ID NLS1_HUMAN Reviewed; 543 AA. AC Q8NA29; A8K675; Q6UWU5; Q96F59; Q9BRC8; DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 24-JAN-2024, entry version 156. DE RecName: Full=Sodium-dependent lysophosphatidylcholine symporter 1 {ECO:0000305}; DE Short=NLS1; DE Short=Sodium-dependent LPC symporter 1; DE AltName: Full=Major facilitator superfamily domain-containing protein 2A; DE Short=HsMFSD2A {ECO:0000303|PubMed:34135507}; DE Short=MFSD2a {ECO:0000303|PubMed:23177091}; GN Name=MFSD2A {ECO:0000303|PubMed:18694395, GN ECO:0000312|HGNC:HGNC:25897}; Synonyms=MFSD2, NLS1; GN ORFNames=HMFN0656, PP9177, UNQ300/PRO341 GN {ECO:0000303|PubMed:12975309}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Placenta, and Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Hepatoblastoma; RX PubMed=15221005; DOI=10.1038/sj.onc.1207782; RA Yamada S., Ohira M., Horie H., Ando K., Takayasu H., Suzuki Y., Sugano S., RA Hirata T., Goto T., Matsunaga T., Hiyama E., Hayashi Y., Ando H., Suita S., RA Kaneko M., Sasaki F., Hashizume K., Ohnuma N., Nakagawara A.; RT "Expression profiling and differential screening between hepatoblastomas RT and the corresponding normal livers: identification of high expression of RT the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas."; RL Oncogene 23:5901-5911(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=15498874; DOI=10.1073/pnas.0404089101; RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X., RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.; RT "Large-scale cDNA transfection screening for genes related to cancer RT development and progression."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=16303743; DOI=10.1093/dnares/12.2.117; RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y., RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., RA Isogai T.; RT "Signal sequence and keyword trap in silico for selection of full-length RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA RT libraries."; RL DNA Res. 12:117-126(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Eye, Muscle, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP IDENTIFICATION. RX PubMed=18694395; DOI=10.1042/bj20080165; RA Angers M., Uldry M., Kong D., Gimble J.M., Jetten A.M.; RT "Mfsd2a encodes a novel major facilitator superfamily domain-containing RT protein highly induced in brown adipose tissue during fasting and adaptive RT thermogenesis."; RL Biochem. J. 416:347-355(2008). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, TISSUE SPECIFICITY, AND RP INTERACTION WITH ERVFRD-1. RX PubMed=18988732; DOI=10.1073/pnas.0807413105; RA Esnault C., Priet S., Ribet D., Vernochet C., Bruls T., Lavialle C., RA Weissenbach J., Heidmann T.; RT "A placenta-specific receptor for the fusogenic, endogenous retrovirus- RT derived, human syncytin-2."; RL Proc. Natl. Acad. Sci. U.S.A. 105:17532-17537(2008). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-230 AND ASN-240, AND RP MUTAGENESIS OF ARG-103; ASP-106; ASP-110; ASN-230; ASN-240 AND LYS-449. RX PubMed=21677192; DOI=10.1073/pnas.1018098108; RA Reiling J.H., Clish C.B., Carette J.E., Varadarajan M., Brummelkamp T.R., RA Sabatini D.M.; RT "A haploid genetic screen identifies the major facilitator domain RT containing 2A (MFSD2A) transporter as a key mediator in the response to RT tunicamycin."; RL Proc. Natl. Acad. Sci. U.S.A. 108:11756-11765(2011). RN [12] RP FUNCTION. RX PubMed=23177091; DOI=10.1016/j.placenta.2012.10.012; RA Toufaily C., Vargas A., Lemire M., Lafond J., Rassart