{"gene":"GLG1","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":1995,"finding":"ESL-1 (GLG1) was identified as the major E-selectin ligand on myeloid cells; fucosylation of ESL-1 is required for affinity binding to E-selectin-IgG, and a fucosylated recombinant form of ESL-1 supports adhesion of E-selectin-transfected CHO cells. Antibodies against ESL-1 block binding of myeloid cells to E-selectin.","method":"Affinity isolation with recombinant E-selectin-IgG, cell adhesion assay with E-selectin-transfected CHO cells, antibody blocking experiment, cDNA cloning","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods (affinity pulldown, cell adhesion assay, antibody blocking), replicated across labs subsequently","pmids":["7531823"],"is_preprint":false},{"year":1989,"finding":"MG-160 (GLG1) is a 160 kDa sialoglycoprotein localized specifically to the medial cisternae of the Golgi apparatus in neurons, glia, pituitary cells, and PC12 cells; it contains asparagine-linked carbohydrates, sialic acid, N-acetylglucosamine, and intrachain disulfide bonds; it resides in the membrane and/or luminal face of Golgi cisternae.","method":"Immunoelectron microscopy, immunoaffinity purification, biochemical characterization (glycosidase treatment, Triton X-114 extraction), monoclonal antibody-based localization","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct subcellular localization by immunoelectron microscopy with biochemical fractionation, replicated in multiple cell types and subsequently confirmed by many follow-up studies","pmids":["2909545"],"is_preprint":false},{"year":1995,"finding":"MG-160 (GLG1) binds basic fibroblast growth factor (bFGF); its primary structure contains 16 cysteine-rich repeat domains, a single transmembrane domain, and a short cytoplasmic tail, with 90% identity to chicken CFR (a FGF receptor). It has an upstream open reading frame in its mRNA, a feature shared with growth factors and receptors.","method":"cDNA cloning and sequence analysis, direct bFGF binding assay with purified MG-160 protein from rat brain (recombinant bFGF binding)","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct in vitro binding assay combined with full cDNA sequence determination and structural domain analysis, single lab but rigorous biochemical approach","pmids":["7768993"],"is_preprint":false},{"year":1997,"finding":"ESL-1 (GLG1) localizes both to the Golgi apparatus and to microvilli on the cell surface of 32Dc13 cells and neutrophils; approximately 80% of ESL-1 labeling was found on microvilli, positioning it at sites for initiating cell contacts with endothelium.","method":"Indirect immunofluorescence, flow cytometry, cell surface biotinylation, cell surface immunoprecipitation on intact cells, immunogold scanning electron microscopy","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (immunofluorescence, biotinylation, immunogold EM) in a single study with quantitative analysis","pmids":["9099943"],"is_preprint":false},{"year":1997,"finding":"GLG1 (as LTCP-1, the hamster orthologue) forms a complex with the latency-associated peptide (LAP) of TGF-β1 in CHO cells, and a major part of this complex is secreted; purification and amino acid sequencing confirmed the identity of the 140 kDa component as the hamster counterpart of CFR/ESL-1/MG-160.","method":"Biochemical purification of latent TGF-β complexes from CHO cells, amino acid sequencing, cDNA cloning, immunoprecipitation of LTCP-1 and TGF-β1","journal":"The Biochemical journal","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — protein purification, amino acid sequencing, and immunoprecipitation in a single rigorous study establishing direct complex formation","pmids":["9182700"],"is_preprint":false},{"year":2007,"finding":"ESL-1 (GLG1) on neutrophils is critical for converting initial E-selectin-mediated tethers into steady slow rolling, a distinct function from PSGL-1 (initial capture) and CD44 (rolling velocity); together, ESL-1, PSGL-1, and CD44 account for all E-selectin ligand activity on neutrophils.","method":"Gene- and RNA-targeted loss-of-function (knockout and siRNA), intravital microscopy of leukocyte rolling, genetic epistasis via combined knockouts","journal":"Immunity","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic loss-of-function with multiple knockouts, quantitative intravital microscopy readout, independently confirmed by subsequent studies","pmids":["17442598"],"is_preprint":false},{"year":2005,"finding":"Alternative splicing of the GLG1 gene generates a novel isoform GLG2 with a unique 24-amino-acid C-terminal cytoplasmic extension; the cytoplasmic domain of GLG1 targets expression to the cell surface whereas the GLG2 cytoplasmic domain targets retention in the Golgi, demonstrating that the cytoplasmic tail determines subcellular localization.","method":"cDNA cloning from human monocyte library, transfection of cytoplasmic domain chimeric constructs into HEK293 cells, Northern blot analysis","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — chimeric construct transfection experiment demonstrating domain-specific localization, single lab but two orthogonal approaches (chimeric constructs and Northern blot)","pmids":["15797922"],"is_preprint":false},{"year":2011,"finding":"Two distinct regions of Cfr/GLG1 regulate its subcellular distribution: the C-terminal region retains GLG1 in the Golgi apparatus, while the cysteine-rich repeat region in the extracellular juxtamembrane domain destabilizes GLG1 at the cell surface (independently of cleavage/secretion). A GPI-anchored form of Cfr expressed predominantly on the cell surface affected FGF18 signaling via FGFR3c, indicating that cell surface interaction with FGFs is important for its function.","method":"Mutagenesis analysis, chimeric construct expression (GPI-anchored form), subcellular fractionation, FGF18 signaling assays in Ba/F3 cells","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mutagenesis combined with functional signaling assay, single lab, multiple constructs tested","pmids":["21777203"],"is_preprint":false},{"year":2013,"finding":"ESL-1 (GLG1) plays a dominant role in E-selectin binding and migration of hematopoietic progenitor cells into the bone marrow; in mature neutrophils this role shifts to PSGL-1 dominance. Combined deficiency of PSGL-1 and ESL-1 completely abrogated leukocyte recruitment during inflammation.","method":"Genetic knockout (ESL-1 deficient mice and PSGL-1/ESL-1 double-deficient mice), flow cytometry, intravital microscopy, bone marrow transplantation","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean in vivo genetic loss-of-function with multiple defined cellular and trafficking phenotypes, single lab","pmids":["24106206"],"is_preprint":false},{"year":2016,"finding":"ESL-1 (GLG1) in hematopoietic stem and progenitor cells (HSPCs) limits TGFβ availability in the bone marrow niche; ESL-1-deficient HSPCs produce excess TGFβ, causing aberrant quiescence and niche expansion