Guanine nucleotide-binding protein G(i) subunit alpha-1

UniProt P63096 Organism Homo sapiens Gene GNAI1 EC 3.6.5.-

Also known as: GNAI1

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. 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. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. Required for normal cytokinesis during mitosis. Required for cortical dynein-dynactin complex recruitment during metaphase.

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 · 556

1KJY X-ray 2.70A
1Y3A X-ray 2.50A
2G83 X-ray 2.80A
2GTP X-ray 2.55A
2IK8 X-ray 2.71A
2OM2 X-ray 2.20A
2XNS X-ray 3.41A
3ONW X-ray 2.38A
3QE0 X-ray 3.00A
3QI2 X-ray 2.80A
3UMR X-ray 2.24A
3UMS X-ray 2.60A
… and 544 more

A predicted model is available from AlphaFold.

Gene Ontology · 39

Disease associations

neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities MONDO:0859243

Neighborhood · nearest proteins

Nearest neighbours of Guanine nucleotide-binding protein G(i) subunit alpha-1: 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

Regulator of G protein signaling 14 4 shared papers
G protein-coupled receptor 15 1 shared papers
D(2) dopamine receptor 2 shared papers
N-formyl peptide receptor 1 2 shared papers
Guanine nucleotide-binding protein G(i) subunit alpha-3 8 shared papers
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 12 shared papers
Regulator of G protein signaling 14 2 shared papers
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 11 shared papers
5-hydroxytryptamine receptor 1A 5 shared papers
N-formyl peptide receptor 2 2 shared papers
Regulator of G protein signaling 10 2 shared papers
Guanine nucleotide-binding protein G(q) subunit alpha 3 shared papers

Literature · 48 cited papers

Metabolic signaling of ceramides through the FPR2 receptor inhibits adipocyte thermogenesis. Science · 2025
Molecular recognition of the atypical chemokine-like peptide GPR15L by its cognate receptor GPR15. Cell Discov. · 2024
Bitter taste TAS2R14 activation by intracellular tastants and cholesterol. Nature · 2024
Bitter taste receptor activation by cholesterol and an intracellular tastant. Nature · 2024
Flexible scaffold-based cheminformatics approach for polypharmacological drug design. Cell · 2024
Structural and signaling mechanisms of TAAR1 enabled preferential agonist design. Cell · 2023
Recognition of methamphetamine and other amines by trace amine receptor TAAR1. Nature · 2023
Ligand recognition and G-protein coupling of trace amine receptor TAAR1. Nature · 2023
Structural basis for recognition of N-formyl peptides as pathogen-associated molecular patterns. Nat. Commun. · 2022
Structural insights into the ligand binding and Gi coupling of serotonin receptor 5-HT5A. Cell Discov. · 2022
Activation and allosteric regulation of the orphan GPR88-Gi1 signaling complex. Nat. Commun. · 2022
Molecular recognition of formylpeptides and diverse agonists by the formylpeptide receptors FPR1 and FPR2. Nat. Commun. · 2022
… and 36 more in the literature graph

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