E., Barbeau B.; RT "MFSD2a, the Syncytin-2 receptor, is important for trophoblast fusion."; RL Placenta 34:85-88(2013). RN [13] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=24828040; DOI=10.1038/nature13324; RA Ben-Zvi A., Lacoste B., Kur E., Andreone B.J., Mayshar Y., Yan H., Gu C.; RT "Mfsd2a is critical for the formation and function of the blood-brain RT barrier."; RL Nature 509:507-511(2014). RN [14] RP FUNCTION, DISULFIDE BOND, AND MUTAGENESIS OF GLN-57; PHE-65; PHE-66; RP ASP-73; ARG-103; ASP-110; MET-200; CYS-225; GLU-325; PHE-328; TYR-334; RP ARG-339; PHE-342; LEU-346; ILE-349; MET-350; ILE-357; GLN-361; ALA-404; RP PHE-412; TRP-416; LYS-449; TYR-468 AND CYS-473. RX PubMed=34135507; DOI=10.1038/s41586-021-03650-9; RA Cater R.J., Chua G.L., Erramilli S.K., Keener J.E., Choy B.C., Tokarz P., RA Chin C.F., Quek D.Q.Y., Kloss B., Pepe J.G., Parisi G., Wong B.H., RA Clarke O.B., Marty M.T., Kossiakoff A.A., Khelashvili G., Silver D.L., RA Mancia F.; RT "Structural basis of omega-3 fatty acid transport across the blood-brain RT barrier."; RL Nature 595:315-319(2021). RN [15] RP INVOLVEMENT IN NEDMISBA, VARIANTS NEDMISBA MET-172 AND LEU-179, RP CHARACTERIZATION OF VARIANTS NEDMISBA MET-172 AND LEU-179, FUNCTION, AND RP SUBCELLULAR LOCATION. 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). RN [16] RP INVOLVEMENT IN NEDMISBA, VARIANT NEDMISBA LEU-352, AND CHARACTERIZATION OF RP VARIANT NEDMISBA LEU-352. RX PubMed=26005865; DOI=10.1038/ng.3313; RA Alakbarzade V., Hameed A., Quek D.Q., Chioza B.A., Baple E.L., RA Cazenave-Gassiot A., Nguyen L.N., Wenk M.R., Ahmad A.Q., RA Sreekantan-Nair A., Weedon M.N., Rich P., Patton M.A., Warner T.T., RA Silver D.L., Crosby A.H.; RT "A partially inactivating mutation in the sodium-dependent RT lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly RT syndrome."; RL Nat. Genet. 47:814-817(2015). RN [17] RP VARIANTS NEDMISBA MET-172; MET-211; PHE-263; HIS-339 AND LEU-506, RP CHARACTERIZATION OF VARIANTS MET-211; PHE-263; HIS-339 AND LEU-506, RP MUTAGENESIS OF PRO-177, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=32572202; DOI=10.1038/s41431-020-0669-x; RA Scala M., Chua G.L., Chin C.F., Alsaif H.S., Borovikov A., Riazuddin S., RA Riazuddin S., Chiara Manzini M., Severino M., Kuk A., Fan H., Jamshidi Y., RA Toosi M.B., Doosti M., Karimiani E.G., Salpietro V., Dadali E., RA Baydakova G., Konovalov F., Lozier E., O'Connor E., Sabr Y., Alfaifi A., RA Ashrafzadeh F., Striano P., Zara F., Alkuraya F.S., Houlden H., RA Maroofian R., Silver D.L.; RT "Biallelic MFSD2A variants associated with congenital microcephaly, RT developmental delay, and recognizable neuroimaging features."; RL Eur. J. Hum. Genet. 28:1509-1519(2020). RN [18] RP VARIANT NEDMISBA VAL-81 DEL. RX PubMed=33186761; DOI=10.1016/j.ejmg.2020.104096; RA Razmara E., Azimi H., Tavasoli A.R., Fallahi E., Sheida S.V., Eidi M., RA Bitaraf A., Farjami Z., Daneshmand M.A., Garshasbi M.; RT "Novel neuroclinical findings of autosomal recessive primary microcephaly RT 15 in a consanguineous Iranian family."; RL Eur. J. Med. Genet. 63:104096-104096(2020). CC -!