{"gene":"DYNLL2","run_date":"2026-04-28T17:46:03","timeline":{"discoveries":[{"year":2000,"finding":"DYNLL2 (DLC2, 93% identical to DLC1) was identified as a direct binding partner of GKAP (guanylate kinase domain-associated protein) via yeast two-hybrid screen. A complex containing PSD-95, GKAP, DYNLL2, and myosin-V was co-immunoprecipitated from rat brain extracts. DYNLL2 co-localizes with PSD-95 and F-actin in dendritic spines and is enriched in biochemical purifications of the postsynaptic density (PSD), suggesting a role in trafficking of the PSD-95 scaffold complex via motor proteins.","method":"Yeast two-hybrid screen, co-immunoprecipitation from rat brain, immunofluorescence co-localization, immunogold electron microscopy","journal":"The Journal of Neuroscience","confidence":"High","confidence_rationale":"Tier 1–2 — reciprocal Co-IP from native tissue, yeast two-hybrid, and immunogold EM providing multiple orthogonal lines of evidence","pmids":["10844022"],"is_preprint":false},{"year":2001,"finding":"In healthy cells, the pro-apoptotic BH3-only protein Bmf is sequestered to myosin V motor complexes through direct association with dynein light chain 2 (DYNLL2). Certain damage signals such as loss of cell attachment (anoikis) release Bmf from DYNLL2, allowing it to translocate and bind pro-survival Bcl-2 proteins, thereby triggering apoptosis. This positions DYNLL2 as a cytoskeletal anchor that sequesters a pro-apoptotic sensor.","method":"Co-immunoprecipitation, subcellular fractionation, anoikis assay, functional apoptosis readout","journal":"Science","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP, functional rescue experiments, and defined phenotypic readout (apoptosis) replicated in multiple cell systems","pmids":["11546872"],"is_preprint":false},{"year":2003,"finding":"JNK phosphorylates Bmf, which is normally sequestered by binding to dynein (via DYNLL2) and myosin V motor complexes. JNK-mediated phosphorylation of Bmf causes its release from the motor complexes, providing a mechanistic link between the JNK stress signaling pathway and mitochondrial (Bax/Bak-dependent) apoptosis.","method":"In vitro kinase assay, co-immunoprecipitation, Bax/Bak-dependent apoptosis readout, JNK gene disruption","journal":"Proceedings of the National Academy of Sciences","confidence":"High","confidence_rationale":"Tier 1–2 — in vitro kinase assay combined with genetic loss-of-function and functional apoptosis readout","pmids":["12591950"],"is_preprint":false},{"year":2009,"finding":"CDK11p58 phosphorylates PAK1 at Ser174, and this phosphorylation event promotes the recruitment of PAK1 into a myosin V motor complex through binding to dynein light chain 2 (DYNLL2). The phosphomimetic PAK1(S174E) bound DYNLL2 and accelerated mitotic progression in a nocodazole-blocked cell model, whereas the non-phosphorylatable PAK1(S174A) had the opposite effect, indicating DYNLL2 mediates PAK1's role in mitosis downstream of CDK11p58.","method":"Co-immunoprecipitation, site-directed mutagenesis (S174A/S174E), nocodazole cell-cycle block assay, kinase substrate mapping","journal":"Journal of Biochemistry","confidence":"Medium","confidence_rationale":"Tier 2–3 — Co-IP with mutagenesis and functional cell-cycle assay, single lab","pmids":["19520772"],"is_preprint":false},{"year":2010,"finding":"AMBRA1 tethers the BECLIN1-VPS34 autophagy core complex to the cytoskeleton through interaction with dynein light chains 1 and 2 (including DYNLL2). Upon autophagy induction, ULK1 phosphorylates AMBRA1, releasing the complex from dynein. This releases the autophagy complex to the endoplasmic reticulum, enabling autophagosome nucleation. Thus DYNLL2 participates in cytoskeletal anchoring of the autophagy initiation machinery.","method":"Co-immunoprecipitation, ULK1 kinase assay, autophagy induction assays, subcellular fractionation, fluorescence microscopy","journal":"The Journal of Cell Biology","confidence":"High","confidence_rationale":"Tier 1–2 — kinase assay, Co-IP, and direct imaging of autophagosome relocalization with functional consequence","pmids":["20921139"],"is_preprint":false},{"year":2012,"finding":"DYNLL2 interacts with GKAP in dendritic spines and this interaction stabilizes scaffolding protein expression at the postsynaptic density (PSD) and enhances synaptic NMDA receptor activity. BRET imaging showed the interaction occurs in spines; electrophysiological recording confirmed that disrupting the GKAP-DYNLL2 interaction reduces NMDA receptor-mediated currents. Sustained synaptic activity further promotes GKAP-DYNLL2 interaction, revealing an activity-dependent regulatory pathway.","method":"BRET imaging in living neurons, immunostaining, electrophysiological recording of NMDA receptor currents","journal":"Journal of Cell Science","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (BRET, imaging, electrophysiology) in living neurons with clear functional readout","pmids":["22328512"],"is_preprint":false},{"year":2014,"finding":"Using two-photon scanning number and brightness (sN&B) fluorescence fluctuation microscopy in living neurons, DYNLL2 dimerization was found to be required for its interaction with GKAP, which in turn potentiates GKAP self-association. In dendritic shafts, DYNLL2-GKAP complexes consist mainly of two DLC2 and two GKAP monomers, while in spines the hetero-complexes are much larger (~16 DYNLL2 and ~13 GKAP monomers). Disrupting the GKAP-DYNLL2 interaction decreased spine-preferential GKAP localization and inhibited NMDA receptor activity, demonstrating DYNLL2 functions as a dimerization engine organizing the postsynaptic scaffold.","method":"Two-photon scanning number and brightness (sN&B) fluorescence fluctuation microscopy, electrophysiology, fluorescence imaging in living neurons","journal":"Journal of Cell Science","confidence":"High","confidence_rationale":"Tier 1–2 — quantitative single-molecule microscopy combined with electrophysiology and disruption experiments, multiple orthogonal approaches","pmids":["24938595"],"is_preprint":false},{"year":2014,"finding":"NMR spectroscopy, X-ray crystallography, and molecular dynamics simulations characterized DYNLL2 binding to the myosin 5a (myo5a) tail. The DYNLL2-binding region of myo5a resides in an intrinsically disordered domain with nascent helical character in the free form, which folds into a β-strand upon DYNLL2 binding. One peptide is accommodated in each parallel DYNLL2 binding groove. The myo5a motif has extended flanking contacts beyond the core consensus: N-terminal extension folds back partially blocking the β-sheet edge, while C-terminal extension contacts the dimer interface and interacts with symmetry-related residues of the second myo5a peptide.","method":"NMR spectroscopy, X-ray crystallography, molecular dynamics simulations","journal":"Biochemistry","confidence":"High","confidence_rationale":"Tier 1 — atomic-resolution structure combined with NMR dynamics and MD simulation, multiple orthogonal structural methods","pmids":["25312846"],"is_preprint":false},{"year":2015,"finding":"DYNLL2 protein levels in oxytocin neurons of the hypothalamic paraventricular nucleus (PVN) are regulated by fasted/fed states, being higher in the fed condition. In fed animals, NMDA receptor-mediated EPSCs on oxytocin neurons were increased. DYNLL2 upregulation correlated with increased NMDA receptor-mediated synaptic input, consistent with a role for DYNLL2 in NMDA receptor trafficking to the postsynaptic site in the context of metabolic state-dependent synaptic plasticity.","method":"Whole-cell electrophysiology (mEPSC and NMDA-EPSC recording), western blot for DYNLL2 protein, immunostaining","journal":"Neuropeptides","confidence":"Medium","confidence_rationale":"Tier 3 — correlative western blot and electrophysiology in vivo, single lab, no direct mechanistic manipulation of DYNLL2","pmids":["26344333"],"is_preprint":false},{"year":2022,"finding":"In chicken primary myoblasts, DYNLL2 was identified as a hub gene controlling myoblast differentiation. miR-148a-3p was found to directly target DYNLL2 mRNA; overexpression of miR-148a-3p suppressed DYNLL2 and promoted myosin heavy chain (MYHC) expression and myoblast differentiation. This defines a miR-148a-3p → DYNLL2 regulatory axis in skeletal muscle fiber development.","method":"WGCNA on transcriptome data, miRNA transfection in chicken primary myoblasts, western blot for MYHC protein","journal":"BMC Genomics","confidence":"Medium","confidence_rationale":"Tier 3 — functional miRNA overexpression with protein readout, single lab, chicken ortholog","pmids":["35379193"],"is_preprint":false},{"year":2025,"finding":"DYNLL2 interacts directly with PAK1 to regulate endocytosis of Gram-negative bacterial outer membrane vesicles (OMVs) in macrophages/monocytes. The DYNLL2-PAK1 complex facilitates cytosolic LPS release and subsequent Caspase-11 inflammasome activation, triggering pyroptosis via Gasdermin D (GSDMD) cleavage. Depletion of either DYNLL2 or PAK1 suppressed OMV internalization, Caspase-11/GSDMD cleavage, and proinflammatory cytokine release. The flavonoid Oroxylin A was identified as an inhibitor of the DYNLL2-PAK1 interaction that blocks Caspase-11-dependent pyroptosis in vitro and improves survival in murine endotoxemia models.","method":"Co-immunoprecipitation, DYNLL2/PAK1 knockdown, endotoxemia mouse model, Caspase-11/GSDMD cleavage assay, virtual screening, Oroxylin A pharmacological inhibition","journal":"Biochemical Pharmacology","confidence":"Medium","confidence_rationale":"Tier 2–3 — Co-IP, genetic depletion with defined pyroptosis readout, in vivo model, and pharmacological validation; single lab","pmids":["41360226"],"is_preprint":false}],"current_model":"DYNLL2 (dynein light chain LC8-type 2) is a conserved homodimeric hub protein that, through its paired binding grooves, sequesters diverse partners including the pro-apoptotic protein Bmf (released by JNK phosphorylation or anoikis), the autophagy regulator AMBRA1 (released by ULK1 phosphorylation to enable autophagosome formation), PAK1 (via CDK11p58-mediated phosphorylation, promoting mitotic progression and, in macrophages, OMV endocytosis and Caspase-11 pyroptosis), and the postsynaptic scaffold protein GKAP (where DYNLL2 dimerization drives formation of large hetero-oligomeric complexes in dendritic spines that stabilize the PSD and enhance NMDA receptor activity), while structural studies reveal that binding partners fold from intrinsically disordered regions into β-strands within the DYNLL2 groove with extended flanking contacts that can modify quaternary organization of full-length partners."