{"gene":"STAB2","run_date":"2026-04-28T20:42:08","timeline":{"discoveries":[{"year":2000,"finding":"HARE (STAB2) was identified as the hyaluronan receptor for endocytosis on liver sinusoidal endothelial cells; monoclonal antibodies against the 175-kDa receptor also cross-reacted with the 300-kDa species, and two mAbs inhibited 125I-HA binding and endocytosis, establishing HARE as the bona fide endocytic HA receptor expressed in liver sinusoids, spleen venous sinuses, and lymph node medullary sinuses.","method":"Monoclonal antibody development, 125I-HA binding/endocytosis inhibition assay, indirect immunofluorescence","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — reciprocal antibody blocking of endocytosis plus tissue localization, moderate evidence","pmids":["10952975"],"is_preprint":false},{"year":2002,"finding":"FEEL-1 (STAB1) and FEEL-2 (STAB2) were identified as endocytic receptors for advanced glycation end products (AGEs); CHO cells overexpressing FEEL-2 showed high-affinity specific binding (Kd ~1.68 µg/ml) and receptor-mediated uptake and degradation of 125I-AGE-BSA, inhibited by Ac-LDL and polyanionic scavenger receptor inhibitors (fucoidan, polyinosinic acids, dextran sulfate) but not by native or oxidized LDL.","method":"Radioligand binding assay, endocytosis/degradation assay in CHO cells overexpressing FEEL-2, competition assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — direct binding and functional endocytosis assays in recombinant expression system with competition controls","pmids":["12473645"],"is_preprint":false},{"year":2003,"finding":"Anti-HARE monoclonal antibody mAb-174 specifically blocked 125I-HA uptake by rat liver sinusoidal endothelial cells and inhibited HA clearance and metabolism by perfused ex vivo rat livers, demonstrating that HARE/Stabilin-2 is the physiological receptor responsible for systemic HA clearance by the liver.","method":"Ligand blot assay, 125I-HA endocytosis inhibition by mAb, ex vivo liver perfusion assay, immunohistochemistry","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — functional blocking in both cell culture and intact perfused organ, orthogonal methods","pmids":["12645574"],"is_preprint":false},{"year":2003,"finding":"The recombinant 175-kDa rat HARE isoform (Stab2 small isoform) expressed alone in SK-Hep-1 cells mediates specific 125I-HA endocytosis, receptor recycling (~8.5 min recycling time), and lysosomal HA degradation with Kd ~4.1 nM and 160,000–220,000 binding sites per cell; it binds HA, dermatan sulfate, and chondroitin sulfates A, C, D, and E but not heparin, heparan sulfate, or keratan sulfate, and GAG recognition is temperature-dependent.","method":"Stable transfection of recombinant receptor, 125I-HA endocytosis assay, ligand blot, competition binding at 4°C and 37°C","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1/2 — recombinant receptor reconstitution with quantitative binding and functional endocytosis assays","pmids":["12933790"],"is_preprint":false},{"year":2004,"finding":"The recombinant human 190-kDa HARE isoform (Stab2 small isoform) expressed in Flp-In 293 cells mediates rapid, continuous 125I-HA endocytosis and degradation; ~30–50% of receptors are on the cell surface with a recycling time of ~8.5 min and Kd of 7 nM with ~118,000 HA-binding sites per cell; it binds HA and chondroitin better than dermatan sulfate and chondroitin sulfates A, C, D, and E, but does not bind heparin, heparan sulfate, or keratan sulfate.","method":"Stable transfection, 125I-HA endocytosis assay, competition studies, anti-HARE antibody inhibition","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1/2 — recombinant human receptor reconstitution with quantitative kinetic and specificity analyses","pmids":["15208308"],"is_preprint":false},{"year":2008,"finding":"The identical cytoplasmic domains of both human HARE isoforms contain four candidate AP-2/clathrin-mediated endocytic signaling motifs (YSYFRI, FQHF, NPLY, DPF); deletion mutagenesis showed that YSYFRI, FQHF, and NPLY each contribute redundantly to coated pit-mediated endocytosis (~39–56% reduction each), while DPF has no effect; the tyrosine in NPLY2519 is critical; all four motifs together account for ~95% of endocytic activity.","method":"Site-directed and deletion mutagenesis of cytoplasmic endocytic motifs, stable transfection, 125I-HA endocytosis assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 — reconstitution with multiple site-directed mutants and quantitative functional readout","pmids":["18539600"],"is_preprint":false},{"year":2009,"finding":"HARE/Stabilin-2 is the clearance receptor for both unfractionated heparin (UFH, Kd ~0.06 µM) and low-molecular-weight heparin (LMWH, Kd ~10 µM); anti-HARE antibodies specifically block UFH and LMWH uptake by rat liver sinusoidal endothelial cells and by cells expressing recombinant 190-kDa hHARE; both heparins cross-compete for the same binding sites, and higher affinity for UFH explains its shorter in vivo half-life.","method":"Anti-HARE antibody blocking, 125I-ligand uptake assays in primary SECs and recombinant cells, ELISA-like assay with purified soluble ecto-domain, Kd determination","journal":"American journal of physiology. Gastrointestinal and liver physiology","confidence":"High","confidence_rationale":"Tier 2 — antibody blocking, recombinant receptor assay, and purified ecto-domain binding, multiple orthogonal methods","pmids":["19359419"],"is_preprint":false},{"year":2010,"finding":"N-glycans at the Link domain of human HARE/Stabilin-2 (at N2280) are required for HA binding to the purified soluble ecto-domain (N2280A mutant shows no HA binding by ELISA, pull-down, and surface plasmon resonance) but are not required for cellular endocytosis of HA by membrane-bound HARE.","method":"Site-directed mutagenesis (N2280A), glycoproteomic analysis, ELISA-like binding assay, pull-down, surface plasmon resonance, stable cell lines expressing membrane-bound and soluble ecto-domain variants","journal":"Glycobiology","confidence":"High","confidence_rationale":"Tier 1 — mutagenesis combined with three independent binding assays and functional endocytosis measurement","pmids":["20466649"],"is_preprint":false},{"year":2014,"finding":"Tissue-specific splice variants of HARE/Stabilin-2 are expressed in bone marrow, lymph node, and spleen; five variants with internal splice junctions and four with extensive exon splicing were identified; stable cell lines confirmed protein expression of three cloned variants, suggesting tissue-specific regulatory splicing may alter receptor functionality.","method":"RT-PCR with primer sets spanning splice junctions, gel purification and sequencing, stable mammalian cell line expression","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 3 — RNA-based splice variant identification with protein expression confirmation, single lab, limited functional characterization","pmids":["25446080"],"is_preprint":false},{"year":2018,"finding":"In zebrafish, stabilin-2 (stab2) is essential for anionic nanoparticle uptake by sinusoidal endothelial cells; stab2 knockdown abolishes nanoparticle-SEC interactions and this uptake can be competitively blocked by dextran sulfate, identifying Stab2 as a key scavenger receptor mediating nanoparticle-liver interactions.","method":"Zebrafish stab2 knockdown (morpholino or genetic), nanoparticle biodistribution imaging, dextran sulfate competitive inhibition","journal":"ACS nano","confidence":"Medium","confidence_rationale":"Tier 2 — loss-of-function in vivo model with competitive inhibitor validation, zebrafish ortholog of human STAB2","pmids":["29320626"],"is_preprint":false},{"year":2020,"finding":"Rare damaging variants in STAB2 are associated with unprovoked venous thromboembolism (VTE); in cell culture, VTE-associated STAB2 variants showed reduced surface expression compared with reference STAB2, suggesting haploinsufficiency of stabilin-2 may elevate VTE risk through impaired clearance of procoagulant factors (von Willebrand factor and factor VIII).","method":"Whole-exome sequencing gene-burden analysis, cell culture surface expression assay of VTE-associated variants vs. reference STAB2","journal":"Blood","confidence":"Medium","confidence_rationale":"Tier 2/3 — cell surface expression assay of disease-associated variants provides mechanistic link, supported by population genetics data","pmids":["32457982"],"is_preprint":false},{"year":2020,"finding":"HARE/Stab2-mediated endocytosis or phagocytosis of glycosaminoglycan ligands (HA, heparin, dermatan sulfate, chondroitin and chondroitin sulfates, dextran sulfate) activates intracellular signaling, particularly the ERK1/2 (Extracellular Signal-Regulated Kinase 1/2) pathway; full-length Stab2 mediates phagocytosis of apoptotic cells and bacteria while the HARE isoform mediates endocytosis of all known soluble ligands.","method":"Receptor-mediated endocytosis assays, ERK1/2 signaling readouts, functional domain dissection of full-length Stab2 vs. HARE isoform","journal":"Cells","confidence":"Medium","confidence_rationale":"Tier 2 — review/synthesis of primary experimental data from the Weigel lab identifying ERK1/2 pathway activation as a downstream consequence of ligand-induced endocytosis","pmids":["33126404"],"is_preprint":false}],"current_model":"STAB2/HARE is a type I single-pass transmembrane scavenger receptor expressed on sinusoidal endothelial cells of liver, spleen, and lymph nodes that binds and mediates clathrin/coated pit-dependent endocytosis of at least 22 ligands including hyaluronan, chondroitin sulfates, heparin, AGEs, and modified lipoproteins via multiple redundant cytoplasmic endocytic motifs (YSYFRI, FQHF, NPLY), recycles with ~8.5 min turnover, delivers cargo to lysosomes for degradation, and activates downstream ERK1/2 signaling upon ligand-induced endocytosis; the full-length Stab2 isoform additionally mediates phagocytosis of apoptotic cells and bacteria, while the proteolytically derived 190/175-kDa HARE isoform handles clearance of all known soluble ligands."