{"gene":"SDC2","run_date":"2026-06-10T07:46:30","timeline":{"discoveries":[{"year":1999,"finding":"Activated human macrophages express a single major 48-kDa cell surface HSPG, syndecan-2 (fibroglycan), synthesized de novo upon activation. This macrophage-expressed SDC2 selectively binds FGF-2, VEGF, and HB-EGF, and can present FGF-2 in a form that transactivates FGF-receptor-bearing BaF32 cells, demonstrating SDC2's role in growth factor sequestration and delivery.","method":"De novo RNA/protein synthesis analysis, growth factor binding assays, BaF32 cell transactivation assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — single lab, multiple orthogonal methods (binding assay, functional transactivation assay, Western blot), direct characterization of SDC2 as the sole macrophage HSPG","pmids":["10446183"],"is_preprint":false},{"year":1993,"finding":"Fibroglycan (SDC2) is expressed exclusively on mesenchymal cells during mouse embryogenesis, with peak expression during morphogenetic phases and at sites of cell-cell/cell-matrix interactions (epithelial-mesenchymal interfaces, prechondrogenic condensations), in a pattern distinct from syndecan-1 (epithelial). This spatiotemporal pattern was confirmed by both immunohistochemistry and in situ hybridization.","method":"Immunohistochemistry with anti-human fibroglycan monoclonal antibody (10H4), in situ hybridization, Western blot of embryo extracts","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with orthogonal methods (IHC + ISH), single lab, functionally interpreted in context of morphogenesis","pmids":["8187643"],"is_preprint":false},{"year":2013,"finding":"In zebrafish, Sdc2 (syndecan-2) regulates left-right patterning through cell-autonomous functions in Kupffer's vesicle (KV), including regulation of cell proliferation, adhesion, cilia length, and asymmetric fluid flow. Sdc2 and Tbx16 jointly regulate Fgf2 expression in KV; Fgf2 controls KV morphogenesis (but not cilia length) downstream of Sdc2, and Fgf2 mRNA rescue restores KV morphogenesis in sdc2 morphants, defining a Sdc2-Tbx16-Fgf2 pathway.","method":"Lineage-targeted morpholino knockdown, mRNA rescue, in situ hybridization, cilia length measurement, fluid flow analysis","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — morpholino KD with mRNA rescue (epistasis), multiple orthogonal phenotypic readouts, single lab","pmids":["24046323"],"is_preprint":false},{"year":2016,"finding":"Postsynaptic SDC2 uses its ectodomain to interact with FGF22 and facilitate its targeting to dendritic filopodia, thereby triggering presynaptic maturation. SDC2 also enhances filopodial targeting of NMDAR via interaction with the CASK-mLIN7-MINT1 adaptor complex. Presynaptic maturation promoted by FGF22 feeds back through increased neurotransmitter release to activate NMDAR, promoting the dendritic filopodia-to-spine transition. CaMKII (activated by the NMDAR pathway) further facilitates FGF22 targeting via KIF17 regulation.","method":"Co-immunoprecipitation, transfection/overexpression in neurons, live imaging of dendritic filopodia, immunostaining of synaptic markers","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP identifying SDC2-FGF22 interaction, multiple cellular readouts, single lab","pmids":["27627962"],"is_preprint":false},{"year":2017,"finding":"SDC2 (Syndecan-2) is a surface marker on PAX7-induced human myogenic progenitors derived from pluripotent stem cells. CD54+α9β1+SDC2+ sorted cells contribute to long-term muscle regeneration in vivo, establishing SDC2 as a functional surface marker enabling isolation of myogenic progenitors.","method":"PAX7 genomic target analysis, fluorescent- and magnetic-based cell sorting (FACS/MACS), in vivo muscle engraftment assay","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct sorting and in vivo functional validation, single lab, multiple methods","pmids":["28658631"],"is_preprint":false},{"year":2023,"finding":"SDC2 interacts with the PDK1-PH domain, facilitating PDK1 membrane translocation and AKT activation in gastric cancer cells. SDC2 also functions as a co-receptor for FGF2, contributing to the FGF2-AKT signaling axis. Additionally, the deubiquitinase USP14 stabilizes SDC2 protein by preventing its degradation, and the USP14 inhibitor IU1 decreases SDC2 abundance in GC cells.","method":"Co-immunoprecipitation (SDC2-PDK1 interaction), overexpression/depletion experiments, Western blot for AKT phosphorylation, USP14 inhibitor treatment, bioinformatics","journal":"International journal of biological sciences","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP for SDC2-PDK1 binding, multiple orthogonal functional assays, single lab","pmids":["37496999"],"is_preprint":false},{"year":2024,"finding":"Pleiotrophin (PTN) secreted by Leydig cells signals to spermatogonial stem cells (SSCs) through SDC2 as a receptor. Protein immunoprecipitation confirmed PTN-SDC2 interaction in spermatogonia. SDC2 knockdown in human SSC lines impaired cell proliferation, DNA synthesis, PLZF expression, and downregulated GFRA1 and the HIF-1 signaling pathway. Exogenous PTN rescued proliferation and GFRA1 expression in SDC2 knockdown cells.","method":"Single-cell RNA sequencing analysis, immunofluorescence co-localization, protein immunoprecipitation, SDC2 siRNA knockdown, transcriptome analysis, proliferation/DNA synthesis assays","journal":"Biological research","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP confirming PTN-SDC2 binding, KD