{"gene":"SPIRE1","run_date":"2026-06-10T07:46:40","timeline":{"discoveries":[{"year":2001,"finding":"Spir-1 localizes to Rab11-positive trans-Golgi network, post-Golgi vesicles, and recycling endosomes via its modified FYVE zinc finger motif and Spir-box domain; overexpression of a dominant-negative Spir-1 mutant arrests VSV-G protein transport to the plasma membrane, trapping it in TGN46-positive structures, establishing Spir-1 as a regulator of vesicle transport.","method":"Co-localization of GFP-tagged Rab GTPases with Spir-1 in NIH 3T3 cells; dominant-interfering mutant overexpression; VSV-G transport assay; integrity-of-motif mutants","journal":"Current biology : CB","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization with functional consequence via dominant-negative and motif-disruption mutants, single lab, two orthogonal approaches","pmids":["11747823"],"is_preprint":false},{"year":2009,"finding":"Spire1 is required for actin patch nucleation on early endosomes downstream of annexin A2; these actin patches, which also involve Arp2/3, control endosome biogenesis and transport from early to late endosomes.","method":"siRNA knockdown of Spire1; co-localization imaging; endosome transport assays; Arp2/3 involvement established by complementary knockdowns","journal":"Developmental cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional knockdown with defined endosomal phenotype, multiple factors tested, single lab","pmids":["19289089"],"is_preprint":false},{"year":2011,"finding":"Spire1 and Spire2 cooperate with Formin-2 (Fmn2) to nucleate actin filaments in mouse oocytes, driving two sequential steps: assembly of a cytoplasmic actin network for asymmetric meiotic spindle positioning, and promotion of cleavage furrow assembly for polar body extrusion.","method":"Knockdown/depletion of Spire1/Spire2 in mouse oocytes; live imaging; spindle positioning and polar body extrusion assays; genetic interaction with Fmn2","journal":"Current biology : CB","confidence":"High","confidence_rationale":"Tier 2 / Strong — loss-of-function with specific sequential phenotypic readouts, epistasis with Fmn2, replicated across two related papers in same year","pmids":["21620703"],"is_preprint":false},{"year":2011,"finding":"Vesicles recruit Spire1, Spire2, and Formin-2 to organize their own actin tracks, forming a network that connects vesicles to each other and the plasma membrane; vesicles move directionally along these connections in a myosin-Vb-dependent manner for long-range transport in mouse oocytes.","method":"Live imaging in mouse oocytes; depletion of actin nucleators; myosin-Vb inhibition; microtubule-independent transport assays","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — live imaging with multiple depletions showing actin-dependent, microtubule-independent mechanism, functional linkage to myosin-Vb motor","pmids":["21983562"],"is_preprint":false},{"year":2011,"finding":"Crystal structure of the Spir-1 KIND (kinase non-catalytic C-lobe domain) domain alone and in complex with the Fmn2 FSI (formin SPIR interaction motif) peptide reveals the molecular basis of Spir/formin cooperativity: the KIND domain adopts a protein kinase fold and an acidic groove on its surface engages conserved positively charged residues of the FSI peptide; this interaction inhibits formin nucleation activity and enhances Spire actin nucleation activity.","method":"X-ray crystallography; mutagenesis of interface residues; in vitro protein interaction studies confirming electrostatic nature of binding","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure of complex plus mutagenesis validation and in vitro binding assays in a single rigorous study","pmids":["21705804"],"is_preprint":false},{"year":2013,"finding":"Spire-1 is specifically recruited to invadosomes in Src-activated and cancer cells, where it forms a multi-molecular complex with Src kinase, formin mDia1, and actin; Spire-1 also interacts with the Rab3A GTPase at invadosomes; over- or under-expression of Spire-1 increases or decreases matrix degradation, respectively, demonstrating a functional role at invadosomes in cell invasion.","method":"Immunofluorescence co-localization; co-immunoprecipitation; overexpression and knockdown with matrix degradation assays","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — co-IP and co-localization plus gain/loss-of-function phenotype, single lab, multiple methods","pmids":["24213528"],"is_preprint":false},{"year":2013,"finding":"Spir-1 mutant mice (gene trap disrupting between KIND and WH2 domains) show a specific increase in fear memory in contextual and cued fear conditioning, and a slight reduction in cortical neuron dendritic spine number, pointing to a role for Spire-1 in neuronal circuits governing fear behavior.","method":"Gene trap mouse mutant; behavioral fear conditioning assays; microscopic analysis of dendritic spines","journal":"European journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo loss-of-function with specific behavioral and morphological phenotypes, single lab","pmids":["24345451"],"is_preprint":false},{"year":2015,"finding":"Spire1 acts downstream of Annexin A2 to regulate ATG9A trafficking from endosomes to autophagosomes via actin, enabling autophagosome formation during starvation-induced autophagy; ARP2 is also required in the same Annexin A2 effector pathway.","method":"siRNA knockdown of Spire1; ATG9A trafficking assays; autophagosome formation assays; epistasis with Annexin A2 and ARP2","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — pathway placement by epistasis and knockdown with