S1PR4 Membrane Protein Introduction

Introduction of S1PR4

Sphingosine 1-phosphate receptor 4 (S1PR4), also known as S1P receptor or Edg-6, is encoded by the S1PR4 gene. It belongs to the G-protein-coupled receptor (GPCR) family which has been extensively studied during the past few decades because it offers numerous possibilities for therapeutic applications. Sphingosine-1-phosphate (SPP) is a metabolite of complex sphingolipids that acts as both a second messenger and as a high-affinity ligand for cell surface receptors. SPP receptors specifically bind SPP or the related lipid. S1PR4 is expressed in lymphoid and hematopoietic tissue as well as the lung. Recent studies show that SPP binds specifically to S1PR4 and activates the mitogen-activated protein kinase (MAPK) signal transduction pathway.

Basic Information of S1PR4
Protein Name	Sphingosine 1-phosphate receptor 4
Gene Name	S1PR4
Aliases	S1P receptor 4, S1P4, S1P receptor, Edg-6
Organism	Homo sapiens (Human)
UniProt ID	O95977
Transmembrane Times	7
Length (aa)	384
Sequence	MNATGTPVAPESCQQLAAGGHSRLIVLHYNHSGRLAGRGGPEDGGLGALRGLSVAASCLVVLENLLVLAAITSH MRSRRWVYYCLVNITLSDLLTGAAYLANVLLSGARTFRLAPAQWFLREGLLFTALAASTFSLLFTAGERFATMV RPVAESGATKTSRVYGFIGLCWLLAALLGMLPLLGWNCLCAFDRCSSLLPLYSKRYILFCLVIFAGVLATIMGL YGAIFRLVQASGQKAPRPAARRKARRLLKTVLMILLAFLVCWGPLFGLLLADVFGSNLWAQEYLRGMDWILALA VLNSAVNPIIYSFRSREVCRAVLSFLCCGCLRLGMRGPGDCLARAVEAHSGASTTDSSLRPRDS FRGSRSLSFRMREPLSSISSVRSI

Function of S1PR4 Membrane Protein

The activity of S1PR4 is mediated by G proteins. S1PR4 is specifically expressed in fetal and adult lymphoid and hematopoietic tissue as well as in lung. And it is lower expressed in adult thymus, lymph node, bone marrow, appendix as well as in fetal liver. The expression pattern of S1PR4 is extremely conserved in human and mouse. The human S1PR4 was mapped to chromosome 19p13.3 at the D19S120 marker. Due to the lymphoid-specific expression pattern of S1PR4 and the powerful identity to the phospholipid-binding EDG receptor family, researchers considered that S1PR4 may also serve as a receptor for a lipid-derived ligand. Moreover, it has been reported that S1PR4 may act an important role in lymphocyte cell signaling.

Fig.1 S1P-S1PR1 axis and lymphocyte retention in inflamed tissue. (Aoki, 2016)

Application of S1PR4 Membrane Protein in Literature

Yamazaki Y., et al. Edg-6 as a putative sphingosine 1-phosphate receptor coupling to Ca(2+) signaling pathway. Biochem Biophys Res Commun. 2000, 268(2): 583-9. PubMed ID: 10679247

Author’s team concludes that S1PR4 is one of S1P or lysosphingolipid receptors that couple to phospholipase C-Ca(2+) system through pertussis toxin-sensitive G-proteins.
Van Brooklyn J.R., et al. Sphingosine-1-phosphate is a ligand for the G protein-coupled receptor EDG-6. Blood. 2000, 95(8): 2624-9. PubMed ID: 10753843

This article indicates that S1PR4 is a high-affinity receptor for SPP, which couples to a G(i/o) protein, resulting in the activation of growth-related signaling pathways.
Graler M.H., et al. EDG6, a novel G-protein-coupled receptor related to receptors for bioactive lysophospholipids, is specifically expressed in lymphoid tissue. Genomics. 1998, 53(2): 164-9. PubMed ID: 9790765

Authors in this group propose that EDG6 may also act as a receptor for a lipid-derived ligand. Because of the known mitogenic and chemotactic activity of bioactive lipids, they believe that S1PR4 may serve a key role in lymphocyte cell signaling.
Holdworth G., et al. A single amino acid determines preference between phospholipids and reveals length restriction for activation of the S1P4 receptor. BMC biochem. 2004, 5:12. PubMed ID: 15298705

This article shows glutamic acid in the third transmembrane domain of the S1P receptors is a general selectivity switch regulating response to S1P over the closely related phospholipids, LPA.
Golfier S., et al. Shaping of terminal megakaryocyte differentiation and proplatelet development by sphingosine-1-phosphate receptor S1P4. FASEB J. 2010, 24(12): 4701-10. PubMed ID: 2068610

This article indicates that S1PR4 is involved in shaping the terminal differentiation of megakaryocytes.

S1PR4 Preparation Options

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Reference

Aoki M., et al., (2016). Sphingosine-1-phosphate signaling in immune cells and inflammation: roles and therapeutic potential. Mediators of inflammation. 2016.

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