rescue experiment, transcriptomic pathway analysis, single lab","pmids":["39285301"],"is_preprint":false},{"year":2020,"finding":"In atherosclerosis, SDC2 is highly expressed and miR-9 targets SDC2 to negatively regulate it. SDC2 depletion reduces aortic plaque area, collagen fiber proliferation, macrophage infiltration, and pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) by suppressing the FAK/ERK signaling pathway, placing SDC2 upstream of FAK/ERK in atherosclerotic vascular pathology.","method":"Ectopic miR-9 expression in ACS mice, SDC2 siRNA depletion, Western blot for FAK/ERK pathway proteins, oil red O staining, Masson's trichrome staining, immunohistochemistry","journal":"Frontiers in physiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — in vivo pathway analysis with KD but pathway placement inferred indirectly; single lab, single study","pmids":["32765295"],"is_preprint":false},{"year":2017,"finding":"miR-20a-5p targets SDC2 mRNA to suppress its expression. SDC2 mediates multi-drug resistance in osteosarcoma cells; siRNA-mediated SDC2 knockdown recapitulates the chemosensitizing effect of miR-20a-5p mimic, and SDC2 overexpression restores chemoresistance in miR-20a-5p-overexpressing cells.","method":"miRNA mimic/antagomir transfection, SDC2 siRNA knockdown, SDC2 overexpression, CCK8 cell viability assay, tumor xenograft in nude mice","journal":"Cancer cell international","confidence":"Low","confidence_rationale":"Tier 3 / Weak — functional rescue/epistasis with KD and OE, single lab, limited mechanistic depth on SDC2 mechanism","pmids":["29118673"],"is_preprint":false},{"year":2014,"finding":"Microduplication of chromosome 8q22.1 encompassing GDF6 and SDC2 causes Leri's pleonosteosis. Expression analysis of patient dermal fibroblasts shows overexpression of SDC2 dysregulates extracellular matrix genes and TGF-β pathway components, with markedly decreased inhibitory SMAD6 levels, linking SDC2 overexpression to TGF-β/SMAD signaling dysregulation.","method":"Whole-genome SNP genotyping, gene expression analysis of patient dermal fibroblasts, Western blot for SMAD6","journal":"Annals of the rheumatic diseases","confidence":"Low","confidence_rationale":"Tier 3 / Weak — patient fibroblast expression data, single lab, no direct mechanistic experiment on SDC2-SMAD interaction","pmids":["24442880"],"is_preprint":false},{"year":2020,"finding":"The recombinant ectodomain of syndecan-2 (HaSDC-2 from seahorse) promotes cell proliferation in a concentration-dependent manner and accelerates wound healing in scratch assays when applied exogenously. Overexpression of full-length HaSDC-2 confers significant cell survival against oxidative stressors (H2O2, HED), establishing functional roles for the SDC2 ectodomain in cell survival and proliferation.","method":"Recombinant ectodomain protein treatment, scratch wound healing assay, H2O2/HED stress survival assay, HaSDC-2 + pcDNA transfection","journal":"Fish & shellfish immunology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — seahorse ortholog, single lab, functional assays without defined molecular mechanism","pmids":["31982583"],"is_preprint":false}],"current_model":"SDC2 (syndecan-2/fibroglycan) is a transmembrane heparan sulfate proteoglycan expressed predominantly on mesenchymal cells that functions as a cell-surface co-receptor and scaffold: it binds and presents heparin-binding growth factors (FGF-2, VEGF, HB-EGF, FGF22, PTN) to their signaling receptors, regulates dendritic filopodial targeting of FGF22 and NMDA receptors through interactions with the CASK-mLIN7-MINT1 adaptor complex to coordinate bidirectional synapse maturation, activates AKT signaling by interacting with the PDK1-PH domain to facilitate PDK1 membrane translocation, and is stabilized post-translationally by the deubiquitinase USP14; its expression is regulated in a developmentally restricted, mesenchyme-specific pattern, and its abundance is controlled post-transcriptionally by miR-9 and miR-20a-5p."},"narrative":{"mechanistic_narrative":"SDC2 (syndecan-2/fibroglycan) is a transmembrane heparan sulfate proteoglycan expressed in a mesenchyme-restricted, developmentally regulated pattern that functions as a cell-surface co-receptor and scaffold to capture heparin-binding growth factors and couple them to downstream signaling [PMID:8187643, PMID:10446183]. On activated macrophages it is synthesized de novo as the major surface HSPG and selectively binds FGF-2, VEGF, and HB-EGF, presenting FGF-2 in a form that transactivates FGF-receptor-bearing cells, establishing its role in growth-factor sequestration and delivery [PMID:10446183]. SDC2 organizes morphogenetic signaling across systems: in zebrafish it acts cell-autonomously in Kupffer's vesicle to control left-right patterning via a Sdc2-Tbx16-Fgf2 pathway [PMID:24046323], and at developing synapses its ectodomain binds FGF22 to direct dendritic filopodial targeting and presynaptic maturation while enhancing NMDA-receptor targeting through the CASK-mLIN7-MINT1 adaptor complex [PMID:27627962]. SDC2 also serves as a receptor for pleiotrophin in spermatogonial stem cells, supporting proliferation and GFRA1/HIF-1 signaling [PMID:39285301]. Mechanistically it drives intracellular signaling by interacting with the PDK1 PH domain to facilitate PDK1 membrane translocation and AKT activation, and is itself stabilized post-translationally by the deubiquitinase USP14 [PMID:37496999]. Microduplication of 8q22.1 encompassing SDC2 