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2.A.2.3.8
Major Facilitator Superfamily Domain containing 2A, MFSD2A (543aas, 12 TMSs). Plays a role in thermogenesis via β-adrenergic signaling. Takes up Tunicamycin (TM), a mixture of related species of nucleotide sugar analogs fatty-acylated with alkyl chains of varying lengths and degrees of unsaturation, produced by several Streptomyces species (Bassik and Kampmann, 2011; Reiling et al., 2011).  It is a sodium-dependent lysophosphatidylcholine (LPC) transporter expressed at the blood-brain barrier endothelium. It is the primary route for import of docosahexaenoic acid and other long-chain fatty acids into foetal and adult brain, and is essential for mouse and human brain growth and function (Quek et al. 2016). In addition to a conserved sodium-binding site, three structural features were identified: A phosphate headgroup binding site, a hydrophobic cleft to accommodate a hydrophobic hydrocarbon tail, and three sets of ionic locks that stabilize the outward-open conformation. Ligand docking studies and biochemical assays identified Lys436 as a key residue for transport. It forms a salt bridge with the negative charge on the phosphate headgroup. Mfsd2a transports structurally related acylcarnitines but not a lysolipid without a negative charge, demonstrating the necessity of a negative charged headgroup interaction with Lys436 for transport. These findings support a novel transport mechanism by which LPCs are flipped within the transporter cavity by pivoting about Lys436 leading to net transport from the outer to the inner leaflet of the plasma membrane (Quek et al. 2016).

Accession Number:Q8NA29
Protein Name:Major facilitator superfamily domain-containing protein 2A
Length:543
Molecular Weight:60170.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:10
Location1 / Topology2 / Orientation3: Endoplasmic reticulum membrane1 / Multi-pass membrane protein2
Substrate Lysophosphatidylcholine, Docosahexaenoic acid, Tunicamycin

Cross database links:

Genevestigator: Q8NA29
HEGENOM: HBG445483
Entrez Gene ID: 84879   
Pfam: PF07690   
KEGG: hsa:84879   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0055085 P:transmembrane transport

References (8)

[1] “The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.”  Clark H.F.et.al.   12975309
[2] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[3] “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.”  Yamada S.et.al.   15221005
[4] “Large-scale cDNA transfection screening for genes related to cancer development and progression.”  Wan D.et.al.   15498874
[5] “Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries.”  Otsuki T.et.al.   16303743
[6] “The DNA sequence and biological annotation of human chromosome 1.”  Gregory S.G.et.al.   16710414
[7] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[8] “Mfsd2a encodes a novel major facilitator superfamily domain-containing protein highly induced in brown adipose tissue during fasting and adaptive thermogenesis.”  Angers M.et.al.   18694395

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FASTA formatted sequence
1:	MAKGEGAESG SAAGLLPTSI LQSTERPAQV KKEPKKKKQQ LSVCNKLCYA LGGAPYQVTG 
61:	CALGFFLQIY LLDVAQKDEE VVFCFSSFQV GPFSASIILF VGRAWDAITD PLVGLCISKS 
121:	PWTCLGRLMP WIIFSTPLAV IAYFLIWFVP DFPHGQTYWY LLFYCLFETM VTCFHVPYSA 
181:	LTMFISTEQT ERDSATAYRM TVEVLGTVLG TAIQGQIVGQ ADTPCFQDLN SSTVASQSAN 
241:	HTHGTTSHRE TQKAYLLAAG VIVCIYIICA VILILGVREQ REPYEAQQSE PIAYFRGLRL 
301:	VMSHGPYIKL ITGFLFTSLA FMLVEGNFVL FCTYTLGFRN EFQNLLLAIM LSATLTIPIW 
361:	QWFLTRFGKK TAVYVGISSA VPFLILVALM ESNLIITYAV AVAAGISVAA AFLLPWSMLP 
421:	DVIDDFHLKQ PHFHGTEPIF FSFYVFFTKF ASGVSLGIST LSLDFAGYQT RGCSQPERVK 
481:	FTLNMLVTMA PIVLILLGLL LFKMYPIDEE RRRQNKKALQ ALRDEASSSG CSETDSTELA 
541:	SIL