Folate transporter 1

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Folate transporter 1
Mass / length primary structure 591 amino acids
Secondary to quaternary structure multipass (12 TMS) membrane protein
Identifier
Gene name (s) SLC19A1
External IDs
Transporter classification
TCDB 2.A.48.1.1
designation Reduced folate carrier (RFC)
Occurrence
Homology family RFC
Parent taxon Euteleostomi

The Folattransporter 1 (also: Reduced Folate Carrier ., Abbreviation RFC ) is the protein that the inward and outward reduced folic acid - derivatives in and out of vertebrate facilitates cells. So it is a transport protein . In humans, RFC occurs in all tissue types, but especially in the placenta and liver .

Besides the proton-coupled folate transporter (which only transports folic acid), RFC is the main transport protein for folic acid derivatives. In addition, RFC is the main carrier for folic acid antagonists such as methotrexate . Variants of the protein by mutations of the SLC19A1 - gene can lead to antifolate resistance or metabolic disorders. How RFC works has been well studied, although the structure is not yet fully understood.

The catalyzed membrane transport :

Folate derivative (outside) + anion (inside)     Folate derivative (inside) + anion (outside)

So it is an antiport . It is known that thiamine pyrophosphate (TPP) can act as an anion.

If there is a lack of folate, the production of RFC is initially increased, but if there is a severe deficiency, it is throttled again to prevent it from flowing out of the cell. Chronic alcoholism leads to a reduced expression of RFC in kidney cells and thus to a reduced reuptake of excreted folic acid, which explains the reduced folate plasma content in these patients.

Individual evidence

  1. UniProt P41440
  2. BioGPS entry
  3. Matherly LH, Hou Z: Structure and function of the reduced folate carrier a paradigm of a major facilitator superfamily mammalian nutrient transporter . In: Vitam. Horm. . 79, 2008, pp. 145-84. doi : 10.1016 / S0083-6729 (08) 00405-6 . PMID 18804694 .
  4. TCDB 2.A.48
  5. Zhao R, Gao F, Wang Y, Diaz GA, Gelb BD, Goldman ID: Impact of the reduced folate carrier on the accumulation of active thiamin metabolites in murine leukemia cells . In: J. Biol. Chem. . 276, No. 2, January 2001, pp. 1114-8. doi : 10.1074 / jbc.M007919200 . PMID 11038362 .
  6. Ifergan I, Jansen G, Assaraf YG: The reduced folate carrier (RFC) is cytotoxic to cells under conditions of severe folate deprivation. RFC as a double edged sword in folate homeostasis . In: J. Biol. Chem. . 283, No. 30, July 2008, pp. 20687-95. doi : 10.1074 / jbc.M802812200 . PMID 18499665 .
  7. Hamid A, Kaur J: Decreased expression of transporters reduces folate uptake across renal absorptive surfaces in experimental alcoholism . In: J. Membr. Biol . 220, No. 1-3, December 2007, pp. 69-77. doi : 10.1007 / s00232-007-9075-3 . PMID 18008023 .

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