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{{Short description|Mammalian protein found in Homo sapiens}}
{{DISPLAYTITLE:G<sub>s</sub> alpha subunit}}
{{DISPLAYTITLE:G<sub>s</sub> alpha subunit}}
{{infobox gene}}
{{infobox gene}}
The '''G<sub>s</sub> alpha subunit''' ('''G<sub>αs</sub>''', '''G<sub>s</sub>α''') is a subunit of the [[heterotrimeric G protein]] '''G<sub>s</sub>''' that '''s'''timulates the [[cAMP-dependent pathway]] by activating [[adenylyl cyclase]]. G<sub>s</sub>α is a [[GTPase]] that functions as a cellular signaling protein.
The '''G<sub>s</sub> alpha subunit''' ('''G<sub>αs</sub>''', '''G<sub>s</sub>α''') is a subunit of the [[heterotrimeric G protein]] '''G<sub>s</sub>''' that stimulates the [[cAMP-dependent pathway]] by activating [[adenylyl cyclase]]. G<sub>s</sub>α is a [[GTPase]] that functions as a cellular signaling protein.
G<sub>s</sub>α is the founding member of one of the four families of heterotrimeric G proteins, defined by the [[G alpha subunit|alpha subunits]] they contain: the G<sub>αs</sub> family, [[Gi alpha subunit|G<sub>αi</sub>/G<sub>αo</sub> family]], [[Gq alpha subunit|G<sub>αq</sub> family]], and [[G12/G13 alpha subunits|G<sub>α12</sub>/G<sub>α13</sub> family]].<ref name="pmid15272499">{{cite journal | vauthors = Ellis C, ((Nature Reviews Drug Discovery GPCR Questionnaire Participants)) | title = The state of GPCR research in 2004 | journal = Nature Reviews. Drug Discovery | volume = 3 | issue = 7 | pages = 575, 577–626 | date = July 2004 | pmid = 15272499 | doi = 10.1038/nrd1458 }}</ref> The Gs-family has only two members: the other member is G<sub>olf</sub>, named for its predominant expression in the olfactory system. In humans, G<sub>s</sub>α is encoded by the [[GNAS complex locus]], while G<sub>olf</sub>α is encoded by the [[GNAL]] gene.
G<sub>s</sub>α is the founding member of one of the four families of heterotrimeric G proteins, defined by the [[G alpha subunit|alpha subunits]] they contain: the G<sub>αs</sub> family, [[Gi alpha subunit|G<sub>αi</sub>/G<sub>αo</sub> family]], [[Gq alpha subunit|G<sub>αq</sub> family]], and [[G12/G13 alpha subunits|G<sub>α12</sub>/G<sub>α13</sub> family]].<ref name="pmid15272499">{{cite journal | vauthors = Ellis C, ((Nature Reviews Drug Discovery GPCR Questionnaire Participants)) | title = The state of GPCR research in 2004 | journal = Nature Reviews. Drug Discovery | volume = 3 | issue = 7 | pages = 575, 577–626 | date = July 2004 | pmid = 15272499 | doi = 10.1038/nrd1458 | s2cid = 33620092 }}</ref> The Gs-family has only two members: the other member is G<sub>olf</sub>, named for its predominant expression in the olfactory system. In humans, G<sub>s</sub>α is encoded by the [[GNAS complex locus]], while G<sub>olf</sub>α is encoded by the [[GNAL]] gene.