independent of E-selectin; in vivo or in vitro blockade of TGFβ completely restored homeostatic niche properties. This cell-intrinsic mechanism is transplantable and dominant.","method":"Genetic knockout mice, bone marrow transplantation, TGFβ cytokine measurement, in vivo and in vitro TGFβ blockade, flow cytometry of HSPC populations","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal approaches (genetic KO, transplantation, cytokine rescue), mechanistic pathway placement via TGFβ blockade rescue","pmids":["26742601"],"is_preprint":false},{"year":2016,"finding":"ESL-1 (GLG1) was identified as a novel binding protein for adiponectin (APN) on monocytes; five extracellular amino acids near the N-terminus of ESL-1 are essential for binding adiponectin. APN-mediated suppression of monocyte adhesion to endothelial cells was partially abrogated by ESL-1 shRNA knockdown.","method":"Mass spectrometry-based identification from anti-APN immunoprecipitation of HepG2 cells, serial mutagenesis of ESL-1, shRNA knockdown, cell adhesion assay with fluorescence-labeled THP-1 cells and HUVECs","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — immunoprecipitation/MS for identification plus mutagenesis and functional knockdown, single lab","pmids":["26792720"],"is_preprint":false},{"year":2009,"finding":"CFR/ESL-1 (GLG1) is expressed on hepatic stellate cells (HSC) together with FucT7, conferring functional E-selectin binding activity on their surface; after transient transfection of HSC with CFR cDNA, E-selectin binding activity was released into the supernatant, suggesting shedding. Under hypoxia, E-selectin binding activity decreased despite maintained CFR protein and increased FucT7 mRNA.","method":"Flow cytometry, transfection of HSC with CFR cDNA, measurement of secreted E-selectin binding activity in supernatant, qRT-PCR","journal":"Oncology reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, mainly expression characterization with one functional transfection experiment, limited mechanistic follow-up","pmids":["19148508"],"is_preprint":false},{"year":2001,"finding":"The epitope recognized by anti-CFR-1 (GLG1) monoclonal antibody 103/51 was determined to be an N-linked carbohydrate side chain, as established by glycosidase-digestion experiments, indicating post-translational N-glycosylation is functionally relevant for antibody recognition of the CFR-1/GLG1 protein variant.","method":"Glycosidase-digestion experiments, immunoprecipitation, protein sequencing","journal":"Laboratory investigation","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single biochemical method (glycosidase digestion) in a single lab study primarily focused on clinical characterization","pmids":["11502861"],"is_preprint":false},{"year":2022,"finding":"Memantine treatment causes GLG1 to redistribute from the Golgi apparatus to the cytosol, upregulates full-length and truncated forms of GLG1, and alters splicing variant profiles; since GLG1 functions as a decoy FGF receptor, this redistribution was proposed as a mechanism for cancer-suppressive effects of memantine.","method":"Western blot, immunofluorescence localization, RT-PCR for splicing variants, cell growth assay in glioma and breast cancer cell lines","journal":"International journal of oncology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, descriptive localization and expression changes without direct mechanistic dissection of GLG1's decoy receptor function","pmids":["35543162"],"is_preprint":false},{"year":2024,"finding":"FUT3-mediated Lea glycosylation on GLG1 at specific N-glycosylation sites influences GLG1 distribution in intracellular vesicles; silencing GLG1 inhibited migration and invasion of gastric cancer cells, while silencing FUT3 decreased GLG1 vesicle distribution. IGP analysis revealed Lea structure in 31 N-glycans at 4 glycosites of GLG1.","method":"Lea-antibody capturing coupled with mass spectrometry, immunofluorescence, siRNA knockdown of GLG1 and FUT3, cell migration and invasion assays","journal":"Life sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mass spectrometry glycosite mapping combined with loss-of-function and functional assays, single lab","pmids":["39477144"],"is_preprint":false},{"year":2025,"finding":"FTO, an m6A demethylase, positively regulates GLG1 mRNA stability and expression through m6A methylation modification; FTO knockdown decreased GLG1 expression and mitigated gastric cancer cell aggressiveness, indicating a post-transcriptional regulatory mechanism controlling GLG1 levels.","method":"FTO and GLG1 knockdown experiments in vitro and in vivo (xenograft), western blot, qRT-PCR, m6A methylation analysis","journal":"Journal of gastroenterology and hepatology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, knockdown-based evidence for FTO-GLG1 regulatory axis without direct m6A site mapping on GLG1 mRNA described in abstract","pmids":["41287415"],"is_preprint":false}],"current_model":"GLG1 (also known as MG-160, ESL-1, CFR-1) encodes a multifunctional type I transmembrane cysteine-rich sialoglycoprotein that resides predominantly in medial Golgi cisternae but also traffics to the cell surface (particularly microvilli), where its subcellular distribution is controlled by its C-terminal cytoplasmic tail and cysteine-rich repeat domains; it functions as a high-affinity E-selectin ligand on leukocytes (requiring fucosylation), mediating conversion of tethers to slow rolling during neutrophil extravasation, as a decoy FGF-binding protein in the Golgi that modulates FGF signaling, as a component of latent TGF-β complexes that limits TGFβ availability in the hematopoietic niche, and as a novel adiponectin-binding protein whose N-terminal extracellular domain mediates anti-adhesive signaling."},"narrative":{"mechanistic_narrative":"GLG1 (identified independently as MG-160, ESL-1, and CFR-1) is a type I transmembrane cysteine-rich sialoglycoprotein that resides predominantly in the medial cisternae of the Golgi apparatus but also traffics to the cell surface, where roughly 80% of surface labeling concentrates on microvilli that initiate leukocyte–endothelial contacts [PMID:2909545, PMID:9099943]. Its subcellular partitioning is encoded by distinct protein regions: the C-terminal cytoplasmic tail confers Golgi retention while an alternatively spliced tail or the cysteine-rich juxtamembrane repeat region directs/destabilizes surface display [PMID:15797922, PMID:21777203]. At the cell surface, fucosylated GLG1 acts as a high-affinity E-selectin ligand on myeloid cells, converting initial E-selectin tethers into steady slow rolling — a role distinct from PSGL-1 and CD44 — and is required for hematopoietic progenitor migration into bone marrow [PMID:7531823, PMID:17442598, PMID:24106206]. Through its cysteine-rich repeats GLG1 also binds basic FGF and modulates FGF18/FGFR3c signaling, behaving as an FGF-binding/decoy receptor whose activity depends on surface localization [PMID:7768993, PMID:21777203]. Independently of E-selectin, GLG1 forms a complex with the latency-associated peptide of TGF-β1 and limits TGF-β availability in the bone marrow niche, restraining excess TGF-β that otherwise drives aberrant HSPC quiescence and niche expansion [PMID:9182700, PMID:26742601]. GLG1 additionally binds adiponectin via N-terminal extracellular residues, contributing to suppression of monocyte adhesion [PMID:26792720]. GLG1 function is shaped by its glycosylation: FUT3-mediated Lewis-a glycosylation at defined N-glycosites governs its intracellular vesicle distribution and supports gastric cancer cell migration and invasion [PMID:39477144].","teleology":[{"year":1989,"claim":"Established GLG1's baseline identity and residence — defining it as a Golgi-resident sialoglycoprotein before any functional role was known.","evidence":"Immunoelectron microscopy and biochemical characterization of MG-160 in neurons, glia, and PC12 cells","pmids":["2909545"],"confidence":"High","gaps":["No molecular function assigned at this stage","Sequence/domain architecture not yet resolved"]},{"year":1995,"claim":"Defined GLG1's first molecular activity by showing the affinity-purified protein is the major E-selectin ligand on myeloid cells and requires fucosylation for binding.","evidence":"Affinity isolation with E-selectin-IgG, cell adhesion assays, antibody blocking, and cDNA cloning","pmids":["7531823"],"confidence":"High","gaps":["In vivo contribution to leukocyte rolling not yet tested","Specific fucosylated glycan structures not mapped"]},{"year":1995,"claim":"Linked GLG1 structure to growth-factor biology by demonstrating direct bFGF binding and a 16-cysteine-rich-repeat architecture homologous to chicken CFR.","evidence":"cDNA sequencing, domain analysis, and direct bFGF binding assay with rat brain protein","pmids":["7768993"],"confidence":"High","gaps":["Downstream signaling consequence of FGF binding not established here","Whether binding occurs in Golgi or at surface unresolved"]},{"year":1997,"claim":"Reconciled the Golgi-resident and ligand identities by showing GLG1 also localizes to cell-surface microvilli, positioning it for leukocyte–endothelial contact.","evidence":"Immunofluorescence, surface biotinylation, surface immunoprecipitation, and immunogold SEM in 32Dc13 cells and neutrophils","pmids":["9099943"],"confidence":"High","gaps":["Mechanism partitioning Golgi vs surface pools not yet defined","Functional necessity of microvillar localization untested"]},{"year":1997,"claim":"Revealed a third activity — complex formation with TGF-β1 latency-associated peptide — establishing GLG1 as a component of secreted latent TGF-β complexes.","evidence":"Biochemical purification, amino acid sequencing, and immunoprecipitation of LTCP-1/TGF-β1 in CHO cells","pmids":["9182700"],"confidence":"High","gaps":["Physiological consequence for TGF-β signaling not addressed","Binding interface on GLG1 not mapped"]},{"year":2005,"claim":"Identified the cytoplasmic tail as the localization determinant by showing an alternatively spliced isoform (GLG2) with a divergent tail retains the protein in the Golgi, whereas the GLG1 tail targets the surface.","evidence":"cDNA cloning, chimeric cytoplasmic-domain transfection in HEK293, and Northern blot","pmids":["15797922"],"confidence":"Medium","gaps":["Trafficking machinery recognizing each tail unknown","Relative abundance of isoforms in vivo not quantified"]},{"year":2007,"claim":"Assigned GLG1 a non-redundant step in leukocyte adhesion — converting E-selectin tethers to slow rolling — distinct from PSGL-1 and CD44.","evidence":"Knockout and siRNA loss-of-function with intravital microscopy and combined-knockout epistasis","pmids":["17442598"],"confidence":"High","gaps":["Molecular signaling triggered by GLG1–E-selectin engagement not defined"]},{"year":2009,"claim":"Extended E-selectin ligand function to hepatic stellate cells and raised shedding as a possible regulatory mechanism.","evidence":"Flow cytometry, CFR cDNA transfection, secreted binding-activity assay, and qRT-PCR under hypoxia","pmids":["19148508"],"confidence":"Low","gaps":["Shedding inferred from supernatant activity, not directly demonstrated","Single lab, expression-focused","Hypoxic regulation mechanism unclear"]},{"year":2011,"claim":"Mapped two opposing localization signals and connected surface display to function by showing a GPI-anchored surface form modulates FGF18/FGFR3c signaling.","evidence":"Mutagenesis, chimeric GPI-anchored constructs, fractionation, and FGF18 signaling assays in Ba/F3 cells","pmids":["21777203"],"confidence":"Medium","gaps":["Endogenous balance of the two signals not quantified","Direct effect on FGFR3c phosphorylation not detailed"]},{"year":2013,"claim":"Established the in vivo division of labor between GLG1 and PSGL-1 — GLG1 dominant for progenitor homing, PSGL-1 for mature neutrophils.","evidence":"Single and double knockout mice, flow cytometry, intravital microscopy, bone marrow transplantation","pmids":["24106206"],"confidence":"High","gaps":["Cell-type basis of the dominance switch not mechanistically explained"]},{"year":2016,"claim":"Demonstrated a cell-intrinsic, E-selectin-independent role for GLG1 in limiting TGF-β in the HSPC niche, with TGF-β blockade rescuing the phenotype.","evidence":"Knockout mice, transplantation, TGF-β cytokine measurement, and in vivo/in vitro TGF-β blockade","pmids":["26742601"],"confidence":"High","gaps":["Molecular step by which GLG1 restrains TGF-β production not defined","Relation to the LAP complex from 1997 not directly tested"]},{"year":2016,"claim":"Identified adiponectin as a new GLG1 binding partner and mapped the interaction to five N-terminal extracellular residues, linking GLG1 to anti-adhesive signaling.","evidence":"Anti-adiponectin IP/mass spectrometry, serial mutagenesis, shRNA knockdown, and monocyte–endothelial adhesion assays","pmids":["26792720"],"confidence":"Medium","gaps":["Knockdown only partially abrogated the effect","Downstream signaling pathway unresolved"]},{"year":2024,"claim":"Showed that FUT3-mediated Lewis-a glycosylation at defined N-glycosites controls GLG1 vesicle distribution and supports gastric cancer cell migration and invasion.","evidence":"Lea-antibody capture mass spectrometry, immunofluorescence, siRNA of GLG1 and FUT3, migration/invasion assays","pmids":["39477144"],"confidence":"Medium","gaps":["Causal link between glycosylation, localization, and invasion not fully separated","Single cancer model"]},{"year":2025,"claim":"Identified an upstream post-transcriptional control point, with FTO-mediated m6A demethylation stabilizing GLG1 mRNA and promoting gastric cancer aggressiveness.","evidence":"FTO and GLG1 knockdown in vitro and in xenografts, western blot, qRT-PCR, m6A analysis","pmids":["41287415"],"confidence":"Low","gaps":["m6A sites on GLG1 mRNA not mapped","Knockdown-based, single lab","Mechanism of stability change unspecified"]},{"year":null,"claim":"How