ID NLS1A_DANRE Reviewed; 532 AA. AC Q5U3U7; DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot. DT 07-DEC-2004, sequence version 1. DT 29-MAY-2024, entry version 94. DE RecName: Full=Sodium-dependent lysophosphatidylcholine symporter 1-A; DE Short=NLS1-A; DE Short=Sodium-dependent LPC symporter 1-A; DE AltName: Full=Major facilitator superfamily domain-containing protein 2A-A; GN Name=mfsd2aa; Synonyms=mfsd2a, nls1a; ORFNames=zgc:101615; OS Danio rerio (Zebrafish) (Brachydanio rerio). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes; OC Danionidae; Danioninae; Danio. OX NCBI_TaxID=7955; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Embryo; RG NIH - Zebrafish Gene Collection (ZGC) project; RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases. RN [2] RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. RX PubMed=26005868; DOI=10.1038/ng.3311; RA Guemez-Gamboa A., Nguyen L.N., Yang H., Zaki M.S., Kara M., Ben-Omran T., RA Akizu N., Rosti R.O., Rosti B., Scott E., Schroth J., Copeland B., RA Vaux K.K., Cazenave-Gassiot A., Quek D.Q., Wong B.H., Tan B.C., Wenk M.R., RA Gunel M., Gabriel S., Chi N.C., Silver D.L., Gleeson J.G.; RT "Inactivating mutations in MFSD2A, required for omega-3 fatty acid RT transport in brain, cause a lethal microcephaly syndrome."; RL Nat. Genet. 47:809-813(2015). CC -!- FUNCTION: Sodium-dependent lysophosphatidylcholine (LPC) symporter, CC which plays an essential role for blood-brain barrier formation and CC function. Specifically expressed in endothelium of the blood-brain CC barrier of micro-vessels and transports LPC into the brain. Transport CC of LPC is essential because it constitutes the major mechanism by which CC docosahexaenoic acid (DHA), an omega-3 fatty acid that is essential for CC normal brain growth and cognitive function, enters the brain. CC Transports LPC carrying long-chain fatty acids such LPC oleate and LPC CC palmitate with a minimum acyl chain length of 14 carbons. Does not CC transport docosahexaenoic acid in unesterified fatty acid. CC {ECO:0000250|UniProtKB:Q9DA75}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1-acyl-sn-glycero-3-phosphocholine(in) + Na(+)(in) = a 1- CC acyl-sn-glycero-3-phosphocholine(out) + Na(+)(out); CC Xref=Rhea:RHEA:44376, ChEBI:CHEBI:29101, ChEBI:CHEBI:58168; CC Evidence={ECO:0000250|UniProtKB:Q9DA75}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3- CC phosphocholine(in) + Na(+)(in) = 1-(4Z,7Z,10Z,13Z,16Z,19Z- CC docosahexaenoyl)-sn-glycero-3-phosphocholine(out) + Na(+)(out); CC Xref=Rhea:RHEA:43860, ChEBI:CHEBI:29101, ChEBI:CHEBI:73873; CC Evidence={ECO:0000250|UniProtKB:Q9DA75}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine(in) + CC Na(+)(in) = 1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine(out) + CC Na(+)(out); Xref=Rhea:RHEA:43856, ChEBI:CHEBI:28610, CC ChEBI:CHEBI:29101; Evidence={ECO:0000250|UniProtKB:Q9DA75}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine(in) + Na(+)(in) = CC 1-hexadecanoyl-sn-glycero-3-phosphocholine(out) + Na(+)(out); CC Xref=Rhea:RHEA:43864, ChEBI:CHEBI:29101, ChEBI:CHEBI:72998; CC Evidence={ECO:0000250|UniProtKB:Q9DA75}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1-acyl-sn-glycero-3-phosphoethanolamine(in) + Na(+)(in) = a CC 1-acyl-sn-glycero-3-phosphoethanolamine(out) + Na(+)(out); CC Xref=Rhea:RHEA:43868, ChEBI:CHEBI:29101, ChEBI:CHEBI:64381; CC Evidence={ECO:0000250|UniProtKB:Q9DA75}; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9DA75}; CC Multi-pass membrane protein {ECO:0000255}. Endoplasmic reticulum CC membrane {ECO:0000250|UniProtKB:Q9DA75}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- TISSUE SPECIFICITY: Expressed in the developing nervous system. CC {ECO:0000269|PubMed:26005868}. CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the gene results in early CC postnatal lethality and microcephaly. {ECO:0000269|PubMed:26005868}. CC -!- SIMILARITY: Belongs to the major facilitator superfamily. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BC085388; AAH85388.1; -; mRNA. DR RefSeq; NP_001007452.1; NM_001007451.1. DR AlphaFoldDB; Q5U3U7; -. DR SMR; Q5U3U7; -. DR STRING; 7955.ENSDARP00000046114; -. DR GlyCosmos; Q5U3U7; 3 sites, No reported glycans. DR PaxDb; 7955-ENSDARP00000046114; -. DR GeneID; 492810; -. DR KEGG; dre:492810; -. DR AGR; ZFIN:ZDB-GENE-041114-166; -. DR CTD; 492810; -. DR ZFIN; ZDB-GENE-041114-166; mfsd2aa. DR eggNOG; KOG4830; Eukaryota. DR InParanoid; Q5U3U7; -. DR OrthoDB; 6761at2759; -. DR PhylomeDB; Q5U3U7; -. DR PRO; PR:Q5U3U7; -. DR Proteomes; UP000000437; Chromosome 13. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0015245; F:fatty acid transmembrane transporter activity; IBA:GO_Central. DR GO; GO:0051978; F:lysophospholipid:sodium symporter activity; ISS:UniProtKB. DR GO; GO:0015293; F:symporter activity; ISS:UniProtKB. DR GO; GO:0008643; P:carbohydrate transport; IEA:InterPro. DR GO; GO:0060856; P:establishment of blood-brain barrier; ISS:UniProtKB. DR GO; GO:0015908; P:fatty acid transport; ISS:UniProtKB. DR GO; GO:1990379; P:lipid transport across blood-brain barrier; ISS:UniProtKB. DR GO; GO:0140329; P:lysophospholipid translocation; IBA:GO_Central. DR GO; GO:0051977; P:lysophospholipid transport; IDA:ZFIN. DR GO; GO:0035633; P:maintenance of blood-brain barrier; IMP:ZFIN. DR GO; GO:0045056; P:transcytosis; ISS:UniProtKB. DR CDD; cd17451; MFS_NLS1_MFSD2A; 1. DR Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 1. DR InterPro; IPR039672; MFS_2. DR InterPro; IPR036259; MFS_trans_sf. DR PANTHER; PTHR11328; MAJOR FACILITATOR SUPERFAMILY DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR11328:SF29; SODIUM-DEPENDENT LYSOPHOSPHATIDYLCHOLINE SYMPORTER 1; 1. DR Pfam; PF13347; MFS_2; 1. DR SUPFAM; SSF103473; MFS general substrate transporter; 1. PE 2: Evidence at transcript level; KW Cell membrane; Disulfide bond; Endoplasmic reticulum; Glycoprotein; KW Lipid transport; Membrane; Reference proteome; Symport; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..532 FT /note="Sodium-dependent lysophosphatidylcholine symporter FT 1-A" FT /id="PRO_0000273390" FT TOPO_DOM 1..40 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 41..70 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 71..81 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 82..102 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 103..114 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 115..134 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 135..144 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 145..169 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 170..176 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 177..208 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 209..232 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 233..266 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 267..297 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 298..324 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 325..335 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 336..354 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 355..358 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 359..380 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 381..383 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 384..420 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 421..430 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 431..457 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 458..469 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 470..493 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 494..532 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT CARBOHYD 214 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 220 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 229 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 212..464 FT /evidence="ECO:0000250|UniProtKB:Q9DA75" SQ SEQUENCE 532 AA; 59266 MW; 387709380163A7F2 CRC64; MARGEGAEQF SSGLLPTAKS VTQNEIKMVK LPKQQERKRA LTVWSKVCFA IGGAPYQITG TALGFFLQIF LLDVAQLNPL NASVILFVGR AWDAVTDPTV GFLVSRTPWT RHGRMMPWIL VSTIPAVLCY FLIWVVPPIE QGKMMWYLLF YCLFQTLQTC FHVPYSALTM FISTEQRERD SATAYRMTVE VFGTVVGTAI QGQIVGMANT PCKNNTSPNN SSNDLIQSNN SHIPLKSNIF DERCAYMIAS AVISLIYVVC AAVLFFGVRE QDVQGELKAQ KRVSFQKGLR LVMGHGPYVK LVLAFLFTSL AFMLLEGNFA VFIKYTLGFR EDFQNILLVI MVSATVSIPM WQWFLCRFGK KTAVYIGITW AVPFMILVVS VNSSLIVSYI VSIAAGVSVG AAFLLPWSML PDVVDDFKLQ NPTSQGHEAI FYSFYVFFTK FASGVSLGVS TLALSFAGYE TGVCVQSDSV NLTLKLLVSA APVSLIALGL LIFMTYPIDE ERREYNNKQL QLLLRNEEEE DEMEVLKPDI TA //