# Gi alpha subunit

G$_i$ protein alpha subunit is a family of heterotrimeric G protein alpha subunits. This family is also commonly called the G$_{i/o}$ (G$_i$/G$_o$) family or G$_{i/o/z/t}$ family to include closely related family members. G alpha subunits may be referred to as G$_i$ alpha, G$_{αi}$, or G$_i$α.

## Family members

There are four distinct subtypes of alpha subunits in the G$_{i/o/z/t}$ alpha subunit family that define four families of heterotrimeric G proteins:
* G$_i$ proteins: G$_{i1}$α, G$_{i2}$α, and G$_{i3}$α
* G$_o$ protein: G$_o$α (in mouse there is alternative splicing to generate G$_{o1}$α and G$_{o2}$α)
* G$_z$ protein: G$_z$α
* Transducins (G$_t$ proteins): G$_{t1}$α, G$_{t2}$α, G$_{t3}$α

### G$_i$α proteins
#### G$_{i1}$α

G$_{i1}$α is encoded by the gene GNAI1.

#### G$_{i2}$α

G$_{i2}$α is encoded by the gene GNAI2.

#### G$_{i3}$α

G$_{i3}$α is encoded by the gene GNAI3.

### G$_o$α protein

G$_{o1}$α is encoded by the gene GNAO1.

### G$_z$α protein

G$_z$α is encoded by the gene GNAZ.

### Transducin proteins
#### G$_{t1}$α

Transducin/G$_{t1}$α is encoded by the gene GNAT1.

#### G$_{t2}$α

Transducin 2/G$_{t2}$α is encoded by the gene GNAT2.

#### G$_{t3}$α

Gustducin/G$_{t3}$α is encoded by the gene GNAT3.

## Function

The general function of G$_{i/o/z/t}$ is to activate intracellular signaling pathways in response to activation of cell surface G protein-coupled receptors (GPCRs). GPCRs function as part of a three-component system of receptor-transducer-effector. The transducer in this system is a heterotrimeric G protein, composed of three subunits: a Gα protein such as G$_i$α, and a complex of two tightly linked proteins called Gβ and Gγ in a Gβγ complex. When not stimulated by a receptor, Gα is bound to GDP and to Gβγ to form the inactive G protein trimer. When the receptor binds an activating ligand outside the cell (such as a hormone or neurotransmitter), the activated receptor acts as a guanine nucleotide exchange factor to promote GDP release from and GTP binding to Gα, which drives dissociation of GTP-bound Gα from Gβγ. GTP-bound Gα and Gβγ are then freed to activate their respective downstream signaling enzymes.
G$_i$ proteins primarily inhibit the cAMP dependent pathway by inhibiting adenylyl cyclase activity, decreasing the production of cAMP from ATP, which, in turn, results in decreased activity of cAMP-dependent protein kinase. Therefore, the ultimate effect of G$_i$ is the inhibition of the cAMP-dependent protein kinase. The Gβγ liberated by activation of G$_i$ and G$_o$ proteins is particularly able to activate downstream signaling to effectors such as G protein-coupled inwardly-rectifying potassium channels (GIRKs). G$_i$ and G$_o$ proteins are substrates for pertussis toxin, produced by Bordetella pertussis, the infectious agent in whooping cough. Pertussis toxin is an ADP-ribosylase enzyme that adds an ADP-ribose moiety to a particular cysteine residue in G$_i$α and G$_o$α proteins, preventing their coupling to and activation by GPCRs, thus turning off G$_i$ and G$_o$ cell signaling pathways.
G$_z$ proteins also can link GPCRs to inhibition of adenylyl cyclase, but G$_z$ is distinct from G$_i$/G$_o$ by being insensitive to inhibition by pertussis toxin.
G$_t$ proteins function in sensory transduction. The Transducins G$_{t1}$ and G$_{t2}$ serve to transduce signals from G protein-coupled receptors that receive light during vision. Rhodopsin in dim light night vision in retinal rod cells couples to G$_{t1}$, and color photopsins in color vision in retinal cone cells couple to G$_{t2}$, respectively. G$_{t3}$/Gustducin subunits transduce signals in the sense of taste (gustation) in taste buds by coupling to G protein-coupled receptors activated by sweet or bitter substances.

## Receptors

The following G protein-coupled receptors couple to G$_{i/o}$ subunits:
* 5-HT$_1$ and 5-HT$_5$ serotonergic receptors
* Acetylcholine M$_2$ & M$_4$ receptors
* Adenosine A$_1$ & A$_3$ receptors
* Adrenergic α$_{2A}$, α$_{2B}$, & α$_{2C}$ receptors
* Apelin receptors
* Calcium-sensing receptor
* Cannabinoid receptors (CB1 and CB2)
* Chemokine CXCR4 receptor
* Dopamine D$_2$, D$_3$ and D$_4$ receptors
* GABA$_B$ receptor
* Glutamate mGluR2, mGluR3, mGluR4, mGluR6, mGluR7, & mGluR8 receptors
* Histamine H$_3$ & H$_4$ receptors
* Melatonin MT$_1$, MT$_2$, & MT$_3$ receptors
* Hydroxycarboxylic acid receptors: HCA1, HCA2, & HCA3
* Opioid δ, κ, μ, & nociceptin receptors
* Prostaglandin EP$_1$, EP$_3$, FP, & TP receptors
* Short chain fatty acid receptors: FFAR2 & FFAR3
* Somatostatin sst1, sst2, sst3, sst4 & sst5 receptors
* Trace amine-associated receptor 8