causes Leri's pleonosteosis, with SDC2 overexpression dysregulating extracellular-matrix genes and TGF-β/SMAD signaling [PMID:24442880].","teleology":[{"year":1993,"claim":"Established that SDC2 (fibroglycan) marks the mesenchymal compartment during embryogenesis, distinguishing it spatially from epithelial syndecan-1 and implicating it in morphogenetic cell-cell/cell-matrix interactions.","evidence":"IHC, in situ hybridization, and Western blot of mouse embryo extracts","pmids":["8187643"],"confidence":"Medium","gaps":["Localization pattern alone does not define a molecular function","No binding partners or signaling readouts identified"]},{"year":1999,"claim":"Showed SDC2 acts as a growth-factor co-receptor, answering how the proteoglycan engages signaling: it binds FGF-2, VEGF, and HB-EGF and presents FGF-2 to activate FGF-receptor-bearing cells.","evidence":"De novo synthesis analysis, growth factor binding assays, and BaF32 transactivation assay in activated macrophages","pmids":["10446183"],"confidence":"Medium","gaps":["Does not resolve which structural domain (HS chains vs core protein) mediates binding","No downstream intracellular signaling defined"]},{"year":2013,"claim":"Placed SDC2 within a defined developmental signaling cascade, showing it controls left-right asymmetry cell-autonomously through a Sdc2-Tbx16-Fgf2 axis.","evidence":"Lineage-targeted morpholino knockdown with Fgf2 mRNA rescue and phenotypic readouts in zebrafish Kupffer's vesicle","pmids":["24046323"],"confidence":"Medium","gaps":["Morpholino-based knockdown without genetic mutant confirmation","Mechanism linking Sdc2 to cilia length distinct from Fgf2 unresolved"]},{"year":2016,"claim":"Defined a synaptic scaffolding role: SDC2's ectodomain binds FGF22 to drive bidirectional synapse maturation and couples NMDAR targeting to the CASK-mLIN7-MINT1 adaptor complex.","evidence":"Co-IP, neuronal overexpression, live imaging of dendritic filopodia, and synaptic marker immunostaining","pmids":["27627962"],"confidence":"Medium","gaps":["Co-IP interactions not validated by structural or reconstitution data","Stoichiometry within the adaptor complex undefined"]},{"year":2017,"claim":"Identified SDC2 as a functional surface marker of myogenic progenitors capable of long-term muscle regeneration, extending its role to stem/progenitor cell identity.","evidence":"PAX7 target analysis, FACS/MACS sorting, and in vivo muscle engraftment of CD54+α9β1+SDC2+ cells","pmids":["28658631"],"confidence":"Medium","gaps":["Marker status does not establish a mechanistic role in myogenesis","Signaling downstream of SDC2 in progenitors not examined"]},{"year":2017,"claim":"Linked SDC2 abundance to post-transcriptional control by miR-20a-5p and connected SDC2 levels to chemoresistance in osteosarcoma.","evidence":"miRNA mimic/antagomir, SDC2 siRNA knockdown and overexpression rescue, viability assays, and xenografts","pmids":["29118673"],"confidence":"Low","gaps":["Limited mechanistic depth on how SDC2 mediates drug resistance","Single lab, no orthogonal confirmation of the miR-20a-5p–SDC2 axis"]},{"year":2020,"claim":"Connected SDC2 to vascular inflammatory pathology, placing it upstream of FAK/ERK signaling and under negative control by miR-9 in atherosclerosis.","evidence":"Ectopic miR-9 expression and SDC2 siRNA depletion in ACS mice with FAK/ERK Western blot and histology","pmids":["32765295"],"confidence":"Low","gaps":["Pathway placement upstream of FAK/ERK inferred indirectly","Single study, not independently replicated"]},{"year":2023,"claim":"Revealed an intracellular signaling mechanism: SDC2 binds the PDK1 PH domain to promote PDK1 membrane translocation and AKT activation, and is stabilized by the deubiquitinase USP14.","evidence":"Co-IP of SDC2-PDK1, overexpression/depletion, AKT phosphorylation Western blot, and USP14 inhibitor (IU1) treatment in gastric cancer cells","pmids":["37496999"],"confidence":"Medium","gaps":["Direct vs indirect nature of SDC2-PDK1 binding not structurally resolved","How a transmembrane HSPG engages the cytosolic PDK1 PH domain mechanistically unclear"]},{"year":2024,"claim":"Established SDC2 as a pleiotrophin receptor in spermatogonial stem cells required for proliferation, PLZF/GFRA1 expression, and HIF-1 signaling.","evidence":"scRNA-seq, immunofluorescence co-localization, PTN-SDC2 immunoprecipitation, siRNA knockdown with PTN rescue, and transcriptome analysis in human SSC lines","pmids":["39285301"],"confidence":"Medium","gaps":["Whether SDC2 signals alone or with a co-receptor for PTN unresolved","Direct interaction not validated by reciprocal or structural methods"]},{"year":null,"claim":"How SDC2's heparan sulfate chains versus core protein, and its transmembrane/cytoplasmic domains, mechanistically partition between extracellular growth-factor presentation and intracellular PDK1/AKT signaling across cell types remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of SDC2 in any signaling complex","Domain-resolution mapping of growth-factor vs adaptor binding lacking","Tissue-specific determinants of co-receptor partner choice unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0038024","term_label":"cargo receptor activity","supporting_discovery_ids":[0,6]},{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[3,5,6]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[3,5]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,1,3]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[5,6]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[1,2]}],"complexes":[],"partners":["FGF2","VEGF","HBEGF","FGF22","PTN","PDK1","USP14"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P34741","full_name":"Syndecan-2","aliases":["Fibroglycan","Heparan