SLC19A1
entrez
6573
canonical
uniprot
P41440
canonical
ensembl
ENSG00000173638
resolver
ensp
ENSP00000308895
resolver
ensp
ENSP00000369347
resolver
ensp
ENSP00000441772
resolver
ensp
ENSP00000498221
resolver
ensp
ENSP00000529529
resolver
ensp
ENSP00000529534
resolver
ensp
ENSP00000529536
resolver
ensp
ENSP00000529540
resolver
ensp
ENSP00000600905
resolver
ensp
ENSP00000600908
resolver
ensp
ENSP00000673051
resolver
ensp
ENSP00000705914
resolver
genesymbol
SLC19A1
resolver
genesymbol_syn
FLOT1
resolver
genesymbol_syn
RFC1
resolver
hgnc
HGNC:10937
resolver
uniprot
B2R7U8
resolver
uniprot
B7Z8C3
resolver
uniprot
E9PFY4
resolver
uniprot
O00553
resolver
uniprot
O60227
resolver
uniprot
Q13026
resolver
uniprot
Q9BTX8
resolver
uniprot_entry
S19A1_HUMAN
resolver
uniprot_sec
B2R7U8
resolver
uniprot_sec
B7Z8C3
resolver
uniprot_sec
E9PFY4
resolver
uniprot_sec
O00553
resolver
uniprot_sec
O60227
resolver
uniprot_sec
Q13026
resolver
uniprot_sec
Q9BTX8
resolver
amino_acid_sequence
MVPSSPAVEKQVPVEPGPDPELRSWRHLVCYLCFYGFMAQIRPGESFITPYLLGPDKNFTREQVTNEITPVLSYSYLAVLVPVFLLTDYLRYTPVLLLQGLSFVSVWLLLLLGHSVAHMQLMELFYSVTMAARIAYSSYIFSLVRPARYQRVAGYSRAAVLLGVFTSSVLGQLLVTVGRVSFSTLNYISLAFLTFSVVLALFLKRPKRSLFFNRDDRGRCETSASELERMNPGPGGKLGHALRVACGDSVLARMLRELGDSLRRPQLRLWSLWWVFNSAGYYLVVYYVHILWNEVDPTTNSARVYNGAADAASTLLGAITSFAAGFVKIRWARWSKLLIAGVTATQAGLVFLLAHTRHPSSIWLCYAAFVLFRGSYQFLVPIATFQIASSLSKELCALVFGVNTFFATIVKTIITFIVSDVRGLGLPVRKQFQLYSVYFLILSIIYFLGAMLDGLRHCQRGHHPRQPPAQGLRSAAEEKAAQALSVQDKGLGGLQPAQSPPLSPEDSLGAVGPASLEQRQSDPYLAQAPAPQAAEFLSPVTTPSPCTLCSAQASGPEAADETCPQLAVHPPGVSKLGLQCLPSDGVQNVNQ
uniprot
proteins
disease_involvement
DISEASE: Megaloblastic anemia, folate-responsive (MEGAF) [MIM:601775]: 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. {ECO:0000269|PubMed:32276275}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Immunodeficiency 114, folate-responsive (IMD114) [MIM:620603]: An autosomal recessive immunologic disorder manifesting in early infancy and characterized by recurrent skin and respiratory infections, mucosal bleeding, oral ulcers, chronic diarrhea, and poor overall growth. Affected individuals have lymphopenia, low serum immunoglobulins, and impaired T cell proliferation. Some patients have global developmental delay. {ECO:0000269|PubMed:36517554, ECO:0000269|PubMed:36745868}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Antiporter that mediates the import of reduced folates or a subset of cyclic dinucleotides, driven by the export of organic anions (PubMed:10787414, PubMed:15337749, PubMed:16115875, PubMed:22554803, PubMed:31126740, PubMed:31511694, PubMed:32276275, PubMed:36071163, PubMed:36265513, PubMed:36575193, PubMed:7826387, PubMed:9041240). 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:31126740, PubMed:31511694, PubMed:36745868). 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:31126740, PubMed:31511694). Has high affinity for N5-methyltetrahydrofolate, the predominant circulating form of folate (PubMed:10787414, PubMed:14609557, PubMed:22554803, PubMed:36071163, PubMed:36265513, PubMed:36575193). Also mediates the import of antifolate drug methotrexate (PubMed:22554803, PubMed:36071163, PubMed:7615551, PubMed:7641195, PubMed:9767079). 5-amino-4-imidazolecarboxamide riboside (AICAR), when phosphorylated to AICAR monophosphate, can serve as an organic anion for antiporter activity (PubMed:22554803). {ECO:0000269|PubMed:10787414, ECO:0000269|PubMed:14609557, ECO:0000269|PubMed:15337749, ECO:0000269|PubMed:16115875, ECO:0000269|PubMed:22554803, ECO:0000269|PubMed:31126740, ECO:0000269|PubMed:31511694, ECO:0000269|PubMed:32276275, ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193, ECO:0000269|PubMed:36745868, ECO:0000269|PubMed:7615551, ECO:0000269|PubMed:7641195, ECO:0000269|PubMed:7826387, ECO:0000269|PubMed:9041240, ECO:0000269|PubMed:9767079}.
