Guanine nucleotide-binding protein G(i) subunit alpha-2

UniProt P04899 Organism Homo sapiens Gene GNAI2, GNAI2B EC 3.6.5.-

Also known as: GNAI2, GNAI2B

Function

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. Examples of interacting GPCRs include the adenosine A1 receptor/ADORA1, CNR1, and FPR2. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. 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 of ADCY1, ADCY5 and ADCY6, leading to decreased intracellular cAMP levels. Plays an important role in the activation of the transcription factor NFAT in endothelial cells to promote angiogenesis. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. Plays an essential role for neutrophil recruitment in the context of acute inflammation suggesting a linked function of both GNAI2 in neutrophils and endothelial cells for polymorphonuclear neutrophils transmigration (By similarity).

Classification

Family (Pfam): PF00503 G-alpha
InterPro: Gprotein_alpha_I, Gprotein_alpha_su, GproteinA_insert, P-loop_NTPase
Functional cluster: Small GTPases (Ras/Rab) & related

Experimental structures · PDB · 37

6D9H EM 3.60A
7F8V EM 3.30A
7LD3 EM 3.20A
7LD4 EM 3.30A
7RYC EM 2.90A
7WV9 EM 3.36A
7WVV EM 2.90A
7WVW EM 3.10A
7WVX EM 2.80A
7WVY EM 3.00A
7XXI EM 3.00A
7YJ4 EM 3.19A
… and 25 more

A predicted model is available from AlphaFold.

Gene Ontology · 41

Neighborhood · nearest proteins

Nearest neighbours of Guanine nucleotide-binding protein G(i) subunit alpha-2: 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

Adenosine receptor A1 1 shared papers
Guanine nucleotide-binding protein G(i) subunit alpha-3 6 shared papers
Cannabinoid receptor 1 1 shared papers
Netrin receptor UNC5B 1 shared papers
N-formyl peptide receptor 2 1 shared papers
D(2) dopamine receptor 1 shared papers
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 1 shared papers
Guanine nucleotide-binding protein G(i) subunit alpha-1 5 shared papers
Guanine nucleotide-binding protein G(i) subunit alpha-3 2 shared papers
C-X-C chemokine receptor type 2 1 shared papers
C-X-C chemokine receptor type 1 1 shared papers
Guanine nucleotide-binding protein G(i) subunit alpha-2 2 shared papers

Literature · 25 cited papers

G protein subunit alpha i2's pivotal role in angiogenesis. Theranostics · 2024
Molecular mechanism of allosteric modulation for the cannabinoid receptor CB1. Nat. Chem. Biol. · 2022
Structural basis of FPR2 in recognition of Abeta42 and neuroprotection by humanin. Nat. Commun. · 2022
Structure of the adenosine-bound human adenosine A1 receptor-Gi complex. Nature · 2018
A Mutation in the G-Protein Gene GNB2 Causes Familial Sinus Node and Atrioventricular Conduction Dysfunction. Circ. Res. · 2017
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
Multifunctional reagents for quantitative proteome-wide analysis of protein modification in human cells and dynamic profiling of protein lipidation during vertebrate development. Angew. Chem. Int. Ed. · 2015
Global profiling of co- and post-translationally N-myristoylated proteomes in human cells. Nat. Commun. · 2014
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
A bacterial toxin catalyzing tyrosine glycosylation of Rho and deamidation of Gq and Gi proteins. Nat. Struct. Mol. Biol. · 2013
Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features. Mol. Cell. Proteomics · 2012
… and 13 more in the literature graph

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