View source for Small GTPase

{{Short description|Class of enzymes}}
{{Infobox enzyme
| Name       = Small monomeric GTPase
| EC_number  = 3.6.5.2
| CAS_number =
| GO_code    = 
| image      = 
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}}
'''Small GTPases''' ({{EC number|3.6.5.2}}), also known as '''small G-proteins''', are a family of [[hydrolase]] [[enzymes]] that can [[Molecular binding|bind]] and [[hydrolyze]] [[guanosine triphosphate]] (GTP). They are a type of [[G-protein]] found in the [[cytosol]] that are [[Sequence homology|homologous]] to the alpha subunit of [[heterotrimeric G-protein]]s, but unlike the alpha subunit of G proteins, a small GTPase can function independently as a hydrolase enzyme to bind to and hydrolyze a guanosine triphosphate (GTP) to form [[guanosine diphosphate]] (GDP). The best-known members are the [[Ras (protein)|Ras GTPases]] and hence they are sometimes called '''[[Ras subfamily]] GTPases'''.

A typical G-protein is active when bound to GTP and inactive when bound to GDP (i.e. when the GTP is hydrolyzed to GDP). The GDP can then be replaced by free GTP. Therefore, a G-protein can be switched on and off. GTP hydrolysis is accelerated by [[GTPase-activating proteins|GTPase activating proteins]] (GAPs), while GTP exchange is catalyzed by [[guanine nucleotide exchange factors]] (GEFs). Activation of a GEF typically activates its cognate G-protein, while activation of a GAP results in inactivation of the cognate G-protein.
[[Guanosine nucleotide dissociation inhibitors]] (GDI) maintain small GTPases in the inactive state.

Small GTPases regulate a wide variety of processes in the [[Cell (biology)|cell]], including growth, [[cellular differentiation]], cell movement and [[lipid]] [[vesicle (biology)|vesicle]] transport.

== The Ras superfamily ==
{{Main|Ras superfamily}}
There are more than a hundred proteins in the Ras superfamily.<ref name="pmid15731001">{{cite journal | vauthors = Wennerberg K, Rossman KL, Der CJ | title = The Ras superfamily at a glance | journal = J. Cell Sci. | volume = 118 | issue = Pt 5 | pages = 843–6 |date=March 2005 | pmid = 15731001 | doi = 10.1242/jcs.01660 | doi-access =  }}</ref> Based on structure, sequence and function, the Ras superfamily is divided into five main families, (Ras, [[Rho family of GTPases|Rho]], [[Ran (biology)|Ran]], [[Rab (G-protein)|Rab]] and [[ADP ribosylation factor|Arf]] GTPases).<ref>{{cite book|last1=Goitre|first1=L|last2=Trapani|first2=E|last3=Trabalzini|first3=L|last4=Retta|first4=SF|title=The Ras superfamily of small GTPases: the unlocked secrets.|journal=<!--Bypass Citation bot -->|date=26 December 2013|volume=1120|pages=1–18|doi=10.1007/978-1-62703-791-4_1|pmid=24470015|series=Methods in Molecular Biology|isbn=978-1-62703-790-7}}</ref> The Ras family itself is further divided into 6 subfamilies: [[Ras subfamily|Ras]], Ral ([[Ral-A]] and [[Ral-B]]), Rit ([[Rit1]] and [[Rit2]]), [[Rap GTP-binding protein|Rap]], [[Rheb]], and [[RRAD (gene)|Rad]]. ''Miro'' is a recent contributor to the superfamily.{{citation needed|date=March 2023}}

Each subfamily shares the common core G domain, which provides essential GTPase and nucleotide exchange activity.{{citation needed|date=March 2023}}

The surrounding sequence helps determine the functional specificity of the small GTPase, for example the 'Insert Loop', common to the Rho subfamily, specifically contributes to binding to effector proteins such as [[IQGAP]] and [[Wiskott-Aldrich syndrome protein|WASP]].{{citation needed|date=March 2023}}

The Ras family is generally responsible for cell proliferation, Rho for cell morphology, Ran for nuclear transport and Rab and Arf for vesicle transport.<ref name=Munemitsu>{{cite journal |vauthors =Munemitsu S, Innis M, Clark R, McCormick F, Ullrich A, Polakis P |year=1990 |title=Molecular cloning and expression of a G25K cDNA, the human homolog of the yeast cell cycle gene CDC42 |journal=Mol Cell Biol |volume=10 |issue=11 |pages=5977–82 |issn=0270-7306 |pmid=2122236 |pmc=361395 |doi=10.1128/MCB.10.11.5977}}</ref>

==See also==
* [[GTP-binding protein regulators]]

==References==
{{Reflist}}

==External links==
* {{MeshName|Small+GTPases}}

{{Vesicular transport proteins}}
{{Intracellular signaling peptides and proteins}}
{{Acid anhydride hydrolases}}
{{Enzymes}}
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[[Category:G proteins]]
[[Category:Peripheral membrane proteins]]