{"gene":"BAIAP2L1","run_date":"2026-06-09T22:02:44","timeline":{"discoveries":[{"year":2007,"finding":"IRTKS contains an IMD (IRSp53/MIM homology domain) that bundles actin filaments and binds Rac GTPase, but unlike IRSp53, does not interact with Cdc42. Its C-terminal WH2-like extension interacts with actin filaments (not monomers) and modulates/shortens actin bundle length induced by the IMD both in vitro and in cells.","method":"In vitro actin bundling assays, co-immunoprecipitation, cell expression assays, deletion/domain mapping","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution of actin bundling, mutagenesis/domain deletion, multiple orthogonal methods in single rigorous study","pmids":["17430976"],"is_preprint":false},{"year":2018,"finding":"IRTKS localizes to the distal tips of actively growing epithelial microvilli via its N-terminal I-BAR domain, and promotes microvillar elongation through two mechanisms: (1) its C-terminal WH2 domain for actin polymerization at tips, and (2) its SH3 domain recruiting the bundling protein EPS8 to microvillar tips.","method":"Super-resolution microscopy, live imaging, domain deletion/mutation constructs, loss-of-function and rescue experiments in differentiating epithelial cells","journal":"Current biology : CB","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (live imaging, super-resolution, domain dissection with rescue), clear functional readout","pmids":["30197089"],"is_preprint":false},{"year":2015,"finding":"The FGFR3-BAIAP2L1 fusion protein drives oncogenic transformation through constitutive dimerization mediated by the BAR domain of BAIAP2L1, which promotes constitutive FGFR3 kinase activation. Deletion of the BAR domain decreased FGFR3 phosphorylation, dimerization, and tumorigenic activity.","method":"Stable transfection in Rat-2 cells, in vitro and in vivo tumorigenicity assays, BAR domain deletion mutant, FGFR inhibitor treatment, gene signature analysis","journal":"Molecular cancer therapeutics","confidence":"High","confidence_rationale":"Tier 2 / Strong — domain deletion mutant with functional rescue, in vitro and in vivo validation, mechanistic inhibitor confirmation","pmids":["25589496"],"is_preprint":false},{"year":2009,"finding":"During C. rodentium and EHEC infection, IRTKS (but not IRSp53) is recruited to bacterial attachment sites on intestinal epithelium. IRTKS recruitment depends on Tir NPY451 motif (Y451 in Tir(CR)), establishing IRTKS as a specific downstream effector of Tir-mediated actin polymerization in vivo.","method":"C. rodentium murine infection model, human ileal explant EHEC infection, tir tyrosine mutants, immunofluorescence, competitive mixed infection","journal":"Molecular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo infection model with defined genetic mutants and competitive fitness assay, replicated in human tissue explants","pmids":["19889090"],"is_preprint":false},{"year":2015,"finding":"IRTKS suppresses antiviral innate immunity by recruiting the E2 SUMO ligase Ubc9 to sumoylate PCBP2 in the nucleus, causing PCBP2 cytoplasmic translocation during viral infection. Sumoylated PCBP2 then associates with MAVS to initiate its degradation, thereby downregulating RIG-I-MAVS antiviral signaling.","method":"IRTKS-deficient mouse/cell models, viral infection assays, sumoylation assays, co-immunoprecipitation, subcellular fractionation, MAVS degradation assays","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with defined pathway placement, sumoylation biochemistry, multiple orthogonal methods","pmids":["26348439"],"is_preprint":false},{"year":2013,"finding":"IRTKS acts as an adaptor for the insulin receptor (IR), modulating IR-IRS1-PI3K-AKT signaling by regulating IR phosphorylation. IRTKS-deficient mice exhibit insulin resistance; ectopic IRTKS can rescue insulin resistance in deficient and diabetic mice.","method":"IRTKS-knockout mice, glucose/insulin tolerance tests, ectopic IRTKS rescue, western blot of signaling components, diabetic mouse models","journal":"Cell research","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with defined physiological and molecular phenotypes, rescue experiment, multiple orthogonal methods","pmids":["23896986"],"is_preprint":false},{"year":2017,"finding":"IRTKS overexpression promotes p53 ubiquitination and degradation via MDM2. Under DNA damage, IRTKS is phosphorylated at Ser331 by activated Chk2 kinase, causing IRTKS to dissociate from the p53-MDM2 complex, thereby attenuating p53 ubiquitination and degradation.","method":"Co-immunoprecipitation, ubiquitination assays, Chk2 kinase assay, IRTKS-deficient mice/MEFs, in vivo tumorigenicity, phospho-site identification","journal":"Gut","confidence":"High","confidence_rationale":"Tier 2 / Strong — Co-IP, ubiquitination assay, kinase phosphorylation site mapping, in vivo genetic validation in mouse models","pmids":["28647685"],"is_preprint":false},{"year":2016,"finding":"IRTKS interacts with Rif GTPase through its I-BAR domain and signals through Eps8 and WAVE2 to generate dorsal membrane ruffles and filopodia. Eps8 regulates the size and number of dorsal filopodia downstream of Rif-IRTKS, and WAVE2 modulates dorsal membrane ruffling. The bacterial protein Tir may compete with Rif for binding to the IRTKS I-BAR domain.","method":"Co-immunoprecipitation, IRTKS-KO cells, dominant-negative Rif, live cell imaging, domain interaction mapping","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and KO validation with defined phenotype, single lab","pmids":["27278019"],"is_preprint":false},{"year":2019,"finding":"The SH3 domain of IRTKS directly binds the catalytic domain (INPP5c) of SHIP2 phosphatase, suppressing SHIP2 activity and thereby reducing conversion of PIP3 to PI(3,4)P2. IRTKS-KO increases PI(3,4)P2 and decreases PIP3; IRTKS overexpression increases PIP3 and activates AKT-mTOR signaling. The IRTKS-SHIP2 interaction is dynamically regulated by insulin.","method":"Co-immunoprecipitation, domain binding assays, lipid phosphatase activity assay, PIP3/PI(3,4)P2 measurement, IRTKS-KO cells, AKT-mTOR signaling readouts","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct biochemical interaction with enzyme activity assay and KO validation, single lab","pmids":["31212584"],"is_preprint":false},{"year":2011,"finding":"Active Src kinase phosphorylates IRTKS at six tyrosine residues (Y37, Y156, Y163, Y274, Y293, and Y439) both in vivo and in vitro. Src-stimulated IRTKS phosphorylation is required for IRTKS-enhanced cell migration (wound closure); phosphorylation-deficient mutants abolish the pro-migratory effect.","method":"In vitro kinase assay, in vivo phosphorylation, deletion and point mutation mapping, wound closure assay with HT1080 cells","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro kinase assay with mutagenesis confirming sites, functional readout, single lab","pmids":["21840312"],"is_preprint":false},{"year":2017,"finding":"Double knockout of IRSp53 and IRTKS results in complete embryonic lethality with exacerbated placental abnormalities (particularly in spongiotrophoblast differentiation), demonstrating genetic interaction and partial functional redundancy between IRSp53 and IRTKS in placental development.","method":"Single and double KO mice, histological and developmental analysis of placentas and embryos","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis by double KO with defined developmental phenotype, single lab","pmids":["28067313"],"is_preprint":false},{"year":2022,"finding":"IRTKS is a binding partner of formin FMNL2; coexpression promotes cooperative filopodia assembly. IRTKS, but not IRSp53, is required for FMNL2-induced filopodia assembly. FMNL2 initiates filopodia assembly by bending the plasma membrane to recruit IRTKS, with FMNL2 and IRTKS acting as mutually dependent cofactors.","method":"Co-immunoprecipitation, domain mapping, KO cell lines, filopodia quantification by microscopy, rescue experiments","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP with KO validation and domain dissection, specific functional readout, single lab","pmids":["36259517"],"is_preprint":false},{"year":2023,"finding":"IRTKS promotes accumulation of histone methyltransferase SETDB1 by recruiting deubiquitinase OTUD4 to remove Lys48-linked polyubiquitination at SETDB1 K182/K1050 sites, thereby blocking proteasomal SETDB1 degradation. Elevated SETDB1 increases H3K9me3, reduces chromatin accessibility at the CDH1 locus, suppresses E-cadherin expression, and promotes EMT and tumor metastasis.","method":"Co-immunoprecipitation, ubiquitination assays, ATAC-seq/chromatin accessibility, ChIP for H3K9me3, E-cadherin expression, metastasis assays","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical deubiquitination mechanism with epigenomic readout, multiple orthogonal methods, single lab","pmids":["37739210"],"is_preprint":false},{"year":2024,"finding":"IRTKS is required for constitutive heterochromatin formation via liquid-liquid phase separation (LLPS). IRTKS condensates infiltrate HP1α/nucleosome heterochromatin condensates. IRTKS recruits Ubc9 to SUMOylate HP1α, enabling larger phase-separated HP1α droplets. IRTKS deficiency causes heterochromatin loss, aberrant repetitive element transcription, cGAS-STING activation, and cellular senescence/SASP.","method":"Phase separation assays, live cell imaging of condensates, FRAP, SUMOylation assay, ATAC-seq, RNA-seq, cGAS-STING pathway analysis, IRTKS-KO cells","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — reconstitution of LLPS, biochemical SUMOylation, KO phenotypes with multiple genomic and signaling readouts, multiple orthogonal methods","pmids":["39192031"],"is_preprint":false},{"year":2016,"finding":"The SH3 domain of IRTKS (absent in MIM) is required for IRTKS-dependent promotion of serum-induced cell migration, cellular polarity, and p38 MAPK phosphorylation. Deletion of the SH3 domain attenuates cell motility and p38 activation; a chimeric MIM-IRTKS containing the IRTKS SH3 domain recapitulates IRTKS migratory function.","method":"Domain deletion and chimeric mutant constructs, wound migration assays, Rac1/Cdc42 activation assays, kinase phosphorylation assays, p38 inhibitor treatment","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain deletion/chimera with defined functional readout, multiple signaling assays, single lab","pmids":["27693783"],"is_preprint":false},{"year":2012,"finding":"IRTKS expression is specifically induced during osteoclast fusion and IRTKS interacts with the adaptor Tks5 in osteoclasts, suggesting a role in formation of fusion-competent podosome/invadopodia-like protrusions via its BAR domain.","method":"Expression analysis during osteoclastogenesis, co-immunoprecipitation of IRTKS and Tks5","journal":"Communicative & integrative biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP with expression data, no functional rescue or mutagenesis","pmids":["23739834"],"is_preprint":false},{"year":2024,"finding":"BAIAP2L1 localizes to the tips of tallest-row stereocilia in inner ear hair cells in a manner dependent on row-1 complex proteins EPS8 and MYO15A. This localization is calcium-independent (unlike BAIAP2L2). Loss of BAIAP2L1 does not affect the row-1 protein complex or auditory/balance function in mice.","method":"Immunofluorescence localization, BAIAP2L1 KO mice, auditory brainstem response, vestibular function tests, co-localization with EPS8/MYO15A","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by immunofluorescence with genetic dependency shown, KO functional phenotyping, single lab","pmids":["39093051"],"is_preprint":false},{"year":2024,"finding":"IRTKS directly interacts with PTEN via its SH3 domain binding to the C-terminal tail of PTEN, and inhibits PTEN phosphorylation to promote PI3K-AKT signaling, thereby driving osteogenic differentiation of bone marrow mesenchymal stem cells.","method":"Co-immunoprecipitation, domain mapping (SH3), AKT signaling readouts, BMSC differentiation assays, PTEN rescue experiment","journal":"Biomedicine & pharmacotherapy","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP with domain mapping and signaling readout, no in vitro phosphatase assay, single lab","pmids":["38908202"],"is_preprint":false},{"year":2022,"finding":"A novel BAIAP2L1-BRAF fusion transforms immortalized human thyroid cells in a kinase- and coiled-coil (CC) domain-dependent manner, identifying BAIAP2L1 as a fusion partner that provides dimerization activity enabling constitutive BRAF kinase activation.","method":"PCR/sequencing identification of fusion, stable transfection in thyroid cells, kinase-dead and CC-domain mutants, 3D spheroid growth assays, RNA interference","journal":"Molecular cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain mutant functional validation with 3D spheroid model and loss-of-function, single lab","pmids":["36217175"],"is_preprint":false},{"year":2026,"finding":"IRTKS promotes EHEC Tir accumulation in the host plasma membrane, facilitating bacterial attachment. IRTKS gain- and loss-of-function experiments revealed that perturbing IRTKS disrupted Tir distribution/abundance, and ectopic IRTKS enhanced Tir membrane insertion in absence of other virulence factors, positioning IRTKS upstream of Tir in pedestal formation.","method":"IRTKS gain- and loss-of-function models in epithelial cells, immunofluorescence quantification of Tir distribution, ectopic Tir insertion assay","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple gain/loss-of-function models with quantitative readout, preprint not yet peer-reviewed","pmids":["42239090"],"is_preprint":true},{"year":2025,"finding":"In zebrafish, baiap2l1a localizes to microridges prior to actin formation, and its I-BAR domain alone is sufficient for microridge localization and partial rescue of microridge elongation. A 39-amino-acid deletion removing one α-helix impairs I-BAR microridge localization and fails to rescue elongation. Baiap2l1a genetically interacts with eps8like1a in microridge elongation.","method":"CRISPR/Cas9 knockdown in zebrafish, domain deletion constructs, AlphaFold2 structural modeling, live imaging of localization, genetic interaction analysis","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — CRISPR KO with domain rescue in zebrafish ortholog, preprint not yet peer-reviewed","pmids":[],"is_preprint":true},{"year":2026,"finding":"IRTKS forms lysosome-localized membrane-associated condensates that interact with the GTPase RRAGD, a key upstream regulator of mTORC1, thereby enhancing mTORC1 sensitivity to free amino acids. Hepatic IRTKS knockin drives mTORC1 hyperactivation, obesity, steatosis, and MASLD-to-HCC progression; genetic ablation or mTORC1 inhibition reverses these phenotypes.","method":"Phospho-antibody array screening, co-immunoprecipitation with RRAGD, lysosomal fractionation/condensate imaging, hepatic knockin and KO mice, mTORC1 activity assays, histological/metabolic phenotyping","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — condensate biochemistry with identified interactor (RRAGD), in vivo knockin/KO models with defined pathway and phenotypic rescue, multiple orthogonal methods","pmids":["41575860"],"is_preprint":false},{"year":2022,"finding":"BAIAP2L1 interacts with ribosomal protein L3 (RPL3) via its SH3 domain (binding AA202-288 of RPL3); loss of the SH3 domain abolishes AKT signaling transduction by promoting PIK3CA degradation, identifying RPL3 as an IRTKS binding partner linking it to PI3K/AKT pathway activation in breast cancer.","method":"Co-immunoprecipitation, SH3 domain deletion mutants, AKT/PIK3CA signaling western blot, in vitro and in vivo overexpression/knockdown","journal":"Cancer science","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP with domain deletion, mechanistic pathway placement indirect, single lab","pmids":["36308067"],"is_preprint":false}],"current_model":"BAIAP2L1/IRTKS is an I-BAR domain scaffold protein that deforms membranes and bundles actin filaments via its IMD/I-BAR domain (which binds Rac but not Cdc42), promotes actin-based protrusions (filopodia, microvilli, microridges) by recruiting EPS8 and WAVE2 through its SH3 domain and polymerizing actin via its WH2 domain, acts as an insulin receptor adaptor that activates IR-IRS1-PI3K-AKT signaling while suppressing SHIP2 phosphatase activity to maintain PIP3 levels, is phosphorylated by Src (at 6 tyrosines) and Chk2 (at Ser331) to regulate cell migration and p53 stability respectively, promotes constitutive heterochromatin via LLPS by SUMOylating HP1α through Ubc9, suppresses antiviral signaling by SUMOylating PCBP2 to drive MAVS degradation, promotes SETDB1 stability via OTUD4-mediated deubiquitination to epigenetically suppress E-cadherin, and activates mTORC1 by forming lysosome-localized condensates that interact with RRAGD."},"narrative":{"mechanistic_narrative":"BAIAP2L1 (IRTKS) is a membrane-deforming I-BAR/IMD scaffold protein that couples plasma-membrane curvature to actin-based protrusion formation, while moonlighting as a signaling adaptor in insulin, antiviral, p53, and chromatin pathways [PMID:17430976, PMID:30197089, PMID:23896986]. Its N-terminal IMD/I-BAR domain bundles actin filaments and binds Rac (but not Cdc42), and its C-terminal WH2 extension binds actin filaments to modulate bundle length [PMID:17430976]. Through the I-BAR domain it engages curvature-coupled partners including Rif GTPase and the formin FMNL2, and through its SH3 domain it recruits EPS8 and WAVE2 to drive filopodia, dorsal ruffles, and microvillar/stereociliary/microridge elongation at protrusion tips [PMID:30197089, PMID:27278019, PMID:36259517, PMID:39093051]. As an insulin-receptor adaptor it sustains IR–IRS1–PI3K–AKT signaling, in part by its SH3 domain binding the SHIP2 catalytic domain to suppress PIP3 hydrolysis; IRTKS-deficient mice are insulin resistant [PMID:23896986, PMID:31212584]. IRTKS also recruits the SUMO E2 ligase Ubc9 to two distinct substrates: it SUMOylates PCBP2 to drive MAVS degradation and dampen RIG-I antiviral signaling [PMID:26348439], and it SUMOylates HP1α to promote liquid-liquid phase-separated constitutive heterochromatin, whose loss derepresses repetitive elements and triggers cGAS-STING-driven senescence [PMID:39192031]. Additional regulatory roles include Chk2-dependent phosphorylation at Ser331 that controls IRTKS occupancy of the p53-MDM2 complex and thereby p53 stability [PMID:28647685], Src-dependent tyrosine phosphorylation that enables pro-migratory function [PMID:21840312], OTUD4 recruitment that stabilizes SETDB1 to epigenetically silence E-cadherin and promote EMT/metastasis [PMID:37739210], and formation of lysosomal condensates that engage RRAGD to potentiate amino-acid-sensitive mTORC1 activation, driving steatosis and MASLD-to-HCC progression in mouse liver [PMID:41575860]. Recurrent gene fusions in which the BAIAP2L1 dimerization (BAR/coiled-coil) domain is fused to FGFR3 or BRAF produce constitutive kinase activation and oncogenic transformation [PMID:25589496, PMID:36217175].","teleology":[{"year":2007,"claim":"Established the biochemical core activity of IRTKS by showing its IMD/I-BAR domain bundles actin and binds Rac, distinguishing it from the paralog IRSp53 which also engages Cdc42.","evidence":"In vitro actin bundling assays, co-IP, and domain deletion in cells","pmids":["17430976"],"confidence":"High","gaps":["Did not define in vivo protrusion phenotypes","WH2 mechanism of bundle-length modulation not structurally resolved"]},{"year":2009,"claim":"Placed IRTKS as a specific host effector of enteropathogenic bacteria, showing it (not IRSp53) is recruited to Tir attachment sites via the Tir NPY451 motif during infection.","evidence":"C. rodentium mouse model and EHEC human ileal explants with tir tyrosine mutants and competitive infection","pmids":["19889090"],"confidence":"High","gaps":["Did not resolve which IRTKS domain binds Tir","Downstream actin polymerization machinery not yet mapped"]},{"year":2011,"claim":"Connected IRTKS to migration control by mapping six Src phosphorylation sites required for its pro-migratory effect.","evidence":"In vitro/in vivo kinase assays, point mutants, wound closure in HT1080 cells","pmids":["21840312"],"confidence":"Medium","gaps":["Single lab","How tyrosine phosphorylation alters IRTKS partner binding unresolved"]},{"year":2013,"claim":"Defined a metabolic signaling role, showing IRTKS is an insulin-receptor adaptor whose loss causes insulin resistance reversible by ectopic IRTKS.","evidence":"IRTKS-KO and diabetic mice, tolerance tests, rescue, signaling western blots","pmids":["23896986"],"confidence":"High","gaps":["Molecular contact with IR not structurally defined at this stage","Tissue-specific contributions not dissected"]},{"year":2015,"claim":"Revealed an antiviral suppression mechanism via Ubc9-mediated SUMOylation of PCBP2 leading to MAVS degradation.","evidence":"IRTKS-deficient cells/mice, viral infection, SUMOylation and MAVS degradation assays, fractionation","pmids":["26348439"],"confidence":"High","gaps":["How viral infection triggers IRTKS-Ubc9 engagement unclear","Relationship to its cytoskeletal roles not addressed"]},{"year":2015,"claim":"Demonstrated oncogenic fusion biology, showing the FGFR3-BAIAP2L1 fusion drives transformation through BAR-domain-mediated constitutive FGFR3 dimerization/activation.","evidence":"Stable transfection, BAR deletion mutant, in vitro/in vivo tumorigenicity, FGFR inhibitor","pmids":["25589496"],"confidence":"High","gaps":["Does not address full-length BAIAP2L1 function","Tumor-type specificity of fusion not delineated"]},{"year":2016,"claim":"Linked the I-BAR domain to Rif GTPase signaling and SH3-domain-dependent migration, mapping EPS8/WAVE2 as effectors of dorsal protrusion formation and p38 activation.","evidence":"Reciprocal Co-IP, KO cells, dominant-negative Rif, chimeric SH3 constructs, live imaging","pmids":["27278019","27693783"],"confidence":"Medium","gaps":["Single lab","Mechanistic basis for Tir/Rif competition on I-BAR not resolved"]},{"year":2017,"claim":"Established a DNA-damage-responsive role in p53 control, showing Chk2 phosphorylation at Ser331 evicts IRTKS from the p53-MDM2 complex to stabilize p53.","evidence":"Co-IP, ubiquitination assays, Chk2 kinase assay, IRTKS-KO MEFs/mice, tumorigenicity","pmids":["28647685"],"confidence":"High","gaps":["How IRTKS facilitates MDM2-mediated p53 ubiquitination structurally unclear","Nuclear vs cytoplasmic pools not distinguished"]},{"year":2017,"claim":"Demonstrated genetic redundancy with IRSp53 in development, with double knockout causing embryonic lethality and placental defects.","evidence":"Single and double KO mice with developmental/histological analysis","pmids":["28067313"],"confidence":"Medium","gaps":["Molecular basis of redundancy in spongiotrophoblast not defined","Single lab"]},{"year":2018,"claim":"Resolved tip-targeted protrusion mechanism in epithelia: I-BAR localizes IRTKS to microvillar tips, while WH2 polymerizes actin and SH3 recruits EPS8 for elongation.","evidence":"Super-resolution and live imaging, domain mutants, loss-of-function and rescue","pmids":["30197089"],"confidence":"High","gaps":["How tip enrichment is maintained dynamically unresolved"]},{"year":2019,"claim":"Provided the enzymatic basis for IRTKS lipid signaling, showing its SH3 domain binds and inhibits the SHIP2 catalytic domain to preserve PIP3 and activate AKT-mTOR.","evidence":"Co-IP, domain binding, lipid phosphatase activity assay, PIP3/PI(3,4)P2 quantification in KO cells","pmids":["31212584"],"confidence":"Medium","gaps":["Single lab","Insulin-dependent dynamics of the interaction only partially characterized"]},{"year":2022,"claim":"Identified FMNL2 as a curvature-coupled cofactor, with FMNL2 bending membrane to recruit IRTKS for cooperative filopodia assembly, a function specific to IRTKS over IRSp53.","evidence":"Co-IP, domain mapping, KO cell lines, filopodia quantification, rescue","pmids":["36259517"],"confidence":"Medium","gaps":["Single lab","Order of FMNL2/IRTKS recruitment in vivo not fully resolved"]},{"year":2022,"claim":"Extended fusion oncogenesis to BRAF, showing BAIAP2L1 provides coiled-coil-dependent dimerization for constitutive BRAF kinase activation in thyroid cells.","evidence":"Fusion identification, kinase-dead and CC-domain mutants, 3D spheroid assays, RNAi","pmids":["36217175"],"confidence":"Medium","gaps":["Single lab","Clinical prevalence of the fusion not established"]},{"year":2023,"claim":"Uncovered an epigenetic metastasis-promoting mechanism: IRTKS recruits OTUD4 to deubiquitinate and stabilize SETDB1, raising H3K9me3 to silence E-cadherin and drive EMT.","evidence":"Co-IP, ubiquitination assays, ATAC-seq, H3K9me3 ChIP, metastasis assays","pmids":["37739210"],"confidence":"Medium","gaps":["Single lab","How IRTKS selects SETDB1/OTUD4 versus other deubiquitination substrates unclear"]},{"year":2024,"claim":"Defined a phase-separation function in heterochromatin: IRTKS condensates and Ubc9-mediated HP1α SUMOylation maintain constitutive heterochromatin, preventing repeat derepression and cGAS-STING senescence.","evidence":"LLPS reconstitution, FRAP, SUMOylation assay, ATAC-seq/RNA-seq, cGAS-STING analysis in KO cells","pmids":["39192031"],"confidence":"High","gaps":["How nuclear IRTKS pool is regulated relative to cytoplasmic functions unclear","Sequence determinants of IRTKS phase separation not mapped"]},{"year":2024,"claim":"Showed BAIAP2L1 targets stereocilia tips dependent on EPS8/MYO15A in a calcium-independent manner, but its loss is dispensable for hearing/balance, indicating functional redundancy in this tissue.","evidence":"Immunofluorescence, KO mice, auditory brainstem response and vestibular tests","pmids":["39093051"],"confidence":"Medium","gaps":["Compensating protein not identified","Single lab"]},{"year":2024,"claim":"Linked IRTKS to PTEN regulation in mesenchymal stem cell osteogenesis via SH3-domain binding to the PTEN C-terminal tail.","evidence":"Co-IP, SH3 domain mapping, AKT readouts, BMSC differentiation, PTEN rescue","pmids":["38908202"],"confidence":"Low","gaps":["No in vitro phosphatase assay confirming PTEN inhibition","Single Co-IP, single lab"]},{"year":2026,"claim":"Defined a lysosomal mTORC1-activating role: IRTKS forms membrane-associated condensates that interact with RRAGD to heighten amino-acid sensing, with hepatic knockin driving obesity, steatosis, and MASLD-to-HCC.","evidence":"Phospho-array screening, RRAGD Co-IP, lysosomal fractionation/condensate imaging, hepatic knockin/KO mice with mTORC1 inhibition rescue","pmids":["41575860"],"confidence":"High","gaps":["How IRTKS condensates assemble at the lysosome unresolved","Relationship to its other condensate (heterochromatin) behavior unclear"]},{"year":null,"claim":"It remains unresolved how IRTKS partitions among its cytoskeletal, plasma-membrane signaling, lysosomal, and nuclear/heterochromatin functions, and what determines context-specific recruitment of Ubc9, OTUD4, RRAGD, and SHIP2 to a single scaffold.","evidence":"No timeline study integrates the multiple condensate, SUMOylation, and adaptor functions into one regulatory logic","pmids":[],"confidence":"Low","gaps":["No unified model of IRTKS spatial regulation","Structural basis for SH3/I-BAR partner switching not solved"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,1,7,11]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[5,6,8]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[4,8,13]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[1,3,7,16]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,1,11]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[4,13]},{"term_id":"GO:0005764","term_label":"lysosome","supporting_discovery_ids":[21]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[13]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[5,8]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[4]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[13,12]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[4,6,12,21]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[2,18,21]}],"complexes":[],"partners":["EPS8","WAVE2","SHIP2","FMNL2","UBC9","OTUD4","RRAGD","MYO15A"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9UHR4","full_name":"BAR/IMD domain-containing adapter protein 2-like 1","aliases":["Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1","BAI1-associated protein 2-like protein 1","Insulin receptor tyrosine kinase substrate"],"length_aa":511,"mass_kda":56.9,"function":"May function as adapter protein. Involved in the formation of clusters of actin bundles. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection","subcellular_location":"Cytoplasm, cytoskeleton","url":"https://www.uniprot.org/uniprotkb/Q9UHR4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/BAIAP2L1","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000006453","cell_line_id":"CID000666","localizations":[{"compartment":"cell_contact","grade":3},{"compartment":"membrane","grade":3},{"compartment":"cytoplasmic","grade":2}],"interactors":[{"gene":"ACTG1","stoichiometry":4.0},{"gene":"ACTB","stoichiometry":0.2},{"gene":"BAIAP2","stoichiometry":0.2},{"gene":"CAPZB","stoichiometry":0.2},{"gene":"CSNK1G3","stoichiometry":0.2},{"gene":"DNAJC13","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000666","total_profiled":1310},"omim":[{"mim_id":"611877","title":"BAI1-ASSOCIATED PROTEIN 2-LIKE 1; BAIAP2L1","url":"https://www.omim.org/entry/611877"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Plasma membrane","reliability":"Enhanced"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"stomach 1","ntpm":55.5}],"url":"https://www.proteinatlas.org/search/BAIAP2L1"},"hgnc":{"alias_symbol":["IRTKS"],"prev_symbol":[]},"alphafold":{"accession":"Q9UHR4","domains":[{"cath_id":"1.20.1270.60","chopping":"6-240","consensus_level":"high","plddt":95.1097,"start":6,"end":240},{"cath_id":"2.30.30.40","chopping":"344-400","consensus_level":"high","plddt":91.3186,"start":344,"end":400}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UHR4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UHR4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UHR4-F1-predicted_aligned_error_v6.png","plddt_mean":72.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=BAIAP2L1","jax_strain_url":"https://www.jax.org/strain/search?query=BAIAP2L1"},"sequence":{"accession":"Q9UHR4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UHR4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UHR4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UHR4"}},"corpus_meta":[{"pmid":"17430976","id":"PMC_17430976","title":"Characterisation of IRTKS, a novel IRSp53/MIM family actin regulator with distinct filament bundling properties.","date":"2007","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/17430976","citation_count":71,"is_preprint":false},{"pmid":"30197089","id":"PMC_30197089","title":"IRTKS (BAIAP2L1) Elongates Epithelial Microvilli Using EPS8-Dependent and Independent Mechanisms.","date":"2018","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/30197089","citation_count":60,"is_preprint":false},{"pmid":"25589496","id":"PMC_25589496","title":"Mechanism of Oncogenic Signal Activation by the Novel Fusion Kinase FGFR3-BAIAP2L1.","date":"2015","source":"Molecular cancer therapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/25589496","citation_count":51,"is_preprint":false},{"pmid":"19889090","id":"PMC_19889090","title":"Dissecting the role of the Tir:Nck and Tir:IRTKS/IRSp53 signalling pathways in vivo.","date":"2009","source":"Molecular 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survival time of patients with gastric cancer.","date":"2017","source":"Gut","url":"https://pubmed.ncbi.nlm.nih.gov/28647685","citation_count":25,"is_preprint":false},{"pmid":"27278019","id":"PMC_27278019","title":"The Rho GTPase Rif signals through IRTKS, Eps8 and WAVE2 to generate dorsal membrane ruffles and filopodia.","date":"2016","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/27278019","citation_count":24,"is_preprint":false},{"pmid":"31212584","id":"PMC_31212584","title":"IRTKS Promotes Insulin Signaling Transduction through Inhibiting SHIP2 Phosphatase Activity.","date":"2019","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/31212584","citation_count":18,"is_preprint":false},{"pmid":"28067313","id":"PMC_28067313","title":"Redundant functions of I-BAR family members, IRSp53 and IRTKS, are essential for embryonic development.","date":"2017","source":"Scientific 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biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/35150389","citation_count":11,"is_preprint":false},{"pmid":"36308067","id":"PMC_36308067","title":"BAIAP2L1 accelerates breast cancer progression and chemoresistance by activating AKT signaling through binding with ribosomal protein L3.","date":"2022","source":"Cancer science","url":"https://pubmed.ncbi.nlm.nih.gov/36308067","citation_count":10,"is_preprint":false},{"pmid":"27693783","id":"PMC_27693783","title":"The SH3 domain distinguishes the role of I-BAR proteins IRTKS and MIM in chemotactic response to serum.","date":"2016","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/27693783","citation_count":9,"is_preprint":false},{"pmid":"39192031","id":"PMC_39192031","title":"Heterochromatin formation and remodeling by IRTKS condensates counteract cellular senescence.","date":"2024","source":"The EMBO 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pharmacotherapie","url":"https://pubmed.ncbi.nlm.nih.gov/38908202","citation_count":3,"is_preprint":false},{"pmid":"38869721","id":"PMC_38869721","title":"IRTKS contributes to the malignant progression of cervical cancer cells.","date":"2024","source":"Medical oncology (Northwood, London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/38869721","citation_count":1,"is_preprint":false},{"pmid":"41575860","id":"PMC_41575860","title":"Lysosome-localized IRTKS condensates promote mTORC1 activity leading to MASLD and HCC.","date":"2026","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/41575860","citation_count":1,"is_preprint":false},{"pmid":"42239090","id":"PMC_42239090","title":"IRTKS promotes Tir membrane insertion for intimate bacterial attachment and subsequent pedestal formation.","date":"2026","source":"bioRxiv : the preprint server for 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structures","date":"2025-09-10","source":"bioRxiv","url":"https://doi.org/10.1101/2025.09.09.675250","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":15421,"output_tokens":5931,"usd":0.067614,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":14514,"output_tokens":5596,"usd":0.106235,"stage2_stop_reason":"end_turn"},"total_usd":0.173849,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"IRTKS contains an IMD (IRSp53/MIM homology domain) that bundles actin filaments and binds Rac GTPase, but unlike IRSp53, does not interact with Cdc42. Its C-terminal WH2-like extension interacts with actin filaments (not monomers) and modulates/shortens actin bundle length induced by the IMD both in vitro and in cells.\",\n      \"method\": \"In vitro actin bundling assays, co-immunoprecipitation, cell expression assays, deletion/domain mapping\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution of actin bundling, mutagenesis/domain deletion, multiple orthogonal methods in single rigorous study\",\n      \"pmids\": [\"17430976\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"IRTKS localizes to the distal tips of actively growing epithelial microvilli via its N-terminal I-BAR domain, and promotes microvillar elongation through two mechanisms: (1) its C-terminal WH2 domain for actin polymerization at tips, and (2) its SH3 domain recruiting the bundling protein EPS8 to microvillar tips.\",\n      \"method\": \"Super-resolution microscopy, live imaging, domain deletion/mutation constructs, loss-of-function and rescue experiments in differentiating epithelial cells\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (live imaging, super-resolution, domain dissection with rescue), clear functional readout\",\n      \"pmids\": [\"30197089\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The FGFR3-BAIAP2L1 fusion protein drives oncogenic transformation through constitutive dimerization mediated by the BAR domain of BAIAP2L1, which promotes constitutive FGFR3 kinase activation. Deletion of the BAR domain decreased FGFR3 phosphorylation, dimerization, and tumorigenic activity.\",\n      \"method\": \"Stable transfection in Rat-2 cells, in vitro and in vivo tumorigenicity assays, BAR domain deletion mutant, FGFR inhibitor treatment, gene signature analysis\",\n      \"journal\": \"Molecular cancer therapeutics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — domain deletion mutant with functional rescue, in vitro and in vivo validation, mechanistic inhibitor confirmation\",\n      \"pmids\": [\"25589496\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"During C. rodentium and EHEC infection, IRTKS (but not IRSp53) is recruited to bacterial attachment sites on intestinal epithelium. IRTKS recruitment depends on Tir NPY451 motif (Y451 in Tir(CR)), establishing IRTKS as a specific downstream effector of Tir-mediated actin polymerization in vivo.\",\n      \"method\": \"C. rodentium murine infection model, human ileal explant EHEC infection, tir tyrosine mutants, immunofluorescence, competitive mixed infection\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo infection model with defined genetic mutants and competitive fitness assay, replicated in human tissue explants\",\n      \"pmids\": [\"19889090\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"IRTKS suppresses antiviral innate immunity by recruiting the E2 SUMO ligase Ubc9 to sumoylate PCBP2 in the nucleus, causing PCBP2 cytoplasmic translocation during viral infection. Sumoylated PCBP2 then associates with MAVS to initiate its degradation, thereby downregulating RIG-I-MAVS antiviral signaling.\",\n      \"method\": \"IRTKS-deficient mouse/cell models, viral infection assays, sumoylation assays, co-immunoprecipitation, subcellular fractionation, MAVS degradation assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with defined pathway placement, sumoylation biochemistry, multiple orthogonal methods\",\n      \"pmids\": [\"26348439\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"IRTKS acts as an adaptor for the insulin receptor (IR), modulating IR-IRS1-PI3K-AKT signaling by regulating IR phosphorylation. IRTKS-deficient mice exhibit insulin resistance; ectopic IRTKS can rescue insulin resistance in deficient and diabetic mice.\",\n      \"method\": \"IRTKS-knockout mice, glucose/insulin tolerance tests, ectopic IRTKS rescue, western blot of signaling components, diabetic mouse models\",\n      \"journal\": \"Cell research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with defined physiological and molecular phenotypes, rescue experiment, multiple orthogonal methods\",\n      \"pmids\": [\"23896986\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"IRTKS overexpression promotes p53 ubiquitination and degradation via MDM2. Under DNA damage, IRTKS is phosphorylated at Ser331 by activated Chk2 kinase, causing IRTKS to dissociate from the p53-MDM2 complex, thereby attenuating p53 ubiquitination and degradation.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assays, Chk2 kinase assay, IRTKS-deficient mice/MEFs, in vivo tumorigenicity, phospho-site identification\",\n      \"journal\": \"Gut\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — Co-IP, ubiquitination assay, kinase phosphorylation site mapping, in vivo genetic validation in mouse models\",\n      \"pmids\": [\"28647685\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"IRTKS interacts with Rif GTPase through its I-BAR domain and signals through Eps8 and WAVE2 to generate dorsal membrane ruffles and filopodia. Eps8 regulates the size and number of dorsal filopodia downstream of Rif-IRTKS, and WAVE2 modulates dorsal membrane ruffling. The bacterial protein Tir may compete with Rif for binding to the IRTKS I-BAR domain.