sulfate proteoglycan core protein","HSPG"],"length_aa":201,"mass_kda":22.2,"function":"Cell surface proteoglycan which regulates dendritic arbor morphogenesis","subcellular_location":"Membrane","url":"https://www.uniprot.org/uniprotkb/P34741/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SDC2","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/SDC2","total_profiled":1310},"omim":[{"mim_id":"619563","title":"MICAL-LIKE PROTEIN 1; MICALL1","url":"https://www.omim.org/entry/619563"},{"mim_id":"610971","title":"TRAFFICKING PROTEIN PARTICLE COMPLEX, SUBUNIT 4; TRAPPC4","url":"https://www.omim.org/entry/610971"},{"mim_id":"609423","title":"HUMAN IMMUNODEFICIENCY VIRUS TYPE 1, SUSCEPTIBILITY TO","url":"https://www.omim.org/entry/609423"},{"mim_id":"605888","title":"EH DOMAIN-CONTAINING 1; EHD1","url":"https://www.omim.org/entry/605888"},{"mim_id":"601147","title":"GROWTH/DIFFERENTIATION FACTOR 6; GDF6","url":"https://www.omim.org/entry/601147"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Plasma membrane","reliability":"Enhanced"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"liver","ntpm":430.0},{"tissue":"thyroid gland","ntpm":397.8}],"url":"https://www.proteinatlas.org/search/SDC2"},"hgnc":{"alias_symbol":["fibroglycan","SYND2","CD362"],"prev_symbol":["HSPG","HSPG1"]},"alphafold":{"accession":"P34741","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P34741","model_url":"https://alphafold.ebi.ac.uk/files/AF-P34741-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P34741-F1-predicted_aligned_error_v6.png","plddt_mean":60.84},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SDC2","jax_strain_url":"https://www.jax.org/strain/search?query=SDC2"},"sequence":{"accession":"P34741","fasta_url":"https://rest.uniprot.org/uniprotkb/P34741.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P34741/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P34741"}},"corpus_meta":[{"pmid":"12015973","id":"PMC_12015973","title":"HSPG modification by the secreted enzyme Notum shapes the Wingless morphogen 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gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/39292188","citation_count":5,"is_preprint":false},{"pmid":"38226561","id":"PMC_38226561","title":"Evaluating the clinical performance of SDC2/NDRG4 methylation for colorectal cancer detection.","date":"2024","source":"Epigenomics","url":"https://pubmed.ncbi.nlm.nih.gov/38226561","citation_count":5,"is_preprint":false},{"pmid":"36855658","id":"PMC_36855658","title":"Value of Methylation Status of RPRM, SDC2, and TCF4 Genes in Plasma for Gastric Adenocarcinoma Screening.","date":"2023","source":"International journal of general medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36855658","citation_count":5,"is_preprint":false},{"pmid":"37072315","id":"PMC_37072315","title":"[Methylated SDC2 testing in stool DNA for early screening of colorectal cancer in Shipai Town, Dongguan City].","date":"2023","source":"Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery","url":"https://pubmed.ncbi.nlm.nih.gov/37072315","citation_count":5,"is_preprint":false},{"pmid":"19272950","id":"PMC_19272950","title":"A computational model of FGF-2 binding and HSPG regulation under flow.","date":"2008","source":"IEEE transactions on bio-medical engineering","url":"https://pubmed.ncbi.nlm.nih.gov/19272950","citation_count":5,"is_preprint":false},{"pmid":"37193183","id":"PMC_37193183","title":"Diagnostic value of human fecal SDC2 gene in colorectal cancer.","date":"2023","source":"American journal of translational research","url":"https://pubmed.ncbi.nlm.nih.gov/37193183","citation_count":4,"is_preprint":false},{"pmid":"35968354","id":"PMC_35968354","title":"SEPTIN9-SDC2-VIM methylation signature as a biomarker for the early diagnosis of colorectal cancer.","date":"2022","source":"American journal of cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/35968354","citation_count":4,"is_preprint":false},{"pmid":"31982583","id":"PMC_31982583","title":"Molecular insights and immune responses of big belly seahorse syndecan-2 (CD362): Involvement of ectodomain in regulating cell survival, proliferation, and wound healing.","date":"2020","source":"Fish & shellfish immunology","url":"https://pubmed.ncbi.nlm.nih.gov/31982583","citation_count":3,"is_preprint":false},{"pmid":"40294072","id":"PMC_40294072","title":"Ephrin-B1 regulates cell surface residency of heparan sulfate proteoglycans (HSPGs) and complexes with the HSPG CD44V3-10 and fibroblast growth factor receptors.","date":"2025","source":"Glycobiology","url":"https://pubmed.ncbi.nlm.nih.gov/40294072","citation_count":3,"is_preprint":false},{"pmid":"39569371","id":"PMC_39569371","title":"Interlaboratory consistency of SDC2 promoter methylation detection in colorectal cancer using the post-optimized 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monoclonal anti-HSPG isolated from human liver.","date":"2011","source":"Anticancer research","url":"https://pubmed.ncbi.nlm.nih.gov/22199263","citation_count":3,"is_preprint":false},{"pmid":"38593345","id":"PMC_38593345","title":"Cancer-associated point mutations within the extracellular domain of PTPRD affect protein stability and HSPG interaction.","date":"2024","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/38593345","citation_count":2,"is_preprint":false},{"pmid":"40940401","id":"PMC_40940401","title":"SDC2 and FN as cargo proteins in circulating extracellular vesicles in obese breast cancer patients with lymph node metastasis.