{"gene":"MOSPD2","run_date":"2026-06-10T02:59:50","timeline":{"discoveries":[{"year":2018,"finding":"MOSPD2 is an ER-anchored protein containing a Major Sperm Protein (MSP) domain that binds FFAT motifs, enabling it to tether the ER to endosomes, mitochondria, and Golgi by interacting with FFAT-containing proteins on those organelles. In vitro membrane tethering assays confirmed the MSP domain is sufficient for this function.","method":"Unbiased proteomic approach, in vitro membrane tethering assay, subcellular fractionation, co-immunoprecipitation","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro reconstitution of tethering activity, reciprocal Co-IP with multiple organelle-resident FFAT-containing partners, direct localization experiments; multiple orthogonal methods in a focused study","pmids":["29858488"],"is_preprint":false},{"year":2020,"finding":"Phosphorylation of a serine/threonine residue within a non-conventional 'Phospho-FFAT' motif is critical for binding to the MOSPD2 MSP domain, acting as a molecular switch for inter-organelle contact formation. Structural analysis of the MSP domain alone and in complex with conventional and Phospho-FFAT peptides revealed new mechanisms of FFAT recognition.","method":"Crystal structure determination, in vitro binding assays, phosphomimetic and phospho-dead mutagenesis, sterol transfer functional assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structures with and without ligands, mutagenesis of key residues, functional lipid transfer assay; multiple orthogonal methods in one rigorous study","pmids":["33124732"],"is_preprint":false},{"year":2022,"finding":"MOSPD2 forms ER-lipid droplet (LD) contacts through its CRAL-TRIO domain via direct protein-membrane interaction. An amphipathic helix within the CRAL-TRIO domain has affinity for lipid packing defects at the LD surface, and absence of MOSPD2 markedly disturbs lipid droplet assembly.","method":"Live-cell imaging, in vitro lipid-binding assays, amphipathic helix mutagenesis, MOSPD2 knockout cells, subcellular fractionation","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — direct protein-membrane interaction assay, domain mutagenesis, KO phenotype with specific LD assembly readout; multiple orthogonal methods","pmids":["35389430"],"is_preprint":false},{"year":2017,"finding":"MOSPD2 is expressed on the cytoplasmic membrane of human monocytes and neutrophils. Silencing or neutralizing MOSPD2 restricts monocyte migration induced by multiple chemokines and inhibits chemokine-receptor-downstream signaling events.","method":"siRNA knockdown, neutralizing antibody blockade, chemotaxis migration assays, signaling pathway phosphorylation analysis","journal":"Journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — clean KD and antibody blockade with defined cellular phenotype, signaling readout; single lab, two orthogonal perturbation methods","pmids":["28137892"],"is_preprint":false},{"year":2018,"finding":"MOSPD2 is expressed on invasive breast cancer cell membranes and is required for cancer cell chemotaxis migration; silencing MOSPD2 abates phosphorylation events involved in breast tumor cell chemotaxis and impairs metastasis to the lungs in vivo.","method":"siRNA knockdown in multiple breast cancer cell lines, chemotaxis assay, phosphorylation signaling analysis, in vivo metastasis mouse model","journal":"International journal of cancer","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — KD with defined in vitro and in vivo phenotypes plus signaling readout; single lab, orthogonal in vitro and in vivo methods","pmids":["29978511"],"is_preprint":false},{"year":2020,"finding":"MOSPD2 knockout mice show suppressed EAE development, markedly reduced inflammatory monocytes in blood, and T cells from KO mice display reduced proinflammatory cytokines and increased IL-4. Anti-MOSPD2 monoclonal antibodies abrogated EAE development, establishing MOSPD2 as a key regulator of inflammatory monocyte migration in vivo.","method":"MOSPD2 knockout mouse generation, EAE induction model, flow cytometry for immune cell subsets, cytokine analysis, monoclonal antibody treatment","journal":"Clinical and experimental immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO mouse with specific inflammatory phenotype, antibody rescue experiment; single lab, multiple in vivo readouts","pmids":["32353176"],"is_preprint":false},{"year":2025,"finding":"MOSPD2 regulates monocyte adhesion/migration balance by maintaining integrin αLβ2 (LFA-1/CD11a/CD18) in an inactive low-affinity conformation. Silencing or antibody blockade of MOSPD2 shifts LFA-1 to an active high-affinity form and induces adhesion-associated signaling. Co-immunoprecipitation showed MOSPD2 binds integrin-β2 (CD18) but not integrin-β1 (CD29).","method":"siRNA knockdown, humanized anti-MOSPD2 monoclonal antibody (IW-601), co-immunoprecipitation, integrin conformation assay, adhesion assays to ECM and adhesion molecules, in vivo RA and IBD models","journal":"Immunologic research","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — Co-IP establishing direct binding to integrin-β2, KD and antibody blockade with specific integrin activation readout; single lab, multiple orthogonal methods","pmids":["40312574"],"is_preprint":false},{"year":2020,"finding":"In teleost fish (mudskipper), MOSPD2 acts as a surface receptor for LEAP-2 on monocytes/macrophages. Direct interaction between BpLEAP-2 and BpMOSPD2 was confirmed by co-immunoprecipitation; knockdown of MOSPD2 inhibited LEAP-2-induced chemotaxis, bacterial killing, and