{"gene":"FARP1","run_date":"2026-04-28T17:46:03","timeline":{"discoveries":[{"year":1997,"finding":"FARP1 (originally named CDEP) was cloned and characterized as a novel human protein containing an ezrin-like FERM domain (band 4.1 superfamily) and Dbl homology (DH) and pleckstrin homology (PH) domains, establishing its domain architecture as a putative Rho guanine nucleotide exchange factor involved in cytoskeletal organization.","method":"cDNA cloning, sequence analysis, Northern blot","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 3 — initial cloning and domain characterization, single lab, sequence-based inference of GEF activity","pmids":["9425278"],"is_preprint":false},{"year":2001,"finding":"CDEP/FARP1 DH-PH domain peptide stimulates GDP dissociation from RhoA in vitro, confirming it functions as a Rho guanine nucleotide exchange factor; truncated CDEP induces focus formation in NIH3T3 cells, demonstrating transforming activity.","method":"In vitro [3H]GDP dissociation assay using recombinant DH-PH domain peptide; NIH3T3 focus formation assay with truncated CDEP cDNA transfection","journal":"Osteoarthritis and cartilage","confidence":"High","confidence_rationale":"Tier 1 — direct in vitro GEF activity assay plus cell-based transforming activity, two orthogonal methods","pmids":["11680691"],"is_preprint":false},{"year":2009,"finding":"FARP1 acts as a specific effector of transmembrane Semaphorin6A/PlexinA4 signaling to promote dendritic growth in lateral motor column (LMC) spinal motor neurons; its Rho-GEF domain is required for this function, and retinoid signaling induces FARP1 expression upstream of this pathway.","method":"Loss-of-function and gain-of-function in chick spinal cord; morphological analysis of dendrites; domain deletion (Rho-GEF domain mutant); epistasis with Sema6A/PlexA4 signaling","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 — genetic epistasis with defined pathway, domain mutants, loss- and gain-of-function with specific morphological readout","pmids":["19217374"],"is_preprint":false},{"year":2012,"finding":"FARP1 is recruited to the postsynapse where its FERM domain directly binds the synaptic adhesion molecule SynCAM 1, forming a synaptic complex; FARP1 activates Rac1 in spines downstream of SynCAM 1 clustering, promotes F-actin assembly, increases synapse number, modulates spine morphology, and triggers a retrograde signal regulating active zone composition via SynCAM 1. SynCAM 1 requires FARP1 to promote spines, and FARP1 requires SynCAM 1 to elevate spine density (mutual epistasis).","method":"Proteomic analysis of SynCAM 1 KO synaptic membranes; co-immunoprecipitation (FERM domain–SynCAM 1); live imaging of dendritic filopodia; overexpression/knockdown with spine/synapse morphology readout; Rac1 activation assay; F-actin staining; genetic epistasis (SynCAM 1 KO × Farp1 manipulation)","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP, epistasis, Rac1 activity assay, multiple orthogonal methods in one study","pmids":["23209303"],"is_preprint":false},{"year":2014,"finding":"FARP1 interacts with the Neuropilin-1/PlexinA1 receptor complex and colocalizes with PlexinA1 along dendritic shafts; FARP1 is required for Sema3A-induced dendritic arborization of hippocampal neurons and mediates Sema3A-dependent F-actin redistribution in dendrites. Neuronal activity stabilizes PlexinA1 in dendrites (via proteasome-dependent pathway), gating FARP1-mediated Sema3A responses.","method":"Co-immunoprecipitation (FARP1–Neuropilin-1/PlexinA1); immunofluorescence colocalization; FARP1 knockdown with dendritic morphology readout; F-actin distribution assay; neuronal activity manipulation with proteasome inhibition","journal":"The Journal of neuroscience","confidence":"High","confidence_rationale":"Tier 2 — Co-IP, KD with defined morphological phenotype, multiple orthogonal methods","pmids":["24899721"],"is_preprint":false},{"year":2015,"finding":"MAP4K4 directly phosphorylates FARP1 at a pTL motif and co-immunoprecipitates with FARP1; MAP4K4 inhibition increases neurite outgrowth in SH-SY5Y cells, a process known to involve FARP1, suggesting MAP4K4 regulates cytoskeletal dynamics partly via FARP1 phosphorylation.","method":"Phosphoproteomic analysis of MAP4K4-inhibited cells; in vitro kinase assay with recombinant proteins; co-immunoprecipitation; neurite outgrowth assay with MAP4K4 inhibitor","journal":"ACS chemical biology","confidence":"High","confidence_rationale":"Tier 1-2 — direct in vitro phosphorylation assay, Co-IP, and cell-based functional readout in one study","pmids":["26422651"],"is_preprint":false},{"year":2016,"finding":"siRNA-mediated knockdown of FARP1 in PC12 cells significantly inhibits Cdc42 activity, establishing FARP1 as a GEF that activates Cdc42 in neuroendocrine cells.","method":"siRNA knockdown in PC12 cells; ELISA-based Cdc42/Rac1 activity assay","journal":"Endocrine-related cancer","confidence":"Medium","confidence_rationale":"Tier 2 — KD with defined GTPase activity readout, single lab","pmids":["26911374"],"is_preprint":false},{"year":2018,"finding":"Crystal structures of the FARP1 FERM domain (from zebrafish) revealed a three-lobed clover fold with a conserved positively charged surface patch; in vitro lipid-binding experiments showed the FERM domain binds specific phospholipids via this patch; cell-based analysis demonstrated the positively charged patch mediates plasma membrane localization of FARP1, and FERM domain