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/40940401","citation_count":2,"is_preprint":false},{"pmid":"36810922","id":"PMC_36810922","title":"Development of a new heparan sulfate proteoglycan (HSPG) chromolith LC column to study the pH dependence binding of peptide vaccines to HSPG and role of human serum albumin on its binding.","date":"2023","source":"Analytical methods : advancing methods and applications","url":"https://pubmed.ncbi.nlm.nih.gov/36810922","citation_count":2,"is_preprint":false},{"pmid":"36276265","id":"PMC_36276265","title":"Integrated computational approach towards identification of HSPG and ACE2 mimicking moieties for SARS-CoV-2 inhibition.","date":"2022","source":"Journal of molecular liquids","url":"https://pubmed.ncbi.nlm.nih.gov/36276265","citation_count":2,"is_preprint":false},{"pmid":"37783044","id":"PMC_37783044","title":"Value of faecal exfoliated cells in colorectal tumour screening using SDC2 methylation test.","date":"2023","source":"Annals of medicine","url":"https://pubmed.ncbi.nlm.nih.gov/37783044","citation_count":2,"is_preprint":false},{"pmid":"36536564","id":"PMC_36536564","title":"[Application study of stool-based methylated SDC2 test in the screening of colorectal neoplasms for physical examination population].","date":"2022","source":"Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]","url":"https://pubmed.ncbi.nlm.nih.gov/36536564","citation_count":2,"is_preprint":false},{"pmid":"39872370","id":"PMC_39872370","title":"Fecal methylated syndecan-2 (SDC2) testing for early screening of colorectal cancerous and precancerous lesions: A real-world retrospective study in China.","date":"2024","source":"Cancer pathogenesis and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/39872370","citation_count":2,"is_preprint":false},{"pmid":"40066557","id":"PMC_40066557","title":"Early Diagnosis of Colorectal Cancer via Plasma-Derived SDC2, KCNQ5, and IKZF1 Methylation Levels.","date":"2025","source":"Clinical laboratory","url":"https://pubmed.ncbi.nlm.nih.gov/40066557","citation_count":1,"is_preprint":false},{"pmid":"40990394","id":"PMC_40990394","title":"An Automated Multi-Sample Digital LAMP Platform for Quantitative Detection of SDC2 Methylation in Colorectal Cancer.","date":"2025","source":"Analytical chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/40990394","citation_count":1,"is_preprint":false},{"pmid":"20506637","id":"PMC_20506637","title":"[Effects of qufengtongluo recipe on expressions of HSPG mRNA and protein in adriamycin-induced nephropathy rats].","date":"2010","source":"Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition","url":"https://pubmed.ncbi.nlm.nih.gov/20506637","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":53422,"output_tokens":3696,"usd":0.107853,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10731,"output_tokens":3333,"usd":0.06849,"stage2_stop_reason":"end_turn"},"total_usd":0.176343,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the papers, I need to identify which ones are specifically about SDC2 (syndecan-2/fibroglycan/SYND2/CD362/HSPG1) and contain mechanistic findings.\n\nMost papers are about generic HSPG biology, other syndecans, or CRC methylation biomarkers (purely diagnostic/expression, not mechanistic). I'll focus on papers with direct mechanistic experiments about SDC2 specifically.\n\nKey papers to extract from:\n- PMID:10446183 (SDC2 on macrophages, FGF-2 binding/presentation)\n- PMID:8187643 (fibroglycan expression during development)\n- PMID:27627962 (SDC2-FGF22 transsynaptic signaling)\n- PMID:24046323 (Sdc2-Tbx16-Fgf2 pathway in zebrafish KV)\n- PMID:28658631 (SDC2 as myogenic progenitor marker)\n- PMID:37496999 (SDC2-PDK1, USP14, AKT signaling in gastric cancer)\n- PMID:39285301 (PTN-SDC2-GFRA1 in SSCs)\n- PMID:32765295 (SDC2-FAK/ERK in atherosclerosis)\n- PMID:29118673 (miR-20a-5p/SDC2 in osteosarcoma chemoresistance)\n- PMID:24442880 (SDC2 microduplication, TGF-β/SMAD pathway)\n- PMID:9259269 (X;8 translocation near SDC2)\n- PMID:31982583 (seahorse SDC2 ectodomain, cell proliferation/wound healing)\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"Activated human macrophages express a single major 48-kDa cell surface HSPG, syndecan-2 (fibroglycan), synthesized de novo upon activation. This macrophage-expressed SDC2 selectively binds FGF-2, VEGF, and HB-EGF, and can present FGF-2 in a form that transactivates FGF-receptor-bearing BaF32 cells, demonstrating SDC2's role in growth factor sequestration and delivery.\",\n      \"method\": \"De novo RNA/protein synthesis analysis, growth factor binding assays, BaF32 cell transactivation assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — single lab, multiple orthogonal methods (binding assay, functional transactivation assay, Western blot), direct characterization of SDC2 as the sole macrophage HSPG\",\n      \"pmids\": [\"10446183\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1993,\n      \"finding\": \"Fibroglycan (SDC2) is expressed exclusively on mesenchymal cells during mouse embryogenesis, with peak expression during morphogenetic phases and at sites of cell-cell/cell-matrix interactions (epithelial-mesenchymal interfaces, prechondrogenic condensations), in a pattern distinct from syndecan-1 (epithelial). This spatiotemporal pattern was confirmed by both immunohistochemistry and in situ hybridization.