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 18-JAN-2017, entry version 69. 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 Cyprinidae; 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., RA Ben-Omran T., Akizu N., Rosti R.O., Rosti B., Scott E., Schroth J., RA Copeland B., Vaux K.K., Cazenave-Gassiot A., Quek D.Q., Wong B.H., RA Tan B.C., Wenk M.R., Gunel M., Gabriel S., Chi N.C., Silver D.L., RA 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) CC symporter, which plays an essential role for blood-brain barrier CC formation and function. Specifically expressed in endothelium of CC the blood-brain barrier of micro-vessels and transports LPC into CC the brain. Transport of LPC is essential because it constitutes CC the major mechanism by which docosahexaenoic acid (DHA), an omega- CC 3 fatty acid that is essential for normal brain growth and CC cognitive function, enters the brain. Transports LPC carrying CC long-chain fatty acids such LPC oleate and LPC palmitate with a CC minimum acyl chain length of 14 carbons. Does not transport CC docosahexaenoic acid in unesterified fatty acid. Specifically CC required for blood-brain barrier formation and function, probably CC by mediating lipid transport (By similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cell membrane CC {ECO:0000250|UniProtKB:Q9DA75}; Multi-pass membrane protein CC {ECO:0000255}. Endoplasmic reticulum membrane CC {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 CC early postnatal lethality and microcephaly. CC {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 UniGene; Dr.86869; -. DR ProteinModelPortal; Q5U3U7; -. DR STRING; 7955.ENSDARP00000046114; -. DR PaxDb; Q5U3U7; -. DR GeneID; 492810; -. DR KEGG; dre:492810; -. DR CTD; 492810; -. DR ZFIN; ZDB-GENE-041114-166; mfsd2aa. DR eggNOG; KOG4830; Eukaryota. DR eggNOG; COG2211; LUCA. DR HOGENOM; HOG000294186; -. DR HOVERGEN; HBG080097; -. DR InParanoid; Q5U3U7; -. DR PhylomeDB; Q5U3U7; -. DR PRO; PR:Q5U3U7; -. DR Proteomes; UP000000437; Unplaced. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB. DR GO; GO:0005548; F:phospholipid transporter activity; ISS:UniProtKB. DR GO; GO:0015293; F:symporter activity; ISS:UniProtKB. 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:0051977; P:lysophospholipid transport; IDA:ZFIN. DR GO; GO:0035633; P:maintenance of permeability of blood-brain barrier; IMP:ZFIN. DR GO; GO:0045056; P:transcytosis; ISS:UniProtKB. DR InterPro; IPR020846; MFS_dom. DR SUPFAM; SSF103473; SSF103473; 2. PE 2: Evidence at transcript level; KW Cell membrane; Complete proteome; Endoplasmic reticulum; Glycoprotein; KW Lipid transport; Membrane; Reference proteome; Symport; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1 532 Sodium-dependent lysophosphatidylcholine FT symporter 1-A. FT /FTId=PRO_0000273390. FT TOPO_DOM 1 46 Extracellular. {ECO:0000255}. FT TRANSMEM 47 67 Helical. {ECO:0000255}. FT TOPO_DOM 68 68 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 69 89 Helical. {ECO:0000255}. FT TOPO_DOM 90 118 Extracellular. {ECO:0000255}. FT TRANSMEM 119 139 Helical. {ECO:0000255}. FT TOPO_DOM 140 143 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 144 164 Helical. {ECO:0000255}. FT TOPO_DOM 165 247 Extracellular. {ECO:0000255}. FT TRANSMEM 248 268 Helical. {ECO:0000255}. FT TOPO_DOM 269 302 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 303 323 Helical. {ECO:0000255}. FT TOPO_DOM 324 335 Extracellular. {ECO:0000255}. FT TRANSMEM 336 356 Helical. {ECO:0000255}. FT TOPO_DOM 357 361 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 362 382 Helical. {ECO:0000255}. FT TOPO_DOM 383 384 Extracellular. {ECO:0000255}. FT TRANSMEM 385 405 Helical. {ECO:0000255}. FT TOPO_DOM 406 428 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 429 449 Helical. {ECO:0000255}. FT TOPO_DOM 450 475 Extracellular. {ECO:0000255}. FT TRANSMEM 476 496 Helical. {ECO:0000255}. FT TOPO_DOM 497 532 Cytoplasmic. {ECO:0000255}. FT CARBOHYD 214 214 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 220 220 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 229 229 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 471 471 N-linked (GlcNAc...). {ECO:0000255}. 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 //