interactions recruit FARP1 to postsynaptic sites in neurons.","method":"X-ray crystallography; in vitro phospholipid-binding assay; mutagenesis of charged surface patch; cell-based localization assay (fluorescence imaging); synaptic fractionation","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 1 — crystal structure, mutagenesis, in vitro lipid binding, and cell-based functional validation in one study","pmids":["29992992"],"is_preprint":false},{"year":2021,"finding":"FARP1 acts as an essential Rac-GEF downstream of EGFR and c-Met receptor tyrosine kinases (via the AXL-Gab1-PI3K axis) to drive Rac1-mediated cell migration and ruffle dynamics in human lung adenocarcinoma cells, operating in a non-redundant manner with ARHGEF39 and TIAM2.","method":"siRNA/shRNA knockdown; Rac1 activity assay; live-cell imaging of ruffle dynamics; epistasis with RTK inhibitors (EGFR, c-Met) and PI3K inhibitors","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 — KD with defined Rac1 activity and morphological readouts, epistasis with multiple pathway inhibitors, consistent across multiple GEFs","pmids":["34731623"],"is_preprint":false},{"year":2022,"finding":"In Drosophila border cells, the FARP1 ortholog Cdep functions downstream of Scribble/Dlg/Lgl basolateral polarity proteins and upstream of Rac to promote follower-cell crawling and cluster cohesion during collective migration; relocalization of Cdep::GFP partially rescues Scribble knockdown, establishing a Scrib/Cdep/Rac epistatic pathway.","method":"Genetic epistasis (Scribble, Dlg, Lgl knockdown); live imaging of border-cell migration; Cdep::GFP relocalization rescue experiment; Rac1 activity readout","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 2 — genetic epistasis with rescue experiment and live imaging, multiple orthogonal approaches","pmids":["36347240"],"is_preprint":false},{"year":2023,"finding":"FARP1 mediates Gi/o-coupled GPCR (OXER1, LPA receptor)-induced tunneling nanotube (TNT) formation in adrenocortical cancer cells via a Gβγ/PKCα/FARP1/Cdc42 axis; FARP1 acts downstream of PI3K and PKCα signaling and upstream of Cdc42 to drive actin-rich TNT biogenesis.","method":"Pertussis toxin treatment; siRNA knockdown of FARP1; Cdc42 activity assay; pharmacological inhibition (PI3K, PKCα, EGFR transactivation); live imaging of TNT formation","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — KD with specific actin-structure readout, epistasis with multiple pathway inhibitors, Cdc42 activity assay","pmids":["37390986"],"is_preprint":false},{"year":2026,"finding":"FARP1 is recruited by the lactate receptor GPR81 to activate RAC1, thereby promoting GLUT4 translocation to the plasma membrane and insulin-independent glucose uptake in skeletal muscle; GPR81 knockout impairs this axis while GPR81 activation enhances it.","method":"GPR81 KO mouse model; co-immunoprecipitation (GPR81–FARP1); RAC1 activity assay; GLUT4 translocation assay; genetic upregulation/downregulation of lactate production (LDHA KO)","journal":"Cell research","confidence":"High","confidence_rationale":"Tier 2 — Co-IP, KO models, Rac1 activity assay, GLUT4 translocation as specific functional readout, multiple orthogonal methods","pmids":["41530347"],"is_preprint":false}],"current_model":"FARP1 is a multi-domain (FERM–DH–PH) Rho guanine nucleotide exchange factor whose FERM domain binds phospholipids and interacts with transmembrane partners (SynCAM 1, PlexinA4, PlexinA1, GPR81) to recruit it to specific membrane compartments (postsynapse, plasma membrane), where its DH domain activates Rac1 and/or Cdc42 to drive F-actin remodeling underlying synapse formation, dendritic growth, cell migration, tunneling nanotube biogenesis, and insulin-independent GLUT4 translocation; its activity is regulated upstream by retinoid-induced transcription, MAP4K4-mediated phosphorylation, PI3K/PKCα signaling, and Scribble-dependent polarity complexes."},"narrative":{"teleology":[{"year":1997,"claim":"Cloning of FARP1 (CDEP) established its multi-domain architecture (FERM–DH–PH), predicting it as a Rho-family GEF linked to cytoskeletal regulation—answering the basic question of gene identity and domain composition.","evidence":"cDNA cloning, sequence analysis, and Northern blot from human tissues","pmids":["9425278"],"confidence":"Medium","gaps":["GEF activity was inferred from sequence homology, not biochemically demonstrated","substrate GTPase specificity unknown"]},{"year":2001,"claim":"Biochemical demonstration that the FARP1 DH-PH domain catalyzes GDP dissociation from RhoA in vitro confirmed it is a bona fide Rho-GEF, and its truncated form's transforming activity in fibroblasts linked GEF activity to a cellular outcome.","evidence":"In vitro [³H]GDP dissociation assay with recombinant DH-PH domain; NIH3T3 focus formation assay","pmids":["11680691"],"confidence":"High","gaps":["Initial assay used RhoA as substrate; later studies showed primary activity toward Rac1/Cdc42, raising questions about in vivo substrate preference","mechanism of autoinhibition by FERM domain not addressed"]},{"year":2009,"claim":"Placing FARP1 as an effector of Semaphorin6A/PlexinA4 signaling in motor neuron dendritic growth established the first physiological receptor-to-GEF pathway for FARP1, showing its GEF domain is required for dendritic morphogenesis and that retinoid signaling induces FARP1 expression.","evidence":"Loss- and gain-of-function in chick spinal cord; GEF-domain deletion