Gi alpha subunit

{{Short description|InterPro Family}} {{DISPLAYTITLE:G_i alpha subunit}} {{infobox protein | Name = G protein subunit alpha i1 | caption = | image = | width = | HGNCid = 4384 | Symbol = GNAI1 | AltSymbols = | EntrezGene = 2770 | OMIM = 139310 | RefSeq = NM_002069 | UniProt = P63096 | PDB = 3UMR | ECnumber = | Chromosome = 7 | Arm = q | Band = 21 | LocusSupplementaryData = -q22 }} {{infobox protein | Name = G protein subunit alpha i2 | caption = | image = | width = | HGNCid = 4385 | Symbol = GNAI2 | AltSymbols = | EntrezGene = 2771 | OMIM = 139360 | RefSeq = NM_002070 | UniProt = P04899 | PDB = | ECnumber = | Chromosome = 3 | Arm = p | Band = 21 | LocusSupplementaryData = }} {{infobox protein | Name = G protein subunit alpha i3 | caption = | image = | width = | HGNCid = 4387 | Symbol = GNAI3 | AltSymbols = | EntrezGene = 2773 | OMIM = 139370 | RefSeq = NM_006496 | UniProt = P08754 | PDB = 2ODE | ECnumber = | Chromosome = 1 | Arm = p | Band = 13 | LocusSupplementaryData = }} {{infobox protein | Name = G protein subunit alpha o1 | caption = | image = | width = | HGNCid = 4389 | Symbol = GNAO1 | AltSymbols = | EntrezGene = 2775 | OMIM = 139311 | RefSeq = NM_020988 | UniProt = P09471, | PDB = | ECnumber = | Chromosome = 16 | Arm = q | Band = 13 | LocusSupplementaryData = }} {{infobox protein | Name = G protein subunit alpha z | caption = | image = | width = | HGNCid = 4395 | Symbol = GNAZ | AltSymbols = | EntrezGene = 2781 | OMIM = 139160 | RefSeq = NM_002073 | UniProt = P19086 | PDB = | ECnumber = | Chromosome = 22 | Arm = q | Band = 11.22-11.23 | LocusSupplementaryData = }} {{infobox protein | Name = G protein subunit alpha t1, Transducin 1 (rod) | caption = | image = | width = | HGNCid = 4393 | Symbol = GNAT1 | AltSymbols = | EntrezGene = 2779 | OMIM = 139330 | RefSeq = NM_000172 | UniProt = P11488 | PDB = | ECnumber = | Chromosome = 3 | Arm = p | Band = 21.31 | LocusSupplementaryData = }} {{infobox protein | Name = G protein subunit alpha t2, Transducin 2 (cone) | caption = | image = | width = | HGNCid = 4394 | Symbol = GNAT2 | AltSymbols = | EntrezGene = 2780 | OMIM = 139340 | RefSeq = NM_005272 | UniProt = P19087 | PDB = | ECnumber = | Chromosome = 1 | Arm = p | Band = 13.3 | LocusSupplementaryData = }} {{infobox protein | Name = G protein subunit alpha t3, Gustducin | caption = | image = | width = | HGNCid = 22800 | Symbol = GNAT3 | AltSymbols = | EntrezGene = 346562 | OMIM = 139395 | RefSeq = NM_001102386 | UniProt = A8MTJ3 | PDB = | ECnumber = | Chromosome = 7 | Arm = q | Band = 21.11 | LocusSupplementaryData = }}

'''G_i protein alpha subunit''' is a family of heterotrimeric G protein alpha subunits. G_i proteins primarily inhibit the cAMP dependent pathway by inhibiting adenylyl cyclase activity, resulting in decreased activity of cAMP-dependent protein kinase (PKA). 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.

The G_i/o/z/t family is one of the four families of G protein alpha subunits, which are a core component of G-protein-coupled receptor signaling: one of the largest families of cell receptors. In particular, G_i/o/z/t proteins are important for the proper functioning of a diverse group of signaling molecules, from adrenaline to melatonin to calcium ions.

== 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

=== G_iα proteins === ==== G_i1α ==== <!--Gia1 redirects here--> G_i1α is encoded by the gene GNAI1. ==== G_i2α ==== <!--Gia2 redirects here--> G_i2α is encoded by the gene GNAI2. ==== G_i3α ==== <!--Gia3 redirects here--> G_i3α is encoded by the gene GNAI3.

