DAB2IP (Disabled homolog 2-interacting protein, also known as AIP1) is a multifunctional tumor suppressor that serves as both a GTPase-activating protein (GAP) and a signaling scaffold. The protein contains PH, C2, GAP, PER, and proline-rich domains that enable it to coordinate multiple signaling pathways. Core enzymatic functions include GAP activity toward Ras, ARF6, and RAB40C GTPases. As a scaffold, DAB2IP coordinates opposing pathways: inhibiting PI3K-AKT (survival) while activating ASK1-JNK (apoptosis) in response to TNF-alpha. DAB2IP inhibits multiple oncogenic pathways including Ras-MAPK, NF-kappaB, Wnt/beta-catenin, VEGFR2, and JAK-STAT signaling. Loss of DAB2IP through promoter methylation or EZH2-mediated silencing drives cancer progression, EMT, metastasis, and therapy resistance. Also functions in vascular biology (anti-inflammatory, anti-angiogenic) and neuronal migration during cortical development.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005096 GTPase activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: GTPase activator activity is the core enzymatic function of DAB2IP. The GAP domain catalyzes GTP hydrolysis on Ras, ARF6, and RAB40C substrates. Supporting Evidence: file:human/DAB2IP/DAB2IP-deep-research-perplexity.md The primary enzymatic function of DAB2IP resides in its GAP domain, which catalyzes the hydrolysis of GTP to GDP on several small GTPase substrates file:human/DAB2IP/DAB2IP-deep-research-falcon.md See deep research file for comprehensive analysis |
| GO:1902531 regulation of intracellular signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: DAB2IP regulates multiple intracellular signaling pathways through both GAP activity and scaffold functions. Core function. |
| GO:0001525 angiogenesis | IEA GO_REF:0000043 | MODIFY | Summary: DAB2IP inhibits angiogenesis; this should be annotated as negative regulation. Proposed replacements: negative regulation of angiogenesis |
| GO:0002376 immune system process | IEA GO_REF:0000043 | ACCEPT | Summary: General immune process term. DAB2IP regulates inflammatory signaling. |
| GO:0005096 GTPase activator activity | IEA GO_REF:0000043 | ACCEPT | Summary: Consistent with IBA annotation. Core function. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Cytoplasmic localization is well-supported. Core localization. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Plasma membrane localization for interaction with receptor signaling complexes. |
| GO:0006915 apoptotic process | IEA GO_REF:0000043 | ACCEPT | Summary: DAB2IP promotes apoptosis through ASK1-JNK activation. Core function. |
| GO:0006954 inflammatory response | IEA GO_REF:0000043 | ACCEPT | Summary: DAB2IP regulates inflammatory response (generally as negative regulator). |
| GO:0006986 response to unfolded protein | IEA GO_REF:0000043 | ACCEPT | Summary: DAB2IP transduces IRE1-mediated ER stress response. Well-supported. |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: General membrane localization. PH domain binds phosphoinositides. |
| GO:0030425 dendrite | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Neuronal localization related to developmental function. |
| GO:0045087 innate immune response | IEA GO_REF:0000043 | ACCEPT | Summary: DAB2IP regulates TLR4 signaling as Arf6-GAP in innate immunity. |
| GO:0005515 protein binding | IPI PMID:12813029 AIP1 mediates TNF-alpha-induced ASK1 activation by facilitat... | REMOVE | Summary: This paper shows DAB2IP mediates TNF-alpha-induced ASK1 activation via TRAF2/14-3-3. Generic protein binding is uninformative per curation guidelines. Reason: Generic protein binding; specific TRAF2/ASK1 interactions captured by functional annotations. Supporting Evidence: PMID:12813029 AIP1 binds to the C-terminal domain of ASK1 via a lysine-rich cluster within the N-terminal C2 domain |
| GO:0005515 protein binding | IPI Q5VWQ8-2 PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal trans... | REMOVE | Summary: Paper on DAB2IP modulating EMT and metastasis through PP2A interaction. Generic protein binding uninformative. Reason: Generic protein binding; PP2A binding captured by specific term. Supporting Evidence: PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal transition and prostate cancer metastasis. |
| GO:0042802 identical protein binding | IPI PMID:12813029 AIP1 mediates TNF-alpha-induced ASK1 activation by facilitat... | ACCEPT | Summary: DAB2IP forms homodimers. Functionally relevant for complex formation. Supporting Evidence: PMID:12813029 AIP1 exists in a closed form through an intramolecular interaction between the N-terminus and the C-terminus |
| GO:0010596 negative regulation of endothelial cell migration | IEA GO_REF:0000107 | ACCEPT | Summary: DAB2IP inhibits endothelial cell migration through VEGFR2-PI3K pathway inhibition. Well-supported by literature. Supporting Evidence: file:human/DAB2IP/DAB2IP-deep-research-perplexity.md DAB2IP acts as a negative regulator of the VEGFR2-PI3K-mediated angiogenic signaling pathway by directly inhibiting endothelial cell migration |
| GO:0010976 positive regulation of neuron projection development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal development function. Secondary to core tumor suppressor role. |
| GO:0016525 negative regulation of angiogenesis | IEA GO_REF:0000107 | ACCEPT | Summary: Anti-angiogenic function is well-documented. Core function in vascular biology. |
| GO:0019901 protein kinase binding | IEA GO_REF:0000107 | ACCEPT | Summary: DAB2IP binds multiple kinases (ASK1, PI3K, JAK2). Core adaptor function. |
| GO:0021814 cell motility involved in cerebral cortex radial glia guided migration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal migration function. Non-core function. |
| GO:0021819 layer formation in cerebral cortex | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cortical development function. Non-core. |
| GO:0030424 axon | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal localization. Non-core. |
