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Protein

Sodium-dependent lysophosphatidylcholine symporter 1

Gene

Mfsd2a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Sodium-dependent lysophosphatidylcholine (LPC) symporter, which plays an essential role for blood-brain barrier formation and function (PubMed:24828044, PubMed:24828040). Specifically expressed in endothelium of the blood-brain barrier of micro-vessels and transports LPC into the brain. Transport of LPC is essential because it constitutes the major mechanism by which docosahexaenoic acid (DHA), an omega-3 fatty acid that is essential for normal brain growth and cognitive function, enters the brain. Transports LPC carrying long-chain fatty acids such LPC oleate and LPC palmitate with a minimum acyl chain length of 14 carbons. Does not transport docosahexaenoic acid in unesterified fatty acid (PubMed:24828044). Specifically required for blood-brain barrier formation and function, probably by mediating lipid transport. Not required for central nervous system vascular morphogenesis (PubMed:24828040). Acts as a transporter for tunicamycin, an inhibitor of asparagine-linked glycosylation.4 Publications

GO - Molecular functioni

  • fatty acid transmembrane transporter activity Source: BHF-UCL
  • lysophospholipid transporter activity Source: BHF-UCL
  • phospholipid transporter activity Source: UniProtKB
  • symporter activity Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processLipid transport, Symport, Transport

Enzyme and pathway databases

ReactomeiR-MMU-1483191 Synthesis of PC

Chemistry databases

SwissLipidsiSLP:000000999

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium-dependent lysophosphatidylcholine symporter 1
Short name:
NLS1
Short name:
Sodium-dependent LPC symporter 1
Alternative name(s):
Major facilitator superfamily domain-containing protein 2A
Gene namesi
Name:Mfsd2a
Synonyms:Mfsd2, Nls1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1923824 Mfsd2a

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 45ExtracellularSequence analysisAdd BLAST45
Transmembranei46 – 66HelicalSequence analysisAdd BLAST21
Topological domaini67CytoplasmicSequence analysis1
Transmembranei68 – 88HelicalSequence analysisAdd BLAST21
Topological domaini89 – 114ExtracellularSequence analysisAdd BLAST26
Transmembranei115 – 135HelicalSequence analysisAdd BLAST21
Topological domaini136 – 146CytoplasmicSequence analysisAdd BLAST11
Transmembranei147 – 167HelicalSequence analysisAdd BLAST21
Topological domaini168 – 247ExtracellularSequence analysisAdd BLAST80
Transmembranei248 – 268HelicalSequence analysisAdd BLAST21
Topological domaini269 – 301CytoplasmicSequence analysisAdd BLAST33
Transmembranei302 – 322HelicalSequence analysisAdd BLAST21
Topological domaini323 – 335ExtracellularSequence analysisAdd BLAST13
Transmembranei336 – 356HelicalSequence analysisAdd BLAST21
Topological domaini357 – 361CytoplasmicSequence analysis5
Transmembranei362 – 382HelicalSequence analysisAdd BLAST21
Topological domaini383 – 384ExtracellularSequence analysis2
Transmembranei385 – 405HelicalSequence analysisAdd BLAST21
Topological domaini406 – 428CytoplasmicSequence analysisAdd BLAST23
Transmembranei429 – 449HelicalSequence analysisAdd BLAST21
Topological domaini450 – 475ExtracellularSequence analysisAdd BLAST26
Transmembranei476 – 496HelicalSequence analysisAdd BLAST21
Topological domaini497 – 534CytoplasmicSequence analysisAdd BLAST38

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice were born at Mendelian ratios, but show increased postnatal mortality early in life (PubMed:24828044). Mice are smaller, leaner and have decreased serum, liver and brown adipose triglycerides (PubMed:23209793). After weaning, mice display motor dysfunction with front-paw clasping during tail suspension. Brain size and weight are also significantly lower. behavioral tests indicate that mice have deficits in learning, and short- and long-term memory, as well as severe anxiety, a phenotype related to omega-3 fatty-acid deficiency. Lipidomic analysis of knockout mice show strongly reduced levels of docosahexaenoic acid (DHA) in brain accompanied by neuronal cell loss in hippocampus and cerebellum (PubMed:24828044). Mice also show a leaky blood-brain barrier from embryonic stages through to adulthood, while the normal patterning of vascular networks is maintained. Electron microscopy analysis shows an increase in central nervous system-endothelial-cell vesicular transcytosis not associated with tight-junction defects (PubMed:24828040). Mice have an increase in plasma levels of LPC (PubMed:26005868).4 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi92D → A: Abolishes lysophosphatidylcholine (LPC) transport; when associated with A-96. 1 Publication1
Mutagenesisi96D → A: Abolishes lysophosphatidylcholine (LPC) transport; when associated with A-92. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002733881 – 534Sodium-dependent lysophosphatidylcholine symporter 1Add BLAST534

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi221N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi231N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ9DA75
PaxDbiQ9DA75
PRIDEiQ9DA75

PTM databases

PhosphoSitePlusiQ9DA75

Expressioni

Tissue specificityi

Widely expressed. Exhibits an oscillatory pattern of expression in brown adipose tissue and liver consistent with a circadian rhythm. Enriched in brain micro-vessels, where it is specifically present in endothelium constituting the blood-brain barrier (at protein level) (PubMed:24828044, PubMed:24828040).4 Publications