- FUNCTION: Sodium-dependent lysophosphatidylcholine (LPC) symporter, CC which plays an essential role for blood-brain barrier formation and CC function (PubMed:24828040, PubMed:34135507, PubMed:32572202). CC Specifically expressed in endothelium of the blood-brain barrier of CC micro-vessels and transports LPC into the brain (By similarity). CC Transport of LPC is essential because it constitutes the major CC mechanism by which docosahexaenoic acid (DHA), an omega-3 fatty acid CC that is essential for normal brain growth and cognitive function, CC enters the brain (PubMed:34135507, PubMed:26005868). Transports LPC CC carrying long-chain fatty acids such LPC oleate and LPC palmitate with CC a minimum acyl chain length of 14 carbons (By similarity). Does not CC transport docosahexaenoic acid in unesterified fatty acid (By CC similarity). Specifically required for blood-brain barrier formation CC and function, probably by mediating lipid transport (By similarity). CC Not required for central nervous system vascular morphogenesis (By CC similarity). Acts as a transporter for tunicamycin, an inhibitor of CC asparagine-linked glycosylation (PubMed:21677192). In placenta, acts as CC a receptor for ERVFRD-1/syncytin-2 and is required for trophoblast CC fusion (PubMed:18988732, PubMed:23177091). CC {ECO:0000250|UniProtKB:Q9DA75, ECO:0000269|PubMed:18988732, CC ECO:0000269|PubMed:21677192, ECO:0000269|PubMed:23177091, CC ECO:0000269|PubMed:24828040, ECO:0000269|PubMed:26005868, CC ECO:0000269|PubMed:34135507}. 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:0000269|PubMed:24828040}; 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:0000269|PubMed:24828040}; 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:0000269|PubMed:24828040}; 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 -!- SUBUNIT: Interacts with ERVFRD-1/syncytin-2. CC {ECO:0000269|PubMed:18988732}. CC -!- INTERACTION: CC Q8NA29-2; Q9NWH2: TMEM242; NbExp=3; IntAct=EBI-9641334, EBI-10315004; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26005868, CC ECO:0000269|PubMed:32572202}; Multi-pass membrane protein CC {ECO:0000255}. Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q9DA75}; Multi-pass membrane protein CC {ECO:0000255}. Note=Cytoplasmic punctae that may represent vesicles CC shuttling between the endoplasmic reticulum and the plasma membrane CC (PubMed:21677192). {ECO:0000269|PubMed:21677192}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q8NA29-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8NA29-2; Sequence=VSP_022539; CC Name=3; CC IsoId=Q8NA29-3; Sequence=VSP_022540; CC -!- TISSUE SPECIFICITY: In placenta, associated with trophoblast cells. CC {ECO:0000269|PubMed:18988732}. CC -!- DISEASE: Neurodevelopmental disorder with progressive microcephaly, CC spasticity, and brain imaging abnormalities (NEDMISBA) [MIM:616486]: An CC autosomal recessive disorder characterized by impaired intellectual CC development with poor speech, progressive microcephaly, and CC appendicular spasticity. Brain imaging usually shows abnormalities, CC including enlarged ventricles, white matter defects, and atrophy or CC hypoplasia of brain tissue. Some patients have a more severe phenotype CC with seizures, lack of developmental milestones, and early death. CC {ECO:0000269|PubMed:26005865, ECO:0000269|PubMed:26005868, CC ECO:0000269|PubMed:32572202, ECO:0000269|PubMed:33186761}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. 