GLG1 mechanistically restrains TGF-β production in the niche, and whether its Golgi FGF-binding and surface E-selectin/adiponectin roles are coordinately regulated by a single trafficking switch, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of GLG1 with any ligand","Integration of multiple ligand activities into one regulatory logic unestablished"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098631","term_label":"cell adhesion mediator activity","supporting_discovery_ids":[0,5,8]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2,4,9]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[1,3,6,7]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[3,7]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[14]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[0,5,8]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,7,9]}],"complexes":["latent TGF-β1 (LAP) complex"],"partners":["SELE","FGF2","FGF18","FGFR3","TGFB1","ADIPOQ","FUT3"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q92896","full_name":"Golgi apparatus protein 1","aliases":["CFR-1","Cysteine-rich fibroblast growth factor receptor","E-selectin ligand 1","ESL-1","Golgi sialoglycoprotein MG-160"],"length_aa":1179,"mass_kda":134.6,"function":"Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils)","subcellular_location":"Golgi apparatus membrane; Golgi outpost; Cytoplasm, cytoskeleton, microtubule organizing center","url":"https://www.uniprot.org/uniprotkb/Q92896/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/GLG1","classification":"Not Classified","n_dependent_lines":4,"n_total_lines":1208,"dependency_fraction":0.0033112582781456954},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CANX","stoichiometry":0.2},{"gene":"OSBPL8","stoichiometry":0.2},{"gene":"SRP9","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/GLG1","total_profiled":1310},"omim":[{"mim_id":"603918","title":"HYPERTENSION, ESSENTIAL, SUSCEPTIBILITY TO, 1","url":"https://www.omim.org/entry/603918"},{"mim_id":"600753","title":"GOLGI APPARATUS PROTEIN 1; GLG1","url":"https://www.omim.org/entry/600753"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Golgi apparatus","reliability":"Supported"},{"location":"Mid piece","reliability":"Additional"},{"location":"Principal piece","reliability":"Additional"},{"location":"End piece","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/GLG1"},"hgnc":{"alias_symbol":["MG-160","ESL-1","CFR-1"],"prev_symbol":[]},"alphafold":{"accession":"Q92896","domains":[{"cath_id":"-","chopping":"557-582_590-630","consensus_level":"medium","plddt":70.7603,"start":557,"end":630},{"cath_id":"-","chopping":"1061-1127","consensus_level":"medium","plddt":86.4782,"start":1061,"end":1127}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q92896","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q92896-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q92896-F1-predicted_aligned_error_v6.png","plddt_mean":77.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GLG1","jax_strain_url":"https://www.jax.org/strain/search?query=GLG1"},"sequence":{"accession":"Q92896","fasta_url":"https://rest.uniprot.org/uniprotkb/Q92896.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q92896/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q92896"}},"corpus_meta":[{"pmid":"7531823","id":"PMC_7531823","title":"The E-selectin-ligand ESL-1 is a variant of a receptor for fibroblast growth factor.","date":"1995","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/7531823","citation_count":305,"is_preprint":false},{"pmid":"17442598","id":"PMC_17442598","title":"Complete identification of E-selectin ligands on neutrophils reveals distinct functions of PSGL-1, ESL-1, and CD44.","date":"2007","source":"Immunity","url":"https://pubmed.ncbi.nlm.nih.gov/17442598","citation_count":238,"is_preprint":false},{"pmid":"2909545","id":"PMC_2909545","title":"MG-160. A novel sialoglycoprotein of the medial cisternae of the Golgi apparatus [published eeratum appears in J Biol Chem 1989 Mar 5;264(7):4264].","date":"1989","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/2909545","citation_count":160,"is_preprint":false},{"pmid":"2355176","id":"PMC_2355176","title":"Immunocytochemical visualization of the Golgi apparatus in several species, including human, and tissues with an antiserum against MG-160, a sialoglycoprotein of rat Golgi apparatus.","date":"1990","source":"The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society","url":"https://pubmed.ncbi.nlm.nih.gov/2355176","citation_count":89,"is_preprint":false},{"pmid":"9099943","id":"PMC_9099943","title":"The E-selectin-ligand ESL-1 is located in the Golgi as well as on microvilli on the cell surface.","date":"1997","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/9099943","citation_count":64,"is_preprint":false},{"pmid":"7768993","id":"PMC_7768993","title":"MG-160, a membrane sialoglycoprotein of the medial cisternae of the rat Golgi apparatus, binds basic fibroblast growth factor and exhibits a high level of sequence identity to a chicken fibroblast growth factor receptor.","date":"1995","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/7768993","citation_count":52,"is_preprint":false},{"pmid":"24106206","id":"PMC_24106206","title":"Coordinated and unique functions of the E-selectin ligand ESL-1 during inflammatory and hematopoietic recruitment in mice.","date":"2013","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/24106206","citation_count":30,"is_preprint":false},{"pmid":"11502861","id":"PMC_11502861","title":"A novel proliferation-associated variant of CFR-1 defined by a human monoclonal antibody.","date":"2001","source":"Laboratory investigation; a journal of technical methods and pathology","url":"https://pubmed.ncbi.nlm.nih.gov/11502861","citation_count":26,"is_preprint":false},{"pmid":"9182700","id":"PMC_9182700","title":"Latent transforming growth factor-beta complex in Chinese hamster ovary cells contains the multifunctional cysteine-rich fibroblast growth factor receptor, also termed E-selectin-ligand or MG-160.","date":"1997","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/9182700","citation_count":26,"is_preprint":false},{"pmid":"15010872","id":"PMC_15010872","title":"CFR-1 receptor as target for tumor-specific apoptosis induced by the natural human monoclonal antibody PAM-1.","date":"2004","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/15010872","citation_count":23,"is_preprint":false},{"pmid":"32164354","id":"PMC_32164354","title":"High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma.","date":"2020","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/32164354","citation_count":18,"is_preprint":false},{"pmid":"15797922","id":"PMC_15797922","title":"A novel isoform of human Golgi complex-localized glycoprotein-1 (also known as E-selectin ligand-1, MG-160 and cysteine-rich fibroblast growth factor receptor) targets differential subcellular