{"gene":"PALLD","run_date":"2026-06-10T05:19:53","timeline":{"discoveries":[{"year":2006,"finding":"The P239S missense mutation in palladin (proline to serine in a conserved region) causes cytoskeletal changes, abnormal actin bundle assembly, and increased cell migration when expressed in HeLa cells, demonstrating a gain-of-function effect on actin organization and motility.","method":"Transfection of wild-type and P239S mutant palladin constructs into HeLa cells; phenotypic analysis of actin bundle assembly and migration","journal":"PLoS medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct functional transfection experiment with mutant vs. wild-type comparison, single lab, two readouts (actin morphology + migration)","pmids":["17194196"],"is_preprint":false},{"year":2007,"finding":"Palladin knockout (Palld−/−) in mice causes defective definitive erythropoiesis in fetal liver due to a compromised erythropoietic microenvironment; specifically, mutant macrophages lose the ability to bind erythroblasts and fail to form erythroblastic islands, while mutant fetal liver cells can still reconstitute hematopoiesis in irradiated recipients.","method":"Palld−/− knockout mouse model; colony-forming assays; in vitro erythroblastic island formation with wild-type vs. mutant macrophages and erythroblasts; bone marrow reconstitution experiments","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic knockout with multiple orthogonal functional assays (colony forming, island reconstitution, transplantation), clear cellular phenotype localized to macrophage function","pmids":["17431131"],"is_preprint":false},{"year":2016,"finding":"Palladin Ig domains 3 and 34 interact with the head group of PI(4,5)P2 with moderate affinity (apparent Kd ~17 µM); PI(4,5)P2 binding inhibits palladin's actin polymerization and crosslinking/bundling activity. Residues K38 and K51 on β-sheets C and D of Ig3 form salt bridges with PI(4,5)P2, and charge neutralization at K38 severely limits actin polymerizing and bundling activity.","method":"In vitro actin polymerization and bundling assays; NMR titration; molecular docking; site-directed mutagenesis (K38 charge neutralization)","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro biochemical reconstitution combined with NMR structural mapping and mutagenesis in a single study, multiple orthogonal methods","pmids":["27487483"],"is_preprint":false},{"year":2017,"finding":"PALLD regulates phagocytosis by facilitating phagocytic receptor clustering via actin polymerization and c-Src dynamic activation during particle binding and early phagosome formation, and recruits phosphatase OCRL (oculocerebrorenal syndrome of Lowe) to the nascent phagosome to regulate PI(4,5)P2 hydrolysis and actin depolymerization for phagosome closure.","method":"PALLD knockdown/overexpression in myeloid leukemia cells; phagocytosis assays (IgG- and complement-opsonized particles); imaging of receptor clustering, c-Src activation, OCRL recruitment, PI(4,5)P2 levels","journal":"Journal of immunology","confidence":"High","confidence_rationale":"Tier 2 / Strong — loss-of-function with multiple defined molecular readouts (receptor clustering, c-Src activation, OCRL recruitment, PI(4,5)P2 hydrolysis), mechanistic pathway placement","pmids":["28739877"],"is_preprint":false},{"year":2013,"finding":"In Sertoli cells, the 140 kDa palladin isoform is cleaved, with its C-terminus localizing to the nucleus and N-terminus remaining cytoplasmic. Nuclear localization of the C-terminal fragment is regulated by a putative nuclear export signal, and this nuclear translocation coincides with onset of puberty.","method":"Immunofluorescence and fractionation of testis tissue; isoform identification by Western blot; nuclear export signal analysis in Sertoli cells","journal":"Molecular reproduction and development","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiments with fractionation and isoform characterization, single lab, functional context (puberty onset) established","pmids":["23559268"],"is_preprint":false},{"year":2014,"finding":"PALLD nuclear localization in Sertoli cells is regulated by FSH signaling: PALLD shuttles from nucleus to cytoplasm upon F-actin depolymerization triggered by cAMP signaling, and nuclear localization is reduced in FSH receptor-mutant (but not LH receptor- or androgen receptor-mutant) mice.","method":"Primary Sertoli cell culture with serum stimulation; pharmacological F-actin depolymerization; analysis of LH receptor, androgen receptor, and FSH receptor knockout mouse testes by immunofluorescence","journal":"Reproduction","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple receptor-mutant mouse models tested with direct localization readout, single lab, functional pathway (FSH-cAMP-actin) identified","pmids":["24989903"],"is_preprint":false},{"year":2023,"finding":"Conditional cardiomyocyte-specific ablation of PALLD in adult mice causes progressive cardiac dilation, systolic dysfunction, reduced cardiomyocyte contractility, intercalated disc abnormalities, and fibrosis. Yeast two-hybrid screening identified CARP/Ankrd1 and FHOD1 as novel interaction partners of the N-terminal region of PALLD.","method":"Inducible cardiomyocyte-specific PALLD knockout mice (cPKOi); echocardiography; contractility assays; yeast two-hybrid screening; double knockout with MYPN","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with multiple cardiac phenotype readouts plus yeast two-hybrid for interaction partners, replicated across two conditional models (cPKO and cPKOi)","pmids":["36927816"],"is_preprint":false},{"year":2024,"finding":"PALLD binds directly to STAT3 via its immunoglobulin domain 3, interacting with STAT3's DNA-binding domain and SH2 domain. Loss of PALLD in megakaryocytes attenuates