\",\n      \"method\": \"Co-immunoprecipitation, IRTKS-KO cells, dominant-negative Rif, live cell imaging, domain interaction mapping\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and KO validation with defined phenotype, single lab\",\n      \"pmids\": [\"27278019\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"The SH3 domain of IRTKS directly binds the catalytic domain (INPP5c) of SHIP2 phosphatase, suppressing SHIP2 activity and thereby reducing conversion of PIP3 to PI(3,4)P2. IRTKS-KO increases PI(3,4)P2 and decreases PIP3; IRTKS overexpression increases PIP3 and activates AKT-mTOR signaling. The IRTKS-SHIP2 interaction is dynamically regulated by insulin.\",\n      \"method\": \"Co-immunoprecipitation, domain binding assays, lipid phosphatase activity assay, PIP3/PI(3,4)P2 measurement, IRTKS-KO cells, AKT-mTOR signaling readouts\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct biochemical interaction with enzyme activity assay and KO validation, single lab\",\n      \"pmids\": [\"31212584\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Active Src kinase phosphorylates IRTKS at six tyrosine residues (Y37, Y156, Y163, Y274, Y293, and Y439) both in vivo and in vitro. Src-stimulated IRTKS phosphorylation is required for IRTKS-enhanced cell migration (wound closure); phosphorylation-deficient mutants abolish the pro-migratory effect.\",\n      \"method\": \"In vitro kinase assay, in vivo phosphorylation, deletion and point mutation mapping, wound closure assay with HT1080 cells\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro kinase assay with mutagenesis confirming sites, functional readout, single lab\",\n      \"pmids\": [\"21840312\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Double knockout of IRSp53 and IRTKS results in complete embryonic lethality with exacerbated placental abnormalities (particularly in spongiotrophoblast differentiation), demonstrating genetic interaction and partial functional redundancy between IRSp53 and IRTKS in placental development.\",\n      \"method\": \"Single and double KO mice, histological and developmental analysis of placentas and embryos\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis by double KO with defined developmental phenotype, single lab\",\n      \"pmids\": [\"28067313\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"IRTKS is a binding partner of formin FMNL2; coexpression promotes cooperative filopodia assembly. IRTKS, but not IRSp53, is required for FMNL2-induced filopodia assembly. FMNL2 initiates filopodia assembly by bending the plasma membrane to recruit IRTKS, with FMNL2 and IRTKS acting as mutually dependent cofactors.\",\n      \"method\": \"Co-immunoprecipitation, domain mapping, KO cell lines, filopodia quantification by microscopy, rescue experiments\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP with KO validation and domain dissection, specific functional readout, single lab\",\n      \"pmids\": [\"36259517\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"IRTKS promotes accumulation of histone methyltransferase SETDB1 by recruiting deubiquitinase OTUD4 to remove Lys48-linked polyubiquitination at SETDB1 K182/K1050 sites, thereby blocking proteasomal SETDB1 degradation. Elevated SETDB1 increases H3K9me3, reduces chromatin accessibility at the CDH1 locus, suppresses E-cadherin expression, and promotes EMT and tumor metastasis.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assays, ATAC-seq/chromatin accessibility, ChIP for H3K9me3, E-cadherin expression, metastasis assays\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical deubiquitination mechanism with epigenomic readout, multiple orthogonal methods, single lab\",\n      \"pmids\": [\"37739210\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"IRTKS is required for constitutive heterochromatin formation via liquid-liquid phase separation (LLPS). IRTKS condensates infiltrate HP1α/nucleosome heterochromatin condensates. IRTKS recruits Ubc9 to SUMOylate HP1α, enabling larger phase-separated HP1α droplets. IRTKS deficiency causes heterochromatin loss, aberrant repetitive element transcription, cGAS-STING activation, and cellular senescence/SASP.\",\n      \"method\": \"Phase separation assays, live cell imaging of condensates, FRAP, SUMOylation assay, ATAC-seq, RNA-seq, cGAS-STING pathway analysis, IRTKS-KO cells\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — reconstitution of LLPS, biochemical SUMOylation, KO phenotypes with multiple genomic and signaling readouts, multiple orthogonal methods\",\n      \"pmids\": [\"39192031\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"The SH3 domain of IRTKS (absent in MIM) is required for IRTKS-dependent promotion of serum-induced cell migration, cellular polarity, and p38 MAPK phosphorylation. Deletion of the SH3 domain attenuates cell motility and p38 activation; a chimeric MIM-IRTKS containing the IRTKS SH3 domain recapitulates IRTKS migratory function.\",\n      \"method\": \"Domain deletion and chimeric mutant constructs, wound migration assays, Rac1/Cdc42 activation assays, kinase phosphorylation assays, p38 inhibitor treatment\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain deletion/chimera with defined functional readout, multiple signaling assays, single lab\",\n      \"pmids\": [\"27693783\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"IRTKS expression is specifically induced during osteoclast fusion and IRTKS interacts with the adaptor Tks5 in osteoclasts, suggesting a role in formation of fusion-competent podosome/invadopodia-like protrusions via its BAR domain.\",\n      \"method\": \"Expression analysis during osteoclastogenesis, co-immunoprecipitation of IRTKS and Tks5\",\n      \"journal\": \"Communicative & integrative biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP with expression data, no functional rescue or mutagenesis\",\n      \"pmids\": [\"23739834\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"BAIAP2L1 localizes to the tips of tallest-row stereocilia in inner ear hair cells in a manner dependent on row-1 complex proteins EPS8 and MYO15A. This localization is calcium-independent (unlike BAIAP2L2). Loss of BAIAP2L1 does not affect the row-1 protein complex or auditory/balance function in mice.\",\n      \"method\": \"Immunofluorescence localization, BAIAP2L1 KO mice, auditory brainstem response, vestibular function tests, co-localization with EPS8/MYO15A\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by immunofluorescence with genetic dependency shown, KO functional phenotyping, single lab\",\n      \"pmids\": [\"39093051\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"IRTKS directly interacts with PTEN via its SH3 domain binding to the C-terminal tail of PTEN, and inhibits PTEN phosphorylation to promote PI3K-AKT signaling, thereby driving osteogenic differentiation of bone marrow mesenchymal stem cells.\",\n      \"method\": \"Co-immunoprecipitation, domain mapping (SH3), AKT signaling readouts, BMSC differentiation assays, PTEN rescue experiment\",\n      \"journal\": \"Biomedicine & pharmacotherapy\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP with domain mapping and signaling readout, no in vitro phosphatase assay, single lab\",\n      \"pmids\": [\"38908202\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"A novel BAIAP2L1-BRAF fusion transforms immortalized human thyroid cells in a kinase- and coiled-coil (CC) domain-dependent manner, identifying BAIAP2L1 as a fusion partner that provides dimerization activity enabling constitutive BRAF kinase activation.\",\n      \"method\": \"PCR/sequencing identification of fusion, stable transfection in thyroid cells, kinase-dead and CC-domain mutants, 3D spheroid growth assays, RNA interference\",\n      \"journal\": \"Molecular cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain mutant functional validation with 3D spheroid model and loss-of-function, single lab\",\n      \"pmids\": [\"36217175\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"IRTKS promotes EHEC Tir accumulation in the host plasma membrane, facilitating bacterial attachment. IRTKS gain- and loss-of-function experiments revealed that perturbing IRTKS disrupted Tir distribution/abundance, and ectopic IRTKS enhanced Tir membrane insertion in absence of other virulence factors, positioning IRTKS upstream of Tir in pedestal formation.