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SLC46A1  -  solute carrier family 46 (folate...

Homo sapiens

Synonyms: G21, HCP1, Heme carrier protein 1, MGC9564, PCFT, ...
 
 
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Disease relevance of SLC46A1

  • HCP 1 mRNA was highly expressed in duodenum and regulated by hypoxia [1].
  • The major mechanisms by which Gram-negative bacteria acquire heme from host heme-carrier proteins involve either direct binding to specific outer membrane receptors or release of bacterial hemophores that take up heme from host heme carriers and shuttle it back to specific receptors [2].
  • Intestinal Hcp1 mRNA content was not significantly changed by iron overload (600 mg/kg); however, it was increased to 170 % of controls 72 h after withdrawal of 0.7 ml of blood; the same treatment increased intestinal Cybrd1 mRNA to 900 % of controls [3].
 

High impact information on SLC46A1

  • However, the current study establishes that a major function of this gene product is proton-coupled folate transport required for folate homeostasis in man, and we have thus amended the name to PCFT/HCP1 [4].
  • HCP 1 protein was iron regulated and localized to the brush-border membrane of duodenal enterocytes in iron deficiency [1].
  • Haem-carrier protein 1 (HCP1) has recently been cloned and characterized as a putative transporter in the apical region of the duodenum, and is responsible for uptake of haem into the gut cells [5].
  • Here we report the identification from bovine RPE of a heme transporter bHcp1 (bovine heme carrier protein 1) that is homologous to mouse intestinal HCP1 expressed in duodenal enterocytes [6].
  • Heme carrier protein 1 (HCP1) expression and functional analysis in the retina and retinal pigment epithelium [6].
 

Biological context of SLC46A1

  • The uptake of (55)Fe labeled haem was determined in cells under different experimental conditions and HCP1 expression was measured by RT-PCR and immunohistochemistry. mRNA and protein expressions increased in Caco-2 cells transduced with HCP1 adenoviral plasmid, and consequently (55)Fe haem uptake was higher in these cells [7].
 

Anatomical context of SLC46A1

  • The current studies describe the expression and functional analysis of HCP1 in cultured Caco-2 cells, a commonly used model of human intestinal cells [7].
  • Haem carrier protein 1 (HCP1): Expression and functional studies in cultured cells [7].
 

Associations of SLC46A1 with chemical compounds

  • Preincubation of cells with desferrioxamine (DFO, to deplete cells of iron) had no effect on HCP1 expression or haem uptake [7].
  • Cotransfection of FRalpha and PCFT resulted in enhanced folate transport into cytosol as compared with transfection of FRalpha alone [8].
  • In electrophysiological studies in Xenopus oocytes, both WT-PCFT- and H281A-PCFT-mediated folic acid uptake produced current and acidification, and both exhibited a low level of folate-independent proton transport (slippage) [9].
 

Analytical, diagnostic and therapeutic context of SLC46A1

  • Recent genetic, biochemical and crystallization studies have started to unravel the mechanism and molecular interactions between heme-carrier proteins and components of bacterial heme assimilation systems [2].
  • Using quantitative real-time PCR, we examined the expression of Hcp1 and other intestinal iron-transporting proteins in male C57BL/6 mice with experimentally altered iron homeostasis [3].

References

  1. Identification of an intestinal heme transporter. Shayeghi, M., Latunde-Dada, G.O., Oakhill, J.S., Laftah, A.H., Takeuchi, K., Halliday, N., Khan, Y., Warley, A., McCann, F.E., Hider, R.C., Frazer, D.M., Anderson, G.J., Vulpe, C.D., Simpson, R.J., McKie, A.T. Cell (2005) [Pubmed]
  2. Bacterial heme sources: the role of heme, hemoprotein receptors and hemophores. Wandersman, C., Stojiljkovic, I. Curr. Opin. Microbiol. (2000) [Pubmed]
  3. Effect of lipopolysaccharide and bleeding on the expression of intestinal proteins involved in iron and haem transport. Krijt, J., Vokurka, M., Sefc, L., Duricov??, D., Necas, E. Folia Biol. (Praha) (2006) [Pubmed]
  4. Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Qiu, A., Jansen, M., Sakaris, A., Min, S.H., Chattopadhyay, S., Tsai, E., Sandoval, C., Zhao, R., Akabas, M.H., Goldman, I.D. Cell (2006) [Pubmed]
  5. Recent advances in mammalian haem transport. Latunde-Dada, G.O., Simpson, R.J., McKie, A.T. Trends Biochem. Sci. (2006) [Pubmed]
  6. Heme carrier protein 1 (HCP1) expression and functional analysis in the retina and retinal pigment epithelium. Sharma, S., Dimasi, D., Bröer, S., Kumar, R., Della, N.G. Exp. Cell Res. (2007) [Pubmed]
  7. Haem carrier protein 1 (HCP1): Expression and functional studies in cultured cells. Latunde-Dada, G.O., Takeuchi, K., Simpson, R.J., McKie, A.T. FEBS Lett. (2006) [Pubmed]
  8. A role for the proton-coupled folate transporter (PCFT-SLC46A1) in folate receptor-mediated endocytosis. Zhao, R., Min, S.H., Wang, Y., Campanella, E., Low, P.S., Goldman, I.D. J. Biol. Chem. (2009) [Pubmed]
  9. The functional roles of the His247 and His281 residues in folate and proton translocation mediated by the human proton-coupled folate transporter SLC46A1. Unal, E.S., Zhao, R., Chang, M.H., Fiser, A., Romero, M.F., Goldman, I.D. J. Biol. Chem. (2009) [Pubmed]
 
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