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; AY358636; AAQ88999.1; -; mRNA. DR EMBL; AK093223; BAC04100.1; -; mRNA. DR EMBL; AB073383; BAD38634.1; -; mRNA. DR EMBL; AF289609; AAL55793.1; -; mRNA. DR EMBL; AK075183; BAC11456.1; -; mRNA. DR EMBL; AK291540; BAF84229.1; -; mRNA. DR EMBL; AL663070; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX07248.1; -; Genomic_DNA. DR EMBL; BC006353; AAH06353.2; -; mRNA. DR EMBL; BC011587; AAH11587.1; -; mRNA. DR EMBL; BC092414; AAH92414.1; -; mRNA. DR CCDS; CCDS44118.1; -. [Q8NA29-1] DR CCDS; CCDS446.1; -. [Q8NA29-2] DR RefSeq; NP_001129965.1; NM_001136493.2. [Q8NA29-1] DR RefSeq; NP_001274737.1; NM_001287808.1. DR RefSeq; NP_001274738.1; NM_001287809.1. DR RefSeq; NP_116182.2; NM_032793.4. [Q8NA29-2] DR PDB; 7OIX; EM; 3.60 A; B=1-543. DR PDBsum; 7OIX; -. DR AlphaFoldDB; Q8NA29; -. DR EMDB; EMD-12935; -. DR SMR; Q8NA29; -. DR BioGRID; 124323; 3. DR DIP; DIP-47306N; -. DR IntAct; Q8NA29; 4. DR MINT; Q8NA29; -. DR STRING; 9606.ENSP00000361895; -. DR SwissLipids; SLP:000001000; -. DR TCDB; 2.A.2.3.8; the glycoside-pentoside-hexuronide (gph):cation symporter family. DR GlyCosmos; Q8NA29; 2 sites, No reported glycans. DR GlyGen; Q8NA29; 2 sites. DR iPTMnet; Q8NA29; -. DR PhosphoSitePlus; Q8NA29; -. DR BioMuta; MFSD2A; -. DR DMDM; 74751132; -. DR EPD; Q8NA29; -. DR MassIVE; Q8NA29; -. DR PaxDb; 9606-ENSP00000361895; -. DR PeptideAtlas; Q8NA29; -. DR ProteomicsDB; 72626; -. [Q8NA29-1] DR ProteomicsDB; 72627; -. [Q8NA29-2] DR ProteomicsDB; 72628; -. [Q8NA29-3] DR Antibodypedia; 31983; 143 antibodies from 22 providers. DR DNASU; 84879; -. DR Ensembl; ENST00000372809.5; ENSP00000361895.5; ENSG00000168389.18. [Q8NA29-1] DR Ensembl; ENST00000372811.10; ENSP00000361898.6; ENSG00000168389.18. [Q8NA29-2] DR GeneID; 84879; -. DR KEGG; hsa:84879; -. DR MANE-Select; ENST00000372811.10; ENSP00000361898.6; NM_032793.5; NP_116182.2. [Q8NA29-2] DR UCSC; uc001ceu.5; human. [Q8NA29-1] DR AGR; HGNC:25897; -. DR CTD; 84879; -. DR DisGeNET; 84879; -. DR GeneCards; MFSD2A; -. DR HGNC; HGNC:25897; MFSD2A. DR HPA; ENSG00000168389; Tissue enhanced (epididymis, liver, skin). DR MalaCards; MFSD2A; -. DR MIM; 614397; gene. DR MIM; 616486; phenotype. DR neXtProt; NX_Q8NA29; -. DR OpenTargets; ENSG00000168389; -. DR Orphanet; 2512; Autosomal recessive primary microcephaly. DR PharmGKB; PA165751549; -. DR VEuPathDB; HostDB:ENSG00000168389; -. DR eggNOG; KOG4830; Eukaryota. DR GeneTree; ENSGT00390000005318; -. DR HOGENOM; CLU_027408_6_1_1; -. DR InParanoid; Q8NA29; -. DR OMA; VPYVAMP; -. DR OrthoDB; 6761at2759; -. DR PhylomeDB; Q8NA29; -. DR TreeFam; TF331194; -. DR PathwayCommons; Q8NA29; -. DR Reactome; R-HSA-1483191; Synthesis of PC. DR SignaLink; Q8NA29; -. DR BioGRID-ORCS; 84879; 12 hits in 1142 CRISPR screens. DR ChiTaRS; MFSD2A; human. DR GeneWiki; MFSD2; -. DR GenomeRNAi; 84879; -. DR Pharos; Q8NA29; Tbio. DR PRO; PR:Q8NA29; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q8NA29; Protein. DR Bgee; ENSG00000168389; Expressed in right lobe of liver and 169 other cell types or tissues. DR ExpressionAtlas; Q8NA29; baseline and differential. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; TAS:ARUK-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL. DR GO; GO:0015245; F:fatty acid transmembrane transporter activity; ISS:BHF-UCL. DR GO; GO:0005324; F:long-chain fatty acid transporter activity; IMP:ARUK-UCL. DR GO; GO:0140348; F:lysophosphatidylcholine flippase activity; IEA:Ensembl. DR GO; GO:0051978; F:lysophospholipid:sodium symporter activity; IDA:UniProtKB. DR GO; GO:1901480; F:oleate transmembrane transporter activity; IMP:ARUK-UCL. DR GO; GO:0005548; F:phospholipid transporter activity; TAS:Reactome. DR GO; GO:0007420; P:brain development; IMP:ARUK-UCL. DR GO; GO:0008643; P:carbohydrate transport; IEA:InterPro. DR GO; GO:0009267; P:cellular response to starvation; ISS:ARUK-UCL. DR GO; GO:0050890; P:cognition; IMP:ARUK-UCL. DR GO; GO:0097009; P:energy homeostasis; ISS:ARUK-UCL. DR