STAT3 Y705 phosphorylation and impedes STAT3 nuclear translocation, impairing proplatelet formation, polyploidization, and platelet production. A peptide (C-P3) based on the PALLD-STAT3 binding sequence facilitates megakaryocyte differentiation in vivo.","method":"Megakaryocyte/platelet-specific Palld knockout mice; Co-IP mapping PALLD Ig3 with STAT3 domains; phospho-STAT3 (Y705) Western blot; STAT3 nuclear translocation imaging; proplatelet formation assays; in vivo peptide rescue","journal":"Haematologica","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — domain-level binding mapping, KO mouse model, phosphorylation and nuclear translocation readouts, and in vivo rescue with structure-based peptide, multiple orthogonal methods","pmids":["38813732"],"is_preprint":false},{"year":2021,"finding":"A germline PALLD mutation (D52N) identified in a familial pancreatic cancer family shows predominant expression in cancer-associated fibroblasts (CAFs) by compartment-specific gene expression analysis and IHC, suggesting a stromal predisposition mechanism for familial pancreatic cancer.","method":"Whole exome sequencing of tumor and blood; germline mutation confirmation by PCR; compartment-specific gene expression analysis; immunohistochemistry for PALLD in CAFs","journal":"JCI insight","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — genetic identification with IHC/expression localization to CAFs, but functional consequence of the mutation not directly tested in vitro; replicated across two siblings","pmids":["33764904"],"is_preprint":false},{"year":2022,"finding":"Palladin promotes cancer stem cell-like properties in lung cancer cells by activating Wnt/β-catenin signaling; palladin overexpression increases β-catenin accumulation, and Wnt/β-catenin pathway inhibition blocks palladin-induced sphere-forming enhancement.","method":"In vitro overexpression/knockdown in NSCLC cell lines; sphere-forming assays; Western blot for β-catenin; xenograft models; Wnt/β-catenin inhibitor rescue experiments","journal":"Cancer medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional rescue with pathway inhibitor establishes pathway placement, in vitro and in vivo, single lab","pmids":["36047666"],"is_preprint":false},{"year":2025,"finding":"STAU2 RNA-binding protein directly binds and regulates PALLD mRNA, and STAU2 promotes PDAC metastasis via an EMT pathway involving PALLD and IQGAP1; ASO-mediated knockdown of STAU2 suppresses PALLD expression and inhibits PDAC progression in vitro and in vivo.","method":"RNA-binding protein immunoprecipitation; ASO knockdown; in vitro and xenograft in vivo models; EMT marker analysis; omics analyses","journal":"Advanced science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding of STAU2 to PALLD mRNA shown, ASO functional rescue in vitro and in vivo, single lab","pmids":["40539383"],"is_preprint":false},{"year":2020,"finding":"Palladin promoter regions for the 90 kDa, 140 kDa, and 200 kDa isoforms were identified and contain transcriptional regulatory elements including TATA box, GATA, MyoD, myogenin, MEF, Nkx2-5, and Tcf3 binding sites, with transcriptome profiling confirming active roles for these predicted transcription factors in mouse.","method":"Promoter prediction programs; identification of transcription start sites; luciferase reporter assays; transcriptome profiling in mouse","journal":"BMC research notes","confidence":"Low","confidence_rationale":"Tier 3 / Weak — computational prediction of promoter elements with transcriptome confirmation, no direct functional mutagenesis of promoter elements, single lab","pmids":["32620172"],"is_preprint":false},{"year":2023,"finding":"miR-96 and miR-182 downregulate PALLD at both transcript and protein levels in glioblastoma (U251 MG) cells, and overexpression of palladin rescues the inhibition of cell motility caused by miR-96 or miR-182 overexpression, demonstrating that palladin is a functional downstream target of these miRNAs in GBM motility.","method":"miRNA overexpression; RT-PCR and Western blot for PALLD; cell motility assays; palladin rescue experiments in miRNA-transfected cells","journal":"Cytoskeleton","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — rescue experiments establish palladin as functional effector downstream of miR-96/182 in motility, multiple readouts, single lab","pmids":["36961307"],"is_preprint":false}],"current_model":"Palladin (PALLD) is a scaffold and actin-crosslinking/bundling phosphoprotein that organizes the actin cytoskeleton through its immunoglobulin domains (particularly Ig3), directly crosslinks and polymerizes actin filaments in a manner inhibited by PI(4,5)P2 binding; it interacts with STAT3 (via Ig3) to promote STAT3 Y705 phosphorylation and nuclear translocation in megakaryocytes driving platelet biogenesis, interacts with CARP/Ankrd1 and FHOD1 in cardiomyocytes where it is essential for intercalated disc integrity and cardiac function, regulates phagocytosis by coordinating actin dynamics and OCRL recruitment, controls macrophage-mediated erythroblastic island formation in fetal liver, undergoes isoform-specific nuclear-cytoplasmic shuttling in Sertoli cells regulated by FSH-cAMP signaling, and promotes cancer cell invasiveness and Wnt/β-catenin-driven stem-like properties, with its expression regulated post-transcriptionally by STAU2 and miR-96/182."