{"gene":"MFAP2","run_date":"2026-04-28T18:30:28","timeline":{"discoveries":[{"year":1996,"finding":"MAGP-2 (MP25/MFAP2) was identified as a distinct component of elastin-associated microfibrils by immunofluorescence and immunoelectron microscopy, and its primary structure was determined by cDNA cloning. It shares significant structural similarity with MAGP-1, confined to a central 60-amino acid region with 7 conserved cysteines, but lacks the proline/glutamine/tyrosine-rich sequences and hydrophobic carboxyl terminus of MAGP-1, and contains an RGD motif, suggesting distinct functions.","method":"cDNA cloning, immunofluorescence, immunoelectron microscopy, sequence analysis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 — original molecular characterization with direct localization by immunoelectron microscopy and complete sequence determination; foundational paper","pmids":["8557636"],"is_preprint":false},{"year":1998,"finding":"MAGP-2 is specifically associated with fibrillin-containing microfibrils in multiple tissues (nuchal ligament, dermis, adventitia of aorta, glomerular mesangium, perimysium) as demonstrated by immunoelectron microscopy, but shows more restricted tissue distribution than MAGP-1, being absent from the medial layer of fetal thoracic aorta, peritubular matrix of kidney, and ocular zonule.","method":"Immunoelectron microscopy, immunolocalization, Northern blotting","journal":"The journal of histochemistry and cytochemistry","confidence":"High","confidence_rationale":"Tier 2 — direct localization by immunoelectron microscopy with functional tissue distribution mapping; corroborates MAGP-1 studies","pmids":["9671438"],"is_preprint":false},{"year":1997,"finding":"MAGP-1 (MFAP2 paralog) binds specifically to the collagenous domain of the alpha3(VI) chain of type VI collagen in solid-phase binding assays (Kd ~5.6×10⁻⁷ M) but MAGP-2 does not bind type VI collagen. The binding site on MAGP-1 resides in its N-terminal, cysteine-free domain (amino acids 29-38), and tropoelastin competes for the same binding site on MAGP-1.","method":"Solid-phase binding assay, affinity blotting, inhibition experiments with peptides and reduction/alkylation","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 — in vitro binding assays with domain mapping, mutagenesis-equivalent peptide inhibition, Kd measurements; demonstrates MAGP-2 does NOT bind collagen VI","pmids":["9278443"],"is_preprint":false},{"year":2002,"finding":"MAGP-2 specifically interacts with fibrillin-1 and fibrillin-2 via yeast two-hybrid and co-immunoprecipitation. The binding site on fibrillin-1 and -2 is a calcium-binding EGF repeat-containing region near the C terminus, distinct from the MAGP-1 binding site on fibrillin-1. The interacting domain on MAGP-2 is a core region containing 48% identity with MAGP-1 and 7 conserved cysteines.","method":"Yeast two-hybrid screen, deletion analysis, co-immunoprecipitation from transfected COS-7 cells","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — reciprocal yeast two-hybrid plus co-IP with domain mapping; two orthogonal methods","pmids":["12122015"],"is_preprint":false},{"year":2005,"finding":"MAGP-2 interacts with the Notch ligand Jagged1 via EGF-like repeats of Jagged1, as shown by yeast two-hybrid and co-immunoprecipitation. MAGP-2 co-expression induces metalloproteinase-dependent shedding of the Jagged1 extracellular domain. MAGP-2 also interacts with Jagged2 and Delta1, but does not induce their shedding. MAGP-1 interacts with DSL ligands but cannot facilitate Jagged1 shedding.","method":"Yeast two-hybrid, co-immunoprecipitation, conditioned media analysis, metalloproteinase inhibitor (BB3103)","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP plus yeast two-hybrid, pharmacological inhibition, two orthogonal methods","pmids":["15788413"],"is_preprint":false},{"year":2006,"finding":"MAGP-2 and MAGP-1 interact with EGF-like repeats of Notch1 and induce dissociation of the Notch1 extracellular domain from the cell surface, leading to activation of Notch signaling. The C-terminal domain of MAGP-2 is required for Notch1 binding and activation. MAGP-2-induced Notch1 extracellular domain release requires prior furin-like cleavage (heterodimer formation) but does not require ADAM metalloprotease cleavage.","method":"Co-expression/co-immunoprecipitation, domain deletion analysis, reporter assays, ADAM inhibitor experiments","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (Co-IP, reporter assay, domain mapping, pharmacological dissection) in a single study","pmids":["16492672"],"is_preprint":false},{"year":2006,"finding":"MAGP-2 overexpression stimulates elastic fiber assembly in vitro, as shown by increased elastic fiber levels in cells conditionally overexpressing MAGP-2. Electron microscopy confirmed MAGP-2 associates specifically with microfibrils and elastin globules colocalize with MAGP-2-associated microfibrils. The RGD motif of MAGP-2 is not required for this activity, and overexpression of MAGP-2 did not alter levels of fibrillin-1, MAGP-1, fibulin-2, fibulin-5, or emilin-1 in the matrix.","method":"Conditional overexpression (doxycycline-regulated), immunofluorescence, electron microscopy, mutational analysis (RGD motif)","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — clean gain-of-function with specific phenotypic readout, mutagenesis, and electron microscopy confirmation","pmids":["17099216"],"is_preprint":false},{"year":2008,"finding":"MAGP-2 promotes angiogenic cell sprouting by antagonizing Notch signaling in endothelial cells. MAGP-2 decreased basal and Jagged1-induced Hes-1 promoter activity in endothelial cells and blocked Jagged1-stimulated Notch1 receptor processing. Constitutive Notch pathway activation blocked MAGP-2-induced sprouting. Notably, MAGP-2 had the opposite effect (activating Notch) in heterologous non-endothelial cell types.","method":"Luciferase reporter assay (Hes-1 promoter), Notch1 receptor processing assay, angiogenic sprouting assay, constitutively active Notch rescue experiment","journal":"Microvascular research","confidence":"High","confidence_rationale":"Tier 2 — epistasis via constitutive activation rescue, reporter assay, and functional sprouting assay; multiple orthogonal methods","pmids":["18417156"],"is_preprint":false},{"year":2020,"finding":"MFAP2 promotes gastric cancer cell motility through the integrin α5β1/FAK/ERK signaling pathway. Silencing MFAP2 by shRNA inhibited motility and was rescued by fibronectin (another FAK activator). MFAP2 regulated integrin expression through ERK1/2 activation. miR-29 was identified as a regulator of MFAP2 expression. In vivo, MFAP2 silencing inhibited tumorigenicity and metastasis in nude mice.","method":"shRNA knockdown, rescue with fibronectin, ERK1/2 signaling assays, in vivo xenograft, miRNA regulation experiments","journal":"Oncogenesis","confidence":"Medium","confidence_rationale":"Tier 2 — KO with defined phenotypic readout and pathway rescue, in vitro and in vivo; single lab","pmids":["32054827"],"is_preprint":false},{"year":2018,"finding":"MFAP2 promotes epithelial-mesenchymal transition (EMT) in gastric cancer cells by activating the TGF-β/SMAD2/3 signaling pathway, as demonstrated by gain- and loss-of-function experiments measuring EMT markers and SMAD phosphorylation.","method":"Gain- and loss-of-function experiments, Western blot for SMAD2/3 phosphorylation and EMT markers","journal":"OncoTargets and therapy","confidence":"Medium","confidence_rationale":"Tier 3 — KD/OE with pathway placement but limited mechanistic depth; single lab, single paper","pmids":["30034240"],"is_preprint":false},{"year":2022,"finding":"MFAP2 promotes CRC cell invasion through CLK3 as a downstream target; MFAP2 depletion induces autophagic degradation of CLK3, and the pro-invasive effect of MFAP2 in CRC cells is dependent on CLK3. CLK3 was identified as a MFAP2 target by mass spectrometry.","method":"Mass spectrometry (downstream target screening), siRNA knockdown, CLK3 rescue experiments, transwell invasion assays, peritoneal metastasis mouse model","journal":"Cancer medicine","confidence":"Medium","confidence_rationale":"Tier 2-3 — MS-based target identification plus genetic rescue; single lab","pmids":["36583532"],"is_preprint":false},{"year":2024,"finding":"MFAP2 promotes ESCC metastasis by binding to the FERM domain of focal adhesion