| GO:0030948 negative regulation of vascular endothelial growth factor receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: VEGFR2 signaling inhibition is a core function in vascular biology. |
| GO:0032809 neuronal cell body membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal localization. Non-core. |
| GO:0035148 tube formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Related to angiogenesis inhibition. |
| GO:0035924 cellular response to vascular endothelial growth factor stimulus | IEA GO_REF:0000107 | ACCEPT | Summary: VEGF response through VEGFR2 regulation. Core vascular function. |
| GO:0036324 vascular endothelial growth factor receptor-2 signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: VEGFR2 pathway regulation. Core function. |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal localization. Non-core. |
| GO:0043065 positive regulation of apoptotic process | IEA GO_REF:0000107 | ACCEPT | Summary: Pro-apoptotic function through ASK1-JNK activation. Core tumor suppressor function. Supporting Evidence: file:human/DAB2IP/DAB2IP-deep-research-perplexity.md DAB2IP functions as a critical activator of apoptosis signal-regulating kinase 1 (ASK1) and the downstream c-Jun N-terminal kinase (JNK) cascade |
| GO:0043122 regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000107 | ACCEPT | Summary: NF-kappaB regulation is core function. DAB2IP generally inhibits NF-kappaB. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000107 | UNDECIDED | Summary: DAB2IP is primarily a negative regulator of NF-kappaB. This annotation may be context-dependent or incorrect. Reason: Literature primarily supports negative regulation of NF-kappaB by DAB2IP. |
| GO:0043254 regulation of protein-containing complex assembly | IEA GO_REF:0000107 | ACCEPT | Summary: DAB2IP scaffolds multiple protein complexes. Core adaptor function. |
| GO:0044300 cerebellar mossy fiber | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cerebellar localization. Non-core. |
| GO:0044301 climbing fiber | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cerebellar localization. Non-core. |
| GO:0045732 positive regulation of protein catabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Related to ubiquitin-mediated degradation regulation. Non-core. |
| GO:0046330 positive regulation of JNK cascade | IEA GO_REF:0000107 | ACCEPT | Summary: JNK cascade activation through ASK1 is core pro-apoptotic function. Supporting Evidence: file:human/DAB2IP/DAB2IP-deep-research-perplexity.md DAB2IP mediates TNF-alpha-induced apoptosis by facilitating dissociation of the 14-3-3 inhibitor from ASK1 |
| GO:0048147 negative regulation of fibroblast proliferation | IEA GO_REF:0000107 | ACCEPT | Summary: Anti-proliferative function. Core tumor suppressor role. |
| GO:0048812 neuron projection morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal development. Non-core. |
| GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | IEA GO_REF:0000107 | ACCEPT | Summary: IRE1-mediated ER stress response is well-documented function. Core function. Supporting Evidence: file:human/DAB2IP/DAB2IP-deep-research-perplexity.md AIP1 is critical in transducing IRE1-mediated endoplasmic reticulum stress response |
| GO:0071222 cellular response to lipopolysaccharide | IEA GO_REF:0000107 | ACCEPT | Summary: TLR4 signaling regulation via Arf6-GAP activity. Core innate immune function. |
| GO:0071347 cellular response to interleukin-1 | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Inflammatory cytokine response. Non-core. |
| GO:0071356 cellular response to tumor necrosis factor | IEA GO_REF:0000107 | ACCEPT | Summary: TNF response through ASK1-JNK pathway is core function. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Wnt signaling inhibition through GSK-3beta activation. Core tumor suppressor function. Supporting Evidence: file:human/DAB2IP/DAB2IP-deep-research-perplexity.md DAB2IP negatively regulates the canonical Wnt/beta-catenin signaling pathway through activation of glycogen synthase kinase 3 beta (GSK-3beta) |
| GO:0090129 positive regulation of synapse maturation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Synaptic development. Non-core. |
| GO:1900006 positive regulation of dendrite development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Dendrite development. Non-core. |
| GO:1900744 regulation of p38MAPK cascade | IEA GO_REF:0000107 | ACCEPT | Summary: p38MAPK regulation through ASK1. Related to core function. |
| GO:1900747 negative regulation of vascular endothelial growth factor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: VEGF signaling inhibition. Core vascular function. |
| GO:1990032 parallel fiber | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cerebellar localization. Non-core. |
| GO:1990597 AIP1-IRE1 complex | IEA GO_REF:0000107 | ACCEPT | Summary: ER stress response complex. Core function. |
| GO:2001224 positive regulation of neuron migration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal migration. Non-core. |
| GO:0005096 GTPase activator activity | IMP PMID:29156729 A RasGAP, DAB2IP, regulates lipid droplet homeostasis by ser... | ACCEPT | Summary: Direct evidence for GAP activity toward RAB40C. Core function. Supporting Evidence: PMID:29156729 Ras GTPase activating protein (GAP), DAB2IP, bound to RAB40C mainly via its GAP domain and could serve as RAB40C GAP |
| GO:0005737 cytoplasm | IDA PMID:29156729 A RasGAP, DAB2IP, regulates lipid droplet homeostasis by ser... | ACCEPT | Summary: Cytoplasmic localization confirmed. Supporting Evidence: PMID:29156729 DAB2IP negatively regulated the effect of RAB40C on LD homeostasis |
| GO:0043547 positive regulation of GTPase activity | IMP PMID:29156729 A RasGAP, DAB2IP, regulates lipid droplet homeostasis by ser... | ACCEPT | Summary: GAP activity regulation. Core function. Supporting Evidence: PMID:29156729 Ras GTPase activating protein (GAP), DAB2IP, bound to RAB40C mainly via its GAP domain and could serve as RAB40C GAP |
| GO:0005886 plasma membrane | IDA PMID:29156729 A RasGAP, DAB2IP, regulates lipid droplet homeostasis by ser... | ACCEPT | Summary: Plasma membrane localization confirmed. Supporting Evidence: PMID:29156729 DAB2IP negatively regulated the effect of RAB40C on LD homeostasis |
| GO:0016020 membrane | IDA PMID:29156729 A RasGAP, DAB2IP, regulates lipid droplet homeostasis by ser... | ACCEPT | Summary: Membrane localization. General term. Supporting Evidence: PMID:29156729 DAB2IP negatively regulated the effect of RAB40C on LD homeostasis |
| GO:0140042 lipid droplet formation | IMP PMID:29156729 A RasGAP, DAB2IP, regulates lipid droplet homeostasis by ser... | KEEP AS NON CORE | Summary: Novel function through RAB40C GAP activity regulating lipid droplet homeostasis. Supporting Evidence: file:human/DAB2IP/DAB2IP-deep-research-perplexity.md DAB2IP has been identified as a GAP for RAB40C, a Rab GTPase involved in lipid droplet homeostasis PMID:29156729 DAB2IP negatively regulated the effect of RAB40C on LD homeostasis |
| GO:0043409 negative regulation of MAPK cascade | IMP PMID:20154697 An oncogene-tumor suppressor cascade drives metastatic prost... | ACCEPT | Summary: MAPK cascade inhibition through Ras-GAP activity. Core tumor suppressor function. Supporting Evidence: PMID:20154697 loss of the RasGAP gene DAB2IP induces metastatic prostate cancer in a murine model |
| GO:0046580 negative regulation of Ras protein signal transduction | IMP PMID:20154697 An oncogene-tumor suppressor cascade drives metastatic prost... | ACCEPT | Summary: Ras signaling inhibition is core GAP function. Supporting Evidence: file:human/DAB2IP/DAB2IP-deep-research-perplexity.md By accelerating Ras GTP hydrolysis, DAB2IP suppresses Ras-dependent activation of this pathway PMID:20154697 DAB2IP functions as a signaling scaffold that coordinately regulates Ras and NF-ΞΊB through distinct domains to promote tumor initiation and metastasis, respectively |
| GO:1901223 negative regulation of non-canonical NF-kappaB signal transduction | IMP PMID:20154697 An oncogene-tumor suppressor cascade drives metastatic prost... | ACCEPT | Summary: NF-kappaB inhibition. Core tumor suppressor function. Supporting Evidence: PMID:20154697 DAB2IP -loss promotes primary tumor growth by activating Ras and drives metastasis through NF-ΞΊB |
| GO:0046330 positive regulation of JNK cascade | IDA PMID:15310755 AIP1/DAB2IP, a novel member of the Ras-GAP family, transduce... | ACCEPT | Summary: JNK activation through ASK1. Core apoptotic function. Supporting Evidence: PMID:15310755 A PERIOD-like domain (amino acids 591-719) of AIP1 binds to the intact RING finger of TRAF2, and specifically enhances TRAF2-induced ASK1 activation |
| GO:0033209 tumor necrosis factor-mediated signaling pathway | IDA PMID:12813029 AIP1 mediates TNF-alpha-induced ASK1 activation by facilitat... | ACCEPT | Summary: TNF signaling. Core function. Supporting Evidence: PMID:12813029 AIP1 mediates TNF-alpha-induced ASK1 activation by facilitating dissociation of inhibitor 14-3-3 from ASK1, a novel mechanism by which TNF-alpha activates ASK1 |
| GO:0046330 positive regulation of JNK cascade | IDA PMID:12813029 AIP1 mediates TNF-alpha-induced ASK1 activation by facilitat... | ACCEPT | Summary: Duplicate of above. JNK activation. Supporting Evidence: PMID:12813029 Recruited AIP1 enhances ASK1-induced JNK activation, and the ASK1 binding and the GAP activity of AIP1 are critical for AIP1-enhanced ASK1 activation |
| GO:0051721 protein phosphatase 2A binding | IPI PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal trans... | ACCEPT | Summary: PP2A binding through C2 domain. Functionally important for ASK1 dephosphorylation. Supporting Evidence: file:human/DAB2IP/DAB2IP-deep-research-perplexity.md DAB2IP recruits the PP2A phosphatase complex to ASK1 through its C2 domain PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal transition and prostate cancer metastasis. |
| GO:0035556 intracellular signal transduction | IMP PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal trans... | ACCEPT | Summary: Signal transduction. General term but core function. Supporting Evidence: PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal transition and prostate cancer metastasis. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | ISS GO_REF:0000024 | UNDECIDED | Summary: Literature primarily supports DAB2IP as negative regulator of NF-kappaB. Reason: Inconsistent with primary literature. |
| GO:0035591 signaling adaptor activity | IDA PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell ... | ACCEPT | Summary: Adaptor/scaffold function coordinating PI3K-AKT and ASK1 pathways. Core function. Supporting Evidence: file:human/DAB2IP/DAB2IP-deep-research-perplexity.md Beyond its enzymatic GAP activity, DAB2IP functions as a multivalent signaling scaffold PMID:19903888 DAB2IP is a scaffold protein capable of bridging both survival and death signal molecules, which implies its role in maintaining cell homeostasis |
| GO:0043539 protein serine/threonine kinase activator activity | IDA PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell ... | ACCEPT | Summary: ASK1 kinase activation. Core apoptotic function. Supporting Evidence: PMID:19903888 DAB2IP can suppress the PI3K-Akt pathway and enhance ASK1 activation leading to cell apoptosis |
| GO:0031334 positive regulation of protein-containing complex assembly | IDA PMID:18281285 AIP1 is critical in transducing IRE1-mediated endoplasmic re... | ACCEPT | Summary: Complex assembly for IRE1 signaling. Supporting Evidence: PMID:18281285 AIP1-IRE1 association facilitates IRE1 dimerization, a critical step for activation of IRE1 signaling |
| GO:0034620 cellular response to unfolded protein | TAS PMID:22013210 The unfolded protein response: integrating stress signals th... | ACCEPT | Summary: ER stress response. Supporting Evidence: PMID:22013210 The unfolded protein response: integrating stress signals through the stress sensor IRE1Ξ±. |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | KEEP AS NON CORE | Summary: E-cadherin interactome study. Context for EMT regulation. Supporting Evidence: PMID:25468996 E-cadherin interactome complexity and robustness resolved by quantitative proteomics. |
