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Gene Review

SLC20A1  -  solute carrier family 20 (phosphate...

Homo sapiens

Synonyms: GLVR-1, GLVR1, Gibbon ape leukemia virus receptor 1, Glvr-1, Leukemia virus receptor 1 homolog, ...
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Disease relevance of SLC20A1

  • Growth plate chondrocyte hypertrophy is associated with expression of the type III sodium-dependent inorganic phosphate (Pi) cotransporter phosphate transporter/retrovirus receptor 1 (PiT-1) [1].
  • This study was undertaken to test the hypothesis that IL-8 promotes chondrocyte hypertrophy by modulating chondrocyte PiT-1 expression and sodium-dependent Pi uptake, and to assess differential roles in this activity [1].
  • CONCLUSION: Our results link low-grade IL-8-mediated cartilaginous inflammation in OA to altered chondrocyte differentiation and disease progression through PiT-1 expression and sodium-dependent Pi uptake mediated by CXCR1 signaling [1].
  • We have identified two Streptococcus pneumoniae genetic loci, pit1 and pit2, encoding homologues of ABC iron transporters that are required for iron uptake by this organism [2].
  • A stretch of nine amino acids (region A) in the predicted fourth extracellular loop was previously shown to be critical for the function of Glvr1 as receptor for GALV and FeLV-B [3].

High impact information on SLC20A1

  • RNA analysis shows wide but distinct tissue distributions, with Glvr-1 expression being highest in bone marrow and Ram-1 in heart [4].
  • Overexpression of Ram-1 severely repressed Glvr-1 synthesis in fibroblasts, suggesting that transporter expression may be controlled by net phosphate accumulation [4].
  • By expression in Xenopus laevis oocytes and in mammalian cells, we have identified Glvr-1 and Ram-1 as sodium-dependent phosphate symporters [4].
  • The increase in transduction with PG13 vectors correlated with Northern blotting and reverse transcription-polymerase chain reaction studies that indicated that both K562 cells and the LAD EBV B cells express transcripts for the gibbon ape leukemia virus receptor at higher levels than for the amphotropic virus receptor [5].
  • Type III sodium-dependent phosphate (NaP(i)) cotransporters, Pit1 and Pit2, have been assigned housekeeping P(i) transport functions and suggested involved in chondroblastic and osteoblastic mineralization and ectopic calcification [6].

Biological context of SLC20A1

  • In addition, the regulation of Glvr-1 gene expression also has potential applications to gene therapy, since retroviral vectors carrying gibbon ape leukemia virus envelope proteins are used for gene delivery into different cell types [7].
  • Characterization of the human Glvr-1 phosphate transporter/retrovirus receptor gene and promoter region [7].
  • The aim of this study was thus to clone the human Glvr-1 gene in order to describe its structure and its promoter region.Our results indicate that the Glvr-1 gene consists of 11 exons and 10 introns spread over 18kb of genomic DNA [7].
  • Moreover, the downregulation of 10A1 receptor function by changes in region A of human Pit1 indicates that this region is also involved in 10A1 entry [8].
  • These transporters, called PiT-1 and PiT-2, respectively, are approximately 59% identical in amino acid sequence and are members of a gene family distinct from the renal type I and type II NaPi sodium-dependent phosphate transporters [9].

Anatomical context of SLC20A1

  • Rapid amplification of cDNA ends (5'-RACE) suggests that, in human SaOS-2 osteoblast-like cells, transcription of Glvr-1 is initiated at multiple sites, mostly located between bp 32 and 50 of the published cDNA sequence, which was initially obtained from HL-60 cells [7].
  • However, at least in one cell line it used Pit1 more efficiently for entry [10].
  • We then analyzed whether this enhanced expression of GLVR-1 correlated with increased infectivity of lymphocytes by retroviral vectors that utilize the GALV envelope compared to those that use the amphotropic envelope [11].
  • The superior transduction efficacy of CD8+ T cells by MuLV-10A1 correlates with a longer half-life of this pseudotype in comparison with A-MuLV and, as shown by interference analysis with the human T cell line HUT78, by the utilization of both the A-MuLV receptor (Pit2) and the GaLV receptor (Pit1) for cell entry [12].
  • Hormonal treatment or P(i) starvation of tooth germs in vitro did not alter Pit2 levels or patterns of expression, indicating mechanisms of regulation different from those of PiT-1 or other cell types [13].

