Alternative titles; symbols
HGNC Approved Gene Symbol: S1PR4
Cytogenetic location: 19p13.3 Genomic coordinates (GRCh38) : 19:3,178,769-3,180,332 (from NCBI)
The lysolipid mediators lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) signal cells through a set of G protein-coupled receptors (GPCRs) known as EDG receptors. Some EDG receptors (e.g., EDG1, 601974) are S1P receptors; others (e.g., EDG2, 602282) are LPA receptors (summary by Chun et al., 2002).
Chun et al. (2002) proposed a nomenclature scheme for the LPA and S1P receptors that is consistent with the International Union of Pharmacology (IUP) guidelines. According to these guidelines, a receptor is to be named with the abbreviation of the natural agonist with the highest potency, followed by a subscripted arabic number. Thus they suggested that the designation EDG6 should be changed to S1P4.
By PCR with degenerate oligonucleotides derived from regions conserved among GPCRs, Graler et al. (1998) cloned differentiated dendritic cell cDNAs encoding EDG6. The predicted 384-amino acid EDG6 protein has 7 transmembrane domains. The EDG6 protein shares 82% sequence identity with mouse Edg6, 46% identity with human EDG3 (601965), 44% identity with human EDG1, 39% identity with human EDG4 (605110), and 37% identity with human EDG2. Northern blot analysis indicated that EDG6 is expressed as a 1.7-kb transcript in fetal and adult lymphoid and hematopoietic tissues, lung, and Burkitt lymphoma cell lines. By Northern blot analysis, Contos et al. (2002) determined that mouse Gna15 (139314) and Edg6, which they designated Slp4, were coexpressed at the same relative levels in all tissues examined, with the highest expression in adult spleen and lung. They hypothesized that, due to their tandem chromosomal orientation as well as coexpression, the 2 genes may be under the control of the same enhancer elements, and the proteins may couple in vivo.
Graler et al. (1998) noted that the 3-prime end of their EDG6 cDNA is identical to a short sequence encompassing the dinucleotide repeat polymorphism D19S120 (GenBank X65642), which was assigned to 19p13.3 by Jedlicka et al. (1994). By PCR of human genomic DNA using a gene-specific primer to EDG6 and a primer to the D19S120 amplicon, Graler et al. (1998) localized the EDG6 gene to 19p13.3.
Contos et al. (2002) determined that the EDG6 gene is intronless. In the mouse, the Edg6 gene contains 2 exons and the first exon is untranslated. The promoters contain no TATA box elements. Contos et al. (2002) determined that in both the mouse and human genomes, the GNA11 (139313), GNA15, and EDG6 genes are arranged in tandem. The human cluster occupies 80 kb and the mouse cluster occupies 50 kb.
Chun, J., Goetzl, E. J., Hla, T., Igarashi, Y., Lynch, K. R., Moolenaar, W., Pyne, S., Tigyi, G. International Union of Pharmacology. XXXIV. Lysophospholipid receptor nomenclature. Pharm. Rev. 54: 265-269, 2002. [PubMed: 12037142] [Full Text: https://doi.org/10.1124/pr.54.2.265]
Contos, J. J., Ye, X., Sah, V. P., Chun, J. Tandem genomic arrangement of a G protein (Gna15) and G protein-coupled receptor (s1p(4)/lp(C1)/Edg6) gene. FEBS Lett. 531: 99-102, 2002. [PubMed: 12401211] [Full Text: https://doi.org/10.1016/s0014-5793(02)03409-9]
Graler, M. H., Bernhardt, G., Lipp, M. EDG6, a novel G-protein-coupled receptor related to receptors for bioactive lysophospholipids, is specifically expressed in lymphoid tissue. Genomics 53: 164-169, 1998. [PubMed: 9790765] [Full Text: https://doi.org/10.1006/geno.1998.5491]
Jedlicka, A. E., Taylor, E. W., Meyers, D. A., Liu, Z., Levitt, R. C. Localization of the highly polymorphic locus D19S120 to 19p13.3 by linkage. Cytogenet. Cell. Genet. 65: 140 only, 1994. [PubMed: 8404068] [Full Text: https://doi.org/10.1159/000133621]