Guanine nucleotide-binding protein G(i) subunit alpha-3

UniProt P08754 Organism Homo sapiens Gene GNAI3

Also known as: GNAI3

Function

Heterotrimeric guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (By similarity). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins. Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels. Stimulates the activity of receptor-regulated K(+) channels. The active GTP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division. The active GTP-bound form activates the calcium permeant TRPC5 ion channels.

Classification

Family (Pfam): PF00503 G-alpha
InterPro: Gprotein_alpha_I, Gprotein_alpha_su, GproteinA_insert, P-loop_NTPase
Functional cluster: Ribosome-Recycling & Clp Protease Factors

Experimental structures · PDB · 26

2IHB X-ray 2.71A
2ODE X-ray 1.90A
2V4Z X-ray 2.80A
4G5O X-ray 2.90A
4G5R X-ray 3.48A
4G5S X-ray 3.62A
7E9H EM 4.00A
7KH0 EM 2.80A
7RA3 EM 3.24A
7RGP EM 2.90A
7T10 EM 2.50A
7T11 EM 2.70A
… and 14 more

A predicted model is available from AlphaFold.

Gene Ontology · 23

Disease associations

auriculocondylar syndrome 1 MONDO:0011234

Neighborhood · nearest proteins

Nearest neighbours of Guanine nucleotide-binding protein G(i) subunit alpha-3: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 3 shared papers
Guanine nucleotide-binding protein G(i) subunit alpha-2 6 shared papers
Girdin 5 shared papers
Regulator of G protein signaling 2 2 shared papers
Guanine nucleotide-binding protein G(i) subunit alpha-3 5 shared papers
Guanine nucleotide-binding protein G(i) subunit alpha-1 8 shared papers
Short transient receptor potential channel 5 1 shared papers
Regulator of G protein signaling 10 2 shared papers
Protein Daple 2 shared papers
G protein-signaling modulator 2 1 shared papers
Guanine nucleotide-binding protein G(i) subunit alpha-2 3 shared papers
Guanine nucleotide-binding protein G(i) subunit alpha-1 3 shared papers

Literature · 30 cited papers

Molecular architecture of the Galphai-bound TRPC5 ion channel. Nat. Commun. · 2023
Further delineation of auriculocondylar syndrome based on 14 novel cases and reassessment of 25 published cases. Hum. Mutat. · 2022
Prenatal diagnosis of auriculocondylar syndrome with a novel missense variant of GNAI3: a case report. BMC Pregnancy Childbirth · 2021
A biochemical and genetic discovery pipeline identifies PLCdelta4b as a nonreceptor activator of heterotrimeric G-proteins. J. Biol. Chem. · 2018
Membrane recruitment of the non-receptor protein GIV/Girdin (Galpha-interacting, Vesicle-associated Protein/Girdin) is sufficient for activating heterotrimeric G protein signaling. J. Biol. Chem. · 2016
Daple is a novel non-receptor GEF required for trimeric G protein activation in Wnt signaling. Elife · 2015
N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
Global profiling of co- and post-translationally N-myristoylated proteomes in human cells. Nat. Commun. · 2014
Structural basis for activation of trimeric Gi proteins by multiple growth factor receptors via GIV/Girdin. Mol. Biol. Cell · 2014
A bacterial toxin catalyzing tyrosine glycosylation of Rho and deamidation of Gq and Gi proteins. Nat. Struct. Mol. Biol. · 2013
Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome. J. Med. Genet. · 2013
Crystal structures of the scaffolding protein LGN reveal the general mechanism by which GoLoco binding motifs inhibit the release of GDP from Galphai. J. Biol. Chem. · 2012
… and 18 more in the literature graph

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