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UniProt functional annotation for P41440 | ||
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| UniProt code: P41440. |
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| Organism: | |
Homo sapiens (Human). |
| Taxonomy: | |
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. |
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| Function: | |
Transporter that mediates the import of reduced folates and a subset of cyclic dinucleotides (PubMed:7826387, PubMed:9041240, PubMed:10787414, PubMed:15337749, PubMed:16115875, PubMed:31126740, PubMed:31511694). 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). 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 (PubMed:31126740, PubMed:31511694). Mechanistically, acts as an antiporter, which export of intracellular organic anions to facilitate uptake of its substrates (PubMed:22554803, PubMed:31126740, PubMed:31511694). 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:7615551, ECO:0000269|PubMed:7641195, ECO:0000269|PubMed:7826387, ECO:0000269|PubMed:9041240, ECO:0000269|PubMed:9767079}. |
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| Catalytic activity: | |
Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate(out) + 5-amino-1-(5- phospho-beta-D-ribosyl)imidazole-4-carboxamide(in) = (6S)-5-methyl- 5,6,7,8-tetrahydrofolate(in) + 5-amino-1-(5-phospho-beta-D- ribosyl)imidazole-4-carboxamide(out); Xref=Rhea:RHEA:60460, ChEBI:CHEBI:18608, ChEBI:CHEBI:58475; Evidence={ECO:0000269|PubMed:14609557, ECO:0000269|PubMed:22554803}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60461; Evidence={ECO:0000269|PubMed:14609557, ECO:0000269|PubMed:22554803}; |
| Catalytic activity: | |
Reaction=2',3'-cGAMP(out) + 5-amino-1-(5-phospho-beta-D- ribosyl)imidazole-4-carboxamide(in) = 2',3'-cGAMP(in) + 5-amino-1-(5- phospho-beta-D-ribosyl)imidazole-4-carboxamide(out); Xref=Rhea:RHEA:60464, ChEBI:CHEBI:58475, ChEBI:CHEBI:143093; Evidence={ECO:0000269|PubMed:31126740, ECO:0000305|PubMed:31511694}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60465; Evidence={ECO:0000269|PubMed:31126740, ECO:0000305|PubMed:31511694}; |
| Catalytic activity: | |
Reaction=3',3'-cGAMP(out) + 5-amino-1-(5-phospho-beta-D- ribosyl)imidazole-4-carboxamide(in) = 3',3'-cGAMP(in) + 5-amino-1-(5- phospho-beta-D-ribosyl)imidazole-4-carboxamide(out); Xref=Rhea:RHEA:60468, ChEBI:CHEBI:58475, ChEBI:CHEBI:71501; Evidence={ECO:0000269|PubMed:31126740}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60469; Evidence={ECO:0000269|PubMed:31126740}; |
| Subcellular location: | |
Cell membrane {ECO:0000269|PubMed:10347183, ECO:0000269|PubMed:10787414, ECO:0000269|PubMed:15337749, ECO:0000269|PubMed:16115875, ECO:0000269|PubMed:9767079}; Multi-pass membrane protein {ECO:0000255}. Apical cell membrane {ECO:0000269|PubMed:10787414}; Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane {ECO:0000269|PubMed:10787414}; Multi-pass membrane protein {ECO:0000255}. |
| Tissue specificity: | |
Placenta, liver, and to a much smaller extent, in lung. {ECO:0000269|PubMed:7826387}. |
| Similarity: | |
Belongs to the reduced folate carrier (RFC) transporter (TC 2.A.48) family. {ECO:0000305}. |
| Sequence caution: | |
Sequence=CAB90483.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; |
Annotations taken from UniProtKB at the EBI.