\",\n      \"method\": \"IRTKS gain- and loss-of-function models in epithelial cells, immunofluorescence quantification of Tir distribution, ectopic Tir insertion assay\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple gain/loss-of-function models with quantitative readout, preprint not yet peer-reviewed\",\n      \"pmids\": [\"42239090\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In zebrafish, baiap2l1a localizes to microridges prior to actin formation, and its I-BAR domain alone is sufficient for microridge localization and partial rescue of microridge elongation. A 39-amino-acid deletion removing one α-helix impairs I-BAR microridge localization and fails to rescue elongation. Baiap2l1a genetically interacts with eps8like1a in microridge elongation.\",\n      \"method\": \"CRISPR/Cas9 knockdown in zebrafish, domain deletion constructs, AlphaFold2 structural modeling, live imaging of localization, genetic interaction analysis\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — CRISPR KO with domain rescue in zebrafish ortholog, preprint not yet peer-reviewed\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"IRTKS forms lysosome-localized membrane-associated condensates that interact with the GTPase RRAGD, a key upstream regulator of mTORC1, thereby enhancing mTORC1 sensitivity to free amino acids. Hepatic IRTKS knockin drives mTORC1 hyperactivation, obesity, steatosis, and MASLD-to-HCC progression; genetic ablation or mTORC1 inhibition reverses these phenotypes.\",\n      \"method\": \"Phospho-antibody array screening, co-immunoprecipitation with RRAGD, lysosomal fractionation/condensate imaging, hepatic knockin and KO mice, mTORC1 activity assays, histological/metabolic phenotyping\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — condensate biochemistry with identified interactor (RRAGD), in vivo knockin/KO models with defined pathway and phenotypic rescue, multiple orthogonal methods\",\n      \"pmids\": [\"41575860\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"BAIAP2L1 interacts with ribosomal protein L3 (RPL3) via its SH3 domain (binding AA202-288 of RPL3); loss of the SH3 domain abolishes AKT signaling transduction by promoting PIK3CA degradation, identifying RPL3 as an IRTKS binding partner linking it to PI3K/AKT pathway activation in breast cancer.\",\n      \"method\": \"Co-immunoprecipitation, SH3 domain deletion mutants, AKT/PIK3CA signaling western blot, in vitro and in vivo overexpression/knockdown\",\n      \"journal\": \"Cancer science\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP with domain deletion, mechanistic pathway placement indirect, single lab\",\n      \"pmids\": [\"36308067\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"BAIAP2L1/IRTKS is an I-BAR domain scaffold protein that deforms membranes and bundles actin filaments via its IMD/I-BAR domain (which binds Rac but not Cdc42), promotes actin-based protrusions (filopodia, microvilli, microridges) by recruiting EPS8 and WAVE2 through its SH3 domain and polymerizing actin via its WH2 domain, acts as an insulin receptor adaptor that activates IR-IRS1-PI3K-AKT signaling while suppressing SHIP2 phosphatase activity to maintain PIP3 levels, is phosphorylated by Src (at 6 tyrosines) and Chk2 (at Ser331) to regulate cell migration and p53 stability respectively, promotes constitutive heterochromatin via LLPS by SUMOylating HP1α through Ubc9, suppresses antiviral signaling by SUMOylating PCBP2 to drive MAVS degradation, promotes SETDB1 stability via OTUD4-mediated deubiquitination to epigenetically suppress E-cadherin, and activates mTORC1 by forming lysosome-localized condensates that interact with RRAGD.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"BAIAP2L1 (IRTKS) is a membrane-deforming I-BAR/IMD scaffold protein that couples plasma-membrane curvature to actin-based protrusion formation, while moonlighting as a signaling adaptor in insulin, antiviral, p53, and chromatin pathways [#0, #1, #5]. Its N-terminal IMD/I-BAR domain bundles actin filaments and binds Rac (but not Cdc42), and its C-terminal WH2 extension binds actin filaments to modulate bundle length [#0]. Through the I-BAR domain it engages curvature-coupled partners including Rif GTPase and the formin FMNL2, and through its SH3 domain it recruits EPS8 and WAVE2 to drive filopodia, dorsal ruffles, and microvillar/stereociliary/microridge elongation at protrusion tips [#1, #7, #11, #16]. As an insulin-receptor adaptor it sustains IR–IRS1–PI3K–AKT signaling, in part by its SH3 domain binding the SHIP2 catalytic domain to suppress PIP3 hydrolysis; IRTKS-deficient mice are insulin resistant [#5, #8]. IRTKS also recruits the SUMO E2 ligase Ubc9 to two distinct substrates: it SUMOylates PCBP2 to drive MAVS degradation and dampen RIG-I antiviral signaling [#4], and it SUMOylates HP1\\u03b1 to promote liquid-liquid phase-separated constitutive heterochromatin, whose loss derepresses repetitive elements and triggers cGAS-STING-driven senescence [#13]. Additional regulatory roles include Chk2-dependent phosphorylation at Ser331 that controls IRTKS occupancy of the p53-MDM2 complex and thereby p53 stability [#6], Src-dependent tyrosine phosphorylation that enables pro-migratory function [#9], OTUD4 recruitment that stabilizes SETDB1 to epigenetically silence E-cadherin and promote EMT/metastasis [#12], and formation of lysosomal condensates that engage RRAGD to potentiate amino-acid-sensitive mTORC1 activation, driving steatosis and MASLD-to-HCC progression in mouse liver [#21]. Recurrent gene fusions in which the BAIAP2L1 dimerization (BAR/coiled-coil) domain is fused to FGFR3 or BRAF produce constitutive kinase activation and oncogenic transformation [#2, #18].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Established the biochemical core activity of IRTKS by showing its IMD/I-BAR domain bundles actin and binds Rac, distinguishing it from the paralog IRSp53 which also engages Cdc42.\",\n      \"evidence\": \"In vitro actin bundling assays, co-IP, and domain deletion in cells\",\n      \"pmids\": [\"17430976\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define in vivo protrusion phenotypes\", \"WH2 mechanism of bundle-length modulation not structurally resolved\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Placed IRTKS as a specific host effector of enteropathogenic bacteria, showing it (not IRSp53) is recruited to Tir attachment sites via the Tir NPY451 motif during infection.\",\n      \"evidence\": \"C. rodentium mouse model and EHEC human ileal explants with tir tyrosine mutants and competitive infection\",\n      \"pmids\": [\"19889090\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve which IRTKS domain binds Tir\", \"Downstream actin polymerization machinery not yet mapped\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Connected IRTKS to migration control by mapping six Src phosphorylation sites required for its pro-migratory effect.\",\n      \"evidence\": \"In vitro/in vivo kinase assays, point mutants, wound closure in HT1080 cells\",\n      \"pmids\": [\"21840312\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"How tyrosine phosphorylation alters IRTKS partner binding unresolved\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Defined a metabolic signaling role, showing IRTKS is an insulin-receptor adaptor whose loss causes insulin resistance reversible by ectopic IRTKS.\",\n      \"evidence\": \"IRTKS-KO and diabetic mice, tolerance tests, rescue, signaling western blots\",\n      \"pmids\": [\"23896986\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular contact with IR not structurally defined at this stage\", \"Tissue-specific contributions not dissected\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Revealed an antiviral suppression mechanism via Ubc9-mediated SUMOylation of PCBP2 leading to MAVS degradation.