Editing GTPase (section)

== G domain GTPases ==
In most GTPases, the specificity for the base [[guanine]] versus other nucleotides is imparted by the base-recognition motif, which has the consensus sequence [N/T]KXD. The following classification is based on shared features; some examples have mutations in the base-recognition motif that shift their substrate specificity, most commonly to ATP.<ref name="pmid11916378">{{cite journal |author=Leipe D.D. |author2=Wolf Y.I. |author3=Koonin E.V. |author4=Aravind, L. |name-list-style=amp |title=Classification and evolution of P-loop GTPases and related ATPases |journal=J. Mol. Biol. |volume=317 |issue=1 |pages=41–72 |year=2002 |doi=10.1006/jmbi.2001.5378 |pmid=11916378 |url= https://zenodo.org/record/1229904}}</ref>

=== TRAFAC class ===
The TRAFAC class of G domain proteins is named after the prototypical member, the translation factor G proteins. They play roles in translation, signal transduction, and cell motility.<ref name="pmid11916378"/>

====Translation factor superfamily{{anchor|Translation factor family}}====
{{see also|EF-G#Evolution|EF-Tu#Evolution}}
Multiple classical [[Translation (biology)|translation]] factor family GTPases play important roles in [[Transcription (genetics)#initiation|initiation]], [[Eukaryotic translation#Elongation|elongation]] and termination of [[protein biosynthesis]]. Sharing a similar mode of [[ribosome]] binding due to the β-EI domain following the GTPase, the most well-known members of the family are [[eEF-1|EF-1A]]/[[EF-Tu]], [[eEF-2|EF-2]]/[[EF-G]],<ref name="pmid6113539">{{cite journal |last1=Parmeggiani |first1=A |last2=Sander |first2=G |date=1981 |title=Properties and regulation of the GTPase activities of elongation factors Tu and G, and of initiation factor 2 |journal=Molecular and Cellular Biochemistry |volume=35 |issue=3 |pages=129–158 |doi=10.1007/BF02357085 |pmid=6113539 |s2cid=1388090 }}</ref> and class 2 [[release factor]]s. Other members include [[EF-4]] (LepA), [[BipA]] (TypA),<ref name="pmid29235176">{{cite journal |last1=Gibbs |first1=MR |last2=Fredrick |first2=K |date=2018 |title=Roles of elusive translational GTPases come to light and inform on the process of ribosome biogenesis in bacteria |journal=Molecular Microbiology |volume=107 |issue=4 |pages=445–454 |doi=10.1111/mmi.13895 |pmid=29235176 |pmc=5796857 }}</ref> ''SelB'' (bacterial selenocysteinyl-tRNA EF-Tu paralog), ''Tet'' ([[tetracycline]] resistance by ribosomal protection),<ref>{{cite journal |last1=Margus |first1=Tõnu |last2=Remm |first2=Maido |last3=Tenson |first3=Tanel |title=Phylogenetic distribution of translational GTPases in bacteria |journal=BMC Genomics |date=December 2007 |volume=8 |issue=1 |pages=15 |doi=10.1186/1471-2164-8-15|pmid=17214893 |pmc=1780047 |doi-access=free }}</ref> and [[HBS1L]] (eukaryotic [[ribosomal pause|ribosome rescue]] protein similar to release factors).

The superfamily also includes the Bms1 family from yeast.<ref name="pmid11916378"/>

=====Heterotrimeric G proteins=====
{{main|Heterotrimeric G protein}}
[[Heterotrimeric G protein]] complexes are composed of three distinct protein subunits named ''[[G alpha subunit|alpha]]'' (α), ''beta'' (β) and ''gamma'' (γ) [[protein subunit|subunit]]s.<ref name="pmid10819326">{{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> The alpha subunits contain the GTP binding/GTPase domain flanked by long regulatory regions, while the beta and gamma subunits form a stable dimeric complex referred to as the [[G beta-gamma complex|beta-gamma complex]].<ref name="pmid9131251">{{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> When activated, a heterotrimeric G protein dissociates into activated, GTP-bound alpha subunit and separate beta-gamma subunit, each of which can perform distinct signaling roles.<ref name="pmid3113327"/><ref name="pmid7579038"/> The α and γ subunit are modified by [[lipid anchor]]s to increase their association with the inner leaflet of the plasma membrane.<ref name="pmid11313912">{{cite journal |last1=Chen |first1=CA |last2=Manning |first2=DR |date=2001 |title=Regulation of G proteins by covalent modification |journal=Oncogene |volume=20 |issue=13 |pages=1643–1652 |doi=10.1038/sj.onc.1204185 |pmid=11313912 |doi-access=free }}</ref>

Heterotrimeric G proteins act as the transducers of [[G protein-coupled receptor]]s, coupling receptor activation to downstream signaling effectors and [[second messenger]]s.<ref name="pmid3113327"/><ref name="pmid7579038"/><ref name="pmid12209124">{{cite journal |last1=Pierce |first1=KL |last2=Premont |first2=RT |last3=Lefkowitz |first3=RJ |date=2002 |title=Seven-transmembrane receptors |journal= Nature Reviews Molecular Cell Biology|volume=3 |issue=9 |pages=639–650 |doi=10.1038/nrm908 |pmid=12209124 |s2cid=23659116 }}</ref> In unstimulated cells, heterotrimeric G proteins are assembled as the GDP bound, inactive trimer (G<sub>α</sub>-GDP-G<sub>βγ</sub> complex).<ref name="pmid3113327"/><ref name= "pmid7579038"/> Upon receptor activation, the activated receptor intracellular domain acts as GEF to release GDP from the G protein complex and to promote binding of GTP in its place.<ref name="pmid3113327"/><ref name="pmid7579038"/> The GTP-bound complex undergoes an activating conformation shift that dissociates it from the receptor and also breaks the complex into its component G protein alpha and beta-gamma subunit components.<ref name="pmid3113327"/><ref name="pmid7579038"/> While these activated G protein subunits are now free to activate their effectors, the active receptor is likewise free to activate additional G proteins – this allows catalytic activation and amplification where one receptor may activate many G proteins.<ref name="pmid3113327"/><ref name="pmid7579038"/>

G protein signaling is terminated by hydrolysis of bound GTP to bound GDP.<ref name="pmid3113327"/><ref name="pmid7579038"/> This can occur through the intrinsic GTPase activity of the α subunit, or be accelerated by separate regulatory proteins that act as [[GTPase-activating protein]]s (GAPs), such as members of the [[Regulator of G protein signaling]] (RGS) family).<ref name="pmid9430654"/> The speed of the hydrolysis reaction works as an internal clock limiting the length of the signal. Once G<sub>α</sub> is returned to being GDP bound, the two parts of the heterotrimer re-associate to the original, inactive state.<ref name="pmid3113327"/><ref name="pmid7579038"/>

The heterotrimeric G proteins can be classified by [[sequence homology]] of the α unit and by their functional targets into four families: G<sub>s</sub> family, G<sub>i</sub> family, G<sub>q</sub> family and G<sub>12</sub> family.<ref name="pmid10819326"/> Each of these G<sub>α</sub> protein families contains multiple members, such that the mammals have 16 distinct <sub>α</sub>-subunit genes.<ref name="pmid10819326"/> The G<sub>β</sub> and G<sub>γ</sub> are likewise composed of many members, increasing heterotrimer structural and functional diversity.<ref name="pmid10819326"/> Among the target molecules of the specific G proteins are the second messenger-generating enzymes [[adenylyl cyclase]] and [[phospholipase C]], as well as various [[ion channel]]s.<ref name="pmid12040175">{{cite journal |last1=Neves |first1=SR |last2=Ram |first2=PT |last3=Iyengar |first3=R |date=2002 |title=G protein pathways |journal=Science |volume=296 |issue=5573 |pages=1636–1639 |doi=10.1126/science.1071550 |pmid=12040175 |bibcode=2002Sci...296.1636N |s2cid=20136388 }}</ref>

=====Small GTPases=====
{{Main|Small GTPase}}
[[Small GTPase]]s function as monomers and have a molecular weight of about 21 kilodaltons that consists primarily of the GTPase domain.<ref name="pmid11152757">{{cite journal |last1=Takai |first1=Y |last2=Sasaki |first2=T |last3=Matozaki |first3=T |date=2001 |title=Small GTP-binding proteins |journal=Physiological Reviews |volume=81 |issue=1 |pages=153–208 |doi=10.1152/physrev.2001.81.1.153 |pmid=11152757 }}</ref> They are also called small or monomeric guanine nucleotide-binding regulatory proteins, small or monomeric GTP-binding proteins, or small or monomeric G-proteins, and because they have significant homology with the first-identified such protein, named [[Ras (protein)|Ras]], they are also referred to as [[Ras superfamily]] GTPases. Small GTPases generally serve as molecular switches and signal transducers for a wide variety of cellular signaling events, often involving membranes, vesicles or cytoskeleton.<ref name="pmid2116664">{{cite journal |last1=Hall |first1=A |date=1990 |title=The cellular functions of small GTP-binding proteins |journal=Science |volume= 249|issue=4969 |pages=635–640 |doi=10.1126/science.2116664 |pmid=2116664 |bibcode=1990Sci...249..635H }}</ref><ref name="pmid11152757"/> According to their primary amino acid sequences and biochemical properties, the many Ras superfamily small GTPases are further divided into five subfamilies with distinct functions: [[Ras (protein)|Ras]], [[Rho family of GTPases|Rho]] ("Ras-homology"), [[Rab (G-protein)|Rab]], [[ADP ribosylation factor|Arf]] and [[Ran protein|Ran]].<ref name="pmid11152757"/> While many small GTPases are activated by their GEFs in response to intracellular signals emanating from cell surface receptors (particularly [[growth factor receptor]]s), regulatory GEFs for many other small GTPases are activated in response to intrinsic cell signals, not cell surface (external) signals.

==== Myosin-kinesin superfamily ====
This class is defined by loss of two beta-strands and additional N-terminal strands. Both namesakes of this superfamily, [[myosin]] and [[kinesin]], have shifted to use ATP.<ref name="pmid11916378"/>

=====Large GTPases=====
See [[dynamin]] as a prototype for large monomeric GTPases.

=== SIMIBI class ===
Much of the SIMIBI class of GTPases is activated by dimerization.<ref name="pmid11916378"/> Named after the signal recognition particle (SRP), MinD, and BioD, the class is involved in protein localization, chromosome partitioning, and membrane transport. Several members of this class, including MinD and Get3, has shifted in substrate specificity to become ATPases.<ref name=pmid27658684>{{cite journal |last1=Shan |first1=SO |title=ATPase and GTPase Tangos Drive Intracellular Protein Transport. |journal=Trends in Biochemical Sciences |date=December 2016 |volume=41 |issue=12 |pages=1050–1060 |doi=10.1016/j.tibs.2016.08.012 |pmid=27658684 |pmc=5627767 |doi-access=free}}</ref>

====Translocation factors====
{{missing information|section|FlhF, which is not involved in the SRP at all but has a similar structure to Ffh and FtsY|date=October 2021}}
For a discussion of [[Protein translocation|Translocation]] factors and the role of GTP, see [[signal recognition particle]] (SRP).