defined trafficking phenotype, single lab","pmids":["26289944"],"is_preprint":false},{"year":2016,"finding":"Genome-wide siRNA screen identified SPIRE1 and SPIRE2 as host factors in Salmonella Typhimurium SipA-dependent invasion; stage-specific follow-up in knockout fibroblasts showed SPIRE1 affects bacterial binding to host cells, while SPIRE2 influences intracellular replication, suggesting non-redundant functions.","method":"Genome-wide siRNA screen; gentamicin protection assay; SPIRE1/SPIRE2 knockout fibroblasts; co-localization analysis","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — knockout cells with stage-specific functional assays, but mechanistic detail at binding step is limited; single lab","pmids":["27627128"],"is_preprint":false},{"year":2020,"finding":"SPIRE1 (predominantly) functions as a Rab27a effector on melanosomes, co-operating with formin-1 to generate actin tracks required for myosin-Va-dependent long-range melanosome dispersion in melanocytes; Rab27a recruits SPIREs to the organelle membrane, integrating motor and track assembly activity.","method":"Co-immunoprecipitation; organelle fractionation; live imaging; knockdown/knockout of SPIRE1 and Rab27a in melanocytes; myosin-Va transport assays","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, direct organelle localization with functional consequence, multiple orthogonal assays, identifies SPIRE1 as Rab27a effector","pmids":["32661310"],"is_preprint":false},{"year":2021,"finding":"lnc-SMaRT represses Spire1 translation by base-pairing with a G-quadruplex-forming sequence in Spire1 mRNA within a complex containing the DHX36 helicase; Spire1 modulation participates in the regulation of proper skeletal muscle differentiation timing.","method":"RNA immunoprecipitation; translation reporter assays; G-quadruplex mutagenesis; Spire1 knockdown/overexpression during myoblast differentiation","journal":"Journal of molecular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct RNA-binding interaction established with functional consequence in differentiation, single lab, multiple approaches","pmids":["34863993"],"is_preprint":false},{"year":2022,"finding":"Spire1 and Myosin Vc (MyoVc) associate with mature Weibel-Palade bodies (WPB) in endothelial cells; upon Ca2+-evoked exocytosis, they concentrate in actin ring structures at WPB-plasma membrane fusion sites; depletion of either Spire1 or MyoVc reduces actin ring formation and decreases VWF externalization after histamine stimulation.","method":"Immunofluorescence co-localization; siRNA knockdown; ELISA for VWF secretion; live imaging of Ca2+-evoked exocytosis","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization tied to functional exocytosis readout, loss-of-function with two proteins, single lab","pmids":["35084586"],"is_preprint":false},{"year":2022,"finding":"Spir-1 promotes innate immune signalling downstream of RIG-I/MDA-5 RNA sensing; in Spir-1 KO cells IRF3 and NF-κB-dependent gene activation is impaired; Spir-1 overexpression enhances IRF3 activation; vaccinia virus virulence factor K7 binds directly to Spir-1 via a diphenylalanine motif required for Spir-1-mediated IRF3 activation, and KO cells show increased vaccinia virus and Zika virus titres.","method":"SPIRE1 knockout cells (human and mouse); overexpression studies; direct binding assay of K7-Spire1; IRF3/NF-κB reporter assays; viral plaque/titre assays; diphenylalanine motif mutagenesis","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — KO cells, direct binding with mutagenesis, multiple orthogonal functional readouts (signalling reporters, viral titres), two distinct viruses tested","pmids":["35148361"],"is_preprint":false},{"year":2023,"finding":"The Spire1C splice variant localises to mitochondria and, together with the ER-anchored formin INF2, polymerizes actin at mitochondria-ER contact sites to promote mitochondrial fission; depletion of Spire1C blocks Myo19-driven fission and reduces mitochondria-ER contacts as measured by a split-luciferase system.","method":"Spire1C depletion; super-resolution imaging; split-luciferase ER-mitochondria contact assay; mitochondrial morphology quantification; genetic epistasis with INF2 and Myo19","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct localization to mitochondria tied to fission phenotype, epistasis with INF2 and Myo19, quantitative contact-site assay, multiple orthogonal methods","pmids":["36744380"],"is_preprint":false},{"year":2023,"finding":"MEK inhibition decreases cortical Spire-1 levels in polar body extrusion (PBE) oocytes, while PKA inhibition increases cortical Spire-1 levels at the spindle migration stage; combined inhibition compensates the Spire-1 decrease, indicating that MEK and PKA signalling post-translationally regulate Spire-1 cortical localization during oocyte maturation.","method":"Chemical inhibition (PD98059/H89) during in vitro oocyte maturation; immunofluorescence and western blot for Spire-1 at defined maturation stages","journal":"Cellular and molecular biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — pharmacological inhibition only, single lab, no direct phosphorylation mapping or writer identification","pmids":["38158690"],"is_preprint":false}],"current_model":"SPIRE1 is a WH2-domain actin nucleator that forms a cooperative complex with formin family members (Fmn2/formin-1) via its KIND domain—whose crystal structure reveals an electrostatic interface with the formin FSI motif—to assemble actin filaments at organelle membranes; it acts as a Rab27a effector on melanosomes and other vesicles to generate myosin V-dependent actin tracks for long-range transport, drives asymmetric spindle positioning and polar body extrusion in oocytes, promotes endosome biogenesis and autophagosome formation via an Annexin A2 pathway, organizes actin rings at Weibel-Palade body fusion sites for VWF secretion, and through its mitochondria-targeted Spire1C splice variant cooperates with INF2 at ER-mitochondria contacts to promote mitochondrial fission; additionally, Spire1 functions as a virus restriction factor by enhancing RIG-I/MDA-5-dependent IRF3/NF-κB signalling, an activity that is directly antagonized by the vaccinia virus K7 protein binding to Spire1's diphenylalanine motif."},"narrative":{"mechanistic_narrative":"SPIRE1 is a WH2-domain actin nucleator that assembles actin filaments at organelle membranes to power membrane trafficking, organelle dynamics, and cytoskeletal organization across diverse cellular contexts [PMID:21983562, PMID:32661310]. Its central biochemical activity is cooperative actin nucleation with formin family members: the SPIRE KIND domain adopts a protein kinase fold whose acidic groove electrostatically engages the positively charged FSI motif of Formin-2, an interaction that couples and reciprocally tunes the nucleation activities of the two proteins [PMID:21705804]. SPIRE1 acts as a Rab27a effector recruited to melanosome membranes, where it builds actin tracks together with formin-1 that support myosin-Va-dependent long-range melanosome transport [PMID:32661310]; the same SPIRE–formin–myosin logic organizes vesicle-connecting actin networks for directional, microtubule-independent transport and drives asymmetric meiotic spindle positioning and polar body extrusion in oocytes [PMID:21620703, PMID:21983562]. SPIRE1 nucleates actin patches on early endosomes downstream of Annexin A2 to control endosome biogenesis and ATG9A trafficking into autophagosomes [PMID:19289089, PMID:26289944], organizes actin rings at Weibel-Palade body fusion sites to promote VWF secretion [PMID:35084586], and through its mitochondria-targeted Spire1C splice variant cooperates with the ER-anchored formin INF2 at ER–mitochondria contacts to drive mitochondrial fission [PMID:36744380]. Beyond its trafficking roles, SPIRE1 functions as a virus restriction factor that enhances RIG-I/MDA-5-dependent IRF3 and NF-κB signalling, an activity directly antagonized by the vaccinia virus K7 protein binding to a SPIRE1 diphenylalanine motif [PMID:35148361].","teleology":[{"year":2001,"claim":"Established SPIRE1 as a membrane-associated regulator of vesicle transport, defining where it acts before its actin-nucleating function was understood.","evidence":"Co-localization of GFP-Rab GTPases with Spir-1, motif-disruption mutants, and a VSV-G transport assay in NIH 3T3 cells","pmids":["11747823"],"confidence":"Medium","gaps":["Does not establish actin nucleation as the molecular mechanism","FYVE and Spir-box contributions to membrane targeting not separated functionally"]},{"year":2009,"claim":"Placed SPIRE1 in an Annexin A2 endosomal pathway, showing it nucleates actin patches that drive early-to-late endosome transport alongside Arp2/3.","evidence":"siRNA knockdown, co-localization imaging, and endosome transport assays","pmids":["19289089"],"confidence":"Medium","gaps":["Relationship between SPIRE1 nucleation and Arp2/3 nucleation not resolved","Direct interaction with Annexin A2 not shown"]},{"year":2011,"claim":"Defined the core SPIRE–formin actin machine in vivo and structurally, showing SPIRE1/2 cooperate with Fmn2 to build actin networks for spindle positioning, polar body extrusion, and myosin-Vb-dependent vesicle transport.","evidence":"Oocyte depletion with live imaging and Fmn2 epistasis; vesicle actin-track imaging with myosin-Vb inhibition; KIND–FSI crystal structure with interface mutagenesis","pmids":["21620703","21983562","21705804"],"confidence":"High","gaps":["Mechanism of SPIRE/formin recruitment to specific membranes not defined","How nucleation activity is switched on at the organelle surface unclear"]},{"year":2013,"claim":"Extended SPIRE1's actin-nucleating role to disease-relevant contexts, linking it to invadosome-driven matrix degradation and to neuronal circuits governing fear behavior.","evidence":"Co-IP and co-localization with Src/mDia1/Rab3A plus matrix degradation assays; gene-trap mouse with fear conditioning and dendritic spine analysis","pmids":["24213528","24345451"],"confidence":"Medium","gaps":["Invadosome partner interactions are Co-IP based without reciprocal validation","Molecular basis of the neuronal phenotype not mapped to actin nucleation"]},{"year":2015,"claim":"Connected SPIRE1 actin function to autophagy by showing it routes ATG9A from endosomes to autophagosomes downstream of Annexin A2.","evidence":"siRNA knockdown, ATG9A trafficking and autophagosome formation assays, epistasis with Annexin A2 and ARP2","pmids":["26289944"],"confidence":"Medium","gaps":["Direct actin requirement at ATG9A vesicles not visualized","Selectivity for starvation-induced versus basal autophagy unclear"]},{"year":2016,"claim":"Identified SPIRE1 (distinct from SPIRE2) as a non-redundant host factor for Salmonella invasion at the bacterial binding step.","evidence":"Genome-wide siRNA screen, gentamicin protection assays, and stage-specific analysis in SPIRE1/SPIRE2 knockout fibroblasts","pmids":["27627128"],"confidence":"Medium","gaps":["Mechanistic detail at the binding step limited","Whether actin nucleation underlies the binding defect not established"]},{"year":2020,"claim":"Resolved how SPIRE1 is targeted to organelles, identifying it as a Rab27a