Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
Also known as: GNAS, GNAS1, GSP
Function
Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs). 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 involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP. Functions downstream of beta-adrenergic receptors. Stimulates the Ras signaling pathway via RAPGEF2.
Classification
- Family (Pfam)
- PF00503 G-alpha
- InterPro
- Gprotein_alpha_S, Gprotein_alpha_su, GproteinA_insert, P-loop_NTPase
- Functional cluster
- Small GTPases (Ras/Rab) & related
Experimental structures · PDB · 460
- 5G53 X-ray 3.40A
- 5UZ7 EM 4.10A
- 5VAI EM 4.10A
- 6AU6 X-ray 1.70A
- 6B3J EM 3.30A
- 6E3Y EM 3.30A
- 6E67 X-ray 3.70A
- 6EG8 X-ray 2.80A
- 6GDG EM 4.11A
- 6LI3 EM 3.32A
- 6LMK EM 3.70A
- 6LPB EM 3.90A
- … and 448 more
A predicted model is available from AlphaFold.
Gene Ontology · 41
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0070062 extracellular exosome
- GO:0005834 heterotrimeric G-protein complex
- GO:0016020 membrane
- GO:0005886 plasma membrane
- GO:0032588 trans-Golgi network membrane
- GO:0010856 adenylate cyclase activator activity
- GO:0031748 D1 dopamine receptor binding
- GO:0003925 G protein activity
- GO:0031683 G-protein beta/gamma-subunit complex binding
- GO:0005525 GTP binding
- GO:0003924 GTPase activity
- GO:0046872 metal ion binding
- GO:0007190 activation of adenylate cyclase activity
- GO:0071880 adenylate cyclase-activating adrenergic receptor signaling pathway
- GO:0007191 adenylate cyclase-activating dopamine receptor signaling pathway
- GO:0038184 adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway
- GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
- GO:0007192 adenylate cyclase-activating serotonin receptor signaling pathway
- GO:0060348 bone development
- GO:0071468 cellular response to acidic pH
- GO:0071870 cellular response to catecholamine stimulus
- GO:0071377 cellular response to glucagon stimulus
- GO:0071380 cellular response to prostaglandin E stimulus
- GO:0050890 cognition
- GO:0048589 developmental growth
- GO:0007186 G protein-coupled receptor signaling pathway
- GO:0060789 hair follicle placode formation
- GO:0001678 intracellular glucose homeostasis
- GO:0046907 intracellular transport
- GO:0002862 negative regulation of inflammatory response to antigenic stimulus
- GO:0070527 platelet aggregation
- GO:0120162 positive regulation of cold-induced thermogenesis
- GO:0032024 positive regulation of insulin secretion
- GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus
- GO:0014819 regulation of skeletal muscle contraction
- GO:0003091 renal water homeostasis
- GO:0034695 response to prostaglandin E
- GO:0007608 sensory perception of smell
- GO:0097700 vascular endothelial cell response to laminar fluid shear stress
Disease associations
- pseudohypoparathyroidism type 1A MONDO:0007078
- progressive osseous heteroplasia MONDO:0008153
- McCune-Albright syndrome MONDO:0018919
- ACTH-independent macronodular adrenal hyperplasia 1 MONDO:0020735
- pseudohypoparathyroidism type 1B MONDO:0011301
- pseudohypoparathyroidism type 1C MONDO:0012911
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 1.00
- Guanine nucleotide-binding protein G(s) subunit alpha 1.00
- Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 1.00
- Guanine nucleotide-binding protein G(s) subunit alpha 1.00
- Guanine nucleotide-binding protein G(s) subunit alpha 1.00
- Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 1.00
- Guanine nucleotide-binding protein G(s) subunit alpha 0.98
- Guanine nucleotide-binding protein G(olf) subunit alpha 0.97
- Guanine nucleotide-binding protein G(s) subunit alpha 0.96
- Guanine nucleotide-binding protein G(olf) subunit alpha 0.96
- Guanine nucleotide-binding protein G(olf) subunit alpha 0.96
- Guanine nucleotide-binding protein G(s) subunit alpha 0.96
Co-cited proteins · studied together in the literature
- Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas 9 shared papers
- Protein ALEX 8 shared papers
- Glucagon receptor 2 shared papers
- Neuroendocrine secretory protein 55 8 shared papers
- G protein-coupled receptor 3 2 shared papers
- Histamine H2 receptor 1 shared papers
- Adenylate cyclase type 5 1 shared papers
- G protein-coupled receptor 12 1 shared papers
- G protein-coupled receptor 6 1 shared papers
- Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 9 shared papers
- Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 9 shared papers
- Guanine nucleotide-binding protein G(olf) subunit alpha 2 shared papers
Literature · 69 cited papers
- Structural insights into the high basal activity and inverse agonism of the orphan receptor GPR6 implicated in Parkinson's disease. Sci. Signal. · 2024
- Bitter taste TAS2R14 activation by intracellular tastants and cholesterol. Nature · 2024
- Molecular Determinant Underlying Selective Coupling of Primary G-Protein by Class A GPCRs. Adv. Sci. · 2024
- Lipid-Dependent Activation of the Orphan G Protein-Coupled Receptor, GPR3. Biochemistry · 2024
- Molecular features of the ligand-free GLP-1R, GCGR and GIPR in complex with Gs proteins. Cell Discov. · 2024
- Structural and functional characterization of the endogenous agonist for orphan receptor GPR3. Cell Res. · 2024
- 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 insight into the selective agonist ST1936 binding of serotonin receptor 5-HT6. Biochem. Biophys. Res. Commun. · 2023
- Structures of Ric-8B in complex with Galpha protein folding clients reveal isoform specificity mechanisms. Structure · 2023
- Structural insight into the constitutive activity of human orphan receptor GPR12. Sci. Bull. · 2023
- Structures of the ADGRG2-Gs complex in apo and ligand-bound forms. Nat. Chem. Biol. · 2022
- … and 57 more in the literature graph