},"narrative":{"teleology":[{"year":2000,"claim":"Identification of HARE as the endocytic hyaluronan receptor on liver sinusoidal endothelial cells resolved the long-standing question of which receptor mediates systemic HA clearance, revealing both 175-kDa and 300-kDa species recognized by blocking monoclonal antibodies.","evidence":"Monoclonal antibody development with 125I-HA binding/endocytosis inhibition on rat liver SECs and tissue immunofluorescence","pmids":["10952975"],"confidence":"High","gaps":["Molecular identity and cDNA of HARE not yet cloned","Relationship between 175-kDa and 300-kDa species unclear"]},{"year":2002,"claim":"Demonstration that STAB2 (FEEL-2) binds and endocytoses AGE-modified proteins with scavenger receptor-like pharmacology expanded its ligand repertoire beyond glycosaminoglycans to include damaged proteins.","evidence":"125I-AGE-BSA binding, uptake, and degradation assays in CHO cells overexpressing FEEL-2 with polyanionic competitor controls","pmids":["12473645"],"confidence":"High","gaps":["Structural basis for AGE recognition unknown","Physiological relevance of AGE clearance by STAB2 in vivo not tested"]},{"year":2003,"claim":"Antibody-blocking experiments in ex vivo perfused rat livers established HARE/Stabilin-2 as the physiological receptor for systemic HA clearance, moving beyond cell-line evidence to organ-level function; parallel reconstitution of the 175-kDa isoform revealed its GAG specificity, recycling kinetics, and lysosomal delivery pathway.","evidence":"Anti-HARE mAb blocking in perfused liver and primary SECs; recombinant 175-kDa receptor in SK-Hep-1 cells with 125I-HA endocytosis, recycling, and ligand competition assays","pmids":["12645574","12933790"],"confidence":"High","gaps":["Whether the 300-kDa full-length form has identical GAG specificity not determined","In vivo knockout model not yet available"]},{"year":2004,"claim":"Reconstitution of the human 190-kDa HARE isoform confirmed rapid, continuous HA endocytosis with ~8.5-min recycling and established quantitative binding parameters (Kd ~7 nM), validating cross-species conservation of receptor function.","evidence":"Stable Flp-In 293 cells expressing human 190-kDa HARE, 125I-HA endocytosis with kinetic and competition analyses","pmids":["15208308"],"confidence":"High","gaps":["Full-length human Stab2 not yet functionally reconstituted","Structural basis of HA–Link domain interaction unresolved"]},{"year":2008,"claim":"Systematic mutagenesis of the cytoplasmic tail identified three redundant endocytic motifs (YSYFRI, FQHF, NPLY) that together mediate ~95% of coated-pit-dependent HA internalization, establishing the molecular mechanism of receptor sorting.","evidence":"Site-directed and deletion mutagenesis of cytoplasmic motifs in stable cell lines, quantitative 125I-HA endocytosis assay","pmids":["18539600"],"confidence":"High","gaps":["Direct interaction with AP-2 subunits not biochemically demonstrated","Whether motif usage differs for non-HA ligands unknown"]},{"year":2009,"claim":"Identification of HARE/Stabilin-2 as the clearance receptor for both unfractionated and low-molecular-weight heparin explained the differential pharmacokinetics of clinical heparins through affinity differences (Kd ~0.06 vs. ~10 µM).","evidence":"Anti-HARE antibody blocking in primary SECs, recombinant receptor and purified soluble ecto-domain binding assays","pmids":["19359419"],"confidence":"High","gaps":["Whether STAB2-mediated heparin clearance is rate-limiting in vivo not confirmed by knockout","Binding site for heparin vs. HA not structurally resolved"]},{"year":2010,"claim":"Mutagenesis of N-glycosylation at the Link domain (N2280) dissociated HA binding to the soluble ecto-domain from cellular endocytosis, revealing that N-glycans are required for ligand capture by the ecto-domain but not for membrane-bound receptor function.","evidence":"N2280A mutagenesis with ELISA, pull-down, surface plasmon resonance, and endocytosis assays","pmids":["20466649"],"confidence":"High","gaps":["How membrane context compensates for loss of N-glycan-dependent binding is mechanistically unexplained","No crystal structure of Link domain available"]},{"year":2018,"claim":"Zebrafish loss-of-function demonstrated that Stab2 is essential for anionic nanoparticle uptake by sinusoidal endothelial cells in vivo, extending the receptor's scavenger function to synthetic nanomaterials.","evidence":"Zebrafish stab2 morpholino knockdown, nanoparticle biodistribution imaging, dextran sulfate competitive inhibition","pmids":["29320626"],"confidence":"Medium","gaps":["Morpholino knockdown may have off-target effects; genetic null not confirmed in this study","Relevance to mammalian nanoparticle pharmacokinetics not directly shown"]},{"year":2020,"claim":"Rare damaging STAB2 variants linked to venous thromboembolism showed reduced cell-surface expression, connecting receptor haploinsufficiency to impaired clearance of procoagulant factors and human disease.","evidence":"Whole-exome sequencing gene-burden analysis in VTE cohorts; cell-surface expression assay of VTE-associated STAB2 variants","pmids":["32457982"],"confidence":"Medium","gaps":["Direct demonstration that STAB2 clears VWF or FVIII not shown in this study","Animal model rescue not performed","Variant effects on ligand binding and endocytosis not measured"]},{"year":2020,"claim":"Functional dissection established that full-length Stab2 mediates phagocytosis of apoptotic cells and bacteria while the HARE isoform handles all known soluble ligands, and that ligand-induced endocytosis activates ERK1/2 signaling, adding a signaling dimension to the receptor's clearance role.","evidence":"Endocytosis and phagocytosis assays, ERK1/2 signaling readouts, domain dissection of full-length vs. HARE isoform","pmids":["33126404"],"confidence":"Medium","gaps":["Downstream targets of ERK1/2 activation in SECs not identified","Physiological consequence of STAB2-mediated ERK signaling unknown"]},{"year":null,"claim":"Key unresolved questions include the structural basis of STAB2's broad ligand recognition, how the full-length isoform enables phagocytosis that the HARE isoform cannot, the physiological significance of STAB2-activated ERK1/2 signaling, and the direct causal mechanism linking STAB2 deficiency to venous thromboembolism.","evidence":"","pmids":[],"confidence":"High","gaps":["No crystal or cryo-EM structure of STAB2 ecto-domain","Mammalian Stab2 knockout phenotype not comprehensively described in the timeline","Direct clearance of coagulation factors by STAB2 not biochemically demonstrated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0038024","term_label":"cargo receptor activity","supporting_discovery_ids":[0,1,3,4,6,9]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[11]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,3,4,5,10]},{"term_id":"GO:0005764","term_label":"lysosome","supporting_discovery_ids":[3,4]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[3,4,5,6]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[11]},{"term_id":"R-HSA-109582","term_label":"Hemostasis","supporting_discovery_ids":[10]}],"complexes":[],"partners":[],"other_free_text":[]},"mechanistic_narrative":"STAB2 (Stabilin-2/HARE) is a type I transmembrane scavenger receptor on sinusoidal endothelial cells of liver, spleen, and lymph nodes that mediates clathrin-dependent endocytic clearance of hyaluronan, chondroitin sulfates, heparin, advanced glycation end products, and other polyanionic ligands, and activates ERK1/2 signaling upon ligand internalization [PMID:10952975, PMID:12473645, PMID:33126404]. The receptor recycles with an ~8.5-minute turnover and delivers cargo to lysosomes for degradation, with endocytosis driven by three redundant cytoplasmic motifs (YSYFRI, FQHF, NPLY) that together account for ~95% of coated-pit-mediated uptake [PMID:12933790, PMID:18539600]. The full-length Stab2 isoform additionally mediates phagocytosis of apoptotic cells and bacteria, whereas a proteolytically derived 190-kDa HARE isoform handles clearance of all known soluble ligands including unfractionated and low-molecular-weight heparin [PMID:19359419, PMID:33126404]. Rare damaging STAB2 variants with reduced surface expression are associated with venous thromboembolism, consistent with impaired clearance of procoagulant factors [PMID:32457982]."