\",\n      \"method\": \"Immunohistochemistry with anti-human fibroglycan monoclonal antibody (10H4), in situ hybridization, Western blot of embryo extracts\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with orthogonal methods (IHC + ISH), single lab, functionally interpreted in context of morphogenesis\",\n      \"pmids\": [\"8187643\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"In zebrafish, Sdc2 (syndecan-2) regulates left-right patterning through cell-autonomous functions in Kupffer's vesicle (KV), including regulation of cell proliferation, adhesion, cilia length, and asymmetric fluid flow. Sdc2 and Tbx16 jointly regulate Fgf2 expression in KV; Fgf2 controls KV morphogenesis (but not cilia length) downstream of Sdc2, and Fgf2 mRNA rescue restores KV morphogenesis in sdc2 morphants, defining a Sdc2-Tbx16-Fgf2 pathway.\",\n      \"method\": \"Lineage-targeted morpholino knockdown, mRNA rescue, in situ hybridization, cilia length measurement, fluid flow analysis\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — morpholino KD with mRNA rescue (epistasis), multiple orthogonal phenotypic readouts, single lab\",\n      \"pmids\": [\"24046323\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Postsynaptic SDC2 uses its ectodomain to interact with FGF22 and facilitate its targeting to dendritic filopodia, thereby triggering presynaptic maturation. SDC2 also enhances filopodial targeting of NMDAR via interaction with the CASK-mLIN7-MINT1 adaptor complex. Presynaptic maturation promoted by FGF22 feeds back through increased neurotransmitter release to activate NMDAR, promoting the dendritic filopodia-to-spine transition. CaMKII (activated by the NMDAR pathway) further facilitates FGF22 targeting via KIF17 regulation.\",\n      \"method\": \"Co-immunoprecipitation, transfection/overexpression in neurons, live imaging of dendritic filopodia, immunostaining of synaptic markers\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP identifying SDC2-FGF22 interaction, multiple cellular readouts, single lab\",\n      \"pmids\": [\"27627962\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"SDC2 (Syndecan-2) is a surface marker on PAX7-induced human myogenic progenitors derived from pluripotent stem cells. CD54+α9β1+SDC2+ sorted cells contribute to long-term muscle regeneration in vivo, establishing SDC2 as a functional surface marker enabling isolation of myogenic progenitors.\",\n      \"method\": \"PAX7 genomic target analysis, fluorescent- and magnetic-based cell sorting (FACS/MACS), in vivo muscle engraftment assay\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct sorting and in vivo functional validation, single lab, multiple methods\",\n      \"pmids\": [\"28658631\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SDC2 interacts with the PDK1-PH domain, facilitating PDK1 membrane translocation and AKT activation in gastric cancer cells. SDC2 also functions as a co-receptor for FGF2, contributing to the FGF2-AKT signaling axis. Additionally, the deubiquitinase USP14 stabilizes SDC2 protein by preventing its degradation, and the USP14 inhibitor IU1 decreases SDC2 abundance in GC cells.\",\n      \"method\": \"Co-immunoprecipitation (SDC2-PDK1 interaction), overexpression/depletion experiments, Western blot for AKT phosphorylation, USP14 inhibitor treatment, bioinformatics\",\n      \"journal\": \"International journal of biological sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP for SDC2-PDK1 binding, multiple orthogonal functional assays, single lab\",\n      \"pmids\": [\"37496999\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Pleiotrophin (PTN) secreted by Leydig cells signals to spermatogonial stem cells (SSCs) through SDC2 as a receptor. Protein immunoprecipitation confirmed PTN-SDC2 interaction in spermatogonia. SDC2 knockdown in human SSC lines impaired cell proliferation, DNA synthesis, PLZF expression, and downregulated GFRA1 and the HIF-1 signaling pathway. Exogenous PTN rescued proliferation and GFRA1 expression in SDC2 knockdown cells.\",\n      \"method\": \"Single-cell RNA sequencing analysis, immunofluorescence co-localization, protein immunoprecipitation, SDC2 siRNA knockdown, transcriptome analysis, proliferation/DNA synthesis assays\",\n      \"journal\": \"Biological research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP confirming PTN-SDC2 binding, KD rescue experiment, transcriptomic pathway analysis, single lab\",\n      \"pmids\": [\"39285301\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In atherosclerosis, SDC2 is highly expressed and miR-9 targets SDC2 to negatively regulate it. SDC2 depletion reduces aortic plaque area, collagen fiber proliferation, macrophage infiltration, and pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) by suppressing the FAK/ERK signaling pathway, placing SDC2 upstream of FAK/ERK in atherosclerotic vascular pathology.\",\n      \"method\": \"Ectopic miR-9 expression in ACS mice, SDC2 siRNA depletion, Western blot for FAK/ERK pathway proteins, oil red O staining, Masson's trichrome staining, immunohistochemistry\",\n      \"journal\": \"Frontiers in physiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — in vivo pathway analysis with KD but pathway placement inferred indirectly; single lab, single study\",\n      \"pmids\": [\"32765295\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"miR-20a-5p targets SDC2 mRNA to suppress its expression. SDC2 mediates multi-drug resistance in osteosarcoma cells; siRNA-mediated SDC2 knockdown recapitulates the chemosensitizing effect of miR-20a-5p mimic, and SDC2 overexpression restores chemoresistance in miR-20a-5p-overexpressing cells.