},"narrative":{"mechanistic_narrative":"Palladin (PALLD) is an actin-associated scaffold phosphoprotein that organizes the actin cytoskeleton and converts it into specialized cellular machinery across migration, phagocytosis, and tissue-specific differentiation programs [PMID:17194196, PMID:27487483, PMID:28739877]. Its immunoglobulin domains carry out the core biochemistry: Ig3 (and Ig34) directly crosslinks, bundles, and polymerizes actin filaments, an activity gated by binding to the membrane lipid PI(4,5)P2, which docks via salt bridges to residues K38 and K51 on Ig3 and inhibits filament assembly [PMID:27487483]. The P239S substitution in a conserved region acts as a gain-of-function lesion that drives aberrant actin bundling and increased cell migration [PMID:17194196]. Beyond filament organization, palladin functions as an adaptor coupling actin dynamics to signaling: during phagocytosis it promotes receptor clustering and c-Src activation while recruiting the phosphatase OCRL to nascent phagosomes to drive PI(4,5)P2 hydrolysis and actin depolymerization for phagosome closure [PMID:28739877], and in megakaryocytes its Ig3 domain binds STAT3 directly, promoting STAT3 Y705 phosphorylation and nuclear translocation to support proplatelet formation and platelet production [PMID:38813732]. Palladin is required for tissue integrity and microenvironment formation in vivo: cardiomyocyte-specific ablation causes dilated cardiomyopathy and intercalated disc abnormalities, where palladin's N-terminus binds CARP/Ankrd1 and FHOD1 [PMID:36927816], and germline knockout impairs fetal liver erythropoiesis by abolishing the ability of macrophages to bind erythroblasts and form erythroblastic islands [PMID:17431131]. Palladin also displays isoform-specific nuclear-cytoplasmic shuttling in Sertoli cells that is controlled by FSH-cAMP signaling and F-actin state [PMID:23559268, PMID:24989903], and it promotes cancer cell invasiveness and Wnt/β-catenin-driven stem-like properties, with its expression controlled post-transcriptionally by the RNA-binding protein STAU2 and by miR-96/miR-182 [PMID:36047666, PMID:40539383, PMID:36961307].","teleology":[{"year":2006,"claim":"Established that a single conserved-region missense change in palladin is sufficient to reorganize actin and enhance motility, defining palladin as an active determinant of cytoskeletal architecture rather than a passive marker.","evidence":"Transfection of wild-type vs P239S mutant constructs in HeLa cells, scoring actin bundles and migration","pmids":["17194196"],"confidence":"Medium","gaps":["Does not establish the biochemical mechanism by which P239S alters actin binding","Phenotype shown only in HeLa overexpression, not endogenous tissue"]},{"year":2007,"claim":"Showed palladin is required non-cell-autonomously for the erythropoietic microenvironment, localizing its essential role to macrophage adhesion in erythroblastic island formation.","evidence":"Palld-/- knockout mice with colony-forming, island reconstitution, and bone marrow transplantation assays","pmids":["17431131"],"confidence":"High","gaps":["Molecular partners mediating macrophage-erythroblast binding not identified","Does not define which palladin isoform drives the macrophage function"]},{"year":2013,"claim":"Revealed isoform-specific proteolytic processing and compartmentalized localization of palladin in Sertoli cells, implicating a nuclear function distinct from cytoskeletal scaffolding.","evidence":"Immunofluorescence, fractionation, and isoform Western blotting of testis tissue with NES analysis","pmids":["23559268"],"confidence":"Medium","gaps":["Identity/function of the nuclear C-terminal fragment not determined","Cleavage protease unknown"]},{"year":2014,"claim":"Connected palladin's nuclear-cytoplasmic shuttling to a defined upstream hormonal pathway, showing FSH-cAMP signaling and actin state govern its localization.","evidence":"Primary Sertoli cell culture, pharmacological F-actin depolymerization, and FSH/LH/androgen receptor-mutant mouse testes imaging","pmids":["24989903"],"confidence":"Medium","gaps":["Nuclear target genes or activity of palladin not defined","Mechanism linking F-actin state to import/export not resolved"]},{"year":2016,"claim":"Provided the structural-biochemical basis for palladin actin organization and its lipid regulation, mapping PI(4,5)P2 binding to specific Ig3 residues that gate bundling activity.","evidence":"In vitro actin polymerization/bundling assays, NMR titration, docking, and K38 charge-neutralization mutagenesis","pmids":["27487483"],"confidence":"High","gaps":["Does not show PI(4,5)P2 regulation of palladin in a cellular context","Relative contributions of Ig3 vs Ig34 in cells not resolved"]},{"year":2017,"claim":"Placed palladin in the phagocytic pathway as a coordinator linking actin polymerization, c-Src activation, and OCRL-mediated PI(4,5)P2 hydrolysis for phagosome closure.","evidence":"PALLD knockdown/overexpression in myeloid leukemia cells with phagocytosis assays and imaging of receptor clustering, c-Src, OCRL, and PI(4,5)P2","pmids":["28739877"],"confidence":"High","gaps":["Direct vs indirect nature of the palladin-OCRL recruitment not defined","Whether the PI(4,5)P2-gated bundling activity (#2) operates here is untested"]},{"year":2020,"claim":"Characterized isoform-specific promoter architecture of palladin, predicting muscle and developmental transcription factor inputs.","evidence":"Promoter prediction, transcription start site mapping, luciferase reporters, and transcriptome profiling in mouse","pmids":["32620172"],"confidence":"Low","gaps":["Computational prediction without direct mutagenesis of promoter elements","Functional requirement of the predicted TF sites not tested"]},{"year":2021,"claim":"Identified a germline palladin mutation segregating in familial pancreatic cancer with predominant stromal (CAF) expression, implicating a microenvironmental predisposition mechanism.","evidence":"Whole exome sequencing, germline confirmation, compartment-specific expression analysis, and CAF IHC in a family","pmids":["33764904"],"confidence":"Medium","gaps":["Functional consequence of D52N not tested in vitro","Causality vs association in