G_q protein alpha subunit is a family of

heterotrimeric G protein Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPases) are membrane-associated G proteins that form a heterotrimeric complex. The biggest non-structu ...

alpha subunits. This family is also commonly called the G_q/11 (G_q/G₁₁) family or G_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 to

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

s to activate beta-type phospholipase C (PLC-β) enzymes. PLC-β in turn hydrolyzes

phosphatidylinositol 4,5-bisphosphate Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number o ...

(PIP₂) to

diacyl glycerol A diglyceride, or diacylglycerol (DAG), is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. Two possible forms exist, 1,2-diacylglycerols and 1,3-diacylglycerols. DAGs can act as su ...

(DAG) and

inositol trisphosphate Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the p ...

(IP₃). IP₃ acts as a second messenger to release stored calcium into the cytoplasm, while DAG acts as a second messenger that activates protein kinase C (PKC).

Family members

In humans, there are four distinct proteins in the G_q alpha subunit family: * G_αq is encoded by the gene

GNAQ Guanine nucleotide-binding protein G(q) subunit alpha is a protein that in humans is encoded by the ''GNAQ'' gene. Together with GNA11 (its paralogue), it functions as a Gq alpha subunit. Function Guanine nucleotide-binding proteins are a fam ...

. * G_α11 is encoded by the gene

GNA11 Guanine nucleotide-binding protein subunit alpha-11 is a protein that in humans is encoded by the ''GNA11'' gene. Together with GNAQ (its paralogue), it functions as a Gq alpha subunit.GNA14 Guanine nucleotide-binding protein subunit alpha-14 is a protein that in humans is encoded by the ''GNA14'' gene.GNA15 Guanine nucleotide-binding protein subunit alpha-15 is a protein that in humans is encoded by the ''GNA15'' gene.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. The transducer in this system is a

, composed of three subunits: a Gα protein such as G_αq, and a complex of two tightly linked proteins called Gβ and Gγ in a Gβγ complex. When not stimulated by a receptor, Gα is bound to guanosine diphosphate (GDP) and to Gβγ to form the inactive G protein trimer. When the receptor binds an activating ligand outside the cell (such as a

hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are require ...

or neurotransmitter), the activated receptor acts as a

guanine nucleotide exchange factor Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated struc ...

to promote GDP release from and guanosine triphosphate (GTP) binding to Gα, which drives dissociation of GTP-bound Gα from Gβγ. Recent evidence suggests that Gβγ and Gαq-GTP could maintain partial interaction via the N-α-helix region of Gαq. GTP-bound Gα and Gβγ are then freed to activate their respective downstream signaling enzymes. G_q/11/14/15 proteins all activate beta-type phospholipase C (PLC-β) to signal through calcium and PKC signaling pathways. PLC-β then cleaves a specific plasma membrane phospholipid,

(PIP₂) into

(DAG) and

inositol 1,4,5-trisphosphate Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the ...

(IP₃). DAG remains bound to the membrane, and IP₃ is released as a soluble molecule into the

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...

. IP₃ diffuses to bind to IP₃ receptors, a specialized calcium channel in the endoplasmic reticulum (ER). These channels are specific to

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...

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. : ''Further reading:

Calcium function in vertebrates Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contractio ...

'' 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. : ''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.

Receptors

The following

G protein-coupled receptors G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

couple to G_q subunits: * 5-HT₂ serotonergic receptors *

Alpha-1 adrenergic receptor alpha-1 (α1) adrenergic receptors are G protein-coupled receptors (GPCRs) associated with the Gq heterotrimeric G protein. α1-adrenergic receptors are subdivided into three highly homologous subtypes, i.e., α1A-, α1B-, and α1D-adrenerg ...

* Vasopressin type 1 receptors: 1A and 1B *

Angiotensin II receptor type 1 Angiotensin II receptor type 1 (AT1) is the best characterized angiotensin receptor. It is encoded in humans by the ''AGTR1'' gene. AT1 has vasopressor effects and regulates aldosterone secretion. It is an important effector controlling blood pre ...

Calcitonin receptor The calcitonin receptor (CT) is a G protein-coupled receptor that binds the peptide hormone calcitonin and is involved in maintenance of calcium homeostasis, particularly with respect to bone formation and metabolism. CT works by activating the ...

Histamine H1 receptor The H1 receptor is a histamine receptor belonging to the family of rhodopsin-like G-protein-coupled receptors. This receptor is activated by the biogenic amine histamine. It is expressed in smooth muscles, on vascular endothelial cells, in the h ...

Metabotropic glutamate receptor The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate re ...

, Group I * M₁, M₃, and M₅

muscarinic receptors Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...

Trace amine-associated receptor 1 Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is an intracellular amine-activated and G protein-coupled receptor (GPCR) that is primarily ex ...

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.

References

External links

* {{Portal bar, Biology, border=no G proteins Peripheral membrane proteins

Family members

Receptors

See also

References

External links