==Function==
==Function==
{{Main|Heterotrimeric G protein}}
{{Main|Heterotrimeric G protein}}
The general function of G<sub>s</sub> is to activate [[signal transduction|intracellular signaling pathways]] in response to activation of cell surface [[G protein-coupled receptor | G protein-coupled receptors (GPCRs)]]. GPCRs function as part of a three-component system of receptor-transducer-effector.<ref name="pmid3113327">{{cite journal | vauthors = Gilman AG |date=1987 |title= G proteins: transducers of receptor-generated signals |url= https://semanticscholar.org/paper/101a0d785c1f74416c0f3182f3743522103402df|journal= Annual Review of Biochemistry |volume=56 |issue= |pages=615–649 |doi=10.1146/annurev.bi.56.070187.003151 |pmid=3113327 |access-date= }}</ref><ref name="pmid7579038">{{cite journal | vauthors = Rodbell M |date=1995 |title=Nobel Lecture: Signal transduction: Evolution of an idea |url= |journal=Bioscience Reports |volume=15 |issue=3 |pages=117–133 |doi=10.1007/bf01207453 |pmid=7579038 |access-date= }}</ref> The transducer in this system is a [[heterotrimeric G protein]], composed of three subunits: a Gα protein such as G<sub>s</sub>α, and a complex of two tightly linked proteins called Gβ and Gγ in a [[G beta-gamma complex|Gβγ complex]].<ref name="pmid3113327"/><ref name="pmid7579038"/> When not stimulated by a receptor, Gα is bound to [[Guanosine diphosphate|GDP]] and to Gβγ to form the inactive G protein trimer.<ref name="pmid3113327"/><ref name="pmid7579038"/> 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 [[Guanosine triphosphate|GTP]] binding to Gα, which drives dissociation of GTP-bound Gα from Gβγ.<ref name="pmid3113327"/><ref name="pmid7579038"/> In particular, GTP-bound, activated G<sub>s</sub>α binds to [[adenylyl cyclase]] to produce the [[second messenger]] [[cyclic AMP|cAMP]], which in turn activates the [[Protein kinase A|cAMP-dependent protein kinase (also called Protein Kinase A or PKA)]].<ref name="pmid3113327"/><ref name="pmid7579038"/> Cellular effects of G<sub>s</sub>α acting through PKA are described [[function of cAMP-dependent protein kinase|here]].
The general function of G<sub>s</sub> is to activate [[signal transduction|intracellular signaling pathways]] in response to activation of cell surface [[G protein-coupled receptor | G protein-coupled receptors (GPCRs)]]. GPCRs function as part of a three-component system of receptor-transducer-effector.<ref name="pmid3113327">{{cite journal | vauthors = Gilman AG |date=1987 |title= G proteins: transducers of receptor-generated signals |journal= Annual Review of Biochemistry |volume=56 |pages=615–649 |doi=10.1146/annurev.bi.56.070187.003151 |pmid=3113327 |s2cid=33992382 }}</ref><ref name="pmid7579038">{{cite journal | vauthors = Rodbell M |date=1995 |title=Nobel Lecture: Signal transduction: Evolution of an idea |journal=Bioscience Reports |volume=15 |issue=3 |pages=117–133 |doi=10.1007/bf01207453 |pmid=7579038 |s2cid=11025853 |pmc=1519115 }}</ref> The transducer in this system is a [[heterotrimeric G protein]], composed of three subunits: a Gα protein such as G<sub>s</sub>α, and a complex of two tightly linked proteins called Gβ and Gγ in a [[G beta-gamma complex|Gβγ complex]].<ref name="pmid3113327"/><ref name="pmid7579038"/> When not stimulated by a receptor, Gα is bound to [[Guanosine diphosphate|GDP]] and to Gβγ to form the inactive G protein trimer.<ref name="pmid3113327"/><ref name="pmid7579038"/> 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 [[Guanosine triphosphate|GTP]] binding to Gα, which drives dissociation of GTP-bound Gα from Gβγ.<ref name="pmid3113327"/><ref name="pmid7579038"/> In particular, GTP-bound, activated G<sub>s</sub>α binds to [[adenylyl cyclase]] to produce the [[second messenger]] [[cyclic AMP|cAMP]], which in turn activates the [[Protein kinase A|cAMP-dependent protein kinase (also called Protein Kinase A or PKA)]].<ref name="pmid3113327"/><ref name="pmid7579038"/> Cellular effects of G<sub>s</sub>α acting through PKA are described [[function of cAMP-dependent protein kinase|here]].