},"narrative":{"teleology":[{"year":2000,"claim":"Identification of DYNLL2 as a postsynaptic density component that directly binds GKAP established its first known scaffolding interaction and linked it to the PSD-95–myosin V trafficking complex in dendritic spines.","evidence":"Yeast two-hybrid, co-IP from rat brain, immunogold EM","pmids":["10844022"],"confidence":"High","gaps":["Whether DYNLL2-GKAP binding is functionally required for synaptic transmission was untested","Stoichiometry and oligomeric state of the complex unknown","No distinction from DYNLL1 function at synapses"]},{"year":2001,"claim":"Discovery that DYNLL2 sequesters the pro-apoptotic BH3-only protein Bmf on the actin cytoskeleton revealed a general mechanism — cytoskeletal anchoring of a death sensor — and showed that anoikis releases Bmf to trigger apoptosis.","evidence":"Co-IP, subcellular fractionation, anoikis and apoptosis assays in multiple cell types","pmids":["11546872"],"confidence":"High","gaps":["Phosphorylation-based mechanism of Bmf release was not yet defined","Whether DYNLL1 and DYNLL2 are redundant in Bmf sequestration was unclear"]},{"year":2003,"claim":"Demonstration that JNK phosphorylates Bmf to cause its release from DYNLL2-containing motor complexes provided the upstream kinase signal linking stress-activated MAPK signaling to the cytoskeletal sequestration/release mechanism.","evidence":"In vitro JNK kinase assay, JNK knockout cells, Bax/Bak-dependent apoptosis readout","pmids":["12591950"],"confidence":"High","gaps":["Precise phospho-site(s) on Bmf that disrupt DYNLL2 binding not structurally mapped","In vivo physiological contexts for JNK-Bmf-DYNLL2 axis beyond UV damage not explored"]},{"year":2009,"claim":"CDK11p58-mediated phosphorylation of PAK1 at Ser174 was shown to promote PAK1 recruitment to DYNLL2, linking DYNLL2 to mitotic kinase signaling and cell-cycle progression.","evidence":"Co-IP with phosphomimetic/non-phosphorylatable PAK1 mutants, nocodazole cell-cycle block","pmids":["19520772"],"confidence":"Medium","gaps":["Single-lab study; independent replication pending","Whether DYNLL2 binding activates PAK1 catalytically or simply relocates it was not resolved","In vivo mitotic phenotype of DYNLL2 depletion not tested"]},{"year":2010,"claim":"DYNLL2 was found to anchor the AMBRA1–Beclin 1–VPS34 autophagy initiation complex to dynein/cytoskeleton; ULK1-mediated phosphorylation of AMBRA1 releases the complex for ER-localized autophagosome nucleation, extending the sequestration-and-release paradigm to autophagy.","evidence":"Co-IP, ULK1 kinase assay, autophagy induction, subcellular fractionation, fluorescence microscopy","pmids":["20921139"],"confidence":"High","gaps":["Relative contributions of DYNLL1 vs DYNLL2 to AMBRA1 tethering not separated","Structural basis of AMBRA1–DYNLL2 interaction unknown"]},{"year":2012,"claim":"BRET imaging and electrophysiology in living neurons demonstrated that the DYNLL2-GKAP interaction stabilizes the PSD and enhances NMDA receptor-mediated currents, with synaptic activity further promoting the interaction — establishing DYNLL2 as an activity-dependent regulator of excitatory synaptic strength.","evidence":"BRET in cultured neurons, NMDA-EPSC recording, immunostaining","pmids":["22328512"],"confidence":"High","gaps":["Quantitative stoichiometry of complexes in spines vs shafts not determined","Upstream signals regulating activity-dependent DYNLL2-GKAP association unidentified"]},{"year":2014,"claim":"Quantitative fluorescence fluctuation microscopy revealed that DYNLL2 dimerization drives formation of large hetero-oligomeric GKAP–DYNLL2 assemblies preferentially in dendritic spines (~16 DYNLL2 + ~13 GKAP monomers), while shaft complexes are smaller tetramers — defining DYNLL2 as a dimerization engine for postsynaptic scaffold organization.","evidence":"Two-photon sN&B microscopy in living neurons, electrophysiology, disruption of GKAP-DYNLL2 binding","pmids":["24938595"],"confidence":"High","gaps":["Mechanism driving spine-specific oligomer growth vs shaft tetramer is unknown","Contribution of other PSD components to the large complex not assessed"]},{"year":2014,"claim":"Atomic-resolution structures of DYNLL2 bound to the myosin 5a tail revealed that intrinsically disordered partner segments fold into β-strands within the DYNLL2 binding groove, with extended flanking contacts modifying quaternary organization — providing the structural basis for DYNLL2's role as a hub that orders disordered partners.","evidence":"NMR spectroscopy, X-ray crystallography, molecular dynamics simulation","pmids":["25312846"],"confidence":"High","gaps":["Structures with other partners (Bmf, AMBRA1, GKAP) not yet solved","How flanking contacts influence selectivity among the many DYNLL2 partners is not clear"]},{"year":2025,"claim":"DYNLL2–PAK1 interaction was shown to regulate OMV endocytosis in macrophages, enabling cytosolic LPS release and Caspase-11/GSDMD-dependent pyroptosis, expanding DYNLL2's roles to innate immune signaling and identifying Oroxylin A as a pharmacological disruptor of this interaction.","evidence":"Co-IP, DYNLL2/PAK1 knockdown, Caspase-11/GSDMD cleavage assay, murine endotoxemia model, virtual screening and Oroxylin A treatment","pmids":["41360226"],"confidence":"Medium","gaps":["Single-lab finding; independent replication and structural validation of Oroxylin A binding site needed","Whether DYNLL2 directly controls vesicle trafficking machinery or acts solely through PAK1 kinase activity is unresolved","Specificity of DYNLL2 vs DYNLL1 in this innate immune pathway not tested"]},{"year":null,"claim":"A unifying structural and selectivity model explaining how DYNLL2 discriminates among its many disordered partners and how phosphorylation at partner sites allosterically disrupts binding remains to be established, as does the degree of functional redundancy with the 93%-identical paralog DYNLL1 across its diverse cellular roles.","evidence":"","pmids":[],"confidence":"High","gaps":["No systematic comparison of DYNLL1 vs DYNLL2 partner selectivity or knockout phenotypes","Structural basis of phosphorylation-induced partner release not determined for any partner","In vivo phenotype of DYNLL2-specific loss in mammalian systems not reported"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,5,6,7]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,1,7]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,4,3]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,1,4,7]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[1,4]}],"pathway":[{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[4]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[1,2]},{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[0,5,6]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[10]}],"complexes":["Myosin V motor complex","Dynein complex (LC8 light chain)","PSD-95–GKAP–DYNLL2 postsynaptic scaffold"],"partners":["GKAP","BMF","PAK1","AMBRA1","MYO5A","DLG4","BECN1"],"other_free_text":[]},"mechanistic_narrative":"DYNLL2 is a conserved homodimeric hub protein of the LC8 dynein light chain family that functions as a dimerization engine and cytoskeletal anchor, sequestering diverse partners through paired binding grooves until signal-dependent phosphorylation triggers their release. It sequesters the pro-apoptotic BH3-only protein Bmf on myosin V motor complexes; JNK phosphorylation or anoikis releases Bmf to activate Bax/Bak-dependent apoptosis [PMID:11546872, PMID:12591950]. DYNLL2 similarly tethers the AMBRA1–Beclin 1–VPS34 autophagy initiation complex to the cytoskeleton, with ULK1 phosphorylation of AMBRA1 liberating the complex for autophagosome nucleation [PMID:20921139], and recruits PAK1 downstream of CDK11p58 phosphorylation to promote mitotic progression and, in macrophages, OMV endocytosis leading to Caspase-11 inflammasome activation [PMID:19520772, PMID:41360226]. At excitatory synapses, DYNLL2 dimerization drives large-scale hetero-oligomerization of GKAP at the postsynaptic density, stabilizing the PSD-95 scaffold and enhancing NMDA receptor-mediated currents in an activity-dependent manner [PMID:22328512, PMID:24938595]."},"prefetch_data":{"uniprot":{"accession":"Q96FJ2","full_name":"Dynein light chain 2, cytoplasmic","aliases":["8 kDa dynein light chain b","DLC8b","Dynein light chain LC8-type 2"],"length_aa":89,"mass_kda":10.3,"function":"Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in changing or maintaining the spatial distribution of cytoskeletal structures (By similarity)","subcellular_location":"Cytoplasm, cytoskeleton","url":"https://www.uniprot.org/uniprotkb/Q96FJ2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DYNLL2","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000264364","cell_line_id":"CID001412","localizations":[{"compartment":"centrosome","grade":3},{"compartment":"nuclear_punctae","grade":3},{"compartment":"cell_contact","grade":2},{"compartment":"cytoplasmic","grade":2},{"compartment":"nucleoplasm","grade":2},{"compartment":"cytoskeleton","grade":1}],"interactors":[{"gene":"DYNLL1","stoichiometry":10.0},{"gene":"ZMYM4","stoichiometry":10.0},{"gene":"FAM117B","stoichiometry":10.0},{"gene":"AMOT","stoichiometry":10.0},{"gene":"GLCCI1","stoichiometry":10.0},{"gene":"GOLGB1","stoichiometry":10.0},{"gene":"STRN3","stoichiometry":10.0},{"gene":"CTTNBP2NL","stoichiometry":10.0},{"gene":"DYNC1LI1","stoichiometry":10.0},{"gene":"UBQLN1","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/target/CID001412","total_profiled":1310},"omim":[{"mim_id":"608942","title":"DYNEIN, LIGHT CHAIN, LC8 TYPE, 2; DYNLL2","url":"https://www.omim.org/entry/608942"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Nucleoplasm","reliability":"Uncertain"},{"location":"Cytosol","reliability":"Uncertain"},{"location":"Mid piece","reliability":"Uncertain"},{"location":"Principal piece","reliability":"Uncertain"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DYNLL2"},"hgnc":{"alias_symbol":["MGC17810","Dlc2","DNCL1B","RSPH22"],"prev_symbol":[]},"alphafold":{"accession":"Q96FJ2","domains":[{"cath_id":"3.30.740.10","chopping":"5-86","consensus_level":"high","plddt":97.292,"start":5,"end":86}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96FJ2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96FJ2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96FJ2-F1-predicted_aligned_error_v6.png","plddt_mean":95.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DYNLL2","jax_strain_url":"https://www.jax.org/strain/search?query=DYNLL2"},"sequence":{"accession":"Q96FJ2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96FJ2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96FJ2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96FJ2"}},"corpus_meta":[{"pmid":"16217026","id":"PMC_16217026","title":"Deleted in liver cancer 2 (DLC2) suppresses cell transformation by means of inhibition of RhoA activity.","date":"2005","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/16217026","citation_count":96,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20208559","id":"PMC_20208559","title":"DLC2 modulates angiogenic responses in vascular endothelial cells by regulating cell attachment and migration.","date":"2010","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/20208559","citation_count":33,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"16364308","id":"PMC_16364308","title":"Mitochondrial targeting of growth suppressor protein DLC2 through the START domain.","date":"2005","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/16364308","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"19668331","id":"PMC_19668331","title":"Deleted in liver cancer 2 (DLC2) was dispensable for development and its deficiency did not aggravate hepatocarcinogenesis.","date":"2009","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/19668331","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25518808","id":"PMC_25518808","title":"The tumour suppressor DLC2 ensures mitotic fidelity by coordinating spindle positioning and cell-cell adhesion.","date":"2014","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/25518808","citation_count":20,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"19250640","id":"PMC_19250640","title":"START-GAP2/DLC2 is localized in focal adhesions via its N-terminal region.","date":"2009","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/19250640","citation_count":20,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22614672","id":"PMC_22614672","title":"DLC2/StarD13 plays a role of a tumor suppressor in astrocytoma.","date":"2012","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/22614672","citation_count":20,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22328512","id":"PMC_22328512","title":"GKAP-DLC2 interaction organizes the postsynaptic scaffold complex to enhance synaptic NMDA receptor activity.","date":"2012","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/22328512","citation_count":19,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"26344333","id":"PMC_26344333","title":"Fasted/fed states regulate postsynaptic hub protein DYNLL2 and glutamatergic transmission in oxytocin neurons in the hypothalamic paraventricular nucleus.","date":"2015","source":"Neuropeptides","url":"https://pubmed.ncbi.nlm.nih.gov/26344333","citation_count":18,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25312846","id":"PMC_25312846","title":"DYNLL2 dynein light chain binds to an extended linear motif of myosin 5a tail that has structural plasticity.","date":"2014","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25312846","citation_count":16,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17519008","id":"PMC_17519008","title":"The NMR structure of the murine DLC2 SAM domain reveals a variant fold that is similar to a four-helix bundle.","date":"2007","source":"BMC structural biology","url":"https://pubmed.ncbi.nlm.nih.gov/17519008","citation_count":15,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"29218825","id":"PMC_29218825","title":"In vivo evidence supporting a metastasis suppressor role for Stard13 (Dlc2) in ErbB2 (Neu) oncogene induced mouse mammary tumors.","date":"2017","source":"Genes, chromosomes & cancer","url":"https://pubmed.ncbi.nlm.nih.gov/29218825","citation_count":14,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"35379193","id":"PMC_35379193","title":"Weighted gene co-expression network indicates that the DYNLL2 is an important regulator of chicken breast muscle development and is regulated by miR-148a-3p.","date":"2022","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/35379193","citation_count":13,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"19520772","id":"PMC_19520772","title":"CDK11p58 phosphorylation of PAK1 Ser174 promotes DLC2 binding and roles on cell cycle progression.","date":"2009","source":"Journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19520772","citation_count":11,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31323253","id":"PMC_31323253","title":"Role of DLC2 and RhoA/ROCK pathway in formalin induced inflammatory pain in mice.","date":"2019","source":"Neuroscience letters","url":"https://pubmed.ncbi.nlm.nih.gov/31323253","citation_count":10,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24938595","id":"PMC_24938595","title":"The stoichiometry of scaffold complexes in living neurons - DLC2 functions as a dimerization engine for GKAP.","date":"2014","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/24938595","citation_count":9,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22204965","id":"PMC_22204965","title":"The RhoA GTPase-activating protein DLC2 modulates RhoA activity and hyperalgesia to noxious thermal and inflammatory stimuli.","date":"2011","source":"Neuro-Signals","url":"https://pubmed.ncbi.nlm.nih.gov/22204965","citation_count":9,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30719106","id":"PMC_30719106","title":"DLC2 operates as a tumor suppressor gene in breast cancer via the RhoGTPase pathway.","date":"2018","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/30719106","citation_count":8,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30094094","id":"PMC_30094094","title":"DLC2 inhibits development of glioma through regulating the expression ratio of TAp73α/TAp73β.","date":"2018","source":"American journal of cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/30094094","citation_count":8,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22907632","id":"PMC_22907632","title":"Comparative next-generation mapping of the Phytophthora infestans resistance gene Rpi-dlc2 in a European accession of Solanum dulcamara.","date":"2012","source":"TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik","url":"https://pubmed.ncbi.nlm.nih.gov/22907632","citation_count":7,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"41360226","id":"PMC_41360226","title":"Targeting the DYNLL2-PAK1 axis inhibits caspase-11-dependent pyroptosis to alleviate sepsis.","date":"2025","source":"Biochemical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/41360226","citation_count":1,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"16189514","id":"PMC_16189514","title":"Towards a proteome-scale map of the human protein-protein interaction network.","date":"2005","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/16189514","citation_count":2090,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12477932","id":"PMC_12477932","title":"Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.","date":"2002","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/12477932","citation_count":1479,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"19615732","id":"PMC_19615732","title":"Defining the human deubiquitinating enzyme interaction landscape.","date":"2009","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/19615732","citation_count":1282,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26777405","id":"PMC_26777405","title":"ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure.","date":"2016","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26777405","citation_count":1233,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26186194","id":"PMC_26186194","title":"The BioPlex Network: A Systematic Exploration of the Human Interactome.","date":"2015","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26186194","citation_count":1118,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"28514442","id":"PMC_28514442","title":"Architecture of the human interactome defines protein communities and disease networks.","date":"2017","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/28514442","citation_count":1085,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"25416956","id":"PMC_25416956","title":"A proteome-scale map of the human interactome network.","date":"2014","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/25416956","citation_count":977,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12591950","id":"PMC_12591950","title":"JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis.","date":"2003","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/12591950","citation_count":881,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"32296183","id":"PMC_32296183","title":"A reference map of the human binary protein interactome.","date":"2020","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/32296183","citation_count":849,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"19490893","id":"PMC_19490893","title":"A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene.","date":"2009","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/19490893","citation_count":843,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"17353931","id":"PMC_17353931","title":"Large-scale mapping of human protein-protein interactions by mass spectrometry.","date":"2007","source":"Molecular systems biology","url":"https://pubmed.ncbi.nlm.nih.gov/17353931","citation_count":733,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"33961781","id":"PMC_33961781","title":"Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.","date":"2021","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/33961781","citation_count":705,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21873635","id":"PMC_21873635","title":"Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium.","date":"2011","source":"Briefings in bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/21873635","citation_count":656,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"11546872","id":"PMC_11546872","title":"Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis.","date":"2001","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/11546872","citation_count":501,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"15489334","id":"PMC_15489334","title":"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).","date":"2004","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/15489334","citation_count":438,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26638075","id":"PMC_26638075","title":"A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface.","date":"2015","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26638075","citation_count":433,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"35271311","id":"PMC_35271311","title":"OpenCell: Endogenous tagging for the cartography of human cellular organization.","date":"2022","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/35271311","citation_count":432,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"20360068","id":"PMC_20360068","title":"Systematic analysis of human protein complexes identifies chromosome segregation proteins.","date":"2010","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/20360068","citation_count":421,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"16344560","id":"PMC_16344560","title":"Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.","date":"2005","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/16344560","citation_count":409,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26344197","id":"PMC_26344197","title":"Panorama of ancient metazoan macromolecular complexes.","date":"2015","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/26344197","citation_count":407,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"20921139","id":"PMC_20921139","title":"The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy.","date":"2010","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/20921139","citation_count":395,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"15146197","id":"PMC_15146197","title":"Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation.","date":"2004","source":"Nature biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/15146197","citation_count":266,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21399614","id":"PMC_21399614","title":"Novel asymmetrically localizing components of human centrosomes identified by complementary proteomics methods.","date":"2011","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/21399614","citation_count":265,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"22810585","id":"PMC_22810585","title":"Viral immune modulators perturb the human molecular network by common and unique strategies.","date":"2012","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/22810585","citation_count":219,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"27705803","id":"PMC_27705803","title":"A High-Density Map for Navigating the Human Polycomb Complexome.","date":"2016","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/27705803","citation_count":216,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"25281560","id":"PMC_25281560","title":"Proximity biotinylation and affinity purification are complementary approaches for the interactome mapping of chromatin-associated protein complexes.","date":"2014","source":"Journal of proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/25281560","citation_count":215,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"27173435","id":"PMC_27173435","title":"An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.","date":"2016","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/27173435","citation_count":211,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21988832","id":"PMC_21988832","title":"Toward an understanding of the protein interaction network of the human liver.","date":"2011","source":"Molecular systems biology","url":"https://pubmed.ncbi.nlm.nih.gov/21988832","citation_count":207,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21516116","id":"PMC_21516116","title":"Next-generation sequencing to generate interactome datasets.","date":"2011","source":"Nature methods","url":"https://pubmed.ncbi.nlm.nih.gov/21516116","citation_count":200,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"10844022","id":"PMC_10844022","title":"Interaction of the postsynaptic density-95/guanylate kinase domain-associated protein complex with a light chain of myosin-V and dynein.","date":"2000","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/10844022","citation_count":196,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10650,"output_tokens":3082,"usd":0.03909},"stage2":{"model":"claude-opus-4-6","input_tokens":6466,"output_tokens":6589,"usd":0.295583},"total_usd":0.559279,"stage1_batch_id":"msgbatch_0118RScg3WGaGkaZRtWZbtce","stage2_batch_id":"msgbatch_01Cpfzvtbj42aqp5oYZ5Te2s","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":21977,"output_tokens":3783,"usd":0.061338},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":7014,"output_tokens":2951,"usd":0.163268}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2005,\n      \"finding\": \"DLC2 (STARD13) functions as a RhoGAP specific for RhoA and Cdc42; ectopic expression suppresses LPA-induced stress fiber formation and reduces RhoA activity, while a GAP-domain point mutant fails to do so, establishing the GAP domain as essential for its tumor suppressor activity.\",\n      \"method\": \"RhoA pull-down activity assay, site-directed mutagenesis of GAP domain, ectopic expression in mouse fibroblasts and HepG2 cells with morphology and stress fiber readouts\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal methods (pull-down activity assay, mutagenesis, cell morphology) in two cell systems, strong evidence\",\n      \"pmids\": [\"16217026\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"DLC2 localizes to mitochondria and to cytoplasmic speckles near lipid droplets; this mitochondrial targeting is mediated specifically by its START (StAR-related lipid transfer) domain.\",\n      \"method\": \"Co-localization imaging, subcellular biochemical fractionation, START-domain-only deletion construct expression\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — two orthogonal methods (imaging + fractionation) in a single study\",\n      \"pmids\": [\"16364308\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"The SAM domain of DLC2 adopts an atypical four-helix bundle fold (rather than the canonical five-helix SAM fold), suggesting it may interact with a distinct set of ligands compared to other SAM domain proteins.\",\n      \"method\": \"NMR solution structure determination of the isolated SAM domain\",\n      \"journal\": \"BMC structural biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — NMR structure with structural comparison and functional inference\",\n      \"pmids\": [\"17519008\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"DLC2 (START-GAP2) localizes to focal adhesions through a focal adhesion targeting (FAT) region in its N-terminal half; it competes with DLC1 (START-GAP1) for focal adhesion targeting and directly interacts with the C-terminus of tensin2.\",\n      \"method\": \"Fluorescence localization of deletion constructs, direct binding assay with tensin2, competition assay with DLC1\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — direct binding and localization experiments in a single study\",\n      \"pmids\": [\"19250640\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"CDK11p58 phosphorylates PAK1 at Ser174, and the phospho-mimetic PAK1(S174E) binds DYNLL2 (DLC2), recruiting PAK1 into the myosin V motor complex; this interaction accelerates mitotic progression.\",\n      \"method\": \"Kinase assay, phospho-site mutagenesis (S174A/S174E), co-immunoprecipitation, cell cycle progression assay with nocodazole block\",\n      \"journal\": \"Journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — phospho-site mutagenesis combined with co-IP and functional cell assay in a single study\",\n      \"pmids\": [\"19520772\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"DLC2 negatively regulates RhoA in endothelial cells to control cell attachment, migration, and tube formation; silencing of RhoA rescues the enhanced migration and angiogenic responses caused by DLC2 loss, placing DLC2 upstream of RhoA in endothelial angiogenic signaling.\",\n      \"method\": \"RNAi knockdown in human endothelial cells, epistasis rescue by RhoA co-silencing, matrigel angiogenesis assay in DLC2-knockout mice\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis (rescue), in vivo mouse model, and multiple cellular assays\",\n      \"pmids\": [\"20208559\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"DYNLL2 interacts with the postsynaptic scaffold protein GKAP (DLGAP1) in dendritic spines; this interaction stabilizes GKAP at the PSD and enhances synaptic NMDA receptor activity, with the interaction potentiated by sustained synaptic activity.\",\n      \"method\": \"BRET imaging in neurons, immunostaining, electrophysiological recording of NMDA receptor activity\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (BRET, electrophysiology, immunostaining) in a single study\",\n      \"pmids\": [\"22328512\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"DYNLL2 dimerization is required for its interaction with GKAP; DLC2 acts as a dimerization engine that promotes GKAP self-association, forming large hetero-oligomeric complexes (~16 DLC2 and ~13 GKAP monomers) preferentially in dendritic spines, which is required for spine localization of GKAP and NMDA receptor activity.\",\n      \"method\": \"Two-photon scanning number and brightness (sN&B) fluorescence fluctuation microscopy in living neurons, disruption of GKAP-DLC2 interaction\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — quantitative single-molecule imaging in living cells with functional validation of NMDA receptor activity\",\n      \"pmids\": [\"24938595\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"DYNLL2 binds a linear motif in the intrinsically disordered tail of myosin 5a (myo5a); upon binding, the disordered myo5a region folds into a β-strand accommodated in each of the two parallel DYNLL2 binding grooves, with flanking residues making additional contacts that lengthen the binding motif and may influence myo5a quaternary structure.\",\n      \"method\": \"NMR spectroscopy, X-ray crystallography, molecular dynamics simulations of free and DYNLL2-bound myo5a peptide\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — atomic-resolution structure by NMR and crystallography combined with MD simulations\",\n      \"pmids\": [\"25312846\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"DLC2, a negative regulator of Cdc42, interacts with the kinesin Kif1B to coordinate planar spindle positioning and cell-cell junction maintenance in epithelial cells; DLC2 loss induces Kif1B mislocalization, increased Cdc42 activity, cortical recruitment of the Cdc42 effector mDia3, microtubule stabilization, defective spindle positioning, chromosome misalignment, and aneuploidy.\",\n      \"method\": \"siRNA depletion, live-cell imaging of spindle positioning, immunofluorescence, co-immunoprecipitation of DLC2-Kif1B, Cdc42 activity assay\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal co-IP, Cdc42 activity assay, and multiple epistatic phenotypic readouts in a single study\",\n      \"pmids\": [\"25518808\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"DLC2 deficiency in mice increases RhoA activity in the spinal cord following formalin injection and elevates ERK1/2 phosphorylation; DLC2-knockout mice display inflammatory hyperalgesia, establishing DLC2 as a regulator of RhoA/ERK signaling in pain modulation.\",\n      \"method\": \"DLC2-knockout mice, RhoA pull-down activity assay, phospho-ERK immunostaining, behavioral pain tests\",\n      \"journal\": \"Neuro-Signals\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vivo knockout with biochemical (RhoA activity) and cellular (p-ERK) readouts\",\n      \"pmids\": [\"22204965\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"DLC2 directly interacts with TAp73α via its SAM domain and promotes TAp73α ubiquitination and degradation; SAM domain deletion abolishes the interaction and abrogates the anti-tumorigenic effect, identifying the SAM domain as mediating this non-canonical tumor suppressor function.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, SAM domain deletion mutagenesis, cell proliferation/apoptosis assays\",\n      \"journal\": \"American journal of cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — co-IP with domain-deletion mutagenesis and functional ubiquitination assay in a single study\",\n      \"pmids\": [\"30094094\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DYNLL2 interacts with PAK1 to regulate endocytosis of bacterial outer membrane vesicles (OMVs), facilitating cytosolic LPS release and subsequent Caspase-11/Gasdermin D cleavage and pyroptosis; depletion of DYNLL2 or PAK1 suppresses OMV internalization and pyroptotic signaling.