphosphate in Escherichia coli: a hypothetical role of YjbB in phosphate export and polyphosphate accumulation". FEMS Microbiology Letters. 320 (1): 25–32. doi: 10.1111/j.1574-6968.2011.02285.x . PMID   21488939.
  3. 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" (PDF). The Journal of Biological Chemistry. 275 (9): 6284–7. doi: 10.1074/jbc.275.9.6284 . PMID   10692425.
  4. 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" (PDF). The Journal of Biological Chemistry. 275 (34): 26113–20. doi: 10.1074/jbc.M003564200 . PMID   10859311.
  5. 1 2 Saier, Milton. "Transporter Classification Database: 2.A.58 The Phosphate:Na+ Symporter (PNaS) Family". tcdb.org.
  6. 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" (PDF). The Journal of Biological Chemistry. 276 (12): 9206–13. doi: 10.1074/jbc.M008745200 . PMID   11099500.
  7. "Entrez Gene: Solute carrier family 34 (sodium phosphate), member 1".
  8. Yin BW, Kiyamova R, Chua R, Caballero OL, Gout I, Gryshkova V, Bhaskaran N, Souchelnytskyi S, Hellman U, Filonenko V, Jungbluth AA, Odunsi K, Lloyd KO, Old LJ, Ritter G (2008). "Monoclonal antibody MX35 detects the membrane transporter NaPi2b (SLC34A2) in human carcinomas". Cancer Immun. 8: 3. PMC   2935786 . PMID   18251464.
  9. 1 2 3 Verri, Tiziano; Werner, Andreas (2019). "Type II Na+-phosphate Cotransporters and Phosphate Balance in Teleost Fish". Pflügers Archiv - European Journal of Physiology. 471 (1): 193–212. doi:10.1007/s00424-018-2239-4. ISSN   0031-6768.

Further reading