},"prefetch_data":{"uniprot":{"accession":"Q8WWQ8","full_name":"Stabilin-2","aliases":["FAS1 EGF-like and X-link domain-containing adhesion molecule 2","Fasciclin, EGF-like, laminin-type EGF-like and link domain-containing scavenger receptor 2","FEEL-2","Hyaluronan receptor for endocytosis"],"length_aa":2551,"mass_kda":277.0,"function":"Phosphatidylserine receptor that enhances the engulfment of apoptotic cells. Hyaluronan receptor that binds to and mediates endocytosis of hyaluronic acid (HA). Also acts, in different species, as a primary systemic scavenger receptor for heparin (Hep), chondroitin sulfate (CS), dermatan sulfate (DS), nonglycosaminoglycan (GAG), acetylated low-density lipoprotein (AcLDL), pro-collagen propeptides and advanced glycation end products (AGE). May serve to maintain tissue integrity by supporting extracellular matrix turnover or it may contribute to maintaining fluidity of bodily liquids by resorption of hyaluronan. Counter receptor which plays an important role in lymphocyte recruitment in the hepatic vasculature. Binds to both Gram-positive and Gram-negative bacteria and may play a role in defense against bacterial infection. The proteolytically processed 190 kDa form also functions as an endocytosis receptor for heparin internalization as well as HA and CS","subcellular_location":"Cell membrane; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q8WWQ8/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/STAB2","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/STAB2","total_profiled":1310},"omim":[{"mim_id":"616065","title":"PILR-ALPHA-ASSOCIATED NEURAL PROTEIN; PIANP","url":"https://www.omim.org/entry/616065"},{"mim_id":"608561","title":"STABILIN 2; STAB2","url":"https://www.omim.org/entry/608561"},{"mim_id":"608560","title":"STABILIN 1; STAB1","url":"https://www.omim.org/entry/608560"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Cytosol","reliability":"Supported"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"lymphoid tissue","ntpm":63.4}],"url":"https://www.proteinatlas.org/search/STAB2"},"hgnc":{"alias_symbol":["DKFZP434E0321","FELL","STAB-2","HARE","FEEL-2","SCARH1"],"prev_symbol":[]},"alphafold":{"accession":"Q8WWQ8","domains":[{"cath_id":"-","chopping":"34-47_54-100","consensus_level":"medium","plddt":61.8374,"start":34,"end":100},{"cath_id":"2.10.25.10","chopping":"877-921","consensus_level":"medium","plddt":60.3362,"start":877,"end":921},{"cath_id":"2.30.180.10","chopping":"994-1134","consensus_level":"medium","plddt":77.9962,"start":994,"end":1134},{"cath_id":"2.30.180.10","chopping":"1137-1272","consensus_level":"medium","plddt":79.4496,"start":1137,"end":1272},{"cath_id":"-","chopping":"1355-1448_1456-1472_1481-1523","consensus_level":"medium","plddt":69.115,"start":1355,"end":1523},{"cath_id":"2.30.180.10","chopping":"1601-1732","consensus_level":"medium","plddt":85.044,"start":1601,"end":1732},{"cath_id":"2.30.180.10","chopping":"1734-1885","consensus_level":"medium","plddt":78.3018,"start":1734,"end":1885},{"cath_id":"3.10.100.10","chopping":"2124-2298","consensus_level":"medium","plddt":75.2228,"start":2124,"end":2298},{"cath_id":"2.30.180.10","chopping":"2326-2443","consensus_level":"high","plddt":76.2765,"start":2326,"end":2443},{"cath_id":"2.10.25","chopping":"324-357","consensus_level":"medium","plddt":70.8756,"start":324,"end":357}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WWQ8","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WWQ8-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WWQ8-F1-predicted_aligned_error_v6.png","plddt_mean":70.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=STAB2","jax_strain_url":"https://www.jax.org/strain/search?query=STAB2"},"sequence":{"accession":"Q8WWQ8","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8WWQ8.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8WWQ8/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WWQ8"}},"corpus_meta":[{"pmid":"10952975","id":"PMC_10952975","title":"Identification of the hyaluronan receptor for endocytosis (HARE).","date":"2000","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10952975","citation_count":214,"is_preprint":false},{"pmid":"19426257","id":"PMC_19426257","title":"The sensitive hare: sublethal effects of predator stress on reproduction in snowshoe hares.","date":"2009","source":"The Journal of animal ecology","url":"https://pubmed.ncbi.nlm.nih.gov/19426257","citation_count":199,"is_preprint":false},{"pmid":"19958398","id":"PMC_19958398","title":"Fell-Muir Lecture: Proteoglycans and more--from molecules to biology.","date":"2009","source":"International journal of experimental pathology","url":"https://pubmed.ncbi.nlm.nih.gov/19958398","citation_count":198,"is_preprint":false},{"pmid":"29320626","id":"PMC_29320626","title":"Directing Nanoparticle Biodistribution through Evasion and Exploitation of Stab2-Dependent Nanoparticle Uptake.","date":"2018","source":"ACS nano","url":"https://pubmed.ncbi.nlm.nih.gov/29320626","citation_count":182,"is_preprint":false},{"pmid":"12473645","id":"PMC_12473645","title":"FEEL-1 and FEEL-2 are endocytic receptors for advanced glycation end products.","date":"2002","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12473645","citation_count":150,"is_preprint":false},{"pmid":"15969727","id":"PMC_15969727","title":"Invasion from the cold past: extensive introgression of mountain hare (Lepus timidus) mitochondrial DNA into three other hare species in northern Iberia.","date":"2005","source":"Molecular ecology","url":"https://pubmed.ncbi.nlm.nih.gov/15969727","citation_count":112,"is_preprint":false},{"pmid":"559104","id":"PMC_559104","title":"Three unique viral RNA species of snowshoe hare and La Crosse bunyaviruses.","date":"1977","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/559104","citation_count":100,"is_preprint":false},{"pmid":"1662098","id":"PMC_1662098","title":"Diagnosis of viral haemorrhagic disease of rabbits and the European brown hare syndrome.","date":"1991","source":"Revue scientifique et technique (International Office of Epizootics)","url":"https://pubmed.ncbi.nlm.nih.gov/1662098","citation_count":96,"is_preprint":false},{"pmid":"7050911","id":"PMC_7050911","title":"The complete sequence and coding content of snowshoe hare bunyavirus small (S) viral RNA species.","date":"1982","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/7050911","citation_count":85,"is_preprint":false},{"pmid":"25546317","id":"PMC_25546317","title":"Fell-Muir Lecture: Syndecans: from peripheral coreceptors to mainstream regulators of cell behaviour.","date":"2014","source":"International journal of experimental pathology","url":"https://pubmed.ncbi.nlm.nih.gov/25546317","citation_count":81,"is_preprint":false},{"pmid":"7518531","id":"PMC_7518531","title":"European brown hare syndrome virus: relationship to rabbit hemorrhagic disease virus and other caliciviruses.","date":"1994","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/7518531","citation_count":77,"is_preprint":false},{"pmid":"16155232","id":"PMC_16155232","title":"Cloning, characterization and expression of escapin, a broadly antimicrobial FAD-containing L-amino acid oxidase from ink of the sea hare Aplysia californica.","date":"2005","source":"The Journal of experimental biology","url":"https://pubmed.ncbi.nlm.nih.gov/16155232","citation_count":76,"is_preprint":false},{"pmid":"12645574","id":"PMC_12645574","title":"A blocking antibody to the hyaluronan receptor for endocytosis (HARE) inhibits hyaluronan clearance by perfused liver.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12645574","citation_count":72,"is_preprint":false},{"pmid":"4020962","id":"PMC_4020962","title":"Analyses of the mRNA transcription processes of snowshoe hare bunyavirus S and M RNA species.","date":"1985","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/4020962","citation_count":71,"is_preprint":false},{"pmid":"2974218","id":"PMC_2974218","title":"Organization of the middle RNA segment of snowshoe hare Bunyavirus.","date":"1988","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/2974218","citation_count":71,"is_preprint":false},{"pmid":"15208308","id":"PMC_15208308","title":"Endocytic function, glycosaminoglycan specificity, and antibody sensitivity of the recombinant human 190-kDa hyaluronan receptor for endocytosis (HARE).","date":"2004","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15208308","citation_count":70,"is_preprint":false},{"pmid":"18508749","id":"PMC_18508749","title":"The ubiquitous mountain hare mitochondria: multiple introgressive hybridization in hares, genus Lepus.","date":"2008","source":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/18508749","citation_count":65,"is_preprint":false},{"pmid":"25964779","id":"PMC_25964779","title":"Targeting the IGF-1R: The Tale of the Tortoise and the Hare.","date":"2015","source":"Frontiers in endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/25964779","citation_count":64,"is_preprint":false},{"pmid":"22264297","id":"PMC_22264297","title":"Fell-Muir Lecture: chondroitin sulphate glycosaminoglycans: fun for some and confusion for others.","date":"2012","source":"International journal of experimental pathology","url":"https://pubmed.ncbi.nlm.nih.gov/22264297","citation_count":63,"is_preprint":false},{"pmid":"18539600","id":"PMC_18539600","title":"The cytoplasmic domain of the hyaluronan receptor for endocytosis (HARE) contains multiple endocytic motifs targeting coated pit-mediated internalization.","date":"2008","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/18539600","citation_count":61,"is_preprint":false},{"pmid":"34777364","id":"PMC_34777364","title":"Adeno-Associated Viruses (AAV) and Host Immunity - A Race Between the Hare and the Hedgehog.","date":"2021","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/34777364","citation_count":57,"is_preprint":false},{"pmid":"28508516","id":"PMC_28508516","title":"Fell Muir Lecture: Collagen fibril formation in vitro and in vivo.","date":"2017","source":"International journal of experimental pathology","url":"https://pubmed.ncbi.nlm.nih.gov/28508516","citation_count":57,"is_preprint":false},{"pmid":"592468","id":"PMC_592468","title":"Formation of recombinants between snowshoe hare and La Crosse bunyaviruses.","date":"1977","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/592468","citation_count":55,"is_preprint":false},{"pmid":"18043803","id":"PMC_18043803","title":"Pericosines, antitumour metabolites from the sea hare-derived fungus Periconia byssoides. Structures and biological activities.","date":"2007","source":"Organic & biomolecular chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/18043803","citation_count":54,"is_preprint":false},{"pmid":"1402816","id":"PMC_1402816","title":"Non-random reassortment between the tripartite RNA genomes of La Crosse and snowshoe hare viruses.","date":"1992","source":"The Journal of general virology","url":"https://pubmed.ncbi.nlm.nih.gov/1402816","citation_count":49,"is_preprint":false},{"pmid":"513192","id":"PMC_513192","title":"Genome complexities of the three mRNA species of snowshoe hare bunyavirus and in vitro translation of S mRNA to viral N polypeptide.","date":"1979","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/513192","citation_count":49,"is_preprint":false},{"pmid":"1760585","id":"PMC_1760585","title":"Epidemiology and diagnosis of the European brown hare syndrome in Scandinavian countries: a review.","date":"1991","source":"Revue scientifique et technique (International Office of Epizootics)","url":"https://pubmed.ncbi.nlm.nih.gov/1760585","citation_count":46,"is_preprint":false},{"pmid":"26150665","id":"PMC_26150665","title":"The tortoise or the hare? Impacts of within-host dynamics on transmission success of arthropod-borne viruses.","date":"2015","source":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/26150665","citation_count":45,"is_preprint":false},{"pmid":"10620225","id":"PMC_10620225","title":"Species distinction and evolutionary relationships of the Italian hare (Lepus corsicanus) as described by mitochondrial DNA sequencing.","date":"1999","source":"Molecular ecology","url":"https://pubmed.ncbi.nlm.nih.gov/10620225","citation_count":45,"is_preprint":false},{"pmid":"15254642","id":"PMC_15254642","title":"Peribysins A-D, potent cell-adhesion inhibitors from a sea hare-derived culture of Periconia species.","date":"2004","source":"Organic & biomolecular chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15254642","citation_count":44,"is_preprint":false},{"pmid":"12933790","id":"PMC_12933790","title":"Characterization of the recombinant rat 175-kDa hyaluronan receptor for endocytosis (HARE).","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12933790","citation_count":43,"is_preprint":false},{"pmid":"9161014","id":"PMC_9161014","title":"The occurrence of mountain hare mitochondrial DNA in wild brown hares.","date":"1997","source":"Molecular ecology","url":"https://pubmed.ncbi.nlm.nih.gov/9161014","citation_count":43,"is_preprint":false},{"pmid":"32457982","id":"PMC_32457982","title":"Whole-exome sequencing identifies rare variants in STAB2 associated with venous thromboembolic disease.","date":"2020","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/32457982","citation_count":42,"is_preprint":false},{"pmid":"8760416","id":"PMC_8760416","title":"European brown hare syndrome virus: molecular cloning and sequencing of the genome.","date":"1996","source":"The Journal of general virology","url":"https://pubmed.ncbi.nlm.nih.gov/8760416","citation_count":42,"is_preprint":false},{"pmid":"31181645","id":"PMC_31181645","title":"Genetic Characterization of a Recombinant Myxoma Virus in the Iberian Hare (Lepus granatensis).","date":"2019","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/31181645","citation_count":39,"is_preprint":false},{"pmid":"3664472","id":"PMC_3664472","title":"Purification and characterization of aplysianin E, an antitumor factor from sea hare eggs.","date":"1987","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/3664472","citation_count":38,"is_preprint":false},{"pmid":"23110747","id":"PMC_23110747","title":"Fell-Muir lecture: Connective tissue growth factor (CCN2) -- a pernicious and pleiotropic player in the development of kidney fibrosis.","date":"2012","source":"International journal of experimental pathology","url":"https://pubmed.ncbi.nlm.nih.gov/23110747","citation_count":36,"is_preprint":false},{"pmid":"15579381","id":"PMC_15579381","title":"The shaping of mitochondrial DNA phylogeographic patterns of the brown hare (Lepus europaeus) under the combined influence of Late Pleistocene climatic fluctuations and anthropogenic translocations.","date":"2005","source":"Molecular phylogenetics and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/15579381","citation_count":36,"is_preprint":false},{"pmid":"12733273","id":"PMC_12733273","title":"Apoptosis and proliferation during seasonal testis regression in the brown hare (Lepus europaeus L.).","date":"2003","source":"Anatomia, histologia, embryologia","url":"https://pubmed.ncbi.nlm.nih.gov/12733273","citation_count":34,"is_preprint":false},{"pmid":"32429122","id":"PMC_32429122","title":"Role of the Hyaluronan Receptor, Stabilin-2/HARE, in Health and Disease.","date":"2020","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/32429122","citation_count":33,"is_preprint":false},{"pmid":"19359419","id":"PMC_19359419","title":"Rat and human HARE/stabilin-2 are clearance receptors for high- and low-molecular-weight heparins.","date":"2009","source":"American journal of physiology. Gastrointestinal and liver physiology","url":"https://pubmed.ncbi.nlm.nih.gov/19359419","citation_count":33,"is_preprint":false},{"pmid":"15974628","id":"PMC_15974628","title":"Hectochlorin and morpholine derivatives from the Thai sea hare, Bursatella leachii.","date":"2005","source":"Journal of natural products","url":"https://pubmed.ncbi.nlm.nih.gov/15974628","citation_count":33,"is_preprint":false},{"pmid":"30358404","id":"PMC_30358404","title":"Exciton Transport in Singlet Fission Materials: A New Hare and Tortoise Story.","date":"2018","source":"The journal of physical chemistry letters","url":"https://pubmed.ncbi.nlm.nih.gov/30358404","citation_count":28,"is_preprint":false},{"pmid":"513193","id":"PMC_513193","title":"Recombination between snowhoe hare and La Crosse bunyaviruses.","date":"1979","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/513193","citation_count":28,"is_preprint":false},{"pmid":"31322320","id":"PMC_31322320","title":"Myxoma virus jumps species to the Iberian hare.","date":"2019","source":"Transboundary and emerging diseases","url":"https://pubmed.ncbi.nlm.nih.gov/31322320","citation_count":26,"is_preprint":false},{"pmid":"29879480","id":"PMC_29879480","title":"Identification of circular single-stranded DNA viruses in faecal samples of Canada lynx (Lynx canadensis), moose (Alces alces) and snowshoe hare (Lepus americanus) inhabiting the Colorado San Juan Mountains.","date":"2018","source":"Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/29879480","citation_count":26,"is_preprint":false},{"pmid":"19104797","id":"PMC_19104797","title":"Evolutionary history of an MHC gene in two leporid species: characterisation of Mhc-DQA in the European brown hare and comparison with the European rabbit.","date":"2008","source":"Immunogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/19104797","citation_count":26,"is_preprint":false},{"pmid":"20434970","id":"PMC_20434970","title":"The transcriptome of the early life history stages of the California Sea Hare Aplysia californica.","date":"2010","source":"Comparative biochemistry and physiology. Part D, Genomics & proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/20434970","citation_count":26,"is_preprint":false},{"pmid":"28500774","id":"PMC_28500774","title":"The transcriptional landscape of seasonal coat colour moult in the snowshoe hare.","date":"2017","source":"Molecular ecology","url":"https://pubmed.ncbi.nlm.nih.gov/28500774","citation_count":25,"is_preprint":false},{"pmid":"1661785","id":"PMC_1661785","title":"Acute hepatosis in the European brown hare (Lepus europaeus) in Italy.","date":"1991","source":"Journal of wildlife diseases","url":"https://pubmed.ncbi.nlm.nih.gov/1661785","citation_count":25,"is_preprint":false},{"pmid":"25113393","id":"PMC_25113393","title":"The hidden history of the snowshoe hare, Lepus americanus: extensive mitochondrial DNA introgression inferred from multilocus genetic variation.","date":"2014","source":"Molecular ecology","url":"https://pubmed.ncbi.nlm.nih.gov/25113393","citation_count":24,"is_preprint":false},{"pmid":"16280485","id":"PMC_16280485","title":"Photobacterium aplysiae sp. nov., a lipolytic marine bacterium isolated from eggs of the sea hare Aplysia kurodai.","date":"2005","source":"International journal of systematic and evolutionary microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/16280485","citation_count":23,"is_preprint":false},{"pmid":"31336723","id":"PMC_31336723","title":"Ligand Binding and Signaling of HARE/Stabilin-2.","date":"2019","source":"Biomolecules","url":"https://pubmed.ncbi.nlm.nih.gov/31336723","citation_count":22,"is_preprint":false},{"pmid":"32732066","id":"PMC_32732066","title":"Applying a new pomelo peel derived biochar in microbial fell cell for enhancing sulfonamide antibiotics removal in swine wastewater.","date":"2020","source":"Bioresource technology","url":"https://pubmed.ncbi.nlm.nih.gov/32732066","citation_count":22,"is_preprint":false},{"pmid":"17617694","id":"PMC_17617694","title":"Cell-adhesion inhibitors produced by a sea hare-derived Periconia sp.","date":"2007","source":"The Journal of antibiotics","url":"https://pubmed.ncbi.nlm.nih.gov/17617694","citation_count":22,"is_preprint":false},{"pmid":"16354780","id":"PMC_16354780","title":"Packaging of chemicals in the defensive secretory glands of the sea hare Aplysia californica.","date":"2006","source":"The Journal of experimental biology","url":"https://pubmed.ncbi.nlm.nih.gov/16354780","citation_count":22,"is_preprint":false},{"pmid":"26230115","id":"PMC_26230115","title":"The European Hare (Lepus europaeus): A Picky Herbivore Searching for Plant Parts Rich in Fat.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26230115","citation_count":21,"is_preprint":false},{"pmid":"30997155","id":"PMC_30997155","title":"The discovery of three new hare lagoviruses reveals unexplored viral diversity in this genus.","date":"2019","source":"Virus evolution","url":"https://pubmed.ncbi.nlm.nih.gov/30997155","citation_count":21,"is_preprint":false},{"pmid":"2086268","id":"PMC_2086268","title":"Bacteriostatic and cytolytic activity of purple fluid from the sea hare.","date":"1990","source":"Developmental and comparative immunology","url":"https://pubmed.ncbi.nlm.nih.gov/2086268","citation_count":21,"is_preprint":false},{"pmid":"31500161","id":"PMC_31500161","title":"Discovery of the Liver Hyaluronan Receptor for Endocytosis (HARE) and Its Progressive Emergence as the Multi-Ligand Scavenger Receptor Stabilin-2.","date":"2019","source":"Biomolecules","url":"https://pubmed.ncbi.nlm.nih.gov/31500161","citation_count":21,"is_preprint":false},{"pmid":"20722764","id":"PMC_20722764","title":"The tortoise and the hare: slowly evolving T-cell responses take hastily evolving KIR.","date":"2010","source":"Immunology","url":"https://pubmed.ncbi.nlm.nih.gov/20722764","citation_count":20,"is_preprint":false},{"pmid":"9367366","id":"PMC_9367366","title":"Structural, antigenic and immunogenic relationships between European brown hare syndrome virus and rabbit haemorrhagic disease virus.","date":"1997","source":"The Journal of general virology","url":"https://pubmed.ncbi.nlm.nih.gov/9367366","citation_count":20,"is_preprint":false},{"pmid":"33190340","id":"PMC_33190340","title":"Multisystem inflammatory syndrome in children rose and fell with the first wave of the COVID-19 pandemic in France.","date":"2020","source":"Acta paediatrica (Oslo, Norway : 1992)","url":"https://pubmed.ncbi.nlm.nih.gov/33190340","citation_count":20,"is_preprint":false},{"pmid":"12061795","id":"PMC_12061795","title":"The hyaluronan receptor for endocytosis (HARE) is not CD44 or CD54 (ICAM-1).","date":"2002","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/12061795","citation_count":19,"is_preprint":false},{"pmid":"21750681","id":"PMC_21750681","title":"Identification of a mutation associated with fatal Foal Immunodeficiency Syndrome in the Fell and Dales pony.","date":"2011","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/21750681","citation_count":19,"is_preprint":false},{"pmid":"28120863","id":"PMC_28120863","title":"Range expansion underlies historical introgressive hybridization in the Iberian hare.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28120863","citation_count":19,"is_preprint":false},{"pmid":"24814937","id":"PMC_24814937","title":"Conservation implications of the evolutionary history and genetic diversity hotspots of the snowshoe hare.","date":"2014","source":"Molecular ecology","url":"https://pubmed.ncbi.nlm.nih.gov/24814937","citation_count":19,"is_preprint":false},{"pmid":"29370301","id":"PMC_29370301","title":"Widespread introgression of mountain hare genes into Fennoscandian brown hare populations.","date":"2018","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/29370301","citation_count":18,"is_preprint":false},{"pmid":"8722266","id":"PMC_8722266","title":"European brown hare syndrome in free-ranging hares in Poland.","date":"1996","source":"Journal of wildlife diseases","url":"https://pubmed.ncbi.nlm.nih.gov/8722266","citation_count":18,"is_preprint":false},{"pmid":"33126404","id":"PMC_33126404","title":"Systemic Glycosaminoglycan Clearance by HARE/Stabilin-2 Activates Intracellular Signaling.","date":"2020","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/33126404","citation_count":17,"is_preprint":false},{"pmid":"8586697","id":"PMC_8586697","title":"Typing of LaCrosse, snowshoe hare, and Tahyna viruses by analyses of single-strand conformation polymorphisms of the small RNA segments.","date":"1995","source":"Journal of clinical microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/8586697","citation_count":17,"is_preprint":false},{"pmid":"22151585","id":"PMC_22151585","title":"Chasing the hare - evaluating the phylogenetic utility of a nuclear single copy gene region at and below species level within the species rich group Peperomia (Piperaceae).","date":"2011","source":"BMC evolutionary biology","url":"https://pubmed.ncbi.nlm.nih.gov/22151585","citation_count":17,"is_preprint":false},{"pmid":"32282064","id":"PMC_32282064","title":"Convergent evolution of seasonal camouflage in response to reduced snow cover across the snowshoe hare range.","date":"2020","source":"Evolution; international journal of organic evolution","url":"https://pubmed.ncbi.nlm.nih.gov/32282064","citation_count":17,"is_preprint":false},{"pmid":"19747090","id":"PMC_19747090","title":"Purification and biochemical characterization of a D-galactose binding lectin from Japanese sea hare (Aplysia kurodai) eggs.","date":"2009","source":"Biochemistry. Biokhimiia","url":"https://pubmed.ncbi.nlm.nih.gov/19747090","citation_count":17,"is_preprint":false},{"pmid":"2598320","id":"PMC_2598320","title":"Purification and characterization of a cytolytic protein from purple fluid of the sea hare, Dolabella auricularia.","date":"1989","source":"Chemical & pharmaceutical bulletin","url":"https://pubmed.ncbi.nlm.nih.gov/2598320","citation_count":16,"is_preprint":false},{"pmid":"10758276","id":"PMC_10758276","title":"Purification of a novel antibacterial and haemagglutinating protein from the purple gland of the sea hare, Aplysia dactylomela rang, 1828.","date":"2000","source":"Toxicon : official journal of the International Society on Toxinology","url":"https://pubmed.ncbi.nlm.nih.gov/10758276","citation_count":15,"is_preprint":false},{"pmid":"23473645","id":"PMC_23473645","title":"Is there a difference between hare syphilis and rabbit syphilis? Cross infection experiments between rabbits and hares.","date":"2013","source":"Veterinary microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/23473645","citation_count":15,"is_preprint":false},{"pmid":"20466649","id":"PMC_20466649","title":"N-Glycans on the link domain of human HARE/Stabilin-2 are needed for hyaluronan binding to purified ecto-domain, but not for cellular endocytosis of hyaluronan.","date":"2010","source":"Glycobiology","url":"https://pubmed.ncbi.nlm.nih.gov/20466649","citation_count":15,"is_preprint":false},{"pmid":"12713272","id":"PMC_12713272","title":"Histological and immunohistological investigation of the lymphoid tissue in normal and mycobacteria-affected specimens of the Rufous Hare-wallaby (Lagorchestes hirsutus).","date":"2003","source":"Journal of anatomy","url":"https://pubmed.ncbi.nlm.nih.gov/12713272","citation_count":15,"is_preprint":false},{"pmid":"20711803","id":"PMC_20711803","title":"Ticks infesting the endangered Italian hare (Lepus corsicanus) and their habitat in an ecological park in southern Italy.","date":"2010","source":"Experimental & applied acarology","url":"https://pubmed.ncbi.nlm.nih.gov/20711803","citation_count":15,"is_preprint":false},{"pmid":"33028004","id":"PMC_33028004","title":"Detection of recombinant Hare Myxoma Virus in wild rabbits (Oryctolagus cuniculus algirus).","date":"2020","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/33028004","citation_count":14,"is_preprint":false},{"pmid":"15651734","id":"PMC_15651734","title":"Immunoglobulin and peripheral B-lymphocyte concentrations in Fell pony foal syndrome.","date":"2005","source":"Equine veterinary journal","url":"https://pubmed.ncbi.nlm.nih.gov/15651734","citation_count":14,"is_preprint":false},{"pmid":"6639070","id":"PMC_6639070","title":"Isolation and characterization of uteroglobin from the lung of the hare (Lepus capensis).","date":"1983","source":"Archives of biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/6639070","citation_count":14,"is_preprint":false},{"pmid":"16915818","id":"PMC_16915818","title":"Cell-adhesion inhibitors produced by a sea hare-derived Periconia sp. II. Absolute stereostructures of peribysins H and I.","date":"2006","source":"The Journal of antibiotics","url":"https://pubmed.ncbi.nlm.nih.gov/16915818","citation_count":14,"is_preprint":false},{"pmid":"25446080","id":"PMC_25446080","title":"Tissue-specific splice variants of HARE/Stabilin-2 are expressed in bone marrow, lymph node, and spleen.","date":"2014","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/25446080","citation_count":13,"is_preprint":false},{"pmid":"34076595","id":"PMC_34076595","title":"A simple vapor-diffusion method enables protein crystallization inside the HARE serial crystallography chip.","date":"2021","source":"Acta crystallographica. Section D, Structural biology","url":"https://pubmed.ncbi.nlm.nih.gov/34076595","citation_count":13,"is_preprint":false},{"pmid":"31719660","id":"PMC_31719660","title":"Distribution of aquaporins and sodium transporters in the gastrointestinal tract of a desert hare, Lepus yarkandensis.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31719660","citation_count":13,"is_preprint":false},{"pmid":"31824711","id":"PMC_31824711","title":"Ocean acidification affects acid-base physiology and behaviour in a model invertebrate, the California sea hare (Aplysia californica).","date":"2019","source":"Royal Society open science","url":"https://pubmed.ncbi.nlm.nih.gov/31824711","citation_count":13,"is_preprint":false},{"pmid":"19854229","id":"PMC_19854229","title":"Conservation of the egg-laying hormone neuropeptide and attractin pheromone in the spotted sea hare, Aplysia dactylomela.","date":"2009","source":"Peptides","url":"https://pubmed.ncbi.nlm.nih.gov/19854229","citation_count":13,"is_preprint":false},{"pmid":"7200877","id":"PMC_7200877","title":"Serum creatine kinase and isoenzyme responses of veteran class fell runners.","date":"1982","source":"European journal of applied physiology and occupational physiology","url":"https://pubmed.ncbi.nlm.nih.gov/7200877","citation_count":12,"is_preprint":false},{"pmid":"30804494","id":"PMC_30804494","title":"Gut microbiota of the European Brown Hare (Lepus europaeus).","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/30804494","citation_count":12,"is_preprint":false},{"pmid":"34537065","id":"PMC_34537065","title":"First detected case of rabbit Haemorrhagic disease virus 2 (RHDV2) in the Irish hare (Lepus timidus hibernicus).","date":"2021","source":"Irish veterinary journal","url":"https://pubmed.ncbi.nlm.nih.gov/34537065","citation_count":12,"is_preprint":false},{"pmid":"25147784","id":"PMC_25147784","title":"Characterization of a GHF45 cellulase, AkEG21, from the common sea hare Aplysia kurodai.","date":"2014","source":"Frontiers in chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25147784","citation_count":12,"is_preprint":false},{"pmid":"37904591","id":"PMC_37904591","title":"STAB2: an updated spatio-temporal cell atlas of the human and mouse brain.","date":"2024","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/37904591","citation_count":11,"is_preprint":false},{"pmid":"14655104","id":"PMC_14655104","title":"Hematology and serum chemistry values of the European brown hare.","date":"2003","source":"Veterinary clinical pathology","url":"https://pubmed.ncbi.nlm.nih.gov/14655104","citation_count":11,"is_preprint":false},{"pmid":"32603021","id":"PMC_32603021","title":"Widespread occurrence of the non-pathogenic hare calicivirus (HaCV Lagovirus GII.2) in captive-reared and free-living wild hares in Europe.","date":"2020","source":"Transboundary and emerging diseases","url":"https://pubmed.ncbi.nlm.nih.gov/32603021","citation_count":11,"is_preprint":false},{"pmid":"11922391","id":"PMC_11922391","title":"Cytotoxic cyplasin of the sea hare, Aaplysia punctata, cDNA cloning, and expression of bioactive recombinants in insect cells.","date":"2002","source":"Neoplasia (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/11922391","citation_count":11,"is_preprint":false},{"pmid":"31080730","id":"PMC_31080730","title":"Cysticercosis by Taenia pisiformis in Brown Hare (Lepus europaeus) in Northern Italy: Epidemiologic and pathologic features.","date":"2019","source":"International journal for parasitology. Parasites and wildlife","url":"https://pubmed.ncbi.nlm.nih.gov/31080730","citation_count":11,"is_preprint":false},{"pmid":"28307100","id":"PMC_28307100","title":"Carbon isotope discrimination in Quercus ilex resprouts after fire and tree-fell.","date":"1996","source":"Oecologia","url":"https://pubmed.ncbi.nlm.nih.gov/28307100","citation_count":11,"is_preprint":false},{"pmid":"27187480","id":"PMC_27187480","title":"The Complete Chloroplast Genome of the Hare's Ear Root, Bupleurum falcatum: Its Molecular Features.","date":"2016","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/27187480","citation_count":11,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":46495,"output_tokens":3441,"usd":0.09555},"stage2":{"model":"claude-opus-4-6","input_tokens":6811,"output_tokens":2792,"usd":0.155782},"total_usd":0.251332,"stage1_batch_id":"msgbatch_011rkcQdVV1RaFq9XhcG6df6","stage2_batch_id":"msgbatch_01RzgrJafdF4EWHhj5mNi6dh","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"HARE (STAB2) was identified as the hyaluronan receptor for endocytosis on liver sinusoidal endothelial cells; monoclonal antibodies against the 175-kDa receptor also cross-reacted with the 300-kDa species, and two mAbs inhibited 125I-HA binding and endocytosis, establishing HARE as the bona fide endocytic HA receptor expressed in liver sinusoids, spleen venous sinuses, and lymph node medullary sinuses.\",\n      \"method\": \"Monoclonal antibody development, 125I-HA binding/endocytosis inhibition assay, indirect immunofluorescence\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal antibody blocking of endocytosis plus tissue localization, moderate evidence\",\n      \"pmids\": [\"10952975\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"FEEL-1 (STAB1) and FEEL-2 (STAB2) were identified as endocytic receptors for advanced glycation end products (AGEs); CHO cells overexpressing FEEL-2 showed high-affinity specific binding (Kd ~1.68 µg/ml) and receptor-mediated uptake and degradation of 125I-AGE-BSA, inhibited by Ac-LDL and polyanionic scavenger receptor inhibitors (fucoidan, polyinosinic acids, dextran sulfate) but not by native or oxidized LDL.\",\n      \"method\": \"Radioligand binding assay, endocytosis/degradation assay in CHO cells overexpressing FEEL-2, competition assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct binding and functional endocytosis assays in recombinant expression system with competition controls\",\n      \"pmids\": [\"12473645\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Anti-HARE monoclonal antibody mAb-174 specifically blocked 125I-HA uptake by rat liver sinusoidal endothelial cells and inhibited HA clearance and metabolism by perfused ex vivo rat livers, demonstrating that HARE/Stabilin-2 is the physiological receptor responsible for systemic HA clearance by the liver.