{"gene":"MOB4","run_date":"2026-04-28T18:30:28","timeline":{"discoveries":[{"year":2008,"finding":"MOB4 (Mob3/phocein) was identified as a component of the STRIPAK (striatin-interacting phosphatase and kinase) complex, which contains PP2A catalytic and scaffolding subunits, striatins, STRIP1/2, CCM3, and GCK III family kinases, establishing MOB4 as a member of this large multiprotein assembly.","method":"Iterative affinity purification/mass spectrometry (AP-MS)","journal":"Molecular & cellular proteomics : MCP","confidence":"High","confidence_rationale":"Tier 2 — reciprocal AP-MS with multiple subunits, foundational discovery replicated across many subsequent studies","pmids":["18782753"],"is_preprint":false},{"year":2011,"finding":"Striatin binds MOB4 (Mob3) at two distinct regions: one N-terminal (including the coiled-coil domain) and one more C-terminal (including the WD-repeat domain). MOB4 can associate with striatin sequences C-terminal to the Mst3 binding site and proximal to striatin-associated PP2A, consistent with a role for MOB4 in regulating Mst3 by PP2A within the STRIPAK complex.","method":"Structure-function analysis of striatin by deletion mutants, co-immunoprecipitation","journal":"BMC biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 — multiple deletion constructs with co-IP validation in single lab","pmids":["21985334"],"is_preprint":false},{"year":2018,"finding":"MST4 forms a complex with MOB4 in a phosphorylation-dependent manner, and the overall structure of the MST4-MOB4 complex resembles that of the MST1-MOB1 complex. MST4-MOB4 promotes growth and migration of PANC-1 cells (oncogenic), contrasting with the tumor-suppressive MST1-MOB1 complex. MST4 and MOB4 disrupt assembly of the MST1-MOB1 complex through alternative pairing, thereby increasing YAP activity.","method":"Co-immunoprecipitation, structural analysis, cell growth/migration assays, YAP activity measurement","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (co-IP, structural, functional assays) in single study demonstrating mechanism","pmids":["30072378"],"is_preprint":false},{"year":2021,"finding":"Cryo-EM structure of the human STRIPAK core (PP2AA, PP2AC, STRN3, STRIP1, and MOB4) at 3.2-Å resolution revealed that STRIPAK is a noncanonical PP2A complex: it contains four copies of STRN3 forming an elongated homotetrameric scaffold and one copy each of PP2AA-C heterodimer, STRIP1, and MOB4. An inositol hexakisphosphate (IP6) was identified as a structural cofactor of STRIP1. Mutations at key subunit interfaces disrupt STRIPAK integrity and cause aberrant Hippo pathway activation.","method":"Cryo-EM structure determination at 3.2 Å, mutagenesis of interface residues, Hippo pathway activity assays","journal":"Nature structural & molecular biology","confidence":"High","confidence_rationale":"Tier 1 — cryo-EM structure with mutagenesis validation and functional consequence","pmids":["33633399"],"is_preprint":false},{"year":2010,"finding":"Drosophila DMob4 (phocein, ortholog of human MOB4) regulates axonal transport, membrane excitability, microtubule network organization, and synaptic bouton growth at neuromuscular junctions. Human phocein transgene rescues lethality of DMob4 null mutants, demonstrating conservation of function.","method":"Generation of null and hypomorphic alleles, in vivo cell biological and physiological analysis, RNAi, transgenic rescue with human phocein","journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience","confidence":"High","confidence_rationale":"Tier 2 — null alleles, multiple phenotypic readouts, cross-species rescue in single study","pmids":["20392941"],"is_preprint":false},{"year":2008,"finding":"Drosophila Mob4 (ortholog of human MOB4) localizes to the nucleus during interphase and to spindle poles and kinetochores during mitosis. RNAi depletion of Mob4 causes kinetochore fiber (K fiber) splaying and loss of spindle pole focus both in the presence and absence of functional centrosomes, without substantially affecting Asp localization, indicating Mob4 controls a mitotic kinase that regulates K fiber focusing.","method":"RNAi screen, time-lapse microscopy of mitotic cells, Mob4-GFP live imaging","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 — RNAi with time-lapse imaging and GFP localization in single study","pmids":["18388316"],"is_preprint":false},{"year":2019,"finding":"In Drosophila neural stem cells (NSCs), Mob4 (along with Cka/STRIP and PP2A/Mts) is required for NSC reactivation from quiescence. Mob4 and Cka recruit PP2A/Mts into a complex with Hippo kinase, resulting in Hippo pathway inhibition, which promotes NSC reactivation and coordinates Hippo and InR/PI3K/Akt pathways.","method":"Transcriptome analysis of individual NSCs, genetic loss-of-function, co-immunoprecipitation showing Mob4/Cka/PP2A complex with Hippo kinase","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 — co-IP of complex plus genetic epistasis with defined cellular phenotype in Drosophila ortholog","pmids":["31167138"],"is_preprint":false},{"year":2020,"finding":"In planarians, inhibition of mob4 dramatically increases posterior body length through expansion of a wnt1+ signaling center in midline muscle cells. wnt1 is required for tail expansion after mob4 inhibition, identifying STRIPAK/MOB4 as a negative regulator of Wnt signaling that controls body scaling via stem cell-dependent regulation of signaling-center size.","method":"RNAi knockdown of mob4/striatin, epistasis with wnt1 RNAi, stem cell dependence assays","journal":"Current biology : CB","confidence":"Medium","confidence_rationale":"Tier 2 — genetic epistasis with multiple RNAi and defined molecular pathway in planarian ortholog","pmids":["31928872"],"is_preprint":false},{"year":2022,"finding":"In zebrafish, mob4 mutants have impaired actin biogenesis resulting in