Editing G protein

{{Short description|Type of proteins}}
{{distinguish|Protein G}}
{{Use dmy dates|date=July 2020}}
[[File:1b9x opm.png|thumb|250px|[[Phosducin]]-[[transducin]] beta-gamma complex. Beta and gamma subunits of G-protein are shown by blue and red, respectively.]]
[[File:Guanosindiphosphat protoniert.svg|thumb|180px|[[Guanosine diphosphate]]]]
[[File:Guanosintriphosphat protoniert.svg|thumb|180px|[[Guanosine triphosphate]]]]

'''G proteins''', also known as '''guanine nucleotide-binding proteins''', are a [[Protein family|family of proteins]] that act as [[molecular switch]]es inside cells, and are involved in transmitting signals from a variety of stimuli outside a [[cell (biology)|cell]] to its interior.  Their activity is regulated by factors that control their ability to bind to and hydrolyze [[guanosine triphosphate]] (GTP) to [[guanosine diphosphate]] (GDP). When they are bound to GTP, they are 'on', and, when they are bound to GDP, they are 'off'. G proteins belong to the larger group of [[enzyme]]s called [[GTPase]]s.

There are two classes of G proteins. The first function as [[monomeric]] [[small GTPase]]s (small G-proteins), while the second function as [[heterotrimeric G protein]] [[protein complex|complexes]]. The latter class of complexes is made up of ''[[G alpha subunit|alpha]]'' (G<sub>α</sub>), ''beta'' (G<sub>β</sub>) and ''gamma'' (G<sub>γ</sub>) [[protein subunit|subunit]]s.<ref name="Hurowitz_2000">{{cite journal | vauthors = Hurowitz EH, Melnyk JM, Chen YJ, Kouros-Mehr H, Simon MI, Shizuya H | title = Genomic characterization of the human heterotrimeric G protein alpha, beta, and gamma subunit genes | journal = DNA Research | volume = 7 | issue = 2 | pages = 111–20 | date = April 2000 | pmid = 10819326 | doi = 10.1093/dnares/7.2.111 | doi-access = free }}</ref> In addition, the beta and gamma subunits can form a stable [[Protein dimer|dimeric complex]] referred to as the [[G beta-gamma complex|beta-gamma complex]]
.<ref name="Clapham">{{cite journal |vauthors=Clapham DE, Neer EJ |title=G protein beta gamma subunits |journal=Annual Review of Pharmacology and Toxicology |volume=37 |pages=167–203 |year=1997 |pmid=9131251 |doi=10.1146/annurev.pharmtox.37.1.167}}</ref>