| GO:1903896 positive regulation of IRE1-mediated unfolded protein response | TAS PMID:22013210 The unfolded protein response: integrating stress signals th... | ACCEPT | Summary: IRE1-mediated UPR. Core ER stress function. Supporting Evidence: PMID:22013210 The unfolded protein response: integrating stress signals through the stress sensor IRE1Ξ±. |
| GO:0019901 protein kinase binding | IDA PMID:18281285 AIP1 is critical in transducing IRE1-mediated endoplasmic re... | ACCEPT | Summary: Binds multiple kinases. Core adaptor function. Supporting Evidence: PMID:18281285 ER stress induced formation of an AIP1-IRE1 complex, and the PH domain of AIP1 is critical for the IRE1 interaction |
| GO:1990597 AIP1-IRE1 complex | IDA PMID:18281285 AIP1 is critical in transducing IRE1-mediated endoplasmic re... | ACCEPT | Summary: AIP1 (DAB2IP) forms complex with IRE1 for ER stress response. Supporting Evidence: PMID:18281285 AIP1 via its PH domain associates with IRE1. Moreover, the PH domain of AIP1 is critical for AIP1-mediated IRE1 activation |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5658231 | ACCEPT | Summary: Cytosolic localization for Ras-GAP function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5658435 | ACCEPT | Summary: Cytosolic localization. |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | IMP PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell ... | ACCEPT | Summary: Death receptor signaling through TNF pathway. Core apoptotic function. Supporting Evidence: PMID:19903888 Here, we show that DAB2IP protein, often down-regulated in PCa, is a potent growth inhibitor by inducing G(0)/G(1) cell cycle arrest and is proapoptotic in response to stress |
| GO:0072577 endothelial cell apoptotic process | TAS PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell ... | KEEP AS NON CORE | Summary: Endothelial apoptosis in vascular biology. Supporting Evidence: PMID:19903888 DAB2IP can suppress the PI3K-Akt pathway and enhance ASK1 activation leading to cell apoptosis |
| GO:0005737 cytoplasm | IDA PMID:19948740 AIP1 functions as Arf6-GAP to negatively regulate TLR4 signa... | ACCEPT | Summary: Cytoplasmic localization. Supporting Evidence: PMID:19948740 AIP1 disrupts formation of the TLR4- TIRAP-MyD88 complex without directly binding to any of the complex components |
| GO:0005886 plasma membrane | IDA PMID:19948740 AIP1 functions as Arf6-GAP to negatively regulate TLR4 signa... | ACCEPT | Summary: Plasma membrane localization. Supporting Evidence: PMID:19948740 Deletion of AIP1 from mouse endothelial cells can enhance cellular PIP 2 levels, in turn enhancing LPS-induced NF-ΞΊB and MAPK signaling |
| GO:0030139 endocytic vesicle | IDA PMID:19948740 AIP1 functions as Arf6-GAP to negatively regulate TLR4 signa... | ACCEPT | Summary: Endocytic vesicle localization for TLR4 signaling regulation. Supporting Evidence: PMID:19948740 We further show that AIP1 is a novel GTPase-activating protein (GAP) for Arf6, a small GTPase regulating cellular PIP(2) production and formation of the TLR4-TIRAP-MyD88 complex |
| GO:0032266 phosphatidylinositol-3-phosphate binding | IDA PMID:19948740 AIP1 functions as Arf6-GAP to negatively regulate TLR4 signa... | ACCEPT | Summary: PI3P binding through PH domain. Important for membrane localization. Supporting Evidence: file:human/DAB2IP/DAB2IP-deep-research-perplexity.md The PH domain located at the N-terminus binds specifically to phosphorylated phosphatidylinositol derivatives, including phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 3-phosphate (PtdIns3P) PMID:19948740 AIP1 via its pleckstrin homology and C2 domains binds to phosphatidylinositol 4-phosphate, a lipid precursor of PIP 2 |
| GO:0034144 negative regulation of toll-like receptor 4 signaling pathway | IDA PMID:19948740 AIP1 functions as Arf6-GAP to negatively regulate TLR4 signa... | ACCEPT | Summary: TLR4 signaling inhibition via Arf6-GAP activity. Core innate immune function. Supporting Evidence: file:human/DAB2IP/DAB2IP-deep-research-perplexity.md DAB2IP acts as a GAP for ARF6 and negatively regulates phosphatidylinositol 4,5-bisphosphate-dependent TLR4-TIRAP-MyD88 signaling pathways PMID:19948740 AIP1 functions as a novel Arf6-GAP to negatively regulate PIP 2 -dependent TLR4-TIRAP-MyD88 signaling |
| GO:0034260 negative regulation of GTPase activity | ISS GO_REF:0000024 | REMOVE | Summary: This conflicts with core GAP function which stimulates GTPase activity. DAB2IP activates GTPase activity (enhances GTP hydrolysis). Reason: Incorrect; DAB2IP is a GAP that stimulates (not inhibits) GTPase activity. |
| GO:0035662 Toll-like receptor 4 binding | IDA NOT PMID:19948740 AIP1 functions as Arf6-GAP to negatively regulate TLR4 signa... | ACCEPT | Summary: This is a NOT annotation indicating DAB2IP does not directly bind TLR4. The cited study shows DAB2IP disrupts the TLR4-TIRAP-MyD88 complex rather than acting as a direct TLR4-binding factor. Supporting Evidence: PMID:19948740 AIP1 disrupts formation of the TLR4- TIRAP-MyD88 complex without directly binding to any of the complex components |
| GO:0043087 regulation of GTPase activity | ISS GO_REF:0000024 | ACCEPT | Summary: GTPase activity regulation through GAP function. |
| GO:0043122 regulation of canonical NF-kappaB signal transduction | ISS GO_REF:0000024 | ACCEPT | Summary: NF-kappaB regulation. Core function. |
| GO:0043254 regulation of protein-containing complex assembly | IDA PMID:19948740 AIP1 functions as Arf6-GAP to negatively regulate TLR4 signa... | ACCEPT | Summary: Complex assembly regulation. Supporting Evidence: PMID:19948740 AIP1 disrupts formation of the TLR4- TIRAP-MyD88 complex without directly binding to any of the complex components |
| GO:0045732 positive regulation of protein catabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Protein degradation regulation. |
| GO:0070273 phosphatidylinositol-4-phosphate binding | IDA PMID:19948740 AIP1 functions as Arf6-GAP to negatively regulate TLR4 signa... | ACCEPT | Summary: PI4P binding through PH domain. Supporting Evidence: PMID:19948740 AIP1 via its pleckstrin homology and C2 domains binds to phosphatidylinositol 4-phosphate, a lipid precursor of PIP 2 |
| GO:0071222 cellular response to lipopolysaccharide | IDA PMID:19948740 AIP1 functions as Arf6-GAP to negatively regulate TLR4 signa... | ACCEPT | Summary: LPS response through TLR4 regulation. Supporting Evidence: PMID:19948740 Deletion of AIP1 from mouse endothelial cells can enhance cellular PIP 2 levels, in turn enhancing LPS-induced NF-ΞΊB and MAPK signaling |
| GO:0071347 cellular response to interleukin-1 | IDA PMID:19948740 AIP1 functions as Arf6-GAP to negatively regulate TLR4 signa... | KEEP AS NON CORE | Summary: IL-1 response. Supporting Evidence: PMID:19948740 Deletion of AIP1 from mouse endothelial cells can enhance cellular PIP 2 levels, in turn enhancing LPS-induced NF-ΞΊB and MAPK signaling |
| GO:1900744 regulation of p38MAPK cascade | ISS GO_REF:0000024 | ACCEPT | Summary: p38MAPK regulation. |
| GO:0005515 protein binding | IPI PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell ... | REMOVE | Summary: Generic protein binding. Uninformative. Reason: Generic protein binding per curation guidelines. Supporting Evidence: PMID:19903888 DAB2IP is a scaffold protein capable of bridging both survival and death signal molecules |
| GO:0008285 negative regulation of cell population proliferation | IDA PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell ... | ACCEPT | Summary: Anti-proliferative function. Core tumor suppressor activity. Supporting Evidence: PMID:19903888 Here, we show that DAB2IP protein, often down-regulated in PCa, is a potent growth inhibitor by inducing G(0)/G(1) cell cycle arrest |
| GO:0036312 phosphatidylinositol 3-kinase regulatory subunit binding | IDA PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell ... | ACCEPT | Summary: PI3K p85 subunit binding through PR domain. Core adaptor function. Supporting Evidence: file:human/DAB2IP/DAB2IP-deep-research-perplexity.md DAB2IP binds directly to the regulatory subunit (p85) of PI3K via its PR domain through interaction with p85's SH3 domain PMID:19903888 the first four prolines in the DAB2IP-PR domain is a critical binding site for the p85-SH3 domain |
| GO:0042177 negative regulation of protein catabolic process | IDA PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell ... | KEEP AS NON CORE | Summary: Protein stability regulation. Supporting Evidence: PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell survival and apoptosis. |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell ... | ACCEPT | Summary: Pro-apoptotic function. Core tumor suppressor activity. Supporting Evidence: PMID:19903888 DAB2IP can suppress the PI3K-Akt pathway and enhance ASK1 activation leading to cell apoptosis |
| GO:0043410 positive regulation of MAPK cascade | IDA PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell ... | ACCEPT | Summary: Context-dependent. DAB2IP activates ASK1-JNK/p38 MAPK while inhibiting Ras-ERK MAPK. Reason: Activates pro-apoptotic MAPK (JNK/p38) while inhibiting proliferative MAPK (ERK). Supporting Evidence: PMID:19903888 loss of DAB2IP expression resulted in PI3K-Akt activation and ASK1-JNK inactivation leading to accelerated PCa growth in vivo |
| GO:0044877 protein-containing complex binding | IDA PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell ... | ACCEPT | Summary: Complex binding as scaffold. Supporting Evidence: PMID:19903888 DAB2IP is a scaffold protein capable of bridging both survival and death signal molecules |
| GO:0046330 positive regulation of JNK cascade | IDA PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell ... | ACCEPT | Summary: JNK activation. Core apoptotic function. Supporting Evidence: PMID:19903888 DAB2IP can suppress the PI3K-Akt pathway and enhance ASK1 activation leading to cell apoptosis |
| GO:0051726 regulation of cell cycle | IDA PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell ... | ACCEPT | Summary: Cell cycle regulation through multiple pathways. Supporting Evidence: PMID:19903888 Here, we show that DAB2IP protein, often down-regulated in PCa, is a potent growth inhibitor by inducing G(0)/G(1) cell cycle arrest |
| GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IDA PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell ... | ACCEPT | Summary: PI3K-AKT pathway inhibition. Core tumor suppressor function. Supporting Evidence: file:human/DAB2IP/DAB2IP-deep-research-perplexity.md DAB2IP inhibits the phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling axis through multiple complementary mechanisms PMID:19903888 DAB2IP is able to inhibit PI3K activity by sequestering and stabilizing p85-p110 complex and then further inactivating Akt |
| GO:0070317 negative regulation of G0 to G1 transition | IDA PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell ... | ACCEPT | Summary: Cell cycle arrest function. Supporting Evidence: PMID:19903888 Here, we show that DAB2IP protein, often down-regulated in PCa, is a potent growth inhibitor by inducing G(0)/G(1) cell cycle arrest |
| GO:0070373 negative regulation of ERK1 and ERK2 cascade | IDA PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell ... | ACCEPT | Summary: ERK cascade inhibition through Ras-GAP activity. Core tumor suppressor function. Supporting Evidence: PMID:19903888 loss of DAB2IP expression resulted in PI3K-Akt activation and ASK1-JNK inactivation leading to accelerated PCa growth in vivo |
| GO:2001235 positive regulation of apoptotic signaling pathway | IDA PMID:19903888 DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell ... | ACCEPT | Summary: Apoptotic signaling activation. Core function. Supporting Evidence: PMID:19903888 DAB2IP can suppress the PI3K-Akt pathway and enhance ASK1 activation leading to cell apoptosis |
