IQGAP3
Ras GTPase-activating-like protein IQGAP3 · UniProt Q86VI3
- Length
- 1631 aa
- Mass
- 184.7 kDa
- Annotated
- 2026-04-28
49 papers in source corpus
28 papers cited in narrative
28 extracted findings
Mechanistic narrative
Synthesis pass · prose summary of the discoveries below
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Mechanism profile
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Evidence
Reading pass · 28 per-paper findings extracted from the source corpus
| Year | Finding | Method | Journal | Conf | PMIDs |
|---|---|---|---|---|---|
| 2007 | IQGAP3 is a direct effector of active Rac1 and Cdc42 GTPases, associates directly with actin filaments, accumulates asymmetrically at the distal region of axons in hippocampal neurons, and is required for neurite/axon outgrowth; depletion causes disorganized cytoskeleton and impairs Rac1/Cdc42-promoted neurite outgrowth in PC12 cells. | Co-immunoprecipitation with active GTPases, actin co-sedimentation assay, immunofluorescence localization, siRNA knockdown with morphological readout in primary neurons and PC12 cells | Journal of cell science | High | 17244649 |
| 2008 | IQGAP3 specifically binds the active (GTP-bound) form of Ras and is necessary and sufficient to drive epithelial cell proliferation through Ras-dependent ERK activation; knockdown reduces Ras and ERK activity, and IQGAP3 overexpression induces cell-cycle re-entry blocked by MEK inhibitor U0126. | Co-immunoprecipitation with GTP-locked Ras, siRNA knockdown, ectopic overexpression, MEK inhibitor epistasis, ERK activity assay | Nature cell biology | High | 18604197 |
| 2011 | All four IQ-motifs of IQGAP3 interact with calmodulin (CaM) in the presence of calcium ions, with variable stability; the first IQ-motif of IQGAP3 also forms a transient interaction with myosin essential light chain (Mlc1sa), but none interact with S100B. | Synthetic peptide binding assays, native gel electrophoresis, molecular modelling | Bioscience reports | Medium | 21299499 |
| 2014 | IQGAP3 interacts with ERK1 and enhances its phosphorylation following EGF treatment, placing IQGAP3 in the EGFR-ERK signaling cascade in lung cancer cells. | Co-immunoprecipitation, Western blot for phospho-ERK after EGF stimulation, siRNA knockdown | PloS one | Medium | 24849319 |
| 2015 | IQGAP3 plays a non-redundant, essential role in epidermal tumorigenesis downstream of oncogenic Ras-MAPK signaling; sub-physiologic IQGAP3 suffices for normal homeostasis but higher levels are required for tumor support, demonstrated by IQGAP decoy domain competition in vivo. | Genetically engineered human skin tissue in vivo, IQGAP1-IQ decoy domain competition, MAPK signaling assays | The Journal of investigative dermatology | Medium | 25848980 |
| 2015 | In zebrafish, IQGAP3 loss-of-function phenocopies dominant-negative FGFR1 or dominant-negative Ras, and co-injection of IQGAP3 mRNA rescues dominant-negative FGFR1 or Ras phenotypes, placing IQGAP3 as a downstream regulator of the FGFR1-Ras signaling pathway controlling cell proliferation and motility. | Morpholino knockdown in zebrafish, genetic epistasis with dominant-negative FGFR1/Ras, mRNA rescue experiments | Cytoskeleton (Hoboken, N.J.) | High | 26286209 |
| 2017 | IQGAP3 promotes epithelial-mesenchymal transition (EMT) and metastasis in hepatocellular carcinoma by constitutively activating TGF-β signaling. | Ectopic overexpression and siRNA knockdown, in vitro migration/invasion assays, orthotopic mouse metastasis model, Western blot for TGF-β pathway markers | Journal of translational medicine | Medium | 28810875 |
| 2018 | During cytokinesis, IQGAP3 normally localizes to the actomyosin ring and midbody stembody; in binucleating cardiomyocytes, IQGAP3 fails to localize properly due to aberrant astral microtubule distribution, linking IQGAP3 localization to successful cleavage furrow ingression. | Time-lapse imaging, immunofluorescence localization in dividing vs. binucleating cardiomyocytes in vitro and in vivo | Cardiovascular research | Medium | 29522098 |
| 2019 | E2F1 transcriptionally activates IQGAP3; IQGAP3 then interacts with PKCδ and competitively inhibits the PKCδ-PKCα interaction, resulting in PKCα phosphorylation and activation, promoting HCC cell proliferation. | Co-immunoprecipitation, competitive binding assay, Western blot for phospho-PKCα, chromatin immunoprecipitation/transcriptional activation assay | American journal of cancer research | Medium | 30906629 |
| 2020 | IQGAP3 interacts with Rad17 and controls its expression, recruiting the Mre11-Rad50-Nbs1 (MRN) complex to activate ATM/Chk2 and ATR/Chk1 DNA damage signaling pathways, conferring radioresistance in lung cancer. | Co-immunoprecipitation, siRNA knockdown, in vitro and in vivo radioresistance assays, Western blot for ATM/Chk2 and ATR/Chk1 phosphorylation | Cancer letters | Medium | 32896617 |
| 2020 | IQGAP3 accumulates at the leading edge of migrating cells and at the cleavage furrow of dividing cells; it interacts with Rho family GTPases and reduces cell-cell adhesion via interactions with E-cadherin and β-catenin, promoting migration and cytokinesis. | Immunofluorescence localization, Co-immunoprecipitation with E-cadherin/β-catenin and Rho GTPases, siRNA knockdown with migration/invasion readout, overexpression morphology assay | Biomolecules | Medium | 32824461 |
| 2020 | The Iqgap3-Ras signaling axis is essential for proliferation of isthmus stem cells in the stomach corpus; Iqgap3 expression is required for stem cell maintenance and proliferative potential, and is robustly induced after tissue damage to drive repair. | Iqgap3-2A-tdTomato mouse lineage tracing, conditional depletion, transcriptomic analysis, immunofluorescence | Gut | High | 33293280 |
| 2021 | IQGAP3 is a transcriptional target of YAP; IQGAP3 knockdown causes S-phase delay, multipolar spindle formation, aneuploidy, and decreased MMS19 protein levels; IQGAP3 interacts with MMS19 and modulates the cell cycle via the MMS19/XPD/CAK axis (XPD knockdown partially rescues IQGAP3 KD proliferation defect). | YAP ChIP/reporter assay, siRNA knockdown, cell cycle FACS, immunofluorescence for spindle, protein-protein interaction studies, epistasis rescue with XPD siRNA | Molecular cancer research : MCR | Medium | 34183451 |
| 2022 | CDC42 regulates IQGAP3 expression and promotes the Ras/ERK pathway through IQGAP3; overexpression of IQGAP3 rescues proliferation and apoptosis suppression caused by CDC42 knockdown in bladder cancer cells, placing IQGAP3 downstream of CDC42 in the Ras/ERK axis. | siRNA knockdown, overexpression rescue, Western blot for Ras/ERK pathway components, flow cytometry for apoptosis | Biochemical genetics | Medium | 35412170 |
| 2022 | IGF2BP1 binds and stabilizes m6A-modified IQGAP3 transcripts, maintaining IQGAP3 expression in cancer stem cells; downstream transcription factors SRF and FOXM1 also upregulate IQGAP3 expression. | RNA immunoprecipitation (RIP), m6A modification assays, gene expression analysis in Iqgap3-2A-tdTomato mouse model, transcription factor binding assays | iScience | Medium | 36217548 |
| 2022 | hnRNPC directly interacts with IQGAP3 and stabilizes it, promoting pancreatic cancer cell growth and invasion through activation of epithelial-mesenchymal transition. | Co-immunoprecipitation, siRNA knockdown, in vitro and in vivo metastasis models, Western blot | BioMed research international | Low | 35355828 |
| 2023 | FOXD2 transcriptionally activates IQGAP3 by binding to its promoter region, leading to increased intracellular Ca2+ levels and promotion of gastric adenocarcinoma cell proliferation. | Chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay, Fluo-3 Ca2+ measurement, siRNA knockdown, overexpression | The Kaohsiung journal of medical sciences | Medium | 37724892 |
| 2024 | IQGAP3 promotes microvascular invasion in hepatocellular carcinoma via dual mechanism: (1) sustaining GTPase Rac1 activity to remodel the cytoskeleton and enhance trans-endothelial migration of cancer cells, and (2) inducing activation and detachment of hepatic stellate cells from endothelium via upregulation of multiple cytokines. | Proteomic analysis, RNA-sequencing, coculture modeling, orthotopic xenograft mouse model, siRNA nanoparticle delivery, immunofluorescence for Rac1 activity | Clinical cancer research | Medium | 38470497 |
| 2024 | IQGAP3 interacts with PAK6; IQGAP3 depletion disrupts RhoA activity and actomyosin contractility in triple negative breast cancer cells, impairing migration and invadopodia formation; PAK6 overexpression rescues the IQGAP3 depletion phenotype, defining a PAK6-IQGAP3-RhoA pathway. | Co-immunoprecipitation, siRNA knockdown, PAK6 overexpression rescue, RhoA activity assay, time-lapse migration assay, invadopodia assay | Cellular signalling | Medium | 38763182 |
| 2024 | IQGAP3 activates the Hedgehog-GLI1 signaling pathway to promote lung cancer stemness and metastasis; IQGAP3 knockdown reduces GLI1 mRNA and protein and impairs sphere-forming, migration, and invasion, with GLI1 identified as the primary downstream effector by RNA-sequencing. | siRNA knockdown, RNA sequencing, Western blot for Hedgehog/GLI1 pathway, sphere-forming assay, migration/invasion assay | Scientific reports | Medium | 39732803 |
| 2024 | PRKN (Parkin) ubiquitinates IQGAP3 and promotes its proteasomal degradation; reduced PRKN in early-onset colorectal cancer leads to IQGAP3 accumulation, which promotes tumor cell growth, metastasis, and suppresses ferroptosis. | Co-immunoprecipitation, ubiquitination assay, Western blot, siRNA knockdown, overexpression, xenograft tumor models | Journal of bioenergetics and biomembranes | Medium | 39343867 |
| 2025 | IQGAP3 is a Wnt target gene that participates in a positive feedback loop: IQGAP3 interacts with Axin1 and CK1α (identified by TurboID proximity proteomics), disrupts Axin1-CK1α interaction, thereby inhibiting β-catenin phosphorylation and promoting its accumulation in gastric cancer cells. | TurboID proximity labeling proteomics, Co-immunoprecipitation, overexpression, siRNA knockdown, β-catenin phosphorylation assays | Oncogene | High | 40830657 |
| 2025 | IQGAP3 knockdown attenuates KRAS/MEK/ERK signaling via phosphorylation blockade in gastric cancer and reduces TGFβ1 levels, disrupting the RAS-TGFβ signaling crosstalk and tumor microenvironment formation; IQGAP3 maintains intratumoral functional heterogeneity required for malignant growth. | RNA-sequencing, phosphoproteomics, xenograft tumorigenesis/lung metastasis assay, digital spatial transcriptomics, immunofluorescence for TGFβ/SMAD and αSMA | Gut | High | 39438124 |
| 2025 | METTL3-catalyzed m6A modification of IQGAP3 mRNA stabilizes IQGAP3 transcripts via IGF2BP2 (m6A reader) binding, increasing IQGAP3 protein levels and driving HCC metastasis through activation of TGF-β/Smad signaling and EMT. | RNA immunoprecipitation (RIP) for IGF2BP2-IQGAP3 mRNA interaction, m6A assay, METTL3/IGF2BP2 knockdown, mRNA stability assay, in vitro and in vivo metastasis models | Pathology, research and practice | Medium | 40945199 |
| 2025 | IFFO1 directly interacts with IQGAP3 through its 2A coiled-coil domain and inhibits IQGAP3's interaction with its effector Cdc42 in a dose-dependent manner, suppressing lung cancer cell migration. | Co-immunoprecipitation, domain-deletion mutant binding assays, competitive binding assay for IQGAP3-Cdc42 interaction, siRNA knockdown with migration readout | Cell death & disease | Medium | 40634295 |
| 2025 | IQGAP3 regulates macrophage polarization by binding and sequestering IGF2BP2 at the cell periphery, limiting IGF2BP2-mediated stabilization of FYN mRNA, which reduces FYN expression and decreases STAT1 phosphorylation, thereby driving immunosuppressive M2 polarization. | Co-immunoprecipitation, immunofluorescence for IGF2BP2 localization, mRNA stability assay, Western blot for FYN and phospho-STAT1, macrophage-cancer coculture, xenograft model with anti-PD-1 combination | Cellular and molecular life sciences : CMLS | Medium | 41467907 |
| 2025 | IQGAP3 deficiency leads to hereditary hearing loss via inhibition of CDC42 enzymatic activity and blockade of the Wnt-β-catenin pathway, impairing inner ear progenitor cell proliferation in zebrafish and mouse models. | iqgap3 morpholino knockdown zebrafish, IQGAP3-KO HEK293T cells, primary mouse inner ear progenitor cell culture, EdU/Ki67 proliferation assays, CDC42 activity assay, Wnt pathway readout | International journal of pediatric otorhinolaryngology | Medium | 40239295 |
| 2026 | IQGAP3 is required for Marburg virus transcription/replication, nucleocapsid long-distance transport, and virus release; IQGAP3 knockout (and IQGAP1 KO) reduces spatial displacement efficiency of motile nucleocapsids, while actin tail formation persists, indicating IQGAP3 modulates actin dynamics to support viral processes. | CRISPR/Cas9 single/combined/triple IQGAP KO in Huh-7 cells, live-cell imaging of nucleocapsid transport, viral replication/transcription assays, rescue by individual IQGAP expression | Cellular and molecular life sciences : CMLS | Medium | 41661241 |
Source papers
Stage 0 corpus · 49 papers · ranked by NIH iCite citations
| Year | Title | Journal | Citations | PMID |
|---|---|---|---|---|
| 2007 | IQGAP3, a novel effector of Rac1 and Cdc42, regulates neurite outgrowth. | Journal of cell science | 141 | 17244649 |
| 2008 | IQGAP3 regulates cell proliferation through the Ras/ERK signalling cascade. | Nature cell biology | 98 | 18604197 |
| 2014 | IQGAP3 promotes EGFR-ERK signaling and the growth and metastasis of lung cancer cells. | PloS one | 70 | 24849319 |
| 2017 | Role of IQGAP3 in metastasis and epithelial-mesenchymal transition in human hepatocellular carcinoma. | Journal of translational medicine | 54 | 28810875 |
| 2016 | Expression and diagnostic value of CCT3 and IQGAP3 in hepatocellular carcinoma. | Cancer cell international | 54 | 27390551 |
| 2018 | Cardiomyocyte binucleation is associated with aberrant mitotic microtubule distribution, mislocalization of RhoA and IQGAP3, as well as defective actomyosin ring anchorage and cleavage furrow ingression. | Cardiovascular research | 49 | 29522098 |
| 2020 | Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair. | Gut | 48 | 33293280 |
| 2019 | E2F1 transactivates IQGAP3 and promotes proliferation of hepatocellular carcinoma cells through IQGAP3-mediated PKC-alpha activation. | American journal of cancer research | 34 | 30906629 |
| 2016 | Overexpression and biological function of IQGAP3 in human pancreatic cancer. | American journal of translational research | 34 | 28078013 |
| 2018 | Urinary cell-free nucleic acid IQGAP3: a new non-invasive diagnostic marker for bladder cancer. | Oncotarget | 33 | 29581849 |
| 2015 | IQGAP1 and IQGAP3 Serve Individually Essential Roles in Normal Epidermal Homeostasis and Tumor Progression. | The Journal of investigative dermatology | 29 | 25848980 |
| 2011 | IQ-motif selectivity in human IQGAP2 and IQGAP3: binding of calmodulin and myosin essential light chain. | Bioscience reports | 28 | 21299499 |
| 2020 | Enhancement of Migration and Invasion of Gastric Cancer Cells by IQGAP3. | Biomolecules | 27 | 32824461 |
| 2020 | IQGAP3 interacts with Rad17 to recruit the Mre11-Rad50-Nbs1 complex and contributes to radioresistance in lung cancer. | Cancer letters | 25 | 32896617 |
| 2009 | Involvement of IQGAP3, a regulator of Ras/ERK-related cascade, in hepatocyte proliferation in mouse liver regeneration and development. | Journal of cellular physiology | 25 | 19452445 |
| 2016 | RNA Interference of IQ Motif Containing GTPase-Activating Protein 3 (IQGAP3) Inhibits Cell Proliferation and Invasion in Breast Carcinoma Cells. | Oncology research | 23 | 28281966 |
| 2021 | IQGAP3, a YAP Target, Is Required for Proper Cell-Cycle Progression and Genome Stability. | Molecular cancer research : MCR | 21 | 34183451 |
| 2020 | IQGAP3 promotes cancer proliferation and metastasis in high-grade serous ovarian cancer. | Oncology letters | 21 | 32724358 |
| 2023 | The Antithetic Roles of IQGAP2 and IQGAP3 in Cancers. | Cancers | 18 | 36831467 |
| 2022 | CDC42 Regulates Cell Proliferation and Apoptosis in Bladder Cancer via the IQGAP3-Mediated Ras/ERK Pathway. | Biochemical genetics | 18 | 35412170 |
| 2018 | Diagnostic value of combined IQGAP3/BMP4 and IQGAP3/FAM107A expression ratios in urinary cell-free DNA for discriminating bladder cancer from hematuria. | Urologic oncology | 18 | 30446454 |
| 2020 | Integrative Analysis of the IQ Motif-Containing GTPase-Activating Protein Family Indicates That the IQGAP3-PIK3C2B Axis Promotes Invasion in Colon Cancer. | OncoTargets and therapy | 14 | 32903879 |
| 2019 | IQ Motif Containing GTPase-Activating Protein 3 (IQGAP3) Inhibits Kaempferol-Induced Apoptosis in Breast Cancer Cells by Extracellular Signal-Regulated Kinases 1/2 (ERK1/2) Signaling Activation. | Medical science monitor : international medical journal of experimental and clinical research | 14 | 31605603 |
| 2022 | Oncofetal protein IGF2BP1 regulates IQGAP3 expression to maintain stem cell potential in cancer. | iScience | 13 | 36217548 |
| 2015 | IQGAP3 is essential for cell proliferation and motility during zebrafish embryonic development. | Cytoskeleton (Hoboken, N.J.) | 13 | 26286209 |
| 2024 | Infiltrative Vessel Co-optive Growth Pattern Induced by IQGAP3 Overexpression Promotes Microvascular Invasion in Hepatocellular Carcinoma. | Clinical cancer research : an official journal of the American Association for Cancer Research | 12 | 38470497 |
| 2022 | hnRNPC Promotes Malignancy in Pancreatic Cancer through Stabilization of IQGAP3. | BioMed research international | 12 | 35355828 |
| 2025 | IQGAP3 signalling mediates intratumoral functional heterogeneity to enhance malignant growth. | Gut | 10 | 39438124 |