sarcomere defects and reduced myofibril number, while transgenic mob4 overexpression increases myofibril number. Genetic analysis revealed interaction of Mob4 with the actin-folding chaperonin TRiC, suggesting Mob4 impacts TRiC to control actin biogenesis and myofibril growth. mob4geh mutants also show defective microtubule networks. strn3-deficient zebrafish show similar characteristics, confirming Mob4 as a core STRIPAK component with a role in sarcomerogenesis.","method":"Forward genetic screen, reverse genetics (nonsense mutant), transgenic expression, genetic interaction with TRiC, electron microscopy and histology","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 — multiple mutant alleles, transgenic rescue, genetic interaction in vertebrate model","pmids":["35737712"],"is_preprint":false},{"year":2023,"finding":"Drosophila Mob4 is essential for spermatogenesis: loss leads to male sterility with defective spermatid individualization, expansion of outer axonemal microtubule doublets, and defective mitochondrial organization. STRIPAK components Strip and Cka show similarly impaired male fertility when depleted. Human MOB4 transgene rescues all phenotypes of Drosophila mob4 downregulation.","method":"RNAi knockdown, transmission electron microscopy of spermatids, transgenic rescue with human MOB4","journal":"Genetics","confidence":"Medium","confidence_rationale":"Tier 2 — RNAi with EM phenotyping and human gene rescue demonstrating conserved function","pmids":["37259670"],"is_preprint":false},{"year":2022,"finding":"MOB3A (a MOB4 subfamily member; MOB3A and MOB3C are the human MOB4 orthologs/paralogs) bypasses oncogene-induced senescence by inhibiting Hippo/MST/LATS signaling. Constitutive MOB3A membrane localization phenocopies OIS bypass seen with elevated YAP expression, and inhibition of MOB3 family members decreases proliferation and tumor growth.","method":"Kinase/kinase-regulatory protein library screen, constitutive expression constructs, membrane localization assays, Hippo pathway activity measurements, tumor growth assays","journal":"Molecular cancer research : MCR","confidence":"Medium","confidence_rationale":"Tier 2 — multiple functional assays demonstrating mechanism in single study; MOB3A is a direct paralog/family member of MOB4","pmids":["35046109"],"is_preprint":false},{"year":2023,"finding":"Proximity-dependent biotin identification (BioID) mapped the interactome of all seven human MOB proteins. MOB4 interactome data in HeLa and HEK293 cells established differential interaction networks. MOB3C (a MOB4 subfamily member) specifically interacts with 7 of 10 subunits of the RNase P complex, validated by affinity purification-mass spectrometry and pre-tRNA cleavage assays.","method":"BioID proximity labeling in HeLa and HEK293 cells, affinity purification-mass spectrometry, pre-tRNA cleavage assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — orthogonal validation (BioID + AP-MS + functional assay) for MOB3C; MOB4 interactome dataset generated but mechanistic follow-up focused on MOB3C","pmids":["37536630"],"is_preprint":false},{"year":2025,"finding":"MOB4 is identified as a coordinator of collective cell migration; MOB4 knockout MCF10A cells display increased collective migration with loss of migration orientation. MOB4 relocalizes to the front edge of leader and follower cells during wound healing. The role of MOB4 in controlling collective migration requires YAP1, as MOB4 KO cells fail to activate YAP1 and the phenotype is rescued by constitutively active YAP1.","method":"CRISPR/Cas9 knockout, wound healing assay, live imaging of cell migration, YAP1 activity assays, constitutively active YAP1 rescue","journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","confidence":"Medium","confidence_rationale":"Tier 2 — CRISPR KO with multiple functional assays and epistasis rescue in human cell line","pmids":["41276909"],"is_preprint":false},{"year":2025,"finding":"Striatin-3 and MOB4 are Rac1 interactors in Schwann cells. Schwann-cell-specific ablation of striatin-3 causes defects in lamellipodia formation, and conditional Schwann cell knockout for striatins causes severe delay in radial sorting. Deletion of Rac1 or striatin-1/3 causes defects in activation of Hippo pathway effectors YAP and TAZ and in expression of extracellular matrix receptors co-regulated by YAP/TAZ.","method":"Co-immunoprecipitation (Rac1 interaction), conditional cell-type-specific knockout, lamellipodia/radial sorting assays, Hippo pathway activity assays","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 — co-IP demonstrating Rac1-MOB4 interaction plus conditional KO with defined cellular and signaling phenotypes","pmids":["40056414"],"is_preprint":false},{"year":2018,"finding":"In striatal neurons, striatin-1 (a STRIPAK scaffold) recruits MOB4 (Mob3) to the complex, and a MOB4-binding-deficient striatin-1 construct fails to rescue the dendritic complexity and spine density phenotype caused by striatin-1 knockdown, establishing that MOB4 binding to striatin is required for striatin's role in striatal neuron dendritic development.","method":"shRNA knockdown, mutant rescue with PP2A- and Mob3-binding-deficient striatin-1 constructs, dendritic morphology and spine density analysis in primary neuronal cultures","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — loss-of-function with structure-function rescue constructs in primary neurons","pmids":["29802198"],"is_preprint":false}],"current_model":"MOB4 is a core, non-catalytic component of the STRIPAK complex (together with PP2A-A/C, striatins, STRIP1/2, and GCK-III kinases), where it occupies a defined position in the cryo-EM-resolved four-STRN3-subunit assembly; within this complex it contributes to PP2A-mediated dephosphorylation/inhibition of associated Ste20-like kinases, inhibition of Hippo (MST/LATS) signaling to promote YAP activity, and regulation of actin/microtubule cytoskeletal dynamics, collective cell migration, neural stem cell reactivation, spermatogenesis, and sarcomere assembly, while also forming a phosphorylation-dependent complex with MST4 that opposes MST1-MOB1-mediated Hippo activation."},"narrative":{"teleology":[{"year":2008,"claim":"The initial question of where MOB4 operates was answered by identifying it as a stable subunit of the newly defined STRIPAK complex containing PP2A, striatins, STRIP1/2, CCM3, and GCK-III kinases, establishing MOB4 as part of a major phosphatase–kinase signaling assembly rather than functioning as an isolated Hippo pathway component.","evidence":"Iterative AP-MS of multiple STRIPAK subunits in mammalian cells","pmids":["18782753"],"confidence":"High","gaps":["Stoichiometry and architecture of MOB4 within the complex unknown","Direct binding partners within STRIPAK not mapped"]},{"year":2008,"claim":"In parallel, the Drosophila ortholog DMob4 was shown to localize to spindle poles and kinetochores and to be required for kinetochore-fiber focusing during mitosis, suggesting MOB4 controls a mitotic kinase that organizes spindle microtubules.","evidence":"RNAi screen and Mob4-GFP live imaging in Drosophila S2 cells","pmids":["18388316"],"confidence":"Medium","gaps":["Identity of the regulated mitotic kinase not determined","Relevance of spindle function to mammalian MOB4 not tested"]},{"year":2010,"claim":"Null alleles of Drosophila DMob4 revealed conserved roles in axonal transport, microtubule network organization, and neuromuscular junction growth, and cross-species rescue by human phocein demonstrated functional conservation.","evidence":"Drosophila null/hypomorphic alleles with physiological and cell-biological phenotyping; transgenic rescue with human MOB4","pmids":["20392941"],"confidence":"High","gaps":["Mechanism by which MOB4 influences microtubule organization not resolved","Whether STRIPAK-dependent or -independent functions exist unclear"]},{"year":2011,"claim":"Structure–function mapping of striatin revealed that MOB4 binds at two distinct regions (N-terminal coiled-coil and C-terminal WD-repeat domain) positioned near the PP2A and Mst3 binding sites, providing a rationale for how MOB4 could facilitate PP2A-mediated regulation of GCK-III kinases.","evidence":"Co-immunoprecipitation of striatin deletion mutants with MOB4","pmids":["21985334"],"confidence":"Medium","gaps":["Direct effect of MOB4 on PP2A-mediated Mst3 dephosphorylation not demonstrated","Binding affinities not quantified"]},{"year":2018,"claim":"MOB4 binding to striatin-1 was shown to be functionally essential for striatal neuron dendritic arborization, as a MOB4-binding-deficient striatin-1 construct failed to rescue dendritic and spine phenotypes caused by striatin-1 knockdown.","evidence":"shRNA knockdown with structure–function rescue constructs in primary striatal neurons","pmids":["29802198"],"confidence":"Medium","gaps":["Downstream signaling targets of MOB4–striatin in neurons not identified","Whether MOB4 also contributes independently of striatin not addressed"]},{"year":2018,"claim":"The MST4–MOB4 complex was structurally and functionally characterized, revealing a phosphorylation-dependent interaction that mimics MST1–MOB1 but instead promotes cell growth and migration by disrupting MST1–MOB1 assembly and increasing YAP activity — establishing MOB4 as a direct antagonist of canonical Hippo tumor suppression.","evidence":"Co-immunoprecipitation, structural analysis, cell growth/migration assays, and YAP activity measurements in PANC-1 cells","pmids":["30072378"],"confidence":"High","gaps":["Whether MST4–MOB4 operates within or outside the STRIPAK complex unclear","In vivo relevance of this complex in tumorigenesis not tested"]},{"year":2019,"claim":"In Drosophila neural stem cells, Mob4 together with Cka/Strip recruits PP2A to Hippo kinase, inhibiting Hippo signaling to promote reactivation from quiescence — providing a defined developmental context for STRIPAK-mediated Hippo regulation.","evidence":"Genetic loss-of-function, co-immunoprecipitation of Mob4/Cka/PP2A/Hippo complex, single-NSC transcriptomics","pmids":["31167138"],"confidence":"Medium","gaps":["Direct biochemical demonstration of PP2A dephosphorylation of Hippo in this context lacking","Mammalian NSC relevance not established"]},{"year":2021,"claim":"A 3.2-Å cryo-EM structure of the STRIPAK core resolved MOB4's precise position in the complex — one copy associating with a four-STRN3 elongated scaffold, one PP2A-A/C heterodimer, and one STRIP1 — and interface mutations disrupting STRIPAK integrity caused aberrant Hippo pathway activation, providing atomic-level understanding of how the assembly controls signaling.","evidence":"Cryo-EM structure determination, interface mutagenesis, Hippo pathway activity assays","pmids":["33633399"],"confidence":"High","gaps":["How GCK-III kinases and CCM3 integrate into the core structure not resolved","Conformational dynamics and regulation of MOB4 within the complex unknown"]},{"year":2022,"claim":"Zebrafish mob4 mutants linked STRIPAK to sarcomere assembly and actin biogenesis through genetic interaction with the chaperonin TRiC, while mob4 overexpression increased myofibril number, establishing a cytoskeletal scaffolding role beyond signaling.","evidence":"Forward genetic screen, nonsense mutant, transgenic rescue, TRiC genetic interaction, electron microscopy in zebrafish","pmids":["35737712"],"confidence":"Medium","gaps":["Whether MOB4–TRiC interaction is direct or mediated through other STRIPAK subunits unknown","Mammalian muscle relevance not demonstrated"]},{"year":2023,"claim":"MOB4 was shown to be essential for Drosophila spermatogenesis — controlling spermatid individualization, axonemal