effector that builds formin-1-dependent actin tracks for myosin-Va melanosome transport.","evidence":"Reciprocal Co-IP, organelle fractionation, live imaging, and knockdown/knockout of SPIRE1 and Rab27a in melanocytes","pmids":["32661310"],"confidence":"High","gaps":["Direct structural basis of Rab27a–SPIRE1 binding not defined","Generality of Rab-effector recruitment to other organelles not tested here"]},{"year":2021,"claim":"Revealed post-transcriptional control of SPIRE1, showing lnc-SMaRT and DHX36 repress its translation via an mRNA G-quadruplex to time skeletal muscle differentiation.","evidence":"RNA immunoprecipitation, translation reporter assays, G-quadruplex mutagenesis, and SPIRE1 modulation during myoblast differentiation","pmids":["34863993"],"confidence":"Medium","gaps":["Actin-dependent mechanism in muscle differentiation not defined","Physiological trigger for translational repression unclear"]},{"year":2022,"claim":"Broadened SPIRE1's roles to regulated secretion and innate antiviral immunity, organizing actin rings for VWF release and enhancing RIG-I/MDA-5 signalling targeted by vaccinia K7.","evidence":"WPB co-localization with knockdown and VWF ELISA; SPIRE1 KO cells, K7 direct binding with diphenylalanine motif mutagenesis, IRF3/NF-κB reporters, and viral titres","pmids":["35084586","35148361"],"confidence":"High","gaps":["Whether antiviral signalling depends on SPIRE1 actin nucleation not resolved","Mechanism linking the diphenylalanine motif to IRF3 activation unclear"]},{"year":2023,"claim":"Established a mitochondria-specific SPIRE1 isoform function, showing Spire1C polymerizes actin with INF2 at ER–mitochondria contacts to enable Myo19-driven fission.","evidence":"Spire1C depletion, super-resolution imaging, split-luciferase ER–mitochondria contact assay, and epistasis with INF2 and Myo19","pmids":["36744380"],"confidence":"High","gaps":["How the Spire1C splice variant is targeted to mitochondria not defined","Coordination of fission with the broader fission machinery (Drp1) not addressed"]},{"year":2023,"claim":"Provided a first link between MEK/PKA signalling and SPIRE1, indicating its cortical localization in oocytes is regulated post-translationally during maturation.","evidence":"Pharmacological MEK and PKA inhibition during in vitro oocyte maturation with immunofluorescence and western blot","pmids":["38158690"],"confidence":"Low","gaps":["No direct phosphorylation site mapping or kinase identification","Inhibitor-based evidence only, no genetic confirmation"]},{"year":null,"claim":"How SPIRE1's single core actin-nucleation activity is selectively deployed and regulated across its many membrane and signalling contexts remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model of how Rab/effector recruitment, splice variants, and post-translational signals direct SPIRE1 to specific organelles","Whether antiviral signalling and bacterial-invasion roles require actin nucleation is untested","Direct structural basis of organelle-targeting interactions beyond KIND–FSI not defined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[1,2,3,4,9,13]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[10]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[4,9]}],"localization":[{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[0,3,9,11]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[1,7]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0]},{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[13]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[3,11]}],"pathway":[{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[7]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[12]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0,3,9]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[13]},{"term_id":"R-HSA-109582","term_label":"Hemostasis","supporting_discovery_ids":[11]}],"complexes":[],"partners":["FMN2","FMN1","INF2","RAB27A","ANXA2","MYO19"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q08AE8","full_name":"Protein spire homolog 1","aliases":[],"length_aa":756,"mass_kda":85.5,"function":"Acts as an actin nucleation factor, remains associated with the slow-growing pointed end of the new filament (PubMed:11747823, PubMed:21620703). Involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport (PubMed:11747823). Required for asymmetric spindle positioning and asymmetric cell division during meiosis (PubMed:21620703). Required for normal formation of the cleavage furrow and for polar body extrusion during female germ cell meiosis (PubMed:21620703). Also acts in the nucleus: together with FMN2, promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage (PubMed:26287480). In addition, promotes innate immune signaling downstream of dsRNA sensing (PubMed:35148361). Mechanistically, contributes to IRF3 phosphorylation and activation downstream of MAVS and upstream of TBK1 (PubMed:35148361)","subcellular_location":"Cytoplasm, cytoskeleton; Cytoplasm, perinuclear region; Cell membrane; Cytoplasmic vesicle membrane","url":"https://www.uniprot.org/uniprotkb/Q08AE8/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SPIRE1","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":[{"gene":"ACTB","stoichiometry":0.2},{"gene":"ACTG1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/SPIRE1","total_profiled":1310},"omim":[{"mim_id":"609217","title":"SPIRE-TYPE ACTIN NUCLEATION FACTOR 2; SPIRE2","url":"https://www.omim.org/entry/609217"},{"mim_id":"609216","title":"SPIRE-TYPE ACTIN NUCLEATION FACTOR 1; SPIRE1","url":"https://www.omim.org/entry/609216"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"},{"location":"Plasma membrane","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SPIRE1"},"hgnc":{"alias_symbol":["spir-1","KIAA1135"],"prev_symbol":[]},"alphafold":{"accession":"Q08AE8","domains":[{"cath_id":"1.10.510.10","chopping":"38-103_119-165_191-250_266-284_297-320","consensus_level":"medium","plddt":86.1437,"start":38,"end":320},{"cath_id":"3.30.40.10","chopping":"555-648_694-734","consensus_level":"high","plddt":81.7647,"start":555,"end":734}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q08AE8","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q08AE8-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q08AE8-F1-predicted_aligned_error_v6.png","plddt_mean":64.