cytokine modulation.","method":"Yeast two-hybrid cDNA library screening, co-immunoprecipitation, RNA interference knockdown, chemotaxis assay, cytokine mRNA quantification","journal":"Zoological research","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — direct binding confirmed by Co-IP after Y2H screen, KD with defined functional phenotypes; single lab in a fish ortholog model","pmids":["33124217"],"is_preprint":false},{"year":2025,"finding":"In teleost monocytes/macrophages, LEAP2 stimulation triggers retromer-dependent trafficking of MOSPD2 from the ER to early endosomes and then to the plasma membrane, and this redistribution is required for LEAP2-induced chemotaxis. Core retromer subunits VPS35, VPS26, and VPS29 are required; Co-IP with mass spectrometry confirmed direct binding between MOSPD2 and VPS35.","method":"Subcellular fractionation, immunofluorescence, siRNA knockdown of retromer subunits, co-immunoprecipitation plus mass spectrometry, domain-mapping experiments, chemotaxis assay","journal":"Zoological research","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — Co-IP+MS confirmed MOSPD2–VPS35 interaction, KD of retromer subunits with defined trafficking and migration phenotypes; single lab, multiple orthogonal methods in a fish ortholog","pmids":["41017400"],"is_preprint":false},{"year":2023,"finding":"At the Toxoplasma PVM-host interface, MOSPD2 association requires its CRAL/TRIO domain and tail anchor. Immunoprecipitation with LC-MS/MS from MOSPD2-expressing host cells enriched PVM-localized parasite proteins, and most MOSPD2 at the PVM is newly translated after infection. MOSPD2 KO results in at most modest impairment of Toxoplasma growth in vitro.","method":"Immunoprecipitation, LC-MS/MS, domain-deletion mutagenesis, MOSPD2 KO cells, immunofluorescence microscopy","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — domain mutagenesis defining required regions, IP-MS for interacting parasite proteins, KO growth assay; single lab, multiple orthogonal methods","pmids":["37341482"],"is_preprint":false},{"year":2025,"finding":"VAPA, VAPB, and MOSPD2 together mediate ER-parasitophorous vacuole membrane (PVM) contact sites in Toxoplasma-infected cells; cells deficient in all three fail to recruit host ER to the PV, and parasites show growth defects. A parasite protein TgVIP1 harbours an FFAT-like motif that binds VAPA/VAPB to establish this contact.","method":"Genetic knockout of VAPA/VAPB/MOSPD2, fluorescence microscopy, FFAT-motif interaction assays","journal":"Nature microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — triple KO with specific ER-PV contact and parasite growth phenotype; single study with genetic epistasis and microscopy readouts","pmids":["41073664"],"is_preprint":false}],"current_model":"MOSPD2 is an ER-anchored membrane protein that functions as a general ER tether: its MSP domain binds FFAT (and phospho-FFAT) motifs on organelle-resident proteins to form ER-endosome, ER-mitochondria, ER-Golgi, and ER-lipid droplet contact sites (the last via a CRAL-TRIO domain that senses lipid packing defects on LD surfaces), while on the surface of myeloid cells it acts as an adhesion checkpoint by holding integrin αLβ2 in an inactive conformation and coupling chemokine receptor signaling to directional migration, and in lower vertebrates it serves as a surface receptor for the innate immune peptide LEAP-2, whose binding triggers retromer-dependent MOSPD2 trafficking from the ER to the plasma membrane to promote monocyte/macrophage chemotaxis."},"narrative":{"mechanistic_narrative":"MOSPD2 is an ER-anchored membrane protein that functions as a general inter-organelle tether, using its Major Sperm Protein (MSP) domain to bind FFAT motifs on organelle-resident partners and thereby form ER-endosome, ER-mitochondria, and ER-Golgi contact sites [PMID:29858488]. Recognition is regulated by a phosphorylation switch: phosphorylation of a serine/threonine residue within a non-conventional 'phospho-FFAT' motif controls binding to the MSP domain, a mechanism resolved at atomic resolution by crystal structures of the MSP domain alone and bound to conventional and phospho-FFAT peptides [PMID:33124732]. Beyond FFAT-dependent tethering, MOSPD2 also forms ER-lipid droplet contacts through a CRAL-TRIO domain whose amphipathic helix senses lipid packing defects at the droplet surface, and its loss disturbs lipid droplet assembly [PMID:35389430]. In a distinct membrane context, MOSPD2 is displayed on the surface of myeloid cells where it controls chemokine-driven directional migration and couples to receptor-downstream signaling [PMID:28137892]; mechanistically it binds integrin-β2 (CD18) and holds integrin αLβ2 (LFA-1) in an inactive low-affinity conformation, acting as an adhesion checkpoint [PMID:40312574]. This migratory function underlies pro-inflammatory monocyte recruitment in vivo, as MOSPD2 knockout or antibody blockade suppresses experimental autoimmune encephalomyelitis [PMID:32353176] and breast cancer cell chemotaxis and lung metastasis [PMID:29978511]. In teleost orthologs MOSPD2 serves as a surface receptor for the antimicrobial peptide LEAP-2, whose binding triggers retromer (VPS35/VPS26/VPS29)-dependent trafficking of MOSPD2 from the ER to the plasma membrane to drive monocyte/macrophage chemotaxis [PMID:33124217, PMID:41017400]. MOSPD2 is also exploited at pathogen interfaces, where it and the VAP proteins establish ER-parasitophorous vacuole membrane contact sites in Toxoplasma-infected cells [PMID:37341482, PMID:41073664].","teleology":[{"year":2017,"claim":"Established the first cellular role for MOSPD2, identifying it as a surface protein on myeloid cells required for chemokine-induced migration rather than a purely intracellular factor.","evidence":"siRNA knockdown and neutralizing antibody blockade with chemotaxis and signaling readouts in human monocytes and neutrophils","pmids":["28137892"],"confidence":"Medium","gaps":["Did not identify the molecular binding partner mediating migration","Surface expression mechanism not resolved given ER localization shown later"]},{"year":2018,"claim":"Defined the core molecular function: MOSPD2 is an ER-anchored MSP-domain protein that tethers the ER to multiple organelles via FFAT-motif partners, placing it in the membrane contact site machinery.","evidence":"Unbiased proteomics, in vitro membrane tethering reconstitution, fractionation, and reciprocal Co-IP","pmids":["29858488"],"confidence":"High","gaps":["Structural basis of FFAT recognition not resolved","Reconciliation with reported plasma-membrane/migration role not addressed"]},{"year":2018,"claim":"Extended the migration phenotype to a disease-relevant context, showing MOSPD2 is required for tumor cell chemotaxis and metastasis in vivo.","evidence":"siRNA knockdown across breast cancer lines, chemotaxis, phospho-signaling, and an in vivo lung metastasis mouse model","pmids":["29978511"],"confidence":"Medium","gaps":["Direct receptor/partner mediating tumor chemotaxis not identified","Mechanistic link to ER tethering function unclear"]},{"year":2020,"claim":"Resolved how FFAT recognition is regulated, revealing a phosphorylation-controlled molecular switch via crystal structures of the MSP domain with conventional and phospho-FFAT ligands.","evidence":"Crystal structures with and without peptides, phosphomimetic/phospho-dead mutagenesis, and sterol transfer assays","pmids":["33124732"],"confidence":"High","gaps":["Kinases/phosphatases controlling the phospho-FFAT switch not identified","In vivo regulation of contact-site dynamics not addressed"]},{"year":2020,"claim":"Demonstrated the in vivo physiological consequence of MOSPD2-dependent migration, establishing it as a regulator of inflammatory monocyte recruitment in autoimmune disease.","evidence":"MOSPD2 knockout mice in an EAE model, flow cytometry, cytokine profiling, and monoclonal antibody treatment","pmids":["32353176"],"confidence":"Medium","gaps":["Surface receptor/effector mediating the phenotype not defined","T-cell cytokine shift mechanism unresolved"]},{"year":2020,"claim":"Identified a surface-receptor function for the MOSPD2 ortholog, showing it binds the antimicrobial peptide LEAP-2 to drive macrophage chemotaxis and antibacterial responses.","evidence":"Yeast two-hybrid screen, Co-IP, RNAi knockdown, and chemotaxis/cytokine assays in mudskipper","pmids":["33124217"],"confidence":"Medium","gaps":["Conservation of LEAP-2 receptor function in mammals not tested","Signaling downstream of LEAP-2/MOSPD2 not mapped"]},{"year":2022,"claim":"Expanded the tethering repertoire to lipid droplets and showed MOSPD2 can engage membranes directly, independent of FFAT proteins, through a lipid-packing-defect-sensing amphipathic helix.","evidence":"Live-cell imaging, in vitro lipid binding, amphipathic helix mutagenesis, and lipid droplet assembly phenotype in KO cells","pmids":["35389430"],"confidence":"High","gaps":["Mechanism linking ER-LD contact to lipid droplet assembly not defined","Coordination between CRAL-TRIO and MSP domain functions unclear"]},{"year":2023,"claim":"Showed MOSPD2 is recruited to the Toxoplasma parasitophorous vacuole membrane via its CRAL/TRIO domain and tail anchor, implicating its contact-site machinery at a pathogen interface.","evidence":"IP-LC-MS/MS, domain-deletion mutagenesis, KO growth assays, and immunofluorescence in infected host cells","pmids":["37341482"],"confidence":"Medium","gaps":["Functional importance is modest (limited growth defect)","Direct parasite-side binding partner of MOSPD2 not defined"]},{"year":2025,"claim":"Defined the molecular basis of the myeloid adhesion checkpoint, showing MOSPD2 binds integrin-β2 and locks LFA-1 in a low-affinity state, explaining its control of migration vs. adhesion balance.","evidence":"siRNA, humanized anti-MOSPD2 antibody, Co-IP, integrin conformation and adhesion assays, and in vivo RA/IBD models","pmids":["40312574"],"confidence":"Medium","gaps":["How an ER-resident protein reaches the cell surface to engage integrins not resolved","Structural basis of the MOSPD2-CD18 interaction unknown"]},{"year":2025,"claim":"Resolved how MOSPD2 reaches the surface, showing LEAP2 triggers retromer-dependent trafficking from ER to endosomes to plasma membrane required for chemotaxis.","evidence":"Fractionation, immunofluorescence, retromer-subunit knockdown, Co-IP/MS confirming MOSPD2-VPS35 binding, and chemotaxis assays in teleost cells","pmids":["41017400"],"confidence":"Medium","gaps":["Whether retromer-dependent surface trafficking operates in mammalian cells untested","Trigger linking LEAP2 binding to retromer recruitment not defined"]},{"year":2025,"claim":"Established that ER-PVM contact in Toxoplasma infection is mediated by VAPA/VAPB/MOSPD2 acting redundantly, with a parasite FFAT-like protein engaging the VAPs.","evidence":"Triple genetic knockout, fluorescence microscopy, and FFAT-motif interaction assays","pmids":["41073664"],"confidence":"Medium","gaps":["Relative contribution of MOSPD2 vs VAPA/VAPB not dissected","Consequence of ER-PVM contact for the parasite