uniprot
proteins
mass_dalton
64868
uniprot
proteins
mutagenesis
MUTAGEN 42; /note="R->A: Reduces methotrexate uptake."; /evidence="ECO:0000269|PubMed:36071163"; MUTAGEN 42; /note="R->E: Reduces methotrexate uptake. Reduces methotrexate uptake; when associated with K-45."; /evidence="ECO:0000269|PubMed:36071163"; MUTAGEN 42; /note="R->K: Enhances methotrexate uptake."; /evidence="ECO:0000269|PubMed:36071163"; MUTAGEN 45; /note="E->A: Enhances methotrexate uptake."; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36575193"; MUTAGEN 45; /note="E->K: Reduces methotrexate uptake. Reduces methotrexate uptake; when associated with E-42."; /evidence="ECO:0000269|PubMed:36071163"; MUTAGEN 48; /note="I->A: Reduces methotrexate uptake. Reduces methotrexate uptake; when associated with A-126 and A-286."; /evidence="ECO:0000269|PubMed:36071163"; MUTAGEN 48; /note="I->F: No effect on methotrexate uptake but shifts selectivity towards folinate and pemetrexed."; /evidence="ECO:0000269|PubMed:36071163"; MUTAGEN 49; /note="T->A: Reduces methotrexate uptake. Reduces the expression of IFNB1 and CXCL10 upon cGAMP stimulation."; /evidence="ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193"; MUTAGEN 58; /note="N->Q: Completely abolishes N-glycosylation without affecting subcellular location or folate:anion antiporter activity."; /evidence="ECO:0000269|PubMed:9767079"; MUTAGEN 68; /note="I->A: Reduces methotrexate uptake."; /evidence="ECO:0000269|PubMed:36575193"; MUTAGEN 69; /note="T->A,Y: Reduces methotrexate uptake."; /evidence="ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193"; MUTAGEN 72; /note="L->A,W: Reduces methotrexate uptake."; /evidence="ECO:0000269|PubMed:36575193"; MUTAGEN 76; /note="Y->A: Reduces methotrexate uptake."; /evidence="ECO:0000269|PubMed:36071163"; MUTAGEN 123; /note="E->A,D: Reduces methotrexate uptake."; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193"; MUTAGEN 126; /note="Y->A: Reduces methotrexate uptake. Reduces methotrexate uptake; when associated with A-48 and A-286."; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36575193"; MUTAGEN 130; /note="M->T: Reduces methotrexate uptake."; /evidence="ECO:0000269|PubMed:36575193"; MUTAGEN 133; /note="R->A: Reduces methotrexate uptake. Reduces IRF3 phosphorylation upon cGAMP stimulation."; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193"; MUTAGEN 133; /note="R->E: Reduces methotrexate uptake."; /evidence="ECO:0000269|PubMed:36575193"; MUTAGEN 149; /note="Y->A: Reduces methotrexate uptake. Reduces IRF3 phosphorylation upon cGAMP stimulation."; /evidence="ECO:0000269|PubMed:36265513"; MUTAGEN 150; /note="Q->A: Reduces methotrexate uptake. Reduces IRF3 phosphorylation upon cGAMP stimulation."; /evidence="ECO:0000269|PubMed:36265513"; MUTAGEN 157; /note="R->A: Reduces IRF3 phosphorylation upon cGAMP stimulation. Reduces methotrexate uptake."; /evidence="ECO:0000269|PubMed:36265513"; MUTAGEN 157; /note="R->K: Abolishes methotrexate uptake."; /evidence="ECO:0000269|PubMed:36071163"; MUTAGEN 204..214; /note="Missing: Reduces IRF3 phosphorylation upon cGAMP stimulation."; /evidence="ECO:0000269|PubMed:36265513"; MUTAGEN 281; /note="Y->A: Reduces methotrexate uptake."; /evidence="ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193"; MUTAGEN 285; /note="V->A: Reduces methotrexate uptake."; /evidence="ECO:0000269|PubMed:36575193"; MUTAGEN 286; /note="Y->A: Reduces methotrexate uptake. Reduces methotrexate uptake; when