Transforming protein RhoA (RHOA)
The protein contains 193 amino acids for an estimated molecular weight of 21768 Da.
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. Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers (PubMed:8910519, PubMed:9121475, PubMed:31570889). 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, P (updated: June 17, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Actin cytoskeleton organization
Actin cytoskeleton reorganization
Actin filament bundle assembly
Actin filament organization
Alpha-beta T cell lineage commitment
Androgen receptor signaling pathway
Angiotensin-mediated vasoconstriction involved in regulation of systemic arterial blood pressure
Apical junction assembly
Apolipoprotein A-I-mediated signaling pathway
Axon guidance
Beta selection
Blood coagulation
Cell junction assembly
Cell migration
Cell-matrix adhesion
Cellular response to calcium ion
Cellular response to chemokine
Cellular response to cytokine stimulus
Cellular response to lipopolysaccharide
Cerebral cortex cell migration
Cleavage furrow formation
Cortical cytoskeleton organization
Cytoplasmic microtubule organization
Endothelial cell migration
Endothelial tube lumen extension
Ephrin receptor signaling pathway
Establishment of epithelial cell apical/basal polarity
Establishment or maintenance of actin cytoskeleton polarity
Establishment or maintenance of cell polarity
Forebrain radial glial cell differentiation
G protein-coupled receptor signaling pathway
GTP metabolic process
Metabolic process
Mitotic cleavage furrow formation
Mitotic spindle assembly
Negative chemotaxis
Negative regulation of axonogenesis
Negative regulation of cell migration involved in sprouting angiogenesis
Negative regulation of cell size
Negative regulation of cell-substrate adhesion
Negative regulation of I-kappaB kinase/NF-kappaB signaling
Negative regulation of intracellular steroid hormone receptor signaling pathway
Negative regulation of neuron apoptotic process
Negative regulation of oxidative phosphorylation
Negative regulation of reactive oxygen species biosynthetic process
Neuron projection morphogenesis
Neurotrophin TRK receptor signaling pathway
Neutrophil degranulation
Odontogenesis
Ossification involved in bone maturation
Phosphatidylinositol-mediated signaling
Platelet activation
Positive regulation of actin filament polymerization
Positive regulation of alpha-beta T cell differentiation
Positive regulation of axonogenesis
Positive regulation of cell growth
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
Positive regulation of cytokinesis
Positive regulation of I-kappaB kinase/NF-kappaB signaling
Positive regulation of leukocyte adhesion to vascular endothelial cell
Positive regulation of lipase activity
Positive regulation of neuron apoptotic process
Positive regulation of neuron differentiation
Positive regulation of NF-kappaB import into nucleus
Positive regulation of NIK/NF-kappaB signaling
Positive regulation of podosome assembly
Positive regulation of protein serine/threonine kinase activity
Positive regulation of stress fiber assembly
Positive regulation of T cell migration
Positive regulation of translation
Positive regulation of vascular associated smooth muscle contraction
Protein deubiquitination
Regulation of actin cytoskeleton organization
Regulation of axonogenesis
Regulation of calcium ion transport
Regulation of cell migration
Regulation of cell motility
Regulation of cell shape
Regulation of dendrite development
Regulation of focal adhesion assembly
Regulation of microtubule cytoskeleton organization
Regulation of modification of postsynaptic actin cytoskeleton
Regulation of modification of synaptic structure
Regulation of neural precursor cell proliferation
Regulation of osteoblast proliferation
Regulation of small GTPase mediated signal transduction
Regulation of systemic arterial blood pressure by endothelin
Regulation of transcription by RNA polymerase II
Response to amino acid
Response to drug
Response to ethanol
Response to glucocorticoid
Response to glucose
Response to hypoxia
Response to mechanical stimulus
Rho protein signal transduction
Roundabout signaling pathway
Skeletal muscle satellite cell migration
Skeletal muscle tissue development
Small GTPase mediated signal transduction
Stress fiber assembly
Stress-activated protein kinase signaling cascade
Substantia nigra development
Substrate adhesion-dependent cell spreading
Trabecula morphogenesis
Transforming growth factor beta receptor signaling pathway