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SPIRE1","jax_strain_url":"https://www.jax.org/strain/search?query=SPIRE1"},"sequence":{"accession":"Q08AE8","fasta_url":"https://rest.uniprot.org/uniprotkb/Q08AE8.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q08AE8/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q08AE8"}},"corpus_meta":[{"pmid":"33417682","id":"PMC_33417682","title":"The 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dominant-interfering mutant overexpression; VSV-G transport assay; integrity-of-motif mutants\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization with functional consequence via dominant-negative and motif-disruption mutants, single lab, two orthogonal approaches\",\n      \"pmids\": [\"11747823\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Spire1 is required for actin patch nucleation on early endosomes downstream of annexin A2; these actin patches, which also involve Arp2/3, control endosome biogenesis and transport from early to late endosomes.\",\n      \"method\": \"siRNA knockdown of Spire1; co-localization imaging; endosome transport assays; Arp2/3 involvement established by complementary knockdowns\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional knockdown with defined endosomal phenotype, multiple factors tested, single lab\",\n      \"pmids\": [\"19289089\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Spire1 and Spire2 cooperate with Formin-2 (Fmn2) to nucleate actin filaments in mouse oocytes, driving two sequential steps: assembly of a cytoplasmic actin network for asymmetric meiotic spindle positioning, and promotion of cleavage furrow assembly for polar body extrusion.\",\n      \"method\": \"Knockdown/depletion of Spire1/Spire2 in mouse oocytes; live imaging; spindle positioning and polar body extrusion assays; genetic interaction with Fmn2\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — loss-of-function with specific sequential phenotypic readouts, epistasis with Fmn2, replicated across two related papers in same year\",\n      \"pmids\": [\"21620703\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Vesicles recruit Spire1, Spire2, and Formin-2 to organize their own actin tracks, forming a network that connects vesicles to each other and the plasma membrane; vesicles move directionally along these connections in a myosin-Vb-dependent manner for long-range transport in mouse oocytes.\",\n      \"method\": \"Live imaging in mouse oocytes; depletion of actin nucleators; myosin-Vb inhibition; microtubule-independent transport assays\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — live imaging with multiple depletions showing actin-dependent, microtubule-independent mechanism, functional linkage to myosin-Vb motor\",\n      \"pmids\": [\"21983562\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Crystal structure of the Spir-1 KIND (kinase non-catalytic C-lobe domain) domain alone and in complex with the Fmn2 FSI (formin SPIR interaction motif) peptide reveals the molecular basis of Spir/formin cooperativity: the KIND domain adopts a protein kinase fold and an acidic groove on its surface engages conserved positively charged residues of the FSI peptide; this interaction inhibits formin nucleation activity and enhances Spire actin nucleation activity.\",\n      \"method\": \"X-ray crystallography; mutagenesis of interface residues; in vitro protein interaction studies confirming electrostatic nature of binding\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure of complex plus mutagenesis validation and in vitro binding assays in a single rigorous study\",\n      \"pmids\": [\"21705804\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Spire-1 is specifically recruited to invadosomes in Src-activated and cancer cells, where it forms a multi-molecular complex with Src kinase, formin mDia1, and actin; Spire-1 also interacts with the Rab3A GTPase at invadosomes; over- or under-expression of Spire-1 increases or decreases matrix degradation, respectively, demonstrating a functional role at invadosomes in cell invasion.\",\n      \"method\": \"Immunofluorescence co-localization; co-immunoprecipitation; overexpression and knockdown with matrix degradation assays\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — co-IP and co-localization plus gain/loss-of-function phenotype, single lab, multiple methods\",\n      \"pmids\": [\"24213528\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Spir-1 mutant mice (gene trap disrupting between KIND and WH2 domains) show a specific increase in fear memory in contextual and cued fear conditioning, and a slight reduction in cortical neuron dendritic spine number, pointing to a role for Spire-1 in neuronal circuits governing fear behavior.