NLS1A_DANRE
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 03-AUG-2022, entry version 88.
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 PaxDb; Q5U3U7; -.
DR GeneID; 492810; -.
DR KEGG; dre:492810; -.
DR CTD; 492810; -.
DR ZFIN; ZDB-GENE-041114-166; mfsd2aa.
DR eggNOG; KOG4830; Eukaryota.
DR InParanoid; Q5U3U7; -.
DR OrthoDB; 827101at2759; -.
DR PhylomeDB; Q5U3U7; -.
DR PRO; PR:Q5U3U7; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; 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: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:0051977; P:lysophospholipid transport; IDA:ZFIN.
DR GO; GO:0035633; P:maintenance of blood-brain barrier; IMP:ZFIN.
DR GO; GO:0071702; P:organic substance transport; IBA:GO_Central.
DR GO; GO:0045056; P:transcytosis; ISS:UniProtKB.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR039672; MFS_2.
DR InterPro; IPR036259; MFS_trans_sf.
DR PANTHER; PTHR11328; PTHR11328; 1.
DR SUPFAM; SSF103473; SSF103473; 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