GO; GO:0060856; P:establishment of blood-brain barrier; ISS:UniProtKB. DR GO; GO:0015908; P:fatty acid transport; IMP:ARUK-UCL. DR GO; GO:0021766; P:hippocampus development; ISS:BHF-UCL. DR GO; GO:1990379; P:lipid transport across blood-brain barrier; IMP:ARUK-UCL. DR GO; GO:0015909; P:long-chain fatty acid transport; ISS:ARUK-UCL. DR GO; GO:0140329; P:lysophospholipid translocation; IMP:ARUK-UCL. DR GO; GO:0051977; P:lysophospholipid transport; IDA:BHF-UCL. DR GO; GO:0035633; P:maintenance of blood-brain barrier; ISS:ARUK-UCL. DR GO; GO:0061744; P:motor behavior; ISS:ARUK-UCL. DR GO; GO:0031999; P:negative regulation of fatty acid beta-oxidation; ISS:ARUK-UCL. DR GO; GO:0071702; P:organic substance transport; IBA:GO_Central. DR GO; GO:0006656; P:phosphatidylcholine biosynthetic process; TAS:Reactome. DR GO; GO:0008594; P:photoreceptor cell morphogenesis; ISS:ARUK-UCL. DR GO; GO:0035845; P:photoreceptor cell outer segment organization; ISS:ARUK-UCL. DR GO; GO:0030307; P:positive regulation of cell growth; ISS:ARUK-UCL. DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; ISS:ARUK-UCL. DR GO; GO:0050773; P:regulation of dendrite development; ISS:ARUK-UCL. DR GO; GO:0040014; P:regulation of multicellular organism growth; ISS:ARUK-UCL. DR GO; GO:0150011; P:regulation of neuron projection arborization; ISS:ARUK-UCL. DR GO; GO:0150172; P:regulation of phosphatidylcholine metabolic process; IMP:ARUK-UCL. DR GO; GO:0150175; P:regulation of phosphatidylethanolamine metabolic process; ISS:ARUK-UCL. DR GO; GO:0150178; P:regulation of phosphatidylserine metabolic process; ISS:ARUK-UCL. DR GO; GO:0060042; P:retina morphogenesis in camera-type eye; ISS:ARUK-UCL. DR GO; GO:0003406; P:retinal pigment epithelium development; ISS:ARUK-UCL. DR GO; GO:0045056; P:transcytosis; ISS:UniProtKB. DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL. DR GO; GO:0034379; P:very-low-density lipoprotein particle assembly; ISS:ARUK-UCL. DR CDD; cd17451; MFS_NLS1_MFSD2A; 1. DR Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 2. 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. DR Genevisible; Q8NA29; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disease variant; KW Disulfide bond; Endoplasmic reticulum; Glycoprotein; Lipid transport; KW Membrane; Primary microcephaly; Reference proteome; Symport; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..543 FT /note="Sodium-dependent lysophosphatidylcholine symporter FT 1" FT /id="PRO_0000273387" 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..94 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 95..115 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 116..127 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 128..147 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 148..157 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 158..182 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 183..189 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 190..221 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 222..241 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 242..275 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 276..306 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 307..333 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 334..344 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 345..363 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 364..367 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 368..389 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 390..392 