Heterotrimeric G proteins located within the cell are activated by [[G protein-coupled receptor]]s (GPCRs) that span the [[cell membrane]].<ref>{{Cite web|url=http://www.ibiology.org/ibioseminars/cell-biology/robert-lefkowitz-part-1.html|title=Seven Transmembrane Receptors: Robert Lefkowitz|date=2012-09-09|access-date=2016-07-11}}</ref> [[Cell signaling|Signaling molecule]]s bind to a domain of the GPCR located outside the cell, and an intracellular GPCR domain then in turn activates a particular G protein. Some active-state GPCRs have also been shown to be "pre-coupled" with G proteins, whereas in other cases a collision coupling mechanism is thought to occur.<ref name="Kou Qin"/><ref name="Lewitski78">{{cite journal | vauthors = Tolkovsky AM, Levitzki A | title = Mode of coupling between the beta-adrenergic receptor and adenylate cyclase in turkey erythrocytes | journal = Biochemistry | volume = 17 | issue = 18 | pages = 3795–3810 | date = 1978 | doi = 10.1021/bi00611a020| pmid = 212105 }}</ref><ref name="Boltz22">{{cite journal | vauthors = Boltz HH, Sirbu A, Stelzer N, de Lanerolle P, Winkelmann S, Annibale P | title = The Impact of Membrane Protein Diffusion on GPCR Signaling | journal = Cells | volume = 11 | issue = 10 | date = 2022 | page = 1660 | doi = 10.3390/cells11101660| pmid = 35626696 | pmc = 9139411 | doi-access = free }}</ref> The G protein triggers a [[Biochemical cascade#Signaling cascades|cascade of further signaling event]]s that finally results in a change in cell function. G protein-coupled receptors and G proteins working together transmit signals from many [[hormone]]s, [[neurotransmitter]]s, and other signaling factors.<ref name="Campbell">{{cite book | vauthors = Reece J, C N | title = Biology | publisher = Benjamin Cummings | location = San Francisco | year = 2002 | isbn = 0-8053-6624-5 | url-access = registration | url = https://archive.org/details/biologyc00camp }}</ref> G proteins regulate metabolic [[enzyme]]s, [[ion channel]]s, [[membrane transport protein|transporter proteins]], and other parts of the cell machinery, controlling [[transcription (genetics)|transcription]], [[motility]], [[contractility]], and [[secretion]], which in turn regulate diverse systemic functions such as [[embryonic development]], learning and memory, and [[homeostasis]].<ref name="pmid12040175">{{cite journal | vauthors = Neves SR, Ram PT, Iyengar R | title = G protein pathways | journal = Science | volume = 296 | issue = 5573 | pages = 1636–9 | date = May 2002 | pmid = 12040175 | doi = 10.1126/science.1071550 | bibcode = 2002Sci...296.1636N | s2cid = 20136388 }}</ref>

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== History ==
G proteins were discovered in 1980 when [[Alfred G. Gilman]] and [[Martin Rodbell]] investigated stimulation of cells by [[adrenaline]]. They found that when adrenaline binds to a receptor, the receptor does not stimulate enzymes (inside the cell) directly. Instead, the receptor stimulates a G protein, which then stimulates an enzyme. An example is [[adenylate cyclase]], which produces the [[second messenger]] [[cyclic AMP]].<ref name="nobelprize.org">[http://nobelprize.org/nobel_prizes/medicine/laureates/1994/illpres/signal.html The Nobel Prize in Physiology or Medicine 1994], Illustrated Lecture.</ref> For this discovery, they won the 1994 [[Nobel Prize in Physiology or Medicine]].<ref>[http://nobelprize.org/nobel_prizes/medicine/laureates/1994/press.html Press Release:] The Nobel Assembly at the Karolinska Institute decided to award the Nobel Prize in Physiology or Medicine for 1994 jointly to Alfred G. Gilman and Martin Rodbell for their discovery of "G-proteins and the role of these proteins in signal transduction in cells". 10 October 1994</ref>

Nobel prizes have been awarded for many aspects of signaling by G proteins and GPCRs. These include [[receptor antagonist]]s, [[neurotransmitters]], neurotransmitter [[reuptake]], [[G protein-coupled receptor]]s, G proteins, [[second messenger]]s, the enzymes that trigger protein [[phosphorylation]] in response to [[Cyclic adenosine monophosphate|cAMP]], and consequent metabolic processes such as [[glycogenolysis]].

Prominent examples include (in chronological order of awarding):