microtubule organization, and mitochondrial morphology — with human MOB4 rescuing all phenotypes, confirming deep functional conservation of STRIPAK-dependent cytoskeletal regulation.","evidence":"RNAi knockdown, transmission electron microscopy, human MOB4 transgenic rescue in Drosophila","pmids":["37259670"],"confidence":"Medium","gaps":["Which STRIPAK-dependent kinase targets drive spermatid phenotypes not identified","Role in mammalian spermatogenesis not tested"]},{"year":2025,"claim":"MOB4 was established as a coordinator of collective cell migration: knockout in MCF10A cells increased but disoriented migration, MOB4 relocalized to the leading edge during wound healing, and the phenotype required YAP1, as constitutively active YAP1 rescued orientation defects.","evidence":"CRISPR/Cas9 knockout, wound healing assay, live imaging, YAP1 epistasis rescue in MCF10A cells","pmids":["41276909"],"confidence":"Medium","gaps":["How MOB4 leading-edge localization is regulated unclear","Whether STRIPAK-associated phosphatase or kinase activity mediates the migration phenotype not dissected"]},{"year":2025,"claim":"MOB4 and STRN3 were identified as Rac1 interactors in Schwann cells, linking STRIPAK to lamellipodia formation, radial sorting, and YAP/TAZ-dependent extracellular matrix gene expression — broadening the signaling inputs (Rac1) and cell-type contexts of MOB4 function.","evidence":"Co-immunoprecipitation of Rac1 with STRN3/MOB4, conditional Schwann cell knockout, lamellipodia and radial sorting assays","pmids":["40056414"],"confidence":"Medium","gaps":["Whether Rac1 binds MOB4 directly or via striatin not resolved","Relative contributions of MOB4 versus other STRIPAK subunits in Schwann cells not determined"]},{"year":null,"claim":"Key unresolved questions include: how MOB4 is regulated (post-translational modifications, conformational switching), whether MOB4 has STRIPAK-independent functions, how the MST4–MOB4 and STRIPAK-resident pools are partitioned in cells, and which direct kinase substrates mediate MOB4-dependent cytoskeletal and signaling phenotypes.","evidence":"","pmids":[],"confidence":"Low","gaps":["No post-translational modification map of MOB4 exists","No structural data for MOB4 within GCK-III kinase–containing holo-STRIPAK","STRIPAK-independent functions of MOB4 not tested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,1,3,14]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,3]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[5]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[12]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,3,6,10,12,13]}],"complexes":["STRIPAK"],"partners":["STRN","STRN3","STRIP1","MST4","PPP2CA","PPP2R1A","RAC1"],"other_free_text":[]},"mechanistic_narrative":"MOB4 is a conserved, non-catalytic scaffolding subunit of the STRIPAK complex that links PP2A phosphatase activity to regulation of Hippo signaling, cytoskeletal organization, and collective cell migration. Within STRIPAK, MOB4 binds striatin family proteins at both N-terminal and C-terminal regions, and the cryo-EM structure of the STRIPAK core places one copy of MOB4 alongside PP2A-A/C, STRN3 homotetramer, and STRIP1, with interface mutations causing aberrant Hippo pathway activation [PMID:33633399, PMID:21985334]. MOB4 also forms a phosphorylation-dependent complex with the GCK-III kinase MST4 that structurally mimics MST1–MOB1, and this MST4–MOB4 complex antagonizes canonical Hippo signaling by disrupting MST1–MOB1 assembly and thereby promoting YAP activity, cell growth, and migration [PMID:30072378]. Conserved organismal functions include regulation of axonal transport and microtubule organization at neuromuscular junctions, neural stem cell reactivation from quiescence via Hippo pathway inhibition, spermatid individualization, and sarcomere assembly through genetic interaction with the actin-folding chaperonin TRiC, with human MOB4 transgenes rescuing Drosophila and zebrafish loss-of-function phenotypes [PMID:20392941, PMID:31167138, PMID:37259670, PMID:35737712]."},"prefetch_data":{"uniprot":{"accession":"Q9Y3A3","full_name":"MOB-like protein phocein","aliases":["2C4D","Class II mMOB1","Mob1 homolog 3","Mob3","Mps one binder kinase activator-like 3","Preimplantation protein 3"],"length_aa":225,"mass_kda":26.0,"function":"Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation","subcellular_location":"Cytoplasm, perinuclear region; Membrane; Golgi apparatus, Golgi stack membrane","url":"https://www.uniprot.org/uniprotkb/Q9Y3A3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/MOB4","classification":"Common Essential","n_dependent_lines":752,"n_total_lines":1208,"dependency_fraction":0.6225165562913907},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/MOB4","total_profiled":1310},"omim":[{"mim_id":"609361","title":"MOB FAMILY, MEMBER 4; MOB4","url":"https://www.omim.org/entry/609361"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MOB4"},"hgnc":{"alias_symbol":["MOB3","DKFZP564M112","CGI-95","2C4D","PHOCN"],"prev_symbol":["PREI3","MOBKL3"]},"alphafold":{"accession":"Q9Y3A3","domains":[{"cath_id":"1.20.140.30","chopping":"83-207","consensus_level":"medium","plddt":95.4407,"start":83,"end":207}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y3A3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y3A3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y3A3-F1-predicted_aligned_error_v6.png","plddt_mean":90.