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 393..429 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 430..439 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 440..466 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 467..478 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TRANSMEM 479..502 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT TOPO_DOM 503..543 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q9DA75" FT REGION 1..34 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 230 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000305|PubMed:21677192" FT CARBOHYD 240 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000305|PubMed:21677192" FT DISULFID 225..473 FT /evidence="ECO:0000305|PubMed:34135507" FT VAR_SEQ 1..186 FT /note="MAKGEGAESGSAAGLLPTSILQSTERPAQVKKEPKKKKQQLSVCNKLCYALG FT GAPYQVTGCALGFFLQIYLLDVAQKDEEVVFCFSSFQVGPFSASIILFVGRAWDAITDP FT LVGLCISKSPWTCLGRLMPWIIFSTPLAVIAYFLIWFVPDFPHGQTYWYLLFYCLFETM FT VTCFHVPYSALTMFIS -> MWLRWALSLPPSSCLWAEPGMPSQTPWWASASANPPGPA FT WVALCPGSSSPRPWPSLPTSSSGSCPTSHTARPIGTCFSIASLKQWSRVSMFPTRLSPC FT SSA (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12975309" FT /id="VSP_022540" FT VAR_SEQ 77..89 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15221005, ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:15498874, ECO:0000303|PubMed:16303743" FT /id="VSP_022539" FT VARIANT 81 FT /note="Missing (in NEDMISBA; uncertain significance; FT dbSNP:rs1570238098)" FT /evidence="ECO:0000269|PubMed:33186761" FT /id="VAR_085538" FT VARIANT 172 FT /note="T -> M (in NEDMISBA; no effect on cell membrane FT localization; loss of LPC transport activity; FT dbSNP:rs1057517688)" FT /evidence="ECO:0000269|PubMed:26005868, FT ECO:0000269|PubMed:32572202" FT /id="VAR_074624" FT VARIANT 179 FT /note="S -> L (in NEDMISBA; no effect on cell membrane FT localization; decreased LPC transport activity; FT dbSNP:rs1057517689)" FT /evidence="ECO:0000269|PubMed:26005868" FT /id="VAR_074625" FT VARIANT 211 FT /note="T -> M (in NEDMISBA; reduced expression; no effect FT on cell membrane localization; decreased LPC transport FT activity; dbSNP:rs756467073)" FT /evidence="ECO:0000269|PubMed:32572202" FT /id="VAR_085539" FT VARIANT 263 FT /note="V -> F (in NEDMISBA; reduced expression; no effect FT on cell membrane localization; decreased LPC transport FT activity)" FT /evidence="ECO:0000269|PubMed:32572202" FT /id="VAR_085540" FT VARIANT 339 FT /note="R -> H (in NEDMISBA; reduced expression; no effect FT on cell membrane localization; no effect on LPC transport FT activity; dbSNP:rs776741331)" FT /evidence="ECO:0000269|PubMed:32572202" FT /id="VAR_085541" FT VARIANT 352 FT /note="S -> L (in NEDMISBA; no effect on cell membrane FT localization; decreased LPC transport activity; FT dbSNP:rs1057519087)" FT /evidence="ECO:0000269|PubMed:26005865" FT /id="VAR_074626" FT VARIANT 506 FT /note="P -> L (in NEDMISBA; reduced expression; no effect FT on cell membrane localization; loss of LPC transport FT activity)" FT /evidence="ECO:0000269|PubMed:32572202" FT /id="VAR_085542" FT MUTAGEN 57 FT /note="Q->E: Does not affect lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 57 FT /note="Q->L: Abolished lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 65 FT /note="F->A: Abolished lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 66 FT /note="F->A: Abolished lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 73 FT /note="D->A: Abolished lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 