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Gi protein alpha subunit is a family of heterotrimeric G protein alpha subunits. This family is also commonly called the Gi/o (Gi /Go ) family or Gi/o/z/t family to include closely related family members. G alpha subunits may be referred to as Gi alpha, Gαi, or Giα.


Family members

There are four distinct subtypes of alpha subunits in the Gi/o/z/t alpha subunit family that define four families of heterotrimeric G proteins: * Gi proteins: Gi1α, Gi2α, and Gi3α * Go protein: Goα (in mouse there is alternative splicing to generate Go1α and Go2α) * Gz protein: Gzα * Transducins (Gt proteins): Gt1α, Gt2α, Gt3α


Giα proteins


Gi1α

Gi1α is encoded by the gene GNAI1.


Gi2α

Gi2α is encoded by the gene GNAI2.


Gi3α

Gi3α is encoded by the gene
GNAI3 Guanine nucleotide-binding protein G(k) subunit alpha is a protein that in humans is encoded by the ''GNAI3'' gene. Interactions GNAI3 has been shown to interact with: * RGS10 * RGS12, * RGS14, * RGS16, * RGS18, * RGS19, * RGS5, * RIC8A, ...
.


Goα protein

Go1α is encoded by the gene GNAO1.


Gzα protein

Gzα is encoded by the gene GNAZ.


Transducin proteins


Gt1α

Transducin/Gt1α is encoded by the gene GNAT1.


Gt2α

Transducin 2/Gt2α is encoded by the gene GNAT2.


Gt3α

Gustducin Gustducin is a G protein associated with taste and the gustatory system, found in some taste receptor cells. Research on the discovery and isolation of gustducin is recent. It is known to play a large role in the transduction of bitter, sweet a ...
/Gt3α is encoded by the gene GNAT3.


Function

The general function of Gi/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 Giα, 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 A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...
), 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. Gi proteins primarily inhibit the cAMP dependent pathway by inhibiting adenylyl cyclase activity, decreasing the production of cAMP from
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, which, in turn, results in decreased activity of cAMP-dependent protein kinase. Therefore, the ultimate effect of Gi is the inhibition of the cAMP-dependent protein kinase. The Gβγ liberated by activation of Gi and Go proteins is particularly able to activate downstream signaling to effectors such as G protein-coupled inwardly-rectifying potassium channels (GIRKs). Gi and Go 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 Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...
residue in Giα and Goα proteins, preventing their coupling to and activation by GPCRs, thus turning off Gi and Go cell signaling pathways. Gz proteins also can link GPCRs to inhibition of adenylyl cyclase, but Gz is distinct from Gi/Go by being insensitive to inhibition by pertussis toxin. Gt proteins function in sensory transduction. The Transducins Gt1 and Gt2 serve to transduce signals from G protein-coupled receptors that receive light during vision.
Rhodopsin Rhodopsin, also known as visual purple, is a protein encoded by the RHO gene and a G-protein-coupled receptor (GPCR). It is the opsin of the rod cells in the retina and a light-sensitive receptor protein that triggers visual phototransduction ...
in dim light
night vision Night vision is the ability to see in low-light conditions, either naturally with scotopic vision or through a night-vision device. Night vision requires both sufficient spectral range and sufficient intensity range. Humans have poor night vi ...
in retinal
rod cell Rod cells are photoreceptor cells in the retina of the eye that can function in lower light better than the other type of visual photoreceptor, cone cells. Rods are usually found concentrated at the outer edges of the retina and are used in per ...
s couples to Gt1, and color photopsins in color vision in retinal
cone cell Cone cells, or cones, are photoreceptor cells in the retinas of vertebrate eyes including the human eye. They respond differently to light of different wavelengths, and the combination of their responses is responsible for color vision. Cone ...
s couple to Gt2, respectively. Gt3/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 Gi/o subunits: *
Acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
M2 & M4 receptors *
Adenosine Adenosine ( symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building ...
A1 & A3 receptors * Adrenergic α2A, α2B, & α2C receptors * Apelin receptors * Calcium-sensing receptor * Cannabinoid receptors ( CB1 and CB2) * Chemokine CXCR4 receptor *
Dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
D2, D3, D4 * GABAB receptor *
Glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
mGlu2, mGlu3, mGlu4, mGlu6, mGlu7, & mGlu8 receptors * Histamine H3 & H4 receptors *
Melatonin Melatonin is a natural product found in plants and animals. It is primarily known in animals as a hormone released by the pineal gland in the brain at night, and has long been associated with control of the sleep–wake cycle. In vertebrates ...
MT1, MT2, & MT3 receptors *
Hydroxycarboxylic acid receptors The hydroxycarboxylic acid receptor (abbreviated HCA receptor and HCAR) family includes the following human proteins: * Hydroxycarboxylic acid receptor 1 (HCA1, formerly known as GPR81) * Hydroxycarboxylic acid receptor 2 (HCA2, formerly known as n ...
: HCA1, HCA2, & HCA3 * Opioid δ, κ, μ, &
nociceptin Nociceptin/orphanin FQ (N/OFQ), a 17-amino acid neuropeptide, is the endogenous ligand for the nociceptin receptor (NOP, ORL-1). Nociceptin acts as a potent anti-analgesic, effectively counteracting the effect of pain-relievers; it's activation i ...
receptors *
Prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...
EP1, EP3, FP, & TP receptors *
Serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
5-HT1 & 5-HT5 receptors * Short chain fatty acid receptors: FFAR2 & FFAR3 *
Somatostatin Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-couple ...
sst1, sst2, sst3, sst4 & sst5 receptors *
Trace amine-associated receptor 8 Trace amine-associated receptor 8 is a protein that in humans is encoded by the ''TAAR8'' gene. In humans, TAAR8 is the only trace amine-associated receptor that is known to be Gi/o-coupled. In humans, molecular modelling and docking experiments ...


See also

* Second messenger system * G protein-coupled receptor * Heterotrimeric G protein * Adenylyl cyclase * Protein kinase A * Gs alpha subunit * Gq alpha subunit * G12/G13 alpha subunits * Retina * Taste


References


External links

* {{Portal bar, Biology, border=no * Peripheral membrane proteins