tumorigenesis not established"]},{"year":2022,"claim":"Placed palladin upstream of Wnt/β-catenin in driving cancer stem cell-like properties, extending its role from motility to stemness.","evidence":"Overexpression/knockdown in NSCLC lines with sphere assays, β-catenin Western blot, xenografts, and Wnt inhibitor rescue","pmids":["36047666"],"confidence":"Medium","gaps":["Molecular link between palladin and β-catenin accumulation not defined","Single lung cancer context"]},{"year":2023,"claim":"Established palladin as essential for adult cardiac structure and contractility and identified CARP/Ankrd1 and FHOD1 as N-terminal interaction partners at the intercalated disc.","evidence":"Inducible cardiomyocyte-specific knockout mice with echocardiography, contractility assays, MYPN double knockout, and yeast two-hybrid screening","pmids":["36927816"],"confidence":"High","gaps":["Yeast two-hybrid interactions not validated biochemically in cardiomyocytes","How loss of these interactions causes disc disruption not mechanistically resolved"]},{"year":2023,"claim":"Identified palladin as a functional effector downstream of miR-96/miR-182 controlling glioblastoma cell motility.","evidence":"miRNA overexpression with RT-PCR/Western blot and palladin rescue of motility in U251 MG cells","pmids":["36961307"],"confidence":"Medium","gaps":["Direct vs indirect miRNA targeting of PALLD transcript not fully resolved","Single GBM cell line"]},{"year":2024,"claim":"Revealed a non-cytoskeletal signaling role in which palladin Ig3 binds STAT3 to promote its activation and nuclear entry during platelet biogenesis, and validated this with a structure-based rescue peptide.","evidence":"Megakaryocyte/platelet-specific Palld knockout mice, Co-IP domain mapping, phospho-STAT3 Western blot, nuclear translocation imaging, and in vivo C-P3 peptide rescue","pmids":["38813732"],"confidence":"High","gaps":["Mechanism by which palladin binding enhances STAT3 Y705 phosphorylation not defined","Generalizability of palladin-STAT3 axis beyond megakaryocytes untested"]},{"year":2025,"claim":"Connected post-transcriptional control of PALLD by STAU2 to PDAC metastasis through an EMT axis involving IQGAP1.","evidence":"RNA-binding protein immunoprecipitation, ASO knockdown, EMT marker analysis, and in vitro/xenograft models","pmids":["40539383"],"confidence":"Medium","gaps":["Direct functional contribution of palladin (vs STAU2's other targets) to metastasis not isolated","Mechanistic role of IQGAP1-palladin interaction not detailed"]},{"year":null,"claim":"How palladin's lipid-gated actin-bundling biochemistry, its scaffolding interactions, and its emerging nuclear/signaling functions are integrated within a single isoform repertoire across tissues remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model linking isoform-specific localization to distinct molecular functions","Cellular relevance of PI(4,5)P2 gating across the documented contexts untested","Nuclear activity of palladin fragments uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,2,3]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[3,6,7]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[2]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,2]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[4,5]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[4]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[1,3,7]},{"term_id":"R-HSA-397014","term_label":"Muscle contraction","supporting_discovery_ids":[6]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[7,9]}],"complexes":[],"partners":["STAT3","OCRL","ANKRD1","FHOD1","STAU2","IQGAP1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8WX93","full_name":"Palladin","aliases":["SIH002","Sarcoma antigen NY-SAR-77"],"length_aa":1383,"mass_kda":150.6,"function":"Cytoskeletal protein required for organization of normal actin cytoskeleton. Roles in establishing cell morphology, motility, cell adhesion and cell-extracellular matrix interactions in a variety of cell types. May function as a scaffolding molecule with the potential to influence both actin polymerization and the assembly of existing actin filaments into higher-order arrays. Binds to proteins that bind to either monomeric or filamentous actin. Localizes at sites where active actin remodeling takes place, such as lamellipodia and membrane ruffles. Different isoforms may have functional differences. Involved in the control of morphological and cytoskeletal changes associated with dendritic cell maturation. Involved in targeting ACTN to specific subcellular foci","subcellular_location":"Cytoplasm, cytoskeleton; Cell junction, focal adhesion; Cytoplasm, myofibril, sarcomere, Z line; Cell projection, ruffle; Cell projection, podosome; Cell projection, lamellipodium; Cell projection, axon; Cell projection, growth cone","url":"https://www.uniprot.org/uniprotkb/Q8WX93/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PALLD","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/PALLD","total_profiled":1310},"omim":[{"mim_id":"608092","title":"PALLADIN, CYTOSKELETAL-ASSOCIATED PROTEIN; PALLD","url":"https://www.omim.org/entry/608092"},{"mim_id":"606856","title":"PANCREATIC CANCER, SUSCEPTIBILITY TO, 1","url":"https://www.omim.org/entry/606856"},{"mim_id":"260350","title":"PANCREATIC CANCER","url":"https://www.omim.org/entry/260350"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Actin filaments","reliability":"Supported"},{"location":"Plasma