Regulates G protein-coupled receptor signaling cascades, including signaling via muscarinic acetylcholine receptor CHRM2 and dopamine receptor DRD2 (By similarity). Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Binds selectively to GNAZ and GNAI2 subunits, accelerates their GTPase activity and regulates their signaling activities. Negatively regulates mu-opioid receptor-mediated activation of the G-proteins. Interacts with GNAI1 and GNAQ (By similarity). Interacts with GNAZ and GNAI2 (PubMed:15827571, PubMed:16900103). Interacts with OPRM1 (PubMed:15827571). Forms a complex with mu-opioid receptors and G(alpha)z/i2 subunits, including GNAZ and GNAI2; the formation of this complex results in mu-opioid receptor desensitization (PubMed:15827571). Interacts with HINT1 (PubMed:31088288). Detected in brain (at protein level) (PubMed:15827571, PubMed:16900103). Highly expressed in the hypothalamus, periaqueductal gray matter, and pons-medulla. Lower levels in the thalamus, cortex and spinal cord. Weak expression in the striatum and cerebellum. N- and O-glycosylated in synapsomal membranes. Serine phosphorylated in synapsomal membranes. Sumoylated with SUMO1 and SUM02 in synaptosomes. The sumoylated forms act as a scaffold for sequestering mu-opioid receptor-activated G(alpha) subunits (PubMed:16900103). Desumoylated by HINT1 (PubMed:31088288).