associated with A-48 and A-126."; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36575193"; MUTAGEN 286; /note="Y->N: Reduces methotrexate uptake."; /evidence="ECO:0000269|PubMed:36575193"; MUTAGEN 289; /note="H->A: Reduces methotrexate uptake."; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36575193"; MUTAGEN 289; /note="H->Q: Reduces methotrexate uptake."; /evidence="ECO:0000269|PubMed:36575193"; MUTAGEN 310; /note="D->A: Abolishes methotrexate uptake."; /evidence="ECO:0000269|PubMed:36071163"; MUTAGEN 328; /note="K->A: Reduces IRF3 phosphorylation upon cGAMP stimulation."; /evidence="ECO:0000269|PubMed:36265513"; MUTAGEN 373; /note="R->A: Reduces methotrexate uptake."; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193"; MUTAGEN 376; /note="Y->A: Reduces IRF3 phosphorylation upon cGAMP stimulation."; /evidence="ECO:0000269|PubMed:36265513"; MUTAGEN 377; /note="Q->A: Reduces methotrexate uptake. Reduces IRF3 phosphorylation upon cGAMP stimulation."; /evidence="ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193"; MUTAGEN 377; /note="Q->M: Reduces methotrexate uptake."; /evidence="ECO:0000269|PubMed:36575193"; MUTAGEN 384; /note="T->A: Reduces methotrexate uptake. Reduces IRF3 phosphorylation upon cGAMP stimulation."; /evidence="ECO:0000269|PubMed:36265513"; MUTAGEN 393; /note="K->A: Reduces methotrexate uptake. Reduces IRF3 phosphorylation upon cGAMP stimulation."; /evidence="ECO:0000269|PubMed:36265513"; MUTAGEN 396; /note="C->A: Reduces methotrexate uptake. Reduces IRF3 phosphorylation upon cGAMP stimulation."; /evidence="ECO:0000269|PubMed:36265513"; MUTAGEN 400; /note="F->A: Reduces methotrexate uptake. Reduces IRF3 phosphorylation upon cGAMP stimulation."; /evidence="ECO:0000269|PubMed:36265513"; MUTAGEN 411; /note="K->A: Abolishes methotrexate uptake."; /evidence="ECO:0000269|PubMed:36071163
uniprot
proteins
protein_family
Reduced folate carrier (RFC) transporter (TC 2.A.48) family
uniprot
proteins
pubmed
10347183
uniprot
proteins
pubmed
10787414
uniprot
proteins
pubmed
10830953
uniprot
proteins
pubmed
14609557
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15337749
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16115875
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
22554803
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
31126740
uniprot
proteins
pubmed
31511694
uniprot
proteins
pubmed
32276275
uniprot
proteins
pubmed
36071163
uniprot
proteins
pubmed
36265513
uniprot
proteins
pubmed
36517554
uniprot
proteins
pubmed
36575193
uniprot
proteins
pubmed
36745868
uniprot
proteins
pubmed
7615551
uniprot
proteins
pubmed
7641195
uniprot
proteins
pubmed
7826387
uniprot
proteins
pubmed
7852378
uniprot
proteins
pubmed
9041240
uniprot
proteins
pubmed
9602167
uniprot
proteins
pubmed
9767079
uniprot
proteins
sequence_length
591
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10347183, ECO:0000269|PubMed:10787414, ECO:0000269|PubMed:15337749, ECO:0000269|PubMed:16115875, ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193, ECO:0000269|PubMed:36745868, ECO:0000269|PubMed:9767079}; Multi-pass membrane protein {ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193}. Apical cell membrane {ECO:0000269|PubMed:10787414}; Multi-pass membrane protein {ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193}. Basolateral cell membrane {ECO:0000269|PubMed:10787414}; Multi-pass membrane protein {ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193}.