\",\n      \"method\": \"miRNA mimic/antagomir transfection, SDC2 siRNA knockdown, SDC2 overexpression, CCK8 cell viability assay, tumor xenograft in nude mice\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — functional rescue/epistasis with KD and OE, single lab, limited mechanistic depth on SDC2 mechanism\",\n      \"pmids\": [\"29118673\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Microduplication of chromosome 8q22.1 encompassing GDF6 and SDC2 causes Leri's pleonosteosis. Expression analysis of patient dermal fibroblasts shows overexpression of SDC2 dysregulates extracellular matrix genes and TGF-β pathway components, with markedly decreased inhibitory SMAD6 levels, linking SDC2 overexpression to TGF-β/SMAD signaling dysregulation.\",\n      \"method\": \"Whole-genome SNP genotyping, gene expression analysis of patient dermal fibroblasts, Western blot for SMAD6\",\n      \"journal\": \"Annals of the rheumatic diseases\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — patient fibroblast expression data, single lab, no direct mechanistic experiment on SDC2-SMAD interaction\",\n      \"pmids\": [\"24442880\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The recombinant ectodomain of syndecan-2 (HaSDC-2 from seahorse) promotes cell proliferation in a concentration-dependent manner and accelerates wound healing in scratch assays when applied exogenously. Overexpression of full-length HaSDC-2 confers significant cell survival against oxidative stressors (H2O2, HED), establishing functional roles for the SDC2 ectodomain in cell survival and proliferation.\",\n      \"method\": \"Recombinant ectodomain protein treatment, scratch wound healing assay, H2O2/HED stress survival assay, HaSDC-2 + pcDNA transfection\",\n      \"journal\": \"Fish & shellfish immunology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — seahorse ortholog, single lab, functional assays without defined molecular mechanism\",\n      \"pmids\": [\"31982583\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SDC2 (syndecan-2/fibroglycan) is a transmembrane heparan sulfate proteoglycan expressed predominantly on mesenchymal cells that functions as a cell-surface co-receptor and scaffold: it binds and presents heparin-binding growth factors (FGF-2, VEGF, HB-EGF, FGF22, PTN) to their signaling receptors, regulates dendritic filopodial targeting of FGF22 and NMDA receptors through interactions with the CASK-mLIN7-MINT1 adaptor complex to coordinate bidirectional synapse maturation, activates AKT signaling by interacting with the PDK1-PH domain to facilitate PDK1 membrane translocation, and is stabilized post-translationally by the deubiquitinase USP14; its expression is regulated in a developmentally restricted, mesenchyme-specific pattern, and its abundance is controlled post-transcriptionally by miR-9 and miR-20a-5p.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SDC2 (syndecan-2/fibroglycan) is a transmembrane heparan sulfate proteoglycan expressed in a mesenchyme-restricted, developmentally regulated pattern that functions as a cell-surface co-receptor and scaffold to capture heparin-binding growth factors and couple them to downstream signaling [#1, #0]. On activated macrophages it is synthesized de novo as the major surface HSPG and selectively binds FGF-2, VEGF, and HB-EGF, presenting FGF-2 in a form that transactivates FGF-receptor-bearing cells, establishing its role in growth-factor sequestration and delivery [#0]. SDC2 organizes morphogenetic signaling across systems: in zebrafish it acts cell-autonomously in Kupffer's vesicle to control left-right patterning via a Sdc2-Tbx16-Fgf2 pathway [#2], and at developing synapses its ectodomain binds FGF22 to direct dendritic filopodial targeting and presynaptic maturation while enhancing NMDA-receptor targeting through the CASK-mLIN7-MINT1 adaptor complex [#3]. SDC2 also serves as a receptor for pleiotrophin in spermatogonial stem cells, supporting proliferation and GFRA1/HIF-1 signaling [#6]. Mechanistically it drives intracellular signaling by interacting with the PDK1 PH domain to facilitate PDK1 membrane translocation and AKT activation, and is itself stabilized post-translationally by the deubiquitinase USP14 [#5]. Microduplication of 8q22.1 encompassing SDC2 causes Leri's pleonosteosis, with SDC2 overexpression dysregulating extracellular-matrix genes and TGF-\\u03b2/SMAD signaling [#9].\",\n  \"teleology\": [\n    {\n      \"year\": 1993,\n      \"claim\": \"Established that SDC2 (fibroglycan) marks the mesenchymal compartment during embryogenesis, distinguishing it spatially from epithelial syndecan-1 and implicating it in morphogenetic cell-cell/cell-matrix interactions.\",\n      \"evidence\": \"IHC, in situ hybridization, and Western blot of mouse embryo extracts\",\n      \"pmids\": [\"8187643\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Localization pattern alone does not define a molecular function\", \"No binding partners or signaling readouts identified\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Showed SDC2 acts as a growth-factor co-receptor, answering how the proteoglycan engages signaling: it binds FGF-2, VEGF, and HB-EGF and presents FGF-2 to activate FGF-receptor-bearing cells.