Vascular endothelial growth factor receptor signaling pathway
Viral process
Wnt signaling pathway, planar cell polarity pathway
Wound healing, spreading of cells
Cellular Component
Apical junction complex
Axon
Cell cortex
Cell division site
Cell junction
Cell periphery
Cell projection
Cleavage furrow
Cytoplasm
Cytoplasmic vesicle
Cytoskeleton
Cytosol
Dendritic spine
Endoplasmic reticulum membrane
Endosome
Extracellular exosome
Extrinsic component of cytoplasmic side of plasma membrane
Ficolin-1-rich granule membrane
Focal adhesion
Glutamatergic synapse
Intracellular membrane-bounded organelle
Lamellipodium
Midbody
Mitochondrion
Neuron projection
Nucleus
Plasma membrane
Postsynapse
Ruffle membrane
Secretory granule membrane
Vesicle
The reference OMIM entry for this protein is 165390
Ras homolog gene family, member a; rhoa
Aplysia ras-related homolog 12; arh12
Arha
Oncogene rho h12; rhoh12; rho12
CLONING
Madaule and Axel (1985) identified a new family of Ras genes, the Rho genes, related to a gene originally identified in Aplysia. Human cDNAs encoding 3 Rho, or ARH (Aplysia Ras-related homolog), proteins were isolated and designated H6 (RHOB; 165370), H9 (RHOC; 165380), and H12 (RHOA). RHOA encodes a 191-amino acid protein that shares 85% homology with RHOB and 35% homology with HRAS (190020) (Yeramian et al., 1987).MAPPING
Cannizzaro et al. (1990) mapped 1 member of the ARH family, the H12 (RHOA) gene, to chromosome 3p21 by in situ hybridization. Kiss et al. (1997) assigned the RHOA gene to chromosome 3p21.3 by fluorescence in situ hybridization and by PCR study of somatic cell hybrids.BIOCHEMICAL FEATURES
Maesaki et al. (1999) reported the 2.2-angstrom crystal structure of RhoA bound to an effector domain of protein kinase PRKCL1 (601302). The structure revealed the antiparallel coiled-coil finger (ACC finger) fold of the effector domain that binds to the Rho specificity-determining regions containing switch I, beta strands B2 and B3, and the C-terminal alpha helix A5, predominantly by specific hydrogen bonds. The ACC finger fold is distinct from those for other small G proteins and provides evidence for the diverse ways of effector recognition. Sequence analysis based on the structure suggested that the ACC finger fold is widespread in Rho effector proteins. Lutz et al. (2007) determined the crystal structure of the G-alpha-q (600998)-p63RhoGEF (610215)-RhoA complex, detailing the interactions of G-alpha-q with the Dbl and pleckstrin homology (DH and PH) domains of p63RhoGEF. These interactions involved the effector-binding site and the C-terminal region of G-alpha-q and appeared to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio (601893), Duet (604605), and p63RhoGEF were shown to constitute a family of G-alpha-q effectors that appear to activate RhoA both in vitro and in intact cells. Lutz et al. (2007) proposed that this structure represents the crux of an ancient signal transduction pathway that is expected to be important in an array of physiologic processes.GENE FUNCTION
The small guanosine triphosphatase (GTP) Rho regulates remodeling of the actin cytoskeleton during cell morphogenesis and motility. In their Figure 3C, Maekawa et al. (1999) diagrammed proposed signaling pathways for Rho-induced remodeling of the actin cytoskeleton. They demonstrated that active Rho signals to its downstream effector ROCK1 (601702), which phosphorylates and activates LIM kinase (see 601329). LIM kinase, in turn, phosphorylates cofilin (601442), inhibiting its actin-depolymerizing activity. Nakamura et al. (2001) studied the role of Rho in the migration of corneal epithelial cells in rabbit. They detected both ROCK1 and ROCK2 (604002) in the corneal epithelium at protein and mRNA levels. They found that exoenzyme C3, a Rho inhibitor, inhibits corneal epithelial migration in a dose-dependent manner and prevents the stimulatory effect of the Rho activator lysophosphatidic acid (LPA). Both cytochalasin B, an inhibitor of actin filament assembly, and ML7, an inhibitor of myosin light chain kinase, also prevent LPA stimulation of epithelial migration. The authors suggested that Rho mediates corneal epithelial migration in response to external stimuli by regulating the organization of the actin cytoskeleton. Rao et al. (2001) investigated the role of Rho kinase in the modu ... More on the omim web site
June 29, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
July 4, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 165390 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed