{"gene":"SEC24B","run_date":"2026-06-10T07:46:30","timeline":{"discoveries":[{"year":2008,"finding":"Crystal structures of all four human SEC24 isoforms revealed that the IxM packaging signal binds in a surface groove of SEC24C and SEC24D, but this groove is occluded in SEC24A and SEC24B. Conversely, LxxLE class transport signals and the DxE signal of VSV glycoprotein are selectively bound by SEC24A and SEC24B. This structural analysis established the molecular basis for cargo discrimination among human COPII SEC24 subunits.","method":"X-ray crystallography combined with biochemical binding assays and functional COPII vesicle packaging assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structures of all four isoforms with functional validation via vesicle packaging assays, single rigorous study with multiple orthogonal methods","pmids":["18843296"],"is_preprint":false},{"year":2009,"finding":"SEC24B selectively sorts Vangl2 (a core planar cell polarity component) into COPII vesicles for ER-to-Golgi transport. The SEC24B Y613 mutant mouse exhibits craniorachischisis, convergent extension defects, and other PCP phenotypes. Vangl2 looptail point mutants (D255E and S464N) fail to sort into COPII vesicles and are trapped in the ER, and SEC24B Y613 genetically interacts with loss-of-function Vangl2 allele to increase spina bifida prevalence.","method":"Forward genetic screen in mice, COPII vesicle budding assays, genetic epistasis (double mutant analysis), ER retention assays in cultured cells","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal genetic interaction, direct cargo sorting assay, replicated by independent lab (PMID:20215345), multiple orthogonal methods","pmids":["19966784"],"is_preprint":false},{"year":2010,"finding":"Independent confirmation that SEC24B deficiency specifically impairs trafficking of the PCP core protein Vangl2 in vivo. SEC24B mutant mice display craniorachischisis, abnormal outflow tract vessel arrangement, and cochlear defects, and genetic interaction with the PCP gene scribble was demonstrated.","method":"ENU mutagenesis screen, analysis of Sec24b mutant mouse embryos and primary cells, genetic interaction with scribble","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 2 / Strong — independent replication of Vangl2 trafficking by SEC24B across two labs (PMID:19966784 and PMID:20215345) with consistent cellular and in vivo phenotypes","pmids":["20215345"],"is_preprint":false},{"year":2007,"finding":"Knockdown of SEC24B alone preferentially impairs di-leucine signal-mediated ER export of ERGIC-53. Double knockdown of SEC24B with SEC24C or SEC24D preferentially affected di-leucine-mediated transport. In vitro binding preferences of transport signals correlated with isoform-selective transport effects.","method":"siRNA-mediated knockdown of individual and pairs of SEC24 isoforms; in vitro binding assays of transport signals to SEC24 isoforms","journal":"EMBO reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal methods (knockdown functional assay + in vitro binding), single lab","pmids":["17255961"],"is_preprint":false},{"year":2013,"finding":"Human SEC24B mutations (p.Phe227Ser, p.Phe682Leu, p.Arg1248Gln, p.Ala1251Gly) found in NTD patients impair SEC24B protein stability and/or physical interaction with VANGL2 (co-IP), affect VANGL2 subcellular localization in cultured cells, and display loss-of-function effects in zebrafish overexpression/rescue assays.","method":"Co-immunoprecipitation, subcellular localization assays in cultured cells, zebrafish overexpression and dosage-dependent rescue","journal":"Human mutation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal functional evidence in two model systems (cell culture + zebrafish) with multiple mutant alleles, single lab","pmids":["23592378"],"is_preprint":false},{"year":2013,"finding":"SEC24A and SEC24B show partial overlap in cargo selectivity. SEC24A-deficient mice exhibit markedly reduced plasma cholesterol due to selective dependence of PCSK9 on SEC24A for ER exit; residual secretion implies partial SEC24B redundancy for some cargoes. Mutations in Apoe and Ldlr are epistatic to Sec24a, placing PCSK9/LDLR regulation downstream of SEC24A.","method":"Genetic deficiency mouse model, epistasis with Apoe and Ldlr mutations, hepatocyte fractionation and LDLR/PCSK9 measurements","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis plus biochemical measurements of cargo, single lab, SEC24B involvement inferred from overlap rather than direct assay","pmids":["23580231"],"is_preprint":false},{"year":2018,"finding":"Upon nutrient starvation, ULK1-phosphorylated (pSer186) SEC23B associates with SEC24A and SEC24B (but not SEC24C or SEC24D) and re-localizes to the ER-Golgi intermediate compartment, promoting autophagic flux. FBXW5 targets SEC23B for proteasomal degradation in nutrient-replete conditions, limiting COPII-mediated autophagosome biogenesis.","method":"Co-immunoprecipitation of SEC23B with SEC24 isoforms, phosphorylation site mutagenesis, autophagy flux assays, ULK1 kinase assays","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP with isoform specificity and phosphorylation mutagenesis, single lab","pmids":["30596474"],"is_preprint":false},{"year":2016,"finding":"EGF stimulation increases ER-to-plasma membrane transport of newly synthesized EGFR, coinciding with transcriptional up-regulation of SEC23B, SEC24B, and SEC24D by the endosomal transcriptional regulator RNF11. Knockdown experiments showed that SEC24B (and SEC24D) are specifically required for EGFR transport.","method":"siRNA knockdown, pulse-chase transport assays, RUSH system, transcriptional reporter assays","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — knockdown with defined transport phenotype plus transcriptional mechanism, single lab, two orthogonal methods","pmids":["27872256"],"is_preprint":false},{"year":2020,"finding":"SEC24A, SEC24B, and SEC24C (but not SEC24D) knockdown reduces secretion of full-length PCSK9 from human hepatocytes; this reduction is not observed with a PCSK9 C-terminal deletion mutant (PCSK91-446), indicating that SEC24B (along with SEC24A/C) facilitates PCSK9 secretion through recognition of the C-terminal domain.","method":"siRNA knockdown of individual SEC24 isoforms in hepatocytes, PCSK9 secretion assays with wild-type and deletion mutants","journal":"Biochimica et biophysica acta. Molecular and cell biology of lipids","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple isoform-specific knockdowns with mutant cargo dissection, single lab","pmids":["32058034"],"is_preprint":false},{"year":2021,"finding":"Manipulation of the cargo-binding domain in COPII SEC24B prohibits cargo accumulation at ER exit sites (ERES). Live-cell and electron microscopy showed that the COPII coat (including SEC24B) remains bound to the ER-ERES boundary during protein export rather than coating Golgi-bound carriers, establishing SEC24B's role in concentrating cargo at ERES.","method":"CRISPR/Cas12a endogenous tagging, live-cell microscopy, RUSH system, pharmaceutical and genetic perturbations of ER-Golgi transport, electron microscopy","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (live imaging, EM, genetic perturbation) in single study, single lab","pmids":["33852719"],"is_preprint":false},{"year":2020,"finding":"BMP2K splicing variants interact with SEC16A and differentially regulate distribution of SEC24B and abundance of SEC31A at COPII assemblies; SEC24B-positive assemblies are specifically affected by BMP2K isoforms, linking SEC24B to autophagy regulation in erythroid cells.","method":"Co-immunoprecipitation of BMP2K with SEC16A, variant-specific siRNA depletion, fluorescence microscopy of COPII assemblies","journal":"eLife","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP and localization data, SEC24B involvement inferred from assembly marker analysis, single lab","pmids":["32795391"],"is_preprint":false},{"year":2022,"finding":"A genome-wide CRISPR screen in iPSC-derived microglia identified SEC24B as a novel regulator of ferroptosis. Loss of SEC24B function modifies the iron-overload-induced ferroptotic response in microglia, placing SEC24B in the vesicle trafficking pathway that controls microglial iron homeostasis.","method":"Genome-wide CRISPR screen in iPSC-derived microglia tri-culture system with iron overload/ferroptosis as phenotypic readout","journal":"Nature neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide CRISPR screen with defined cellular phenotype (ferroptosis), single lab, mechanistic follow-up limited in abstract","pmids":["36536241"],"is_preprint":false},{"year":2025,"finding":"During DNA viral infection, LUBAC-mediated linear ubiquitination of STING promotes its trafficking from the ER to the Golgi through binding to SEC24B of the COPII complex. OTULIN subsequently removes linear ubiquitin chains to limit excessive antiviral signaling, identifying SEC24B as the COPII adaptor that recognizes linearly ubiquitinated STING for ER export.","method":"Co-immunoprecipitation of ubiquitinated STING with SEC24B, LUBAC/OTULIN gain- and loss-of-function, STING trafficking assays","journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP of modified STING with SEC24B plus functional trafficking assay, single lab, two orthogonal methods","pmids":["40536345"],"is_preprint":false},{"year":2025,"finding":"SEC24B