ARHGAP29, also called PARG1, is an intracellular Rho-family GTPase-activating protein that accelerates GTP hydrolysis, with preference for Rho over Rac and Cdc42 in the original biochemical assay. Its activity reduces the active Rho-GTP signaling state. In endothelial cells, ARHGAP29 works with RASIP1 and RADIL downstream of Rap1 to limit Rho-dependent actomyosin tension and support junctional barrier function. Depletion in cultured human endothelial cells disrupts lumen formation. Cytosolic localization and interactions with signaling partners help position its regulatory activity; its C-terminal tail binds the fourth PDZ domain of PTPL1. Human ARHGAP29 variants are associated with nonsyndromic orofacial clefting.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005096 GTPase activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: ARHGAP29 accelerates hydrolysis by Rho-family GTPases. Reason: The inherited GAP function agrees with the original PARG1 biochemical study and the curated human RHOA-GAP event. This is activation of GTP hydrolysis, which reduces the active GTP-bound signaling state. The exact PAINT node placement has not been reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN004470214 · PTN004470214 UNRESOLVED Target biochemical evidence corroborates the inherited GAP activity. The actual ancestral source is retained; its IBD placement and alignment remain uninspected. Supporting Evidence: PMID:9305890 The GAP domain is active on Rho, Rac, and Cdc42 in vitro but with a clear preference for Rho |
| GO:0005096 GTPase activator activity | TAS PMID:9305890 A novel GTPase-activating protein for Rho interacts with a P... | ACCEPT | Summary: The PARG1 GAP domain stimulates Rho-family GTP hydrolysis. Reason: The cited original study identifies PARG1 and reports GAP activity on Rho, Rac and Cdc42 with a preference for Rho. UniProt maps this cloning study to human ARHGAP29. The accessible normal record is abstract-only, so the precise substrate and construct methods are not independently reconstructed here; the stated catalytic role is explicit. Supporting Evidence: PMID:9305890 The GAP domain is active on Rho, Rac, and Cdc42 in vitro but with a clear preference for Rho |
| GO:0005096 GTPase activator activity | TAS Reactome:R-HSA-8981637 | ACCEPT | Summary: ARHGAP29 contributes GAP activity to the RHOA inactivation reaction. Reason: The Reactome event explicitly includes ARHGAP29 among supported RHOA GAPs. Its summary separates binding-only high-throughput evidence from experiments establishing stimulation of hydrolysis. This agrees with the original PARG1 biochemical result and identifies ARHGAP29 as the catalytic regulator, rather than the RHOA substrate. Supporting Evidence: Reactome:R-HSA-8981637 ARHGAP29 (Saras et al. 1997; Müller et al. 2020; supported by Bagci et al. 2020) PMID:9305890 The GAP domain is active on Rho, Rac, and Cdc42 in vitro but with a clear preference for Rho |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: A cytoplasmic ARHGAP29 pool is supported. Reason: The current Human Protein Atlas target summary independently reports cytoplasmic tissue expression and a cytosolic pool, consistent with the inherited broad cytoplasm annotation. This does not imply exclusive localization. ARHGAP29 in its own PAINT descendant evidence is expected experimental grounding, not circularity; the historical target-specific microscopy table is assessed separately. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002689839 · PTN002689839 UNRESOLVED Independent target localization supports a cytoplasmic pool. The exact ancestral placement was not read; target self-inclusion does not establish an inference error. Supporting Evidence: file:human/ARHGAP29/ARHGAP29-notes.md The current Human Protein Atlas summary reports cytoplasmic expression and includes cytosol among additional subcellular locations. |
| GO:0005737 cytoplasm | IDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | ACCEPT | Summary: Accept the cytoplasmic pool and defer to the original experimental curator. Reason: Independent target-specific localization establishes a cytoplasmic pool, so accept the broad location and defer to the experimental curator. The exact PMID:25468996 supplementary image/table has not been independently read; its original source remains intact and the Human Protein Atlas corroboration is separately attributed. Supporting Evidence: file:human/ARHGAP29/ARHGAP29-notes.md The current Human Protein Atlas summary reports cytoplasmic expression and includes cytosol among additional subcellular locations. |
| GO:0005829 cytosol | IEA GO_REF:0000117 | ACCEPT | Summary: ARHGAP29 has a cytosolic pool. Reason: The current target-specific Human Protein Atlas summary includes cytosol, and the curated RHOA-GAP reaction has a cytosolic catalyst set. These independently corroborate the localization assigned by ARBA00029243, whose historical rule conditions were not reconstructed. Cytosolic localization is not asserted to be exclusive or the only site of GAP action. Supporting Evidence: file:human/ARHGAP29/ARHGAP29-notes.md The current Human Protein Atlas summary reports cytoplasmic expression and includes cytosol among additional subcellular locations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8981637 | ACCEPT | Summary: The curated RHOA-GAP event includes cytosolic ARHGAP29. Reason: The official human event places the RHOA-GAP catalyst set in cytosol and includes ARHGAP29 as a supported member. This is consistent with independent target localization. The event also contains plasma-membrane RHOA; its multiple reaction compartments are not assigned indiscriminately to every participant. Supporting Evidence: file:human/ARHGAP29/ARHGAP29-notes.md The official human RHOA-GAP event includes ARHGAP29 among supported GAPs and identifies a cytosolic catalyst set. |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | MODIFY | Summary: Broad signal transduction can be refined to the established inhibitory GAP role. Reason: The RhoGAP-domain mapping identifies a signaling regulator, while the original biochemical activity resolves the direction: accelerating GTP hydrolysis inactivates Rho-family switches. Negative regulation of small GTPase-mediated signaling is more informative than the generic signal-transduction parent. The original InterPro source remains unchanged. Proposed replacements: negative regulation of small GTPase mediated signal transduction Supporting Evidence: PMID:9305890 The GAP domain is active on Rho, Rac, and Cdc42 in vitro but with a clear preference for Rho |