kinase (FAK), alleviating FAK intramolecular inhibition, enhancing FAK–integrin β4 (ITGB4) interaction, and activating the FAK-AKT signaling pathway. Treatment with FAK inhibitor PND-1186 reduced MFAP2-driven FAK-AKT activation and suppressed lung metastasis in vivo.","method":"Co-immunoprecipitation (MFAP2-FAK interaction), domain binding analysis, FAK inhibitor (PND-1186) experiments, in vivo metastasis model, shRNA knockdown","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 2 — direct protein-protein interaction (Co-IP with domain specificity) plus pharmacological validation in vivo; single lab","pmids":["39698924"],"is_preprint":false},{"year":2023,"finding":"MFAP2 promotes hepatic stellate cell (HSC) activation in liver fibrosis through upregulation of fibrillin-1 (FBN1) and downstream TGF-β/Smad3 signaling. MFAP2 knockdown inhibited HSC proliferation and collagen deposition, and attenuated fibrosis in a CCl4-induced mouse model.","method":"Bioinformatics, MFAP2 overexpression/knockdown, qRT-PCR, Western blot, in vivo CCl4 mouse fibrosis model","journal":"Journal of cellular and molecular medicine","confidence":"Low","confidence_rationale":"Tier 3 — pathway placement via KD/OE with phenotypic readout, but no direct protein-protein interaction data for MFAP2-FBN1; single lab","pmids":["37635348"],"is_preprint":false},{"year":2020,"finding":"MFAP2 transcription is activated by the lncRNA LCPAT1 through recruitment of the chromatin remodeler RBBP4 to the MFAP2 promoter, as shown by RNA immunoprecipitation and ChIP assays. Restoration of MFAP2 rescued the proliferative and migratory effects of LCPAT1 knockdown in breast cancer cells.","method":"RNA immunoprecipitation, ChIP assay, MFAP2 restoration rescue experiment, in vitro/in vivo functional assays","journal":"Molecular therapy. Nucleic acids","confidence":"Medium","confidence_rationale":"Tier 2 — direct identification of upstream transcriptional regulator by ChIP and rescue experiments; single lab","pmids":["32791452"],"is_preprint":false},{"year":2025,"finding":"TWIST1 directly binds the MFAP2 promoter to transcriptionally activate MFAP2 expression in ovarian cancer, as validated by dual-luciferase reporter assay and ChIP-qPCR. TWIST1 promotes ovarian cancer cell growth, migration, and invasion via MFAP2-dependent activation of FOXM1/β-catenin signaling.","method":"Dual-luciferase reporter assay, ChIP-qPCR, gain/loss-of-function experiments, xenograft model","journal":"Journal of biochemical and molecular toxicology","confidence":"Medium","confidence_rationale":"Tier 2 — direct promoter binding validated by two complementary methods; single lab","pmids":["39829397"],"is_preprint":false},{"year":2025,"finding":"FOXA1 transcriptionally activates MFAP2 by binding to its promoter region in uterine corpus endometrial carcinoma, as validated by ChIP assay and dual-luciferase reporter assay. FOXA1-mediated MFAP2 upregulation promotes UCEC cell growth, metastasis, and cisplatin resistance.","method":"ChIP assay, dual-luciferase reporter assay, siRNA knockdown, colony formation, transwell, xenograft model","journal":"Naunyn-Schmiedeberg's archives of pharmacology","confidence":"Medium","confidence_rationale":"Tier 2 — two orthogonal methods validating direct promoter binding; single lab","pmids":["40153018"],"is_preprint":false},{"year":2026,"finding":"CAF-derived MFAP2 interacts with integrin β8 (ITGB8) on colorectal cancer cell surfaces, activating the FAK-ERK1/2 signaling cascade. ERK1/2 phosphorylates ETS2 transcription factor, which upregulates CYP27A1 to suppress CD8+ T cell function via LXRβ signaling, establishing a MFAP2-ITGB8-FAK-ERK1/2-ETS2-CYP27A1-LXRβ axis.","method":"Co-immunoprecipitation (MFAP2-ITGB8), phosphorylation analysis, in vitro/in vivo functional assays, immunosuppression experiments","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 — direct protein-protein interaction (Co-IP) plus multi-step pathway validation in vitro and in vivo; single lab","pmids":["41617683"],"is_preprint":false},{"year":2025,"finding":"Mfap2 loss in mouse kidney disrupts tissue architecture and aggravates acute kidney injury. Mechanistically, Mfap2 deficiency suppresses tubular HMGCS2 expression via ESR2-mediated transcriptional repression, increases protein succinylation, and hyperactivates MAP kinases and LATS1 in tubular cells. LATS1 suppresses ESR2 transcription independently of canonical YAP/TAZ effectors. ESR2 agonist treatment restored kidney function in Mfap2-deficient models.","method":"Mfap2 knockout mouse model, global proteomics, phosphoproteomics, spatial transcriptomics, pharmacological rescue (ESR2 agonist)","journal":"bioRxiv (preprint)","confidence":"Medium","confidence_rationale":"Tier 2 — multi-omics plus genetic KO with pharmacological rescue; preprint, not yet peer reviewed","pmids":["bio_10.1101_2025.06.22.660927"],"is_preprint":true}],"current_model":"MFAP2/MAGP-2 is a small extracellular matrix glycoprotein that is an integral component of fibrillin-containing microfibrils, where it binds fibrillin-1 and fibrillin-2 at a C-terminal EGF repeat region to promote elastic fiber assembly; outside the matrix, MAGP-2 modulates cell signaling by binding EGF-like repeats on Notch1 (via its C-terminal domain) and the Notch ligand Jagged1 to induce their ectodomain shedding, thereby activating or antagonizing Notch signaling in a cell-context-dependent manner; in cancer contexts, secreted MFAP2 promotes invasion and metastasis by engaging integrin receptors (α5β1, β4, β8) to activate FAK-AKT or FAK-ERK signaling cascades, and its expression is transcriptionally controlled upstream by TWIST1 and FOXA1."},"narrative":{"teleology":[{"year":1996,"claim":"Identifying MAGP-2 as a distinct microfibril-associated protein established that elastin-associated microfibrils contain a second MAGP family member with divergent domain architecture and an RGD motif, raising the question of whether it has non-redundant functions relative to MAGP-1.","evidence":"cDNA cloning, immunofluorescence, and immunoelectron microscopy localizing MAGP-2 to microfibrils","pmids":["8557636"],"confidence":"High","gaps":["No binding partners identified beyond microfibril co-localization","Functional significance of the RGD motif untested","No knockout or loss-of-function data"]},{"year":1998,"claim":"Demonstrating that MAGP-2 has a more restricted tissue distribution than MAGP-1 and does not bind type VI collagen established that the two paralogs occupy distinct niches within the extracellular matrix despite their shared microfibril association.","evidence":"Immunoelectron microscopy across multiple tissues; solid-phase binding assays showing no MAGP-2–collagen VI interaction","pmids":["9671438","9278443"],"confidence":"High","gaps":["Direct binding partner on microfibrils not yet identified","No functional consequence of restricted distribution tested"]},{"year":2002,"claim":"Mapping the direct interaction between MAGP-2 and fibrillin-1/fibrillin-2 to a C-terminal EGF repeat region on fibrillins—distinct from the MAGP-1 binding site—revealed that the two MAGPs occupy non-overlapping sites on microfibrils, suggesting independent structural contributions.","evidence":"Yeast two-hybrid screen with deletion analysis plus co-immunoprecipitation from COS-7 cells","pmids":["12122015"],"confidence":"High","gaps":["Functional consequence of MAGP-2–fibrillin binding for microfibril integrity not tested","No in vivo validation"]},{"year":2005,"claim":"Discovering that MAGP-2 binds Jagged1 EGF-like repeats and induces its metalloproteinase-dependent ectodomain shedding expanded MAGP-2's role beyond structural matrix protein to a modulator of Notch ligand availability.","evidence":"Yeast two-hybrid, co-immunoprecipitation, conditioned media analysis, metalloproteinase inhibitor (BB3103)","pmids":["15788413"],"confidence":"High","gaps":["Downstream Notch signaling consequences not measured","In vivo relevance of Jagged1 shedding by MAGP-2 unknown"]},{"year":2006,"claim":"Two studies established that MAGP-2 directly activates Notch1 by inducing furin-dependent extracellular domain dissociation via its C-terminal domain, and independently stimulates elastic fiber assembly without requiring its RGD motif, delineating its dual structural and signaling functions.","evidence":"Co-IP with domain deletions, Notch reporter assays, ADAM