inner coat protein is biochemically isolated in association with HPV16 capsid proteins, and silencing of SEC24B inhibits HPV infection, implicating SEC24B-containing COPII vesicles in post-Golgi HPV trafficking.","method":"Biochemical pulldown/co-isolation of HPV capsid with SEC24B; siRNA knockdown with HPV pseudovirus infection assay","journal":"Viruses","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single pulldown and knockdown experiment, single lab, limited mechanistic resolution","pmids":["40431628"],"is_preprint":false},{"year":2023,"finding":"SEC24B knockdown abolishes HDAC-inhibitor (TSA/NaB)-induced secretion of PEDV virions via COPII-coated vesicles, demonstrating that SEC24B is required for COPII-mediated ER budding of PEDV particles.","method":"siRNA knockdown of SEC24B, PEDV secretion assays, colocalization by fluorescence microscopy, ultrastructural EM","journal":"Viruses","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single knockdown with viral secretion readout, single lab, no direct cargo-binding evidence","pmids":["37766280"],"is_preprint":false}],"current_model":"SEC24B is a cargo-selective subunit of the COPII vesicle coat that preferentially binds LxxLE and DxE transport signals (but not IxM signals, whose binding site is occluded) to recruit specific transmembrane cargoes—most notably Vangl2 for planar cell polarity signaling and PCSK9—into ER-derived transport vesicles; it concentrates cargo at ER exit sites rather than coating anterograde carriers, and it also serves as the COPII adaptor recognized by linearly ubiquitinated STING during innate immune signaling, with its loss causing neural tube closure defects in mice due to impaired Vangl2 trafficking and additionally modulating ferroptosis in microglia."},"narrative":{"mechanistic_narrative":"SEC24B is a cargo-selective subunit of the COPII vesicle coat that recognizes specific transport signals to concentrate transmembrane cargoes at endoplasmic reticulum exit sites for anterograde transport [PMID:18843296, PMID:33852719]. Crystal structures of all four human SEC24 isoforms established the structural basis for cargo discrimination: SEC24B selectively binds LxxLE-class transport signals and the DxE signal, whereas the IxM-binding groove used by SEC24C/D is occluded in SEC24B [PMID:18843296]. A defining function of SEC24B is the selective sorting of the planar cell polarity protein Vangl2 into COPII vesicles; loss of SEC24B activity traps Vangl2 in the ER and causes neural tube closure defects, with the Y613 mutant mouse exhibiting craniorachischisis and genetic interactions with Vangl2 and scribble [PMID:19966784, PMID:20215345]. Human SEC24B mutations found in neural tube defect patients impair SEC24B stability and its physical interaction with VANGL2 [PMID:23592378]. Beyond Vangl2, SEC24B contributes to ER export of additional cargoes including ERGIC-53 via di-leucine signals [PMID:17255961], EGFR [PMID:27872256], and PCSK9 through recognition of its C-terminal domain [PMID:32058034]. SEC24B also serves as the COPII adaptor that recognizes linearly ubiquitinated STING to promote its ER-to-Golgi trafficking during antiviral signaling [PMID:40536345], and participates in starvation-induced autophagy through phosphorylated SEC23B association at the ER-Golgi intermediate compartment [PMID:30596474]. A genome-wide CRISPR screen additionally identified SEC24B as a regulator of iron-overload-induced ferroptosis in microglia [PMID:36536241].","teleology":[{"year":2007,"claim":"Established that SEC24 isoforms are functionally non-redundant by showing SEC24B preferentially supports a distinct class of transport signals, defining isoform-specific cargo selectivity.","evidence":"siRNA knockdown of individual and paired SEC24 isoforms with in vitro transport-signal binding assays","pmids":["17255961"],"confidence":"Medium","gaps":["Did not resolve the structural basis of signal discrimination","Single lab, limited cargo panel"]},{"year":2008,"claim":"Resolved the molecular basis of cargo discrimination among SEC24 isoforms, explaining why SEC24B binds LxxLE/DxE signals but not IxM signals.","evidence":"X-ray crystallography of all four human SEC24 isoforms with biochemical binding and vesicle packaging assays","pmids":["18843296"],"confidence":"High","gaps":["Structures of full coat assembly with physiological cargo not resolved","Did not address in vivo cargo specificity"]},{"year":2009,"claim":"Identified Vangl2 as a physiological SEC24B cargo and linked SEC24B to planar cell polarity and neural tube closure, connecting COPII cargo selection to a developmental phenotype.","evidence":"Forward genetic