Gi2

Gi2, short for G protein subunit alpha-2, is a member of the Gi/o family of heterotrimeric G proteins. It is encoded by the GNAI2 gene in humans and functions as the alpha subunit that cycles between inactive GDP-bound and active GTP-bound states. In resting cells, Gi2 forms a heterotrimer with Gβ and Gγ subunits anchored to the plasma membrane.

Activation begins when a G protein-coupled receptor engages Gi2. The receptor promotes exchange of GDP for GTP on Gi2, after which the alpha subunit dissociates from the Gβγ dimer. Activated Gi2 inhibits adenylyl cyclase, leading to reduced intracellular cAMP levels and downstream changes in protein kinase A activity. The Gβγ complex, released upon activation, can regulate other effectors such as certain phospholipase C-β isoforms and inward-rectifier potassium channels, influencing calcium signaling and other pathways.

Gi2 is widely expressed in human tissues, with notable levels in the brain, heart, and peripheral tissues. Its signaling contributes to diverse physiological processes, including neurotransmission, cardiac function, insulin release, and vascular tone. The activity of Gi2 is regulated by receptors and by regulator of G protein signaling (RGS) proteins that accelerate GTP hydrolysis, returning Gi2 to its inactive GDP-bound state.

Clinical and research notes: alterations in Gi2 signaling have been investigated in various contexts, including cancer cell behavior and immune signaling, reflecting the pathway’s tissue-specific roles. Structurally, Gi2 belongs to the GTPase superfamily and contains a conserved GTP-binding domain and regions that mediate interaction with GPCRs and effector proteins. See also: GNAI1, GNAI3, G protein-coupled receptors.