G_s alpha subunit

The G_s alpha subunit (G_αs, G_sα) is a subunit of the heterotrimeric G protein G_s that stimulates the cAMP-dependent pathway by activating adenylyl cyclase. G_sα is a GTPase that functions as a cellular signaling protein. G_sα is the founding member of one of the four families of heterotrimeric G proteins, defined by the alpha subunits they contain: the G_αs family, G_αi/G_αo family, G_αq family, and G_α12/G_α13 family.[5] The Gs-family has only two members: the other member is G_olf, named for its predominant expression in the olfactory system. In humans, G_sα is encoded by the GNAS complex locus, while G_olfα is encoded by the GNAL gene.

GNAS
Identifiers
Aliases	GNAS, AHO, C20orf45, GNAS1, GPSA, GSA, GSP, NESP, POH, SCG6, SgVI, GNAS complex locus, PITA3
External IDs	OMIM: 139320 MGI: 95777 HomoloGene: 55534 GeneCards: GNAS
Gene location (Human) Chr. Chromosome 20 (human)[1] Band 20q13.32 Start 58,839,718 bp[1] End 58,911,192 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 H4|2 97.89 cM Start 174,284,320 bp[2] End 174,346,744 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • molecular function • nucleotide binding • G-protein beta/gamma-subunit complex binding • GTP binding • signal transducer activity • metal ion binding • GO:0001948 protein binding • GTPase activity • guanyl nucleotide binding • adenylate cyclase activator activity • insulin-like growth factor receptor binding • mu-type opioid receptor binding • corticotropin-releasing hormone receptor 1 binding • beta-2 adrenergic receptor binding • ionotropic glutamate receptor binding • D1 dopamine receptor binding • G-protein coupled receptor binding Cellular component • cytoplasm • perinuclear region of cytoplasm • extracellular region • transport vesicle • cytoplasmic vesicle • cell nucleus • cytosol • trans-Golgi network membrane • membrane • cell membrane • heterotrimeric G-protein complex • intrinsic component of membrane • extracellular exosome • ruffle • cell projection • dendrite • apical plasma membrane Biological process • female pregnancy • negative regulation of multicellular organism growth • response to parathyroid hormone • protein secretion • positive regulation of cold-induced thermogenesis • hair follicle placode formation • cellular response to catecholamine stimulus • adenylate cyclase-activating dopamine receptor signaling pathway • adenylate cyclase-activating G-protein coupled receptor signaling pathway • cognition • regulation of insulin secretion • cellular response to glucagon stimulus • intracellular transport • positive regulation of cAMP-mediated signaling • activation of adenylate cyclase activity • cellular response to prostaglandin E stimulus • adenylate cyclase-activating adrenergic receptor signaling pathway • sensory perception of smell • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • developmental growth • renal water homeostasis • bone development • platelet aggregation • signal transduction • G-protein coupled receptor signaling pathway • regulation of signal transduction • skeletal system development • genetic imprinting • multicellular organism growth • positive regulation of osteoclast differentiation • endochondral ossification • regulation of parathyroid hormone secretion • post-embryonic development • post-embryonic body morphogenesis • DNA methylation • cartilage development • positive regulation of osteoblast differentiation • tissue homeostasis • sensory perception of chemical stimulus • embryonic cranial skeleton morphogenesis • energy reserve metabolic process • response to drug • skin development • embryonic hindlimb morphogenesis • adenylate cyclase-modulating G-protein coupled receptor signaling pathway • GO:0048554 positive regulation of catalytic activity Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2778	14683
Ensembl	ENSG00000087460	ENSMUSG00000027523
UniProt	O95467 P63092 P84996 Q5JWF2	P63094 Q6R0H7 Q9Z0F1 Q6R0H6
RefSeq (mRNA)	NM_000516 NM_001077488 NM_001077489 NM_001077490 NM_001309840 NM_001309842 NM_001309861 NM_001309883 NM_016592 NM_080425 NM_080426	NM_001077507 NM_001077510 NM_010309 NM_010310 NM_019690 NM_022000 NM_201616 NM_201617 NM_201618 NM_001310083 NM_001310085 NM_001364030
RefSeq (protein)	NP_000507 NP_001070956 NP_001070957 NP_001070958 NP_001296769 NP_001296771 NP_001296790 NP_001296812 NP_057676 NP_536350 NP_536351 NP_000507.1 NP_001070956.1 NP_001070957.1 NP_001070958.1 NP_001296769.1 NP_536350.2 NP_536351.1 NP_001070958.1 NP_001296812.1 NP_001296812.1 NP_536350.2	NP_001070975 NP_001070978 NP_001297012 NP_001297014 NP_034439 NP_062664 NP_068840 NP_963910 NP_963911 NP_963912 NP_001350959 NP_001070975.1 NP_001297014.1 NP_034439.2 NP_963911.1 NP_062664.2 NP_068840.2 NP_001070975.1 NP_001297014.1 NP_963911.1 NP_963912.1
Location (UCSC)	Chr 20: 58.84 – 58.91 Mb	Chr 2: 174.28 – 174.35 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

