Disease relevance of SLC17A1

• Hereditary Hypophosphatemic Rickets with Hypercalciuria Is Caused by Mutations in the Sodium-Phosphate Cotransporter Gene SLC34A3 [1].
• Human PiT2 (PiT2) is a multiple-membrane-spanning protein that functions as a type III sodium phosphate cotransporter and as the receptor for amphotropic murine leukemia virus (A-MuLV) [2].
• The potential importance of Pi as a novel signaling molecule and the poor prognosis of diverse neurodegenerative diseases that involve brain-specific NPT1 have prompted us to define the pathways by which Pi affects mouse brain growth [3].
• Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter [4].

Psychiatry related information on SLC17A1

• This field study examined how butterflies of the polyandric gift-giving species Pieris napi (Lepidoptera: Pieridae) use body resources in their reproduction and how the male donations affect the females use of stored reserves [5].
• 2 large independent cohorts of preterm infants ranging between 32 weeks and term were given a neurobehavioral assessment (the NAPI) that measures, among other things, individual differences in excitation management [6].

High impact information on SLC17A1

• Administration of sFRP-4 to intact rats over 8 hours increased FEPi, decreased serum phosphate (1.95 +/- 0.1 to 1.53 +/- 0.09 mmol/l, P < 0.05) but did not alter serum 1alpha, 25-dihydroxyvitamin D, renal 25-hydroxyvitamin D 1alpha-hydroxylase cytochrome P450, and sodium-phosphate cotransporter mRNA concentrations [7].
• We first identified a PAM locus by homozygosity mapping to 4p15, then identified, by a candidate-gene approach, the gene responsible for the disease as SLC34A2 (the type IIb sodium-phosphate cotransporter gene), which is involved in phosphate homeostasis in several organs [8].
• The predicted amino acid sequence of OATV1 exhibited 60-65% identity to those of human, rat, rabbit, and mouse sodium-dependent phosphate cotransporter type 1 (NPT1), although OATV1 did not transport phosphate [9].
• This result was confirmed by co-transfecting HEK293 cells with the sodium-phosphate cotransporter and wild type AKAP, a mutant AKAP79, or the empty vector [10].
• Mutations in the gene encoding the human sodium-phosphate cotransporter (NPT2), causing reduced phosphate affinity and dominant-negative behavior, were described [11].

Biological context of SLC17A1

• The DNA sequence was identical with that of NPT-1 cDNA published by Chong, Kristjansson, Zoghbi and Hughe (1993) (Genomics, 18, 355-359) [12].
• Npt1 is approximately 29 kb with 12 exons, whereas NPT1 is approximately 49 kb with one additional exon [13].
• This cDNA maps the location of the gene encoding NPT1 to human chromosome 6q21.3-p23 [14].
• Amino acid sequence comparisons indicate a 69.7% identity between human NPT1 and rabbit NaPi-1 polypeptides; the inclusion of conservative substitutions increases the homology between the two proteins to 81.5% [14].
• Characterization of the 5' flanking region of the human NPT-1 Na+/phosphate cotransporter gene [15].

Anatomical context of SLC17A1

• Hybrid depletion with antisense oligonucleotides to NaP(i)-3 and NPT-1 completely inhibited poly(A)+ RNA-induced Na(+)-dependent P(i) uptake in oocytes [12].
• These findings indicate that two high-affinity Na/P(i) cotransporters (NaP(i)-3 and NPT-1) are present in human kidney cortex [12].
• However, despite the identification of multiple isoforms in three gene families (Timmer, R.T., and R.B. Gunn. 1998. Am. J. Physiol. Cell Physiol. 274:C757-C769), the molecular basis for the sodium-phosphate cotransporter in erythrocytes is unknown [16].
• We also show that FGF23 induces tyrosine phosphorylation and inhibits sodium-phosphate cotransporter Npt2a mRNA expression using opossum kidney cells, a model kidney proximal tubule cell line [17].
• A high phosphate diet caused a significant increase in protein expression of NPT1, both in cerebrum and cerebellum [3].

Associations of SLC17A1 with chemical compounds

• Considering its chloride ion sensitivity, Npt1 is expected to function for secretion of PAH from renal proximal tubular cells [18].
• p-aminohippuric acid transport at renal apical membrane mediated by human inorganic phosphate transporter NPT1 [18].
• Human NPT1 also accepted uric acid, benzylpenicillin, faropenem, and estradiol-17beta-glucuronide as substrates [18].
• Candesartan decreased type 2 sodium-phosphate cotransporter abundance in both WKH (52 +/- 7% of control; P<0.05) and BBM (32 +/- 7% of control; P<0.05) [19].
• Males of the green-veined butterfly Pieris napi synthesize and transfer the volatile methyl salicylate (MeS) to females at mating, a substance that is emitted by non-virgin females when courted by males, curtailing courtship and decreasing the likelihood of female re-mating [20].

Other interactions of SLC17A1

• The candidate region contained a sodium-phosphate cotransporter gene, SLC34A3, which has been shown to be expressed in proximal tubulus cells [1].
• Human PiT1 (PiT1), another type III sodium phosphate cotransporter, is a highly related protein that functions as a receptor for gibbon ape leukemia virus but not for A-MuLV [2].
• The opossum kidney (OK) line displays PTH-mediated activation of adenylyl cyclase and phospholipase C and inhibition of phosphate (Pi) uptake via regulation of the type IIa sodium-phosphate cotransporter, consistent with effects in vivo [21].
• The similarities in the kinetics and the expression of only hBNP-1 protein in the two cell types is strong evidence that hBNP-1 is the erythrocyte and K562 cell sodium-phosphate cotransporter [16].
• Furthermore, immunoreactive sodium phosphate cotransporter type II, vasopressin receptor V1a, and CLIC-1 (NCC27) were also identified [22].

Analytical, diagnostic and therapeutic context of SLC17A1

• Northern blotting demonstrated that NPT-1 mRNA is expressed in renal cortex, liver and brain but not in other tissues [12].
• The chromosome locations of the rabbit (Oryctolagus cuniculus) Na+-phosphate cotransporter genes NPT1 and NPT2 were determined by fluorescence in situ hybridization [23].
• Polymerase chain reaction (PCR), using primers specific for two human Na/Pi co-transporters demonstrated that the genes for NaPi-3 was assigned to human chromosome 5 while that for NPT-1 was assigned to human chromosome 6 [24].

References