\",\n      \"evidence\": \"IRTKS-deficient cells/mice, viral infection, SUMOylation and MAVS degradation assays, fractionation\",\n      \"pmids\": [\"26348439\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How viral infection triggers IRTKS-Ubc9 engagement unclear\", \"Relationship to its cytoskeletal roles not addressed\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Demonstrated oncogenic fusion biology, showing the FGFR3-BAIAP2L1 fusion drives transformation through BAR-domain-mediated constitutive FGFR3 dimerization/activation.\",\n      \"evidence\": \"Stable transfection, BAR deletion mutant, in vitro/in vivo tumorigenicity, FGFR inhibitor\",\n      \"pmids\": [\"25589496\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not address full-length BAIAP2L1 function\", \"Tumor-type specificity of fusion not delineated\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Linked the I-BAR domain to Rif GTPase signaling and SH3-domain-dependent migration, mapping EPS8/WAVE2 as effectors of dorsal protrusion formation and p38 activation.\",\n      \"evidence\": \"Reciprocal Co-IP, KO cells, dominant-negative Rif, chimeric SH3 constructs, live imaging\",\n      \"pmids\": [\"27278019\", \"27693783\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Mechanistic basis for Tir/Rif competition on I-BAR not resolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Established a DNA-damage-responsive role in p53 control, showing Chk2 phosphorylation at Ser331 evicts IRTKS from the p53-MDM2 complex to stabilize p53.\",\n      \"evidence\": \"Co-IP, ubiquitination assays, Chk2 kinase assay, IRTKS-KO MEFs/mice, tumorigenicity\",\n      \"pmids\": [\"28647685\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How IRTKS facilitates MDM2-mediated p53 ubiquitination structurally unclear\", \"Nuclear vs cytoplasmic pools not distinguished\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Demonstrated genetic redundancy with IRSp53 in development, with double knockout causing embryonic lethality and placental defects.\",\n      \"evidence\": \"Single and double KO mice with developmental/histological analysis\",\n      \"pmids\": [\"28067313\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis of redundancy in spongiotrophoblast not defined\", \"Single lab\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Resolved tip-targeted protrusion mechanism in epithelia: I-BAR localizes IRTKS to microvillar tips, while WH2 polymerizes actin and SH3 recruits EPS8 for elongation.\",\n      \"evidence\": \"Super-resolution and live imaging, domain mutants, loss-of-function and rescue\",\n      \"pmids\": [\"30197089\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How tip enrichment is maintained dynamically unresolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Provided the enzymatic basis for IRTKS lipid signaling, showing its SH3 domain binds and inhibits the SHIP2 catalytic domain to preserve PIP3 and activate AKT-mTOR.\",\n      \"evidence\": \"Co-IP, domain binding, lipid phosphatase activity assay, PIP3/PI(3,4)P2 quantification in KO cells\",\n      \"pmids\": [\"31212584\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Insulin-dependent dynamics of the interaction only partially characterized\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified FMNL2 as a curvature-coupled cofactor, with FMNL2 bending membrane to recruit IRTKS for cooperative filopodia assembly, a function specific to IRTKS over IRSp53.\",\n      \"evidence\": \"Co-IP, domain mapping, KO cell lines, filopodia quantification, rescue\",\n      \"pmids\": [\"36259517\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Order of FMNL2/IRTKS recruitment in vivo not fully resolved\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Extended fusion oncogenesis to BRAF, showing BAIAP2L1 provides coiled-coil-dependent dimerization for constitutive BRAF kinase activation in thyroid cells.\",\n      \"evidence\": \"Fusion identification, kinase-dead and CC-domain mutants, 3D spheroid assays, RNAi\",\n      \"pmids\": [\"36217175\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Clinical prevalence of the fusion not established\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Uncovered an epigenetic metastasis-promoting mechanism: IRTKS recruits OTUD4 to deubiquitinate and stabilize SETDB1, raising H3K9me3 to silence E-cadherin and drive EMT.\",\n      \"evidence\": \"Co-IP, ubiquitination assays, ATAC-seq, H3K9me3 ChIP, metastasis assays\",\n      \"pmids\": [\"37739210\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"How IRTKS selects SETDB1/OTUD4 versus other deubiquitination substrates unclear\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defined a phase-separation function in heterochromatin: IRTKS condensates and Ubc9-mediated HP1\\u03b1 SUMOylation maintain constitutive heterochromatin, preventing repeat derepression and cGAS-STING senescence.\",\n      \"evidence\": \"LLPS reconstitution, FRAP, SUMOylation assay, ATAC-seq/RNA-seq, cGAS-STING analysis in KO cells\",\n      \"pmids\": [\"39192031\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How nuclear IRTKS pool is regulated relative to cytoplasmic functions unclear\", \"Sequence determinants of IRTKS phase separation not mapped\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Showed BAIAP2L1 targets stereocilia tips dependent on EPS8/MYO15A in a calcium-independent manner, but its loss is dispensable for hearing/balance, indicating functional redundancy in this tissue.\",\n      \"evidence\": \"Immunofluorescence, KO mice, auditory brainstem response and vestibular tests\",\n      \"pmids\": [\"39093051\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Compensating protein not identified\", \"Single lab\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Linked IRTKS to PTEN regulation in mesenchymal stem cell osteogenesis via SH3-domain binding to the PTEN C-terminal tail.\",\n      \"evidence\": \"Co-IP, SH3 domain mapping, AKT readouts, BMSC differentiation, PTEN rescue\",\n      \"pmids\": [\"38908202\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No in vitro phosphatase assay confirming PTEN inhibition\", \"Single Co-IP, single lab\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Defined a lysosomal mTORC1-activating role: IRTKS forms membrane-associated condensates that interact with RRAGD to heighten amino-acid sensing, with hepatic knockin driving obesity, steatosis, and MASLD-to-HCC.\",\n      \"evidence\": \"Phospho-array screening, RRAGD Co-IP, lysosomal fractionation/condensate imaging, hepatic knockin/KO mice with mTORC1 inhibition rescue\",\n      \"pmids\": [\"41575860\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How IRTKS condensates assemble at the lysosome unresolved\", \"Relationship to its other condensate (heterochromatin) behavior unclear\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how IRTKS partitions among its cytoskeletal, plasma-membrane signaling, lysosomal, and nuclear/heterochromatin functions, and what determines context-specific recruitment of Ubc9, OTUD4, RRAGD, and SHIP2 to a single scaffold.\",\n      \"evidence\": \"No timeline study integrates the multiple condensate, SUMOylation, and adaptor functions into one regulatory logic\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No unified model of IRTKS spatial regulation\", \"Structural basis for SH3/I-BAR partner switching not solved\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 1, 7, 11]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [5, 6, 8]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [4, 8, 13]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1, 3, 7, 16]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 1, 11]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [4, 13]},\n      {\"term_id\": \"GO:0005764\", \"supporting_discovery_ids\": [21]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [13]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [5, 8]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [13, 12]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [4, 6, 12, 21]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [2, 18, 21]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"EPS8\", \"WAVE2\", \"SHIP2\", \"FMNL2\", \"Ubc9\", \"OTUD4\", \"RRAGD\", \"MYO15A\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}