Although each GTP-bound G<sub>s</sub>α can activate only one adenylyl cyclase enzyme, amplification of the signal occurs because one receptor can activate multiple copies of G<sub>s</sub> while that receptor remains bound to its activating [[agonist]], and each G<sub>s</sub>α-bound adenylyl cyclase enzyme can generate substantial cAMP to activate many copies of PKA.<ref name=neuro155>{{cite book | veditors = Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia AS, White LE |title=Neuroscience |date=2007 |publisher=W. H. Freeman |location=New York |isbn=978-0-87893-697-7 |edition=4th | page = 155 }}</ref>
Although each GTP-bound G<sub>s</sub>α can activate only one adenylyl cyclase enzyme, amplification of the signal occurs because one receptor can activate multiple copies of G<sub>s</sub> while that receptor remains bound to its activating [[agonist]], and each G<sub>s</sub>α-bound adenylyl cyclase enzyme can generate substantial cAMP to activate many copies of PKA.<ref name=neuro155>{{cite book | veditors = Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia AS, White LE |title=Neuroscience |date=2007 |publisher=W. H. Freeman |location=New York |isbn=978-0-87893-697-7 |edition=4th | page = 155 }}</ref>
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==Receptors==
==Receptors==
The G protein-coupled receptors that couple to the G<sub>s</sub> family proteins include:
The G protein-coupled receptors that couple to the G<sub>s</sub> family proteins include:
* [[5-HT receptor]]s types [[5-HT4 receptor|5-HT<sub>4</sub>]] and [[5-HT7 receptor|5-HT<sub>7</sub>]]
* [[5-HT4 receptor|5-HT<sub>4</sub>]], [[5-HT6 receptor|5-HT<sub>6</sub>]] and [[5-HT7 receptor|5-HT<sub>7</sub>]] [[5-HT receptors|serotonergic receptors]]
⚫
* [[ACTH receptor]] a.k.a. MC2R
* [[Adenosine receptor]] types [[Adenosine receptor A2a|A<sub>2a</sub>]] and [[Adenosine receptor A2b|A<sub>2b</sub>]]
* [[Adenosine receptor]] types [[Adenosine receptor A2a|A<sub>2a</sub>]] and [[Adenosine receptor A2b|A<sub>2b</sub>]]
⚫
* [[ACTH receptor|Adrenocorticotropic hormone receptor]] (a.k.a. [[MC2R]])
* [[Arginine vasopressin receptor 2]]
* [[Arginine vasopressin receptor 2]]
* [[β-adrenergic receptors]] types [[Beta-1 adrenergic receptor|β<sub>1</sub>]], [[Beta-2 adrenergic receptor|β<sub>2</sub>]] and [[Beta-3 adrenergic receptor|β<sub>3</sub>]]
* [[β-adrenergic receptors]] types [[Beta-1 adrenergic receptor|β<sub>1</sub>]], [[Beta-2 adrenergic receptor|β<sub>2</sub>]] and [[Beta-3 adrenergic receptor|β<sub>3</sub>]]
* [[Calcitonin receptor]]
* [[Calcitonin receptor]]
* [[Calcitonin gene-related peptide receptor]]
* [[Calcitonin gene-related peptide receptor]]
*[[Cannabinoid receptor type 2|Cannabinoid receptor 2]] <ref>{{Cite journal|last=Saroz|first=Yurii|last2=Kho|first2=Dan T.|last3=Glass|first3=Michelle|last4=Graham|first4=Euan Scott|last5=Grimsey|first5=Natasha Lillia|date=2019-10-19|title=Cannabinoid Receptor 2 (CB 2 ) Signals via G-alpha-s and Induces IL-6 and IL-10 Cytokine Secretion in Human Primary Leukocytes|journal=ACS Pharmacology & Translational Science|language=en|pages=acsptsci.9b00049|doi=10.1021/acsptsci.9b00049|issn=2575-9108}}</ref>
* [[Corticotropin-releasing hormone receptor]]
* [[Corticotropin-releasing hormone receptor]]
* [[Dopamine receptors]] D<sub>1</sub>-like family ([[dopamine receptor D1|D<sub>1</sub>]] and [[dopamine receptor D5|D<sub>5</sub>]]), mainly through G<sub>olf</sub> in the [[striatum]]
* [[Dopamine]] [[Dopamine_receptor_D1|D<sub>1</sub>]] and [[Dopamine_receptor_D5|D<sub>5</sub>]] receptors
* [[FSH-receptor]]
* [[Follicle-stimulating hormone receptor]]
* [[Gastric inhibitory polypeptide receptor]]
* [[Gastric inhibitory polypeptide receptor]]
* [[Glucagon receptor]]
* [[Glucagon receptor]]
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* [[Histamine H2 receptor|Histamine H<sub>2</sub> receptor]]
* [[Histamine H2 receptor|Histamine H<sub>2</sub> receptor]]
* [[Luteinizing hormone/choriogonadotropin receptor]]
* [[Luteinizing hormone/choriogonadotropin receptor]]
* [[Melanocortin receptor]]: [[MC1R]], [[MC2R]] (a.k.a. ACTH receptor), [[MC3R]], [[MC4R]], [[MC5R]]
* [[Melanocortin receptor]]: [[MC1R]], MC2R (a.k.a. ACTH receptor), [[MC3R]], [[MC4R]], [[MC5R]]
* [[Olfactory receptors]], through G<sub>olf</sub> in the [[olfactory neuron]]s
* [[Olfactory receptors]], through G<sub>olf</sub> in the [[olfactory neuron]]s
* [[Parathyroid hormone receptor 1]]
* [[Parathyroid hormone receptor]]s [[Parathyroid hormone 1 receptor|PTH1R]] and [[Parathyroid hormone 2 receptor|PTH2R]]
* [[Prostaglandin receptor]] types [[Prostaglandin D2 receptor|D<sub>2</sub>]] and [[Prostacyclin receptor|I<sub>2</sub>]]
* [[Prostaglandin receptor]] types [[Prostaglandin D2 receptor|D<sub>2</sub>]] and [[Prostacyclin receptor|I<sub>2</sub>]]
* [[Secretin receptor]]
* [[Secretin receptor]]
* [[Thyrotropin receptor]]
* [[Thyrotropin receptor]]
* [[TAAR1|Trace amine-associated receptor 1]]
* [[TAAR1|Trace amine-associated receptor 1]]
* [[Vasopressin receptor 2]]