* The 1947 [[Nobel Prize in Physiology or Medicine]] to [[Carl Cori]], [[Gerty Cori]] and [[Bernardo Houssay]], for their discovery of how [[glycogen]] is broken down to [[glucose]] and resynthesized in the body, for use as a store and source of energy. [[Glycogenolysis]] is stimulated by numerous [[hormone]]s and [[neurotransmitter]]s including [[adrenaline]].
* The 1970 [[Nobel Prize in Physiology or Medicine]] to [[Julius Axelrod]], [[Bernard Katz]] and [[Ulf von Euler]] for their work on the release and [[reuptake]] of [[neurotransmitter]]s.
* The 1971 [[Nobel Prize in Physiology or Medicine]] to [[Earl Sutherland]] for discovering the key role of [[adenylate cyclase]], which produces the second messenger [[cyclic AMP]].<ref name="nobelprize.org"/>
* The 1988 [[Nobel Prize in Physiology or Medicine]] to [[George H. Hitchings]], [[Sir James Black]] and [[Gertrude Elion]] "for their discoveries of important principles for drug treatment" targeting GPCRs.
* The 1992 [[Nobel Prize in Physiology or Medicine]] to [[Edwin G. Krebs]] and [[Edmond H. Fischer]] for describing how reversible [[phosphorylation]] works as a switch to activate [[protein]]s, and to regulate various cellular processes including [[glycogenolysis]].<ref>{{cite web|title=The Nobel Prize in Physiology or Medicine 1992 Press Release|publisher=[[Nobel Assembly at Karolinska Institutet]]|url=https://www.nobelprize.org/nobel_prizes/medicine/laureates/1992/press.html|access-date=21 August 2013}}</ref>
* The 1994 [[Nobel Prize in Physiology or Medicine]] to [[Alfred G. Gilman]] and [[Martin Rodbell]] for their discovery of "G-proteins and the role of these proteins in signal transduction in cells".<ref>[http://nobelprize.org/nobel_prizes/medicine/laureates/1994/press.html Press Release]</ref>
* The 2000 [[Nobel Prize in Physiology or Medicine]] to [[Eric Kandel]], [[Arvid Carlsson]] and [[Paul Greengard]], for research on [[neurotransmitter]]s such as [[dopamine]], which act via GPCRs.
* The 2004 [[Nobel Prize in Physiology or Medicine]] to [[Richard Axel]] and [[Linda B. Buck]] for their work on G protein-coupled [[olfactory receptor]]s.<ref>{{cite web|title=Press Release: The 2004 Nobel Prize in Physiology or Medicine |url=https://www.nobelprize.org/nobel_prizes/medicine/laureates/2004/press.html |publisher=Nobelprize.org |access-date=8 November 2012}}</ref>
* The 2012 [[Nobel Prize in Chemistry]] to [[Brian Kobilka]] and [[Robert Lefkowitz]] for their work on GPCR function.<ref name="Nobel committee,2012">{{cite news|last=Royal Swedish Academy of Sciences|title=The Nobel Prize in Chemistry 2012 Robert J. Lefkowitz, Brian K. Kobilka|url=https://www.nobelprize.org/nobel_prizes/chemistry/laureates/2012/press.html|access-date=10 October 2012|date=10 October 2012}}</ref>

== Function ==
G proteins are important [[signal transducing]] molecules in cells. "Malfunction of GPCR [G Protein-Coupled Receptor] signaling pathways are involved in many diseases, such as [[diabetes]], blindness, allergies, depression, cardiovascular defects, and certain forms of [[cancer]]. It is estimated that about 30% of the modern drugs' cellular targets are GPCRs."<ref name="Bosch_2013">{{cite journal | vauthors = Bosch DE, Siderovski DP | title = G protein signaling in the parasite Entamoeba histolytica | journal = Experimental & Molecular Medicine | volume = 45 | issue = 1038 | pages = e15 | date = March 2013 | pmid = 23519208 | doi = 10.1038/emm.2013.30 | pmc=3641396}}</ref> The human genome encodes roughly 800<ref name="Baltoumas_2013">{{cite journal | vauthors = Baltoumas FA, Theodoropoulou MC, Hamodrakas SJ | title = Interactions of the α-subunits of heterotrimeric G-proteins with GPCRs, effectors and RGS proteins: a critical review and analysis of interacting surfaces, conformational shifts, structural diversity and electrostatic potentials | journal = Journal of Structural Biology | volume = 182 | issue = 3 | pages = 209–18 | date = June 2013 | pmid = 23523730 | doi = 10.1016/j.jsb.2013.03.004 }}</ref> [[G protein-coupled receptors]], which detect photons of light, hormones, growth factors, drugs, and other endogenous [[Ligand (biochemistry)|ligands]].  Approximately 150 of the GPCRs found in the human genome still have unknown functions.

