Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

RHOA (P61586) - Overview - Molecular Target Synopsis

Protein


RHOA, Transforming protein RhoA
Enzyme Classification 3.6.5.2
UniProt P61586

Also Known as RHOA_HUMAN, RHOA, ARH12, ARHA, RHO12

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 cytoskeletal dynamics, cell migration and cell cycle. Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers (PubMed:8910519, PubMed:9121475). Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis (PubMed:16236794, PubMed:12900402). 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). Regulates KCNA2 potassium channel activity by reducing its location at the cell surface in response to CHRM1 activation; promotes KCNA2 endocytosis (PubMed:9635436, PubMed:19403695). May be an activator of PLCE1 (PubMed:16103226). In neurons, involved in the inhibiton 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)., (Microbial infection) Serves as a target for the yopT cysteine peptidase from Yersinia pestis, vector of the plague. Interacts with ARHGEF28 (By similarity). Interacts (via GTP-bound form) with RIPOR1 (via N-terminus); this interaction links RHOA to STK24 and STK26 kinases (PubMed:27807006). Interacts with RIPOR2 (via active GTP- or inactive GDP-bound forms) isoform 1 and isoform 2; these interactions are direct, block the loading of GTP to RHOA and decrease upon chemokine CCL19 stimulation in primary T lymphocytes (PubMed:25588844). Binds PRKCL1, ROCK1 and ROCK2 (PubMed:10388627, PubMed:8617235, PubMed:8641286). Interacts with ARHGEF2, ARHGEF3, NET1 and RTKN (PubMed:10940294, PubMed:12221096, PubMed:9857026). Interacts with PLCE1 and AKAP13 (PubMed:11696353, PubMed:12900402). Interacts with DIAPH1 (PubMed:23325789). Interacts (in the constitutively activated, GTP-bound form) with DGKQ (PubMed:10066731). Interacts with RACK1; enhances RHOA activation (PubMed:20499158). Interacts with PKP4; the interaction is detected at the midbody (PubMed:17115030). Interacts (GTP-bound form preferentially) with PKN2; the interaction stimulates autophosphorylation and phosphorylation of PKN2 (PubMed:20974804, PubMed:9121475). Interacts with ARHGDIA; this interaction inactivates and stabilizes RHOA (PubMed:20400958). Interacts with ARHGDIB. Interacts (GTP-bound form) with KCNA2 (via cytoplasmic N-terminal domain) (PubMed:9635436).

6R3V
CRYSTAL STRUCTURE OF RHOA-GDP-PI IN COMPLEX WITH RHOGAP
RCSB/PDB
Inspect Structure
See all 3D Structures for RHOA

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


Gene Copy Number Variation


In COSMIC - Cell Lines Project RHOA has gain in 0 cell-lines, loss in 8 cell-lines and no signal in 997 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SN12C, SNB_19, NCI_H226

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H2347, SNU-1, NCI-H2373

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, HSMM, HMEC

(see details)

3D Structures


For RHOA there are:
44 structures (73 chains) solved
37 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


RHOA has been screened with 149 compounds (323 bioactivities). (see details)