First description of the protein: a Dbl-family RhoGEF with a DH-PH tandem and a C-terminal SH3 domain, reported to activate RhoA, Cdc42 and Rac1 by pulldown, with forced expression rearranging the actin cytoskeleton.

Expression is highest in intestine, with liver, heart and kidney also positive.

Human WGEF raises RhoA-GTP in HEK293T cells, and a construct lacking most of the DH-PH module does not.

Neither human nor Xenopus WGEF activates Rac1 or Cdc42, under conditions where Ephexin-1 in the same experiment does.

Binding specificity mirrors exchange specificity: strong for RhoA, very weak for Rac1, absent for Cdc42.

Dishevelled binds WGEF through its PDZ domain, and WGEF binds the N-terminal portion of Daam1 but not the C-terminal portion.

Loss of WGEF in human MCF-7 cells reduces Wnt-1-stimulated RhoA activation.

The N-terminal region is autoinhibitory; deleting it makes the protein hyperactive in RhoA binding, RhoA activation and embryonic phenotype.

The Dishevelled-binding determinant was mapped by deletion to the N-terminal region, since constructs lacking residues 1-213 or comprising only DH-PH failed to bind.

Xenopus WGEF localises preferentially to the plasma membrane and colocalises with cortical actin.

Wgef, like Ngef and Tim, is activated by tyrosine phosphorylation of an N-terminal helix that otherwise blocks the DH domain.

In the Tim subgroup, which includes Wgef, the C-terminal SH3 domain binds a polyproline region N-terminal to the DH domain, providing a second, independent autoinhibitory mode.

CpG sites in exon 1 of WGEF are demethylated during 3T3-L1 adipogenesis, and the region regulates WGEF transcription.

Forced WGEF expression suppresses the adipogenic programme.

RhoGEF19 is a direct transcriptional target of GRHL3, identified by phylogenetic analysis, chromatin immunoprecipitation and expression analysis in Grhl3-null mice.

Knockdown of RhoGEF19 in keratinocytes phenocopies Grhl3 knockdown for actin polymerisation, cell polarity and wound healing, and re-expression of RhoGEF19 rescues the Grhl3 knockdown.

The keratinocytes are human. RhoGEF19 was knocked down by shRNA in the human line HaCaT, and the leading-edge polarity analysis is described as being done on human cells.

RhoGEF19-knockdown human keratinocytes fail to close a scratch wound that control cells close completely, and activated RhoA falls in those cells.

Re-expressing RhoGEF19 in Grhl3-knockdown human keratinocytes restores wound closure from 10% to 73%, placing RhoGEF19 downstream of GRHL3 in the same human cells.

RhoGEF19-knockdown human keratinocytes form only rudimentary, misdirected stress fibres at the wound edge.

In N1E-115 mouse neuroblastoma cells, WGEF knockdown has no effect on Dishevelled-induced neurite retraction, while p114-RhoGEF and Lfc knockdowns do; the authors conclude WGEF is not the relevant GEF in this context.

The WGEF shRNA was shown to be effective in the same cells, so the negative result is not a knockdown failure.

Commentary from the authors of PMID:20643356 framing GRHL3-driven transcription of RhoGEF19 as tissue-specific control of Rho GTPase activity in wound repair.

The developing pronephric anlagen expresses Daam1 together with WGEF, and inhibiting this branch of the planar-cell-polarity pathway reduces pronephric tubulogenesis in Xenopus and zebrafish.

Tubulogenesis requires the Daam1/WGEF/Rho branch specifically.

ARHGEF19 is a direct target of miR-503 in hepatocellular carcinoma cells, and its overexpression counteracts miR-503-mediated suppression of proliferation and metastasis.

A review of Wnt signalling in midbrain dopaminergic neurons, cited by ParkinsonsUK-UCL as the author-statement source for placing ARHGEF19 in the planar-cell-polarity pathway. The cached record is abstract only and the abstract does not mention ARHGEF19 or planar cell polarity, so the supporting statement is in full text that was not accessible here.

