Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by ARBA machine learning models
Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins.
Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer.
Analogues of Y27632 increase gap junction communication and suppress the formation of transformed NIH3T3 colonies.
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ARHGEF16 is used in this paper as a transforming GEF in NIH3T3 focus-formation assays, and is identified there as a then-unpublished Tip-1 binding partner.
"Additional work identified the guanidine exchange factor ARHGEF16 (GEF16) as a novel binding partner for Tip-1"
Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism.
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The purified DH-PH cassette of Ephexin4 catalyses nucleotide exchange on RhoG and not on Rac1, establishing RhoG as the direct substrate.
"Although the DH-PH domain of Ephexin4 did not exchange nucleotide on Rac1, it possessed GEF activity of RhoG in vitro"
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Ephexin4 binds the nucleotide-free forms of RhoG and Rac1 but not those of RhoA or Cdc42, so binding and exchange are separable and only RhoG gets both.
"Flag-tagged Ephexin4 expressed in HEK293T cells bound to the nucleotide-free forms of RhoG and Rac1 but not to those of RhoA and Cdc42"
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Ephexin4 expression does not raise cellular Rac1-GTP or Cdc42-GTP, measured with the CRIB pull-down and with Dock180 and Zizimin1 as positive controls.
"we could observe no obvious increase in the activities of Rac1 and Cdc42 in HEK293T cells by expression of Ephexin4"
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Ephexin4 expression does not raise cellular RhoA-GTP either, measured by Rhotekin-RBD pull-down against Ephexin1 as the comparator.
"we could not detect the increase in RhoA activity in cells expressing Ephexin4"
The HPV16 E6 binding protein Tip-1 interacts with ARHGEF16, which activates Cdc42.
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Recombinant ARHGEF16 activates Cdc42 in vitro, and the activity is increased by adding recombinant Tip-1 and HPV16 E6 - the positive Cdc42 result is cofactor-conditioned throughout.
"In vitro kinetic analysis confirmed that recombinant ARHGEF16 activates Cdc42 and this was increased by the addition of recombinant Tip-1 and E6."
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TAX1BP3 (Tip-1) binds ARHGEF16 through the carboxy-terminal PDZ-binding motif.
"Tax-interacting-protein 1 was shown to interact with ARHGEF16 by its carboxyl PDZ binding motif."
Ephexin4 and EphA2 mediate resistance to anoikis through RhoG and phosphatidylinositol 3-kinase.
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Ephexin4 suppresses anoikis in HeLa cells, and the rescue requires RhoG, PI3K and Akt activation.
"Knockdown of Ephexin4 promoted anoikis in HeLa cells, and experiments using a knockdown-rescue approach showed that activation of RhoG, phosphatidylinositol 3-kinase (PI3K), and Akt was required for the Ephexin4-mediated suppression of anoikis."
Ephexin4-mediated promotion of cell migration and anoikis resistance is regulated by serine 897 phosphorylation of EphA2.
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EphA2 phosphorylated on Ser897 recruits Ephexin4, placing the exchange activity on the ligand-independent arm of Eph signalling.
"S897 phosphorylation of EphA2 strengthens the interaction between EphA2 and Ephexin4, a guanine nucleotide exchange factor for the small GTPase RhoG."
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An EphA2 S897A mutant abolishes EphA2/Ephexin4-mediated RhoG activation, cell migration and anoikis resistance.
"S897A mutation of EphA2 abolished the EphA2/Ephexin4-mediated RhoG activation, promotion of cell migration, and resistance to anoikis."
Arhgef16, a novel Elmo1 binding partner, promotes clearance of apoptotic cells via RhoG-dependent Rac1 activation.
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Murine Arhgef16 promotes engulfment of apoptotic cells, synergistically with Elmo1 and abolished in its absence.
"Expression of Arhgef16 in phagocytes promoted engulfment of apoptotic cells, and engulfment mediated by Arhgef16 increased synergistically in the presence of Elmo1 but was abrogated in the absence of Elmo1."
A proteome-scale map of the human interactome network.
E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
Architecture of the human interactome defines protein communities and disease networks.
Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1.
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Elmo1 competes the SH3 domain off the N-terminal region, relieving the steric block and opening Ephexin4 to RhoG.
"Elmo1 relieves the steric hindrance of Ephexin4 generated by the intermolecular interaction of the SH3 domain and makes Ephexin4 more accessible to RhoG."
Proteome-wide analysis of phospho-regulated PDZ domain interactions.
GLI2 promotes cell proliferation and migration through transcriptional activation of ARHGEF16 in human glioma cells.
The Intermolecular Interaction of Ephexin4 Leads to Autoinhibition by Impeding Binding of RhoG.
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Ephexin4 acts on RhoG rather than RhoA, unlike the other characterised ephexins.
"however, Ephexin4 displays GEF activity for RhoG, rather than for RhoA"
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Mutating the conserved glutamate at the intermolecular interface disrupts autoinhibition and increases RhoG binding and activation.
"Mutation of the glutamate residue at position 295, which is a highly conserved residue located in the region of Ephexin4 required for the intermolecular interaction, to alanine (Ephexin4E295A) disrupted the intermolecular interaction and increased binding of RhoG, resulting in augmented RhoG activation."
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The mutants are numbered on the MURINE protein, so E295 is not a human position - the construct is murine cDNA NM_001112744 (Q3U5C8, 713 aa), and human Q5VV41 position 295 is a serine. Pairwise alignment places murine E295 at human E291.
"All Ephexin4 mutants were generated by a polymerase chain reaction (PCR)-based strategy from the murine Ephexin4 cDNA (NM_001112744)."
Emerging Roles of Ephexins in Physiology and Disease.
Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions.
A reference map of the human binary protein interactome.
FYN is required for ARHGEF16 to promote proliferation and migration in colon cancer cells.
Double inhibition and activation mechanisms of Ephexin family RhoGEFs.
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Crystal structures show Ephexin4 is held shut by two independent autoinhibitory modes, either of which alone blocks RhoG access.
"The crystal structures of partially and fully autoinhibited Ephexin4 reveal that the complete autoinhibition requires both N- and C-terminal inhibitory modes, which can operate independently to impede Ras homolog family member G (RhoG) access."
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PDZ-protein binding to the C-terminal motif relieves one of the two autoinhibitory modes, making the PDZ interactions regulators of this gene's catalytic activity.
"phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4"
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Quantitative fragmentomics allow affinity mapping of interactomes.
A central chaperone-like role for 14-3-3 proteins in human cells.
ARHGEF16 expression correlates with proliferation, migration and invasion of colon cancer cells.
Phosphorylation of Ephexin4 at Ser-41 contributes to chromosome alignment via RhoG activation in cell division.
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Ephexin4 knockdown prolongs M phase and activates the spindle assembly checkpoint, with BubR1 at the kinetochores of misaligned chromosomes.
"Ephexin4 knockdown prolonged the duration of M phase by activating the spindle assembly checkpoint, at which BubR1 was localized at the kinetochores of the misaligned chromosomes."
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Knockdown causes chromosome misalignment and reduces RhoG localization to the plasma membrane; both are rescued by wild type and by the phospho-mimic S41E but not by S41A.
"The Ephexin4 knockdown caused chromosome misalignment and reduced the RhoG localization to the plasma membrane."
p75NTR indirectly activates RAC and Cdc42 via a guanyl-nucleotide exchange factor
ARHGEF16 bioinformatics - results
Affinage mechanistic annotation for ARHGEF16 (human)