NLS1B_DANRE
ID NLS1B_DANRE Reviewed; 523 AA.
AC Q6DEJ6; Q1LYS0;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Sodium-dependent lysophosphatidylcholine symporter 1-B;
DE Short=NLS1-B;
DE Short=Sodium-dependent LPC symporter 1-B;
DE AltName: Full=Major facilitator superfamily domain-containing protein 2A-B;
GN Name=mfsd2ab; Synonyms=nls1b;
GN ORFNames=si:ch211-194e15.3, si:ch211-210b19.5;
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 GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
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. {ECO:0000269|PubMed:26005868}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC {ECO:0000305}.
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DR EMBL; BX000986; CAK04464.1; -; Genomic_DNA.
DR EMBL; BX547927; CAK04287.1; -; Genomic_DNA.
DR EMBL; BC077117; AAH77117.1; -; mRNA.
DR RefSeq; NP_001003570.1; NM_001003570.1.
DR AlphaFoldDB; Q6DEJ6; -.
DR SMR; Q6DEJ6; -.
DR STRING; 7955.ENSDARP00000047460; -.
DR PaxDb; Q6DEJ6; -.
DR Ensembl; ENSDART00000047461; ENSDARP00000047460; ENSDARG00000035909.
DR GeneID; 445176; -.
DR KEGG; dre:445176; -.
DR CTD; 445176; -.
DR ZFIN; ZDB-GENE-040801-89; mfsd2ab.
DR eggNOG; KOG4830; Eukaryota.
DR GeneTree; ENSGT00390000005318; -.
DR HOGENOM; CLU_027408_6_1_1; -.
DR InParanoid; Q6DEJ6; -.
DR OMA; GLYTAWM; -.
DR OrthoDB; 827101at2759; -.
DR PhylomeDB; Q6DEJ6; -.
DR TreeFam; TF331194; -.
DR Reactome; R-DRE-1483191; Synthesis of PC.
DR PRO; PR:Q6DEJ6; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 19.
DR Bgee; ENSDARG00000035909; Expressed in liver and 22 other tissues.
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: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..523
FT /note="Sodium-dependent lysophosphatidylcholine symporter
FT 1-B"
FT /id="PRO_0000273389"
FT TOPO_DOM 1..34
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TRANSMEM 35..64
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TOPO_DOM 65..75
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TRANSMEM 76..96
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TOPO_DOM 97..108
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TRANSMEM 109..128
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TOPO_DOM 129..138
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TRANSMEM 139..163
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TOPO_DOM 164..170
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TRANSMEM 171..202
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TOPO_DOM 203..226
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TRANSMEM 227..260
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TOPO_DOM 261..290
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TRANSMEM 291..317
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TOPO_DOM 318..328
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TRANSMEM 329..347
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TOPO_DOM 348..351
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TRANSMEM 352..373
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TOPO_DOM 374..376
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TRANSMEM 377..413
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TOPO_DOM 414..423
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TRANSMEM 424..450
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TOPO_DOM 451..462
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TRANSMEM 463..486
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT TOPO_DOM 487..523
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
FT REGION 504..523
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 214
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 225
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 206..457
FT /evidence="ECO:0000250|UniProtKB:Q9DA75"
SQ SEQUENCE 523 AA; 57879 MW; 54EFF7F0DAFB1FC4 CRC64;
MAKGEGAEQY TNTSLLQKPS PDEVKLAKHE TKSRLSVCSK LCYAIGGAPY QITGCAIGFF
LQIYLLDVAL LDPFYASIIL FVGRAWDAVT DPTVGFLVSR TPWTRFGRMM PWIVLSTPFA
VLCYFLIWYV PSVDQGKVVW YLIFYCCFQT LQTCFHVPYS ALTMFISTEQ KERDSATAYR
MTVEVLGTLI GTAIQGQIVG MANAPCISTE IDLNSTGLEV APDVNITDPH VSLQDLRNAY
MIASGVICAI YVVCAVVLFL GVKEQKDTCR VRTEPMSFFQ GICMVMGHGP YAKLVMGFLF
TSLAFMLLEG NFALFCIYNL GFRNDFQNVL LVIMLSATLA IPFWQWFLTK FGKKTAVYIG
TTSVVPFLIS VVLVPSSLAV TYIASFAAGV SVAAAFLLPW SMLPDVVDDF KVQNPESQGH
EAIFYSFYVF FTKFASGVSL GVSTLSLDFA GYVTRGCTQP GEVKLTLKIL VSAAPIVLII
IGLLIFISYP INEEKRQGNR KLLNEQRENE MDSETDSTEL NVV