==See also==
==See also==

Latest revision as of 12:10, 31 July 2024

GNAS
Identifiers
AliasesGNAS, AHO, C20orf45, GNAS1, GPSA, GSA, GSP, NESP, POH, SCG6, SgVI, GNAS complex locus, PITA3
External IDsOMIM: 139320; MGI: 95777; HomoloGene: 55534; GeneCards: GNAS; OMA:GNAS - orthologs
Orthologs
SpeciesHumanMouse
Entrez

2778

14683

Ensembl

ENSG00000087460

ENSMUSG00000027523

UniProt

O95467
P63092
P84996
Q5JWF2

P63094
Q6R0H7
Q9Z0F1
Q6R0H6

RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)Chr 20: 58.84 – 58.91 MbChr 2: 174.13 – 174.19 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The Gs alpha subunit (Gαs, Gsα) is a subunit of the heterotrimeric G protein Gs that stimulates the cAMP-dependent pathway by activating adenylyl cyclase. Gsα is a GTPase that functions as a cellular signaling protein. Gsα is the founding member of one of the four families of heterotrimeric G proteins, defined by the alpha subunits they contain: the Gαs family, Gαi/Gαo family, Gαq family, and Gα12/Gα13 family.[5] The Gs-family has only two members: the other member is Golf, named for its predominant expression in the olfactory system. In humans, Gsα is encoded by the GNAS complex locus, while Golfα is encoded by the GNAL gene.

Function

[edit]
Main article: Heterotrimeric G protein

The general function of Gs 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 Gsα, 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 Gsα 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 Gsα acting through PKA are described here.

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

Receptors

[edit]

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

See also

[edit]

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000087460 – Ensembl, May 2017
  2. ^ a b c 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. S2CID 33620092.
  6. ^ a b c d e 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. S2CID 33992382.
  7. ^ a b c d e Rodbell M (1995). "Nobel Lecture: Signal transduction: Evolution of an idea". Bioscience Reports. 15 (3): 117–133. doi:10.1007/bf01207453. PMC 1519115. PMID 7579038. S2CID 11025853.
  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.
[edit]
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