The R12 family consisting of RGS10, 12 and 14. RGS12 and 14 are large proteins with additional domains that can participate in protein-protein interactions and other functions. In contrast, RGS10 is a small protein consisting of the RGS domain and small N- and C-termini, similar to members of the R4 family. However, the sequence homology the RGS10 RGS domain clearly places it in the R12 family [2]. The Gα_i/o-Loco (GoLoco) motif in RGS12 and 14 has GDI activity (for Guanine nucleotide Dissociation Inhibitor) towards Gα_i1, Gα_i2 and Gα_i3 [1,4]. Through this activity RGS12 and RGS14 can inhibit G protein signaling both by accelerating GTP hydrolysis and by preventing G protein activation. Splice variants of RGS12 and RGS14 also contain membrane targeting and protein-protein interaction domains [3,5-6].

1. Kimple RJ, De Vries L, Tronchère H, Behe CI, Morris RA, Gist Farquhar M, Siderovski DP. (2001) RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with guanine nucleotide dissociation inhibitor Activity. J Biol Chem, 276 (31): 29275-81. [PMID:11387333]

2. Lee JK, Tansey MG. (2015) Physiology of RGS10 in Neurons and Immune Cells. Prog Mol Biol Transl Sci, 133: 153-67. [PMID:26123306]

3. Schiff ML, Siderovski DP, Jordan JD, Brothers G, Snow B, De Vries L, Ortiz DF, Diversé-Pierluissi M. (2000) Tyrosine-kinase-dependent recruitment of RGS12 to the N-type calcium channel. Nature, 408 (6813): 723-7. [PMID:11130074]

4. Siderovski DP, Willard FS. (2005) The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits. Int J Biol Sci, 1 (2): 51-66. [PMID:15951850]

5. Snow BE, Brothers GM, Siderovski DP. (2002) Molecular cloning of regulators of G-protein signaling family members and characterization of binding specificity of RGS12 PDZ domain. Meth Enzymol, 344: 740-61. [PMID:11771424]

6. Snow BE, Hall RA, Krumins AM, Brothers GM, Bouchard D, Brothers CA, Chung S, Mangion J, Gilman AG, Lefkowitz RJ et al.. (1998) GTPase activating specificity of RGS12 and binding specificity of an alternatively spliced PDZ (PSD-95/Dlg/ZO-1) domain. J Biol Chem, 273 (28): 17749-55. [PMID:9651375]