mechanistically unresolved"]},{"year":null,"claim":"How a single ER-tail-anchored tethering protein is converted into a cell-surface receptor and integrin regulator in myeloid cells, and whether the LEAP-2/retromer surface-trafficking axis is conserved in mammals, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No mammalian demonstration of LEAP-2 receptor or retromer surface-trafficking function","Topological reconciliation of ER-membrane tether vs plasma-membrane receptor roles missing"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,1]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[2]},{"term_id":"GO:0001618","term_label":"virus receptor activity","supporting_discovery_ids":[7]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[6]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0,2,8]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[3,6,8]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[0,8]},{"term_id":"GO:0005811","term_label":"lipid droplet","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[3,5,7]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[8]},{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[2]}],"complexes":[],"partners":["VAPA","VAPB","ITGB2","VPS35","LEAP2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8NHP6","full_name":"Motile sperm domain-containing protein 2","aliases":[],"length_aa":518,"mass_kda":59.7,"function":"Endoplasmic reticulum-anchored protein that mediates the formation of contact sites between the endoplasmic (ER) and endosomes, mitochondria or Golgi through interaction with conventional- and phosphorylated-FFAT-containing organelle-bound proteins (PubMed:29858488, PubMed:33124732, PubMed:35389430). In addition, forms endoplasmic reticulum (ER)-lipid droplets (LDs) contacts through a direct protein-membrane interaction and participates in LDs homeostasis (PubMed:35389430). The attachment mechanism involves an amphipathic helix that has an affinity for lipid packing defects present at the surface of LDs (PubMed:35389430). Promotes migration of primary monocytes and neutrophils, in response to various chemokines (PubMed:28137892)","subcellular_location":"Endoplasmic reticulum membrane","url":"https://www.uniprot.org/uniprotkb/Q8NHP6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MOSPD2","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":"SRPRA","stoichiometry":0.2},{"gene":"CCDC47","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/MOSPD2","total_profiled":1310},"omim":[{"mim_id":"301086","title":"MOTILE SPERM DOMAIN-CONTAINING PROTEIN 2; MOSPD2","url":"https://www.omim.org/entry/301086"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Endoplasmic reticulum","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MOSPD2"},"hgnc":{"alias_symbol":["MGC26706"],"prev_symbol":[]},"alphafold":{"accession":"Q8NHP6","domains":[{"cath_id":"-","chopping":"2-78","consensus_level":"high","plddt":93.9742,"start":2,"end":78},{"cath_id":"3.40.525.10","chopping":"85-232","consensus_level":"high","plddt":93.8958,"start":85,"end":232},{"cath_id":"2.60.40.10","chopping":"324-445","consensus_level":"high","plddt":86.4725,"start":324,"end":445}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8NHP6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8NHP6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8NHP6-F1-predicted_aligned_error_v6.png","plddt_mean":80.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MOSPD2","jax_strain_url":"https://www.jax.org/strain/search?query=MOSPD2"},"sequence":{"accession":"Q8NHP6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8NHP6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8NHP6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8NHP6"}},"corpus_meta":[{"pmid":"33124732","id":"PMC_33124732","title":"FFAT motif phosphorylation controls formation and lipid transfer function of inter-organelle contacts.","date":"2020","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/33124732","citation_count":115,"is_preprint":false},{"pmid":"29858488","id":"PMC_29858488","title":"Identification of MOSPD2, a novel scaffold for endoplasmic reticulum membrane contact sites.","date":"2018","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/29858488","citation_count":103,"is_preprint":false},{"pmid":"34749525","id":"PMC_34749525","title":"Proximity-Labeling Reveals Novel Host and Parasite Proteins at the Toxoplasma Parasitophorous Vacuole Membrane.","date":"2021","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/34749525","citation_count":35,"is_preprint":false},{"pmid":"35389430","id":"PMC_35389430","title":"MOSPD2 is an endoplasmic reticulum-lipid droplet tether functioning in LD homeostasis.","date":"2022","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/35389430","citation_count":30,"is_preprint":false},{"pmid":"33124217","id":"PMC_33124217","title":"MOSPD2 is a receptor mediating the LEAP-2 effect on monocytes/macrophages in a teleost, Boleophthalmus pectinirostris.","date":"2020","source":"Zoological research","url":"https://pubmed.ncbi.nlm.nih.gov/33124217","citation_count":25,"is_preprint":false},{"pmid":"20423468","id":"PMC_20423468","title":"Pre-gastrula expression of zebrafish extraembryonic genes.","date":"2010","source":"BMC developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/20423468","citation_count":18,"is_preprint":false},{"pmid":"35907914","id":"PMC_35907914","title":"Epstein-Barr virus-encoded microRNA BART22 serves as novel biomarkers and drives malignant transformation of nasopharyngeal