mutants; epistasis with Sema6A/PlexA4","pmids":["19217374"],"confidence":"High","gaps":["Whether FARP1 activates Rac1 or Cdc42 in this context was not resolved","direct physical interaction between FARP1 and PlexinA4 not demonstrated"]},{"year":2012,"claim":"Identification of SynCAM 1 as a direct FERM-domain binding partner at the postsynapse, combined with mutual epistasis and Rac1 activation assays, established FARP1 as a synaptic organizer linking adhesion to actin-based spine remodeling and synapse number regulation.","evidence":"Proteomics of SynCAM 1 KO synaptic membranes; reciprocal Co-IP; Rac1 activity assay; spine/synapse morphology in knockdown/overexpression; F-actin staining","pmids":["23209303"],"confidence":"High","gaps":["Structural basis of FERM–SynCAM 1 interaction unresolved","retrograde signaling mechanism not molecularly defined"]},{"year":2014,"claim":"Demonstrating that FARP1 interacts with Neuropilin-1/PlexinA1 and is required for Sema3A-induced dendritic arborization broadened the repertoire of Semaphorin pathways utilizing FARP1, and revealed that neuronal activity gates this response by stabilizing PlexinA1.","evidence":"Co-IP of FARP1–Neuropilin-1/PlexinA1; FARP1 knockdown with dendritic morphology readout; activity-dependent PlexinA1 stabilization via proteasome inhibition","pmids":["24899721"],"confidence":"High","gaps":["Whether FARP1 binds PlexinA1 directly or via Neuropilin-1 scaffolding not distinguished","GTPase substrate specificity in this pathway not tested"]},{"year":2015,"claim":"Identifying MAP4K4 as a kinase that directly phosphorylates FARP1 at a pTL motif provided the first post-translational regulatory mechanism for FARP1 and connected it to a broader kinase-GEF signaling axis in neurite outgrowth.","evidence":"Phosphoproteomics; in vitro kinase assay with recombinant MAP4K4 and FARP1; Co-IP; neurite outgrowth assay with MAP4K4 inhibitor","pmids":["26422651"],"confidence":"High","gaps":["Functional consequence of phosphorylation on GEF activity not directly measured","phosphorylation site mutant phenotype not tested in neurons"]},{"year":2016,"claim":"Showing that FARP1 knockdown reduces Cdc42 activity in PC12 cells established Cdc42 as a second in vivo substrate, broadening FARP1's GTPase target range beyond Rac1.","evidence":"siRNA knockdown in PC12 cells; ELISA-based Cdc42/Rac1 activity assay","pmids":["26911374"],"confidence":"Medium","gaps":["Single cell line; not confirmed with constitutively active or dominant-negative Cdc42 rescue","whether Cdc42 activation is direct or indirect not resolved"]},{"year":2018,"claim":"Crystal structure of the FERM domain revealed the lipid-binding surface patch that mediates plasma membrane recruitment, providing the first structural basis for how FARP1 is positioned at membranes to activate downstream GTPases.","evidence":"X-ray crystallography of zebrafish FARP1 FERM domain; in vitro phospholipid binding; charge-patch mutagenesis; cell-based localization and synaptic fractionation","pmids":["29992992"],"confidence":"High","gaps":["No full-length structure; autoinhibitory mechanism between FERM and DH domains remains unknown","structure is from zebrafish—human FERM structure not solved"]},{"year":2021,"claim":"Demonstrating FARP1 as an essential non-redundant Rac-GEF downstream of EGFR/c-Met/PI3K extended its role from neurons to cancer cell migration, establishing that multiple RTK pathways converge on FARP1 to drive Rac1-dependent membrane ruffling.","evidence":"siRNA/shRNA knockdown in lung adenocarcinoma cells; Rac1 activity assay; live-cell ruffle dynamics; epistasis with EGFR, c-Met, and PI3K inhibitors","pmids":["34731623"],"confidence":"High","gaps":["How PI3K activates FARP1 (direct PH domain engagement vs. intermediate) not resolved","in vivo tumor model validation not performed"]},{"year":2022,"claim":"Genetic epistasis in Drosophila border cells placed the FARP1 ortholog Cdep downstream of Scribble/Dlg/Lgl polarity proteins and upstream of Rac, establishing a conserved polarity-to-Rac signaling axis for collective cell migration.","evidence":"Scribble/Dlg/Lgl knockdown; Cdep::GFP relocalization rescue; live imaging of border-cell migration in Drosophila","pmids":["36347240"],"confidence":"High","gaps":["Whether Scribble directly binds Cdep/FARP1 or acts indirectly not determined","conservation of this polarity pathway in mammalian collective migration not tested"]},{"year":2023,"claim":"Identification of a Gβγ/PKCα/FARP1/Cdc42 axis for GPCR-induced tunneling nanotube formation expanded FARP1's functional repertoire to intercellular communication structures and added PKCα as an upstream activator.","evidence":"siRNA knockdown of FARP1; pertussis toxin treatment; PI3K and PKCα inhibitors; Cdc42 activity assay; live imaging of TNTs in adrenocortical cancer cells","pmids":["37390986"],"confidence":"High","gaps":["Whether PKCα directly phosphorylates FARP1 not demonstrated","mechanism linking FARP1/Cdc42 to the specific actin architecture of TNTs not resolved"]},{"year":2026,"claim":"Demonstrating that GPR81 recruits FARP1 to activate Rac1 for GLUT4 translocation in skeletal muscle revealed a metabolic function for FARP1, connecting lactate sensing to insulin-independent glucose uptake.","evidence":"GPR81 KO mouse; Co-IP of GPR81–FARP1; Rac1 activity assay; GLUT4 translocation assay; LDHA KO for lactate modulation","pmids":["41530347"],"confidence":"High","gaps":["Whether the FERM domain mediates