\",\n      \"method\": \"Gene trap mouse mutant; behavioral fear conditioning assays; microscopic analysis of dendritic spines\",\n      \"journal\": \"European journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo loss-of-function with specific behavioral and morphological phenotypes, single lab\",\n      \"pmids\": [\"24345451\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Spire1 acts downstream of Annexin A2 to regulate ATG9A trafficking from endosomes to autophagosomes via actin, enabling autophagosome formation during starvation-induced autophagy; ARP2 is also required in the same Annexin A2 effector pathway.\",\n      \"method\": \"siRNA knockdown of Spire1; ATG9A trafficking assays; autophagosome formation assays; epistasis with Annexin A2 and ARP2\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — pathway placement by epistasis and knockdown with defined trafficking phenotype, single lab\",\n      \"pmids\": [\"26289944\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Genome-wide siRNA screen identified SPIRE1 and SPIRE2 as host factors in Salmonella Typhimurium SipA-dependent invasion; stage-specific follow-up in knockout fibroblasts showed SPIRE1 affects bacterial binding to host cells, while SPIRE2 influences intracellular replication, suggesting non-redundant functions.\",\n      \"method\": \"Genome-wide siRNA screen; gentamicin protection assay; SPIRE1/SPIRE2 knockout fibroblasts; co-localization analysis\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — knockout cells with stage-specific functional assays, but mechanistic detail at binding step is limited; single lab\",\n      \"pmids\": [\"27627128\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"SPIRE1 (predominantly) functions as a Rab27a effector on melanosomes, co-operating with formin-1 to generate actin tracks required for myosin-Va-dependent long-range melanosome dispersion in melanocytes; Rab27a recruits SPIREs to the organelle membrane, integrating motor and track assembly activity.\",\n      \"method\": \"Co-immunoprecipitation; organelle fractionation; live imaging; knockdown/knockout of SPIRE1 and Rab27a in melanocytes; myosin-Va transport assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, direct organelle localization with functional consequence, multiple orthogonal assays, identifies SPIRE1 as Rab27a effector\",\n      \"pmids\": [\"32661310\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"lnc-SMaRT represses Spire1 translation by base-pairing with a G-quadruplex-forming sequence in Spire1 mRNA within a complex containing the DHX36 helicase; Spire1 modulation participates in the regulation of proper skeletal muscle differentiation timing.\",\n      \"method\": \"RNA immunoprecipitation; translation reporter assays; G-quadruplex mutagenesis; Spire1 knockdown/overexpression during myoblast differentiation\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct RNA-binding interaction established with functional consequence in differentiation, single lab, multiple approaches\",\n      \"pmids\": [\"34863993\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Spire1 and Myosin Vc (MyoVc) associate with mature Weibel-Palade bodies (WPB) in endothelial cells; upon Ca2+-evoked exocytosis, they concentrate in actin ring structures at WPB-plasma membrane fusion sites; depletion of either Spire1 or MyoVc reduces actin ring formation and decreases VWF externalization after histamine stimulation.\",\n      \"method\": \"Immunofluorescence co-localization; siRNA knockdown; ELISA for VWF secretion; live imaging of Ca2+-evoked exocytosis\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization tied to functional exocytosis readout, loss-of-function with two proteins, single lab\",\n      \"pmids\": [\"35084586\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Spir-1 promotes innate immune signalling downstream of RIG-I/MDA-5 RNA sensing; in Spir-1 KO cells IRF3 and NF-κB-dependent gene activation is impaired; Spir-1 overexpression enhances IRF3 activation; vaccinia virus virulence factor K7 binds directly to Spir-1 via a diphenylalanine motif required for Spir-1-mediated IRF3 activation, and KO cells show increased vaccinia virus and Zika virus titres.\",\n      \"method\": \"SPIRE1 knockout cells (human and mouse); overexpression studies; direct binding assay of K7-Spire1; IRF3/NF-κB reporter assays; viral plaque/titre assays; diphenylalanine motif mutagenesis\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — KO cells, direct binding with mutagenesis, multiple orthogonal functional readouts (signalling reporters, viral titres), two distinct viruses tested\",\n      \"pmids\": [\"35148361\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"The Spire1C splice variant localises to mitochondria and, together with the ER-anchored formin INF2, polymerizes actin at mitochondria-ER contact sites to promote mitochondrial fission; depletion of Spire1C blocks Myo19-driven fission and reduces mitochondria-ER contacts as measured by a split-luciferase system.\",\n      \"method\": \"Spire1C depletion; super-resolution imaging; split-luciferase ER-mitochondria contact assay; mitochondrial morphology quantification; genetic epistasis with INF2 and Myo19\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct localization to mitochondria tied to fission phenotype, epistasis with INF2 and Myo19, quantitative contact-site assay, multiple orthogonal methods\",\n      \"pmids\": [\"36744380\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"MEK inhibition decreases cortical Spire-1 levels in polar body extrusion (PBE) oocytes, while PKA inhibition increases cortical Spire-1 levels at the spindle migration stage; combined inhibition compensates the Spire-1 decrease, indicating that MEK and PKA signalling post-translationally regulate Spire-1 cortical localization during oocyte maturation.