\",\n      \"evidence\": \"De novo synthesis analysis, growth factor binding assays, and BaF32 transactivation assay in activated macrophages\",\n      \"pmids\": [\"10446183\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not resolve which structural domain (HS chains vs core protein) mediates binding\", \"No downstream intracellular signaling defined\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Placed SDC2 within a defined developmental signaling cascade, showing it controls left-right asymmetry cell-autonomously through a Sdc2-Tbx16-Fgf2 axis.\",\n      \"evidence\": \"Lineage-targeted morpholino knockdown with Fgf2 mRNA rescue and phenotypic readouts in zebrafish Kupffer's vesicle\",\n      \"pmids\": [\"24046323\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Morpholino-based knockdown without genetic mutant confirmation\", \"Mechanism linking Sdc2 to cilia length distinct from Fgf2 unresolved\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Defined a synaptic scaffolding role: SDC2's ectodomain binds FGF22 to drive bidirectional synapse maturation and couples NMDAR targeting to the CASK-mLIN7-MINT1 adaptor complex.\",\n      \"evidence\": \"Co-IP, neuronal overexpression, live imaging of dendritic filopodia, and synaptic marker immunostaining\",\n      \"pmids\": [\"27627962\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Co-IP interactions not validated by structural or reconstitution data\", \"Stoichiometry within the adaptor complex undefined\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Identified SDC2 as a functional surface marker of myogenic progenitors capable of long-term muscle regeneration, extending its role to stem/progenitor cell identity.\",\n      \"evidence\": \"PAX7 target analysis, FACS/MACS sorting, and in vivo muscle engraftment of CD54+\\u03b19\\u03b21+SDC2+ cells\",\n      \"pmids\": [\"28658631\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Marker status does not establish a mechanistic role in myogenesis\", \"Signaling downstream of SDC2 in progenitors not examined\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Linked SDC2 abundance to post-transcriptional control by miR-20a-5p and connected SDC2 levels to chemoresistance in osteosarcoma.\",\n      \"evidence\": \"miRNA mimic/antagomir, SDC2 siRNA knockdown and overexpression rescue, viability assays, and xenografts\",\n      \"pmids\": [\"29118673\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Limited mechanistic depth on how SDC2 mediates drug resistance\", \"Single lab, no orthogonal confirmation of the miR-20a-5p\\u2013SDC2 axis\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Connected SDC2 to vascular inflammatory pathology, placing it upstream of FAK/ERK signaling and under negative control by miR-9 in atherosclerosis.\",\n      \"evidence\": \"Ectopic miR-9 expression and SDC2 siRNA depletion in ACS mice with FAK/ERK Western blot and histology\",\n      \"pmids\": [\"32765295\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Pathway placement upstream of FAK/ERK inferred indirectly\", \"Single study, not independently replicated\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Revealed an intracellular signaling mechanism: SDC2 binds the PDK1 PH domain to promote PDK1 membrane translocation and AKT activation, and is stabilized by the deubiquitinase USP14.\",\n      \"evidence\": \"Co-IP of SDC2-PDK1, overexpression/depletion, AKT phosphorylation Western blot, and USP14 inhibitor (IU1) treatment in gastric cancer cells\",\n      \"pmids\": [\"37496999\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs indirect nature of SDC2-PDK1 binding not structurally resolved\", \"How a transmembrane HSPG engages the cytosolic PDK1 PH domain mechanistically unclear\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Established SDC2 as a pleiotrophin receptor in spermatogonial stem cells required for proliferation, PLZF/GFRA1 expression, and HIF-1 signaling.\",\n      \"evidence\": \"scRNA-seq, immunofluorescence co-localization, PTN-SDC2 immunoprecipitation, siRNA knockdown with PTN rescue, and transcriptome analysis in human SSC lines\",\n      \"pmids\": [\"39285301\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether SDC2 signals alone or with a co-receptor for PTN unresolved\", \"Direct interaction not validated by reciprocal or structural methods\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SDC2's heparan sulfate chains versus core protein, and its transmembrane/cytoplasmic domains, mechanistically partition between extracellular growth-factor presentation and intracellular PDK1/AKT signaling across cell types remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model of SDC2 in any signaling complex\", \"Domain-resolution mapping of growth-factor vs adaptor binding lacking\", \"Tissue-specific determinants of co-receptor partner choice unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0038024\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [3, 5, 6]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [3, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 1, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [5, 6]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"FGF2\", \"VEGF\", \"HBEGF\", \"FGF22\", \"PTN\", \"PDK1\", \"USP14\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}