\",\n      \"method\": \"siRNA depletion of DYNLL2/PAK1, co-immunoprecipitation, OMV internalization assay, Caspase-11/GSDMD cleavage assays, murine endotoxemia model\",\n      \"journal\": \"Biochemical pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — co-IP, functional knockdown, and in vivo validation in a single study\",\n      \"pmids\": [\"41360226\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DYNLL2 (DLC2/STARD13) is a homodimeric hub protein with a RhoGAP domain that inactivates RhoA and Cdc42, a START domain that directs mitochondrial localization, and an atypical SAM domain that mediates protein-protein interactions (including binding to TAp73α to promote its ubiquitination); it localizes to focal adhesions via an N-terminal FAT region, interacts with GKAP/DLGAP1 in dendritic spines to oligomerize the postsynaptic scaffold and potentiate NMDA receptor activity, binds PAK1 (whose interaction is promoted by CDK11p58-mediated phosphorylation at Ser174) to regulate OMV endocytosis and Caspase-11-dependent pyroptosis, interacts with kinesin Kif1B to coordinate mitotic spindle positioning via Cdc42/mDia3 signaling, and binds myosin 5a tail through an extended linear motif adopting a β-strand in each DYNLL2 groove.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nI'll classify each paper first, then extract discoveries from KEEP papers only.\n\n**Classification:**\n\n- Papers about DLC2/STARD13 (RhoGAP tumor suppressor): These describe a completely different protein (STARD13/DLC2 = deleted in liver cancer 2, a RhoGAP). DYNLL2 is the dynein light chain LC8-type 2. These are ALIAS COLLISION — EXCLUDE: [1],[2],[3],[4],[5],[6],[7],[11],[12],[15],[17],[18],[19]\n- Paper [20]: Rpi-dlc2 is a plant resistance gene — SYMBOL COLLISION — EXCLUDE\n- Papers about DYNLL2 (dynein light chain LC8-type 2): KEEP: [8],[9],[10],[13],[14],[16],[21]\n- Large interactome/proteome papers that mention DYNLL2 among thousands of proteins: These are general resources. I'll include only if they contain specific mechanistic findings about DYNLL2.\n- gene2pubmed papers: [14] Bmf/DLC2 (DYNLL2) KEEP; [30] GKAP/DLC KEEP; [21] AMBRA1/dynein light chains KEEP; others are general interactome resources — low specificity for DYNLL2.\n\n**KEEP list:** PMID 22328512, 26344333, 25312846, 35379193, 19520772, 41360226, 10844022, 11546872, 20921139\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"DYNLL2 (DLC2, 93% identical to DLC1) was identified as a direct binding partner of GKAP (guanylate kinase domain-associated protein) via yeast two-hybrid screen. A complex containing PSD-95, GKAP, DYNLL2, and myosin-V was co-immunoprecipitated from rat brain extracts. DYNLL2 co-localizes with PSD-95 and F-actin in dendritic spines and is enriched in biochemical purifications of the postsynaptic density (PSD), suggesting a role in trafficking of the PSD-95 scaffold complex via motor proteins.\",\n      \"method\": \"Yeast two-hybrid screen, co-immunoprecipitation from rat brain, immunofluorescence co-localization, immunogold electron microscopy\",\n      \"journal\": \"The Journal of Neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — reciprocal Co-IP from native tissue, yeast two-hybrid, and immunogold EM providing multiple orthogonal lines of evidence\",\n      \"pmids\": [\"10844022\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"In healthy cells, the pro-apoptotic BH3-only protein Bmf is sequestered to myosin V motor complexes through direct association with dynein light chain 2 (DYNLL2). Certain damage signals such as loss of cell attachment (anoikis) release Bmf from DYNLL2, allowing it to translocate and bind pro-survival Bcl-2 proteins, thereby triggering apoptosis. This positions DYNLL2 as a cytoskeletal anchor that sequesters a pro-apoptotic sensor.\",\n      \"method\": \"Co-immunoprecipitation, subcellular fractionation, anoikis assay, functional apoptosis readout\",\n      \"journal\": \"Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP, functional rescue experiments, and defined phenotypic readout (apoptosis) replicated in multiple cell systems\",\n      \"pmids\": [\"11546872\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"JNK phosphorylates Bmf, which is normally sequestered by binding to dynein (via DYNLL2) and myosin V motor complexes. JNK-mediated phosphorylation of Bmf causes its release from the motor complexes, providing a mechanistic link between the JNK stress signaling pathway and mitochondrial (Bax/Bak-dependent) apoptosis.\",\n      \"method\": \"In vitro kinase assay, co-immunoprecipitation, Bax/Bak-dependent apoptosis readout, JNK gene disruption\",\n      \"journal\": \"Proceedings of the National Academy of Sciences\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — in vitro kinase assay combined with genetic loss-of-function and functional apoptosis readout\",\n      \"pmids\": [\"12591950\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"CDK11p58 phosphorylates PAK1 at Ser174, and this phosphorylation event promotes the recruitment of PAK1 into a myosin V motor complex through binding to dynein light chain 2 (DYNLL2). The phosphomimetic PAK1(S174E) bound DYNLL2 and accelerated mitotic progression in a nocodazole-blocked cell model, whereas the non-phosphorylatable PAK1(S174A) had the opposite effect, indicating DYNLL2 mediates PAK1's role in mitosis downstream of CDK11p58.\",\n      \"method\": \"Co-immunoprecipitation, site-directed mutagenesis (S174A/S174E), nocodazole cell-cycle block assay, kinase substrate mapping\",\n      \"journal\": \"Journal of Biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — Co-IP with mutagenesis and functional cell-cycle assay, single lab\",\n      \"pmids\": [\"19520772\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"AMBRA1 tethers the BECLIN1-VPS34 autophagy core complex to the cytoskeleton through interaction with dynein light chains 1 and 2 (including DYNLL2). Upon autophagy induction, ULK1 phosphorylates AMBRA1, releasing the complex from dynein. This releases the autophagy complex to the endoplasmic reticulum, enabling autophagosome nucleation. Thus DYNLL2 participates in cytoskeletal anchoring of the autophagy initiation machinery.\",\n      \"method\": \"Co-immunoprecipitation, ULK1 kinase assay, autophagy induction assays, subcellular fractionation, fluorescence microscopy\",\n      \"journal\": \"The Journal of Cell Biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — kinase assay, Co-IP, and direct imaging of autophagosome relocalization with functional consequence\",\n      \"pmids\": [\"20921139\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"DYNLL2 interacts with GKAP in dendritic spines and this interaction stabilizes scaffolding protein expression at the postsynaptic density (PSD) and enhances synaptic NMDA receptor activity. BRET imaging showed the interaction occurs in spines; electrophysiological recording confirmed that disrupting the GKAP-DYNLL2 interaction reduces NMDA receptor-mediated currents. Sustained synaptic activity further promotes GKAP-DYNLL2 interaction, revealing an activity-dependent regulatory pathway.\",\n      \"method\": \"BRET imaging in living neurons, immunostaining, electrophysiological recording of NMDA receptor currents\",\n      \"journal\": \"Journal of Cell Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (BRET, imaging, electrophysiology) in living neurons with clear functional readout\",\n      \"pmids\": [\"22328512\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Using two-photon scanning number and brightness (sN&B) fluorescence fluctuation microscopy in living neurons, DYNLL2 dimerization was found to be required for its interaction with GKAP, which in turn potentiates GKAP self-association. In dendritic shafts, DYNLL2-GKAP complexes consist mainly of two DLC2 and two GKAP monomers, while in spines the hetero-complexes are much larger (~16 DYNLL2 and ~13 GKAP monomers). Disrupting the GKAP-DYNLL2 interaction decreased spine-preferential GKAP localization and inhibited NMDA receptor activity, demonstrating DYNLL2 functions as a dimerization engine organizing the postsynaptic scaffold.\",\n      \"method\": \"Two-photon scanning number and brightness (sN&B) fluorescence fluctuation microscopy, electrophysiology, fluorescence imaging in living neurons\",\n      \"journal\": \"Journal of Cell Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — quantitative single-molecule microscopy combined with electrophysiology and disruption experiments, multiple orthogonal approaches\",\n      \"pmids\": [\"24938595\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"NMR spectroscopy, X-ray crystallography, and molecular dynamics simulations characterized DYNLL2 binding to the myosin 5a (myo5a) tail. The DYNLL2-binding region of myo5a resides in an intrinsically disordered domain with nascent helical character in the free form, which folds into a β-strand upon DYNLL2 binding. One peptide is accommodated in each parallel DYNLL2 binding groove. The myo5a motif has extended flanking contacts beyond the core consensus: N-terminal extension folds back partially blocking the β-sheet edge, while C-terminal extension contacts the dimer interface and interacts with symmetry-related residues of the second myo5a peptide.\",\n      \"method\": \"NMR spectroscopy, X-ray crystallography, molecular dynamics simulations\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — atomic-resolution structure combined with NMR dynamics and MD simulation, multiple orthogonal structural methods\",\n      \"pmids\": [\"25312846\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"DYNLL2 protein levels in oxytocin neurons of the hypothalamic paraventricular nucleus (PVN) are regulated by fasted/fed states, being higher in the fed condition. In fed animals, NMDA receptor-mediated EPSCs on oxytocin neurons were increased. DYNLL2 upregulation correlated with increased NMDA receptor-mediated synaptic input, consistent with a role for DYNLL2 in NMDA receptor trafficking to the postsynaptic site in the context of metabolic state-dependent synaptic plasticity.\",\n      \"method\": \"Whole-cell electrophysiology (mEPSC and NMDA-EPSC recording), western blot for DYNLL2 protein, immunostaining\",\n      \"journal\": \"Neuropeptides\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — correlative western blot and electrophysiology in vivo, single lab, no direct mechanistic manipulation of DYNLL2\",\n      \"pmids\": [\"26344333\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In chicken primary myoblasts, DYNLL2 was identified as a hub gene controlling myoblast differentiation. miR-148a-3p was found to directly target DYNLL2 mRNA; overexpression of miR-148a-3p suppressed DYNLL2 and promoted myosin heavy chain (MYHC) expression and myoblast differentiation. This defines a miR-148a-3p → DYNLL2 regulatory axis in skeletal muscle fiber development.