GPR81 binding directly not shown","in vivo contribution of FARP1 to whole-body glucose homeostasis not quantified"]},{"year":null,"claim":"A full-length structure of FARP1 explaining FERM-mediated autoinhibition and activation mechanisms, along with in vivo genetic models defining its non-redundant roles across tissues, remain central open questions.","evidence":"","pmids":[],"confidence":"Low","gaps":["No full-length FARP1 structure or autoinhibition mechanism defined","No FARP1 knockout mouse phenotype reported in the literature","Substrate selectivity determinants for Rac1 vs. Cdc42 in different cellular contexts unresolved"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[1,3,6,8,10,11]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[7]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[3,4]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[7,11]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[8]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,4,8,9,10,11]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[2,3,4]},{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[3,4]}],"complexes":[],"partners":["SYNCAM1","PLEXINA1","PLEXINA4","NRP1","MAP4K4","GPR81","RAC1","CDC42"],"other_free_text":[]},"mechanistic_narrative":"FARP1 is a FERM–DH–PH domain-containing Rho guanine nucleotide exchange factor that couples transmembrane receptor signals to Rac1 and Cdc42 activation, driving F-actin remodeling in processes including synaptogenesis, dendritic arborization, cell migration, tunneling nanotube formation, and glucose transporter translocation. Its FERM domain binds phospholipids via a conserved positively charged surface patch and directly engages transmembrane partners—SynCAM 1 at postsynaptic sites, PlexinA1/PlexinA4 in Semaphorin signaling, and GPR81 in skeletal muscle—to recruit FARP1 to the plasma membrane where the DH domain catalyzes GTP loading of Rac1 and Cdc42 [PMID:29992992, PMID:23209303, PMID:19217374, PMID:41530347]. FARP1 operates downstream of diverse upstream inputs including retinoid-induced transcription, PI3K/PKCα signaling from Gi/o-coupled GPCRs, EGFR/c-Met receptor tyrosine kinases, and Scribble-dependent polarity complexes, and is directly phosphorylated by MAP4K4 [PMID:37390986, PMID:34731623, PMID:36347240, PMID:26422651]. In neurons, FARP1 functions as an essential effector linking Semaphorin6A/PlexinA4 and Sema3A/Neuropilin-1/PlexinA1 signaling to dendritic growth and synapse formation, while in non-neuronal cells it drives Rac1-dependent migration ruffles, Cdc42-dependent tunneling nanotubes, and GPR81-mediated insulin-independent GLUT4 translocation [PMID:19217374, PMID:24899721, PMID:34731623, PMID:41530347]."},"prefetch_data":{"uniprot":{"accession":"Q9Y4F1","full_name":"FERM, ARHGEF and pleckstrin domain-containing protein 1","aliases":["Chondrocyte-derived ezrin-like protein","FERM, RhoGEF and pleckstrin domain-containing protein 1","Pleckstrin homology domain-containing family C member 2","PH domain-containing family C member 2"],"length_aa":1045,"mass_kda":118.6,"function":"Functions as a guanine nucleotide exchange factor for RAC1. May play a role in semaphorin signaling. Plays a role in the assembly and disassembly of dendritic filopodia, the formation of dendritic spines, regulation of dendrite length and ultimately the formation of synapses (By similarity)","subcellular_location":"Cell membrane; Synapse; Synapse, synaptosome; Cytoplasm, cytosol; Cell projection, filopodium; Cell projection, dendrite; Cell projection, dendritic spine","url":"https://www.uniprot.org/uniprotkb/Q9Y4F1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/FARP1","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000152767","cell_line_id":"CID000576","localizations":[{"compartment":"membrane","grade":3},{"compartment":"cytoplasmic","grade":1}],"interactors":[{"gene":"SDC3","stoichiometry":10.0},{"gene":"C17ORF80","stoichiometry":4.0}],"url":"https://opencell.sf.czbiohub.org/target/CID000576","total_profiled":1310},"omim":[{"mim_id":"618867","title":"RAS HOMOLOG GENE FAMILY, MEMBER F, FILOPODIA-ASSOCIATED; RHOF","url":"https://www.omim.org/entry/618867"},{"mim_id":"617586","title":"FERM, ARHGEF, AND PLECKSTRIN DOMAINS-CONTAINING PROTEIN 2; FARP2","url":"https://www.omim.org/entry/617586"},{"mim_id":"604280","title":"PLEXIN A4; PLXNA4","url":"https://www.omim.org/entry/604280"},{"mim_id":"602654","title":"FERM, ARHGEF, AND PLECKSTRIN DOMAINS-CONTAINING PROTEIN 1; FARP1","url":"https://www.omim.org/entry/602654"},{"mim_id":"300628","title":"FERM DOMAIN-CONTAINING PROTEIN 7; FRMD7","url":"https://www.omim.org/entry/300628"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/FARP1"},"hgnc":{"alias_symbol":["CDEP","PLEKHC2","MGC87400","PPP1R75","GLCC1"],"prev_symbol":[]},"alphafold":{"accession":"Q9Y4F1","domains":[{"cath_id":"3.10.20.90","chopping":"38-116","consensus_level":"medium","plddt":91.9475,"start":38,"end":116},{"cath_id":"2.30.29.30","chopping":"226-323_337-357","consensus_level":"medium","plddt":88.841,"start":226,"end":357},{"cath_id":"1.20.900.10","chopping":"539-746","consensus_level":"high","plddt":93.3521,"start":539,"end":746},{"cath_id":"2.30.29.30","chopping":"749-861","consensus_level":"high","plddt":92.7157,"start":749,"end":861},{"cath_id":"2.30.29.30","chopping":"934-1025","consensus_level":"high","plddt":92.9967,"start":934,"end":1025}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y4F1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y4F1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y4F1-F1-predicted_aligned_error_v6.png","plddt_mean":76.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=FARP1","jax_strain_url":"https://www.jax.org/strain/search?query=FARP1"},"sequence":{"accession":"Q9Y4F1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9Y4F1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9Y4F1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y4F1"}},"corpus_meta":[{"pmid":"31375671","id":"PMC_31375671","title":"LncRNA 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dermatopathology","url":"https://pubmed.ncbi.nlm.nih.gov/31021836","citation_count":4,"is_preprint":false},{"pmid":"39583578","id":"PMC_39583578","title":"Conserved region of human TDP-43 is structurally similar to membrane binding protein FARP1 and protein chaperons BAG6 and CYP33.","date":"2024","source":"microPublication biology","url":"https://pubmed.ncbi.nlm.nih.gov/39583578","citation_count":1,"is_preprint":false},{"pmid":"41530347","id":"PMC_41530347","title":"Lactate-activated GPR81/FARP1 signaling drives insulin-independent glucose uptake and metabolic control.","date":"2026","source":"Cell research","url":"https://pubmed.ncbi.nlm.nih.gov/41530347","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10533,"output_tokens":3306,"usd":0.040594},"stage2":{"model":"claude-opus-4-6","input_tokens":6693,"output_tokens":3475,"usd":0.18051},"total_usd":0.221104,"stage1_batch_id":"msgbatch_0118RScg3WGaGkaZRtWZbtce","stage2_batch_id":"msgbatch_01Cpfzvtbj42aqp5oYZ5Te2s","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1997,\n      \"finding\": \"FARP1 (originally named CDEP) was cloned and characterized as a novel human protein containing an ezrin-like FERM domain (band 4.1 superfamily) and Dbl homology (DH) and pleckstrin homology (PH) domains, establishing its domain architecture as a putative Rho guanine nucleotide exchange factor involved in cytoskeletal organization.\",\n      \"method\": \"cDNA cloning, sequence analysis, Northern blot\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — initial cloning and domain characterization, single lab, sequence-based inference of GEF activity\",\n      \"pmids\": [\"9425278\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"CDEP/FARP1 DH-PH domain peptide stimulates GDP dissociation from RhoA in vitro, confirming it functions as a Rho guanine nucleotide exchange factor; truncated CDEP induces focus formation in NIH3T3 cells, demonstrating transforming activity.\",\n      \"method\": \"In vitro [3H]GDP dissociation assay using recombinant DH-PH domain peptide; NIH3T3 focus formation assay with truncated CDEP cDNA transfection\",\n      \"journal\": \"Osteoarthritis and cartilage\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — direct in vitro GEF activity assay plus cell-based transforming activity, two orthogonal methods\",\n      \"pmids\": [\"11680691\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"FARP1 acts as a specific effector of transmembrane Semaphorin6A/PlexinA4 signaling to promote dendritic growth in lateral motor column (LMC) spinal motor neurons; its Rho-GEF domain is required for this function, and retinoid signaling induces FARP1 expression upstream of this pathway.\",\n      \"method\": \"Loss-of-function and gain-of-function in chick spinal cord; morphological analysis of dendrites; domain deletion (Rho-GEF domain mutant); epistasis with Sema6A/PlexA4 signaling\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis with defined pathway, domain mutants, loss- and gain-of-function with specific morphological readout\",\n      \"pmids\": [\"19217374\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"FARP1 is recruited to the postsynapse where its FERM domain directly binds the synaptic adhesion molecule SynCAM 1, forming a synaptic complex; FARP1 activates Rac1 in spines downstream of SynCAM 1 clustering, promotes F-actin assembly, increases synapse number, modulates spine morphology, and triggers a retrograde signal regulating active zone composition via SynCAM 1. SynCAM 1 requires FARP1 to promote spines, and FARP1 requires SynCAM 1 to elevate spine density (mutual epistasis).\",\n      \"method\": \"Proteomic analysis of SynCAM 1 KO synaptic membranes; co-immunoprecipitation (FERM domain–SynCAM 1); live imaging of dendritic filopodia; overexpression/knockdown with spine/synapse morphology readout; Rac1 activation assay; F-actin staining; genetic epistasis (SynCAM 1 KO × Farp1 manipulation)\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP, epistasis, Rac1 activity assay, multiple orthogonal methods in one study\",\n      \"pmids\": [\"23209303\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"FARP1 interacts with the Neuropilin-1/PlexinA1 receptor complex and colocalizes with PlexinA1 along dendritic shafts; FARP1 is required for Sema3A-induced dendritic arborization of hippocampal neurons and mediates Sema3A-dependent F-actin redistribution in dendrites. Neuronal activity stabilizes PlexinA1 in dendrites (via proteasome-dependent pathway), gating FARP1-mediated Sema3A responses.