carcinoma.","date":"2022","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/35907914","citation_count":18,"is_preprint":false},{"pmid":"21792907","id":"PMC_21792907","title":"Mospd1, a new player in mesenchymal versus epidermal cell differentiation.","date":"2011","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/21792907","citation_count":17,"is_preprint":false},{"pmid":"31927202","id":"PMC_31927202","title":"Molecular characterization of a MOSPD2 homolog in the barbel steed (Hemibarbus labeo) and its involvement in monocyte/macrophage and neutrophil migration.","date":"2020","source":"Molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/31927202","citation_count":15,"is_preprint":false},{"pmid":"28137892","id":"PMC_28137892","title":"Identification of Motile Sperm Domain-Containing Protein 2 as Regulator of Human Monocyte Migration.","date":"2017","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/28137892","citation_count":14,"is_preprint":false},{"pmid":"32353176","id":"PMC_32353176","title":"MOSPD2 is a therapeutic target for the treatment of CNS inflammation.","date":"2020","source":"Clinical and experimental immunology","url":"https://pubmed.ncbi.nlm.nih.gov/32353176","citation_count":12,"is_preprint":false},{"pmid":"29978511","id":"PMC_29978511","title":"Newly characterized motile sperm domain-containing protein 2 promotes human breast cancer metastasis.","date":"2018","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/29978511","citation_count":9,"is_preprint":false},{"pmid":"37341482","id":"PMC_37341482","title":"Host MOSPD2 enrichment at the parasitophorous vacuole membrane varies between Toxoplasma strains and involves complex interactions.","date":"2023","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/37341482","citation_count":8,"is_preprint":false},{"pmid":"32743492","id":"PMC_32743492","title":"Human MOSPD2: A bacterial Lmb mimicked auto-antigen is involved in immune infertility.","date":"2019","source":"Journal of translational autoimmunity","url":"https://pubmed.ncbi.nlm.nih.gov/32743492","citation_count":5,"is_preprint":false},{"pmid":"41073664","id":"PMC_41073664","title":"Toxoplasma gondii VIP1 mediates parasitophorous vacuole-host endoplasmic reticulum interactions to facilitate parasite development.","date":"2025","source":"Nature microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/41073664","citation_count":5,"is_preprint":false},{"pmid":"41017400","id":"PMC_41017400","title":"LEAP2 triggers retromer-mediated membrane trafficking of MOSPD2 to promote chemotaxis in teleost monocytes/macrophages.","date":"2025","source":"Zoological research","url":"https://pubmed.ncbi.nlm.nih.gov/41017400","citation_count":4,"is_preprint":false},{"pmid":"40312574","id":"PMC_40312574","title":"MOSPD2 regulates the activation state of αLβ2 integrin to control monocyte migration: applicability for treatment of chronic inflammatory diseases.","date":"2025","source":"Immunologic research","url":"https://pubmed.ncbi.nlm.nih.gov/40312574","citation_count":3,"is_preprint":false},{"pmid":"39210919","id":"PMC_39210919","title":"Prochloraz induced alterations in the expression of mRNA in the reproductive system of male offspring mice.","date":"2024","source":"PeerJ","url":"https://pubmed.ncbi.nlm.nih.gov/39210919","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11916,"output_tokens":3033,"usd":0.040621,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10461,"output_tokens":4063,"usd":0.07694,"stage2_stop_reason":"end_turn"},"total_usd":0.117561,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"MOSPD2 is an ER-anchored protein containing a Major Sperm Protein (MSP) domain that binds FFAT motifs, enabling it to tether the ER to endosomes, mitochondria, and Golgi by interacting with FFAT-containing proteins on those organelles. In vitro membrane tethering assays confirmed the MSP domain is sufficient for this function.\",\n      \"method\": \"Unbiased proteomic approach, in vitro membrane tethering assay, subcellular fractionation, co-immunoprecipitation\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro reconstitution of tethering activity, reciprocal Co-IP with multiple organelle-resident FFAT-containing partners, direct localization experiments; multiple orthogonal methods in a focused study\",\n      \"pmids\": [\"29858488\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Phosphorylation of a serine/threonine residue within a non-conventional 'Phospho-FFAT' motif is critical for binding to the MOSPD2 MSP domain, acting as a molecular switch for inter-organelle contact formation. Structural analysis of the MSP domain alone and in complex with conventional and Phospho-FFAT peptides revealed new mechanisms of FFAT recognition.\",\n      \"method\": \"Crystal structure determination, in vitro binding assays, phosphomimetic and phospho-dead mutagenesis, sterol transfer functional assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structures with and without ligands, mutagenesis of key residues, functional lipid transfer assay; multiple orthogonal methods in one rigorous study\",\n      \"pmids\": [\"33124732\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"MOSPD2 forms ER-lipid droplet (LD) contacts through its CRAL-TRIO domain via direct protein-membrane interaction. An amphipathic helix within the CRAL-TRIO domain has affinity for lipid packing defects at the LD surface, and absence of MOSPD2 markedly disturbs lipid droplet assembly.\",\n      \"method\": \"Live-cell imaging, in vitro lipid-binding assays, amphipathic helix mutagenesis, MOSPD2 knockout cells, subcellular fractionation\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — direct protein-membrane interaction assay, domain mutagenesis, KO phenotype with specific LD assembly readout; multiple orthogonal methods\",\n      \"pmids\": [\"35389430\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"MOSPD2 is expressed on the cytoplasmic membrane of human monocytes and neutrophils. Silencing or neutralizing MOSPD2 restricts monocyte migration induced by multiple chemokines and inhibits chemokine-receptor-downstream signaling events.\",\n      \"method\": \"siRNA knockdown, neutralizing antibody blockade, chemotaxis migration assays, signaling pathway phosphorylation analysis\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — clean KD and antibody blockade with defined cellular phenotype, signaling readout; single lab, two orthogonal perturbation methods\",\n      \"pmids\": [\"28137892\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MOSPD2 is expressed on invasive breast cancer cell membranes and is required for cancer cell chemotaxis migration; silencing MOSPD2 abates phosphorylation events involved in breast tumor cell chemotaxis and impairs metastasis to the lungs in vivo.\",\n      \"method\": \"siRNA knockdown in multiple breast cancer cell lines, chemotaxis assay, phosphorylation signaling analysis, in vivo metastasis mouse model\",\n      \"journal\": \"International journal of cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — KD with defined in vitro and in vivo phenotypes plus signaling readout; single lab, orthogonal in vitro and in vivo methods\",\n      \"pmids\": [\"29978511\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"MOSPD2 knockout mice show suppressed EAE development, markedly reduced inflammatory monocytes in blood, and T cells from KO mice display reduced proinflammatory cytokines and increased IL-4. Anti-MOSPD2 monoclonal antibodies abrogated EAE development, establishing MOSPD2 as a key regulator of inflammatory monocyte migration in vivo.\",\n      \"method\": \"MOSPD2 knockout mouse generation, EAE induction model, flow cytometry for immune cell subsets, cytokine analysis, monoclonal antibody treatment\",\n      \"journal\": \"Clinical and experimental immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO mouse with specific inflammatory phenotype, antibody rescue experiment; single lab, multiple in vivo readouts\",\n      \"pmids\": [\"32353176\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MOSPD2 regulates monocyte adhesion/migration balance by maintaining integrin αLβ2 (LFA-1/CD11a/CD18) in an inactive low-affinity conformation. Silencing or antibody blockade of MOSPD2 shifts LFA-1 to an active high-affinity form and induces adhesion-associated signaling. Co-immunoprecipitation showed MOSPD2 binds integrin-β2 (CD18) but not integrin-β1 (CD29).\",\n      \"method\": \"siRNA knockdown, humanized anti-MOSPD2 monoclonal antibody (IW-601), co-immunoprecipitation, integrin conformation assay, adhesion assays to ECM and adhesion molecules, in vivo RA and IBD models\",\n      \"journal\": \"Immunologic research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — Co-IP establishing direct binding to integrin-β2, KD and antibody blockade with specific integrin activation readout; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"40312574\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In teleost fish (mudskipper), MOSPD2 acts as a surface receptor for LEAP-2 on monocytes/macrophages. Direct interaction between BpLEAP-2 and BpMOSPD2 was confirmed by co-immunoprecipitation; knockdown of MOSPD2 inhibited LEAP-2-induced chemotaxis, bacterial killing, and cytokine modulation.\",\n      \"method\": \"Yeast two-hybrid cDNA library screening, co-immunoprecipitation, RNA interference knockdown, chemotaxis assay, cytokine mRNA quantification\",\n      \"journal\": \"Zoological research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — direct binding confirmed by Co-IP after Y2H screen, KD with defined functional phenotypes; single lab in a fish ortholog model\",\n      \"pmids\": [\"33124217\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In teleost monocytes/macrophages, LEAP2 stimulation triggers retromer-dependent trafficking of MOSPD2 from the ER to early endosomes and then to the plasma membrane, and this redistribution is required for LEAP2-induced chemotaxis. Core retromer subunits VPS35, VPS26, and VPS29 are required; Co-IP with mass spectrometry confirmed direct binding between MOSPD2 and VPS35.\",\n      \"method\": \"Subcellular fractionation, immunofluorescence, siRNA knockdown of retromer subunits, co-immunoprecipitation plus mass spectrometry, domain-mapping experiments, chemotaxis assay\",\n      \"journal\": \"Zoological research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — Co-IP+MS confirmed MOSPD2–VPS35 interaction, KD of retromer subunits with defined trafficking and migration phenotypes; single lab, multiple orthogonal methods in a fish ortholog\",\n      \"pmids\": [\"41017400\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"At the Toxoplasma PVM-host interface, MOSPD2 association requires its CRAL/TRIO domain and tail anchor. Immunoprecipitation with LC-MS/MS from MOSPD2-expressing host cells enriched PVM-localized parasite proteins, and most MOSPD2 at the PVM is newly translated after infection. MOSPD2 KO results in at most modest impairment of Toxoplasma growth in vitro.\",\n      \"method\": \"Immunoprecipitation, LC-MS/MS, domain-deletion mutagenesis, MOSPD2 KO cells, immunofluorescence microscopy\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — domain mutagenesis defining required regions, IP-MS for interacting parasite proteins, KO growth assay; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"37341482\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"VAPA, VAPB, and MOSPD2 together mediate ER-parasitophorous vacuole membrane (PVM) contact sites in Toxoplasma-infected cells; cells deficient in all three fail to recruit host ER to the PV, and parasites show growth defects. A parasite protein TgVIP1 harbours an FFAT-like motif that binds VAPA/VAPB to establish this contact.\",\n      \"method\": \"Genetic knockout of VAPA/VAPB/MOSPD2, fluorescence microscopy, FFAT-motif interaction assays\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — triple KO with specific ER-PV contact and parasite growth phenotype; single study with genetic epistasis and microscopy readouts\",\n      \"pmids\": [\"41073664\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MOSPD2 is an ER-anchored membrane protein that functions as a general ER tether: its MSP domain binds FFAT (and phospho-FFAT) motifs on organelle-resident proteins to form ER-endosome, ER-mitochondria, ER-Golgi, and ER-lipid droplet contact sites (the last via a CRAL-TRIO domain that senses lipid packing defects on LD surfaces), while on the surface of myeloid cells it acts as an adhesion checkpoint by holding integrin αLβ2 in an inactive conformation and coupling chemokine receptor signaling to directional migration, and in lower vertebrates it serves as a surface receptor for the innate immune peptide LEAP-2, whose binding triggers retromer-dependent MOSPD2 trafficking from the ER to the plasma membrane to promote monocyte/macrophage chemotaxis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MOSPD2 is an ER-anchored membrane protein that functions as a general inter-organelle tether, using its Major Sperm Protein (MSP) domain to bind FFAT motifs on organelle-resident partners and thereby form ER-endosome, ER-mitochondria, and ER-Golgi contact sites [#0]. Recognition is regulated by a phosphorylation switch: phosphorylation of a serine/threonine residue within a non-conventional 'phospho-FFAT' motif controls binding to the MSP domain, a mechanism resolved at atomic resolution by crystal structures of the MSP domain alone and bound to conventional and phospho-FFAT peptides [#1]. Beyond FFAT-dependent tethering, MOSPD2 also forms ER-lipid droplet contacts through a CRAL-TRIO domain whose amphipathic helix senses lipid packing defects at the droplet surface, and its loss disturbs lipid droplet assembly [#2]. In a distinct membrane context, MOSPD2 is displayed on the surface of myeloid cells where it controls chemokine-driven directional migration and couples to receptor-downstream signaling [#3]; mechanistically it binds integrin-\\u03b22 (CD18) and holds integrin \\u03b1L\\u03b22 (LFA-1) in an inactive low-affinity conformation, acting as an adhesion checkpoint [#6]. This migratory function underlies pro-inflammatory monocyte recruitment in vivo, as MOSPD2 knockout or antibody blockade suppresses experimental autoimmune encephalomyelitis [#5] and breast cancer cell chemotaxis and lung metastasis [#4]. In teleost orthologs MOSPD2 serves as a surface receptor for the antimicrobial peptide LEAP-2, whose binding triggers retromer (VPS35/VPS26/VPS29)-dependent trafficking of MOSPD2 from the ER to the plasma membrane to drive monocyte/macrophage chemotaxis [#7, #8]. MOSPD2 is also exploited at pathogen interfaces, where it and the VAP proteins establish ER-parasitophorous vacuole membrane contact sites in Toxoplasma-infected cells [#9, #10].\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Established the first cellular role for MOSPD2, identifying it as a surface protein on myeloid cells required for chemokine-induced migration rather than a purely intracellular factor.\",\n      \"evidence\": \"siRNA knockdown and neutralizing antibody blockade with chemotaxis and signaling readouts in human monocytes and neutrophils\",\n      \"pmids\": [\"28137892\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not identify the molecular binding partner mediating migration\", \"Surface expression mechanism not resolved given ER localization shown later\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Defined the core molecular function: MOSPD2 is an ER-anchored MSP-domain protein that tethers the ER to multiple organelles via FFAT-motif partners, placing it in the membrane contact site machinery.\",\n      \"evidence\": \"Unbiased proteomics, in vitro membrane tethering reconstitution, fractionation, and reciprocal Co-IP\",\n      \"pmids\": [\"29858488\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of FFAT recognition not resolved\", \"Reconciliation with reported plasma-membrane/migration role not addressed\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Extended the migration phenotype to a disease-relevant context, showing MOSPD2 is required for tumor cell chemotaxis and metastasis in vivo.\",\n      \"evidence\": \"siRNA knockdown across breast cancer lines, chemotaxis, phospho-signaling, and an in vivo lung metastasis mouse model\",\n      \"pmids\": [\"29978511\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct receptor/partner mediating tumor chemotaxis not identified\", \"Mechanistic link to ER tethering function unclear\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Resolved how FFAT recognition is regulated, revealing a phosphorylation-controlled molecular switch via crystal structures of the MSP domain with conventional and phospho-FFAT ligands.