Guanine nucleotide-binding protein G(o) subunit alpha

UniProt P09471 Organism Homo sapiens Gene GNAO1 EC 3.6.5.-

Also known as: GNAO1

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 (By similarity). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (By similarity). Signaling is mediated via effector proteins, such as adenylate cyclase (By similarity). Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (By similarity).

Classification

Family (Pfam): PF00503 G-alpha
InterPro: Gprotein_alpha_I, Gprotein_alpha_su, GproteinA_insert, P-loop_NTPase
Functional cluster: GroEL/Cpn60 Chaperonins

Experimental structures · PDB · 82

6FUF X-ray 3.12A
6G79 EM 3.78A
6K41 EM 2.90A
6OIK EM 3.60A
6WWZ EM 3.34A
7D76 EM 3.10A
7D77 EM 2.90A
7EJ0 EM 3.20A
7EJ8 EM 3.00A
7EJA EM 3.60A
7EJK EM 3.40A
7QVM EM 3.25A
… and 70 more

A predicted model is available from AlphaFold.

Gene Ontology · 25

Disease associations

developmental and epileptic encephalopathy, 17 MONDO:0014199
neurodevelopmental disorder with involuntary movements MONDO:0060491

Neighborhood · nearest proteins

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

Guanine nucleotide-binding protein G(o) subunit alpha 1 shared papers
Adhesion G protein-coupled receptor G3 1 shared papers
Regulator of G protein signaling 19 1 shared papers
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 3 shared papers
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 1 shared papers
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 2 shared papers
5-hydroxytryptamine receptor 1B 1 shared papers
D(2) dopamine receptor 1 shared papers
Excitatory amino acid transporter 2 1 shared papers
Dynamin-1 1 shared papers
UDP-N-acetylglucosamine transferase subunit ALG13 1 shared papers
Voltage-dependent P/Q-type calcium channel subunit alpha-1A 1 shared papers

Literature · 18 cited papers

A neurodevelopmental disorder mutation locks G proteins in the transitory pre-activated state. Nat. Commun. · 2024
Pediatric Encephalopathy: Clinical, Biochemical and Cellular Insights into the Role of Gln52 of GNAO1 and GNAI1 for the Dominant Disease. Cells · 2021
Structures of the glucocorticoid-bound adhesion receptor GPR97-Go complex. Nature · 2021
Cryo-EM structure of the serotonin 5-HT1B receptor coupled to heterotrimeric Go. Nature · 2018
Efficient strategy for the molecular diagnosis of intractable early-onset epilepsy using targeted gene sequencing. BMC Med. Genomics · 2018
GNAO1 encephalopathy: Broadening the phenotype and evaluating treatment and outcome. Neurol. Genet. · 2017
Diagnostic targeted resequencing in 349 patients with drug-resistant pediatric epilepsies identifies causative mutations in 30 different genes. Hum. Mutat. · 2017
Recurrent GNAO1 mutations associated with developmental delay and a movement disorder. J. Child Neurol. · 2016
De novo mutations in SLC1A2 and CACNA1A are important causes of epileptic encephalopathies. Am. J. Hum. Genet. · 2016
Clinical course of six children with GNAO1 mutations causing a severe and distinctive movement disorder. Pediatr. Neurol. · 2016
Clinical whole-exome sequencing reveals a novel missense pathogenic variant of GNAO1 in a patient with infantile-onset epilepsy. Clin. Chim. Acta · 2015
Progressive movement disorder in brothers carrying a GNAO1 mutation responsive to deep brain stimulation. J. Child Neurol. · 2016
… and 6 more in the literature graph

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