RHOA

GeneName

RHOA

Summary

RHOA, also known as p21 or Rho1, is a 22 kDa small GTPase that plays a pivotal role in various cellular processes, including actin cytoskeleton organisation, cell migration, and cell junction assembly. It is localised to multiple cellular components such as the plasma membrane, cytoskeleton, and cell cortex, and is involved in the regulation of focal adhesion assembly and cellular responses to various stimuli. RHOA functions by binding to GTP and interacting with downstream effectors, influencing pathways related to cell morphology and movement.

Importance

RHOA is relevant to: - Regulation of actin dynamics and cell shape, impacting processes like cell migration and adhesion - T cell differentiation and migration, which are crucial for immune responses - Vascular biology, particularly in processes like endothelial cell migration and vasoconstriction - Developmental processes, including kidney and bone formation, indicating its role in tissue morphogenesis - Cancer biology, where its dysregulation may contribute to tumour progression and metastasis

Top Products

For researchers investigating RHOA, we highly recommend the top-selling recombinant antibody, Anti-RhoA antibody [EPR18134] (ab187027). This antibody has been validated in knockout models, ensuring its reliability in various applications, including Western blotting (WB), immunocytochemistry (ICC), and flow cytometry (FC). With 124 citations, it is well-regarded in the research community, making it an excellent choice for those seeking robust and consistent results in their studies of RHOA.

Abcam Product Citation Summary

The data indicates that RHOA is being studied across various species, including humans, rats, and mice, primarily using Western blotting as the application of choice. The studies focus on diverse biological contexts such as cancer, preeclampsia, and the effects of high glucose, highlighting the importance of RHOA in different physiological and pathological processes.

Abcam Product Citation Table

Domain

(Microbial infection) The basic-rich region is essential for yopT recognition and cleavage.

Function

Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. Mainly associated with cytoskeleton organization, in active state binds to a variety of effector proteins to regulate cellular responses such as cytoskeletal dynamics, cell migration and cell cycle (PubMed:23871831). Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers (PubMed:31570889, PubMed:8910519, PubMed:9121475). Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis (PubMed:12900402, PubMed:16236794). Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion (PubMed:20974804, PubMed:23940119). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly (PubMed:19934221). The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (PubMed:20937854). Involved in the reorientation of endothelial cells and their actin stress fibers in response to cellular mechantransduction-mediated activation by ARHGEF40 (By similarity). Regulates KCNA2 potassium channel activity by reducing its location at the cell surface in response to CHRM1 activation; promotes KCNA2 endocytosis (PubMed:19403695, PubMed:9635436). Acts as an allosteric activator of guanine nucleotide exchange factor ECT2 by binding in its activated GTP-bound form to the PH domain of ECT2 which stimulates the release of PH inhibition and promotes the binding of substrate RHOA to the ECT2 catalytic center (PubMed:31888991). May be an activator of PLCE1 (PubMed:16103226). In neurons, involved in the inhibition of the initial spine growth. Upon activation by CaMKII, modulates dendritic spine structural plasticity by relaying CaMKII transient activation to synapse-specific, long-term signaling (By similarity). Acts as a regulator of platelet alpha-granule release during activation and aggregation of platelets (By similarity). When activated by DAAM1 may signal centrosome maturation and chromosomal segregation during cell division. May also be involved in contractile ring formation during cytokinesis.

(Microbial infection) Serves as a target for the yopT cysteine peptidase from Yersinia pestis, vector of the plague.

Involvement in disease

Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies

EDFAOB

A neuroectodermal syndrome characterized by linear hypopigmentation, alopecia, apparently asymptomatic leukoencephalopathy, and facial, ocular, dental and acral anomalies. Patients show no intellectual or neurologic impairment.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

(Microbial infection) Substrate for botulinum ADP-ribosyltransferase.

(Microbial infection) Cleaved by yopT protease when the cell is infected by some Yersinia pathogens. This removes the lipid attachment, and leads to its displacement from plasma membrane and to subsequent cytoskeleton cleavage.

(Microbial infection) AMPylation at Tyr-34 and Thr-37 are mediated by bacterial enzymes in case of infection by H.somnus and V.parahaemolyticus, respectively. AMPylation occurs in the effector region and leads to inactivation of the GTPase activity by preventing the interaction with downstream effectors, thereby inhibiting actin assembly in infected cells. It is unclear whether some human enzyme mediates AMPylation; FICD has such ability in vitro but additional experiments remain to be done to confirm results in vivo.

(Microbial infection) Glycosylated at Tyr-34 by Photorhabdus asymbiotica toxin PAU_02230. Mono-O-GlcNAcylation by PAU_02230 inhibits downstream signaling by an impaired interaction with diverse regulator and effector proteins of Rho and leads to actin disassembly.

(Microbial infection) Glucosylated at Thr-37 by C.difficile toxins TcdA and TcdB in the colonic epithelium (PubMed:24905543, PubMed:7775453, PubMed:7777059). Monoglucosylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption and cell death, resulting in the loss of colonic epithelial barrier function (PubMed:7775453, PubMed:7777059).

(Microbial infection) Glycosylated (O-GlcNAcylated) at Thr-37 by C.novyi toxin TcdA (PubMed:8810274). O-GlcNAcylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption (PubMed:8810274).

(Microbial infection) Stearoylated By S.flexneri N-epsilon-fatty acyltransferase IcsB, thereby disrupting the host actin cytoskeleton.

Phosphorylation by PRKG1 at Ser-188 inactivates RHOA signaling (PubMed:11162591). Phosphorylation by SLK at Ser-188 in response to AGTR2 activation (By similarity).

Ubiquitinated by the BCR(KCTD13) and BCR(TNFAIP1) E3 ubiquitin ligase complexes, leading to its degradation by the proteasome, thereby regulating the actin cytoskeleton and synaptic transmission in neurons (PubMed:19782033). Ubiquitinated at Lys-135 in a FBXL19-mediated manner; leading to proteasomal degradation (PubMed:23871831).

Serotonylation of Gln-63 by TGM2 during activation and aggregation of platelets leads to constitutive activation of GTPase activity.

Sequence Similarities

Belongs to the small GTPase superfamily. Rho family.

Cellular localization

• Cell membrane
• Lipid-anchor
• Cytoplasmic side
• Cytoplasm
• Cytoskeleton
• Cleavage furrow
• Cytoplasm
• Cell cortex
• Midbody
• Cell projection
• Lamellipodium
• Cell projection
• Dendrite
• Nucleus
• Cytoplasm
• Localized to cell-cell contacts in calcium-treated keratinocytes (By similarity). Translocates to the equatorial region before furrow formation in a ECT2-dependent manner. Localizes to the equatorial cell cortex (at the site of the presumptive furrow) in early anaphase in an activated form and in a myosin- and actin-independent manner. Colocalizes with KANK1 at the contractile ring. Colocalizes with DAAM1 and KANK1 around centrosomes.

Alternative names

ARH12, ARHA, RHO12, RHOA, Transforming protein RhoA, Rho cDNA clone 12, h12

Database links

swissprot:P61586 swissprot:P62745 swissprot:P08134 omim:165390 omim:165380 omim:165370 entrezGene:387 entrezGene:388 entrezGene:389