membrane","reliability":"Additional"},{"location":"Mitochondria","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/PALLD"},"hgnc":{"alias_symbol":["KIAA0992","SIH002","CGI-151"],"prev_symbol":[]},"alphafold":{"accession":"Q8WX93","domains":[{"cath_id":"2.60.40.10","chopping":"268-364","consensus_level":"medium","plddt":83.8434,"start":268,"end":364},{"cath_id":"2.60.40.10","chopping":"440-540","consensus_level":"medium","plddt":85.1194,"start":440,"end":540},{"cath_id":"2.60.40.10","chopping":"1005-1094","consensus_level":"medium","plddt":85.0841,"start":1005,"end":1094},{"cath_id":"2.60.40.10","chopping":"1134-1227","consensus_level":"high","plddt":89.4782,"start":1134,"end":1227},{"cath_id":"2.60.40.10","chopping":"1233-1327","consensus_level":"high","plddt":89.0598,"start":1233,"end":1327}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WX93","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WX93-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WX93-F1-predicted_aligned_error_v6.png","plddt_mean":54.16},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PALLD","jax_strain_url":"https://www.jax.org/strain/search?query=PALLD"},"sequence":{"accession":"Q8WX93","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8WX93.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8WX93/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WX93"}},"corpus_meta":[{"pmid":"17194196","id":"PMC_17194196","title":"Palladin 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missense mutation in palladin (proline to serine in a conserved region) causes cytoskeletal changes, abnormal actin bundle assembly, and increased cell migration when expressed in HeLa cells, demonstrating a gain-of-function effect on actin organization and motility.\",\n      \"method\": \"Transfection of wild-type and P239S mutant palladin constructs into HeLa cells; phenotypic analysis of actin bundle assembly and migration\",\n      \"journal\": \"PLoS medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct functional transfection experiment with mutant vs. wild-type comparison, single lab, two readouts (actin morphology + migration)\",\n      \"pmids\": [\"17194196\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Palladin knockout (Palld−/−) in mice causes defective definitive erythropoiesis in fetal liver due to a compromised erythropoietic microenvironment; specifically, mutant macrophages lose the ability to bind erythroblasts and fail to form erythroblastic islands, while mutant fetal liver cells can still reconstitute hematopoiesis in irradiated recipients.\",\n      \"method\": \"Palld−/− knockout mouse model; colony-forming assays; in vitro erythroblastic island formation with wild-type vs. mutant macrophages and erythroblasts; bone marrow reconstitution experiments\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic knockout with multiple orthogonal functional assays (colony forming, island reconstitution, transplantation), clear cellular phenotype localized to macrophage function\",\n      \"pmids\": [\"17431131\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Palladin Ig domains 3 and 34 interact with the head group of PI(4,5)P2 with moderate affinity (apparent Kd ~17 µM); PI(4,5)P2 binding inhibits palladin's actin polymerization and crosslinking/bundling activity. Residues K38 and K51 on β-sheets C and D of Ig3 form salt bridges with PI(4,5)P2, and charge neutralization at K38 severely limits actin polymerizing and bundling activity.\",\n      \"method\": \"In vitro actin polymerization and bundling assays; NMR titration; molecular docking; site-directed mutagenesis (K38 charge neutralization)\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro biochemical reconstitution combined with NMR structural mapping and mutagenesis in a single study, multiple orthogonal methods\",\n      \"pmids\": [\"27487483\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PALLD regulates phagocytosis by facilitating phagocytic receptor clustering via actin polymerization and c-Src dynamic activation during particle binding and early phagosome formation, and recruits phosphatase OCRL (oculocerebrorenal syndrome of Lowe) to the nascent phagosome to regulate PI(4,5)P2 hydrolysis and actin depolymerization for phagosome closure.\",\n      \"method\": \"PALLD knockdown/overexpression in myeloid leukemia cells; phagocytosis assays (IgG- and complement-opsonized particles); imaging of receptor clustering, c-Src activation, OCRL recruitment, PI(4,5)P2 levels\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — loss-of-function with multiple defined molecular readouts (receptor clustering, c-Src activation, OCRL recruitment, PI(4,5)P2 hydrolysis), mechanistic pathway placement\",\n      \"pmids\": [\"28739877\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"In Sertoli cells, the 140 kDa palladin isoform is cleaved, with its C-terminus localizing to the nucleus and N-terminus remaining cytoplasmic. Nuclear localization of the C-terminal fragment is regulated by a putative nuclear export signal, and this nuclear translocation coincides with onset of puberty.\",\n      \"method\": \"Immunofluorescence and fractionation of testis tissue; isoform identification by Western blot; nuclear export signal analysis in Sertoli cells\",\n      \"journal\": \"Molecular reproduction and development\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiments with fractionation and isoform characterization, single lab, functional context (puberty onset) established\",\n      \"pmids\": [\"23559268\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"PALLD nuclear localization in Sertoli cells is regulated by FSH signaling: PALLD shuttles from nucleus to cytoplasm upon F-actin depolymerization triggered by cAMP signaling, and nuclear localization is reduced in FSH receptor-mutant (but not LH receptor- or androgen receptor-mutant) mice.