G_q protein alpha subunit is a family ofheterotrimeric G proteinalpha subunits. This family is also commonly called theG_q/11 (G_q/G₁₁) family orG_q/11/14/15 family to include closely related family members. G alpha subunits may be referred to as G_q alpha, G_αq, or G_qα. G_q proteins couple toG protein-coupled receptors to activate beta-typephospholipase C (PLC-β) enzymes. PLC-β in turn hydrolyzesphosphatidylinositol 4,5-bisphosphate (PIP₂) todiacyl glycerol (DAG) andinositol trisphosphate (IP₃). IP₃ acts as asecond messenger to release stored calcium into the cytoplasm, while DAG acts as a second messenger that activatesprotein kinase C (PKC).

In humans, there are four distinct proteins in the G_q alpha subunit family:

• G_αq is encoded by the geneGNAQ.
• G_α11 is encoded by the geneGNA11.
• G_α14 is encoded by the geneGNA14.
• G_α15 is encoded by the geneGNA15.

The general function of G_q is to activateintracellular 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.^[1][2] The transducer in this system is aheterotrimeric G protein, composed of three subunits: a Gα protein such as G_αq, and a complex of two tightly linked proteins called Gβ and Gγ in aGβγ complex.^[1][2] When not stimulated by a receptor, Gα is bound toguanosine diphosphate (GDP) and to Gβγ to form the inactive G protein trimer.^[1][2] When the receptor binds an activating ligand outside the cell (such as ahormone orneurotransmitter), the activated receptor acts as aguanine nucleotide exchange factor to promote GDP release from andguanosine triphosphate (GTP) binding to Gα, which drives dissociation of GTP-bound Gα from Gβγ.^[1][2] Recent evidence suggests that Gβγ and Gαq-GTP could maintain partial interaction via the N-α-helix region of Gαq.^[3] GTP-bound Gα and Gβγ are then freed to activate their respective downstream signaling enzymes.

G_q/11/14/15 proteins all activate beta-typephospholipase C (PLC-β) to signal through calcium and PKC signaling pathways.^[4] PLC-β then cleaves a specificplasma membranephospholipid,phosphatidylinositol 4,5-bisphosphate (PIP₂) intodiacyl glycerol (DAG) andinositol 1,4,5-trisphosphate (IP₃). DAG remains bound to the membrane, and IP₃ is released as a soluble molecule into thecytoplasm. IP₃ diffuses to bind toIP₃ receptors, a specializedcalcium channel in theendoplasmic reticulum (ER). These channels are specific tocalcium and only allow the passage of calcium from the ER into the cytoplasm. Since cells actively sequester calcium in the ER to keep cytoplasmic levels low, this release causes the cytosolic concentration of calcium to increase, causing a cascade of intracellular changes and activity through calcium binding proteins and calcium-sensitive processes.^[4]

Further reading:Calcium function in vertebrates

DAG works together with released calcium to activate specific isoforms of PKC, which are activated to phosphorylate other molecules, leading to further altered cellular activity.^[4]

Further reading:function of protein kinase C

The Gαq / Gα11 (Q209L) mutation is associated with the development of uveal melanoma and its pharmacological inhibition (cyclic depsipeptide FR900359 inhibitor), decreases tumor growth in preclinical trials.^[5][6]

The followingG protein-coupled receptors couple to G_q subunits:

• 5-HT₂serotonergic receptors
• Alpha-1 adrenergic receptor
• Vasopressin type 1 receptors:1A and1B
• Angiotensin II receptor type 1
• Calcitonin receptor
• GlutamatemGluR1 andmGluR5 receptors
• Gonadotropin-releasing hormone receptor
• Histamine H1 receptor
• M₁,M₃, andM₅muscarinic receptors^[7]
• Thyrotropin-releasing hormone receptor
• Trace amine-associated receptor 1

At least some Gq-coupled receptors (e.g., the muscarinic acetylcholine M₃ receptor) can be found preassembled (pre-coupled) with G_q. The common polybasic domain in the C-tail of G_q-coupled receptors appears necessary for this receptor¬G protein preassembly.^[7]

• The cyclic depsipeptides FR900359 andYM-254890 are strong, highly specific inhibitors of Gq and G11.^[8][9]

• Second messenger system
• G protein-coupled receptor
• Heterotrimeric G protein
• Phospholipase C
• Calcium signaling
• Protein kinase C
• Gs alpha subunit
• Gi alpha subunit
• G12/G13 alpha subunits

• Gq+protein at the U.S. National Library of MedicineMedical Subject Headings (MeSH)

• Genes on human chromosome 9
• Genes on human chromosome 19
• G proteins
• Peripheral membrane proteins

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