8ex5

Structural highlights

Disease

SPNS2_HUMAN The disease is caused by variants affecting the gene represented in this entry.

Function

SPNS2_HUMAN Lipid transporter that specifically mediates export of sphingosine-1-phosphate (sphing-4-enine 1-phosphate, S1P) and sphinganine-1-phosphate in the lymph, thereby playing a role in lymphocyte trafficking (PubMed:19074308, PubMed:21084291, PubMed:23180825). S1P is a bioactive signaling molecule that regulates many physiological processes important for the development and for the immune system (PubMed:19074308, PubMed:23180825). Regulates levels of S1P and the S1P gradient that exists between the high circulating concentrations of S1P and low tissue levels that control lymphocyte trafficking (PubMed:19074308, PubMed:23180825). Required for the egress of T-cells from lymph nodes during an immune response by mediating S1P secretion, which generates a gradient that enables activated T-cells to access lymph (By similarity). Also required for the egress of immature B-cells from the bone marrow (By similarity). In contrast, not involved in S1P release from red blood cells (By similarity). Involved in auditory function (PubMed:30973865). S1P release in the inner ear is required for maintenance of the endocochlear potential in the cochlea (By similarity). In addition to export, also able to mediate S1P import (By similarity).[UniProtKB:Q91VM4]^{[1] [2] [3] [4]}

References

1. ↑ Kawahara A, Nishi T, Hisano Y, Fukui H, Yamaguchi A, Mochizuki N. The sphingolipid transporter spns2 functions in migration of zebrafish myocardial precursors. Science. 2009 Jan 23;323(5913):524-7. PMID:19074308 doi:10.1126/science.1167449
2. ↑ Hisano Y, Kobayashi N, Kawahara A, Yamaguchi A, Nishi T. The sphingosine 1-phosphate transporter, SPNS2, functions as a transporter of the phosphorylated form of the immunomodulating agent FTY720. J Biol Chem. 2011 Jan 21;286(3):1758-66. PMID:21084291 doi:10.1074/jbc.M110.171116
3. ↑ Nagahashi M, Kim EY, Yamada A, Ramachandran S, Allegood JC, Hait NC, Maceyka M, Milstien S, Takabe K, Spiegel S. Spns2, a transporter of phosphorylated sphingoid bases, regulates their blood and lymph levels, and the lymphatic network. FASEB J. 2013 Mar;27(3):1001-11. PMID:23180825 doi:10.1096/fj.12-219618
4. ↑ Ingham NJ, Pearson SA, Vancollie VE, Rook V, Lewis MA, Chen J, Buniello A, Martelletti E, Preite L, Lam CC, Weiss FD, Powis Z, Suwannarat P, Lelliott CJ, Dawson SJ, White JK, Steel KP. Mouse screen reveals multiple new genes underlying mouse and human hearing loss. PLoS Biol. 2019 Apr 11;17(4):e3000194. PMID:30973865 doi:10.1371/journal.pbio.3000194