MFSD2B Membrane Protein Introduction

Introduction of MFSD2B

MFSD2B is an orphan Major Facilitator Superfamily (MFS) transporter with an estimated 12 transmembrane domains. It is located in the plasma membrane and in the inner membrane of the cell. MFSD2B protein is present in the bone marrow and spleen but not in the kidneys and liver. In the blood, MFSD2B protein is significantly expressed in RBC and platelets. MFSD2B is present in the RBC ghost membrane and is sensitive to some trypsin digestion, indicating its plasma membrane localization. Besides, MFSD2B expression is increased in young RBCs, bone marrow, and spleen in 5-fluorouracil (5FU)-treated mice. The MFSD2B transcript is mainly present in the erythroid lineage, producing red blood cells and platelets, but not in the lymphoid lineage. Mouse MFSD2B is also a member of the Major Facilitator Superfamily (MFS) of transporters with 494 amino acid residues. The MFSD2B cDNA has been reported in various mammals. Human MFSD2B showed 83% identity and 96% similarity to mouse MFSD2B. The molecular weight of both human and mouse MFSD2B are detected to be approximate 43 kDa in size.

Basic Information of MFSD2B
Protein Name	Major facilitator superfamily domain-containing protein 2B
Gene Name	MFSD2B
Aliases	hMfsd2b
Organism	Homo sapiens (Human)
UniProt ID	A6NFX1
Transmembrane Times	12
Length (aa)	504
Sequence	MAAPPAPAAKGSPQPEPHAPEPGPGSAKRGREDSRAGRLSFCTKVCYGIGGVPNQIASSATAFYLQLFLLDIAQIPAAQVSLVLFGGKVSGAAADPVAGFFINRSQRTGSGRLMPWVLGCTPFIALAYFFLWFLPPFTSLRGLWYTTFYCLFQALATFFQVPYTALTMLLTPCPRERDSATAYRMTVEMAGTLMGATVHGLIVSGAHRPHRCEATATPGPVTVSPNAAHLYCIAAAVVVVTYPVCISLLCLGVKERPDPSAPASGPGLSFLAGLSLTTRHPPYLKLVISFLFISAAVQVEQSYLVLFCTHASQLHDHVQGLVLTVLVSAVLSTPLWEWVLQRFGKKTSAFGIFAMVPFAILLAAVPTAPVAYVVAFVSGVSIAVSLLLPWSMLPDVVDDFQLQHRHGPGLETIFYSSYVFFTKLSGACALGISTLSLEFSGYKAGVCKQAEEVVVTLKVLIGAVPTCMILAGLCILMVGSTPKTPSRDASSRLSLRRRTSYSLA

Function of MFSD2B Membrane Protein

Sphingosine-1-phosphate (S1P), a potent signaling lipid secreted by red blood cells and platelets, plays numerous biologically significant roles. The Major facilitator superfamily transporter 2b (MFSD2B) is essential for S1P export from red blood cells and platelets. The S1P export conducted by MFSD2B is not driven by the Na⁺ or K⁺ ion gradient, although the alanine substitution of Asp85 alters the S1P transport of MFSD2B. Comprehensive lipidomics analysis showed significant and specific accumulation of S1P species in Mfsd2b knockout red blood cells and platelets compared to wild-type controls. Similarly, biochemical assays in knocked out red blood cells, platelets, and cell lines with over-expressed human and mouse Mfsd2b proteins demonstrated that MFSD2B can actively output S1P. Plasma S1P levels in knockout mice are significantly reduced by 42-54% compared to wild type, indicating that the MFSD2B pathway contributes to approximately half of the plasma S1P pool. The reduction in plasma S1P in knockout mice is not sufficient to cause vascular leakage, but it can make mice more sensitive to anaphylactic shock.

Fig.1 Plasma S1P is mainly contributed by three major cell types: red blood cells, platelets, and endothelial cells. (Ashok, 2017)

Application of MFSD2B Membrane Protein in Literature

Kobayashi N., et al. MFSD2B is a sphingosine 1-phosphate transporter in erythroid cells. Scientific Reports. 2018, 8(1): 4969. PubMed ID: 29563527

This article finds that knockdown of MFSD2B in MEDEP-E14 cells can reduce the S1P export of the cells, indicating that MFSD2B is a novel S1P transporter in erythroid cells.
Vu T.M., et al. Mfsd2b is essential for the sphingosine-1-phosphate export in erythrocytes and platelet. Nature. 2017, 550(7677): 524-528. PubMed ID: 29045386

This paper demonstrates that S1P secretion by Mfsd2b is critical for red blood cell morphology.
Ashok K and Neha A. Mfsd2b, a Novel Sphingosine-1-Phosphate Transporter: Implication in Cancer Therapeutics. Journal of Clinical & Experimental Oncology. 2018, 7: 2.

This article shows that targeting S1P production in a tumor and the host would help reduce both growth and metastasis.

MFSD2B Preparation Options

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Reference

Ashok K and Neha A. (2018). Mfsd2b, a Novel Sphingosine-1-Phosphate Transporter: Implication in Cancer Therapeutics. Journal of Clinical & Experimental Oncology. 7: 2.

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