localization.","date":"2005","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/15797922","citation_count":17,"is_preprint":false},{"pmid":"29712138","id":"PMC_29712138","title":"Synthetic Inhibitors of Cell Adhesion: A Glycopeptide from E-Selectin Ligand 1 (ESL-1) with the Arabino Sialyl Lewisx Structure.","date":"2001","source":"Angewandte Chemie (International ed. in English)","url":"https://pubmed.ncbi.nlm.nih.gov/29712138","citation_count":17,"is_preprint":false},{"pmid":"26742601","id":"PMC_26742601","title":"Haematopoietic ESL-1 enables stem cell proliferation in the bone marrow by limiting TGFβ availability.","date":"2016","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/26742601","citation_count":16,"is_preprint":false},{"pmid":"19148508","id":"PMC_19148508","title":"Expression of E-selectin ligand-1 (CFR/ESL-1) on hepatic stellate cells: implications for leukocyte extravasation and liver metastasis.","date":"2009","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/19148508","citation_count":12,"is_preprint":false},{"pmid":"26792720","id":"PMC_26792720","title":"E-selectin ligand-1 (ESL-1) is a novel adiponectin binding protein on cell adhesion.","date":"2016","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/26792720","citation_count":11,"is_preprint":false},{"pmid":"12684670","id":"PMC_12684670","title":"Identification of MG-160, a FGF binding medial Golgi sialoglycoprotein, in brain tumors: an index of malignancy in astrocytomas.","date":"2003","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/12684670","citation_count":10,"is_preprint":false},{"pmid":"19263101","id":"PMC_19263101","title":"Lipopolysaccharide-induced early response genes in bovine peripheral blood mononuclear cells implicate GLG1/E-selectin as a key ligand-receptor interaction.","date":"2009","source":"Functional & integrative genomics","url":"https://pubmed.ncbi.nlm.nih.gov/19263101","citation_count":8,"is_preprint":false},{"pmid":"10556428","id":"PMC_10556428","title":"Structure of the murine E-selectin ligand 1 (ESL-1) gene and assignment to Chromosome 8.","date":"1999","source":"Mammalian genome : official journal of the International Mammalian Genome Society","url":"https://pubmed.ncbi.nlm.nih.gov/10556428","citation_count":7,"is_preprint":false},{"pmid":"35543162","id":"PMC_35543162","title":"Antitumor effect of memantine is related to the formation of the splicing isoform of GLG1, a decoy FGF‑binding protein.","date":"2022","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/35543162","citation_count":6,"is_preprint":false},{"pmid":"12029485","id":"PMC_12029485","title":"Identification and characterization of an insect homologue of the vertebrate Golgi apparatus protein 1 (MG-160/cysteine-rich fibroblast growth factor receptor/E-selectin ligand-1/latent transforming growth factor-beta complex protein-1) with a Golgi-specific monoclonal antibody.","date":"2002","source":"Histochemistry and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/12029485","citation_count":5,"is_preprint":false},{"pmid":"21777203","id":"PMC_21777203","title":"Retention in the Golgi apparatus and expression on the cell surface of Cfr/Esl-1/Glg-1/MG-160 are regulated by two distinct mechanisms.","date":"2011","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/21777203","citation_count":4,"is_preprint":false},{"pmid":"39477144","id":"PMC_39477144","title":"FUT3 promotes gastric cancer cell migration by synthesizing Lea on ITGA6 and GLG1, affecting adhesion and vesicle distribution.","date":"2024","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39477144","citation_count":3,"is_preprint":false},{"pmid":"41287415","id":"PMC_41287415","title":"FTO Upregulates GLG1 Expression via m6A Methylation Modification to Facilitate Gastric Cancer Cell Migration and Invasion.","date":"2025","source":"Journal of gastroenterology and hepatology","url":"https://pubmed.ncbi.nlm.nih.gov/41287415","citation_count":0,"is_preprint":false},{"pmid":"41490595","id":"PMC_41490595","title":"The circ-GLG1/miR-346/KCNJ9 axis drives malignant progression of bladder cancer by modulating KCNJ9 expression.","date":"2026","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/41490595","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":14445,"output_tokens":4241,"usd":0.053475,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":12148,"output_tokens":4184,"usd":0.08267,"stage2_stop_reason":"end_turn"},"total_usd":0.136145,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1995,\n      \"finding\": \"ESL-1 (GLG1) was identified as the major E-selectin ligand on myeloid cells; fucosylation of ESL-1 is required for affinity binding to E-selectin-IgG, and a fucosylated recombinant form of ESL-1 supports adhesion of E-selectin-transfected CHO cells. Antibodies against ESL-1 block binding of myeloid cells to E-selectin.\",\n      \"method\": \"Affinity isolation with recombinant E-selectin-IgG, cell adhesion assay with E-selectin-transfected CHO cells, antibody blocking experiment, cDNA cloning\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods (affinity pulldown, cell adhesion assay, antibody blocking), replicated across labs subsequently\",\n      \"pmids\": [\"7531823\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1989,\n      \"finding\": \"MG-160 (GLG1) is a 160 kDa sialoglycoprotein localized specifically to the medial cisternae of the Golgi apparatus in neurons, glia, pituitary cells, and PC12 cells; it contains asparagine-linked carbohydrates, sialic acid, N-acetylglucosamine, and intrachain disulfide bonds; it resides in the membrane and/or luminal face of Golgi cisternae.\",\n      \"method\": \"Immunoelectron microscopy, immunoaffinity purification, biochemical characterization (glycosidase treatment, Triton X-114 extraction), monoclonal antibody-based localization\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct subcellular localization by immunoelectron microscopy with biochemical fractionation, replicated in multiple cell types and subsequently confirmed by many follow-up studies\",\n      \"pmids\": [\"2909545\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"MG-160 (GLG1) binds basic fibroblast growth factor (bFGF); its primary structure contains 16 cysteine-rich repeat domains, a single transmembrane domain, and a short cytoplasmic tail, with 90% identity to chicken CFR (a FGF receptor). It has an upstream open reading frame in its mRNA, a feature shared with growth factors and receptors.\",\n      \"method\": \"cDNA cloning and sequence analysis, direct bFGF binding assay with purified MG-160 protein from rat brain (recombinant bFGF binding)\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct in vitro binding assay combined with full cDNA sequence determination and structural domain analysis, single lab but rigorous biochemical approach\",\n      \"pmids\": [\"7768993\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"ESL-1 (GLG1) localizes both to the Golgi apparatus and to microvilli on the cell surface of 32Dc13 cells and neutrophils; approximately 80% of ESL-1 labeling was found on microvilli, positioning it at sites for initiating cell contacts with endothelium.