RHOA

Protein RHOA map

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

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 EMT  map  / CELL_CELL_ADHESIONS  map
 EMT  map  / TIGHT_JUNCTIONS  map
 EMT  map  / CYTOSKELETON_POLARITY  map
 Survival  map  / WNT_NON_CANONICAL  map

References
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

RHOA|​ubi@Cytoplasm

References
e_re344( EMT  map ):
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  map ) Not sure if Rho dissociates when active


Modifications:
In compartment: Cytoplasm
  1. RHOA@Cytoplasm map

  2. RHOA|​ubi@Cytoplasm map

Participates in complexes:
In compartment: Cytoplasm

  1. GDP:​RHOA@Cytoplasm map

  2. GTP:​RHOA@Cytoplasm map
  3. GTP:​RHOA:​RhoA_cytoskeletal_effectors*@Cytoplasm map
  4. DIA*|​open:​GTP:​RHOA@Cytoplasm map
  5. GTP:​RHOA:​ROCK*|​open@Cytoplasm map

Participates in reactions:
As Reactant or Product:

  1. GDP:​RHOA@Cytoplasm map map RHOA|​ubi@Cytoplasm map

  2. RHOA|​ubi@Cytoplasm map map degraded
  3. GTP:​RHOA@Cytoplasm map map Tight junctions@Extracellular space map
  4. GTP:​RHOA@Cytoplasm map map GDP:​RHOA@Cytoplasm map
  5. GDP:​RHOA@Cytoplasm map map GTP:​RHOA@Cytoplasm map
  6. GTP:​RHOA@Cytoplasm map map Establishment of cell polarity@Nucleus map
  7. GTP:​RHOA@Cytoplasm map map Stress fiber formation@Nucleus map
  8. ROCK*|​closed@Nucleus map + GTP:​RHOA@Cytoplasm map map GTP:​RHOA:​ROCK*|​open@Cytoplasm map
  9. GTP:​RHOA@Cytoplasm map + DIA*|​closed@Cytoplasm map map DIA*|​open:​GTP:​RHOA@Cytoplasm map
  10. GTP:​RHOA:​RhoA_cytoskeletal_effectors*@Cytoplasm map map Cytoskeleton remodeling@Nucleus map
  11. GTP:​RHOA@Cytoplasm map + RhoA_cytoskeletal_effectors*@Cytoplasm map map GTP:​RHOA:​RhoA_cytoskeletal_effectors*@Cytoplasm map
  12. GTP:​RHOA:​RhoA_cytoskeletal_effectors*@Cytoplasm map map Actin polymerization@Nucleus map
  13. RhoA_B*@Cytoplasm map map GTP:​RHOA@Cytoplasm map
  14. APC2*:​CK1_epsilon_*:​CTHRC1:​DVL*|​pho|​pho|​pho:​FZD*:​GSK3*:​PAR6*:​RACK1*:​ROR2|​S864_pho|​pho|​pho:​RSPO3:​SYN4*:​VANGL*|​pho|​pho|​pho|​pho:​WNT*:​_beta_-Arrestin2*@Endosome map + WGEF*@Cytoplasm map + DAAM1@Cytoplasm map + RHOA@Cytoplasm map map APC2*:​CK1_epsilon_*:​CTHRC1:​DAAM1:​DVL*|​pho|​pho|​pho:​GSK3*:​ROR2|​S864_pho|​pho|​pho:​RSPO3:​SYN4*:​VANGL*|​pho|​pho|​pho|​pho:​WGEF*:​_beta_-Arrestin2*@Cytoplasm map
  15. APC2*:​CK1_epsilon_*:​CTHRC1:​DAAM1:​DVL*|​pho|​pho|​pho:​GSK3*:​ROR2|​S864_pho|​pho|​pho:​RSPO3:​SYN4*:​VANGL*|​pho|​pho|​pho|​pho:​WGEF*:​_beta_-Arrestin2*@Cytoplasm map map APC2*:​CK1_epsilon_*:​CTHRC1:​DAAM1:​DVL*|​pho|​pho|​pho:​GSK3*:​ROR2|​S864_pho|​pho|​pho:​RSPO3:​SYN4*:​VANGL*|​pho|​pho|​pho|​pho:​WGEF*:​_beta_-Arrestin2*@Cytoplasm map + RHOA@Cytoplasm map
  16. RHOA@Cytoplasm map + ROCK*@Cytoplasm map map s_s_wnc1_s1024

As Catalyser:

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