uniprot
proteins
transmembrane_region
TRANSMEM 30..50; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193, ECO:0007744|PDB:7TX6, ECO:0007744|PDB:7TX7, ECO:0007744|PDB:7XPZ, ECO:0007744|PDB:7XQ0, ECO:0007744|PDB:7XQ1, ECO:0007744|PDB:7XQ2, ECO:0007744|PDB:8DEP, ECO:0007744|PDB:8GOE, ECO:0007744|PDB:8GOF, ECO:0007744|PDB:8HII, ECO:0007744|PDB:8HIJ, ECO:0007744|PDB:8HIK"; TRANSMEM 65..87; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193, ECO:0007744|PDB:7TX6, ECO:0007744|PDB:7TX7, ECO:0007744|PDB:7XPZ, ECO:0007744|PDB:7XQ0, ECO:0007744|PDB:7XQ1, ECO:0007744|PDB:7XQ2, ECO:0007744|PDB:8DEP, ECO:0007744|PDB:8GOE, ECO:0007744|PDB:8GOF, ECO:0007744|PDB:8HII, ECO:0007744|PDB:8HIJ, ECO:0007744|PDB:8HIK"; TRANSMEM 92..112; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193, ECO:0007744|PDB:7TX6, ECO:0007744|PDB:7TX7, ECO:0007744|PDB:7XPZ, ECO:0007744|PDB:7XQ0, ECO:0007744|PDB:7XQ1, ECO:0007744|PDB:7XQ2, ECO:0007744|PDB:8DEP, ECO:0007744|PDB:8GOE, ECO:0007744|PDB:8GOF, ECO:0007744|PDB:8HII, ECO:0007744|PDB:8HIJ, ECO:0007744|PDB:8HIK"; TRANSMEM 117..139; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193, ECO:0007744|PDB:7TX6, ECO:0007744|PDB:7TX7, ECO:0007744|PDB:7XPZ, ECO:0007744|PDB:7XQ0, ECO:0007744|PDB:7XQ1, ECO:0007744|PDB:7XQ2, ECO:0007744|PDB:8DEP, ECO:0007744|PDB:8GOE, ECO:0007744|PDB:8GOF, ECO:0007744|PDB:8HII, ECO:0007744|PDB:8HIJ, ECO:0007744|PDB:8HIK"; TRANSMEM 154..178; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193, ECO:0007744|PDB:7TX6, ECO:0007744|PDB:7TX7, ECO:0007744|PDB:7XPZ, ECO:0007744|PDB:7XQ0, ECO:0007744|PDB:7XQ1, ECO:0007744|PDB:7XQ2, ECO:0007744|PDB:8DEP, ECO:0007744|PDB:8GOE, ECO:0007744|PDB:8GOF, ECO:0007744|PDB:8HII, ECO:0007744|PDB:8HIJ, ECO:0007744|PDB:8HIK"; TRANSMEM 184..202; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193, ECO:0007744|PDB:7TX6, ECO:0007744|PDB:7TX7, ECO:0007744|PDB:7XPZ, ECO:0007744|PDB:7XQ0, ECO:0007744|PDB:7XQ1, ECO:0007744|PDB:7XQ2, ECO:0007744|PDB:8DEP, ECO:0007744|PDB:8GOE, ECO:0007744|PDB:8GOF, ECO:0007744|PDB:8HII, ECO:0007744|PDB:8HIJ, ECO:0007744|PDB:8HIK"; TRANSMEM 