SLC19A1

The membrane protein encoded by this gene is a transporter of folate and is involved in the regulation of intracellular concentrations of folate. Three transcript variants encoding different isoforms have been found for this gene.

Full Name

solute carrier family 19 (folate transporter), member 1

Function

Antiporter that mediates the import of reduced folates or a subset of cyclic dinucleotides, driven by the export of organic anions (PubMed:7826387, PubMed:9041240, PubMed:10787414, PubMed:15337749, PubMed:16115875, PubMed:22554803, PubMed:31511694, PubMed:31126740, PubMed:32276275).
Mechanistically, acts as a secondary active transporter, which exports intracellular organic anions down their concentration gradients to facilitate the uptake of its substrates (PubMed:22554803, PubMed:31511694, PubMed:31126740).
Has high affinity for N5-methyltetrahydrofolate, the predominant circulating form of folate (PubMed:10787414, PubMed:14609557, PubMed:22554803).
Also able to mediate the import of antifolate drug methotrexate (PubMed:7615551, PubMed:7641195, PubMed:9767079, PubMed:22554803).
Also acts as an importer of immunoreactive cyclic dinucleotides, such as cyclic GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol, and its linkage isomer 3'-3'-cGAMP, thus playing a role in triggering larger immune responses (PubMed:31511694, PubMed:31126740).
5-amino-4-imidazolecarboxamide riboside (AICAR), when phosphorylated to AICAR monophosphate, can serve as an organic anion for antiporter activity (PubMed:22554803).

Biological Process

Biological Process cyclic-GMP-AMP transmembrane import across plasma membraneManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process female pregnancyIEA:Ensembl
Biological Process folate import across plasma membraneManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process folate transmembrane transportManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process folic acid metabolic processTAS:Reactome
Biological Process folic acid transportManual Assertion Based On ExperimentIMP:ARUK-UCL
Biological Process methotrexate transportManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process organic anion transportISS:ARUK-UCL
Biological Process transmembrane transportManual Assertion Based On ExperimentIBA:GO_Central
Biological Process transport across blood-brain barrierManual Assertion Based On ExperimentTAS:ARUK-UCL
Biological Process xenobiotic transmembrane transportISS:ARUK-UCL

Cellular Location

Cell membrane
Apical cell membrane
Basolateral cell membrane

Involvement in disease

Megaloblastic anemia, folate-responsive (MEGAF):
An autosomal recessive metabolic disorder characterized by megaloblastic anemia resulting from decreased folate transport into erythrocytes. Disease manifestations include hemolytic anemia, hyperhomocysteinemia, and low vitamin B12. Serum folate levels are normal, but erythrocyte folate levels are decreased. Treatment with oral folate corrects the anemia and normalizes homocysteine.

Topology

Cytoplasmic: 1-23
Helical: 24-44
Extracellular: 45-70
Helical: 71-89
Cytoplasmic: 90-95
Helical: 96-116
Extracellular: 117-123
Helical: 124-144
Cytoplasmic: 145-159
Helical: 160-177
Extracellular: 178-186
Helical: 187-203
Cytoplasmic: 204-259
Helical: 260-287
Extracellular: 288-309
Helical: 310-327
Cytoplasmic: 328-333
Helical: 334-354
Extracellular: 355-360
Helical: 361-378
Cytoplasmic: 379-394
Helical: 395-419
Extracellular: 420-433
Helical: 434-454
Cytoplasmic: 455-591