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MOB4","jax_strain_url":"https://www.jax.org/strain/search?query=MOB4"},"sequence":{"accession":"Q9Y3A3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9Y3A3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9Y3A3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y3A3"}},"corpus_meta":[{"pmid":"18782753","id":"PMC_18782753","title":"A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein.","date":"2008","source":"Molecular & cellular proteomics : MCP","url":"https://pubmed.ncbi.nlm.nih.gov/18782753","citation_count":301,"is_preprint":false},{"pmid":"24333164","id":"PMC_24333164","title":"STRIPAK complexes: structure, biological function, and involvement in human diseases.","date":"2013","source":"The international journal of biochemistry & cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/24333164","citation_count":183,"is_preprint":false},{"pmid":"21666072","id":"PMC_21666072","title":"Identification and characterization of genes required for cell-to-cell fusion in Neurospora crassa.","date":"2011","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/21666072","citation_count":126,"is_preprint":false},{"pmid":"21985334","id":"PMC_21985334","title":"Protein phosphatase 2a 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\"journal\": \"Molecular & cellular proteomics : MCP\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal AP-MS with multiple subunits, foundational discovery replicated across many subsequent studies\",\n      \"pmids\": [\"18782753\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Striatin binds MOB4 (Mob3) at two distinct regions: one N-terminal (including the coiled-coil domain) and one more C-terminal (including the WD-repeat domain). MOB4 can associate with striatin sequences C-terminal to the Mst3 binding site and proximal to striatin-associated PP2A, consistent with a role for MOB4 in regulating Mst3 by PP2A within the STRIPAK complex.\",\n      \"method\": \"Structure-function analysis of striatin by deletion mutants, co-immunoprecipitation\",\n      \"journal\": \"BMC biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple deletion constructs with co-IP validation in single lab\",\n      \"pmids\": [\"21985334\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MST4 forms a complex with MOB4 in a phosphorylation-dependent manner, and the overall structure of the MST4-MOB4 complex resembles that of the MST1-MOB1 complex. MST4-MOB4 promotes growth and migration of PANC-1 cells (oncogenic), contrasting with the tumor-suppressive MST1-MOB1 complex. MST4 and MOB4 disrupt assembly of the MST1-MOB1 complex through alternative pairing, thereby increasing YAP activity.\",\n      \"method\": \"Co-immunoprecipitation, structural analysis, cell growth/migration assays, YAP activity measurement\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (co-IP, structural, functional assays) in single study demonstrating mechanism\",\n      \"pmids\": [\"30072378\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Cryo-EM structure of the human STRIPAK core (PP2AA, PP2AC, STRN3, STRIP1, and MOB4) at 3.2-Å resolution revealed that STRIPAK is a noncanonical PP2A complex: it contains four copies of STRN3 forming an elongated homotetrameric scaffold and one copy each of PP2AA-C heterodimer, STRIP1, and MOB4. An inositol hexakisphosphate (IP6) was identified as a structural cofactor of STRIP1. Mutations at key subunit interfaces disrupt STRIPAK integrity and cause aberrant Hippo pathway activation.\",\n      \"method\": \"Cryo-EM structure determination at 3.2 Å, mutagenesis of interface residues, Hippo pathway activity assays\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — cryo-EM structure with mutagenesis validation and functional consequence\",\n      \"pmids\": [\"33633399\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Drosophila DMob4 (phocein, ortholog of human MOB4) regulates axonal transport, membrane excitability, microtubule network organization, and synaptic bouton growth at neuromuscular junctions. Human phocein transgene rescues lethality of DMob4 null mutants, demonstrating conservation of function.\",\n      \"method\": \"Generation of null and hypomorphic alleles, in vivo cell biological and physiological analysis, RNAi, transgenic rescue with human phocein\",\n      \"journal\": \"The Journal of neuroscience : the official journal of the Society for Neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — null alleles, multiple phenotypic readouts, cross-species rescue in single study\",\n      \"pmids\": [\"20392941\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Drosophila Mob4 (ortholog of human MOB4) localizes to the nucleus during interphase and to spindle poles and kinetochores during mitosis. RNAi depletion of Mob4 causes kinetochore fiber (K fiber) splaying and loss of spindle pole focus both in the presence and absence of functional centrosomes, without substantially affecting Asp localization, indicating Mob4 controls a mitotic kinase that regulates K fiber focusing.\",\n      \"method\": \"RNAi screen, time-lapse microscopy of mitotic cells, Mob4-GFP live imaging\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — RNAi with time-lapse imaging and GFP localization in single study\",\n      \"pmids\": [\"18388316\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In Drosophila neural stem cells (NSCs), Mob4 (along with Cka/STRIP and PP2A/Mts) is required for NSC reactivation from quiescence. Mob4 and Cka recruit PP2A/Mts into a complex with Hippo kinase, resulting in Hippo pathway inhibition, which promotes NSC reactivation and coordinates Hippo and InR/PI3K/Akt pathways.\",\n      \"method\": \"Transcriptome analysis of individual NSCs, genetic loss-of-function, co-immunoprecipitation showing Mob4/Cka/PP2A complex with Hippo kinase\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — co-IP of complex plus genetic epistasis with defined cellular phenotype in Drosophila ortholog\",\n      \"pmids\": [\"31167138\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In planarians, inhibition of mob4 dramatically increases posterior body length through expansion of a wnt1+ signaling center in midline muscle cells. wnt1 is required for tail expansion after mob4 inhibition, identifying STRIPAK/MOB4 as a negative regulator of Wnt signaling that controls body scaling via stem cell-dependent regulation of signaling-center size.