\",\n      \"method\": \"Primary Sertoli cell culture with serum stimulation; pharmacological F-actin depolymerization; analysis of LH receptor, androgen receptor, and FSH receptor knockout mouse testes by immunofluorescence\",\n      \"journal\": \"Reproduction\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple receptor-mutant mouse models tested with direct localization readout, single lab, functional pathway (FSH-cAMP-actin) identified\",\n      \"pmids\": [\"24989903\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Conditional cardiomyocyte-specific ablation of PALLD in adult mice causes progressive cardiac dilation, systolic dysfunction, reduced cardiomyocyte contractility, intercalated disc abnormalities, and fibrosis. Yeast two-hybrid screening identified CARP/Ankrd1 and FHOD1 as novel interaction partners of the N-terminal region of PALLD.\",\n      \"method\": \"Inducible cardiomyocyte-specific PALLD knockout mice (cPKOi); echocardiography; contractility assays; yeast two-hybrid screening; double knockout with MYPN\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with multiple cardiac phenotype readouts plus yeast two-hybrid for interaction partners, replicated across two conditional models (cPKO and cPKOi)\",\n      \"pmids\": [\"36927816\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PALLD binds directly to STAT3 via its immunoglobulin domain 3, interacting with STAT3's DNA-binding domain and SH2 domain. Loss of PALLD in megakaryocytes attenuates STAT3 Y705 phosphorylation and impedes STAT3 nuclear translocation, impairing proplatelet formation, polyploidization, and platelet production. A peptide (C-P3) based on the PALLD-STAT3 binding sequence facilitates megakaryocyte differentiation in vivo.\",\n      \"method\": \"Megakaryocyte/platelet-specific Palld knockout mice; Co-IP mapping PALLD Ig3 with STAT3 domains; phospho-STAT3 (Y705) Western blot; STAT3 nuclear translocation imaging; proplatelet formation assays; in vivo peptide rescue\",\n      \"journal\": \"Haematologica\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — domain-level binding mapping, KO mouse model, phosphorylation and nuclear translocation readouts, and in vivo rescue with structure-based peptide, multiple orthogonal methods\",\n      \"pmids\": [\"38813732\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"A germline PALLD mutation (D52N) identified in a familial pancreatic cancer family shows predominant expression in cancer-associated fibroblasts (CAFs) by compartment-specific gene expression analysis and IHC, suggesting a stromal predisposition mechanism for familial pancreatic cancer.\",\n      \"method\": \"Whole exome sequencing of tumor and blood; germline mutation confirmation by PCR; compartment-specific gene expression analysis; immunohistochemistry for PALLD in CAFs\",\n      \"journal\": \"JCI insight\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — genetic identification with IHC/expression localization to CAFs, but functional consequence of the mutation not directly tested in vitro; replicated across two siblings\",\n      \"pmids\": [\"33764904\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Palladin promotes cancer stem cell-like properties in lung cancer cells by activating Wnt/β-catenin signaling; palladin overexpression increases β-catenin accumulation, and Wnt/β-catenin pathway inhibition blocks palladin-induced sphere-forming enhancement.\",\n      \"method\": \"In vitro overexpression/knockdown in NSCLC cell lines; sphere-forming assays; Western blot for β-catenin; xenograft models; Wnt/β-catenin inhibitor rescue experiments\",\n      \"journal\": \"Cancer medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional rescue with pathway inhibitor establishes pathway placement, in vitro and in vivo, single lab\",\n      \"pmids\": [\"36047666\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"STAU2 RNA-binding protein directly binds and regulates PALLD mRNA, and STAU2 promotes PDAC metastasis via an EMT pathway involving PALLD and IQGAP1; ASO-mediated knockdown of STAU2 suppresses PALLD expression and inhibits PDAC progression in vitro and in vivo.\",\n      \"method\": \"RNA-binding protein immunoprecipitation; ASO knockdown; in vitro and xenograft in vivo models; EMT marker analysis; omics analyses\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding of STAU2 to PALLD mRNA shown, ASO functional rescue in vitro and in vivo, single lab\",\n      \"pmids\": [\"40539383\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Palladin promoter regions for the 90 kDa, 140 kDa, and 200 kDa isoforms were identified and contain transcriptional regulatory elements including TATA box, GATA, MyoD, myogenin, MEF, Nkx2-5, and Tcf3 binding sites, with transcriptome profiling confirming active roles for these predicted transcription factors in mouse.\",\n      \"method\": \"Promoter prediction programs; identification of transcription start sites; luciferase reporter assays; transcriptome profiling in mouse\",\n      \"journal\": \"BMC research notes\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — computational prediction of promoter elements with transcriptome confirmation, no direct functional mutagenesis of promoter elements, single lab\",\n      \"pmids\": [\"32620172\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"miR-96 and miR-182 downregulate PALLD at both transcript and protein levels in glioblastoma (U251 MG) cells, and overexpression of palladin rescues the inhibition of cell motility caused by miR-96 or miR-182 overexpression, demonstrating that palladin is a functional downstream target of these miRNAs in GBM motility.