=== G_oα protein === <!--Goa1 redirects here--> G_o1α is encoded by the gene GNAO1.

=== G_zα protein === G_zα is encoded by the gene GNAZ.

=== Transducin proteins === {{Main| Transducin}}

==== G_t1α ==== Transducin/G_t1α is encoded by the gene GNAT1.

==== G_t2α ==== Transducin 2/G_t2α is encoded by the gene GNAT2.

==== G_t3α ==== {{Main| Gustducin}} Gustducin/G_t3α is encoded by the gene GNAT3.

== Function == {{Main|Heterotrimeric G protein}} 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.<ref name="pmid3113327">{{cite journal | vauthors = Gilman AG | title = G proteins: transducers of receptor-generated signals | journal = Annual Review of Biochemistry | volume = 56 | pages = 615–49 | date = 1987 | pmid = 3113327 | doi = 10.1146/annurev.bi.56.070187.003151 }}</ref><ref name="pmid7579038">{{cite journal | vauthors = Rodbell M | title = Nobel Lecture. Signal transduction: evolution of an idea | journal = Bioscience Reports | volume = 15 | issue = 3 | pages = 117–33 | date = June 1995 | pmid = 7579038 | doi = 10.1007/bf01207453 | s2cid = 11025853 | pmc = 1519115 }}</ref> 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.<ref name="pmid3113327"/><ref name="pmid7579038"/> When not stimulated by a receptor, Gα is bound to GDP and to Gβγ to form the inactive G protein trimer.<ref name="pmid3113327"/><ref name="pmid7579038"/> 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.<ref name="pmid3113327"/><ref name="pmid7579038"/> 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).<ref name="pmid31043612">{{cite journal | vauthors = Kano H, Toyama Y, Imai S, Iwahashi Y, Mase Y, Yokogawa M, Osawa M, Shimada I | display-authors = 6 | title = Structural mechanism underlying G protein family-specific regulation of G protein-gated inwardly rectifying potassium channel | journal = Nature Communications | volume = 10 | issue = 1 | pages = 2008 | date = May 2019 | pmid = 31043612 | pmc = 6494913 | doi = 10.1038/s41467-019-10038-x | bibcode = 2019NatCo..10.2008K }}</ref> 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_iα and G_oα proteins, preventing their coupling to and activation by GPCRs, thus turning off G_i and G_o cell signaling pathways.<ref name="pmid3135154">{{cite journal | vauthors = Pfeuffer T, Helmreich EJ | title = Structural and functional relationships of guanosine triphosphate binding proteins | journal = Current Topics in Cellular Regulation | volume = 29 | pages = 129–216 | date = 1988 | pmid = 3135154 | doi = 10.1016/B978-0-12-152829-4.50006-9 | isbn = 9780121528294 }}</ref>

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.<ref name="pmid11313909">{{cite journal | vauthors = Ho MK, Wong YH | title = G(z) signaling: emerging divergence from G(i) signaling | journal = Oncogene | volume = 20 | issue = 13 | pages = 1615–25 | date = March 2001 | pmid = 11313909 | doi = 10.1038/sj.onc.1204190 | doi-access = free }}</ref>

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-HT₁ and 5-HT₅ serotonergic receptors * Acetylcholine M₂ & M₄ receptors * Adenosine A₁ & A₃ receptors * Adrenergic α_2A, α_2B, & α_2C receptors * Apelin receptors * Calcium-sensing receptor * Cannabinoid receptors (CB1 and CB2) * Chemokine CXCR4 receptor * Dopamine D₂, D₃ and D₄ receptors * GABA_B receptor * Glutamate mGluR2, mGluR3, mGluR4, mGluR6, mGluR7, & mGluR8 receptors * Histamine H₃ & H₄ receptors * Melatonin MT₁, MT₂, & MT₃ receptors * Hydroxycarboxylic acid receptors: HCA1, HCA2, & HCA3 * Opioid δ, κ, μ, & nociceptin receptors * Prostaglandin EP₁, EP₃, FP, & TP receptors * Short chain fatty acid receptors: FFAR2 & FFAR3 * Somatostatin sst1, sst2, sst3, sst4 & sst5 receptors * Trace amine-associated receptor 8

== 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 == {{Reflist}}

== External links == * {{MeshName|Gi+alpha+Subunit}}

{{Intracellular signaling peptides and proteins}} {{Acid anhydride hydrolases}} {{Enzymes}} {{Portal bar|Biology|border=no}}

* Category:Peripheral membrane proteins