G_i protein alpha subunit is a family of

heterotrimeric G protein Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPases) are membrane-associated G proteins that form a Heteromer, heterotrimeric complex. The biggest no ...

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 *

Transducin Transducin (Gt) is a protein naturally expressed in vertebrate retina rods and cones and it is very important in vertebrate phototransduction. It is a type of heterotrimeric G-protein with different α subunits in rod and cone photoreceptors. ...

s (G_t proteins): G_t1α, G_t2α, G_t3α

G_iα proteins

G_i1α

G_i1α is encoded by the gene GNAI1.

G_i2α

G_i2α is encoded by the gene GNAI2.

G_i3α

G_i3α is encoded by the gene GNAI3.

G_oα protein

G_o1α is encoded by the gene GNAO1.

G_zα protein

G_zα is encoded by the gene GNAZ.

Transducin proteins

G_t1α

/G_t1α is encoded by the gene GNAT1.

G_t2α

Transducin 2/G_t2α is encoded by the gene GNAT2.

G_t3α

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 ...

/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

, 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 Gross domestic product (GDP) is a monetary measure of the total market value of all the final goods and services produced and rendered in a specific time period by a country or countries. GDP is often used to measure the economic performance o ...

and to Gβγ to form the inactive G protein trimer. When the receptor binds an activating ligand outside the cell (such as a

hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

), the activated receptor acts as a

guanine nucleotide exchange factor Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structu ...

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 Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :A ...

activity, decreasing the production of

cAMP Camp may refer to: Areas of confinement, imprisonment, or for execution * Concentration camp, an internment camp for political prisoners or politically targeted demographics, such as members of national or minority ethnic groups * Extermination ...

from ATP, which, in turn, results in decreased activity of

cAMP-dependent protein kinase In cell biology, protein kinase A (PKA) is a family of serine-threonine kinases whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (). PKA has several functions in the cell, ...

. 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 Pertussis toxin (PT) is a protein-based AB5-type exotoxin produced by the bacterium '' Bordetella pertussis'', which causes whooping cough. PT is involved in the colonization of the respiratory tract and the establishment of infection. ...

, produced by '' Bordetella pertussis'', the infectious agent in

whooping cough Whooping cough ( or ), also known as pertussis or the 100-day cough, is a highly contagious, Vaccine-preventable diseases, vaccine-preventable Pathogenic bacteria, bacterial disease. Initial symptoms are usually similar to those of the common c ...

. Pertussis toxin is an ADP-ribosylase enzyme that adds an

ADP-ribose Adenosine diphosphate ribose (ADPR) is an ester molecule formed into chains by the enzyme poly ADP ribose polymerase. ADPR is created from cyclic ADP-ribose (cADPR) by the CD38 enzyme using nicotinamide adenine dinucleotide (NAD+) as a cofactor. ...

moiety to a particular

cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...

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 Light, visible light, or visible radiation is electromagnetic radiation that can be visual perception, perceived by the human eye. Visible light spans the visible spectrum and is usually defined as having wavelengths in the range of 400– ...

during

vision Vision, Visions, or The Vision may refer to: Perception Optical perception * Visual perception, the sense of sight * Visual system, the physical mechanism of eyesight * Computer vision, a field dealing with how computers can be made to gain und ...

Rhodopsin Rhodopsin, also known as visual purple, is a protein encoded by the ''RHO'' gene and a G-protein-coupled receptor (GPCR). It is a light-sensitive receptor protein that triggers visual phototransduction in rod cells. Rhodopsin mediates dim ...

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 v ...

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 ...

s couples to G_t1, and color

photopsin Vertebrate visual opsins are a subclass of ciliary opsins and mediate vision in vertebrates. They include the opsins in human rod and cone cells. They are often abbreviated to ''opsin'', as they were the first opsins discovered and are still t ...

s in color vision in retinal

cone cell Cone cells or cones are photoreceptor cells in the retina of the vertebrate eye. Cones are active in daylight conditions and enable photopic vision, as opposed to rod cells, which are active in dim light and enable scotopic vision. Most v ...

s couple to G_t2, respectively. G_t3/Gustducin subunits transduce signals in the sense of

taste The gustatory system or sense of taste is the sensory system that is partially responsible for the perception of taste. Taste is the perception stimulated when a substance in the mouth biochemistry, reacts chemically with taste receptor cells l ...