\",\n      \"method\": \"miRNA overexpression; RT-PCR and Western blot for PALLD; cell motility assays; palladin rescue experiments in miRNA-transfected cells\",\n      \"journal\": \"Cytoskeleton\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — rescue experiments establish palladin as functional effector downstream of miR-96/182 in motility, multiple readouts, single lab\",\n      \"pmids\": [\"36961307\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Palladin (PALLD) is a scaffold and actin-crosslinking/bundling phosphoprotein that organizes the actin cytoskeleton through its immunoglobulin domains (particularly Ig3), directly crosslinks and polymerizes actin filaments in a manner inhibited by PI(4,5)P2 binding; it interacts with STAT3 (via Ig3) to promote STAT3 Y705 phosphorylation and nuclear translocation in megakaryocytes driving platelet biogenesis, interacts with CARP/Ankrd1 and FHOD1 in cardiomyocytes where it is essential for intercalated disc integrity and cardiac function, regulates phagocytosis by coordinating actin dynamics and OCRL recruitment, controls macrophage-mediated erythroblastic island formation in fetal liver, undergoes isoform-specific nuclear-cytoplasmic shuttling in Sertoli cells regulated by FSH-cAMP signaling, and promotes cancer cell invasiveness and Wnt/β-catenin-driven stem-like properties, with its expression regulated post-transcriptionally by STAU2 and miR-96/182.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"Palladin (PALLD) is an actin-associated scaffold phosphoprotein that organizes the actin cytoskeleton and converts it into specialized cellular machinery across migration, phagocytosis, and tissue-specific differentiation programs [#0, #2, #3]. Its immunoglobulin domains carry out the core biochemistry: Ig3 (and Ig34) directly crosslinks, bundles, and polymerizes actin filaments, an activity gated by binding to the membrane lipid PI(4,5)P2, which docks via salt bridges to residues K38 and K51 on Ig3 and inhibits filament assembly [#2]. The P239S substitution in a conserved region acts as a gain-of-function lesion that drives aberrant actin bundling and increased cell migration [#0]. Beyond filament organization, palladin functions as an adaptor coupling actin dynamics to signaling: during phagocytosis it promotes receptor clustering and c-Src activation while recruiting the phosphatase OCRL to nascent phagosomes to drive PI(4,5)P2 hydrolysis and actin depolymerization for phagosome closure [#3], and in megakaryocytes its Ig3 domain binds STAT3 directly, promoting STAT3 Y705 phosphorylation and nuclear translocation to support proplatelet formation and platelet production [#7]. Palladin is required for tissue integrity and microenvironment formation in vivo: cardiomyocyte-specific ablation causes dilated cardiomyopathy and intercalated disc abnormalities, where palladin's N-terminus binds CARP/Ankrd1 and FHOD1 [#6], and germline knockout impairs fetal liver erythropoiesis by abolishing the ability of macrophages to bind erythroblasts and form erythroblastic islands [#1]. Palladin also displays isoform-specific nuclear-cytoplasmic shuttling in Sertoli cells that is controlled by FSH-cAMP signaling and F-actin state [#4, #5], and it promotes cancer cell invasiveness and Wnt/\\u03b2-catenin-driven stem-like properties, with its expression controlled post-transcriptionally by the RNA-binding protein STAU2 and by miR-96/miR-182 [#9, #10, #12].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Established that a single conserved-region missense change in palladin is sufficient to reorganize actin and enhance motility, defining palladin as an active determinant of cytoskeletal architecture rather than a passive marker.\",\n      \"evidence\": \"Transfection of wild-type vs P239S mutant constructs in HeLa cells, scoring actin bundles and migration\",\n      \"pmids\": [\"17194196\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not establish the biochemical mechanism by which P239S alters actin binding\", \"Phenotype shown only in HeLa overexpression, not endogenous tissue\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Showed palladin is required non-cell-autonomously for the erythropoietic microenvironment, localizing its essential role to macrophage adhesion in erythroblastic island formation.\",\n      \"evidence\": \"Palld-/- knockout mice with colony-forming, island reconstitution, and bone marrow transplantation assays\",\n      \"pmids\": [\"17431131\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular partners mediating macrophage-erythroblast binding not identified\", \"Does not define which palladin isoform drives the macrophage function\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Revealed isoform-specific proteolytic processing and compartmentalized localization of palladin in Sertoli cells, implicating a nuclear function distinct from cytoskeletal scaffolding.\",\n      \"evidence\": \"Immunofluorescence, fractionation, and isoform Western blotting of testis tissue with NES analysis\",\n      \"pmids\": [\"23559268\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Identity/function of the nuclear C-terminal fragment not determined\", \"Cleavage protease unknown\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Connected palladin's nuclear-cytoplasmic shuttling to a defined upstream hormonal pathway, showing FSH-cAMP signaling and actin state govern its localization.\",\n      \"evidence\": \"Primary Sertoli cell culture, pharmacological F-actin depolymerization, and FSH/LH/androgen receptor-mutant mouse testes imaging\",\n      \"pmids\": [\"24989903\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Nuclear target genes or activity of palladin not defined\", \"Mechanism linking F-actin state to import/export not resolved\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Provided the structural-biochemical basis for palladin actin organization and its lipid regulation, mapping PI(4,5)P2 binding to specific Ig3 residues that gate bundling activity.