\",\n      \"method\": \"Chemical inhibition (PD98059/H89) during in vitro oocyte maturation; immunofluorescence and western blot for Spire-1 at defined maturation stages\",\n      \"journal\": \"Cellular and molecular biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — pharmacological inhibition only, single lab, no direct phosphorylation mapping or writer identification\",\n      \"pmids\": [\"38158690\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SPIRE1 is a WH2-domain actin nucleator that forms a cooperative complex with formin family members (Fmn2/formin-1) via its KIND domain—whose crystal structure reveals an electrostatic interface with the formin FSI motif—to assemble actin filaments at organelle membranes; it acts as a Rab27a effector on melanosomes and other vesicles to generate myosin V-dependent actin tracks for long-range transport, drives asymmetric spindle positioning and polar body extrusion in oocytes, promotes endosome biogenesis and autophagosome formation via an Annexin A2 pathway, organizes actin rings at Weibel-Palade body fusion sites for VWF secretion, and through its mitochondria-targeted Spire1C splice variant cooperates with INF2 at ER-mitochondria contacts to promote mitochondrial fission; additionally, Spire1 functions as a virus restriction factor by enhancing RIG-I/MDA-5-dependent IRF3/NF-κB signalling, an activity that is directly antagonized by the vaccinia virus K7 protein binding to Spire1's diphenylalanine motif.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SPIRE1 is a WH2-domain actin nucleator that assembles actin filaments at organelle membranes to power membrane trafficking, organelle dynamics, and cytoskeletal organization across diverse cellular contexts [#3, #9]. Its central biochemical activity is cooperative actin nucleation with formin family members: the SPIRE KIND domain adopts a protein kinase fold whose acidic groove electrostatically engages the positively charged FSI motif of Formin-2, an interaction that couples and reciprocally tunes the nucleation activities of the two proteins [#4]. SPIRE1 acts as a Rab27a effector recruited to melanosome membranes, where it builds actin tracks together with formin-1 that support myosin-Va-dependent long-range melanosome transport [#9]; the same SPIRE–formin–myosin logic organizes vesicle-connecting actin networks for directional, microtubule-independent transport and drives asymmetric meiotic spindle positioning and polar body extrusion in oocytes [#2, #3]. SPIRE1 nucleates actin patches on early endosomes downstream of Annexin A2 to control endosome biogenesis and ATG9A trafficking into autophagosomes [#1, #7], organizes actin rings at Weibel-Palade body fusion sites to promote VWF secretion [#11], and through its mitochondria-targeted Spire1C splice variant cooperates with the ER-anchored formin INF2 at ER–mitochondria contacts to drive mitochondrial fission [#13]. Beyond its trafficking roles, SPIRE1 functions as a virus restriction factor that enhances RIG-I/MDA-5-dependent IRF3 and NF-\\u03baB signalling, an activity directly antagonized by the vaccinia virus K7 protein binding to a SPIRE1 diphenylalanine motif [#12].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Established SPIRE1 as a membrane-associated regulator of vesicle transport, defining where it acts before its actin-nucleating function was understood.\",\n      \"evidence\": \"Co-localization of GFP-Rab GTPases with Spir-1, motif-disruption mutants, and a VSV-G transport assay in NIH 3T3 cells\",\n      \"pmids\": [\"11747823\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not establish actin nucleation as the molecular mechanism\", \"FYVE and Spir-box contributions to membrane targeting not separated functionally\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Placed SPIRE1 in an Annexin A2 endosomal pathway, showing it nucleates actin patches that drive early-to-late endosome transport alongside Arp2/3.\",\n      \"evidence\": \"siRNA knockdown, co-localization imaging, and endosome transport assays\",\n      \"pmids\": [\"19289089\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Relationship between SPIRE1 nucleation and Arp2/3 nucleation not resolved\", \"Direct interaction with Annexin A2 not shown\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Defined the core SPIRE–formin actin machine in vivo and structurally, showing SPIRE1/2 cooperate with Fmn2 to build actin networks for spindle positioning, polar body extrusion, and myosin-Vb-dependent vesicle transport.\",\n      \"evidence\": \"Oocyte depletion with live imaging and Fmn2 epistasis; vesicle actin-track imaging with myosin-Vb inhibition; KIND–FSI crystal structure with interface mutagenesis\",\n      \"pmids\": [\"21620703\", \"21983562\", \"21705804\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of SPIRE/formin recruitment to specific membranes not defined\", \"How nucleation activity is switched on at the organelle surface unclear\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Extended SPIRE1's actin-nucleating role to disease-relevant contexts, linking it to invadosome-driven matrix degradation and to neuronal circuits governing fear behavior.