inhibitor experiments; conditional MAGP-2 overexpression with electron microscopy and RGD mutant analysis","pmids":["16492672","17099216"],"confidence":"High","gaps":["Mechanism by which MAGP-2 promotes elastin deposition without altering other matrix components unclear","Physiological relevance of Notch1 activation by MAGP-2 in vivo not shown"]},{"year":2008,"claim":"Showing that MAGP-2 antagonizes Notch signaling specifically in endothelial cells (while activating it in other cell types) to promote angiogenic sprouting revealed that MAGP-2's effect on Notch is cell-context-dependent, resolving an apparent contradiction.","evidence":"Hes-1 reporter assay, Notch1 processing analysis, angiogenic sprouting assay with constitutively active Notch rescue in endothelial cells","pmids":["18417156"],"confidence":"High","gaps":["Molecular basis of cell-type-specific Notch modulation not identified","No in vivo angiogenesis data"]},{"year":2018,"claim":"Linking MFAP2 to epithelial-mesenchymal transition via TGF-β/SMAD2/3 signaling in gastric cancer placed it in a pro-metastatic signaling context beyond its canonical matrix and Notch roles.","evidence":"Gain- and loss-of-function experiments with SMAD2/3 phosphorylation and EMT marker analysis in gastric cancer cells","pmids":["30034240"],"confidence":"Medium","gaps":["No direct MFAP2–TGF-β receptor interaction demonstrated","Single cancer type, single lab"]},{"year":2020,"claim":"Identifying integrin α5β1/FAK/ERK as a direct signaling axis for MFAP2-driven gastric cancer motility, with fibronectin rescue of MFAP2 knockdown, established FAK as a central downstream effector and revealed miR-29 as an upstream regulator of MFAP2 expression.","evidence":"shRNA knockdown with fibronectin rescue, ERK signaling assays, in vivo xenograft, miRNA experiments","pmids":["32054827"],"confidence":"Medium","gaps":["Direct MFAP2–integrin α5β1 physical interaction not demonstrated by co-IP","miR-29 regulation not validated with reporter assays in this study"]},{"year":2020,"claim":"Demonstrating that LCPAT1 lncRNA recruits the chromatin remodeler RBBP4 to the MFAP2 promoter to activate its transcription identified a first epigenetic regulatory mechanism for MFAP2 expression.","evidence":"RNA immunoprecipitation, ChIP assay at MFAP2 promoter, MFAP2 rescue of LCPAT1 knockdown in breast cancer cells","pmids":["32791452"],"confidence":"Medium","gaps":["Whether RBBP4 recruitment alters histone modifications at the MFAP2 locus not shown","Single cancer context"]},{"year":2022,"claim":"Identifying CLK3 as a downstream effector whose autophagic degradation is induced upon MFAP2 depletion revealed a non-canonical intracellular consequence of extracellular MFAP2 signaling in colorectal cancer invasion.","evidence":"Mass spectrometry target screening, siRNA knockdown, CLK3 rescue, transwell invasion, peritoneal metastasis model","pmids":["36583532"],"confidence":"Medium","gaps":["How an extracellular protein regulates intracellular CLK3 degradation is mechanistically unclear","Single lab, single cancer type"]},{"year":2024,"claim":"Demonstrating direct MFAP2 binding to the FERM domain of FAK to relieve intramolecular autoinhibition and enhance FAK–integrin β4 interaction provided the first structural-level explanation for MFAP2-driven FAK-AKT activation in metastasis.","evidence":"Co-immunoprecipitation with domain analysis, FAK inhibitor PND-1186 in vitro and in vivo (ESCC lung metastasis model)","pmids":["39698924"],"confidence":"Medium","gaps":["No crystal structure or biophysical binding data for MFAP2–FERM interaction","Single cancer type"]},{"year":2025,"claim":"Identifying TWIST1 and FOXA1 as direct transcriptional activators of MFAP2 via promoter binding established upstream transcription factor control of MFAP2 in ovarian and endometrial cancers, linking EMT master regulators to MFAP2 induction.","evidence":"ChIP-qPCR and dual-luciferase reporter assays for TWIST1 and FOXA1 binding to MFAP2 promoter; gain/loss-of-function and xenograft models","pmids":["39829397","40153018"],"confidence":"Medium","gaps":["Whether TWIST1 and FOXA1 cooperate or act independently at the MFAP2 promoter unknown","Relevance to non-cancer tissues not tested"]},{"year":2025,"claim":"Demonstrating that cancer-associated fibroblast-secreted MFAP2 engages integrin β8 on colorectal cancer cells to activate FAK-ERK1/2-ETS2-CYP27A1 signaling, suppressing CD8+ T cell function, expanded MFAP2's role to immune evasion in the tumor microenvironment.","evidence":"Co-immunoprecipitation of MFAP2–ITGB8, phosphorylation cascade analysis, in vitro and in vivo immunosuppression experiments","pmids":["41617683"],"confidence":"Medium","gaps":["Whether MFAP2–ITGB8 interaction occurs in non-tumor contexts unknown","Contribution relative to other CAF-derived factors not quantified"]},{"year":null,"claim":"Key unresolved questions include: the structural basis of MFAP2's context-dependent Notch modulation; in vivo phenotypes of Mfap2 genetic deletion in elastic tissue homeostasis; whether MFAP2's integrin/FAK and Notch signaling roles intersect; and the mechanism by which extracellular MFAP2 controls intracellular CLK3 degradation.","evidence":"","pmids":[],"confidence":"Low","gaps":["No Mfap2 constitutive knockout phenotype in elastic tissues published in peer-reviewed literature","Structural basis of cell-context-dependent Notch modulation unknown","Relationship between MFAP2's matrix and signaling functions unresolved"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1,3,6]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[4,5,7]},{"term_id":"GO:0048018","term_label":"receptor ligand activity","supporting_discovery_ids":[8,11,16]}],"localization":[{"term_id":"GO:0031012","term_label":"extracellular matrix","supporting_discovery_ids":[0,1,3,6]},{"term_id":"GO:0005576","term_label":"extracellular region","supporting_discovery_ids":[0,4,5,16]}],"pathway":[{"term_id":"R-HSA-1474244","term_label":"Extracellular matrix organization","supporting_discovery_ids":[0,1,3,6]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[4,5,7,8,9,11,16]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[5,7]}],"complexes":[],"partners":["FBN1","FBN2","JAG1","NOTCH1","FAK","ITGB4","ITGB8","ITGA5"],"other_free_text":[]},"mechanistic_narrative":"MFAP2 (MAGP-2) is a secreted extracellular matrix glycoprotein that serves dual roles as a structural component of fibrillin-containing microfibrils and as a signaling modulator. It binds fibrillin-1 and fibrillin-2 via their C-terminal EGF repeat regions to promote elastic fiber assembly independently of its RGD motif [PMID:12122015, PMID:17099216], and interacts with Notch1 through its own C-terminal domain to induce ectodomain shedding and context-dependent Notch activation or antagonism—activating Notch in heterologous cells while inhibiting Notch signaling in endothelial cells to promote angiogenic sprouting [PMID:16492672, PMID:18417156]. MAGP-2 also binds the Notch ligand Jagged1 and induces its metalloproteinase-dependent ectodomain shedding [PMID:15788413]. In cancer contexts, secreted MFAP2 engages integrin receptors (α5β1, β4, β8) and directly binds the FERM domain of FAK to activate FAK–ERK or FAK–AKT signaling cascades that drive invasion and metastasis, and its transcription is directly activated by TWIST1 and FOXA1 [PMID:32054827, PMID:39698924, PMID:41617683, PMID:39829397]."},"prefetch_data":{"uniprot":{"accession":"P55001","full_name":"Microfibrillar-associated protein 2","aliases":["Microfibril-associated glycoprotein 1","MAGP","MAGP-1"],"length_aa":183,"mass_kda":20.8,"function":"Component of the elastin-associated microfibrils","subcellular_location":"Secreted, extracellular space, extracellular matrix","url":"https://www.uniprot.org/uniprotkb/P55001/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MFAP2","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/MFAP2","total_profiled":1310},"omim":[{"mim_id":"601103","title":"MICROFIBRILLAR-ASSOCIATED PROTEIN 5; MFAP5","url":"https://www.omim.org/entry/601103"},{"mim_id":"600491","title":"MICROFIBRILLAR-ASSOCIATED PROTEIN 3; MFAP3","url":"https://www.omim.org/entry/600491"},{"mim_id":"301870","title":"BIGLYCAN; BGN","url":"https://www.omim.org/entry/301870"},{"mim_id":"156790","title":"MICROFIBRILLAR-ASSOCIATED PROTEIN 2; MFAP2","url":"https://www.omim.org/entry/156790"},{"mim_id":"125255","title":"DECORIN; DCN","url":"https://www.omim.org/entry/125255"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MFAP2"},"hgnc":{"alias_symbol":["MAGP","MAGP-1"],"prev_symbol":[]},"alphafold":{"accession":"P55001","domains":[{"cath_id":"-","chopping":"96-183","consensus_level":"medium","plddt":91.888,"start":96,"end":183}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P55001","model_url":"https://alphafold.ebi.ac.uk/files/AF-P55001-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P55001-F1-predicted_aligned_error_v6.png","plddt_mean":69.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MFAP2","jax_strain_url":"https://www.jax.org/strain/search?query=MFAP2"},"sequence":{"accession":"P55001","fasta_url":"https://rest.uniprot.org/uniprotkb/P55001.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P55001/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P55001"}},"corpus_meta":[{"pmid":"8557636","id":"PMC_8557636","title":"Further characterization of proteins associated with elastic fiber microfibrils including the molecular cloning of MAGP-2 (MP25).","date":"1996","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/8557636","citation_count":130,"is_preprint":false},{"pmid":"11481325","id":"PMC_11481325","title":"Protein interaction studies of MAGP-1 with tropoelastin and fibrillin-1.","date":"2001","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11481325","citation_count":122,"is_preprint":false},{"pmid":"10793130","id":"PMC_10793130","title":"The microfibrillar proteins MAGP-1 and fibrillin-1 form a ternary complex with the chondroitin sulfate proteoglycan decorin.","date":"2000","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/10793130","citation_count":108,"is_preprint":false},{"pmid":"2019589","id":"PMC_2019589","title":"Complementary DNA cloning establishes microfibril-associated glycoprotein (MAGP) to be a discrete component of the elastin-associated microfibrils.","date":"1991","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/2019589","citation_count":107,"is_preprint":false},{"pmid":"16492672","id":"PMC_16492672","title":"Microfibrillar proteins MAGP-1 and MAGP-2 induce Notch1 extracellular domain dissociation and receptor activation.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16492672","citation_count":106,"is_preprint":false},{"pmid":"9278443","id":"PMC_9278443","title":"Microfibril-associated glycoprotein-1 (MAGP-1) binds to the pepsin-resistant domain of the alpha3(VI) chain of type VI collagen.","date":"1997","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/9278443","citation_count":81,"is_preprint":false},{"pmid":"9671438","id":"PMC_9671438","title":"Microfibril-associated glycoprotein-2 (MAGP-2) is specifically associated with fibrillin-containing microfibrils but exhibits more restricted patterns of tissue localization and developmental expression than its structural relative MAGP-1.","date":"1998","source":"The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society","url":"https://pubmed.ncbi.nlm.nih.gov/9671438","citation_count":80,"is_preprint":false},{"pmid":"18417156","id":"PMC_18417156","title":"Microfibril-associate glycoprotein-2 (MAGP-2) promotes angiogenic cell sprouting by blocking notch signaling in endothelial cells.","date":"2008","source":"Microvascular research","url":"https://pubmed.ncbi.nlm.nih.gov/18417156","citation_count":67,"is_preprint":false},{"pmid":"12122015","id":"PMC_12122015","title":"Microfibril-associated glycoprotein-2 interacts with fibrillin-1 and fibrillin-2 suggesting a role for MAGP-2 in elastic fiber assembly.","date":"2002","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12122015","citation_count":63,"is_preprint":false},{"pmid":"2693088","id":"PMC_2693088","title":"The tissue distribution of microfibrils reacting with a monospecific antibody to MAGP, the major glycoprotein antigen of elastin-associated microfibrils.","date":"1989","source":"European journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/2693088","citation_count":63,"is_preprint":false},{"pmid":"17099216","id":"PMC_17099216","title":"Microfibril-associated MAGP-2 stimulates elastic fiber assembly.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17099216","citation_count":53,"is_preprint":false},{"pmid":"32054827","id":"PMC_32054827","title":"MFAP2 is overexpressed in gastric cancer and promotes motility via the MFAP2/integrin α5β1/FAK/ERK pathway.","date":"2020","source":"Oncogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/32054827","citation_count":52,"is_preprint":false},{"pmid":"29524629","id":"PMC_29524629","title":"Microfibril-associated glycoproteins MAGP-1 and MAGP-2 in disease.","date":"2018","source":"Matrix biology : journal of the International Society for Matrix Biology","url":"https://pubmed.ncbi.nlm.nih.gov/29524629","citation_count":49,"is_preprint":false},{"pmid":"15788413","id":"PMC_15788413","title":"The extracellular matrix protein MAGP-2 interacts with Jagged1 and induces its shedding from the cell surface.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15788413","citation_count":48,"is_preprint":false},{"pmid":"30034240","id":"PMC_30034240","title":"MFAP2 promotes epithelial-mesenchymal transition in gastric cancer cells by activating TGF-β/SMAD2/3 signaling pathway.","date":"2018","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/30034240","citation_count":46,"is_preprint":false},{"pmid":"8619823","id":"PMC_8619823","title":"Partial amino acid sequence of a novel 40-kDa human aortic protein, with vitronectin-like, fibrinogen-like, and calcium binding domains: aortic aneurysm-associated protein-40 (AAAP-40) [human MAGP-3, proposed].","date":"1996","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/8619823","citation_count":46,"is_preprint":false},{"pmid":"32791452","id":"PMC_32791452","title":"lncRNA LCPAT1 Upregulation Promotes Breast Cancer Progression via Enhancing MFAP2 Transcription.","date":"2020","source":"Molecular therapy. Nucleic acids","url":"https://pubmed.ncbi.nlm.nih.gov/32791452","citation_count":34,"is_preprint":false},{"pmid":"36583532","id":"PMC_36583532","title":"MFAP2, upregulated by m1A methylation, promotes colorectal cancer invasiveness via CLK3.","date":"2022","source":"Cancer medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36583532","citation_count":32,"is_preprint":false},{"pmid":"15922742","id":"PMC_15922742","title":"36-kDa microfibril-associated glycoprotein (MAGP-36) is an elastin-binding protein increased in chick aortae during development and growth.","date":"2005","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/15922742","citation_count":31,"is_preprint":false},{"pmid":"10424889","id":"PMC_10424889","title":"Ultrastructural distribution of 36-kD microfibril-associated glycoprotein (MAGP-36) in human and bovine tissues.","date":"1999","source":"The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society","url":"https://pubmed.ncbi.nlm.nih.gov/10424889","citation_count":31,"is_preprint":false},{"pmid":"7759096","id":"PMC_7759096","title":"Characterization of the human gene for microfibril-associated glycoprotein (MFAP2), assignment to chromosome 1p36.1-p35, and linkage to D1S170.","date":"1995","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/7759096","citation_count":31,"is_preprint":false},{"pmid":"11284693","id":"PMC_11284693","title":"Posttranslational modifications of microfibril associated glycoprotein-1 (MAGP-1).","date":"2001","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11284693","citation_count":27,"is_preprint":false},{"pmid":"32559183","id":"PMC_32559183","title":"Marker Assisted Gene Pyramiding (MAGP) for bacterial blight and blast resistance into mega rice variety \"Tellahamsa\".","date":"2020","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/32559183","citation_count":26,"is_preprint":false},{"pmid":"8262979","id":"PMC_8262979","title":"Structure, chromosomal localization, and expression pattern of the murine Magp gene.","date":"1993","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/8262979","citation_count":24,"is_preprint":false},{"pmid":"31988245","id":"PMC_31988245","title":"Identification of the growth factor-binding sequence in the extracellular matrix protein MAGP-1.","date":"2020","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31988245","citation_count":22,"is_preprint":false},{"pmid":"32464633","id":"PMC_32464633","title":"Microfibril-Associated