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Identification
HMDB Protein ID HMDBP13909
Secondary Accession Numbers None
Name Sodium-dependent lysophosphatidylcholine symporter 1
Synonyms
  1. NLS1
  2. Sodium-dependent LPC symporter 1
  3. Major facilitator superfamily domain-containing protein 2A
Gene Name MFSD2A
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Sodium-dependent lysophosphatidylcholine (LPC) symporter, which plays an essential role for blood-brain barrier formation and function (PubMed:24828040). Specifically expressed in endothelium of the blood-brain barrier of micro-vessels and transports LPC into the brain (By similarity). 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 (PubMed:26005868). Transports LPC carrying long-chain fatty acids such LPC oleate and LPC palmitate with a minimum acyl chain length of 14 carbons (By similarity). Does not transport docosahexaenoic acid in unesterified fatty acid (By similarity). Specifically required for blood-brain barrier formation and function, probably by mediating lipid transport (By similarity). Not required for central nervous system vascular morphogenesis (By similarity). Acts as a transporter for tunicamycin, an inhibitor of asparagine-linked glycosylation (PubMed:21677192). In placenta, acts as a receptor for ERVFRD-1/syncytin-2 and is required for trophoblast fusion (PubMed:18988732, PubMed:23177091).
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
maintenance of blood-brain barrier
hippocampus development
phosphatidylcholine biosynthetic process
regulation of multicellular organism growth
lysophospholipid transport
fatty acid transport
cognition
brain development
very-low-density lipoprotein particle assembly
positive regulation of cell growth
positive regulation of triglyceride biosynthetic process
cellular response to starvation
negative regulation of fatty acid beta-oxidation
establishment of blood-brain barrier
lipid transport across blood-brain barrier
transcytosis
long-chain fatty acid transport
energy homeostasis
lysophospholipid translocation
motor behavior
photoreceptor cell morphogenesis
photoreceptor cell outer segment organization
regulation of dendrite development
regulation of neuron projection arborization
regulation of phosphatidylcholine metabolic process
regulation of phosphatidylethanolamine metabolic process
carbohydrate transport
regulation of phosphatidylserine metabolic process
retina morphogenesis in camera-type eye
retinal pigment epithelium development
transport across blood-brain barrier
organic substance transport
Cellular Component
endoplasmic reticulum membrane
plasma membrane
integral to membrane
integral to plasma membrane
Molecular Function
long-chain fatty acid transporter activity
fatty acid transporter activity
symporter activity
lysophospholipid:sodium symporter activity
lysophosphatidylcholine flippase activity
oleate transmembrane transporter activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 543
Molecular Weight 60169.66
Theoretical pI 6.944
Pfam Domain Function Not Available
Signals Not Available
Transmembrane Regions
  • 47-67;81-101;129-149;161-181;257-277;311-331;345-365;371-391;394-414;438-458;481-501;
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q8NA29
UniProtKB/Swiss-Prot Entry Name NLS1_HUMAN
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  4. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [PubMed:12975309 ]
  5. Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T: Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries. DNA Res. 2005;12(2):117-26. [PubMed:16303743 ]
  6. Wan D, Gong Y, Qin W, Zhang P, Li J, Wei L, Zhou X, Li H, Qiu X, Zhong F, He L, Yu J, Yao G, Jiang H, Qian L, Yu Y, Shu H, Chen X, Xu H, Guo M, Pan Z, Chen Y, Ge C, Yang S, Gu J: Large-scale cDNA transfection screening for genes related to cancer development and progression. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15724-9. Epub 2004 Oct 21. [PubMed:15498874 ]
  7. Yamada S, Ohira M, Horie H, Ando K, Takayasu H, Suzuki Y, Sugano S, Hirata T, Goto T, Matsunaga T, Hiyama E, Hayashi Y, Ando H, Suita S, Kaneko M, Sasaki F, Hashizume K, Ohnuma N, Nakagawara A: Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas. Oncogene. 2004 Aug 5;23(35):5901-11. [PubMed:15221005 ]
  8. Guemez-Gamboa A, Nguyen LN, Yang H, Zaki MS, Kara M, Ben-Omran T, Akizu N, Rosti RO, Rosti B, Scott E, Schroth J, Copeland B, Vaux KK, Cazenave-Gassiot A, Quek DQ, Wong BH, Tan BC, Wenk MR, Gunel M, Gabriel S, Chi NC, Silver DL, Gleeson JG: Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome. Nat Genet. 2015 Jul;47(7):809-13. doi: 10.1038/ng.3311. Epub 2015 May 25. [PubMed:26005868 ]
  9. Angers M, Uldry M, Kong D, Gimble JM, Jetten AM: Mfsd2a encodes a novel major facilitator superfamily domain-containing protein highly induced in brown adipose tissue during fasting and adaptive thermogenesis. Biochem J. 2008 Dec 15;416(3):347-55. doi: 10.1042/BJ20080165. [PubMed:18694395 ]
  10. Esnault C, Priet S, Ribet D, Vernochet C, Bruls T, Lavialle C, Weissenbach J, Heidmann T: A placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2. Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17532-7. doi: 10.1073/pnas.0807413105. Epub 2008 Nov 6. [PubMed:18988732 ]
  11. Reiling JH, Clish CB, Carette JE, Varadarajan M, Brummelkamp TR, Sabatini DM: A haploid genetic screen identifies the major facilitator domain containing 2A (MFSD2A) transporter as a key mediator in the response to tunicamycin. Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):11756-65. doi: 10.1073/pnas.1018098108. Epub 2011 Jun 15. [PubMed:21677192 ]
  12. Ben-Zvi A, Lacoste B, Kur E, Andreone BJ, Mayshar Y, Yan H, Gu C: Mfsd2a is critical for the formation and function of the blood-brain barrier. Nature. 2014 May 22;509(7501):507-11. doi: 10.1038/nature13324. Epub 2014 May 14. [PubMed:24828040 ]
  13. Alakbarzade V, Hameed A, Quek DQ, Chioza BA, Baple EL, Cazenave-Gassiot A, Nguyen LN, Wenk MR, Ahmad AQ, Sreekantan-Nair A, Weedon MN, Rich P, Patton MA, Warner TT, Silver DL, Crosby AH: A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome. Nat Genet. 2015 Jul;47(7):814-7. doi: 10.1038/ng.3313. Epub 2015 May 25. [PubMed:26005865 ]