| GO:0010633 negative regulation of epithelial cell migration | IMP PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal trans... | ACCEPT | Summary: Epithelial migration inhibition. Anti-metastatic function. Supporting Evidence: PMID:20080667 the loss of DAB2IP expression initiates epithelial-to-mesenchymal transition (EMT) |
| GO:0010719 negative regulation of epithelial to mesenchymal transition | IDA PMID:20154697 An oncogene-tumor suppressor cascade drives metastatic prost... | ACCEPT | Summary: EMT inhibition. Core anti-metastatic tumor suppressor function. Supporting Evidence: file:human/DAB2IP/DAB2IP-deep-research-perplexity.md DAB2IP loss initiates epithelial-to-mesenchymal transition (EMT) PMID:20154697 loss of the RasGAP gene DAB2IP induces metastatic prostate cancer in a murine model |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal trans... | ACCEPT | Summary: Transcriptional regulation through multiple pathways. Supporting Evidence: PMID:20080667 DAB2IP functions as a scaffold protein in regulating EMT by modulating nuclear beta-catenin/T-cell factor activity |
| GO:1901800 positive regulation of proteasomal protein catabolic process | IMP PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal trans... | KEEP AS NON CORE | Summary: Proteasomal degradation regulation. Supporting Evidence: PMID:20080667 In the presence of DAB2IP, interaction of its C2 domain with both PP2A and GSK-3Ξ² facilitates GSK-3Ξ² activation through S9 dephosphorylation |
| GO:0010596 negative regulation of endothelial cell migration | IMP PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated... | ACCEPT | Summary: Endothelial migration inhibition. Anti-angiogenic function. Supporting Evidence: PMID:19033661 VEGF-induced EC migration was inhibited by AIP1 overexpression, whereas it was augmented by both AIP1 knockout and knockdown |
| GO:0010976 positive regulation of neuron projection development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neuronal development. Non-core. |
| GO:0016525 negative regulation of angiogenesis | IDA PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated... | ACCEPT | Summary: Anti-angiogenic function. Core vascular biology function. Supporting Evidence: file:human/DAB2IP/DAB2IP-deep-research-perplexity.md DAB2IP acts as an endogenous inhibitor of vascular endothelial growth factor receptor 2-mediated angiogenic signaling PMID:19033661 AIP1 functions as an endogenous inhibitor in VEGFR2-mediated adaptive angiogenesis in mice |
| GO:0017124 SH3 domain binding | IDA PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated... | ACCEPT | Summary: SH3 domain binding for PI3K p85 interaction. Supporting Evidence: PMID:19033661 AIP1 via its C2 domain associates with VEGFR2 while via its PR domain binds to the SH3 domain of PI3K p85, leading to an inhibition of VEGFR2-mediated angiogenic signaling |
| GO:0021814 cell motility involved in cerebral cortex radial glia guided migration | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neuronal migration. Non-core. |
| GO:0021819 layer formation in cerebral cortex | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cortical development. Non-core. |
| GO:0030424 axon | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Axonal localization. Non-core. |
| GO:0030948 negative regulation of vascular endothelial growth factor receptor signaling pathway | IMP PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated... | ACCEPT | Summary: VEGFR signaling inhibition. Core anti-angiogenic function. Supporting Evidence: PMID:19033661 we present mechanistic data that suggest AIP1 is recruited to the VEGFR2-PI3K complex, binding to both VEGFR2 and PI3K p85, at a late phase of the VEGF response, and that this leads to inhibition of VEGFR2 signaling |
| GO:0032809 neuronal cell body membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neuronal localization. Non-core. |
| GO:0035148 tube formation | IMP PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated... | KEEP AS NON CORE | Summary: Tube formation related to angiogenesis. Supporting Evidence: PMID:19033661 VEGF-induced neovascularization is greatly augmented in KO mice |
| GO:0035924 cellular response to vascular endothelial growth factor stimulus | ISS GO_REF:0000024 | ACCEPT | Summary: VEGF response. |
| GO:0035924 cellular response to vascular endothelial growth factor stimulus | IDA PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated... | ACCEPT | Summary: VEGF response. Duplicate evidence. Supporting Evidence: PMID:19033661 the enhanced EC migration caused by AIP1 knockdown being associated with increased VEGFR2 signaling |
| GO:0036324 vascular endothelial growth factor receptor-2 signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: VEGFR2 pathway. |
| GO:0043025 neuronal cell body | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neuronal localization. Non-core. |
| GO:0043184 vascular endothelial growth factor receptor 2 binding | IPI PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated... | ACCEPT | Summary: VEGFR2 binding through C2 domain. Core anti-angiogenic function. Supporting Evidence: PMID:19033661 AIP1 via its C2 domain associates with VEGFR2 while via its PR domain binds to the SH3 domain of PI3K p85, leading to an inhibition of VEGFR2-mediated angiogenic signaling |
| GO:0043548 phosphatidylinositol 3-kinase binding | IDA PMID:19033661 AIP1 functions as an endogenous inhibitor of VEGFR2-mediated... | ACCEPT | Summary: PI3K binding. Core adaptor function. Supporting Evidence: PMID:19033661 AIP1 is recruited to the VEGFR2-PI3K complex, binding to both VEGFR2 and PI3K p85 |
| GO:0044300 cerebellar mossy fiber | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cerebellar localization. Non-core. |
| GO:0044301 climbing fiber | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cerebellar localization. Non-core. |
| GO:0048812 neuron projection morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neuronal morphogenesis. Non-core. |