Protein 2 (MFAP2) Potentiates Invasion and Migration of Melanoma by EMT and Wnt/β-Catenin Pathway.","date":"2020","source":"Medical science monitor : international medical journal of experimental and clinical research","url":"https://pubmed.ncbi.nlm.nih.gov/32464633","citation_count":21,"is_preprint":false},{"pmid":"11916131","id":"PMC_11916131","title":"Expression of 36-kDa microfibril-associated glycoprotein (MAGP-36) in human keratinocytes and its localization in skin.","date":"2002","source":"Journal of dermatological science","url":"https://pubmed.ncbi.nlm.nih.gov/11916131","citation_count":20,"is_preprint":false},{"pmid":"30338930","id":"PMC_30338930","title":"MAGP-1 and fibronectin control EGFL7 functions by driving its deposition into distinct endothelial extracellular matrix locations.","date":"2018","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/30338930","citation_count":18,"is_preprint":false},{"pmid":"18470678","id":"PMC_18470678","title":"Histochemical localization of the extracellular matrix components in the annular ligament of rat stapediovestibular joint with special reference to fibrillin, 36-kDa microfibril-associated glycoprotein (MAGP-36), and hyaluronic acid.","date":"2008","source":"Medical molecular morphology","url":"https://pubmed.ncbi.nlm.nih.gov/18470678","citation_count":17,"is_preprint":false},{"pmid":"35546486","id":"PMC_35546486","title":"MFAP2 aggravates tumor progression through activating FOXM1/β-catenin-mediated glycolysis in ovarian cancer.","date":"2022","source":"The Kaohsiung journal of medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/35546486","citation_count":16,"is_preprint":false},{"pmid":"34445187","id":"PMC_34445187","title":"Decreased Levels of Microfibril-Associated Glycoprotein (MAGP)-1 in Patients with Colon Cancer and Obesity Are Associated with Changes in Extracellular Matrix Remodelling.","date":"2021","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/34445187","citation_count":14,"is_preprint":false},{"pmid":"37635348","id":"PMC_37635348","title":"MFAP2 promotes HSCs activation through FBN1/TGF-β/Smad3 pathway.","date":"2023","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/37635348","citation_count":11,"is_preprint":false},{"pmid":"9792630","id":"PMC_9792630","title":"The exon structure of the human MAGP-2 gene. Similarity with the MAGP-1 gene is confined to two exons encoding a cysteine-rich region.","date":"1998","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/9792630","citation_count":11,"is_preprint":false},{"pmid":"37592847","id":"PMC_37592847","title":"MFAP2 promotes the progression of oral squamous cell carcinoma by activating the Wnt/β-catenin signaling pathway through autophagy.","date":"2023","source":"Acta biochimica et biophysica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/37592847","citation_count":9,"is_preprint":false},{"pmid":"10723723","id":"PMC_10723723","title":"Organization of the mouse microfibril-associated glycoprotein-2 (MAGP-2) gene.","date":"2000","source":"Mammalian genome : official journal of the International Mammalian Genome Society","url":"https://pubmed.ncbi.nlm.nih.gov/10723723","citation_count":9,"is_preprint":false},{"pmid":"35211173","id":"PMC_35211173","title":"Pan-Cancer Analysis of Microfibrillar-Associated Protein 2 (MFAP2) Based on Bioinformatics and qPCR Verification.","date":"2022","source":"Journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/35211173","citation_count":8,"is_preprint":false},{"pmid":"39698924","id":"PMC_39698924","title":"MFAP2 upregulation promotes ESCC metastasis via FAK-AKT signaling pathway.","date":"2024","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/39698924","citation_count":7,"is_preprint":false},{"pmid":"37304872","id":"PMC_37304872","title":"MFAP2 enhances cisplatin resistance in gastric cancer cells by regulating autophagy.","date":"2023","source":"PeerJ","url":"https://pubmed.ncbi.nlm.nih.gov/37304872","citation_count":7,"is_preprint":false},{"pmid":"15560107","id":"PMC_15560107","title":"The pattern of fibrillin deposition correlates with microfibril-associated glycoprotein 1 (MAGP-1) expression in cultured blood and lymphatic endothelial cells.","date":"2004","source":"Lymphology","url":"https://pubmed.ncbi.nlm.nih.gov/15560107","citation_count":7,"is_preprint":false},{"pmid":"38988940","id":"PMC_38988940","title":"MFAP2 induces epithelial-mesenchymal transformation of osteosarcoma cells by activating the Notch1 pathway.","date":"2024","source":"Translational cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/38988940","citation_count":6,"is_preprint":false},{"pmid":"40131129","id":"PMC_40131129","title":"MFAP2 promotes the malignant progression of gastric cancer via activating the PI3K/AKT signaling pathway.","date":"2025","source":"Journal of receptor and signal transduction research","url":"https://pubmed.ncbi.nlm.nih.gov/40131129","citation_count":3,"is_preprint":false},{"pmid":"10664011","id":"PMC_10664011","title":"Expression of microfibril-associated glycoprotein-1 (MAGP-1) in human epidermal keratinocytes.","date":"2000","source":"Archives of dermatological research","url":"https://pubmed.ncbi.nlm.nih.gov/10664011","citation_count":3,"is_preprint":false},{"pmid":"40153018","id":"PMC_40153018","title":"FOXA1-mediated transcription of MFAP2 facilitates cell growth, metastasis and cisplatin resistance in uterine corpus endometrial carcinoma.","date":"2025","source":"Naunyn-Schmiedeberg's archives of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/40153018","citation_count":2,"is_preprint":false},{"pmid":"40657371","id":"PMC_40657371","title":"MFAP2 promotes the progress of esophageal squamous cell carcinoma by enhancing PTGS2 signaling.","date":"2025","source":"Journal of Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/40657371","citation_count":1,"is_preprint":false},{"pmid":"41716634","id":"PMC_41716634","title":"MFAP2 promotes metastasis and drug resistance by regulating epithelial-to-mesenchymal transition through EGFR signaling pathway in colorectal cancer cells.","date":"2025","source":"Genes & diseases","url":"https://pubmed.ncbi.nlm.nih.gov/41716634","citation_count":0,"is_preprint":false},{"pmid":"41617683","id":"PMC_41617683","title":"Cancer-associated fibroblasts (CAFs) derived from MFAP2 promote CRC proliferation and metastasis while suppressing CD8+ T cell-mediated antitumor immunity.","date":"2026","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/41617683","citation_count":0,"is_preprint":false},{"pmid":"39829397","id":"PMC_39829397","title":"TWIST1 Regulates FOXM1/β-Catenin to Promote the Growth, Migration, and Invasion of Ovarian Cancer Cells by Activating MFAP2.","date":"2025","source":"Journal of biochemical and molecular toxicology","url":"https://pubmed.ncbi.nlm.nih.gov/39829397","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.06.22.660927","title":"Stiffness sensing fuels matrix-driven metabolic reboot for kidney repair and regeneration","date":"2025-06-26","source":"bioRxiv","url":"https://doi.org/10.1101/2025.06.22.660927","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.07.21.604481","title":"The Identification Markers of activated myofibroblast subsets in the Human Lung Fibrosis Ecosystem via integrated omics Analysis","date":"2024-07-23","source":"bioRxiv","url":"https://doi.org/10.1101/2024.07.21.604481","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":26328,"output_tokens":4883,"usd":0.076115},"stage2":{"model":"claude-opus-4-6","input_tokens":8387,"output_tokens":3475,"usd":0.193215},"total_usd":0.26933,"stage1_batch_id":"msgbatch_01Mgbec4vM6c9vXht7JVJzss","stage2_batch_id":"msgbatch_01JkuuH5RB2BdJNsgnhjbC6s","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1996,\n      \"finding\": \"MAGP-2 (MP25/MFAP2) was identified as a distinct component of elastin-associated microfibrils by immunofluorescence and immunoelectron microscopy, and its primary structure was determined by cDNA cloning. It shares significant structural similarity with MAGP-1, confined to a central 60-amino acid region with 7 conserved cysteines, but lacks the proline/glutamine/tyrosine-rich sequences and hydrophobic carboxyl terminus of MAGP-1, and contains an RGD motif, suggesting distinct functions.