\",\n      \"method\": \"Indirect immunofluorescence, flow cytometry, cell surface biotinylation, cell surface immunoprecipitation on intact cells, immunogold scanning electron microscopy\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (immunofluorescence, biotinylation, immunogold EM) in a single study with quantitative analysis\",\n      \"pmids\": [\"9099943\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"GLG1 (as LTCP-1, the hamster orthologue) forms a complex with the latency-associated peptide (LAP) of TGF-β1 in CHO cells, and a major part of this complex is secreted; purification and amino acid sequencing confirmed the identity of the 140 kDa component as the hamster counterpart of CFR/ESL-1/MG-160.\",\n      \"method\": \"Biochemical purification of latent TGF-β complexes from CHO cells, amino acid sequencing, cDNA cloning, immunoprecipitation of LTCP-1 and TGF-β1\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — protein purification, amino acid sequencing, and immunoprecipitation in a single rigorous study establishing direct complex formation\",\n      \"pmids\": [\"9182700\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"ESL-1 (GLG1) on neutrophils is critical for converting initial E-selectin-mediated tethers into steady slow rolling, a distinct function from PSGL-1 (initial capture) and CD44 (rolling velocity); together, ESL-1, PSGL-1, and CD44 account for all E-selectin ligand activity on neutrophils.\",\n      \"method\": \"Gene- and RNA-targeted loss-of-function (knockout and siRNA), intravital microscopy of leukocyte rolling, genetic epistasis via combined knockouts\",\n      \"journal\": \"Immunity\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic loss-of-function with multiple knockouts, quantitative intravital microscopy readout, independently confirmed by subsequent studies\",\n      \"pmids\": [\"17442598\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Alternative splicing of the GLG1 gene generates a novel isoform GLG2 with a unique 24-amino-acid C-terminal cytoplasmic extension; the cytoplasmic domain of GLG1 targets expression to the cell surface whereas the GLG2 cytoplasmic domain targets retention in the Golgi, demonstrating that the cytoplasmic tail determines subcellular localization.\",\n      \"method\": \"cDNA cloning from human monocyte library, transfection of cytoplasmic domain chimeric constructs into HEK293 cells, Northern blot analysis\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — chimeric construct transfection experiment demonstrating domain-specific localization, single lab but two orthogonal approaches (chimeric constructs and Northern blot)\",\n      \"pmids\": [\"15797922\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Two distinct regions of Cfr/GLG1 regulate its subcellular distribution: the C-terminal region retains GLG1 in the Golgi apparatus, while the cysteine-rich repeat region in the extracellular juxtamembrane domain destabilizes GLG1 at the cell surface (independently of cleavage/secretion). A GPI-anchored form of Cfr expressed predominantly on the cell surface affected FGF18 signaling via FGFR3c, indicating that cell surface interaction with FGFs is important for its function.\",\n      \"method\": \"Mutagenesis analysis, chimeric construct expression (GPI-anchored form), subcellular fractionation, FGF18 signaling assays in Ba/F3 cells\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutagenesis combined with functional signaling assay, single lab, multiple constructs tested\",\n      \"pmids\": [\"21777203\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"ESL-1 (GLG1) plays a dominant role in E-selectin binding and migration of hematopoietic progenitor cells into the bone marrow; in mature neutrophils this role shifts to PSGL-1 dominance. Combined deficiency of PSGL-1 and ESL-1 completely abrogated leukocyte recruitment during inflammation.\",\n      \"method\": \"Genetic knockout (ESL-1 deficient mice and PSGL-1/ESL-1 double-deficient mice), flow cytometry, intravital microscopy, bone marrow transplantation\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean in vivo genetic loss-of-function with multiple defined cellular and trafficking phenotypes, single lab\",\n      \"pmids\": [\"24106206\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"ESL-1 (GLG1) in hematopoietic stem and progenitor cells (HSPCs) limits TGFβ availability in the bone marrow niche; ESL-1-deficient HSPCs produce excess TGFβ, causing aberrant quiescence and niche expansion independent of E-selectin; in vivo or in vitro blockade of TGFβ completely restored homeostatic niche properties. This cell-intrinsic mechanism is transplantable and dominant.\",\n      \"method\": \"Genetic knockout mice, bone marrow transplantation, TGFβ cytokine measurement, in vivo and in vitro TGFβ blockade, flow cytometry of HSPC populations\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal approaches (genetic KO, transplantation, cytokine rescue), mechanistic pathway placement via TGFβ blockade rescue\",\n      \"pmids\": [\"26742601\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"ESL-1 (GLG1) was identified as a novel binding protein for adiponectin (APN) on monocytes; five extracellular amino acids near the N-terminus of ESL-1 are essential for binding adiponectin. APN-mediated suppression of monocyte adhesion to endothelial cells was partially abrogated by ESL-1 shRNA knockdown.\",\n      \"method\": \"Mass spectrometry-based identification from anti-APN immunoprecipitation of HepG2 cells, serial mutagenesis of ESL-1, shRNA knockdown, cell adhesion assay with fluorescence-labeled THP-1 cells and HUVECs\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — immunoprecipitation/MS for identification plus mutagenesis and functional knockdown, single lab\",\n      \"pmids\": [\"26792720\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"CFR/ESL-1 (GLG1) is expressed on hepatic stellate cells (HSC) together with FucT7, conferring functional E-selectin binding activity on their surface; after transient transfection of HSC with CFR cDNA, E-selectin binding activity was released into the supernatant, suggesting shedding. Under hypoxia, E-selectin binding activity decreased despite maintained CFR protein and increased FucT7 mRNA.\",\n      \"method\": \"Flow cytometry, transfection of HSC with CFR cDNA, measurement of secreted E-selectin binding activity in supernatant, qRT-PCR\",\n      \"journal\": \"Oncology reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, mainly expression characterization with one functional transfection experiment, limited mechanistic follow-up\",\n      \"pmids\": [\"19148508\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"The epitope recognized by anti-CFR-1 (GLG1) monoclonal antibody 103/51 was determined to be an N-linked carbohydrate side chain, as established by glycosidase-digestion experiments, indicating post-translational N-glycosylation is functionally relevant for antibody recognition of the CFR-1/GLG1 protein variant.