HGNC Approved Gene Symbol: RGS3
Cytogenetic location: 9q32 Genomic coordinates (GRCh38): 9:113,444,730-113,597,738 (from NCBI)
The region of homology between the yeast SST2 gene product, which regulates G protein signaling, and the C. elegans EGL-10 protein defines the 'regulator of G protein signaling' (RGS) domain (see 602517). Proteins containing the RGS domain constitute a family of molecules that appear to function as negative regulators of heterotrimeric G protein signaling. Several mammalian RGS proteins function as GTPase-activating proteins for G protein alpha-subunits; see RGS1 (600323) and RGS2 (600861). Based on Southern blotting, Druey et al. (1996) estimated that there are at least 15 human RGS family members.
Druey et al. (1996) searched for homologs of yeast SST2 and cloned an RGS3 cDNA from a human B-cell cDNA library. It encodes a predicted 519-amino acid protein that has a coiled-coil domain and 4 PEST sequences. By Northern blotting, RGS3 was expressed as 2 major transcripts in all tissues tested. RGS3 partially complemented a yeast SST2 mutation.
Chatterjee et al. (1997) studied RGS3, the largest member of the RGS family then identified. They found that the RGS domain, conserved among all RGS proteins, is encoded by 3 exons, while the unique N-terminal domain of RGS3 is encoded by a single exon.
By screening a mouse embryonic cDNA library using the yeast 2-hybrid system with the cytoplasmic domain of ephrin-B2 (EFNB2; 600527) as bait, Lu et al. (2001) isolated cDNAs encoding a cytoplasmic protein, which they designated Pdz-Rgs3. Pdz-Rgs3 binds ephrin-B2 through a PDZ domain, and it has an RGS domain.
Mouse Pdz-Rgs3 can mediate signaling from the ephrin-B cytoplasmic tail. Lu et al. (2001) showed that Sdf1 (600835), a chemokine with a G protein-coupled receptor, and Bdnf (113505) are chemoattractants for cerebellar granule cells, and that Sdf1 chemoattraction is selectively inhibited by soluble ephrin-B receptor (see 602757). This inhibition could be blocked by a truncated Pdz-Rgs3 protein lacking the RGS domain.
Chatterjee et al. (1997) found that the coding region of the human RGS3 gene spans 14.7 kb and contains 6 exons; the 5-prime untranslated region spans 3.2 kb and contains 2 exons. Comparison of the locations of the intron-exon boundaries of the human RGS3 gene to those of the human RGS2 gene revealed a remarkable similarity. Using 5-prime-RACE analysis, they mapped the transcription start site 517 bp upstream of the translation start site. Many potential regulatory elements were identified in the 5-prime flanking region.
By radiation hybrid mapping, Chatterjee et al. (1997) assigned the RGS3 gene to chromosome 9q31-q33.
Chatterjee, T. K., Eapen, A., Kanis, A. B., Fisher, R. A. Genomic organization, 5-prime-flanking region, and chromosomal localization of the human RGS3 gene. Genomics 45: 429-433, 1997. [PubMed: 9344672] [Full Text: https://doi.org/10.1006/geno.1997.4929]
Druey, K. M., Blumer, K. J., Kang, V. H., Kehrl, J. H. Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family. Nature 379: 742-746, 1996. [PubMed: 8602223] [Full Text: https://doi.org/10.1038/379742a0]
Lu, Q., Sun, E. E., Klein, R. S., Flanagan, J. G. Ephrin-B reverse signaling is mediated by a novel PDZ-RGS protein and selectively inhibits G protein-coupled chemoattraction. Cell 105: 69-79, 2001. [PubMed: 11301003] [Full Text: https://doi.org/10.1016/s0092-8674(01)00297-5]