\",\n      \"method\": \"cDNA cloning, immunofluorescence, immunoelectron microscopy, sequence analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — original molecular characterization with direct localization by immunoelectron microscopy and complete sequence determination; foundational paper\",\n      \"pmids\": [\"8557636\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"MAGP-2 is specifically associated with fibrillin-containing microfibrils in multiple tissues (nuchal ligament, dermis, adventitia of aorta, glomerular mesangium, perimysium) as demonstrated by immunoelectron microscopy, but shows more restricted tissue distribution than MAGP-1, being absent from the medial layer of fetal thoracic aorta, peritubular matrix of kidney, and ocular zonule.\",\n      \"method\": \"Immunoelectron microscopy, immunolocalization, Northern blotting\",\n      \"journal\": \"The journal of histochemistry and cytochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct localization by immunoelectron microscopy with functional tissue distribution mapping; corroborates MAGP-1 studies\",\n      \"pmids\": [\"9671438\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"MAGP-1 (MFAP2 paralog) binds specifically to the collagenous domain of the alpha3(VI) chain of type VI collagen in solid-phase binding assays (Kd ~5.6×10⁻⁷ M) but MAGP-2 does not bind type VI collagen. The binding site on MAGP-1 resides in its N-terminal, cysteine-free domain (amino acids 29-38), and tropoelastin competes for the same binding site on MAGP-1.\",\n      \"method\": \"Solid-phase binding assay, affinity blotting, inhibition experiments with peptides and reduction/alkylation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — in vitro binding assays with domain mapping, mutagenesis-equivalent peptide inhibition, Kd measurements; demonstrates MAGP-2 does NOT bind collagen VI\",\n      \"pmids\": [\"9278443\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"MAGP-2 specifically interacts with fibrillin-1 and fibrillin-2 via yeast two-hybrid and co-immunoprecipitation. The binding site on fibrillin-1 and -2 is a calcium-binding EGF repeat-containing region near the C terminus, distinct from the MAGP-1 binding site on fibrillin-1. The interacting domain on MAGP-2 is a core region containing 48% identity with MAGP-1 and 7 conserved cysteines.\",\n      \"method\": \"Yeast two-hybrid screen, deletion analysis, co-immunoprecipitation from transfected COS-7 cells\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal yeast two-hybrid plus co-IP with domain mapping; two orthogonal methods\",\n      \"pmids\": [\"12122015\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"MAGP-2 interacts with the Notch ligand Jagged1 via EGF-like repeats of Jagged1, as shown by yeast two-hybrid and co-immunoprecipitation. MAGP-2 co-expression induces metalloproteinase-dependent shedding of the Jagged1 extracellular domain. MAGP-2 also interacts with Jagged2 and Delta1, but does not induce their shedding. MAGP-1 interacts with DSL ligands but cannot facilitate Jagged1 shedding.\",\n      \"method\": \"Yeast two-hybrid, co-immunoprecipitation, conditioned media analysis, metalloproteinase inhibitor (BB3103)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP plus yeast two-hybrid, pharmacological inhibition, two orthogonal methods\",\n      \"pmids\": [\"15788413\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"MAGP-2 and MAGP-1 interact with EGF-like repeats of Notch1 and induce dissociation of the Notch1 extracellular domain from the cell surface, leading to activation of Notch signaling. The C-terminal domain of MAGP-2 is required for Notch1 binding and activation. MAGP-2-induced Notch1 extracellular domain release requires prior furin-like cleavage (heterodimer formation) but does not require ADAM metalloprotease cleavage.\",\n      \"method\": \"Co-expression/co-immunoprecipitation, domain deletion analysis, reporter assays, ADAM inhibitor experiments\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (Co-IP, reporter assay, domain mapping, pharmacological dissection) in a single study\",\n      \"pmids\": [\"16492672\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"MAGP-2 overexpression stimulates elastic fiber assembly in vitro, as shown by increased elastic fiber levels in cells conditionally overexpressing MAGP-2. Electron microscopy confirmed MAGP-2 associates specifically with microfibrils and elastin globules colocalize with MAGP-2-associated microfibrils. The RGD motif of MAGP-2 is not required for this activity, and overexpression of MAGP-2 did not alter levels of fibrillin-1, MAGP-1, fibulin-2, fibulin-5, or emilin-1 in the matrix.\",\n      \"method\": \"Conditional overexpression (doxycycline-regulated), immunofluorescence, electron microscopy, mutational analysis (RGD motif)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean gain-of-function with specific phenotypic readout, mutagenesis, and electron microscopy confirmation\",\n      \"pmids\": [\"17099216\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"MAGP-2 promotes angiogenic cell sprouting by antagonizing Notch signaling in endothelial cells. MAGP-2 decreased basal and Jagged1-induced Hes-1 promoter activity in endothelial cells and blocked Jagged1-stimulated Notch1 receptor processing. Constitutive Notch pathway activation blocked MAGP-2-induced sprouting. Notably, MAGP-2 had the opposite effect (activating Notch) in heterologous non-endothelial cell types.\",\n      \"method\": \"Luciferase reporter assay (Hes-1 promoter), Notch1 receptor processing assay, angiogenic sprouting assay, constitutively active Notch rescue experiment\",\n      \"journal\": \"Microvascular research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — epistasis via constitutive activation rescue, reporter assay, and functional sprouting assay; multiple orthogonal methods\",\n      \"pmids\": [\"18417156\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"MFAP2 promotes gastric cancer cell motility through the integrin α5β1/FAK/ERK signaling pathway. Silencing MFAP2 by shRNA inhibited motility and was rescued by fibronectin (another FAK activator). MFAP2 regulated integrin expression through ERK1/2 activation. miR-29 was identified as a regulator of MFAP2 expression. In vivo, MFAP2 silencing inhibited tumorigenicity and metastasis in nude mice.\",\n      \"method\": \"shRNA knockdown, rescue with fibronectin, ERK1/2 signaling assays, in vivo xenograft, miRNA regulation experiments\",\n      \"journal\": \"Oncogenesis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KO with defined phenotypic readout and pathway rescue, in vitro and in vivo; single lab\",\n      \"pmids\": [\"32054827\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MFAP2 promotes epithelial-mesenchymal transition (EMT) in gastric cancer cells by activating the TGF-β/SMAD2/3 signaling pathway, as demonstrated by gain- and loss-of-function experiments measuring EMT markers and SMAD phosphorylation.\",\n      \"method\": \"Gain- and loss-of-function experiments, Western blot for SMAD2/3 phosphorylation and EMT markers\",\n      \"journal\": \"OncoTargets and therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — KD/OE with pathway placement but limited mechanistic depth; single lab, single paper\",\n      \"pmids\": [\"30034240\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"MFAP2 promotes CRC cell invasion through CLK3 as a downstream target; MFAP2 depletion induces autophagic degradation of CLK3, and the pro-invasive effect of MFAP2 in CRC cells is dependent on CLK3. CLK3 was identified as a MFAP2 target by mass spectrometry.\",\n      \"method\": \"Mass spectrometry (downstream target screening), siRNA knockdown, CLK3 rescue experiments, transwell invasion assays, peritoneal metastasis mouse model\",\n      \"journal\": \"Cancer medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — MS-based target identification plus genetic rescue; single lab\",\n      \"pmids\": [\"36583532\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"MFAP2 promotes ESCC metastasis by binding to the FERM domain of focal adhesion kinase (FAK), alleviating FAK intramolecular inhibition, enhancing FAK–integrin β4 (ITGB4) interaction, and activating the FAK-AKT signaling pathway. Treatment with FAK inhibitor PND-1186 reduced MFAP2-driven FAK-AKT activation and suppressed lung metastasis in vivo.