\",\n      \"method\": \"Co-immunoprecipitation (FARP1–Neuropilin-1/PlexinA1); immunofluorescence colocalization; FARP1 knockdown with dendritic morphology readout; F-actin distribution assay; neuronal activity manipulation with proteasome inhibition\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP, KD with defined morphological phenotype, multiple orthogonal methods\",\n      \"pmids\": [\"24899721\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"MAP4K4 directly phosphorylates FARP1 at a pTL motif and co-immunoprecipitates with FARP1; MAP4K4 inhibition increases neurite outgrowth in SH-SY5Y cells, a process known to involve FARP1, suggesting MAP4K4 regulates cytoskeletal dynamics partly via FARP1 phosphorylation.\",\n      \"method\": \"Phosphoproteomic analysis of MAP4K4-inhibited cells; in vitro kinase assay with recombinant proteins; co-immunoprecipitation; neurite outgrowth assay with MAP4K4 inhibitor\",\n      \"journal\": \"ACS chemical biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — direct in vitro phosphorylation assay, Co-IP, and cell-based functional readout in one study\",\n      \"pmids\": [\"26422651\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"siRNA-mediated knockdown of FARP1 in PC12 cells significantly inhibits Cdc42 activity, establishing FARP1 as a GEF that activates Cdc42 in neuroendocrine cells.\",\n      \"method\": \"siRNA knockdown in PC12 cells; ELISA-based Cdc42/Rac1 activity assay\",\n      \"journal\": \"Endocrine-related cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KD with defined GTPase activity readout, single lab\",\n      \"pmids\": [\"26911374\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Crystal structures of the FARP1 FERM domain (from zebrafish) revealed a three-lobed clover fold with a conserved positively charged surface patch; in vitro lipid-binding experiments showed the FERM domain binds specific phospholipids via this patch; cell-based analysis demonstrated the positively charged patch mediates plasma membrane localization of FARP1, and FERM domain interactions recruit FARP1 to postsynaptic sites in neurons.\",\n      \"method\": \"X-ray crystallography; in vitro phospholipid-binding assay; mutagenesis of charged surface patch; cell-based localization assay (fluorescence imaging); synaptic fractionation\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure, mutagenesis, in vitro lipid binding, and cell-based functional validation in one study\",\n      \"pmids\": [\"29992992\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"FARP1 acts as an essential Rac-GEF downstream of EGFR and c-Met receptor tyrosine kinases (via the AXL-Gab1-PI3K axis) to drive Rac1-mediated cell migration and ruffle dynamics in human lung adenocarcinoma cells, operating in a non-redundant manner with ARHGEF39 and TIAM2.\",\n      \"method\": \"siRNA/shRNA knockdown; Rac1 activity assay; live-cell imaging of ruffle dynamics; epistasis with RTK inhibitors (EGFR, c-Met) and PI3K inhibitors\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — KD with defined Rac1 activity and morphological readouts, epistasis with multiple pathway inhibitors, consistent across multiple GEFs\",\n      \"pmids\": [\"34731623\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In Drosophila border cells, the FARP1 ortholog Cdep functions downstream of Scribble/Dlg/Lgl basolateral polarity proteins and upstream of Rac to promote follower-cell crawling and cluster cohesion during collective migration; relocalization of Cdep::GFP partially rescues Scribble knockdown, establishing a Scrib/Cdep/Rac epistatic pathway.\",\n      \"method\": \"Genetic epistasis (Scribble, Dlg, Lgl knockdown); live imaging of border-cell migration; Cdep::GFP relocalization rescue experiment; Rac1 activity readout\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis with rescue experiment and live imaging, multiple orthogonal approaches\",\n      \"pmids\": [\"36347240\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"FARP1 mediates Gi/o-coupled GPCR (OXER1, LPA receptor)-induced tunneling nanotube (TNT) formation in adrenocortical cancer cells via a Gβγ/PKCα/FARP1/Cdc42 axis; FARP1 acts downstream of PI3K and PKCα signaling and upstream of Cdc42 to drive actin-rich TNT biogenesis.\",\n      \"method\": \"Pertussis toxin treatment; siRNA knockdown of FARP1; Cdc42 activity assay; pharmacological inhibition (PI3K, PKCα, EGFR transactivation); live imaging of TNT formation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — KD with specific actin-structure readout, epistasis with multiple pathway inhibitors, Cdc42 activity assay\",\n      \"pmids\": [\"37390986\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"FARP1 is recruited by the lactate receptor GPR81 to activate RAC1, thereby promoting GLUT4 translocation to the plasma membrane and insulin-independent glucose uptake in skeletal muscle; GPR81 knockout impairs this axis while GPR81 activation enhances it.\",\n      \"method\": \"GPR81 KO mouse model; co-immunoprecipitation (GPR81–FARP1); RAC1 activity assay; GLUT4 translocation assay; genetic upregulation/downregulation of lactate production (LDHA KO)\",\n      \"journal\": \"Cell research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP, KO models, Rac1 activity assay, GLUT4 translocation as specific functional readout, multiple orthogonal methods\",\n      \"pmids\": [\"41530347\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"FARP1 is a multi-domain (FERM–DH–PH) Rho guanine nucleotide exchange factor whose FERM domain binds phospholipids and interacts with transmembrane partners (SynCAM 1, PlexinA4, PlexinA1, GPR81) to recruit it to specific membrane compartments (postsynapse, plasma membrane), where its DH domain activates Rac1 and/or Cdc42 to drive F-actin remodeling underlying synapse formation, dendritic growth, cell migration, tunneling nanotube biogenesis, and insulin-independent GLUT4 translocation; its activity is regulated upstream by retinoid-induced transcription, MAP4K4-mediated phosphorylation, PI3K/PKCα signaling, and Scribble-dependent polarity complexes.