Inductioni

By fasting in liver and brown adipose tissue as well as by cold exposure in brown adipose tissue. Expression following fasting is dependent on glucagon signaling and Ppara.2 Publications

Gene expression databases

BgeeiENSMUSG00000028655 Expressed in 171 organ(s), highest expression level in small intestine
CleanExiMM_MFSD2
ExpressionAtlasiQ9DA75 baseline and differential
GenevisibleiQ9DA75 MM

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000030408

Structurei

3D structure databases

ProteinModelPortaliQ9DA75
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the major facilitator superfamily.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4830 Eukaryota
COG2211 LUCA
GeneTreeiENSGT00390000005318
HOGENOMiHOG000294186
HOVERGENiHBG080097
InParanoidiQ9DA75
OMAiYLCSWLA
OrthoDBiEOG091G06N1
PhylomeDBiQ9DA75
TreeFamiTF331194

Family and domain databases

InterProiView protein in InterPro
IPR039672 MFS_2
IPR036259 MFS_trans_sf
PANTHERiPTHR11328 PTHR11328, 1 hit
SUPFAMiSSF103473 SSF103473, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q9DA75-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAKGEGAESG SAAGLLPTSI LQASERPVQV KKEPKKKQQL SICNKLCYAV
60 70 80 90 100
GGAPYQLTGC ALGFFLQIYL LDVAKVEPLP ASIILFVGRA WDAFTDPLVG
110 120 130 140 150
FCISKSSWTR LGRLMPWIIF STPLAIIAYF LIWFVPDFPS GTESSHGFLW
160 170 180 190 200
YLLFYCLFET LVTCFHVPYS ALTMFISTEQ SERDSATAYR MTVEVLGTVI
210 220 230 240 250
GTAIQGQIVG QAKAPCLQDQ NGSVVVSEVA NRTQSTASLK DTQNAYLLAA
260 270 280 290 300
GIIASIYVLC AFILILGVRE QRELYESQQA ESMPFFQGLR LVMGHGPYVK
310 320 330 340 350
LIAGFLFTSL AFMLVEGNFA LFCTYTLDFR NEFQNLLLAI MLSATFTIPI
360 370 380 390 400
WQWFLTRFGK KTAVYIGISS AVPFLILVAL MERNLIVTYV VAVAAGVSVA
410 420 430 440 450
AAFLLPWSML PDVIDDFHLK HPHSPGTEPI FFSFYVFFTK FASGVSLGVS
460 470 480 490 500
TLSLDFANYQ RQGCSQPEQV KFTLKMLVTM APIILILLGL LLFKLYPIDE
510 520 530
EKRRQNKKAL QALREEASSS GCSDTDSTEL ASIL
Length:534
Mass (Da):58,984
Last modified:June 1, 2001 - v1
Checksum:i2DE15EBBB2C1F396
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B1ARS3B1ARS3_MOUSE
Sodium-dependent lysophosphatidylch...
Mfsd2a
106Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti67Q → H in AAH46793 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK006096 mRNA Translation: BAB24407.1
BC046793 mRNA Translation: AAH46793.1
BC060526 mRNA Translation: AAH60526.1
CCDSiCCDS18605.1
RefSeqiNP_083938.2, NM_029662.2
UniGeneiMm.331842

Genome annotation databases

EnsembliENSMUST00000030408; ENSMUSP00000030408; ENSMUSG00000028655
GeneIDi76574
KEGGimmu:76574
UCSCiuc008uoo.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK006096 mRNA Translation: BAB24407.1
BC046793 mRNA Translation: AAH46793.1
BC060526 mRNA Translation: AAH60526.1
CCDSiCCDS18605.1
RefSeqiNP_083938.2, NM_029662.2
UniGeneiMm.331842

3D structure databases

ProteinModelPortaliQ9DA75
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000030408

Chemistry databases

SwissLipidsiSLP:000000999

PTM databases

PhosphoSitePlusiQ9DA75

Proteomic databases

MaxQBiQ9DA75
PaxDbiQ9DA75
PRIDEiQ9DA75

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000030408; ENSMUSP00000030408; ENSMUSG00000028655
GeneIDi76574
KEGGimmu:76574
UCSCiuc008uoo.2 mouse

Organism-specific databases

CTDi84879
MGIiMGI:1923824 Mfsd2a

Phylogenomic databases

eggNOGiKOG4830 Eukaryota
COG2211 LUCA
GeneTreeiENSGT00390000005318
HOGENOMiHOG000294186
HOVERGENiHBG080097
InParanoidiQ9DA75
OMAiYLCSWLA
OrthoDBiEOG091G06N1
PhylomeDBiQ9DA75
TreeFamiTF331194

Enzyme and pathway databases

ReactomeiR-MMU-1483191 Synthesis of PC

Miscellaneous databases

PROiPR:Q9DA75
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028655 Expressed in 171 organ(s), highest expression level in small intestine
CleanExiMM_MFSD2
ExpressionAtlasiQ9DA75 baseline and differential
GenevisibleiQ9DA75 MM

Family and domain databases

InterProiView protein in InterPro
IPR039672 MFS_2
IPR036259 MFS_trans_sf
PANTHERiPTHR11328 PTHR11328, 1 hit
SUPFAMiSSF103473 SSF103473, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNLS1_MOUSE
AccessioniPrimary (citable) accession number: Q9DA75
Secondary accession number(s): Q80ZW8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 23, 2007
Last sequence update: June 1, 2001
Last modified: November 7, 2018
This is version 109 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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