Sphingosine 1-phosphate receptor 4

Function

G protein-coupled receptor highly expressed in immune cells, where it regulates immune response and cytokine production. Functions as a receptor for the lysosphingolipid sphingosine-1-phosphate (S1P). Upon S1P binding, promotes regulatory T-cell differentiation and enhances fatty acid oxidation, through activation of the NRF2/PPARA signaling pathway (By similarity). Modulates also M1 macrophage activation through interaction with FPR2 and the JNK signaling, contributing to the inflammatory response (By similarity). In addition, facilitates early neutrophil mobilization and vascular activation during inflammation, promoting lymphocyte recruitment to draining lymph nodes and supporting the development of germinal centers for an effective adaptive immune response (By similarity).

Classification

Family (Pfam)

PF00001 7tm_1

InterPro

EDG6_rcpt, GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, S1P_rcpt

Functional cluster

Membrane Channels & Lipid-Anchored Proteins

Experimental structures · PDB · 1

• 2DCO NMR

A predicted model is available from AlphaFold.

Gene Ontology · 10

• GO:0005737 cytoplasm
• GO:0005739 mitochondrion
• GO:0005886 plasma membrane
• GO:0098793 presynapse
• GO:0004930 G protein-coupled receptor activity
• GO:0008289 lipid binding
• GO:0038036 sphingosine-1-phosphate receptor activity
• GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
• GO:0007186 G protein-coupled receptor signaling pathway
• GO:0003376 sphingosine-1-phosphate receptor signaling pathway

Drugs targeting this protein · 4

• AMISELIMOD HYDROCHLORIDE modulator
• ETRASIMOD ARGININE modulator
• FINGOLIMOD LAURYL SULFATE binding agent
• FINGOLIMOD HYDROCHLORIDE agonist

Related proteins · sequence + function similarity

• Sphingosine 1-phosphate receptor 4 0.96
• Sphingosine 1-phosphate receptor 5 0.92
• Sphingosine 1-phosphate receptor 5 0.92
• Sphingosine 1-phosphate receptor 5 0.92
• Sphingosine 1-phosphate receptor 5 0.91
• Lysophosphatidic acid receptor 2 0.88
• Lysophosphatidic acid receptor 2 0.88
• G protein-coupled receptor 6 0.87
• Probable G protein-coupled receptor 27 0.86
• Probable G protein-coupled receptor 27 0.86
• Probable G protein-coupled receptor 27 0.86
• G protein-coupled bile acid receptor 1 0.86

Co-cited proteins · studied together in the literature

• Sphingosine 1-phosphate receptor 4 1 shared papers

Literature · 5 cited papers

• Peptide design and structural characterization of a GPCR loop mimetic. Biopolymers · 2007
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Sphingosine-1-phosphate is a ligand for the G protein-coupled receptor EDG-6. Blood · 2000
• Edg-6 as a putative sphingosine 1-phosphate receptor coupling to Ca(2+) signaling pathway. Biochem. Biophys. Res. Commun. · 2000
• EDG6, a novel G protein-coupled receptor related to receptors for bioactive lysophospholipids, is specifically expressed in lymphoid tissue. Genomics · 1998