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"FARP1 is a FERM–DH–PH domain-containing Rho guanine nucleotide exchange factor that couples transmembrane receptor signals to Rac1 and Cdc42 activation, driving F-actin remodeling in processes including synaptogenesis, dendritic arborization, cell migration, tunneling nanotube formation, and glucose transporter translocation. Its FERM domain binds phospholipids via a conserved positively charged surface patch and directly engages transmembrane partners—SynCAM 1 at postsynaptic sites, PlexinA1/PlexinA4 in Semaphorin signaling, and GPR81 in skeletal muscle—to recruit FARP1 to the plasma membrane where the DH domain catalyzes GTP loading of Rac1 and Cdc42 [PMID:29992992, PMID:23209303, PMID:19217374, PMID:41530347]. FARP1 operates downstream of diverse upstream inputs including retinoid-induced transcription, PI3K/PKCα signaling from Gi/o-coupled GPCRs, EGFR/c-Met receptor tyrosine kinases, and Scribble-dependent polarity complexes, and is directly phosphorylated by MAP4K4 [PMID:37390986, PMID:34731623, PMID:36347240, PMID:26422651]. In neurons, FARP1 functions as an essential effector linking Semaphorin6A/PlexinA4 and Sema3A/Neuropilin-1/PlexinA1 signaling to dendritic growth and synapse formation, while in non-neuronal cells it drives Rac1-dependent migration ruffles, Cdc42-dependent tunneling nanotubes, and GPR81-mediated insulin-independent GLUT4 translocation [PMID:19217374, PMID:24899721, PMID:34731623, PMID:41530347].\",\n  \"teleology\": [\n    {\n      \"year\": 1997,\n      \"claim\": \"Cloning of FARP1 (CDEP) established its multi-domain architecture (FERM–DH–PH), predicting it as a Rho-family GEF linked to cytoskeletal regulation—answering the basic question of gene identity and domain composition.\",\n      \"evidence\": \"cDNA cloning, sequence analysis, and Northern blot from human tissues\",\n      \"pmids\": [\"9425278\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"GEF activity was inferred from sequence homology, not biochemically demonstrated\", \"substrate GTPase specificity unknown\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Biochemical demonstration that the FARP1 DH-PH domain catalyzes GDP dissociation from RhoA in vitro confirmed it is a bona fide Rho-GEF, and its truncated form's transforming activity in fibroblasts linked GEF activity to a cellular outcome.\",\n      \"evidence\": \"In vitro [³H]GDP dissociation assay with recombinant DH-PH domain; NIH3T3 focus formation assay\",\n      \"pmids\": [\"11680691\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Initial assay used RhoA as substrate; later studies showed primary activity toward Rac1/Cdc42, raising questions about in vivo substrate preference\", \"mechanism of autoinhibition by FERM domain not addressed\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Placing FARP1 as an effector of Semaphorin6A/PlexinA4 signaling in motor neuron dendritic growth established the first physiological receptor-to-GEF pathway for FARP1, showing its GEF domain is required for dendritic morphogenesis and that retinoid signaling induces FARP1 expression.\",\n      \"evidence\": \"Loss- and gain-of-function in chick spinal cord; GEF-domain deletion mutants; epistasis with Sema6A/PlexA4\",\n      \"pmids\": [\"19217374\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether FARP1 activates Rac1 or Cdc42 in this context was not resolved\", \"direct physical interaction between FARP1 and PlexinA4 not demonstrated\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Identification of SynCAM 1 as a direct FERM-domain binding partner at the postsynapse, combined with mutual epistasis and Rac1 activation assays, established FARP1 as a synaptic organizer linking adhesion to actin-based spine remodeling and synapse number regulation.\",\n      \"evidence\": \"Proteomics of SynCAM 1 KO synaptic membranes; reciprocal Co-IP; Rac1 activity assay; spine/synapse morphology in knockdown/overexpression; F-actin staining\",\n      \"pmids\": [\"23209303\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of FERM–SynCAM 1 interaction unresolved\", \"retrograde signaling mechanism not molecularly defined\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstrating that FARP1 interacts with Neuropilin-1/PlexinA1 and is required for Sema3A-induced dendritic arborization broadened the repertoire of Semaphorin pathways utilizing FARP1, and revealed that neuronal activity gates this response by stabilizing PlexinA1.\",\n      \"evidence\": \"Co-IP of FARP1–Neuropilin-1/PlexinA1; FARP1 knockdown with dendritic morphology readout; activity-dependent PlexinA1 stabilization via proteasome inhibition\",\n      \"pmids\": [\"24899721\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether FARP1 binds PlexinA1 directly or via Neuropilin-1 scaffolding not distinguished\", \"GTPase substrate specificity in this pathway not tested\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Identifying MAP4K4 as a kinase that directly phosphorylates FARP1 at a pTL motif provided the first post-translational regulatory mechanism for FARP1 and connected it to a broader kinase-GEF signaling axis in neurite outgrowth.