Whereas G proteins are activated by [[G protein-coupled receptor]]s, they are inactivated by [[Regulator of G protein signalling|RGS proteins]] (for "Regulator of G protein signalling"). Receptors stimulate GTP binding (turning the G protein on). RGS proteins stimulate GTP hydrolysis (creating GDP, thus turning the G protein off).

== Diversity ==
[[File:Human Ga protein phylogeny.png|thumb|Sequence relationship among the 18 human G<sub>α</sub> proteins.<ref name="Syrovatkina_2016">{{cite journal | vauthors = Syrovatkina V, Alegre KO, Dey R, Huang XY | title = Regulation, Signaling, and Physiological Functions of G-Proteins | journal = Journal of Molecular Biology | volume = 428 | issue = 19 | pages = 3850–68 | date = September 2016 | pmid = 27515397 | pmc = 5023507 | doi = 10.1016/j.jmb.2016.08.002 }}</ref>]]
All eukaryotes use G proteins for signaling and have evolved a large diversity of G proteins. For instance, humans encode 18 different G<sub>α</sub> proteins, 5 G<sub>β</sub> proteins, and 12 G<sub>γ</sub> proteins.<ref name="Syrovatkina_2016" />

== Signaling ==
G protein can refer to two distinct families of proteins. [[Heterotrimeric G protein]]s, sometimes referred to as the "large" G proteins, are activated by [[G protein-coupled receptor]]s and are made up of alpha (α), beta (β), and gamma (γ) [[Protein subunit|subunit]]s. ''"Small" G proteins'' (20-25kDa) belong to the [[Ras (protein)|Ras]] superfamily of [[small GTPase]]s. These proteins are [[Sequence homology|homologous]] to the alpha (α) subunit found in heterotrimers, but are in fact monomeric, consisting of only a single unit. However, like their larger relatives, they also bind GTP and GDP and are involved in [[signal transduction]].

=== Heterotrimeric ===
{{Main|Heterotrimeric G proteins}}
Different types of heterotrimeric G proteins share a common mechanism. They are activated in response to a [[conformational change]] in the GPCR, exchanging GDP for GTP, and dissociating in order to activate other proteins in a particular [[signal transduction]] pathway.<ref>{{Cite book|last=Lim|first=Wendell|url=https://www.worldcat.org/oclc/868641565|title=Cell signaling : principles and mechanisms|date=2015|others=Bruce Mayer, T. Pawson|isbn=978-0-8153-4244-1|location=New York|oclc=868641565}}</ref> The specific mechanisms, however, differ between protein types.

===Mechanism===
[[File:GPCR-Zyklus.png|thumb|450px|Activation cycle of G-proteins (pink) by a G-protein-coupled receptor (GPCR, light blue) receiving a ligand (red). Ligand binding to GPCRs (2) induces a conformation change that facilitates the exchange of GDP for GTP on the α subunit of the heterotrimeric complex (3–4). Both GTP-bound Gα in the active form and the released Gβγ dimer can then go on to stimulate a number of downstream effectors (5). When the GTP on Gα is hydrolyzed to GDP (6) the original receptor is restored (1).<ref>{{Cite book|title=Progress in Molecular Biology and Translational Science|volume = 133|last1=Stewart|first1=Adele|last2=Fisher|first2=Rory A.|year=2015|publisher=Elsevier|isbn=9780128029381|pages=1–11|doi=10.1016/bs.pmbts.2015.03.002|pmid = 26123299}}</ref>]]
Receptor-activated G proteins are bound to the inner surface of the [[cell membrane]]. They consist of the G<sub>α</sub> and the tightly associated G<sub>βγ</sub> subunits. 
There are four main families of G<sub>α</sub> subunits: Gα<sub>s</sub> (G stimulatory), Gα<sub>i</sub> (G inhibitory), Gα<sub>q/11</sub>, and Gα<sub>12/13</sub>.<ref>{{cite journal |last1=Syrovatkina |first1=Viktoriya |last2=Alegre |first2=Kamela O. |last3=Dey |first3=Raja |last4=Huang |first4=Xin-Yun |title=Regulation, Signaling, and Physiological Functions of G-Proteins |journal=Journal of Molecular Biology |date=25 September 2016 |volume=428 |issue=19 |pages=3850–3868 |doi=10.1016/j.jmb.2016.08.002 |pmid=27515397 |pmc=5023507 |language=en |issn=0022-2836}}</ref><ref>{{cite web |title=InterPro |url=https://www.ebi.ac.uk/interpro/entry/InterPro/IPR001019/ |website=www.ebi.ac.uk |access-date=25 May 2023}}</ref> They behave differently in the recognition of the effector molecule, but share a similar mechanism of activation.