\",\n      \"evidence\": \"In vitro actin polymerization/bundling assays, NMR titration, docking, and K38 charge-neutralization mutagenesis\",\n      \"pmids\": [\"27487483\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not show PI(4,5)P2 regulation of palladin in a cellular context\", \"Relative contributions of Ig3 vs Ig34 in cells not resolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Placed palladin in the phagocytic pathway as a coordinator linking actin polymerization, c-Src activation, and OCRL-mediated PI(4,5)P2 hydrolysis for phagosome closure.\",\n      \"evidence\": \"PALLD knockdown/overexpression in myeloid leukemia cells with phagocytosis assays and imaging of receptor clustering, c-Src, OCRL, and PI(4,5)P2\",\n      \"pmids\": [\"28739877\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct vs indirect nature of the palladin-OCRL recruitment not defined\", \"Whether the PI(4,5)P2-gated bundling activity (#2) operates here is untested\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Characterized isoform-specific promoter architecture of palladin, predicting muscle and developmental transcription factor inputs.\",\n      \"evidence\": \"Promoter prediction, transcription start site mapping, luciferase reporters, and transcriptome profiling in mouse\",\n      \"pmids\": [\"32620172\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Computational prediction without direct mutagenesis of promoter elements\", \"Functional requirement of the predicted TF sites not tested\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identified a germline palladin mutation segregating in familial pancreatic cancer with predominant stromal (CAF) expression, implicating a microenvironmental predisposition mechanism.\",\n      \"evidence\": \"Whole exome sequencing, germline confirmation, compartment-specific expression analysis, and CAF IHC in a family\",\n      \"pmids\": [\"33764904\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of D52N not tested in vitro\", \"Causality vs association in tumorigenesis not established\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Placed palladin upstream of Wnt/\\u03b2-catenin in driving cancer stem cell-like properties, extending its role from motility to stemness.\",\n      \"evidence\": \"Overexpression/knockdown in NSCLC lines with sphere assays, \\u03b2-catenin Western blot, xenografts, and Wnt inhibitor rescue\",\n      \"pmids\": [\"36047666\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular link between palladin and \\u03b2-catenin accumulation not defined\", \"Single lung cancer context\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Established palladin as essential for adult cardiac structure and contractility and identified CARP/Ankrd1 and FHOD1 as N-terminal interaction partners at the intercalated disc.\",\n      \"evidence\": \"Inducible cardiomyocyte-specific knockout mice with echocardiography, contractility assays, MYPN double knockout, and yeast two-hybrid screening\",\n      \"pmids\": [\"36927816\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Yeast two-hybrid interactions not validated biochemically in cardiomyocytes\", \"How loss of these interactions causes disc disruption not mechanistically resolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identified palladin as a functional effector downstream of miR-96/miR-182 controlling glioblastoma cell motility.\",\n      \"evidence\": \"miRNA overexpression with RT-PCR/Western blot and palladin rescue of motility in U251 MG cells\",\n      \"pmids\": [\"36961307\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs indirect miRNA targeting of PALLD transcript not fully resolved\", \"Single GBM cell line\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Revealed a non-cytoskeletal signaling role in which palladin Ig3 binds STAT3 to promote its activation and nuclear entry during platelet biogenesis, and validated this with a structure-based rescue peptide.\",\n      \"evidence\": \"Megakaryocyte/platelet-specific Palld knockout mice, Co-IP domain mapping, phospho-STAT3 Western blot, nuclear translocation imaging, and in vivo C-P3 peptide rescue\",\n      \"pmids\": [\"38813732\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which palladin binding enhances STAT3 Y705 phosphorylation not defined\", \"Generalizability of palladin-STAT3 axis beyond megakaryocytes untested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Connected post-transcriptional control of PALLD by STAU2 to PDAC metastasis through an EMT axis involving IQGAP1.\",\n      \"evidence\": \"RNA-binding protein immunoprecipitation, ASO knockdown, EMT marker analysis, and in vitro/xenograft models\",\n      \"pmids\": [\"40539383\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct functional contribution of palladin (vs STAU2's other targets) to metastasis not isolated\", \"Mechanistic role of IQGAP1-palladin interaction not detailed\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How palladin's lipid-gated actin-bundling biochemistry, its scaffolding interactions, and its emerging nuclear/signaling functions are integrated within a single isoform repertoire across tissues remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model linking isoform-specific localization to distinct molecular functions\", \"Cellular relevance of PI(4,5)P2 gating across the documented contexts untested\", \"Nuclear activity of palladin fragments uncharacterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [3, 6, 7]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [4, 5]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [1, 3, 7]},\n      {\"term_id\": \"R-HSA-397014\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [7, 9]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"STAT3\", \"OCRL\", \"ANKRD1\", \"FHOD1\", \"STAU2\", \"IQGAP1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}