\",\n      \"method\": \"Co-immunoprecipitation (MFAP2-FAK interaction), domain binding analysis, FAK inhibitor (PND-1186) experiments, in vivo metastasis model, shRNA knockdown\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct protein-protein interaction (Co-IP with domain specificity) plus pharmacological validation in vivo; single lab\",\n      \"pmids\": [\"39698924\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"MFAP2 promotes hepatic stellate cell (HSC) activation in liver fibrosis through upregulation of fibrillin-1 (FBN1) and downstream TGF-β/Smad3 signaling. MFAP2 knockdown inhibited HSC proliferation and collagen deposition, and attenuated fibrosis in a CCl4-induced mouse model.\",\n      \"method\": \"Bioinformatics, MFAP2 overexpression/knockdown, qRT-PCR, Western blot, in vivo CCl4 mouse fibrosis model\",\n      \"journal\": \"Journal of cellular and molecular medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — pathway placement via KD/OE with phenotypic readout, but no direct protein-protein interaction data for MFAP2-FBN1; single lab\",\n      \"pmids\": [\"37635348\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"MFAP2 transcription is activated by the lncRNA LCPAT1 through recruitment of the chromatin remodeler RBBP4 to the MFAP2 promoter, as shown by RNA immunoprecipitation and ChIP assays. Restoration of MFAP2 rescued the proliferative and migratory effects of LCPAT1 knockdown in breast cancer cells.\",\n      \"method\": \"RNA immunoprecipitation, ChIP assay, MFAP2 restoration rescue experiment, in vitro/in vivo functional assays\",\n      \"journal\": \"Molecular therapy. Nucleic acids\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct identification of upstream transcriptional regulator by ChIP and rescue experiments; single lab\",\n      \"pmids\": [\"32791452\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TWIST1 directly binds the MFAP2 promoter to transcriptionally activate MFAP2 expression in ovarian cancer, as validated by dual-luciferase reporter assay and ChIP-qPCR. TWIST1 promotes ovarian cancer cell growth, migration, and invasion via MFAP2-dependent activation of FOXM1/β-catenin signaling.\",\n      \"method\": \"Dual-luciferase reporter assay, ChIP-qPCR, gain/loss-of-function experiments, xenograft model\",\n      \"journal\": \"Journal of biochemical and molecular toxicology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct promoter binding validated by two complementary methods; single lab\",\n      \"pmids\": [\"39829397\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"FOXA1 transcriptionally activates MFAP2 by binding to its promoter region in uterine corpus endometrial carcinoma, as validated by ChIP assay and dual-luciferase reporter assay. FOXA1-mediated MFAP2 upregulation promotes UCEC cell growth, metastasis, and cisplatin resistance.\",\n      \"method\": \"ChIP assay, dual-luciferase reporter assay, siRNA knockdown, colony formation, transwell, xenograft model\",\n      \"journal\": \"Naunyn-Schmiedeberg's archives of pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — two orthogonal methods validating direct promoter binding; single lab\",\n      \"pmids\": [\"40153018\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"CAF-derived MFAP2 interacts with integrin β8 (ITGB8) on colorectal cancer cell surfaces, activating the FAK-ERK1/2 signaling cascade. ERK1/2 phosphorylates ETS2 transcription factor, which upregulates CYP27A1 to suppress CD8+ T cell function via LXRβ signaling, establishing a MFAP2-ITGB8-FAK-ERK1/2-ETS2-CYP27A1-LXRβ axis.\",\n      \"method\": \"Co-immunoprecipitation (MFAP2-ITGB8), phosphorylation analysis, in vitro/in vivo functional assays, immunosuppression experiments\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct protein-protein interaction (Co-IP) plus multi-step pathway validation in vitro and in vivo; single lab\",\n      \"pmids\": [\"41617683\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Mfap2 loss in mouse kidney disrupts tissue architecture and aggravates acute kidney injury. Mechanistically, Mfap2 deficiency suppresses tubular HMGCS2 expression via ESR2-mediated transcriptional repression, increases protein succinylation, and hyperactivates MAP kinases and LATS1 in tubular cells. LATS1 suppresses ESR2 transcription independently of canonical YAP/TAZ effectors. ESR2 agonist treatment restored kidney function in Mfap2-deficient models.\",\n      \"method\": \"Mfap2 knockout mouse model, global proteomics, phosphoproteomics, spatial transcriptomics, pharmacological rescue (ESR2 agonist)\",\n      \"journal\": \"bioRxiv (preprint)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multi-omics plus genetic KO with pharmacological rescue; preprint, not yet peer reviewed\",\n      \"pmids\": [\"bio_10.1101_2025.06.22.660927\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"MFAP2/MAGP-2 is a small extracellular matrix glycoprotein that is an integral component of fibrillin-containing microfibrils, where it binds fibrillin-1 and fibrillin-2 at a C-terminal EGF repeat region to promote elastic fiber assembly; outside the matrix, MAGP-2 modulates cell signaling by binding EGF-like repeats on Notch1 (via its C-terminal domain) and the Notch ligand Jagged1 to induce their ectodomain shedding, thereby activating or antagonizing Notch signaling in a cell-context-dependent manner; in cancer contexts, secreted MFAP2 promotes invasion and metastasis by engaging integrin receptors (α5β1, β4, β8) to activate FAK-AKT or FAK-ERK signaling cascades, and its expression is transcriptionally controlled upstream by TWIST1 and FOXA1.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"MFAP2 (MAGP-2) is a secreted extracellular matrix glycoprotein that serves dual roles as a structural component of fibrillin-containing microfibrils and as a signaling modulator. It binds fibrillin-1 and fibrillin-2 via their C-terminal EGF repeat regions to promote elastic fiber assembly independently of its RGD motif [PMID:12122015, PMID:17099216], and interacts with Notch1 through its own C-terminal domain to induce ectodomain shedding and context-dependent Notch activation or antagonism—activating Notch in heterologous cells while inhibiting Notch signaling in endothelial cells to promote angiogenic sprouting [PMID:16492672, PMID:18417156]. MAGP-2 also binds the Notch ligand Jagged1 and induces its metalloproteinase-dependent ectodomain shedding [PMID:15788413]. In cancer contexts, secreted MFAP2 engages integrin receptors (α5β1, β4, β8) and directly binds the FERM domain of FAK to activate FAK–ERK or FAK–AKT signaling cascades that drive invasion and metastasis, and its transcription is directly activated by TWIST1 and FOXA1 [PMID:32054827, PMID:39698924, PMID:41617683, PMID:39829397].\",\n  \"teleology\": [\n    {\n      \"year\": 1996,\n      \"claim\": \"Identifying MAGP-2 as a distinct microfibril-associated protein established that elastin-associated microfibrils contain a second MAGP family member with divergent domain architecture and an RGD motif, raising the question of whether it has non-redundant functions relative to MAGP-1.\",\n      \"evidence\": \"cDNA cloning, immunofluorescence, and immunoelectron microscopy localizing MAGP-2 to microfibrils\",\n      \"pmids\": [\"8557636\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No binding partners identified beyond microfibril co-localization\", \"Functional significance of the RGD motif untested\", \"No knockout or loss-of-function data\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Demonstrating that MAGP-2 has a more restricted tissue distribution than MAGP-1 and does not bind type VI collagen established that the two paralogs occupy distinct niches within the extracellular matrix despite their shared microfibril association.\",\n      \"evidence\": \"Immunoelectron microscopy across multiple tissues; solid-phase binding assays showing no MAGP-2–collagen VI interaction\",\n      \"pmids\": [\"9671438\", \"9278443\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct binding partner on microfibrils not yet identified\", \"No functional consequence of restricted distribution tested\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Mapping the direct interaction between MAGP-2 and fibrillin-1/fibrillin-2 to a C-terminal EGF repeat region on fibrillins—distinct from the MAGP-1 binding site—revealed that the two MAGPs occupy non-overlapping sites on microfibrils, suggesting independent structural contributions.