| 2023 | IQGAP3 is relevant to prostate cancer: A detailed presentation of potential pathomechanisms. | Journal of advanced research | 10 | 36681115 |
| 2024 | PAK6 acts downstream of IQGAP3 to promote contractility in triple negative breast cancer cells. | Cellular signalling | 8 | 38763182 |
| 2023 | FOXD2 regulations IQGAP3 mediated Ca2+ signaling pathway to facilitate gastric adenocarcinoma cell promotion. | The Kaohsiung journal of medical sciences | 7 | 37724892 |
| 2022 | lncRNA MIR4435-2HG Accelerates the Development of Bladder Cancer through Enhancing IQGAP3 and CDCA5 Expression. | BioMed research international | 7 | 35993042 |
| 2022 | IQGAP3 in clear cell renal cell carcinoma contributes to drug resistance and genome stability. | PeerJ | 7 | 36275458 |
| 2021 | IQGAP3 May Serve as a Promising Biomarker in Clear Cell Renal Cell Carcinoma. | International journal of general medicine | 4 | 34285569 |
| 2024 | PRKN-mediated the ubiquitination of IQGAP3 regulates cell growth, metastasis and ferroptosis in early-onset colorectal cancer. | Journal of bioenergetics and biomembranes | 3 | 39343867 |
| 2024 | IQGAP3 Is an Important Mediator of Skin Inflammatory Diseases. | International journal of molecular sciences | 2 | 38674130 |
| 2025 | Intermediate filament IFFO1 negatively regulates the migration of lung cancer cells by inhibiting the IQGAP3-Cdc42 interaction. | Cell death & disease | 1 | 40634295 |
| 2025 | METTL3/IGF2BP2 stabilizes IQGAP3 via m6A modification to drive HCC metastasis through TGF-β/Smad signaling and EMT. | Pathology, research and practice | 1 | 40945199 |
| 2025 | The lncRNA MIR4435-2HG Modulates Bladder Cancer Progression and Ferroptosis Through the IQGAP3/Ras/ERK/CREB Pathway. | FASEB journal : official publication of the Federation of American Societies for Experimental Biology | 1 | 41085154 |
| 2023 | Identifying Adult Stomach Tissue Stem/Progenitor Cells Using the Iqgap3-2A-CreERT2 Mouse. | Methods in molecular biology (Clifton, N.J.) | 1 | 37355533 |
| 2026 | IQGAP1 and IQGAP3 are critical host factors for Marburg virus replication, nucleocapsid transport, and cell-to-cell spread. | Cellular and molecular life sciences : CMLS | 0 | 41661241 |
| 2025 | IQGAP3 deficiency leads to non-syndromic hearing loss via inhibition of CDC42 enzyme activity. | International journal of pediatric otorhinolaryngology | 0 | 40239295 |
| 2025 | Transcription Factor MYB Upregulates IQGAP3 to Mediate DNA Repair and Promote 5-FU Resistance in Gastric Cancer Cells. | Drug development research | 0 | 40772604 |
| 2025 | Wnt target IQGAP3 promotes Wnt signaling via disrupting Axin1-CK1α interaction. | Oncogene | 0 | 40830657 |
| 2025 | Wilms' tumor 1-associating protein regulates the stress fiber reservoirs in endothelial cells via KLF2-IQGAP3. | Cellular signalling | 0 | 41317937 |
| 2025 | Targeting IQGAP3 skews macrophages polarization towards M1 phenotype and promotes antitumor immune response. | Cellular and molecular life sciences : CMLS | 0 | 41467907 |
| 2024 | Retracted: lncRNA MIR4435-2HG Accelerates the Development of Bladder Cancer through Enhancing IQGAP3 and CDCA5 Expression. | BioMed research international | 0 | 38550059 |
| 2024 | IQGAP3 activates Hedgehog signaling to confer stemness and metastasis via up-regulating GLI1 in lung cancer. | Scientific reports | 0 | 39732803 |
| 2020 | Intronic variant in IQGAP3 associated with hereditary neuropathy with proximal lower dominancy, urinary disturbance, and paroxysmal dry cough. | Journal of human genetics | 0 | 32341455 |