\",\n      \"method\": \"RNAi knockdown of mob4/striatin, epistasis with wnt1 RNAi, stem cell dependence assays\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis with multiple RNAi and defined molecular pathway in planarian ortholog\",\n      \"pmids\": [\"31928872\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In zebrafish, mob4 mutants have impaired actin biogenesis resulting in sarcomere defects and reduced myofibril number, while transgenic mob4 overexpression increases myofibril number. Genetic analysis revealed interaction of Mob4 with the actin-folding chaperonin TRiC, suggesting Mob4 impacts TRiC to control actin biogenesis and myofibril growth. mob4geh mutants also show defective microtubule networks. strn3-deficient zebrafish show similar characteristics, confirming Mob4 as a core STRIPAK component with a role in sarcomerogenesis.\",\n      \"method\": \"Forward genetic screen, reverse genetics (nonsense mutant), transgenic expression, genetic interaction with TRiC, electron microscopy and histology\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple mutant alleles, transgenic rescue, genetic interaction in vertebrate model\",\n      \"pmids\": [\"35737712\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Drosophila Mob4 is essential for spermatogenesis: loss leads to male sterility with defective spermatid individualization, expansion of outer axonemal microtubule doublets, and defective mitochondrial organization. STRIPAK components Strip and Cka show similarly impaired male fertility when depleted. Human MOB4 transgene rescues all phenotypes of Drosophila mob4 downregulation.\",\n      \"method\": \"RNAi knockdown, transmission electron microscopy of spermatids, transgenic rescue with human MOB4\",\n      \"journal\": \"Genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — RNAi with EM phenotyping and human gene rescue demonstrating conserved function\",\n      \"pmids\": [\"37259670\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"MOB3A (a MOB4 subfamily member; MOB3A and MOB3C are the human MOB4 orthologs/paralogs) bypasses oncogene-induced senescence by inhibiting Hippo/MST/LATS signaling. Constitutive MOB3A membrane localization phenocopies OIS bypass seen with elevated YAP expression, and inhibition of MOB3 family members decreases proliferation and tumor growth.\",\n      \"method\": \"Kinase/kinase-regulatory protein library screen, constitutive expression constructs, membrane localization assays, Hippo pathway activity measurements, tumor growth assays\",\n      \"journal\": \"Molecular cancer research : MCR\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple functional assays demonstrating mechanism in single study; MOB3A is a direct paralog/family member of MOB4\",\n      \"pmids\": [\"35046109\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Proximity-dependent biotin identification (BioID) mapped the interactome of all seven human MOB proteins. MOB4 interactome data in HeLa and HEK293 cells established differential interaction networks. MOB3C (a MOB4 subfamily member) specifically interacts with 7 of 10 subunits of the RNase P complex, validated by affinity purification-mass spectrometry and pre-tRNA cleavage assays.\",\n      \"method\": \"BioID proximity labeling in HeLa and HEK293 cells, affinity purification-mass spectrometry, pre-tRNA cleavage assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — orthogonal validation (BioID + AP-MS + functional assay) for MOB3C; MOB4 interactome dataset generated but mechanistic follow-up focused on MOB3C\",\n      \"pmids\": [\"37536630\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MOB4 is identified as a coordinator of collective cell migration; MOB4 knockout MCF10A cells display increased collective migration with loss of migration orientation. MOB4 relocalizes to the front edge of leader and follower cells during wound healing. The role of MOB4 in controlling collective migration requires YAP1, as MOB4 KO cells fail to activate YAP1 and the phenotype is rescued by constitutively active YAP1.\",\n      \"method\": \"CRISPR/Cas9 knockout, wound healing assay, live imaging of cell migration, YAP1 activity assays, constitutively active YAP1 rescue\",\n      \"journal\": \"Advanced science (Weinheim, Baden-Wurttemberg, Germany)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — CRISPR KO with multiple functional assays and epistasis rescue in human cell line\",\n      \"pmids\": [\"41276909\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Striatin-3 and MOB4 are Rac1 interactors in Schwann cells. Schwann-cell-specific ablation of striatin-3 causes defects in lamellipodia formation, and conditional Schwann cell knockout for striatins causes severe delay in radial sorting. Deletion of Rac1 or striatin-1/3 causes defects in activation of Hippo pathway effectors YAP and TAZ and in expression of extracellular matrix receptors co-regulated by YAP/TAZ.\",\n      \"method\": \"Co-immunoprecipitation (Rac1 interaction), conditional cell-type-specific knockout, lamellipodia/radial sorting assays, Hippo pathway activity assays\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — co-IP demonstrating Rac1-MOB4 interaction plus conditional KO with defined cellular and signaling phenotypes\",\n      \"pmids\": [\"40056414\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"In striatal neurons, striatin-1 (a STRIPAK scaffold) recruits MOB4 (Mob3) to the complex, and a MOB4-binding-deficient striatin-1 construct fails to rescue the dendritic complexity and spine density phenotype caused by striatin-1 knockdown, establishing that MOB4 binding to striatin is required for striatin's role in striatal neuron dendritic development.