==== Activation ====
When a [[ligand (biochemistry)|ligand]] activates the [[G protein-coupled receptor]], it induces a conformational change in the receptor that allows the receptor to function as a [[guanine nucleotide exchange factor]] (GEF) that exchanges GDP for GTP. The GTP (or GDP) is bound to the G<sub>α</sub> subunit in the traditional view of heterotrimeric GPCR activation. This exchange triggers the dissociation of the G<sub>α</sub> subunit (which is bound to GTP) from the G<sub>βγ</sub> dimer and the receptor as a whole. However, models which suggest molecular rearrangement, reorganization, and pre-complexing of effector molecules are beginning to be accepted.<ref name="Kou Qin">{{cite journal | vauthors = Qin K, Dong C, Wu G, Lambert NA | title = Inactive-state preassembly of G(q)-coupled receptors and G(q) heterotrimers | journal = Nature Chemical Biology | volume = 7 | issue = 10 | pages = 740–7 | date = August 2011 | pmid = 21873996 | pmc = 3177959 | doi = 10.1038/nchembio.642 }}</ref><ref name="pmid17095603">{{cite journal | vauthors = Digby GJ, Lober RM, Sethi PR, Lambert NA | title = Some G protein heterotrimers physically dissociate in living cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 47 | pages = 17789–94 | date = November 2006 | pmid = 17095603 | pmc = 1693825 | doi = 10.1073/pnas.0607116103 | bibcode = 2006PNAS..10317789D | doi-access = free }}</ref><ref name="pmid19089952">{{cite journal | vauthors = Khafizov K, Lattanzi G, Carloni P | title = G protein inactive and active forms investigated by simulation methods | journal = Proteins | volume = 75 | issue = 4 | pages = 919–30 | date = June 2009 | pmid = 19089952 | doi = 10.1002/prot.22303 | s2cid = 23909821 }}</ref> Both G<sub>α</sub>-GTP and G<sub>βγ</sub> can then activate different ''signaling cascades'' (or ''[[second messenger]] pathways'') and effector proteins, while the receptor is able to activate the next G protein.<ref name="pmid20348012">{{cite journal | vauthors = Yuen JW, Poon LS, Chan AS, Yu FW, Lo RK, Wong YH | title = Activation of STAT3 by specific Galpha subunits and multiple Gbetagamma dimers | journal = The International Journal of Biochemistry & Cell Biology | volume = 42 | issue = 6 | pages = 1052–9 | date = June 2010 | pmid = 20348012 | doi = 10.1016/j.biocel.2010.03.017 }}</ref>