\",\n      \"evidence\": \"Yeast two-hybrid screen with deletion analysis plus co-immunoprecipitation from COS-7 cells\",\n      \"pmids\": [\"12122015\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of MAGP-2–fibrillin binding for microfibril integrity not tested\", \"No in vivo validation\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Discovering that MAGP-2 binds Jagged1 EGF-like repeats and induces its metalloproteinase-dependent ectodomain shedding expanded MAGP-2's role beyond structural matrix protein to a modulator of Notch ligand availability.\",\n      \"evidence\": \"Yeast two-hybrid, co-immunoprecipitation, conditioned media analysis, metalloproteinase inhibitor (BB3103)\",\n      \"pmids\": [\"15788413\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Downstream Notch signaling consequences not measured\", \"In vivo relevance of Jagged1 shedding by MAGP-2 unknown\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Two studies established that MAGP-2 directly activates Notch1 by inducing furin-dependent extracellular domain dissociation via its C-terminal domain, and independently stimulates elastic fiber assembly without requiring its RGD motif, delineating its dual structural and signaling functions.\",\n      \"evidence\": \"Co-IP with domain deletions, Notch reporter assays, ADAM inhibitor experiments; conditional MAGP-2 overexpression with electron microscopy and RGD mutant analysis\",\n      \"pmids\": [\"16492672\", \"17099216\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which MAGP-2 promotes elastin deposition without altering other matrix components unclear\", \"Physiological relevance of Notch1 activation by MAGP-2 in vivo not shown\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Showing that MAGP-2 antagonizes Notch signaling specifically in endothelial cells (while activating it in other cell types) to promote angiogenic sprouting revealed that MAGP-2's effect on Notch is cell-context-dependent, resolving an apparent contradiction.\",\n      \"evidence\": \"Hes-1 reporter assay, Notch1 processing analysis, angiogenic sprouting assay with constitutively active Notch rescue in endothelial cells\",\n      \"pmids\": [\"18417156\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of cell-type-specific Notch modulation not identified\", \"No in vivo angiogenesis data\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Linking MFAP2 to epithelial-mesenchymal transition via TGF-β/SMAD2/3 signaling in gastric cancer placed it in a pro-metastatic signaling context beyond its canonical matrix and Notch roles.\",\n      \"evidence\": \"Gain- and loss-of-function experiments with SMAD2/3 phosphorylation and EMT marker analysis in gastric cancer cells\",\n      \"pmids\": [\"30034240\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct MFAP2–TGF-β receptor interaction demonstrated\", \"Single cancer type, single lab\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identifying integrin α5β1/FAK/ERK as a direct signaling axis for MFAP2-driven gastric cancer motility, with fibronectin rescue of MFAP2 knockdown, established FAK as a central downstream effector and revealed miR-29 as an upstream regulator of MFAP2 expression.\",\n      \"evidence\": \"shRNA knockdown with fibronectin rescue, ERK signaling assays, in vivo xenograft, miRNA experiments\",\n      \"pmids\": [\"32054827\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct MFAP2–integrin α5β1 physical interaction not demonstrated by co-IP\", \"miR-29 regulation not validated with reporter assays in this study\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Demonstrating that LCPAT1 lncRNA recruits the chromatin remodeler RBBP4 to the MFAP2 promoter to activate its transcription identified a first epigenetic regulatory mechanism for MFAP2 expression.\",\n      \"evidence\": \"RNA immunoprecipitation, ChIP assay at MFAP2 promoter, MFAP2 rescue of LCPAT1 knockdown in breast cancer cells\",\n      \"pmids\": [\"32791452\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether RBBP4 recruitment alters histone modifications at the MFAP2 locus not shown\", \"Single cancer context\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identifying CLK3 as a downstream effector whose autophagic degradation is induced upon MFAP2 depletion revealed a non-canonical intracellular consequence of extracellular MFAP2 signaling in colorectal cancer invasion.\",\n      \"evidence\": \"Mass spectrometry target screening, siRNA knockdown, CLK3 rescue, transwell invasion, peritoneal metastasis model\",\n      \"pmids\": [\"36583532\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How an extracellular protein regulates intracellular CLK3 degradation is mechanistically unclear\", \"Single lab, single cancer type\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Demonstrating direct MFAP2 binding to the FERM domain of FAK to relieve intramolecular autoinhibition and enhance FAK–integrin β4 interaction provided the first structural-level explanation for MFAP2-driven FAK-AKT activation in metastasis.\",\n      \"evidence\": \"Co-immunoprecipitation with domain analysis, FAK inhibitor PND-1186 in vitro and in vivo (ESCC lung metastasis model)\",\n      \"pmids\": [\"39698924\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No crystal structure or biophysical binding data for MFAP2–FERM interaction\", \"Single cancer type\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identifying TWIST1 and FOXA1 as direct transcriptional activators of MFAP2 via promoter binding established upstream transcription factor control of MFAP2 in ovarian and endometrial cancers, linking EMT master regulators to MFAP2 induction.\",\n      \"evidence\": \"ChIP-qPCR and dual-luciferase reporter assays for TWIST1 and FOXA1 binding to MFAP2 promoter; gain/loss-of-function and xenograft models\",\n      \"pmids\": [\"39829397\", \"40153018\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether TWIST1 and FOXA1 cooperate or act independently at the MFAP2 promoter unknown\", \"Relevance to non-cancer tissues not tested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrating that cancer-associated fibroblast-secreted MFAP2 engages integrin β8 on colorectal cancer cells to activate FAK-ERK1/2-ETS2-CYP27A1 signaling, suppressing CD8+ T cell function, expanded MFAP2's role to immune evasion in the tumor microenvironment.\",\n      \"evidence\": \"Co-immunoprecipitation of MFAP2–ITGB8, phosphorylation cascade analysis, in vitro and in vivo immunosuppression experiments\",\n      \"pmids\": [\"41617683\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether MFAP2–ITGB8 interaction occurs in non-tumor contexts unknown\", \"Contribution relative to other CAF-derived factors not quantified\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include: the structural basis of MFAP2's context-dependent Notch modulation; in vivo phenotypes of Mfap2 genetic deletion in elastic tissue homeostasis; whether MFAP2's integrin/FAK and Notch signaling roles intersect; and the mechanism by which extracellular MFAP2 controls intracellular CLK3 degradation.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No Mfap2 constitutive knockout phenotype in elastic tissues published in peer-reviewed literature\", \"Structural basis of cell-context-dependent Notch modulation unknown\", \"Relationship between MFAP2's matrix and signaling functions unresolved\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1, 3, 6]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [4, 5, 7]},\n      {\"term_id\": \"GO:0048018\", \"supporting_discovery_ids\": [8, 11, 16]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0031012\", \"supporting_discovery_ids\": [0, 1, 3, 6]},\n      {\"term_id\": \"GO:0005576\", \"supporting_discovery_ids\": [0, 4, 5, 16]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1474244\", \"supporting_discovery_ids\": [0, 1, 3, 6]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [4, 5, 7, 8, 9, 11, 16]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [5, 7]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"FBN1\",\n      \"FBN2\",\n      \"JAG1\",\n      \"NOTCH1\",\n      \"FAK\",\n      \"ITGB4\",\n      \"ITGB8\",\n      \"ITGA5\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}