| GO:0090129 positive regulation of synapse maturation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Synapse maturation. Non-core. |
| GO:1900006 positive regulation of dendrite development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Dendrite development. Non-core. |
| GO:1900747 negative regulation of vascular endothelial growth factor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: VEGF signaling inhibition. |
| GO:1990032 parallel fiber | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cerebellar localization. Non-core. |
| GO:2001224 positive regulation of neuron migration | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neuronal migration. Non-core. |
| GO:0005515 protein binding | IPI PMID:17389591 RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site ... | REMOVE | Summary: Generic protein binding. Uninformative. Reason: Generic protein binding per curation guidelines. Supporting Evidence: PMID:17389591 RIP1 (the Ser/Thr protein kinase receptor-interacting protein) associates with the GAP domain of AIP1 |
| GO:0019900 kinase binding | IPI PMID:17389591 RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site ... | ACCEPT | Summary: RIP1 kinase binding. Important for TNF signaling. Supporting Evidence: PMID:17389591 RIP1 (the Ser/Thr protein kinase receptor-interacting protein) associates with the GAP domain of AIP1 and mediates TNF-induced AIP1 phosphorylation at Ser-604 and JNK/p38 activation |
| GO:0030163 protein catabolic process | IDA PMID:17389591 RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site ... | KEEP AS NON CORE | Summary: Protein degradation regulation. Supporting Evidence: PMID:17389591 RIP1 synergizes with AIP1 (but not AIP1-S604A) in inducing both JNK/p38 activation and EC apoptosis |
| GO:0031434 mitogen-activated protein kinase kinase binding | IPI PMID:17389591 RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site ... | ACCEPT | Summary: MAP2K binding for MAPK pathway regulation. Supporting Evidence: PMID:17389591 TNF-induced TRAF2-RIP1-AIP1-ASK1 complex formation and for the activation of ASK1-JNK/p38 apoptotic signaling |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:17389591 RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site ... | ACCEPT | Summary: Pro-apoptotic function. Core. Supporting Evidence: PMID:17389591 RIP1 synergizes with AIP1 (but not AIP1-S604A) in inducing both JNK/p38 activation and EC apoptosis |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IDA PMID:17389591 RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site ... | ACCEPT | Summary: NF-kappaB inhibition. Core anti-metastatic function. Supporting Evidence: file:human/DAB2IP/DAB2IP-deep-research-perplexity.md DAB2IP acts as a negative regulator of NF-kappaB signaling PMID:17389591 TNF-induced TRAF2-RIP1-AIP1-ASK1 complex formation and for the activation of ASK1-JNK/p38 apoptotic signaling |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:17389591 RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site ... | KEEP AS NON CORE | Summary: Transcriptional activation through AP-1. Supporting Evidence: PMID:17389591 RIP1-mediated AIP1 phosphorylation at the 14-3-3-binding site Ser-604 is essential for TNF-induced TRAF2-RIP1-AIP1-ASK1 complex formation and for the activation of ASK1-JNK/p38 apoptotic signaling |
| GO:0046330 positive regulation of JNK cascade | IDA PMID:17389591 RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site ... | ACCEPT | Summary: JNK activation. Core. Supporting Evidence: PMID:17389591 RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site is critical for tumor necrosis factor-induced ASK1-JNK/p38 activation |
| GO:0071356 cellular response to tumor necrosis factor | IDA PMID:17389591 RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site ... | ACCEPT | Summary: TNF response. Supporting Evidence: PMID:17389591 TNF treatment of EC induces phosphorylation of AIP1 at Ser-604 as detected by a phospho-specific antibody, with a similar kinetics to ASK1-JNK/p38 activation |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:15310755 AIP1/DAB2IP, a novel member of the Ras-GAP family, transduce... | ACCEPT | Summary: Transcriptional repression of NF-kappaB targets. Supporting Evidence: PMID:15310755 the binding of AIP1 to TRAF2 inhibits TNF-induced IKK-NF-kappaB signaling |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:20154697 An oncogene-tumor suppressor cascade drives metastatic prost... | ACCEPT | Summary: Transcriptional repression. Supporting Evidence: PMID:20154697 DAB2IP is suppressed in human prostate cancer where expression inversely correlates with tumor grade and predicts prognosis |
| GO:0005123 death receptor binding | IPI PMID:15310755 AIP1/DAB2IP, a novel member of the Ras-GAP family, transduce... | ACCEPT | Summary: Death receptor binding for TNF signaling. Supporting Evidence: PMID:15310755 AIP1 is localized on the plasma membrane in resting endothelial cells (EC) in a complex with TNFR1. TNF binding induces release of AIP1 from TNFR1 |
| GO:0005737 cytoplasm | IDA PMID:15310755 AIP1/DAB2IP, a novel member of the Ras-GAP family, transduce... | ACCEPT | Summary: Cytoplasmic localization. Supporting Evidence: PMID:15310755 TNF binding induces release of AIP1 from TNFR1, resulting in cytoplasmic translocation |
| GO:0005886 plasma membrane | IDA PMID:15310755 AIP1/DAB2IP, a novel member of the Ras-GAP family, transduce... | ACCEPT | Summary: Plasma membrane localization. Supporting Evidence: PMID:15310755 AIP1 is localized on the plasma membrane in resting endothelial cells (EC) in a complex with TNFR1 |
| GO:0010633 negative regulation of epithelial cell migration | TAS PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal trans... | ACCEPT | Summary: Epithelial migration inhibition. Supporting Evidence: PMID:20080667 the loss of DAB2IP expression initiates epithelial-to-mesenchymal transition (EMT) |
