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
iα.
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
i1α, G
i2α, and G
i3α
* G
o protein: G
oα (in mouse there is alternative splicing to generate G
o1α and G
o2α)
* G
z protein: G
zα
*
Transducins (G
t proteins): G
t1α, G
t2α, G
t3α
Giα proteins
Gi1α
G
i1α is encoded by the gene
GNAI1.
Gi2α
G
i2α is encoded by the gene
GNAI2.
Gi3α
G
i3α 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
G
o1α is encoded by the gene
GNAO1.
Gzα protein
G
zα is encoded by the gene
GNAZ.
Transducin proteins
Gt1α
Transducin/G
t1α is encoded by the gene
GNAT1.
Gt2α
Transducin 2/G
t2α 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 ...
/G
t3α 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
iα, 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.
G
i proteins primarily inhibit the
cAMP dependent pathway by inhibiting
adenylyl cyclase activity, decreasing the production of
cAMP from
ATP
ATP may refer to:
Companies and organizations
* Association of Tennis Professionals, men's professional tennis governing body
* American Technical Publishers, employee-owned publishing company
* ', a Danish pension
* Armenia Tree Project, non ...
, 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
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 G
iα and G
oα 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
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 G
t1, 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 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:
*
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