Associations of SLC20A1 with chemical compounds


Regulatory relationships of SLC20A1


Other interactions of SLC20A1


Analytical, diagnostic and therapeutic context of SLC20A1


  1. Role of interleukin-8 in PiT-1 expression and CXCR1-mediated inorganic phosphate uptake in chondrocytes. Cecil, D.L., Rose, D.M., Terkeltaub, R., Liu-Bryan, R. Arthritis Rheum. (2005) [Pubmed]
  2. A Streptococcus pneumoniae pathogenicity island encoding an ABC transporter involved in iron uptake and virulence. Brown, J.S., Gilliland, S.M., Holden, D.W. Mol. Microbiol. (2001) [Pubmed]
  3. Chimeras of receptors for gibbon ape leukemia virus/feline leukemia virus B and amphotropic murine leukemia virus reveal different modes of receptor recognition by retrovirus. Pedersen, L., Johann, S.V., van Zeijl, M., Pedersen, F.S., O'Hara, B. J. Virol. (1995) [Pubmed]
  4. Cell-surface receptors for gibbon ape leukemia virus and amphotropic murine retrovirus are inducible sodium-dependent phosphate symporters. Kavanaugh, M.P., Miller, D.G., Zhang, W., Law, W., Kozak, S.L., Kabat, D., Miller, A.D. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  5. Improved transfer of the leukocyte integrin CD18 subunit into hematopoietic cell lines by using retroviral vectors having a gibbon ape leukemia virus envelope. Bauer, T.R., Miller, A.D., Hickstein, D.D. Blood (1995) [Pubmed]
  6. Two highly conserved glutamate residues critical for type III sodium-dependent phosphate transport revealed by uncoupling transport function from retroviral receptor function. Bottger, P., Pedersen, L. J. Biol. Chem. (2002) [Pubmed]
  7. Characterization of the human Glvr-1 phosphate transporter/retrovirus receptor gene and promoter region. Palmer, G., Manen, D., Bonjour, J.P., Caverzasio, J. Gene (1999) [Pubmed]
  8. Single amino acid insertion in loop 4 confers amphotropic murine leukemia virus receptor function upon murine Pit1. Lundorf, M.D., Pedersen, F.S., O'Hara, B., Pedersen, L. J. Virol. (1998) [Pubmed]
  9. Identification and characterization of a widely expressed phosphate transporter/retrovirus receptor family. Kavanaugh, M.P., Kabat, D. Kidney Int. (1996) [Pubmed]
  10. RNA levels of human retrovirus receptors Pit1 and Pit2 do not correlate with infectibility by three retroviral vector pseudotypes. Uckert, W., Willimsky, G., Pedersen, F.S., Blankenstein, T., Pedersen, L. Hum. Gene Ther. (1998) [Pubmed]
  11. Improved gene transfer into human lymphocytes using retroviruses with the gibbon ape leukemia virus envelope. Lam, J.S., Reeves, M.E., Cowherd, R., Rosenberg, S.A., Hwu, P. Hum. Gene Ther. (1996) [Pubmed]
  12. Efficient gene transfer into primary human CD8+ T lymphocytes by MuLV-10A1 retrovirus pseudotype. Uckert, W., Becker, C., Gladow, M., Klein, D., Kammertoens, T., Pedersen, L., Blankenstein, T. Hum. Gene Ther. (2000) [Pubmed]
  13. Expression of Pit2 sodium-phosphate cotransporter during murine odontogenesis is developmentally regulated. Zhao, D., Vaziri Sani, F., Nilsson, J., Rodenburg, M., Stocking, C., Linde, A., Gritli-Linde, A. Eur. J. Oral Sci. (2006) [Pubmed]
  14. Entry of amphotropic murine leukemia virus is influenced by residues in the putative second extracellular domain of its receptor, Pit2. Leverett, B.D., Farrell, K.B., Eiden, M.V., Wilson, C.A. J. Virol. (1998) [Pubmed]
  15. Evolutionary and experimental analyses of inorganic phosphate transporter PiT family reveals two related signature sequences harboring highly conserved aspartic acids critical for sodium-dependent phosphate transport function of human PiT2. Bøttger, P., Pedersen, L. FEBS J. (2005) [Pubmed]
  16. Expression of a newly identified phosphate transporter/retrovirus receptor in human SaOS-2 osteoblast-like cells and its regulation by insulin-like growth factor I. Palmer, G., Bonjour, J.P., Caverzasio, J. Endocrinology (1997) [Pubmed]
  17. Nitrite uptake and metabolism and oxidant stress in human erythrocytes. May, J.M., Qu, Z.C., Xia, L., Cobb, C.E. Am. J. Physiol., Cell Physiol. (2000) [Pubmed]
  18. NaPi-mediated transcellular permeation is the dominant route in intestinal inorganic phosphate absorption in rats. Eto, N., Tomita, M., Hayashi, M. Drug Metab. Pharmacokinet. (2006) [Pubmed]
  19. Role of membrane microdomains in PTH-mediated down-regulation of NaPi-IIa in opossum kidney cells. Nashiki, K., Taketani, Y., Takeichi, T., Sawada, N., Yamamoto, H., Ichikawa, M., Arai, H., Miyamoto, K., Takeda, E. Kidney Int. (2005) [Pubmed]
  20. The molecular basis for Na-dependent phosphate transport in human erythrocytes and K562 cells. Timmer, R.T., Gunn, R.B. J. Gen. Physiol. (2000) [Pubmed]
  21. Identification of an extracellular domain within the human PiT2 receptor that is required for amphotropic murine leukemia virus binding. Feldman, S.A., Farrell, K.B., Murthy, R.K., Russ, J.L., Eiden, M.V. J. Virol. (2004) [Pubmed]
  22. Characterization of novel human ovarian cancer-specific transcripts (HOSTs) identified by serial analysis of gene expression. Rangel, L.B., Sherman-Baust, C.A., Wernyj, R.P., Schwartz, D.R., Cho, K.R., Morin, P.J. Oncogene (2003) [Pubmed]
  23. Vascular calcification: in vitro evidence for the role of inorganic phosphate. Giachelli, C.M. J. Am. Soc. Nephrol. (2003) [Pubmed]
  24. Expression of the gibbon ape leukemia virus receptor-1 in rhesus macaque tissues. Wong, S.W., Swanson, R.M., Bergquam, E.P. J. Med. Primatol. (1997) [Pubmed]
  25. Immunodetection of a type III sodium-dependent phosphate cotransporter in tissues and OK cells. Boyer, C.J., Baines, A.D., Beaulieu, E., Béliveau, R. Biochim. Biophys. Acta (1998) [Pubmed]
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