==== Termination ====
The G<sub>α</sub> subunit will eventually [[Hydrolysis|hydrolyze]] the attached GTP to GDP by its inherent [[enzyme|enzymatic]] activity, allowing it to re-associate with G<sub>βγ</sub> and starting a new cycle. A group of proteins called [[Regulator of G protein signalling]] (RGSs), act as [[GTPase-activating proteins]] (GAPs), are specific for G<sub>α</sub> subunits. These proteins accelerate the hydrolysis of GTP to GDP, thus terminating the transduced signal. In some cases, the effector ''itself'' may possess intrinsic GAP activity, which then can help deactivate the pathway. This is true in the case of [[phospholipase C]]-beta, which possesses GAP activity within its [[C-terminus|C-terminal]] region. This is an alternate form of regulation for the G<sub>α</sub> subunit. Such G<sub>α</sub> GAPs do not have catalytic residues (specific amino acid sequences) to activate the G<sub>α</sub> protein. They work instead by lowering the required [[activation energy]] for the reaction to take place.<ref>{{cite book | vauthors = Sprang SR, Chen Z, Du X | title = Structural basis of effector regulation and signal termination in heterotrimeric Galpha proteins | chapter = Structural Basis of Effector Regulation and Signal Termination in Heterotrimeric Gα Proteins | volume = 74 | pages = 1–65 | year = 2007 | pmid = 17854654 | doi = 10.1016/S0065-3233(07)74001-9 | isbn = 978-0-12-034288-4 | series = Advances in Protein Chemistry }}</ref>

====Specific mechanisms====

=====G<sub>αs</sub>=====
'''[[Gαs|G<sub>αs</sub>]]''' activates the [[cAMP-dependent pathway]] by stimulating the production of [[cyclic AMP]] (cAMP) from [[adenosine triphosphate|ATP]]. This is accomplished by direct stimulation of the membrane-associated enzyme [[adenylate cyclase]]. cAMP can then act as a second messenger that goes on to interact with and activate [[protein kinase A]] (PKA). PKA can phosphorylate a myriad downstream targets.

The [[cAMP-dependent pathway]] is used as a signal transduction pathway for many hormones including:

* [[Antidiuretic hormone|ADH]] – Promotes water retention by the [[kidneys]] (created by the [[magnocellular neurosecretory cell]]s of the [[posterior pituitary]])
* [[GHRH]] – Stimulates the synthesis and release of GH ([[somatotropic cell]]s of the [[anterior pituitary]])
* [[GHIH]] – Inhibits the synthesis and release of GH (somatotropic cells of anterior pituitary)
* [[Corticotropin-releasing hormone|CRH]] – Stimulates the synthesis and release of ACTH (anterior pituitary)
* [[ACTH]] – Stimulates the synthesis and release of [[cortisol]] ([[zona fasciculata]] of the [[adrenal cortex]] in the adrenal glands)
* [[Thyroid-stimulating hormone|TSH]] – Stimulates the synthesis and release of a majority of [[Thyroxine|T4]] (thyroid gland)
* [[Luteinizing hormone|LH]] – Stimulates follicular maturation and ovulation in women; or testosterone production and spermatogenesis in men
* [[Follicle stimulating hormone|FSH]] – Stimulates follicular development in women; or [[spermatogenesis]] in men
* [[Parathyroid hormone|PTH]] – Increases [[blood calcium]] levels.  This is accomplished via the [[parathyroid hormone 1 receptor]] (PTH1) in the kidneys and bones, or via the [[parathyroid hormone 2 receptor]] (PTH2) in the central nervous system and brain, as well as the bones and kidneys.
* [[Calcitonin]] – Decreases blood calcium levels (via the [[calcitonin receptor]] in the intestines, bones, kidneys, and brain)
* [[Glucagon]] – Stimulates [[glycogen]] breakdown in the liver
* [[human chorionic gonadotropin|hCG]] – Promotes cellular differentiation, and is potentially involved in [[apoptosis]].<ref>{{cite journal | vauthors = Cole LA | title = Biological functions of hCG and hCG-related molecules | journal = Reproductive Biology and Endocrinology | volume = 8 | issue = 1 | pages = 102 | date = August 2010 | pmid = 20735820 | pmc = 2936313 | doi = 10.1186/1477-7827-8-102 | doi-access = free }}</ref>
* [[Epinephrine]] – released by the ''[[adrenal medulla]]'' during the fasting state, when body is under metabolic duress.  It stimulates [[glycogenolysis]], in addition to the actions of [[glucagon]].

