Recombinant Human Guanine nucleotide-binding protein G (i) subunit alpha-3 (GNAI3)

Function

Heterotrimeric guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (By similarity). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:18434541, PubMed:19478087, PubMed:8774883). Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (PubMed:19478087). Stimulates the activity of receptor-regulated K(+) channels (PubMed:2535845). The active GTP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division (PubMed:17635935). The active GTP-bound form activates the calcium permeant TRPC5 ion channels (PubMed:37137991)

Subcellular Location

Cytoplasm; Cell membrane (Lipid-anchor); Cytoplasm, cytoskeleton, microtubule organizing center, centrosome

Disease Association

Auriculocondylar syndrome 1 (ARCND1) : An autosomal dominant form of auriculocondylar syndrome, a craniofacial malformation syndrome characterized by variable mandibular anomalies, including mild to severe micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark (question-mark ear). Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia. Glossoptosis, masticatory abnormalities, orthodontic problems, and malocclusion occur in a majority of affected subjects. [The disease is caused by variants affecting the gene represented in this entry]

Subunit

Heterotrimeric G proteins are composed of 3 units; alpha, beta and gamma. The alpha subunit contains the guanine nucleotide binding site (By similarity). GTP binding causes dissociation of the heterotrimer, liberating the individual subunits so that they can interact with downstream effector proteins. Forms a complex with CCDC88A/GIV and EGFR which leads to enhanced EGFR signaling and triggering of cell migration; ligand stimulation is required for recruitment of GNAI3 to the complex (PubMed:20462955). Interacts (inactive GDP-bound form) with CCDC88A/GIV (via GBA motif); the interaction leads to activation of GNAI3 (PubMed:19211784, PubMed:20462955). Interacts (inactive GDP-bound form) with CCDC88C/DAPLE (via GBA motif); the interaction leads to activation of GNAI3 (PubMed:26126266). Interacts (inactive GDP-bound form) with NUCB1 (via GBA motif) and NUCB2 (via GBA motif); the interaction leads to activation of GNAI3 (By similarity). Interacts (inactive GDP-bound form) with PLCD4 (via GBA motif); the interaction leads to activation of GNAI3 (PubMed:30194280). Interacts with INSR; the interaction is probably mediated by CCDC88A/GIV (PubMed:25187647). Interacts with GPSM1 (By similarity). Interacts (GDP-bound form) with GPSM2 (via GoLoco domains) (PubMed:22952234). Does not interact with RGS2 (PubMed:19478087). Interacts with RGS8 and RGS10; this strongly enhances the intrinsic GTPase activity (PubMed:18434541, PubMed:8774883). Interacts with RGS16; this strongly enhances the intrinsic GTPase activity (PubMed:19478087). Interacts with RGS12 (By similarity). Interacts (via active GTP- or inactive GDP-bound form) with RGS14 (By similarity). Interacts (via active GTP-bound form) with TRPC5 (via ANK repeats) in a homotetrameric ion channel; the interaction is direct and activates the channel activity (PubMed:37137991)

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• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)