\",\n      \"method\": \"Ligand blot assay, 125I-HA endocytosis inhibition by mAb, ex vivo liver perfusion assay, immunohistochemistry\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — functional blocking in both cell culture and intact perfused organ, orthogonal methods\",\n      \"pmids\": [\"12645574\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"The recombinant 175-kDa rat HARE isoform (Stab2 small isoform) expressed alone in SK-Hep-1 cells mediates specific 125I-HA endocytosis, receptor recycling (~8.5 min recycling time), and lysosomal HA degradation with Kd ~4.1 nM and 160,000–220,000 binding sites per cell; it binds HA, dermatan sulfate, and chondroitin sulfates A, C, D, and E but not heparin, heparan sulfate, or keratan sulfate, and GAG recognition is temperature-dependent.\",\n      \"method\": \"Stable transfection of recombinant receptor, 125I-HA endocytosis assay, ligand blot, competition binding at 4°C and 37°C\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1/2 — recombinant receptor reconstitution with quantitative binding and functional endocytosis assays\",\n      \"pmids\": [\"12933790\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"The recombinant human 190-kDa HARE isoform (Stab2 small isoform) expressed in Flp-In 293 cells mediates rapid, continuous 125I-HA endocytosis and degradation; ~30–50% of receptors are on the cell surface with a recycling time of ~8.5 min and Kd of 7 nM with ~118,000 HA-binding sites per cell; it binds HA and chondroitin better than dermatan sulfate and chondroitin sulfates A, C, D, and E, but does not bind heparin, heparan sulfate, or keratan sulfate.\",\n      \"method\": \"Stable transfection, 125I-HA endocytosis assay, competition studies, anti-HARE antibody inhibition\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1/2 — recombinant human receptor reconstitution with quantitative kinetic and specificity analyses\",\n      \"pmids\": [\"15208308\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"The identical cytoplasmic domains of both human HARE isoforms contain four candidate AP-2/clathrin-mediated endocytic signaling motifs (YSYFRI, FQHF, NPLY, DPF); deletion mutagenesis showed that YSYFRI, FQHF, and NPLY each contribute redundantly to coated pit-mediated endocytosis (~39–56% reduction each), while DPF has no effect; the tyrosine in NPLY2519 is critical; all four motifs together account for ~95% of endocytic activity.\",\n      \"method\": \"Site-directed and deletion mutagenesis of cytoplasmic endocytic motifs, stable transfection, 125I-HA endocytosis assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — reconstitution with multiple site-directed mutants and quantitative functional readout\",\n      \"pmids\": [\"18539600\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"HARE/Stabilin-2 is the clearance receptor for both unfractionated heparin (UFH, Kd ~0.06 µM) and low-molecular-weight heparin (LMWH, Kd ~10 µM); anti-HARE antibodies specifically block UFH and LMWH uptake by rat liver sinusoidal endothelial cells and by cells expressing recombinant 190-kDa hHARE; both heparins cross-compete for the same binding sites, and higher affinity for UFH explains its shorter in vivo half-life.\",\n      \"method\": \"Anti-HARE antibody blocking, 125I-ligand uptake assays in primary SECs and recombinant cells, ELISA-like assay with purified soluble ecto-domain, Kd determination\",\n      \"journal\": \"American journal of physiology. Gastrointestinal and liver physiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — antibody blocking, recombinant receptor assay, and purified ecto-domain binding, multiple orthogonal methods\",\n      \"pmids\": [\"19359419\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"N-glycans at the Link domain of human HARE/Stabilin-2 (at N2280) are required for HA binding to the purified soluble ecto-domain (N2280A mutant shows no HA binding by ELISA, pull-down, and surface plasmon resonance) but are not required for cellular endocytosis of HA by membrane-bound HARE.\",\n      \"method\": \"Site-directed mutagenesis (N2280A), glycoproteomic analysis, ELISA-like binding assay, pull-down, surface plasmon resonance, stable cell lines expressing membrane-bound and soluble ecto-domain variants\",\n      \"journal\": \"Glycobiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — mutagenesis combined with three independent binding assays and functional endocytosis measurement\",\n      \"pmids\": [\"20466649\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Tissue-specific splice variants of HARE/Stabilin-2 are expressed in bone marrow, lymph node, and spleen; five variants with internal splice junctions and four with extensive exon splicing were identified; stable cell lines confirmed protein expression of three cloned variants, suggesting tissue-specific regulatory splicing may alter receptor functionality.\",\n      \"method\": \"RT-PCR with primer sets spanning splice junctions, gel purification and sequencing, stable mammalian cell line expression\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — RNA-based splice variant identification with protein expression confirmation, single lab, limited functional characterization\",\n      \"pmids\": [\"25446080\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"In zebrafish, stabilin-2 (stab2) is essential for anionic nanoparticle uptake by sinusoidal endothelial cells; stab2 knockdown abolishes nanoparticle-SEC interactions and this uptake can be competitively blocked by dextran sulfate, identifying Stab2 as a key scavenger receptor mediating nanoparticle-liver interactions.\",\n      \"method\": \"Zebrafish stab2 knockdown (morpholino or genetic), nanoparticle biodistribution imaging, dextran sulfate competitive inhibition\",\n      \"journal\": \"ACS nano\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function in vivo model with competitive inhibitor validation, zebrafish ortholog of human STAB2\",\n      \"pmids\": [\"29320626\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Rare damaging variants in STAB2 are associated with unprovoked venous thromboembolism (VTE); in cell culture, VTE-associated STAB2 variants showed reduced surface expression compared with reference STAB2, suggesting haploinsufficiency of stabilin-2 may elevate VTE risk through impaired clearance of procoagulant factors (von Willebrand factor and factor VIII).\",\n      \"method\": \"Whole-exome sequencing gene-burden analysis, cell culture surface expression assay of VTE-associated variants vs. reference STAB2\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2/3 — cell surface expression assay of disease-associated variants provides mechanistic link, supported by population genetics data\",\n      \"pmids\": [\"32457982\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"HARE/Stab2-mediated endocytosis or phagocytosis of glycosaminoglycan ligands (HA, heparin, dermatan sulfate, chondroitin and chondroitin sulfates, dextran sulfate) activates intracellular signaling, particularly the ERK1/2 (Extracellular Signal-Regulated Kinase 1/2) pathway; full-length Stab2 mediates phagocytosis of apoptotic cells and bacteria while the HARE isoform mediates endocytosis of all known soluble ligands.\",\n      \"method\": \"Receptor-mediated endocytosis assays, ERK1/2 signaling readouts, functional domain dissection of full-length Stab2 vs. HARE isoform\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — review/synthesis of primary experimental data from the Weigel lab identifying ERK1/2 pathway activation as a downstream consequence of ligand-induced endocytosis\",\n      \"pmids\": [\"33126404\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"STAB2/HARE is a type I single-pass transmembrane scavenger receptor expressed on sinusoidal endothelial cells of liver, spleen, and lymph nodes that binds and mediates clathrin/coated pit-dependent endocytosis of at least 22 ligands including hyaluronan, chondroitin sulfates, heparin, AGEs, and modified lipoproteins via multiple redundant cytoplasmic endocytic motifs (YSYFRI, FQHF, NPLY), recycles with ~8.5 min turnover, delivers cargo to lysosomes for degradation, and activates downstream ERK1/2 signaling upon ligand-induced endocytosis; the full-length Stab2 isoform additionally mediates phagocytosis of apoptotic cells and bacteria, while the proteolytically derived 190/175-kDa HARE isoform handles clearance of all known soluble ligands.