\",\n      \"method\": \"WGCNA on transcriptome data, miRNA transfection in chicken primary myoblasts, western blot for MYHC protein\",\n      \"journal\": \"BMC Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — functional miRNA overexpression with protein readout, single lab, chicken ortholog\",\n      \"pmids\": [\"35379193\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DYNLL2 interacts directly with PAK1 to regulate endocytosis of Gram-negative bacterial outer membrane vesicles (OMVs) in macrophages/monocytes. The DYNLL2-PAK1 complex facilitates cytosolic LPS release and subsequent Caspase-11 inflammasome activation, triggering pyroptosis via Gasdermin D (GSDMD) cleavage. Depletion of either DYNLL2 or PAK1 suppressed OMV internalization, Caspase-11/GSDMD cleavage, and proinflammatory cytokine release. The flavonoid Oroxylin A was identified as an inhibitor of the DYNLL2-PAK1 interaction that blocks Caspase-11-dependent pyroptosis in vitro and improves survival in murine endotoxemia models.\",\n      \"method\": \"Co-immunoprecipitation, DYNLL2/PAK1 knockdown, endotoxemia mouse model, Caspase-11/GSDMD cleavage assay, virtual screening, Oroxylin A pharmacological inhibition\",\n      \"journal\": \"Biochemical Pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — Co-IP, genetic depletion with defined pyroptosis readout, in vivo model, and pharmacological validation; single lab\",\n      \"pmids\": [\"41360226\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DYNLL2 (dynein light chain LC8-type 2) is a conserved homodimeric hub protein that, through its paired binding grooves, sequesters diverse partners including the pro-apoptotic protein Bmf (released by JNK phosphorylation or anoikis), the autophagy regulator AMBRA1 (released by ULK1 phosphorylation to enable autophagosome formation), PAK1 (via CDK11p58-mediated phosphorylation, promoting mitotic progression and, in macrophages, OMV endocytosis and Caspase-11 pyroptosis), and the postsynaptic scaffold protein GKAP (where DYNLL2 dimerization drives formation of large hetero-oligomeric complexes in dendritic spines that stabilize the PSD and enhance NMDA receptor activity), while structural studies reveal that binding partners fold from intrinsically disordered regions into β-strands within the DYNLL2 groove with extended flanking contacts that can modify quaternary organization of full-length partners.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"DYNLL2 encompasses two functionally distinct identities in the literature: a dynein light chain (LC8-type) homodimer that serves as a dimerization hub, and the RhoGAP/START-domain protein DLC2 (STARD13) that inactivates Rho-family GTPases. As a RhoGAP, DLC2 specifically inactivates RhoA and Cdc42, thereby suppressing stress fiber formation, controlling endothelial cell migration and angiogenesis, coordinating mitotic spindle positioning through Kif1B and the Cdc42/mDia3 axis, and modulating RhoA/ERK-dependent inflammatory pain signaling [PMID:16217026, PMID:20208559, PMID:25518808, PMID:22204965]. DLC2 localizes to focal adhesions via an N-terminal FAT region that binds tensin2, to mitochondria via its START domain, and uses its atypical four-helix SAM domain to interact with TAp73α and promote its ubiquitination [PMID:19250640, PMID:16364308, PMID:17519008, PMID:30094094]. As a dynein light chain hub, DYNLL2 forms homodimers whose binding grooves accommodate β-strand-forming linear motifs in partners such as myosin 5a and GKAP/DLGAP1; dimerization-dependent oligomerization of GKAP in dendritic spines stabilizes the postsynaptic scaffold and potentiates NMDA receptor activity, while the DYNLL2–PAK1 interaction regulates bacterial outer membrane vesicle endocytosis and Caspase-11-dependent pyroptosis [PMID:25312846, PMID:24938595, PMID:22328512, PMID:41360226].\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Establishing that DLC2 functions as a RhoGAP specific for RhoA and Cdc42 resolved the question of which GTPases it targets and demonstrated that GAP activity is essential for its growth-suppressive function.\",\n      \"evidence\": \"RhoA pull-down activity assay, GAP-domain point mutagenesis, ectopic expression in fibroblasts and HepG2 cells\",\n      \"pmids\": [\"16217026\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of GAP-domain specificity for RhoA/Cdc42 over other Rho GTPases not resolved\", \"Endogenous regulation of DLC2 GAP activity unknown\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Demonstrating that the START domain directs DLC2 to mitochondria identified the lipid-transfer domain as a localization determinant, raising the question of whether it also transfers lipids.\",\n      \"evidence\": \"Fluorescence co-localization and subcellular fractionation with START-domain deletion constructs\",\n      \"pmids\": [\"16364308\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No lipid-binding or lipid-transfer activity demonstrated for the START domain\", \"Functional consequence of mitochondrial targeting not established\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Solving the NMR structure of DLC2's SAM domain revealed an atypical four-helix bundle, suggesting a non-canonical interaction repertoire distinct from standard SAM domains.\",\n      \"evidence\": \"NMR solution structure determination of isolated SAM domain\",\n      \"pmids\": [\"17519008\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No binding partners for the SAM domain were identified at this stage\", \"Functional significance of the atypical fold not tested in cells\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Mapping the N-terminal FAT region as the focal adhesion targeting determinant and identifying tensin2 as its binding partner linked DLC2 to integrin-associated adhesion signaling and revealed competition with the related RhoGAP DLC1.\",\n      \"evidence\": \"Fluorescence localization of deletion constructs, direct binding assay with tensin2, competition assay with DLC1\",\n      \"pmids\": [\"19250640\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of tensin2-FAT interaction not determined\", \"Functional consequence of DLC1-DLC2 competition at focal adhesions not tested\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Showing that CDK11p58-mediated phosphorylation of PAK1 at Ser174 promotes PAK1–DYNLL2 binding and recruits PAK1 into a myosin V complex established a phospho-regulated link between DYNLL2 and mitotic kinase signaling.\",\n      \"evidence\": \"In vitro kinase assay, phospho-site mutagenesis (S174A/S174E), co-immunoprecipitation, nocodazole block cell cycle assay\",\n      \"pmids\": [\"19520772\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Only phospho-mimetic mutant tested; endogenous phospho-PAK1–DYNLL2 interaction not confirmed\", \"Mechanism by which this complex accelerates mitotic progression not defined\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Genetic epistasis in endothelial cells and DLC2-knockout mice placed DLC2 as a physiological upstream negative regulator of RhoA in angiogenesis, extending its role beyond tumor suppression.\",\n      \"evidence\": \"RNAi knockdown with RhoA co-silencing rescue, matrigel angiogenesis assay in DLC2-knockout mice\",\n      \"pmids\": [\"20208559\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Endothelial-specific signaling partners of DLC2 not identified\", \"Whether the START or SAM domains contribute to the angiogenic phenotype is unknown\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"DLC2-knockout mice displaying inflammatory hyperalgesia with elevated spinal RhoA and ERK1/2 activity revealed a non-oncogenic in vivo role for DLC2 in pain modulation.\",\n      \"evidence\": \"DLC2-knockout mice, RhoA pull-down, phospho-ERK immunostaining, behavioral pain tests after formalin injection\",\n      \"pmids\": [\"22204965\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cell type within the spinal cord mediating the effect not identified\", \"Whether pain phenotype is RhoA-dependent was not tested by rescue\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Identifying the DYNLL2–GKAP interaction in dendritic spines and its requirement for synaptic NMDA receptor potentiation established DYNLL2 as a postsynaptic scaffold organizer.\",\n      \"evidence\": \"BRET imaging in neurons, immunostaining, electrophysiological recording of NMDA receptor currents\",\n      \"pmids\": [\"22328512\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Stoichiometry and oligomeric state of the complex not yet resolved\", \"Upstream signals regulating the DYNLL2-GKAP interaction not defined\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Quantitative single-molecule imaging showed DYNLL2 dimerization drives GKAP into large hetero-oligomeric assemblies (~16:13 stoichiometry) specifically in spines, establishing a 'dimerization engine' mechanism for postsynaptic scaffold organization.\",\n      \"evidence\": \"Two-photon scanning number and brightness fluorescence fluctuation microscopy in living neurons, disruption of GKAP-DLC2 interaction\",\n      \"pmids\": [\"24938595\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural model of the higher-order oligomer not available\", \"Whether other DYNLL2 partners compete with GKAP for binding in spines is unknown\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Atomic-resolution structures of DYNLL2 bound to the myosin 5a tail revealed that disordered linear motifs fold into β-strands within each DYNLL2 groove, defining the structural basis of partner recognition by the LC8-type dimer.\",\n      \"evidence\": \"NMR spectroscopy, X-ray crystallography, molecular dynamics simulations\",\n      \"pmids\": [\"25312846\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of DYNLL2–myo5a interaction on cargo transport not tested in cells\", \"Whether this binding mode generalizes to all DYNLL2 partners awaits further structures\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstrating that DLC2 interacts with kinesin Kif1B to restrict Cdc42 activity and ensure planar spindle positioning linked the RhoGAP function to mitotic fidelity and genome stability.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation, live-cell spindle imaging, Cdc42 activity assay, siRNA depletion in epithelial cells\",\n      \"pmids\": [\"25518808\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct vs. indirect nature of Kif1B-DLC2 interaction not fully resolved\", \"Whether DLC2 GAP activity is spatially regulated at the spindle is unknown\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Identifying the SAM domain as the interface for DLC2–TAp73α interaction and showing it promotes TAp73α ubiquitination assigned a protein-protein interaction function to the atypical SAM fold resolved a decade earlier.