\",\n      \"method\": \"Glycosidase-digestion experiments, immunoprecipitation, protein sequencing\",\n      \"journal\": \"Laboratory investigation\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single biochemical method (glycosidase digestion) in a single lab study primarily focused on clinical characterization\",\n      \"pmids\": [\"11502861\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Memantine treatment causes GLG1 to redistribute from the Golgi apparatus to the cytosol, upregulates full-length and truncated forms of GLG1, and alters splicing variant profiles; since GLG1 functions as a decoy FGF receptor, this redistribution was proposed as a mechanism for cancer-suppressive effects of memantine.\",\n      \"method\": \"Western blot, immunofluorescence localization, RT-PCR for splicing variants, cell growth assay in glioma and breast cancer cell lines\",\n      \"journal\": \"International journal of oncology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, descriptive localization and expression changes without direct mechanistic dissection of GLG1's decoy receptor function\",\n      \"pmids\": [\"35543162\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"FUT3-mediated Lea glycosylation on GLG1 at specific N-glycosylation sites influences GLG1 distribution in intracellular vesicles; silencing GLG1 inhibited migration and invasion of gastric cancer cells, while silencing FUT3 decreased GLG1 vesicle distribution. IGP analysis revealed Lea structure in 31 N-glycans at 4 glycosites of GLG1.\",\n      \"method\": \"Lea-antibody capturing coupled with mass spectrometry, immunofluorescence, siRNA knockdown of GLG1 and FUT3, cell migration and invasion assays\",\n      \"journal\": \"Life sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mass spectrometry glycosite mapping combined with loss-of-function and functional assays, single lab\",\n      \"pmids\": [\"39477144\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"FTO, an m6A demethylase, positively regulates GLG1 mRNA stability and expression through m6A methylation modification; FTO knockdown decreased GLG1 expression and mitigated gastric cancer cell aggressiveness, indicating a post-transcriptional regulatory mechanism controlling GLG1 levels.\",\n      \"method\": \"FTO and GLG1 knockdown experiments in vitro and in vivo (xenograft), western blot, qRT-PCR, m6A methylation analysis\",\n      \"journal\": \"Journal of gastroenterology and hepatology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, knockdown-based evidence for FTO-GLG1 regulatory axis without direct m6A site mapping on GLG1 mRNA described in abstract\",\n      \"pmids\": [\"41287415\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"GLG1 (also known as MG-160, ESL-1, CFR-1) encodes a multifunctional type I transmembrane cysteine-rich sialoglycoprotein that resides predominantly in medial Golgi cisternae but also traffics to the cell surface (particularly microvilli), where its subcellular distribution is controlled by its C-terminal cytoplasmic tail and cysteine-rich repeat domains; it functions as a high-affinity E-selectin ligand on leukocytes (requiring fucosylation), mediating conversion of tethers to slow rolling during neutrophil extravasation, as a decoy FGF-binding protein in the Golgi that modulates FGF signaling, as a component of latent TGF-β complexes that limits TGFβ availability in the hematopoietic niche, and as a novel adiponectin-binding protein whose N-terminal extracellular domain mediates anti-adhesive signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GLG1 (identified independently as MG-160, ESL-1, and CFR-1) is a type I transmembrane cysteine-rich sialoglycoprotein that resides predominantly in the medial cisternae of the Golgi apparatus but also traffics to the cell surface, where roughly 80% of surface labeling concentrates on microvilli that initiate leukocyte–endothelial contacts [#1, #3]. Its subcellular partitioning is encoded by distinct protein regions: the C-terminal cytoplasmic tail confers Golgi retention while an alternatively spliced tail or the cysteine-rich juxtamembrane repeat region directs/destabilizes surface display [#6, #7]. At the cell surface, fucosylated GLG1 acts as a high-affinity E-selectin ligand on myeloid cells, converting initial E-selectin tethers into steady slow rolling — a role distinct from PSGL-1 and CD44 — and is required for hematopoietic progenitor migration into bone marrow [#0, #5, #8]. Through its cysteine-rich repeats GLG1 also binds basic FGF and modulates FGF18/FGFR3c signaling, behaving as an FGF-binding/decoy receptor whose activity depends on surface localization [#2, #7]. Independently of E-selectin, GLG1 forms a complex with the latency-associated peptide of TGF-β1 and limits TGF-β availability in the bone marrow niche, restraining excess TGF-β that otherwise drives aberrant HSPC quiescence and niche expansion [#4, #9]. GLG1 additionally binds adiponectin via N-terminal extracellular residues, contributing to suppression of monocyte adhesion [#10]. GLG1 function is shaped by its glycosylation: FUT3-mediated Lewis-a glycosylation at defined N-glycosites governs its intracellular vesicle distribution and supports gastric cancer cell migration and invasion [#14].\",\n  \"teleology\": [\n    {\n      \"year\": 1989,\n      \"claim\": \"Established GLG1's baseline identity and residence — defining it as a Golgi-resident sialoglycoprotein before any functional role was known.\",\n      \"evidence\": \"Immunoelectron microscopy and biochemical characterization of MG-160 in neurons, glia, and PC12 cells\",\n      \"pmids\": [\"2909545\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No molecular function assigned at this stage\", \"Sequence/domain architecture not yet resolved\"]\n    },\n    {\n      \"year\": 1995,\n      \"claim\": \"Defined GLG1's first molecular activity by showing the affinity-purified protein is the major E-selectin ligand on myeloid cells and requires fucosylation for binding.\",\n      \"evidence\": \"Affinity isolation with E-selectin-IgG, cell adhesion assays, antibody blocking, and cDNA cloning\",\n      \"pmids\": [\"7531823\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo contribution to leukocyte rolling not yet tested\", \"Specific fucosylated glycan structures not mapped\"]\n    },\n    {\n      \"year\": 1995,\n      \"claim\": \"Linked GLG1 structure to growth-factor biology by demonstrating direct bFGF binding and a 16-cysteine-rich-repeat architecture homologous to chicken CFR.