RHOA

Protein RHOA

Identifiers
ras homolog family member A
HUGO:RHOA hgnc_id:HGNC:667 HGNC:667 ENTREZ:387 UNIPROT:P61586
HUGO:RHOA
HUGO:RHOA, HGNC:667, ENTREZ:387, GENECARDS:GC03M049371, UNIPROT:P61586
ARH12, ARHA, "ras homolog gene family, member A"
HUGO:RHOA HGNC:667 ENTREZ:387 UNIPROT:P61586 GENECARDS:RHOA REACTOME:63078 KEGG:387 ATLASONC:RHOAID42107ch3p21 WIKI:RHOA

Maps_Modules
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / MOTILITY
EMT Senescence / EMT_REGULATORS
EMT Senescence / CELL_CELL_ADHESIONS
EMT Senescence / TIGHT_JUNCTIONS
EMT Senescence / CYTOSKELETON_POLARITY
EMT Senescence / SENESCENCE
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / CASPASES
Regulated Cell Death / MITOCHONDRIAL_GENES
Regulated Cell Death / MITOCHONDRIAL_METABOLISM
Regulated Cell Death / MOMP_REGULATION
Regulated Cell Death / PYROPTOSIS
HMC:AVOIDING_IMMUNE_DESTRUCTION
Innate Immunity / IMMUNOSTIMULATORY_CORE_PATHWAYS
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / WNT_NON_CANONICAL

References
CASCADE:INTEGRIN
CASCADE:LIF
CASCADE:TGFB
CASCADE:EGF
CASCADE:CXCL12
CASCADE:CAV
PMID:18037882
Rho???ROCK function is required in leading fibroblasts probably downstream of integrins a5b1 and a3b1
More detailed analysis of Rho isoforms revealed that RhoA, but not RhoB, is required for fibroblasts to promote SCC invasion
PMID:24857661
siRNA-mediated knockdown of RhoA expression or pharmacological inhibition of Rho-kinase (ROCK) activity resulted in blockade of both TGF-??1 and LIF-dependent proinvasive hDF activity (Figures S2B and S2C). Long-term stimulation of both TGF-?? and LIF cytokines also upregulated RhoA small GTPase and myosin light chain 2 (MLC2) proteins, leading to an increase in MLC2 phosphorylation at ser19, which attests for an increased activity
PMID:18423981
TGF-?? induced a strong activation of RhoA and stress fiber formation in fibroblasts,
EGF down-regulated Rho-GTP levels in fibroblasts, giving permissive signals for Rac1 activation, fibroblast polarization, and invasion.
PMID:21178402
RhoA was thought to be activated mainly at the retracting tail (red) to promote tail contraction, while Rac1 was thought to be activated at the front of the cell to promote lamellipodial protrusion.
PMID:17517963
caveolin-deficient MEFs showed a notable decrease in basal Rho activity and a significant increase in Rac and Cdc42 activity
PMID:20535745
CXCR4 receptor and CXCL12 both are expressed in fibroblasts and probably provides positive loop in fibroblast activation
and promotes RhoA-activation aand actin polymerisation.
Rho???ROCK function is required only in stromal fibroblasts for collective SCC invasion.
PMID:9822605
Members of the Rho/Rac family can be grouped into 3 classes according to amino acid sequence similarities.
The first subfamily is composed of four Rac proteins (Rac-1, Rac-2, Rac-3 and RhoG). Some of these proteins promote the activation of protein kinases such as PAK, c-Jun N-terminal kinase (JNK) and p38MAPK. They are also involved in the activation of other independent pathways regulating membrane ruffling and cell proliferation.
The second subfamily, Rho, includes RhoA, RhoB, RhoC, RhoD, RhoE and TTF proteins. RhoA has been characterized extensively and shown to be involved in cell transforma- tion, formation of stress fibers and focal adhesions, and in the stimulation of protein kinases such as PKN and p160Rock
Finally, the third subfamily is composed of TC10 and the two isoforms of the Cdc42 protein. Cdc42 was shown to be involved in the activation of JNK, PAK and p38MAPK as well as in the formation of filopodia in the plasma membrane
PMID:15761148
PARD6A interacts with TGFB receptors and is phsophorylated by TGFBRIII.
Phosphorylation of Par6 is required for TGFB-dependent EMT in mammary gland epithelial cells
This phosphorylation stimulates the interaction of PARD6A with the E3 ubiquitin ligase Smurf1.
Smurf1, in turn, targets GTPase RhoA for degradation, thereby leading to a loss of tight junctions.
TGFB regulation of the Par6-Smurf1-RhoA pathway is required for EMT.
PMID:14657501
Smurf1 functions as an effector of the polarity complex by mediating localized ubiquitination and degradation of RhoA in cellular protrusions.
Atypical protein kinase C (aPKCZ), an effector of the Cdc42/Rac1-PAR6 polarity complex, recruited Smurf1 to cellular protrusions, where it controlled the local level of RhoA.
PMID:22949611
Signaling molecules act directly on polarity proteins, bypassing transcription factors such as Snail and Zeb1:
TGFBRI binds to the tight junction protein Occludin and locally assembles into a complex containing Par6.
Activated TGFBRII phosphorylates Par6, which binds to Smurf1 and causes RhoA ubiquitylation and the dissolution of junctions.
PMID:14744429
RhoA is the prototypical member of the Rho GTPase family, which regulates many cellular processes, including cellular adhesion, motility, and polarity
RhoA is an important modulator of cell junction formation and stability:
PMID:7479854
Rho protein regulates tight junctions and perjunctional actin organization in polarized epithelia
PMID:9362522
Rho subfamily is necessary for the formation of both the cadherin-based cell???cell adhesion and the tight junction
PMID:9660866
RhoA and Rac1 regulate gate and fence functions of the TJ, and play a role in the spatial organization of TJ proteins at the apex of the lateral membrane
PMID:12361600
PMID:11992112
RhoA functions to maintain apical-basal polarity and cell junctions.
PMID:11739775
PMID:11729192
RhoA can stabilize tight junctions and increase transepithelial resistance
PMID:26885855
PMID:27048821
PMID:27066895
PMID:24919149
Pyrin does not directly recognize Rho
modification, but probably senses an event downstream of Rho modification in the actin cytoskeleton pathway
CASCADE:CR3
NATURAL_KILLER
MACROPHAGE
PMID:12740575
VAV1 activates RHOA and RAC1 downstream of NKG2D.
PMID:11698448
RHOA signaling in NK cells provides development of natural cytotoxicity against tumor cells.
PMID:12194823
Rho-kinase and myosin-II control phagocytic cup formation during CR3, but not FcgammaR, phagocytosis.
inhibition of the Rho --> ROK --> myosin-II pathway caused a decreased accumulation of Arp2/3 complex and F-actin around bound particles, which led to a reduction in CR-mediated phagocytic engulfment. FcgammaR-mediated phagocytosis, in contrast, was independent of Rho or ROK activity and was only dependent on myosin-II for particle internalization, not for actin cup formation. While myosins have been previously implicated in FcgammaR phagocytosis, to our knowledge, this is the first demonstration of a role for myosin-II in CR phagocytosis.