\",\n      \"method\": \"shRNA knockdown, mutant rescue with PP2A- and Mob3-binding-deficient striatin-1 constructs, dendritic morphology and spine density analysis in primary neuronal cultures\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function with structure-function rescue constructs in primary neurons\",\n      \"pmids\": [\"29802198\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MOB4 is a core, non-catalytic component of the STRIPAK complex (together with PP2A-A/C, striatins, STRIP1/2, and GCK-III kinases), where it occupies a defined position in the cryo-EM-resolved four-STRN3-subunit assembly; within this complex it contributes to PP2A-mediated dephosphorylation/inhibition of associated Ste20-like kinases, inhibition of Hippo (MST/LATS) signaling to promote YAP activity, and regulation of actin/microtubule cytoskeletal dynamics, collective cell migration, neural stem cell reactivation, spermatogenesis, and sarcomere assembly, while also forming a phosphorylation-dependent complex with MST4 that opposes MST1-MOB1-mediated Hippo activation.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"MOB4 is a conserved, non-catalytic scaffolding subunit of the STRIPAK complex that links PP2A phosphatase activity to regulation of Hippo signaling, cytoskeletal organization, and collective cell migration. Within STRIPAK, MOB4 binds striatin family proteins at both N-terminal and C-terminal regions, and the cryo-EM structure of the STRIPAK core places one copy of MOB4 alongside PP2A-A/C, STRN3 homotetramer, and STRIP1, with interface mutations causing aberrant Hippo pathway activation [PMID:33633399, PMID:21985334]. MOB4 also forms a phosphorylation-dependent complex with the GCK-III kinase MST4 that structurally mimics MST1–MOB1, and this MST4–MOB4 complex antagonizes canonical Hippo signaling by disrupting MST1–MOB1 assembly and thereby promoting YAP activity, cell growth, and migration [PMID:30072378]. Conserved organismal functions include regulation of axonal transport and microtubule organization at neuromuscular junctions, neural stem cell reactivation from quiescence via Hippo pathway inhibition, spermatid individualization, and sarcomere assembly through genetic interaction with the actin-folding chaperonin TRiC, with human MOB4 transgenes rescuing Drosophila and zebrafish loss-of-function phenotypes [PMID:20392941, PMID:31167138, PMID:37259670, PMID:35737712].\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"The initial question of where MOB4 operates was answered by identifying it as a stable subunit of the newly defined STRIPAK complex containing PP2A, striatins, STRIP1/2, CCM3, and GCK-III kinases, establishing MOB4 as part of a major phosphatase–kinase signaling assembly rather than functioning as an isolated Hippo pathway component.\",\n      \"evidence\": \"Iterative AP-MS of multiple STRIPAK subunits in mammalian cells\",\n      \"pmids\": [\"18782753\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry and architecture of MOB4 within the complex unknown\", \"Direct binding partners within STRIPAK not mapped\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"In parallel, the Drosophila ortholog DMob4 was shown to localize to spindle poles and kinetochores and to be required for kinetochore-fiber focusing during mitosis, suggesting MOB4 controls a mitotic kinase that organizes spindle microtubules.\",\n      \"evidence\": \"RNAi screen and Mob4-GFP live imaging in Drosophila S2 cells\",\n      \"pmids\": [\"18388316\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Identity of the regulated mitotic kinase not determined\", \"Relevance of spindle function to mammalian MOB4 not tested\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Null alleles of Drosophila DMob4 revealed conserved roles in axonal transport, microtubule network organization, and neuromuscular junction growth, and cross-species rescue by human phocein demonstrated functional conservation.\",\n      \"evidence\": \"Drosophila null/hypomorphic alleles with physiological and cell-biological phenotyping; transgenic rescue with human MOB4\",\n      \"pmids\": [\"20392941\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which MOB4 influences microtubule organization not resolved\", \"Whether STRIPAK-dependent or -independent functions exist unclear\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Structure–function mapping of striatin revealed that MOB4 binds at two distinct regions (N-terminal coiled-coil and C-terminal WD-repeat domain) positioned near the PP2A and Mst3 binding sites, providing a rationale for how MOB4 could facilitate PP2A-mediated regulation of GCK-III kinases.\",\n      \"evidence\": \"Co-immunoprecipitation of striatin deletion mutants with MOB4\",\n      \"pmids\": [\"21985334\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct effect of MOB4 on PP2A-mediated Mst3 dephosphorylation not demonstrated\", \"Binding affinities not quantified\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"MOB4 binding to striatin-1 was shown to be functionally essential for striatal neuron dendritic arborization, as a MOB4-binding-deficient striatin-1 construct failed to rescue dendritic and spine phenotypes caused by striatin-1 knockdown.\",\n      \"evidence\": \"shRNA knockdown with structure–function rescue constructs in primary striatal neurons\",\n      \"pmids\": [\"29802198\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Downstream signaling targets of MOB4–striatin in neurons not identified\", \"Whether MOB4 also contributes independently of striatin not addressed\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"The MST4–MOB4 complex was structurally and functionally characterized, revealing a phosphorylation-dependent interaction that mimics MST1–MOB1 but instead promotes cell growth and migration by disrupting MST1–MOB1 assembly and increasing YAP activity — establishing MOB4 as a direct antagonist of canonical Hippo tumor suppression.