267..292; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193, ECO:0007744|PDB:7TX6, ECO:0007744|PDB:7TX7, ECO:0007744|PDB:7XPZ, ECO:0007744|PDB:7XQ0, ECO:0007744|PDB:7XQ1, ECO:0007744|PDB:7XQ2, ECO:0007744|PDB:8DEP, ECO:0007744|PDB:8GOE, ECO:0007744|PDB:8GOF, ECO:0007744|PDB:8HII, ECO:0007744|PDB:8HIJ, ECO:0007744|PDB:8HIK"; TRANSMEM 305..327; /note="Helical; Name=8"; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193, ECO:0007744|PDB:7TX6, ECO:0007744|PDB:7TX7, ECO:0007744|PDB:7XPZ, ECO:0007744|PDB:7XQ0, ECO:0007744|PDB:7XQ1, ECO:0007744|PDB:7XQ2, ECO:0007744|PDB:8DEP, ECO:0007744|PDB:8GOE, ECO:0007744|PDB:8GOF, ECO:0007744|PDB:8HII, ECO:0007744|PDB:8HIJ, ECO:0007744|PDB:8HIK"; TRANSMEM 334..354; /note="Helical; Name=9"; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193, ECO:0007744|PDB:7TX6, ECO:0007744|PDB:7TX7, ECO:0007744|PDB:7XPZ, ECO:0007744|PDB:7XQ0, ECO:0007744|PDB:7XQ1, ECO:0007744|PDB:7XQ2, ECO:0007744|PDB:8DEP, ECO:0007744|PDB:8GOE, ECO:0007744|PDB:8GOF, ECO:0007744|PDB:8HII, ECO:0007744|PDB:8HIJ, ECO:0007744|PDB:8HIK"; TRANSMEM 361..384; /note="Helical; Name=10"; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193, ECO:0007744|PDB:7TX6, ECO:0007744|PDB:7TX7, ECO:0007744|PDB:7XPZ, ECO:0007744|PDB:7XQ0, ECO:0007744|PDB:7XQ1, ECO:0007744|PDB:7XQ2, ECO:0007744|PDB:8DEP, ECO:0007744|PDB:8GOE, ECO:0007744|PDB:8GOF, ECO:0007744|PDB:8HII, ECO:0007744|PDB:8HIJ, ECO:0007744|PDB:8HIK"; TRANSMEM 399..422; /note="Helical; Name=11"; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193, ECO:0007744|PDB:7TX6, ECO:0007744|PDB:7TX7, ECO:0007744|PDB:7XPZ, ECO:0007744|PDB:7XQ0, ECO:0007744|PDB:7XQ1, ECO:0007744|PDB:7XQ2, ECO:0007744|PDB:8DEP, ECO:0007744|PDB:8GOE, ECO:0007744|PDB:8GOF, ECO:0007744|PDB:8HII, ECO:0007744|PDB:8HIJ, ECO:0007744|PDB:8HIK"; TRANSMEM 431..455; /note="Helical; Name=12"; /evidence="ECO:0000269|PubMed:36071163, ECO:0000269|PubMed:36265513, ECO:0000269|PubMed:36575193, ECO:0007744|PDB:7TX6, ECO:0007744|PDB:7TX7, ECO:0007744|PDB:7XPZ, ECO:0007744|PDB:7XQ0, ECO:0007744|PDB:7XQ1, ECO:0007744|PDB:7XQ2, ECO:0007744|PDB:8DEP, ECO:0007744|PDB:8GOE, ECO:0007744|PDB:8GOF, ECO:0007744|PDB:8HII, ECO:0007744|PDB:8HIJ, ECO:0007744|PDB:8HIK
uniprot
proteins