\",\n      \"evidence\": \"Co-immunoprecipitation, ubiquitination assay, SAM domain deletion mutagenesis, cell proliferation/apoptosis assays\",\n      \"pmids\": [\"30094094\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"E3 ligase mediating TAp73α ubiquitination downstream of DLC2 not identified\", \"Whether SAM domain binds TAp73α directly or via an adaptor is not resolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"DYNLL2–PAK1 interaction was shown to regulate bacterial OMV endocytosis and Caspase-11/GSDMD-dependent pyroptosis, extending DYNLL2's role to innate immune signaling against gram-negative bacteria.\",\n      \"evidence\": \"siRNA depletion, co-immunoprecipitation, OMV internalization assay, Caspase-11/GSDMD cleavage, murine endotoxemia model\",\n      \"pmids\": [\"41360226\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which DYNLL2-PAK1 promotes OMV endocytosis (receptor, membrane trafficking step) not defined\", \"Whether the phospho-Ser174 regulation identified earlier applies in the pyroptosis context is untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A unifying model integrating the LC8-type dimerization hub and the RhoGAP/START/SAM multi-domain activities — and whether the gene symbol DYNLL2 in different studies truly refers to the same polypeptide versus the co-named STARD13/DLC2 — remains to be formally clarified at the mechanistic level.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No lipid-binding or transfer activity demonstrated for the START domain\", \"Structural basis of full-length DLC2 auto-regulation (inter-domain interactions) is unknown\", \"Tissue-specific functions and redundancy with DLC1 are poorly mapped\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 5, 9, 10]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [7, 8]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [4, 7, 12]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [7, 8]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0162582\", \"supporting_discovery_ids\": [0, 5, 9]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 5, 9]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [4, 9]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [12]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [6, 7]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"GKAP\", \"PAK1\", \"MYO5A\", \"KIF1B\", \"TNS2\", \"TAP73\"],\n    \"other_free_text\": []\n  }\n}\n```\n\nWait, I need to fix the pathway entries. I accidentally included a GO term format. Let me correct:\n\n```json\n{\n  \"mechanistic_narrative\": \"DYNLL2 encompasses two functionally distinct identities in the literature: a dynein light chain (LC8-type) homodimer that serves as a dimerization hub, and the RhoGAP/START-domain protein DLC2 (STARD13) that inactivates Rho-family GTPases. As a RhoGAP, DLC2 specifically inactivates RhoA and Cdc42, thereby suppressing stress fiber formation, controlling endothelial cell migration and angiogenesis, coordinating mitotic spindle positioning through Kif1B and the Cdc42/mDia3 axis, and modulating RhoA/ERK-dependent inflammatory pain signaling [PMID:16217026, PMID:20208559, PMID:25518808, PMID:22204965]. DLC2 localizes to focal adhesions via an N-terminal FAT region that binds tensin2, to mitochondria via its START domain, and uses its atypical four-helix SAM domain to interact with TAp73α and promote its ubiquitination [PMID:19250640, PMID:16364308, PMID:17519008, PMID:30094094]. As a dynein light chain hub, DYNLL2 forms homodimers whose binding grooves accommodate β-strand-forming linear motifs in partners such as myosin 5a and GKAP/DLGAP1; dimerization-dependent oligomerization of GKAP in dendritic spines stabilizes the postsynaptic scaffold and potentiates NMDA receptor activity, while the DYNLL2–PAK1 interaction regulates bacterial outer membrane vesicle endocytosis and Caspase-11-dependent pyroptosis [PMID:25312846, PMID:24938595, PMID:22328512, PMID:41360226].\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Establishing that DLC2 functions as a RhoGAP specific for RhoA and Cdc42 resolved the question of which GTPases it targets and demonstrated that GAP activity is essential for its growth-suppressive function.\",\n      \"evidence\": \"RhoA pull-down activity assay, GAP-domain point mutagenesis, ectopic expression in fibroblasts and HepG2 cells\",\n      \"pmids\": [\"16217026\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of GAP-domain specificity for RhoA/Cdc42 over other Rho GTPases not resolved\", \"Endogenous regulation of DLC2 GAP activity unknown\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Demonstrating that the START domain directs DLC2 to mitochondria identified the lipid-transfer domain as a localization determinant, raising the question of whether it also transfers lipids.\",\n      \"evidence\": \"Fluorescence co-localization and subcellular fractionation with START-domain deletion constructs\",\n      \"pmids\": [\"16364308\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No lipid-binding or lipid-transfer activity demonstrated for the START domain\", \"Functional consequence of mitochondrial targeting not established\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Solving the NMR structure of DLC2's SAM domain revealed an atypical four-helix bundle, suggesting a non-canonical interaction repertoire distinct from standard SAM domains.\",\n      \"evidence\": \"NMR solution structure determination of isolated SAM domain\",\n      \"pmids\": [\"17519008\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No binding partners for the SAM domain were identified at this stage\", \"Functional significance of the atypical fold not tested in cells\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Mapping the N-terminal FAT region as the focal adhesion targeting determinant and identifying tensin2 as its binding partner linked DLC2 to integrin-associated adhesion signaling and revealed competition with the related RhoGAP DLC1.\",\n      \"evidence\": \"Fluorescence localization of deletion constructs, direct binding assay with tensin2, competition assay with DLC1\",\n      \"pmids\": [\"19250640\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of tensin2-FAT interaction not determined\", \"Functional consequence of DLC1-DLC2 competition at focal adhesions not tested\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Showing that CDK11p58-mediated phosphorylation of PAK1 at Ser174 promotes PAK1–DYNLL2 binding and recruits PAK1 into a myosin V complex established a phospho-regulated link between DYNLL2 and mitotic kinase signaling.\",\n      \"evidence\": \"In vitro kinase assay, phospho-site mutagenesis (S174A/S174E), co-immunoprecipitation, nocodazole block cell cycle assay\",\n      \"pmids\": [\"19520772\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Only phospho-mimetic mutant tested; endogenous phospho-PAK1–DYNLL2 interaction not confirmed\", \"Mechanism by which this complex accelerates mitotic progression not defined\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Genetic epistasis in endothelial cells and DLC2-knockout mice placed DLC2 as a physiological upstream negative regulator of RhoA in angiogenesis, extending its role beyond tumor suppression.\",\n      \"evidence\": \"RNAi knockdown with RhoA co-silencing rescue, matrigel angiogenesis assay in DLC2-knockout mice\",\n      \"pmids\": [\"20208559\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Endothelial-specific signaling partners of DLC2 not identified\", \"Whether the START or SAM domains contribute to the angiogenic phenotype is unknown\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"DLC2-knockout mice displaying inflammatory hyperalgesia with elevated spinal RhoA and ERK1/2 activity revealed a non-oncogenic in vivo role for DLC2 in pain modulation.\",\n      \"evidence\": \"DLC2-knockout mice, RhoA pull-down, phospho-ERK immunostaining, behavioral pain tests after formalin injection\",\n      \"pmids\": [\"22204965\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cell type within the spinal cord mediating the effect not identified\", \"Whether pain phenotype is RhoA-dependent was not tested by rescue\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Identifying the DYNLL2–GKAP interaction in dendritic spines and its requirement for synaptic NMDA receptor potentiation established DYNLL2 as a postsynaptic scaffold organizer.\",\n      \"evidence\": \"BRET imaging in neurons, immunostaining, electrophysiological recording of NMDA receptor currents\",\n      \"pmids\": [\"22328512\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Stoichiometry and oligomeric state of the complex not yet resolved\", \"Upstream signals regulating the DYNLL2-GKAP interaction not defined\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Quantitative single-molecule imaging showed DYNLL2 dimerization drives GKAP into large hetero-oligomeric assemblies (~16:13 stoichiometry) specifically in spines, establishing a 'dimerization engine' mechanism for postsynaptic scaffold organization.\",\n      \"evidence\": \"Two-photon scanning number and brightness fluorescence fluctuation microscopy in living neurons, disruption of GKAP-DLC2 interaction\",\n      \"pmids\": [\"24938595\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural model of the higher-order oligomer not available\", \"Whether other DYNLL2 partners compete with GKAP for binding in spines is unknown\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Atomic-resolution structures of DYNLL2 bound to the myosin 5a tail revealed that disordered linear motifs fold into β-strands within each DYNLL2 groove, defining the structural basis of partner recognition by the LC8-type dimer.\",\n      \"evidence\": \"NMR spectroscopy, X-ray crystallography, molecular dynamics simulations\",\n      \"pmids\": [\"25312846\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of DYNLL2–myo5a interaction on cargo transport not tested in cells\", \"Whether this binding mode generalizes to all DYNLL2 partners awaits further structures\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstrating that DLC2 interacts with kinesin Kif1B to restrict Cdc42 activity and ensure planar spindle positioning linked the RhoGAP function to mitotic fidelity and genome stability.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation, live-cell spindle imaging, Cdc42 activity assay, siRNA depletion in epithelial cells\",\n      \"pmids\": [\"25518808\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct vs. indirect nature of Kif1B-DLC2 interaction not fully resolved\", \"Whether DLC2 GAP activity is spatially regulated at the spindle is unknown\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Identifying the SAM domain as the interface for DLC2–TAp73α interaction and showing it promotes TAp73α ubiquitination assigned a protein-protein interaction function to the atypical SAM fold resolved a decade earlier.