Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by ARBA machine learning models
Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome.
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Zebrafish mfsd2aa transports LPC ligands at a level comparable to human MFSD2A in a cell uptake assay.
"both mfsd2aa and mfsd2ab exhibit similar transport activity of LPC ligands, and to a similar level as human MFSD2A"
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mfsd2aa morphants leak dextran from cranial vessels into brain parenchyma.
"dextran extravasated extensively from vessels as evidenced by fluorescence within the brain parenchyma of mfsd2aa morphant brains"
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Wild-type zebrafish or human MFSD2A mRNA rescues the leak; patient missense variants do not.
"co-injection with either zebrafish and human mRNA largely rescued dextran extravasation"
Suppression of transcytosis regulates zebrafish blood-brain barrier function.
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mfsd2aa mutants show at least twofold increased parenchymal tracer leakage at 5 dpf.
"Mfsd2aa mutants displayed at least a two-fold increase in midbrain and hindbrain parenchymal tracer leakage"
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mfsd2aa mutants have increased endothelial vesicle density with intact tight junctions, i.e. increased transcytosis.
"mfsd2aa mutants have increased vesicular densities"
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mfsd2ab mutants have wild-type barrier permeability, so the requirement is paralog-specific.
"mfsd2ab mutants displayed similarly low levels of parenchymal tracer intensity to wild-type controls at 5 dpf"
UniProtKB entry Q5U3U7 for Danio rerio mfsd2aa
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UniProt describes Mfsd2aa as a sodium-dependent lysophosphatidylcholine symporter of blood-brain barrier endothelium.
"Sodium-dependent lysophosphatidylcholine (LPC) symporter"
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The protein transports LPC-esterified but not free fatty acids.
"Does not transport docosahexaenoic acid in unesterified fatty acid."
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It is a cell-membrane multi-pass protein of barrier microvessel endothelium.
"Specifically expressed in endothelium of the blood-brain barrier of micro-vessels and transports LPC into the brain."
Falcon deep research report for Danio rerio mfsd2aa (UniProt Q5U3U7)
Structure and mechanism of blood-brain-barrier lipid transporter MFSD2A.
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MFSD2A is a sodium-dependent LPC symporter responsible for brain DHA uptake; the structure identifies a conserved sodium-binding site.
"MFSD2A is a sodium-dependent lysophosphatidylcholine symporter that is responsible for the uptake of docosahexaenoic acid into the brain"
Mfsd2a utilizes a flippase mechanism to mediate omega-3 fatty acid lysolipid transport.
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Reconstituted Mfsd2a flips lysophosphatidylserine from the outer to the inner liposome leaflet in a sodium-dependent manner.
"we demonstrate that Mfsd2a flips LPS from the outer to the inner leaflet of a membrane bilayer in a sodium-dependent manner"