| GO:0010719 negative regulation of epithelial to mesenchymal transition | IMP PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal trans... | ACCEPT | Summary: EMT inhibition. Core anti-metastatic function. Supporting Evidence: PMID:20080667 restoring DAB2IP in metastatic PCa cells reversed EMT |
| GO:0019901 protein kinase binding | IPI PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal trans... | ACCEPT | Summary: Kinase binding. Supporting Evidence: PMID:20080667 In the presence of DAB2IP, interaction of its C2 domain with both PP2A and GSK-3Ξ² facilitates GSK-3Ξ² activation |
| GO:0031435 mitogen-activated protein kinase kinase kinase binding | IPI PMID:12813029 AIP1 mediates TNF-alpha-induced ASK1 activation by facilitat... | ACCEPT | Summary: MAP3K (ASK1) binding. Core function. Supporting Evidence: PMID:12813029 In the present study, we identified a novel Ras GTPase-activating protein (Ras-GAP) as an ASK1-interacting protein (AIP1). AIP1 binds to the C-terminal domain of ASK1 via a lysine-rich cluster within the N-terminal C2 domain |
| GO:0035591 signaling adaptor activity | IDA PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal trans... | ACCEPT | Summary: Adaptor function. Core. Supporting Evidence: PMID:20080667 DAB2IP functions as a scaffold protein in regulating EMT by modulating nuclear beta-catenin/T-cell factor activity |
| GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway | ISS PMID:11812785 The mechanism of growth-inhibitory effect of DOC-2/DAB2 in p... | ACCEPT | Summary: EGFR signaling inhibition through Ras-GAP activity. Supporting Evidence: PMID:11812785 2002 Jan 25. The mechanism of growth-inhibitory effect of DOC-2/DAB2 in prostate cancer. |
| GO:0042803 protein homodimerization activity | IPI PMID:12813029 AIP1 mediates TNF-alpha-induced ASK1 activation by facilitat... | ACCEPT | Summary: Homodimerization. Functionally relevant. Supporting Evidence: PMID:12813029 AIP1 exists in a closed form through an intramolecular interaction between the N-terminus and the C-terminus, and TNF-alpha induces unfolding of AIP1 leading to association of AIP1 with ASK1 |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IDA PMID:15310755 AIP1/DAB2IP, a novel member of the Ras-GAP family, transduce... | ACCEPT | Summary: NF-kappaB inhibition. Core function. Supporting Evidence: PMID:15310755 the binding of AIP1 to TRAF2 inhibits TNF-induced IKK-NF-kappaB signaling |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:15310755 AIP1/DAB2IP, a novel member of the Ras-GAP family, transduce... | KEEP AS NON CORE | Summary: AP-1 mediated transcription. Supporting Evidence: PMID:15310755 AIP1 is a novel transducer in TNF-induced TRAF2-dependent activation of ASK1 that mediates a balance between JNK versus NF-kappaB signaling |
| GO:0048147 negative regulation of fibroblast proliferation | ISS GO_REF:0000024 | ACCEPT | Summary: Anti-proliferative function. |
| GO:0050680 negative regulation of epithelial cell proliferation | IMP PMID:20154697 An oncogene-tumor suppressor cascade drives metastatic prost... | ACCEPT | Summary: Epithelial proliferation inhibition. Core tumor suppressor. Supporting Evidence: PMID:20154697 DAB2IP is suppressed in human prostate cancer where expression inversely correlates with tumor grade and predicts prognosis |
| GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | ISS PMID:18281285 AIP1 is critical in transducing IRE1-mediated endoplasmic re... | ACCEPT | Summary: ER stress apoptosis. Core function. Supporting Evidence: PMID:18281285 AIP1 is essential for transducing the IRE1-mediated ER stress response |
| GO:0071356 cellular response to tumor necrosis factor | IDA PMID:12813029 AIP1 mediates TNF-alpha-induced ASK1 activation by facilitat... | ACCEPT | Summary: TNF response. Supporting Evidence: PMID:12813029 TNF-alpha induces unfolding of AIP1 leading to association of AIP1 with ASK1 |
| GO:0071356 cellular response to tumor necrosis factor | IDA PMID:15310755 AIP1/DAB2IP, a novel member of the Ras-GAP family, transduce... | ACCEPT | Summary: TNF response. Supporting Evidence: PMID:15310755 AIP1 is localized on the plasma membrane in resting endothelial cells (EC) in a complex with TNFR1. TNF binding induces release of AIP1 from TNFR1 |
| GO:0071364 cellular response to epidermal growth factor stimulus | ISS PMID:11812785 The mechanism of growth-inhibitory effect of DOC-2/DAB2 in p... | KEEP AS NON CORE | Summary: EGF response. Supporting Evidence: PMID:11812785 2002 Jan 25. The mechanism of growth-inhibitory effect of DOC-2/DAB2 in prostate cancer. |
| GO:0071889 14-3-3 protein binding | IDA PMID:17389591 RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site ... | ACCEPT | Summary: 14-3-3 binding for ASK1 regulation. Important for ASK1 activation. Supporting Evidence: PMID:17389591 Ser-604, located in the C-terminal domain of AIP1, was identified as a 14-3-3-binding site. TNF treatment of EC induces phosphorylation of AIP1 at Ser-604 |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Wnt signaling inhibition. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IMP PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal trans... | ACCEPT | Summary: Wnt signaling inhibition. Core tumor suppressor function. Supporting Evidence: PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal transition and prostate cancer metastasis. |
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Download this section (compressed HTML)Q: How does DAB2IP achieve substrate specificity across structurally diverse GTPase families (Ras, ARF, Rab) with a single GAP domain?
Q: What determines whether DAB2IP promotes apoptosis (through ASK1-JNK) versus cell survival in different cellular contexts?
Experiment: Determine structures of DAB2IP GAP domain bound to different GTPase substrates (Ras, ARF6, RAB40C) to understand substrate recognition mechanisms.
Type: structural biology
Experiment: Generate domain-specific DAB2IP knockin mice (GAP-dead, PER-domain mutant) to dissect contributions of enzymatic vs scaffold functions to tumor suppression.
Type: functional genetics
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