\",\n      \"evidence\": \"Crystal structures with and without peptides, phosphomimetic/phospho-dead mutagenesis, and sterol transfer assays\",\n      \"pmids\": [\"33124732\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinases/phosphatases controlling the phospho-FFAT switch not identified\", \"In vivo regulation of contact-site dynamics not addressed\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Demonstrated the in vivo physiological consequence of MOSPD2-dependent migration, establishing it as a regulator of inflammatory monocyte recruitment in autoimmune disease.\",\n      \"evidence\": \"MOSPD2 knockout mice in an EAE model, flow cytometry, cytokine profiling, and monoclonal antibody treatment\",\n      \"pmids\": [\"32353176\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Surface receptor/effector mediating the phenotype not defined\", \"T-cell cytokine shift mechanism unresolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identified a surface-receptor function for the MOSPD2 ortholog, showing it binds the antimicrobial peptide LEAP-2 to drive macrophage chemotaxis and antibacterial responses.\",\n      \"evidence\": \"Yeast two-hybrid screen, Co-IP, RNAi knockdown, and chemotaxis/cytokine assays in mudskipper\",\n      \"pmids\": [\"33124217\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Conservation of LEAP-2 receptor function in mammals not tested\", \"Signaling downstream of LEAP-2/MOSPD2 not mapped\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Expanded the tethering repertoire to lipid droplets and showed MOSPD2 can engage membranes directly, independent of FFAT proteins, through a lipid-packing-defect-sensing amphipathic helix.\",\n      \"evidence\": \"Live-cell imaging, in vitro lipid binding, amphipathic helix mutagenesis, and lipid droplet assembly phenotype in KO cells\",\n      \"pmids\": [\"35389430\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism linking ER-LD contact to lipid droplet assembly not defined\", \"Coordination between CRAL-TRIO and MSP domain functions unclear\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Showed MOSPD2 is recruited to the Toxoplasma parasitophorous vacuole membrane via its CRAL/TRIO domain and tail anchor, implicating its contact-site machinery at a pathogen interface.\",\n      \"evidence\": \"IP-LC-MS/MS, domain-deletion mutagenesis, KO growth assays, and immunofluorescence in infected host cells\",\n      \"pmids\": [\"37341482\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional importance is modest (limited growth defect)\", \"Direct parasite-side binding partner of MOSPD2 not defined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined the molecular basis of the myeloid adhesion checkpoint, showing MOSPD2 binds integrin-\\u03b22 and locks LFA-1 in a low-affinity state, explaining its control of migration vs. adhesion balance.\",\n      \"evidence\": \"siRNA, humanized anti-MOSPD2 antibody, Co-IP, integrin conformation and adhesion assays, and in vivo RA/IBD models\",\n      \"pmids\": [\"40312574\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How an ER-resident protein reaches the cell surface to engage integrins not resolved\", \"Structural basis of the MOSPD2-CD18 interaction unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Resolved how MOSPD2 reaches the surface, showing LEAP2 triggers retromer-dependent trafficking from ER to endosomes to plasma membrane required for chemotaxis.\",\n      \"evidence\": \"Fractionation, immunofluorescence, retromer-subunit knockdown, Co-IP/MS confirming MOSPD2-VPS35 binding, and chemotaxis assays in teleost cells\",\n      \"pmids\": [\"41017400\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether retromer-dependent surface trafficking operates in mammalian cells untested\", \"Trigger linking LEAP2 binding to retromer recruitment not defined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Established that ER-PVM contact in Toxoplasma infection is mediated by VAPA/VAPB/MOSPD2 acting redundantly, with a parasite FFAT-like protein engaging the VAPs.\",\n      \"evidence\": \"Triple genetic knockout, fluorescence microscopy, and FFAT-motif interaction assays\",\n      \"pmids\": [\"41073664\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Relative contribution of MOSPD2 vs VAPA/VAPB not dissected\", \"Consequence of ER-PVM contact for the parasite mechanistically unresolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How a single ER-tail-anchored tethering protein is converted into a cell-surface receptor and integrin regulator in myeloid cells, and whether the LEAP-2/retromer surface-trafficking axis is conserved in mammals, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No mammalian demonstration of LEAP-2 receptor or retromer surface-trafficking function\", \"Topological reconciliation of ER-membrane tether vs plasma-membrane receptor roles missing\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0001618\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0, 2, 8]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [3, 6, 8]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0, 8]},\n      {\"term_id\": \"GO:0005811\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [3, 5, 7]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [8]},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"VAPA\", \"VAPB\", \"ITGB2\", \"VPS35\", \"LEAP2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}