=====G<sub>αi</sub>=====
'''[[Gαi|G<sub>αi</sub>]]''' inhibits the production of cAMP from ATP.
e.g. somatostatin, prostaglandins

=====G<sub>αq/11</sub>=====
'''[[Gαq|G<sub>αq/11</sub>]]''' stimulates the membrane-bound [[phospholipase C]] beta, which then cleaves [[phosphatidylinositol 4,5-bisphosphate]] (PIP<sub>2</sub>) into two second messengers, [[inositol trisphosphate]] (IP<sub>3</sub>) and [[diacylglycerol]] (DAG). IP<sub>3</sub> induces calcium release from the [[endoplasmic reticulum]]. DAG activates [[protein kinase C]].
The Inositol Phospholipid Dependent Pathway is used as a signal transduction pathway for many hormones including:
* Epinephrine
* ADH ([[Vasopressin]]/AVP) – Induces the synthesis and release of [[glucocorticoid]]s ([[Zona fasciculata]] of [[adrenal cortex]]); Induces vasoconstriction (V1 Cells of [[Posterior pituitary]])
* [[Thyrotropin-releasing hormone|TRH]] – Induces the synthesis and release of TSH ([[Anterior pituitary gland]])
* TSH – Induces the synthesis and release of a small amount of T4 ([[Thyroid Gland]])
* [[Angiotensin#Angiotensin II|Angiotensin II]] – Induces Aldosterone synthesis and release ([[zona glomerulosa]] of adrenal cortex in kidney)
* [[Gonadotropin-releasing hormone|GnRH]] – Induces the synthesis and release of FSH and LH (Anterior Pituitary)

=====G<sub>α12/13</sub>=====
*'''[[G12/G13 alpha subunits|G<sub>α12/13</sub>]]''' are involved in Rho family GTPase signaling (see [[Rho family of GTPases]]).  This is through the RhoGEF superfamily involving the [[RhoGEF domain]] of the proteins' structures). These are involved in control of cell cytoskeleton remodeling, and thus in regulating cell migration.

=====G<sub>β</sub>, G<sub>γ</sub>=====
*The '''[[Beta-gamma complex|G<sub>βγ</sub>]]''' complexes sometimes also have active functions. Examples include coupling to and activating [[G protein-coupled inwardly-rectifying potassium channel]]s.

===Small GTPases===
{{Main|Small GTPase}}

Small GTPases, also known as small G-proteins, bind GTP and GDP likewise, and are involved in [[signal transduction]]. These proteins are homologous to the alpha (α) subunit found in heterotrimers, but exist as monomers.  They are small (20-kDa to 25-kDa) [[protein]]s that bind to guanosine triphosphate ([[Guanosine triphosphate|GTP]]). This family of proteins is homologous to the [[Ras subfamily|Ras GTPases]] and is also called the Ras superfamily [[GTPase]]s.

== Lipidation ==
In order to associate with the inner leaflet of the plasma membrane, many G proteins and small GTPases are lipidated{{Citation needed|date=May 2024|reason=This is a publicly verifiable claim.}}, that is, covalently modified with lipid extensions. They may be [[myristoylated]], [[palmitoylated]] or [[prenylated]].

== References ==
{{reflist|32em}}

==External links==
*{{MeSH name|GTP-Binding+Proteins|3=GTP-Binding Proteins}}

{{Carrier proteins}}
{{Intracellular signaling peptides and proteins}}
{{Acid anhydride hydrolases}}
{{Enzymes}}
{{Signal transduction}}
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[[Category:G proteins| ]]
[[Category:Peripheral membrane proteins]]
[[Category:Cell signaling]]
[[Category:Signal transduction]]
[[Category:EC 3.6]]