| GO:0007266 Rho protein signal transduction | TAS PMID:9305890 A novel GTPase-activating protein for Rho interacts with a P... | ACCEPT | Summary: ARHGAP29 directly regulates the Rho signaling switch. Reason: The protein catalytically controls the nucleotide switch within Rho signaling. Retain this Rho-specific pathway membership, while GO:0051058 separately records the inhibitory direction for small-GTPase signaling; neither term is inferred merely from downstream phenotypes. Supporting Evidence: PMID:9305890 The GAP domain is active on Rho, Rac, and Cdc42 in vitro but with a clear preference for Rho |
| GO:0030165 PDZ domain binding | IDA PMID:23209302 KIF14 negatively regulates Rap1a-Radil signaling during brea... | ACCEPT | Summary: PDZ-domain binding is independently established for PARG1. Reason: PARG1 C-terminal binding to PTPL1 PDZ4 independently establishes PDZ-domain binding (PMID:9305890). Accept that molecular function and defer to the original experimental curator. The ARHGAP29/Radil-specific figure/table in PMID:23209302 remains unread; PTPL1 evidence is explicitly separate corroboration, not a claim to have verified the Radil experiment. Supporting Evidence: PMID:9305890 the four most C-terminal amino acid residues of which specifically interact with the fourth PDZ domain of PTPL1. |
| GO:0032991 protein-containing complex | IDA PMID:26780829 Heart of glass anchors Rasip1 at endothelial cell-cell junct... | KEEP AS NON CORE | Summary: Tagged ARHGAP29 coassociates with a Rasip1-containing protein complex. Reason: Actual Results and Figure 3 supplement 3 demonstrate YFP-ARHGAP29 coimmunoprecipitation with FLAG-Rasip1 in U2OS cells, including HEG1-depletion comparison. Retain the observed broad association without inventing direct binary binding or a stoichiometrically defined core complex. Supporting Evidence: PMID:26780829 As expected, Radil and ARHGAP29 co-immunoprecipitated with Rasip1 |
| GO:0051056 regulation of small GTPase mediated signal transduction | IEA GO_REF:0000117 | ACCEPT | Summary: ARHGAP29 regulates small-GTPase signaling through its GAP activity. Reason: Direct PARG1 GAP activity corroborates the ARBA-regulated small-GTPase signaling assertion. ARHGAP29 performs the hydrolysis-acceleration step; it is not merely a protein affected downstream by Rho signaling. The narrower inhibitory direction is represented by the existing negative-regulation annotation and the core function. Supporting Evidence: PMID:9305890 The GAP domain is active on Rho, Rac, and Cdc42 in vitro but with a clear preference for Rho |
| GO:0051056 regulation of small GTPase mediated signal transduction | TAS Reactome:R-HSA-9012999 | ACCEPT | Summary: ARHGAP29 participates in regulation of the Rho GDP/GTP cycle. Reason: This pathway describes GAP-mediated acceleration of intrinsic Rho GTP hydrolysis and links to the RHOA-GAP event that explicitly contains ARHGAP29. The regulator role is consistent with target biochemistry. The pathway umbrella does not independently establish all Rho-dependent cell migration or developmental functions for ARHGAP29. Supporting Evidence: Reactome:R-HSA-9012999 GTPase activating proteins or GAPs, which stimulate the low intrinsic GTP hydrolysis activity of Rho family members, thus promoting their inactivation. PMID:9305890 The GAP domain is active on Rho, Rac, and Cdc42 in vitro but with a clear preference for Rho |
| GO:0051058 negative regulation of small GTPase mediated signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: GAP activity negatively regulates the active small-GTPase signaling state. Reason: The inherited negative-regulation term agrees with the Rho-directed biochemical GAP activity: faster GTP hydrolysis returns the substrate to its inactive GDP-bound state. This mechanistic participation supports the process independently of donor number or species. The exact PTN004470214 IBD placement remains uninspected. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN004470214 · PTN004470214 UNRESOLVED The original biochemical activity corroborates negative regulation of the nucleotide switch; no loss, divergence or failed node placement is demonstrated. Supporting Evidence: PMID:9305890 The GAP domain is active on Rho, Rac, and Cdc42 in vitro but with a clear preference for Rho |
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Download this section (compressed HTML)Q: Which ARHGAP29 construct and target-specific PDZ-dependent interaction entry underlie the Radil-study annotation in PMID:23209302?
Q: What target-specific localization image and Supplemental Table2 entry support ARHGAP29 cytoplasm in PMID:25468996?
Q: How do the two human ARHGAP29 products differ in partner binding or spatial Rho regulation, and what sequence accession was used for the YFP-ARHGAP29 coassociation construct in PMID:26780829?
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