103 FT /note="R->A,K,E: Reduced lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 103 FT /note="R->A: No effect on cell sensitivity toward FT tunicamycin." FT /evidence="ECO:0000269|PubMed:21677192" FT MUTAGEN 106 FT /note="D->A: No effect on cell sensitivity toward FT tunicamycin." FT /evidence="ECO:0000269|PubMed:21677192" FT MUTAGEN 110 FT /note="D->A: Drastic loss of cell sensitivity toward FT tunicamycin. Abolished lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:21677192, FT ECO:0000269|PubMed:34135507" FT MUTAGEN 177 FT /note="P->T: Reduced expression; no effect on cell membrane FT localization; decreased LPC transport activity." FT /evidence="ECO:0000269|PubMed:32572202" FT MUTAGEN 200 FT /note="M->F: Reduced lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 225 FT /note="C->A: Reduced lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 230 FT /note="N->Q: Loss of glycosylation; when associated with FT Q-240." FT /evidence="ECO:0000269|PubMed:21677192" FT MUTAGEN 240 FT /note="N->Q: Loss of glycosylation; when associated with FT Q-230." FT /evidence="ECO:0000269|PubMed:21677192" FT MUTAGEN 325 FT /note="E->A,D,Q,R: Abolished lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 328 FT /note="F->A,Y: Reduced lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 334 FT /note="Y->A: Does not affect lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 339 FT /note="R->A: Reduced lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 342 FT /note="F->A: Abolished lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 346 FT /note="L->A: Abolished lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 349 FT /note="I->A: Reduced lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 350 FT /note="M->A: Reduced lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 357 FT /note="I->A: Does not affect lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 357 FT /note="I->W: Abolished lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 361 FT /note="Q->W: Reduced lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 404 FT /note="A->W: Abolished lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 412 FT /note="F->I,W: Reduced lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 416 FT /note="W->A,F: Reduced lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 449 FT /note="K->A,R,Q: Reduced lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 449 FT /note="K->A: Loss of plasma membrane localization. Loss of FT cell sensitivity toward tunicamycin." FT /evidence="ECO:0000269|PubMed:21677192" FT MUTAGEN 468 FT /note="Y->A: Abolished lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT MUTAGEN 473 FT /note="C->A: Reduced lysophosphatidylcholine (LPC) FT transport." FT /evidence="ECO:0000269|PubMed:34135507" FT CONFLICT 229 FT /note="L -> F (in Ref. 1; AAQ88999)" FT /evidence="ECO:0000305" SQ SEQUENCE 543 AA; 60170 MW; C9933B79335BFBDE CRC64; MAKGEGAESG SAAGLLPTSI LQSTERPAQV KKEPKKKKQQ LSVCNKLCYA LGGAPYQVTG CALGFFLQIY LLDVAQKDEE VVFCFSSFQV GPFSASIILF VGRAWDAITD PLVGLCISKS PWTCLGRLMP WIIFSTPLAV IAYFLIWFVP DFPHGQTYWY LLFYCLFETM VTCFHVPYSA LTMFISTEQT ERDSATAYRM TVEVLGTVLG TAIQGQIVGQ ADTPCFQDLN SSTVASQSAN HTHGTTSHRE TQKAYLLAAG VIVCIYIICA VILILGVREQ REPYEAQQSE PIAYFRGLRL VMSHGPYIKL ITGFLFTSLA FMLVEGNFVL FCTYTLGFRN EFQNLLLAIM LSATLTIPIW QWFLTRFGKK TAVYVGISSA VPFLILVALM ESNLIITYAV AVAAGISVAA AFLLPWSMLP DVIDDFHLKQ PHFHGTEPIF FSFYVFFTKF ASGVSLGIST LSLDFAGYQT RGCSQPERVK FTLNMLVTMA PIVLILLGLL LFKMYPIDEE RRRQNKKALQ ALRDEASSSG CSETDSTELA SIL //