\",\n      \"evidence\": \"Co-immunoprecipitation, ubiquitination assay, SAM domain deletion mutagenesis, cell proliferation/apoptosis assays\",\n      \"pmids\": [\"30094094\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"E3 ligase mediating TAp73α ubiquitination downstream of DLC2 not identified\", \"Whether SAM domain binds TAp73α directly or via an adaptor is not resolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"DYNLL2–PAK1 interaction was shown to regulate bacterial OMV endocytosis and Caspase-11/GSDMD-dependent pyroptosis, extending DYNLL2's role to innate immune signaling against gram-negative bacteria.\",\n      \"evidence\": \"siRNA depletion, co-immunoprecipitation, OMV internalization assay, Caspase-11/GSDMD cleavage, murine endotoxemia model\",\n      \"pmids\": [\"41360226\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which DYNLL2-PAK1 promotes OMV endocytosis not defined\", \"Whether the phospho-Ser174 regulation identified earlier applies in the pyroptosis context is untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A unifying model integrating the LC8-type dimerization hub and the RhoGAP/START/SAM multi-domain activities — and clarifying whether findings attributed to 'DLC2' in different studies consistently refer to the same gene product — remains to be established.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No lipid-binding or transfer activity demonstrated for the START domain\", \"Structural basis of full-length DLC2 auto-regulation and inter-domain interactions is unknown\", \"Tissue-specific functions and redundancy with DLC1 are poorly mapped\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 5, 9, 10]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [7, 8]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [4, 7, 12]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 5, 9, 10]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [4, 9]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [12]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [6, 7]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"GKAP\", \"PAK1\", \"MYO5A\", \"KIF1B\", \"TNS2\", \"TP73\"],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"DYNLL2 is a conserved homodimeric hub protein of the LC8 dynein light chain family that functions as a dimerization engine and cytoskeletal anchor, sequestering diverse partners through paired binding grooves until signal-dependent phosphorylation triggers their release. It sequesters the pro-apoptotic BH3-only protein Bmf on myosin V motor complexes; JNK phosphorylation or anoikis releases Bmf to activate Bax/Bak-dependent apoptosis [PMID:11546872, PMID:12591950]. DYNLL2 similarly tethers the AMBRA1–Beclin 1–VPS34 autophagy initiation complex to the cytoskeleton, with ULK1 phosphorylation of AMBRA1 liberating the complex for autophagosome nucleation [PMID:20921139], and recruits PAK1 downstream of CDK11p58 phosphorylation to promote mitotic progression and, in macrophages, OMV endocytosis leading to Caspase-11 inflammasome activation [PMID:19520772, PMID:41360226]. At excitatory synapses, DYNLL2 dimerization drives large-scale hetero-oligomerization of GKAP at the postsynaptic density, stabilizing the PSD-95 scaffold and enhancing NMDA receptor-mediated currents in an activity-dependent manner [PMID:22328512, PMID:24938595].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Identification of DYNLL2 as a postsynaptic density component that directly binds GKAP established its first known scaffolding interaction and linked it to the PSD-95–myosin V trafficking complex in dendritic spines.\",\n      \"evidence\": \"Yeast two-hybrid, co-IP from rat brain, immunogold EM\",\n      \"pmids\": [\"10844022\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether DYNLL2-GKAP binding is functionally required for synaptic transmission was untested\",\n        \"Stoichiometry and oligomeric state of the complex unknown\",\n        \"No distinction from DYNLL1 function at synapses\"\n      ]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Discovery that DYNLL2 sequesters the pro-apoptotic BH3-only protein Bmf on the actin cytoskeleton revealed a general mechanism — cytoskeletal anchoring of a death sensor — and showed that anoikis releases Bmf to trigger apoptosis.\",\n      \"evidence\": \"Co-IP, subcellular fractionation, anoikis and apoptosis assays in multiple cell types\",\n      \"pmids\": [\"11546872\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Phosphorylation-based mechanism of Bmf release was not yet defined\",\n        \"Whether DYNLL1 and DYNLL2 are redundant in Bmf sequestration was unclear\"\n      ]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Demonstration that JNK phosphorylates Bmf to cause its release from DYNLL2-containing motor complexes provided the upstream kinase signal linking stress-activated MAPK signaling to the cytoskeletal sequestration/release mechanism.\",\n      \"evidence\": \"In vitro JNK kinase assay, JNK knockout cells, Bax/Bak-dependent apoptosis readout\",\n      \"pmids\": [\"12591950\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Precise phospho-site(s) on Bmf that disrupt DYNLL2 binding not structurally mapped\",\n        \"In vivo physiological contexts for JNK-Bmf-DYNLL2 axis beyond UV damage not explored\"\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"CDK11p58-mediated phosphorylation of PAK1 at Ser174 was shown to promote PAK1 recruitment to DYNLL2, linking DYNLL2 to mitotic kinase signaling and cell-cycle progression.\",\n      \"evidence\": \"Co-IP with phosphomimetic/non-phosphorylatable PAK1 mutants, nocodazole cell-cycle block\",\n      \"pmids\": [\"19520772\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab study; independent replication pending\",\n        \"Whether DYNLL2 binding activates PAK1 catalytically or simply relocates it was not resolved\",\n        \"In vivo mitotic phenotype of DYNLL2 depletion not tested\"\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"DYNLL2 was found to anchor the AMBRA1–Beclin 1–VPS34 autophagy initiation complex to dynein/cytoskeleton; ULK1-mediated phosphorylation of AMBRA1 releases the complex for ER-localized autophagosome nucleation, extending the sequestration-and-release paradigm to autophagy.\",\n      \"evidence\": \"Co-IP, ULK1 kinase assay, autophagy induction, subcellular fractionation, fluorescence microscopy\",\n      \"pmids\": [\"20921139\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Relative contributions of DYNLL1 vs DYNLL2 to AMBRA1 tethering not separated\",\n        \"Structural basis of AMBRA1–DYNLL2 interaction unknown\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"BRET imaging and electrophysiology in living neurons demonstrated that the DYNLL2-GKAP interaction stabilizes the PSD and enhances NMDA receptor-mediated currents, with synaptic activity further promoting the interaction — establishing DYNLL2 as an activity-dependent regulator of excitatory synaptic strength.\",\n      \"evidence\": \"BRET in cultured neurons, NMDA-EPSC recording, immunostaining\",\n      \"pmids\": [\"22328512\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Quantitative stoichiometry of complexes in spines vs shafts not determined\",\n        \"Upstream signals regulating activity-dependent DYNLL2-GKAP association unidentified\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Quantitative fluorescence fluctuation microscopy revealed that DYNLL2 dimerization drives formation of large hetero-oligomeric GKAP–DYNLL2 assemblies preferentially in dendritic spines (~16 DYNLL2 + ~13 GKAP monomers), while shaft complexes are smaller tetramers — defining DYNLL2 as a dimerization engine for postsynaptic scaffold organization.\",\n      \"evidence\": \"Two-photon sN&B microscopy in living neurons, electrophysiology, disruption of GKAP-DYNLL2 binding\",\n      \"pmids\": [\"24938595\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism driving spine-specific oligomer growth vs shaft tetramer is unknown\",\n        \"Contribution of other PSD components to the large complex not assessed\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Atomic-resolution structures of DYNLL2 bound to the myosin 5a tail revealed that intrinsically disordered partner segments fold into β-strands within the DYNLL2 binding groove, with extended flanking contacts modifying quaternary organization — providing the structural basis for DYNLL2's role as a hub that orders disordered partners.\",\n      \"evidence\": \"NMR spectroscopy, X-ray crystallography, molecular dynamics simulation\",\n      \"pmids\": [\"25312846\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structures with other partners (Bmf, AMBRA1, GKAP) not yet solved\",\n        \"How flanking contacts influence selectivity among the many DYNLL2 partners is not clear\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"DYNLL2–PAK1 interaction was shown to regulate OMV endocytosis in macrophages, enabling cytosolic LPS release and Caspase-11/GSDMD-dependent pyroptosis, expanding DYNLL2's roles to innate immune signaling and identifying Oroxylin A as a pharmacological disruptor of this interaction.\",\n      \"evidence\": \"Co-IP, DYNLL2/PAK1 knockdown, Caspase-11/GSDMD cleavage assay, murine endotoxemia model, virtual screening and Oroxylin A treatment\",\n      \"pmids\": [\"41360226\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab finding; independent replication and structural validation of Oroxylin A binding site needed\",\n        \"Whether DYNLL2 directly controls vesicle trafficking machinery or acts solely through PAK1 kinase activity is unresolved\",\n        \"Specificity of DYNLL2 vs DYNLL1 in this innate immune pathway not tested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A unifying structural and selectivity model explaining how DYNLL2 discriminates among its many disordered partners and how phosphorylation at partner sites allosterically disrupts binding remains to be established, as does the degree of functional redundancy with the 93%-identical paralog DYNLL1 across its diverse cellular roles.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No systematic comparison of DYNLL1 vs DYNLL2 partner selectivity or knockout phenotypes\",\n        \"Structural basis of phosphorylation-induced partner release not determined for any partner\",\n        \"In vivo phenotype of DYNLL2-specific loss in mammalian systems not reported\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 5, 6, 7]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 1, 7]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 4, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 1, 4, 7]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [0, 5, 6]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"complexes\": [\n      \"Myosin V motor complex\",\n      \"Dynein complex (LC8 light chain)\",\n      \"PSD-95–GKAP–DYNLL2 postsynaptic scaffold\"\n    ],\n    \"partners\": [\n      \"GKAP\",\n      \"BMF\",\n      \"PAK1\",\n      \"AMBRA1\",\n      \"MYO5A\",\n      \"DLG4\",\n      \"BECN1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}