\",\n      \"evidence\": \"Phosphoproteomics; in vitro kinase assay with recombinant MAP4K4 and FARP1; Co-IP; neurite outgrowth assay with MAP4K4 inhibitor\",\n      \"pmids\": [\"26422651\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of phosphorylation on GEF activity not directly measured\", \"phosphorylation site mutant phenotype not tested in neurons\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Showing that FARP1 knockdown reduces Cdc42 activity in PC12 cells established Cdc42 as a second in vivo substrate, broadening FARP1's GTPase target range beyond Rac1.\",\n      \"evidence\": \"siRNA knockdown in PC12 cells; ELISA-based Cdc42/Rac1 activity assay\",\n      \"pmids\": [\"26911374\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single cell line; not confirmed with constitutively active or dominant-negative Cdc42 rescue\", \"whether Cdc42 activation is direct or indirect not resolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Crystal structure of the FERM domain revealed the lipid-binding surface patch that mediates plasma membrane recruitment, providing the first structural basis for how FARP1 is positioned at membranes to activate downstream GTPases.\",\n      \"evidence\": \"X-ray crystallography of zebrafish FARP1 FERM domain; in vitro phospholipid binding; charge-patch mutagenesis; cell-based localization and synaptic fractionation\",\n      \"pmids\": [\"29992992\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No full-length structure; autoinhibitory mechanism between FERM and DH domains remains unknown\", \"structure is from zebrafish—human FERM structure not solved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Demonstrating FARP1 as an essential non-redundant Rac-GEF downstream of EGFR/c-Met/PI3K extended its role from neurons to cancer cell migration, establishing that multiple RTK pathways converge on FARP1 to drive Rac1-dependent membrane ruffling.\",\n      \"evidence\": \"siRNA/shRNA knockdown in lung adenocarcinoma cells; Rac1 activity assay; live-cell ruffle dynamics; epistasis with EGFR, c-Met, and PI3K inhibitors\",\n      \"pmids\": [\"34731623\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How PI3K activates FARP1 (direct PH domain engagement vs. intermediate) not resolved\", \"in vivo tumor model validation not performed\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Genetic epistasis in Drosophila border cells placed the FARP1 ortholog Cdep downstream of Scribble/Dlg/Lgl polarity proteins and upstream of Rac, establishing a conserved polarity-to-Rac signaling axis for collective cell migration.\",\n      \"evidence\": \"Scribble/Dlg/Lgl knockdown; Cdep::GFP relocalization rescue; live imaging of border-cell migration in Drosophila\",\n      \"pmids\": [\"36347240\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether Scribble directly binds Cdep/FARP1 or acts indirectly not determined\", \"conservation of this polarity pathway in mammalian collective migration not tested\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identification of a Gβγ/PKCα/FARP1/Cdc42 axis for GPCR-induced tunneling nanotube formation expanded FARP1's functional repertoire to intercellular communication structures and added PKCα as an upstream activator.\",\n      \"evidence\": \"siRNA knockdown of FARP1; pertussis toxin treatment; PI3K and PKCα inhibitors; Cdc42 activity assay; live imaging of TNTs in adrenocortical cancer cells\",\n      \"pmids\": [\"37390986\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether PKCα directly phosphorylates FARP1 not demonstrated\", \"mechanism linking FARP1/Cdc42 to the specific actin architecture of TNTs not resolved\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Demonstrating that GPR81 recruits FARP1 to activate Rac1 for GLUT4 translocation in skeletal muscle revealed a metabolic function for FARP1, connecting lactate sensing to insulin-independent glucose uptake.\",\n      \"evidence\": \"GPR81 KO mouse; Co-IP of GPR81–FARP1; Rac1 activity assay; GLUT4 translocation assay; LDHA KO for lactate modulation\",\n      \"pmids\": [\"41530347\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the FERM domain mediates GPR81 binding directly not shown\", \"in vivo contribution of FARP1 to whole-body glucose homeostasis not quantified\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A full-length structure of FARP1 explaining FERM-mediated autoinhibition and activation mechanisms, along with in vivo genetic models defining its non-redundant roles across tissues, remain central open questions.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No full-length FARP1 structure or autoinhibition mechanism defined\", \"No FARP1 knockout mouse phenotype reported in the literature\", \"Substrate selectivity determinants for Rac1 vs. Cdc42 in different cellular contexts unresolved\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [1, 3, 6, 8, 10, 11]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [7, 11]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [8]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": []},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 4, 8, 9, 10, 11]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [2, 3, 4]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"SynCAM1\", \"PlexinA1\", \"PlexinA4\", \"NRP1\", \"MAP4K4\", \"GPR81\", \"RAC1\", \"CDC42\"],\n    \"other_free_text\": []\n  }\n}\n```"}