\",\n      \"evidence\": \"Co-immunoprecipitation, structural analysis, cell growth/migration assays, and YAP activity measurements in PANC-1 cells\",\n      \"pmids\": [\"30072378\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether MST4–MOB4 operates within or outside the STRIPAK complex unclear\", \"In vivo relevance of this complex in tumorigenesis not tested\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"In Drosophila neural stem cells, Mob4 together with Cka/Strip recruits PP2A to Hippo kinase, inhibiting Hippo signaling to promote reactivation from quiescence — providing a defined developmental context for STRIPAK-mediated Hippo regulation.\",\n      \"evidence\": \"Genetic loss-of-function, co-immunoprecipitation of Mob4/Cka/PP2A/Hippo complex, single-NSC transcriptomics\",\n      \"pmids\": [\"31167138\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct biochemical demonstration of PP2A dephosphorylation of Hippo in this context lacking\", \"Mammalian NSC relevance not established\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"A 3.2-Å cryo-EM structure of the STRIPAK core resolved MOB4's precise position in the complex — one copy associating with a four-STRN3 elongated scaffold, one PP2A-A/C heterodimer, and one STRIP1 — and interface mutations disrupting STRIPAK integrity caused aberrant Hippo pathway activation, providing atomic-level understanding of how the assembly controls signaling.\",\n      \"evidence\": \"Cryo-EM structure determination, interface mutagenesis, Hippo pathway activity assays\",\n      \"pmids\": [\"33633399\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How GCK-III kinases and CCM3 integrate into the core structure not resolved\", \"Conformational dynamics and regulation of MOB4 within the complex unknown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Zebrafish mob4 mutants linked STRIPAK to sarcomere assembly and actin biogenesis through genetic interaction with the chaperonin TRiC, while mob4 overexpression increased myofibril number, establishing a cytoskeletal scaffolding role beyond signaling.\",\n      \"evidence\": \"Forward genetic screen, nonsense mutant, transgenic rescue, TRiC genetic interaction, electron microscopy in zebrafish\",\n      \"pmids\": [\"35737712\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether MOB4–TRiC interaction is direct or mediated through other STRIPAK subunits unknown\", \"Mammalian muscle relevance not demonstrated\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"MOB4 was shown to be essential for Drosophila spermatogenesis — controlling spermatid individualization, axonemal microtubule organization, and mitochondrial morphology — with human MOB4 rescuing all phenotypes, confirming deep functional conservation of STRIPAK-dependent cytoskeletal regulation.\",\n      \"evidence\": \"RNAi knockdown, transmission electron microscopy, human MOB4 transgenic rescue in Drosophila\",\n      \"pmids\": [\"37259670\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Which STRIPAK-dependent kinase targets drive spermatid phenotypes not identified\", \"Role in mammalian spermatogenesis not tested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"MOB4 was established as a coordinator of collective cell migration: knockout in MCF10A cells increased but disoriented migration, MOB4 relocalized to the leading edge during wound healing, and the phenotype required YAP1, as constitutively active YAP1 rescued orientation defects.\",\n      \"evidence\": \"CRISPR/Cas9 knockout, wound healing assay, live imaging, YAP1 epistasis rescue in MCF10A cells\",\n      \"pmids\": [\"41276909\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How MOB4 leading-edge localization is regulated unclear\", \"Whether STRIPAK-associated phosphatase or kinase activity mediates the migration phenotype not dissected\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"MOB4 and STRN3 were identified as Rac1 interactors in Schwann cells, linking STRIPAK to lamellipodia formation, radial sorting, and YAP/TAZ-dependent extracellular matrix gene expression — broadening the signaling inputs (Rac1) and cell-type contexts of MOB4 function.\",\n      \"evidence\": \"Co-immunoprecipitation of Rac1 with STRN3/MOB4, conditional Schwann cell knockout, lamellipodia and radial sorting assays\",\n      \"pmids\": [\"40056414\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether Rac1 binds MOB4 directly or via striatin not resolved\", \"Relative contributions of MOB4 versus other STRIPAK subunits in Schwann cells not determined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include: how MOB4 is regulated (post-translational modifications, conformational switching), whether MOB4 has STRIPAK-independent functions, how the MST4–MOB4 and STRIPAK-resident pools are partitioned in cells, and which direct kinase substrates mediate MOB4-dependent cytoskeletal and signaling phenotypes.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No post-translational modification map of MOB4 exists\", \"No structural data for MOB4 within GCK-III kinase–containing holo-STRIPAK\", \"STRIPAK-independent functions of MOB4 not tested\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 1, 3, 14]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [12]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 3, 6, 10, 12, 13]}\n    ],\n    \"complexes\": [\n      \"STRIPAK\"\n    ],\n    \"partners\": [\n      \"STRN\",\n      \"STRN3\",\n      \"STRIP1\",\n      \"MST4\",\n      \"PPP2CA\",\n      \"PPP2R1A\",\n      \"RAC1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}