\",\n      \"evidence\": \"cDNA sequencing, domain analysis, and direct bFGF binding assay with rat brain protein\",\n      \"pmids\": [\"7768993\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Downstream signaling consequence of FGF binding not established here\", \"Whether binding occurs in Golgi or at surface unresolved\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Reconciled the Golgi-resident and ligand identities by showing GLG1 also localizes to cell-surface microvilli, positioning it for leukocyte–endothelial contact.\",\n      \"evidence\": \"Immunofluorescence, surface biotinylation, surface immunoprecipitation, and immunogold SEM in 32Dc13 cells and neutrophils\",\n      \"pmids\": [\"9099943\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism partitioning Golgi vs surface pools not yet defined\", \"Functional necessity of microvillar localization untested\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Revealed a third activity — complex formation with TGF-β1 latency-associated peptide — establishing GLG1 as a component of secreted latent TGF-β complexes.\",\n      \"evidence\": \"Biochemical purification, amino acid sequencing, and immunoprecipitation of LTCP-1/TGF-β1 in CHO cells\",\n      \"pmids\": [\"9182700\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological consequence for TGF-β signaling not addressed\", \"Binding interface on GLG1 not mapped\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Identified the cytoplasmic tail as the localization determinant by showing an alternatively spliced isoform (GLG2) with a divergent tail retains the protein in the Golgi, whereas the GLG1 tail targets the surface.\",\n      \"evidence\": \"cDNA cloning, chimeric cytoplasmic-domain transfection in HEK293, and Northern blot\",\n      \"pmids\": [\"15797922\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Trafficking machinery recognizing each tail unknown\", \"Relative abundance of isoforms in vivo not quantified\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Assigned GLG1 a non-redundant step in leukocyte adhesion — converting E-selectin tethers to slow rolling — distinct from PSGL-1 and CD44.\",\n      \"evidence\": \"Knockout and siRNA loss-of-function with intravital microscopy and combined-knockout epistasis\",\n      \"pmids\": [\"17442598\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular signaling triggered by GLG1–E-selectin engagement not defined\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Extended E-selectin ligand function to hepatic stellate cells and raised shedding as a possible regulatory mechanism.\",\n      \"evidence\": \"Flow cytometry, CFR cDNA transfection, secreted binding-activity assay, and qRT-PCR under hypoxia\",\n      \"pmids\": [\"19148508\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Shedding inferred from supernatant activity, not directly demonstrated\", \"Single lab, expression-focused\", \"Hypoxic regulation mechanism unclear\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Mapped two opposing localization signals and connected surface display to function by showing a GPI-anchored surface form modulates FGF18/FGFR3c signaling.\",\n      \"evidence\": \"Mutagenesis, chimeric GPI-anchored constructs, fractionation, and FGF18 signaling assays in Ba/F3 cells\",\n      \"pmids\": [\"21777203\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Endogenous balance of the two signals not quantified\", \"Direct effect on FGFR3c phosphorylation not detailed\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Established the in vivo division of labor between GLG1 and PSGL-1 — GLG1 dominant for progenitor homing, PSGL-1 for mature neutrophils.\",\n      \"evidence\": \"Single and double knockout mice, flow cytometry, intravital microscopy, bone marrow transplantation\",\n      \"pmids\": [\"24106206\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Cell-type basis of the dominance switch not mechanistically explained\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Demonstrated a cell-intrinsic, E-selectin-independent role for GLG1 in limiting TGF-β in the HSPC niche, with TGF-β blockade rescuing the phenotype.\",\n      \"evidence\": \"Knockout mice, transplantation, TGF-β cytokine measurement, and in vivo/in vitro TGF-β blockade\",\n      \"pmids\": [\"26742601\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular step by which GLG1 restrains TGF-β production not defined\", \"Relation to the LAP complex from 1997 not directly tested\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identified adiponectin as a new GLG1 binding partner and mapped the interaction to five N-terminal extracellular residues, linking GLG1 to anti-adhesive signaling.\",\n      \"evidence\": \"Anti-adiponectin IP/mass spectrometry, serial mutagenesis, shRNA knockdown, and monocyte–endothelial adhesion assays\",\n      \"pmids\": [\"26792720\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Knockdown only partially abrogated the effect\", \"Downstream signaling pathway unresolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Showed that FUT3-mediated Lewis-a glycosylation at defined N-glycosites controls GLG1 vesicle distribution and supports gastric cancer cell migration and invasion.\",\n      \"evidence\": \"Lea-antibody capture mass spectrometry, immunofluorescence, siRNA of GLG1 and FUT3, migration/invasion assays\",\n      \"pmids\": [\"39477144\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Causal link between glycosylation, localization, and invasion not fully separated\", \"Single cancer model\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identified an upstream post-transcriptional control point, with FTO-mediated m6A demethylation stabilizing GLG1 mRNA and promoting gastric cancer aggressiveness.\",\n      \"evidence\": \"FTO and GLG1 knockdown in vitro and in xenografts, western blot, qRT-PCR, m6A analysis\",\n      \"pmids\": [\"41287415\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"m6A sites on GLG1 mRNA not mapped\", \"Knockdown-based, single lab\", \"Mechanism of stability change unspecified\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How GLG1 mechanistically restrains TGF-β production in the niche, and whether its Golgi FGF-binding and surface E-selectin/adiponectin roles are coordinately regulated by a single trafficking switch, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of GLG1 with any ligand\", \"Integration of multiple ligand activities into one regulatory logic unestablished\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098631\", \"supporting_discovery_ids\": [0, 5, 8]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2, 4, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [1, 3, 6, 7]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [3, 7]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [14]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [0, 5, 8]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 7, 9]}\n    ],\n    \"complexes\": [\"latent TGF-\\u03b21 (LAP) complex\"],\n    \"partners\": [\"SELE\", \"FGF2\", \"FGF18\", \"FGFR3\", \"TGFB1\", \"ADIPOQ\", \"FUT3\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}