ARHGEF19 activates MEK1/2 phosphorylation independently of RhoA, through an interaction with BRAF that requires both the DH and the PH domain.

Ephexin-2 is the least studied member of the family, and no Eph receptor interacting with it has been identified.

The Ephexin family is defined by homology, and for Ephexin-2 specifically no Eph receptor partner is known.

Knockdown of ArhGEF19 in MDCKII cells causes loss of primary cilia, as does knockdown of its partner Daam1; knockdown in Xenopus kidney does not reproduce the effect.

A proteome-scale binary interaction map, HuRI, which is the source of the reported ARHGEF19-PAK5 interaction.

In small-cell lung cancer cells and xenografts, the DH and PH domains of ARHGEF19 interact with HRAS and activate MAPK/ERK signalling.

Ephexin-family RhoGEFs are held inactive by two independent modules, an N-terminal inhibitory helix and a C-terminal SH3-mediated mode, each relieved separately.

Phosphorylation of a conserved tyrosine in the N-terminal inhibitory domain and binding of PDZ proteins to a C-terminal PDZ-binding motif relieve the two brakes independently in Ephexin-4.

ARHGEF19 is overexpressed in human breast cancer, promotes proliferation and suppresses apoptosis, and activates the MAPK pathway.

Dvl2-PDZ binding to an internal motif at residues 349-359 of human WGEF relieves autoinhibition and raises exchange activity.

This mapping contradicts the earlier assignment of Dishevelled binding to the N-terminal 1-213, and the authors say so explicitly.

The exchange assays were performed on Xenopus rather than human protein because the human constructs were insoluble or poorly expressed.

The conserved N-terminal inhibitory tyrosine of human WGEF is Y295; the phosphomimetic Y295E is reported to be autoinhibition-free.

Neither crystallisation route produced a WGEF peptide-Dvl2PDZ complex structure, including the fusion construct deposited as PDB 8YR7.

ANKK1 binds WGEF in human SH-SY5Y cells, confirmed by co-immunoprecipitation and proximity ligation, and the WGEF-RhoA interaction increases when ANKK1 is knocked down.

In differentiated cells both ANKK1 and WGEF localise to neurites, although they colocalise poorly.

A reaction whose catalyst is an undifferentiated cytosolic GEF set and whose output is RAC1-GTP; ARHGEF19 participates only by membership of that set.

Generic statement that Rho-family GEFs catalyse GDP-GTP exchange, noting that some GEFs are GTPase-specific and others broad.

Reactome lists ARHGEF19 as a RHOA GEF set member on the evidence of Wang et al. 2004 and Muller et al. 2020.

The parent pathway describing the GDP-GTP cycle of RHO GTPases, within which ARHGEF19 acts as an activator.

The wound-healing IBD sits on a Euteleostomi-level node seeded by exactly one gene product, mouse Arhgef19.

The actin-cytoskeleton IBD is seeded at the eukaryote root by three gene products, one of which is ARHGEF19 itself.

The guanyl-nucleotide-exchange IBD is also at the eukaryote root, seeded entirely by mammalian ephexins.

Affinage's own GO grounding for this gene places it at the plasma membrane and the cilium, and assigns only high-level molecular-function terms.

The narrative correctly records the published negative result, noting that the Wnt/Dvl-induced RhoA activation role is dispensable in N1E-115 cells.

ARHGEF19 presents a complete Dbl-family exchange surface, spanning 24 of the 25 DH positions that contact RhoA in both solved RhoA complexes - the same coverage as the weakest verified-active comparator in the panel.

The same analysis cannot assign a substrate: identity at the exchange surface is 36% for ARHGEF19 against LARG and 36% for Tiam1, a GEF for a different GTPase.

A Pfam DH hit is not evidence of exchange competence: ARHGEF19 isoform 2 clears the gathering threshold at 65.5 bits despite losing half the DH domain plus all of PH and SH3, spanning only 5 of the 25 contact positions.

Eleven of fourteen primary experimental papers on ARHGEF19 have produced no GO annotation of any gene in any species, and twelve of fourteen have produced none on ARHGEF19 itself.