\",\n      \"evidence\": \"Co-IP and co-localization with Src/mDia1/Rab3A plus matrix degradation assays; gene-trap mouse with fear conditioning and dendritic spine analysis\",\n      \"pmids\": [\"24213528\", \"24345451\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Invadosome partner interactions are Co-IP based without reciprocal validation\", \"Molecular basis of the neuronal phenotype not mapped to actin nucleation\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Connected SPIRE1 actin function to autophagy by showing it routes ATG9A from endosomes to autophagosomes downstream of Annexin A2.\",\n      \"evidence\": \"siRNA knockdown, ATG9A trafficking and autophagosome formation assays, epistasis with Annexin A2 and ARP2\",\n      \"pmids\": [\"26289944\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct actin requirement at ATG9A vesicles not visualized\", \"Selectivity for starvation-induced versus basal autophagy unclear\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identified SPIRE1 (distinct from SPIRE2) as a non-redundant host factor for Salmonella invasion at the bacterial binding step.\",\n      \"evidence\": \"Genome-wide siRNA screen, gentamicin protection assays, and stage-specific analysis in SPIRE1/SPIRE2 knockout fibroblasts\",\n      \"pmids\": [\"27627128\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic detail at the binding step limited\", \"Whether actin nucleation underlies the binding defect not established\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Resolved how SPIRE1 is targeted to organelles, identifying it as a Rab27a effector that builds formin-1-dependent actin tracks for myosin-Va melanosome transport.\",\n      \"evidence\": \"Reciprocal Co-IP, organelle fractionation, live imaging, and knockdown/knockout of SPIRE1 and Rab27a in melanocytes\",\n      \"pmids\": [\"32661310\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct structural basis of Rab27a–SPIRE1 binding not defined\", \"Generality of Rab-effector recruitment to other organelles not tested here\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Revealed post-transcriptional control of SPIRE1, showing lnc-SMaRT and DHX36 repress its translation via an mRNA G-quadruplex to time skeletal muscle differentiation.\",\n      \"evidence\": \"RNA immunoprecipitation, translation reporter assays, G-quadruplex mutagenesis, and SPIRE1 modulation during myoblast differentiation\",\n      \"pmids\": [\"34863993\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Actin-dependent mechanism in muscle differentiation not defined\", \"Physiological trigger for translational repression unclear\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Broadened SPIRE1's roles to regulated secretion and innate antiviral immunity, organizing actin rings for VWF release and enhancing RIG-I/MDA-5 signalling targeted by vaccinia K7.\",\n      \"evidence\": \"WPB co-localization with knockdown and VWF ELISA; SPIRE1 KO cells, K7 direct binding with diphenylalanine motif mutagenesis, IRF3/NF-\\u03baB reporters, and viral titres\",\n      \"pmids\": [\"35084586\", \"35148361\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether antiviral signalling depends on SPIRE1 actin nucleation not resolved\", \"Mechanism linking the diphenylalanine motif to IRF3 activation unclear\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Established a mitochondria-specific SPIRE1 isoform function, showing Spire1C polymerizes actin with INF2 at ER–mitochondria contacts to enable Myo19-driven fission.\",\n      \"evidence\": \"Spire1C depletion, super-resolution imaging, split-luciferase ER–mitochondria contact assay, and epistasis with INF2 and Myo19\",\n      \"pmids\": [\"36744380\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How the Spire1C splice variant is targeted to mitochondria not defined\", \"Coordination of fission with the broader fission machinery (Drp1) not addressed\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Provided a first link between MEK/PKA signalling and SPIRE1, indicating its cortical localization in oocytes is regulated post-translationally during maturation.\",\n      \"evidence\": \"Pharmacological MEK and PKA inhibition during in vitro oocyte maturation with immunofluorescence and western blot\",\n      \"pmids\": [\"38158690\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct phosphorylation site mapping or kinase identification\", \"Inhibitor-based evidence only, no genetic confirmation\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SPIRE1's single core actin-nucleation activity is selectively deployed and regulated across its many membrane and signalling contexts remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model of how Rab/effector recruitment, splice variants, and post-translational signals direct SPIRE1 to specific organelles\", \"Whether antiviral signalling and bacterial-invasion roles require actin nucleation is untested\", \"Direct structural basis of organelle-targeting interactions beyond KIND–FSI not defined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [1, 2, 3, 4, 9, 13]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [10]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [4, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [0, 3, 9, 11]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [1, 7]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [13]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [3, 11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [12]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 3, 9]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [13]},\n      {\"term_id\": \"R-HSA-109582\", \"supporting_discovery_ids\": [11]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"FMN2\", \"FMN1\", \"INF2\", \"RAB27A\", \"ANXA2\", \"MYO19\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}