(gustation) in

taste bud Taste buds are clusters of taste receptor cells, which are also known as gustatory cells. The taste receptors are located around the small structures known as papillae found on the upper surface of the tongue, soft palate, upper esophagus, ...

s by coupling to G protein-coupled receptors activated by sweet or bitter substances.

Receptors

The following

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...

s couple to G_i/o subunits: * 5-HT₁ and 5-HT₅ serotonergic receptors *

Acetylcholine Acetylcholine (ACh) is an organic compound 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. Par ...

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 build ...

A₁ & A₃ receptors *

Adrenergic Adrenergic means "working on adrenaline (epinephrine) or noradrenaline (norepinephrine)" (or on their receptors). When not further qualified, it is usually used in the sense of enhancing or mimicking the effects of epinephrine and norepinephrine ...

α_2A, α_2B, & α_2C receptors *

Apelin Apelin (also known as APLN) is a peptide that in humans is encoded by the ''APLN'' gene. Apelin is one of two endogenous ligands for the G-protein-coupled APJ receptor that is expressed at the surface of some cell types. It is widely expressed ...

receptors *

Calcium-sensing receptor The calcium-sensing receptor (CaSR) is a Class C G-protein coupled receptor which senses extracellular levels of calcium ions. It is primarily expressed in the parathyroid gland, the renal tubules of the kidney, pancreatic islets and the br ...

Cannabinoid receptor Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system of vertebrates a class of cell membrane receptors in the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cann ...

s ( CB1 and CB2) *

Chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addit ...

CXCR4 C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the ''CXCR4'' gene. The protein is a CXC chemokine receptor. Function CXCR-4 is an alpha- chemo ...

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 chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

D₂, D₃ and D₄ receptors * GABA_B receptor *

Glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

mGluR2, mGluR3, mGluR4,

mGluR6 Glutamate receptor, metabotropic 6, also known as GRM6 or mGluR6, is a protein which in humans is encoded by the ''GRM6'' gene. Function L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ion ...

, mGluR7, & mGluR8 receptors *

Histamine Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Discovered in 19 ...

H₃ & H₄ receptors *

Melatonin Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cow ...

MT₁, MT₂, & MT₃ receptors * Hydroxycarboxylic acid receptors:

HCA1 Hydroxycarboxylic acid receptor 1 (HCA1), formerly known as G protein-coupled receptor 81 (GPR81), is a protein that in humans is encoded by the ''HCAR1'' gene. HCA1, like the other hydroxycarboxylic acid receptors HCA2 and HCA3, is a G protei ...

HCA2 Hydroxycarboxylic acid receptor 2 (HCA2), also known as GPR109A and niacin receptor 1 (NIACR1), is a protein which in humans is encoded (its formation is directed) by the ''HCAR2'' gene and in rodents by the ''Hcar2'' gene. The human ''HCAR2'' gen ...

, & HCA3 *

Opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...

δ, κ, μ, & nociceptin receptors *

Prostaglandin Prostaglandins (PG) are a group of physiology, physiologically active lipid compounds called eicosanoids that have diverse hormone-like effects in animals. Prostaglandins have been found in almost every Tissue (biology), tissue in humans and ot ...

EP₁, EP₃, FP, & TP receptors * Short chain fatty acid receptors:

FFAR2 Free fatty acid receptor 2 (FFAR2), also known as G-protein coupled receptor 43 (GPR43), is a Rhodopsin-like receptor, rhodopsin-like G-protein coupled receptor (GPCR) encoded by the ''FFAR2'' gene. In humans, the ''FFAR2'' gene is located on the ...

FFAR3 Free fatty acid receptor 3 (FFAR3, also termed GPR41) protein is a G protein coupled receptor (i.e., GPR or GPCR) that in humans is encoded by the ''FFAR3'' gene (i.e., ''GPR41'' gene). GPRs reside on cell surfaces, bind specific signaling molecu ...

Somatostatin Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by #Nomenclature, several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G ...

sst1, sst2, sst3, sst4 & sst5 receptors * Trace amine-associated receptor 8

References

External links

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

Family members

Giα proteins

Gi1α

Gi2α

Gi3α

Goα protein

Gzα protein