RHOA@Nucleus

References
mo_re265:( motility ) PMID:27452906

RHOA|ubi@Cytosol

References
em_emtc_emtc_re344( EMT Senescence ):
PMID:21572392
SMURF1 is an homologous to E6AP C-ter (HECT)-type E3 ubiquitin ligase
SMURF1 performs a crucial role in the regulation of the BMP signalling pathway in both embryonic development and bone remodelling.
PMID:15761148
PARD6A interacts with and is phsophorylated by TGFBR2.
Phosphorylation of Par6 is required for TGFB-dependent EMT in mammary gland epithelial cells
This phosphorylation controls the interaction of PARD6A with the E3 ubiquitin ligase Smurf1.
Smurf1, in turn, targets GTPase RhoA for degradation, thereby leading to a loss of tight junctions.
Ubiquitation of RHO1 by Smurf1 leads to disassembly of tight junctions, an important step in EMT.
PMID:22949611
Signaling molecules act directly on polarity proteins, bypassing transcription factors such as Snail and Zeb1:
TGFBR1 binds to the tight junction protein Occludin and locally assembles into a complex containing Par6.
Activated TGFBR2 phosphorylates Par6, which binds to Smurf1 and causes RhoA ubiquitylation and the dissolution of junctions.
PMID:14657501
SMURF1, but not SMURF2, decreases RHOA level, and this effect is proteasome dependent.
PMID:16472676
Smurf1 could specifically target RhoA but not Cdc42 or Rac1 for degradation.
Smurf1 interacts with the dominant inactive form of RhoA, RhoA N19, which binds constitutively to GEFs in vivo.
Smurf1 also interacts directly with either nucleotide???free or GDP???bound RhoA in vitro;
However, loading with GTPgS inhibits the interaction

RHOA@Cytoplasm

References
s_wnc1_re146:( Survival ) Not sure if Rho dissociates when active

Modifications:
In compartment: Cytoplasm

RHOA@Cytoplasm

In compartment: Cytosol

RHOA|ubi@Cytosol

In compartment: Nucleus

RHOA@Nucleus

Participates in complexes:
In compartment: Cytoplasm

In compartment: INNATE_IMMUNE_CELL_Cytosol

Participates in reactions:
As Reactant or Product:

As Catalyser: