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Literature summary for 3.6.5.2 extracted from

  • Schaefer, A.; Reinhard, N.R.; Hordijk, P.L.
    Toward understanding RhoGTPase specificity: structure, function and local activation (2014), Small GTPases, 5, 6.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.6.5.2

Inhibitors

Inhibitors Comment Organism Structure
additional information most RhoGTPases bind to chaperones, called guanine nucleotide dissociation inhibitors (RhoGDIs), which are cytosolic proteins that lack enzymatic activity. GDIs retain RhoGTPases in the inactive conformation, sequester them from cellular membranes and protect the GTPase from effector binding and proteolytic degradation; most RhoGTPases bind to chaperones, called guanine nucleotide dissociation inhibitors (RhoGDIs), which are cytosolic proteins that lack enzymatic activity. GDIs retain RhoGTPases in the inactive conformation, sequester them from cellular membranes and protect the GTPase from effector binding and proteolytic degradation; most RhoGTPases bind to chaperones, called guanine nucleotide dissociation inhibitors (RhoGDIs), which are cytosolic proteins that lack enzymatic activity. GDIs retain RhoGTPases in the inactive conformation, sequester them from cellular membranes and protect the GTPase from effector binding and proteolytic degradation Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
GTP + H2O Homo sapiens
-
 GDP + phosphate
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P08134
-
-
Homo sapiens P61586
-
-
Homo sapiens P62745
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
lipoprotein the C-terminus of RhoGTPases comprises, next to the hypervariable region, the CAAX-box to which a lipid anchor is attached allowing GTPase binding to membranes. RhoA, RhoB and RhoC differ in this posttranslational lipid modification which has consequences for their subcellular localization. The lipid anchor regulates the interaction with RhoGDIs and with regions within the plasma membrane (RhoA, RhoC) or endosomal vesicles (RhoB). RhoA and RhoC are geranylgeranylated, whereas RhoB has both a palmitoyl anchor and a farnesyl or geranylgeranyl group Homo sapiens
phosphoprotein PKA- and PKG-mediated phosphorylation of RhoA on Ser188, which is located in the hypervariable C-terminus. This phosphorylation serves as a Rho-inactivating signal, as it promotes GDI binding and membrane dissociation and protects RhoA from proteolytic degradation. In addition, this phosphorylation interferes with RhoA binding to ROCK further underscoring a role of the C-terminus in effector interactions Homo sapiens
phosphoprotein RhoC, but not RhoA, is phosphorylated on Ser73 in the alpha2-helix by the kinase Akt in SUM149 breast cancer cells54 although Ser73 is highly conserved among all 3 Rho-isoforms. Intriguingly, phosphorylation of RhoC is required for downstream signaling and invasiveness, which contrasts markedly with the inactivating phosphorylation at Ser188 in RhoA Homo sapiens
side-chain modification wild type and activated RhoA is ubiquitylated on Lys6 and Lys7 in the beta1-strand by the E3 ubiquitin ligase Smurf1 resulting in local RhoA degradation Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
GTP + H2O
-
 Homo sapiens GDP + phosphate
-
 ?

Subunits

Subunits Comment Organism
More structural core of RhoGTPases: the G domain, the Rho insert region, and the C-terminus of RhoGTPases, structure analysis, detailed overview. The hypervariable region also functions as protein binding site and determines, at least in part, specific binding to regulatory or effector proteins. In most RhoGTPases, including RhoA and RhoC, this region of around 10 residues harbors a polybasic stretch that binds the inner leaflet of the plasma membrane. RhoA, RhoB and RhoC have a very similar structure of the G domain and the insert region Homo sapiens

Synonyms

Synonyms Comment Organism
RhoA
-
 Homo sapiens
RhoB
-
 Homo sapiens
RhoGTPase
-
 Homo sapiens

General Information

General Information Comment Organism
additional information Rho GTPase structure-function analysis, comparisons of RhoA, RhoB, and RhoC enzymes, overview. Multiple regions in RhoA/B/C cooperate to provide specificity in binding to regulators and effectors. These specific interactions are highly regulated in time and space. Visualization and analyzsis of localized GTPase activation using biosensors that allow imaging of isoform-specific, localized regulation Homo sapiens
physiological function cell adhesion and migration are regulated through the concerted action of cytoskeletal dynamics and adhesion proteins, the activity of which is governed by RhoGTPases. Specific RhoGTPase signaling requires spatio-temporal activation and coordination of subsequent protein-protein and protein-lipid interactions. The nature, location and duration of these interactions are dependent on polarized extracellular triggers, such as cell-cell contact, and intracellular modifying events, such as phosphorylation. RhoA, RhoB, and RhoC are highly homologous GTPases that, however, succeed in generating specific intracellular responses Homo sapiens