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"STAB2 (Stabilin-2/HARE) is a type I transmembrane scavenger receptor on sinusoidal endothelial cells of liver, spleen, and lymph nodes that mediates clathrin-dependent endocytic clearance of hyaluronan, chondroitin sulfates, heparin, advanced glycation end products, and other polyanionic ligands, and activates ERK1/2 signaling upon ligand internalization [PMID:10952975, PMID:12473645, PMID:33126404]. The receptor recycles with an ~8.5-minute turnover and delivers cargo to lysosomes for degradation, with endocytosis driven by three redundant cytoplasmic motifs (YSYFRI, FQHF, NPLY) that together account for ~95% of coated-pit-mediated uptake [PMID:12933790, PMID:18539600]. The full-length Stab2 isoform additionally mediates phagocytosis of apoptotic cells and bacteria, whereas a proteolytically derived 190-kDa HARE isoform handles clearance of all known soluble ligands including unfractionated and low-molecular-weight heparin [PMID:19359419, PMID:33126404]. Rare damaging STAB2 variants with reduced surface expression are associated with venous thromboembolism, consistent with impaired clearance of procoagulant factors [PMID:32457982].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Identification of HARE as the endocytic hyaluronan receptor on liver sinusoidal endothelial cells resolved the long-standing question of which receptor mediates systemic HA clearance, revealing both 175-kDa and 300-kDa species recognized by blocking monoclonal antibodies.\",\n      \"evidence\": \"Monoclonal antibody development with 125I-HA binding/endocytosis inhibition on rat liver SECs and tissue immunofluorescence\",\n      \"pmids\": [\"10952975\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular identity and cDNA of HARE not yet cloned\", \"Relationship between 175-kDa and 300-kDa species unclear\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Demonstration that STAB2 (FEEL-2) binds and endocytoses AGE-modified proteins with scavenger receptor-like pharmacology expanded its ligand repertoire beyond glycosaminoglycans to include damaged proteins.\",\n      \"evidence\": \"125I-AGE-BSA binding, uptake, and degradation assays in CHO cells overexpressing FEEL-2 with polyanionic competitor controls\",\n      \"pmids\": [\"12473645\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis for AGE recognition unknown\", \"Physiological relevance of AGE clearance by STAB2 in vivo not tested\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Antibody-blocking experiments in ex vivo perfused rat livers established HARE/Stabilin-2 as the physiological receptor for systemic HA clearance, moving beyond cell-line evidence to organ-level function; parallel reconstitution of the 175-kDa isoform revealed its GAG specificity, recycling kinetics, and lysosomal delivery pathway.\",\n      \"evidence\": \"Anti-HARE mAb blocking in perfused liver and primary SECs; recombinant 175-kDa receptor in SK-Hep-1 cells with 125I-HA endocytosis, recycling, and ligand competition assays\",\n      \"pmids\": [\"12645574\", \"12933790\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the 300-kDa full-length form has identical GAG specificity not determined\", \"In vivo knockout model not yet available\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Reconstitution of the human 190-kDa HARE isoform confirmed rapid, continuous HA endocytosis with ~8.5-min recycling and established quantitative binding parameters (Kd ~7 nM), validating cross-species conservation of receptor function.\",\n      \"evidence\": \"Stable Flp-In 293 cells expressing human 190-kDa HARE, 125I-HA endocytosis with kinetic and competition analyses\",\n      \"pmids\": [\"15208308\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full-length human Stab2 not yet functionally reconstituted\", \"Structural basis of HA–Link domain interaction unresolved\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Systematic mutagenesis of the cytoplasmic tail identified three redundant endocytic motifs (YSYFRI, FQHF, NPLY) that together mediate ~95% of coated-pit-dependent HA internalization, establishing the molecular mechanism of receptor sorting.\",\n      \"evidence\": \"Site-directed and deletion mutagenesis of cytoplasmic motifs in stable cell lines, quantitative 125I-HA endocytosis assay\",\n      \"pmids\": [\"18539600\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct interaction with AP-2 subunits not biochemically demonstrated\", \"Whether motif usage differs for non-HA ligands unknown\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Identification of HARE/Stabilin-2 as the clearance receptor for both unfractionated and low-molecular-weight heparin explained the differential pharmacokinetics of clinical heparins through affinity differences (Kd ~0.06 vs. ~10 µM).\",\n      \"evidence\": \"Anti-HARE antibody blocking in primary SECs, recombinant receptor and purified soluble ecto-domain binding assays\",\n      \"pmids\": [\"19359419\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether STAB2-mediated heparin clearance is rate-limiting in vivo not confirmed by knockout\", \"Binding site for heparin vs. HA not structurally resolved\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Mutagenesis of N-glycosylation at the Link domain (N2280) dissociated HA binding to the soluble ecto-domain from cellular endocytosis, revealing that N-glycans are required for ligand capture by the ecto-domain but not for membrane-bound receptor function.\",\n      \"evidence\": \"N2280A mutagenesis with ELISA, pull-down, surface plasmon resonance, and endocytosis assays\",\n      \"pmids\": [\"20466649\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How membrane context compensates for loss of N-glycan-dependent binding is mechanistically unexplained\", \"No crystal structure of Link domain available\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Zebrafish loss-of-function demonstrated that Stab2 is essential for anionic nanoparticle uptake by sinusoidal endothelial cells in vivo, extending the receptor's scavenger function to synthetic nanomaterials.\",\n      \"evidence\": \"Zebrafish stab2 morpholino knockdown, nanoparticle biodistribution imaging, dextran sulfate competitive inhibition\",\n      \"pmids\": [\"29320626\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Morpholino knockdown may have off-target effects; genetic null not confirmed in this study\", \"Relevance to mammalian nanoparticle pharmacokinetics not directly shown\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Rare damaging STAB2 variants linked to venous thromboembolism showed reduced cell-surface expression, connecting receptor haploinsufficiency to impaired clearance of procoagulant factors and human disease.\",\n      \"evidence\": \"Whole-exome sequencing gene-burden analysis in VTE cohorts; cell-surface expression assay of VTE-associated STAB2 variants\",\n      \"pmids\": [\"32457982\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct demonstration that STAB2 clears VWF or FVIII not shown in this study\", \"Animal model rescue not performed\", \"Variant effects on ligand binding and endocytosis not measured\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Functional dissection established that full-length Stab2 mediates phagocytosis of apoptotic cells and bacteria while the HARE isoform handles all known soluble ligands, and that ligand-induced endocytosis activates ERK1/2 signaling, adding a signaling dimension to the receptor's clearance role.\",\n      \"evidence\": \"Endocytosis and phagocytosis assays, ERK1/2 signaling readouts, domain dissection of full-length vs. HARE isoform\",\n      \"pmids\": [\"33126404\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Downstream targets of ERK1/2 activation in SECs not identified\", \"Physiological consequence of STAB2-mediated ERK signaling unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include the structural basis of STAB2's broad ligand recognition, how the full-length isoform enables phagocytosis that the HARE isoform cannot, the physiological significance of STAB2-activated ERK1/2 signaling, and the direct causal mechanism linking STAB2 deficiency to venous thromboembolism.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No crystal or cryo-EM structure of STAB2 ecto-domain\", \"Mammalian Stab2 knockout phenotype not comprehensively described in the timeline\", \"Direct clearance of coagulation factors by STAB2 not biochemically demonstrated\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0038024\", \"supporting_discovery_ids\": [0, 1, 3, 4, 6, 9]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [11]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 3, 4, 5, 10]},\n      {\"term_id\": \"GO:0005764\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [3, 4, 5, 6]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [11]},\n      {\"term_id\": \"R-HSA-109582\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}\n```"}