Main article: Heterotrimeric G protein

The general function of G_s is to activate intracellular signaling pathways in response to activation of cell surface G protein-coupled receptors (GPCRs). GPCRs function as part of a three-component system of receptor-transducer-effector.[6][7] The transducer in this system is a heterotrimeric G protein, composed of three subunits: a Gα protein such as G_sα, and a complex of two tightly linked proteins called Gβ and Gγ in a Gβγ complex.[6][7] When not stimulated by a receptor, Gα is bound to GDP and to Gβγ to form the inactive G protein trimer.[6][7] When the receptor binds an activating ligand outside the cell (such as a hormone or neurotransmitter), the activated receptor acts as a guanine nucleotide exchange factor to promote GDP release from and GTP binding to Gα, which drives dissociation of GTP-bound Gα from Gβγ.[6][7] In particular, GTP-bound, activated G_sα binds to adenylyl cyclase to produce the second messenger cAMP, which in turn activates the cAMP-dependent protein kinase (also called Protein Kinase A or PKA).[6][7] Cellular effects of G_sα acting through PKA are described here.

Although each GTP-bound G_sα can activate only one adenylyl cyclase enzyme, amplification of the signal occurs because one receptor can activate multiple copies of G_s while that receptor remains bound to its activating agonist, and each G_sα-bound adenylyl cyclase enzyme can generate substantial cAMP to activate many copies of PKA.[8]

Receptors

The G protein-coupled receptors that couple to the G_s family proteins include:

• 5-HT receptors types 5-HT₄ and 5-HT₇
• ACTH receptor a.k.a. MC2R
• Adenosine receptor types A_2a and A_2b
• Arginine vasopressin receptor 2
• β-adrenergic receptors types β₁, β₂ and β₃
• Calcitonin receptor
• Calcitonin gene-related peptide receptor
• Cannabinoid receptor 2 [9]
• Corticotropin-releasing hormone receptor
• Dopamine receptors D₁-like family (D₁ and D₅), mainly through G_olf in the striatum
• FSH-receptor
• Gastric inhibitory polypeptide receptor
• Glucagon receptor
• Growth-hormone-releasing hormone receptor
• Histamine H₂ receptor
• Luteinizing hormone/choriogonadotropin receptor
• Melanocortin receptor: MC1R, MC2R (a.k.a. ACTH receptor), MC3R, MC4R, MC5R
• Olfactory receptors, through G_olf in the olfactory neurons
• Parathyroid hormone receptor 1
• Prostaglandin receptor types D₂ and I₂
• Secretin receptor
• Thyrotropin receptor
• Trace amine-associated receptor 1

See also

• Second messenger system
• G protein-coupled receptor
• Heterotrimeric G protein
• Adenylyl cyclase
• Protein kinase A
• Gi alpha subunit
• Gq alpha subunit
• G12/G13 alpha subunits

References

1. GRCh38: Ensembl release 89: ENSG00000087460 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027523 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Ellis C, Nature Reviews Drug Discovery GPCR Questionnaire Participants (July 2004). "The state of GPCR research in 2004". Nature Reviews. Drug Discovery. 3 (7): 575, 577–626. doi:10.1038/nrd1458. PMID 15272499.
6. Gilman AG (1987). "G proteins: transducers of receptor-generated signals". Annual Review of Biochemistry. 56: 615–649. doi:10.1146/annurev.bi.56.070187.003151. PMID 3113327.
7. Rodbell M (1995). "Nobel Lecture: Signal transduction: Evolution of an idea". Bioscience Reports. 15 (3): 117–133. doi:10.1007/bf01207453. PMID 7579038.
8. Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia AS, White LE, eds. (2007). Neuroscience (4th ed.). New York: W. H. Freeman. p. 155. ISBN 978-0-87893-697-7.
9. Saroz, Yurii; Kho, Dan T.; Glass, Michelle; Graham, Euan Scott; Grimsey, Natasha Lillia (2019-10-19). "Cannabinoid Receptor 2 (CB 2 ) Signals via G-alpha-s and Induces IL-6 and IL-10 Cytokine Secretion in Human Primary Leukocytes". ACS Pharmacology & Translational Science: acsptsci.9b00049. doi:10.1021/acsptsci.9b00049. ISSN 2575-9108.

External links

• G(s)alpha at the US National Library of Medicine Medical Subject Headings (MeSH)
• GNAS+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• Overview of all the structural information available in the PDB for UniProt: P63092 (Guanine nucleotide-binding protein G(s) subunit alpha isoforms short) at the PDBe-KB.