screen in mice, COPII budding assays, genetic epistasis with Vangl2, ER retention assays","pmids":["19966784"],"confidence":"High","gaps":["Did not map the exact Vangl2 signal recognized by SEC24B","Full set of SEC24B-dependent PCP cargoes unknown"]},{"year":2010,"claim":"Independently confirmed SEC24B-dependent Vangl2 trafficking and its developmental consequences, strengthening the in vivo cargo assignment.","evidence":"ENU mutagenesis screen with mutant mouse embryo and primary cell analysis, genetic interaction with scribble","pmids":["20215345"],"confidence":"High","gaps":["Mechanism of genetic interaction with scribble not defined at molecular level"]},{"year":2013,"claim":"Extended SEC24B-Vangl2 biology to human disease by showing patient mutations impair SEC24B stability and VANGL2 binding, supporting a causal role in neural tube defects.","evidence":"Co-IP, subcellular localization in cultured cells, zebrafish overexpression/rescue with multiple mutant alleles","pmids":["23592378"],"confidence":"Medium","gaps":["Causality in human NTD population not established by family segregation","Single lab"]},{"year":2013,"claim":"Demonstrated partial overlap between SEC24A and SEC24B cargo handling, with PCSK9 export revealing functional redundancy among paralogs.","evidence":"SEC24A-deficient mouse model, epistasis with Apoe and Ldlr, hepatocyte fractionation and cargo measurements","pmids":["23580231"],"confidence":"Medium","gaps":["SEC24B contribution inferred from residual secretion rather than direct assay","Extent of redundancy per cargo undefined"]},{"year":2016,"claim":"Placed SEC24B in regulated receptor trafficking by showing it is transcriptionally induced and required for EGFR ER export upon EGF stimulation.","evidence":"siRNA knockdown, pulse-chase transport assays, RUSH system, transcriptional reporters","pmids":["27872256"],"confidence":"Medium","gaps":["Direct EGFR-SEC24B binding not demonstrated","Signal recognized on EGFR unidentified"]},{"year":2018,"claim":"Connected SEC24B to autophagy through nutrient-regulated, ULK1-phosphorylated SEC23B association at the ERGIC, defining a context where COPII components support autophagosome biogenesis.","evidence":"Reciprocal Co-IP with isoform specificity, phosphorylation site mutagenesis, autophagy flux and ULK1 kinase assays","pmids":["30596474"],"confidence":"Medium","gaps":["Specific cargo carried by SEC24B in autophagy not identified","Single lab"]},{"year":2020,"claim":"Dissected the PCSK9 secretion requirement, showing SEC24B (with SEC24A/C) acts through the PCSK9 C-terminal domain.","evidence":"Isoform-specific siRNA knockdowns in hepatocytes with wild-type and C-terminal deletion cargo","pmids":["32058034"],"confidence":"Medium","gaps":["Direct binding of SEC24B to the PCSK9 C-terminus not shown","Relative isoform contribution not quantified"]},{"year":2020,"claim":"Linked SEC24B-positive COPII assemblies to autophagy regulation in erythroid cells via BMP2K and SEC16A.","evidence":"Co-IP of BMP2K with SEC16A, variant-specific siRNA, fluorescence microscopy of COPII assemblies","pmids":["32795391"],"confidence":"Low","gaps":["SEC24B involvement inferred from assembly markers rather than direct interaction","Single Co-IP, single lab"]},{"year":2021,"claim":"Refined the spatial model of SEC24B function, showing the coat concentrates cargo at the ER-ERES boundary rather than coating Golgi-bound carriers.","evidence":"CRISPR endogenous tagging, live-cell and electron microscopy, RUSH system, genetic and pharmacological perturbation","pmids":["33852719"],"confidence":"Medium","gaps":["Generalizability across all cargo classes not established","Single lab"]},{"year":2022,"claim":"Identified SEC24B as a regulator of microglial ferroptosis, implicating its trafficking activity in iron homeostasis.","evidence":"Genome-wide CRISPR screen in iPSC-derived microglia tri-culture with iron overload/ferroptosis readout","pmids":["36536241"],"confidence":"Medium","gaps":["Cargo or trafficking event mediating ferroptosis effect unknown","Mechanistic follow-up limited"]},{"year":2025,"claim":"Defined SEC24B as the COPII adaptor recognizing linearly ubiquitinated STING, coupling a ubiquitin mark to ER export in antiviral signaling.","evidence":"Co-IP of ubiquitinated STING with SEC24B, LUBAC/OTULIN gain- and loss-of-function, STING trafficking assays","pmids":["40536345"],"confidence":"Medium","gaps":["Structural basis for recognition of linear ubiquitin by SEC24B not resolved","Single lab"]},{"year":2025,"claim":"Implicated SEC24B-containing COPII vesicles in viral trafficking, extending its cargo repertoire to pathogen components.","evidence":"Biochemical co-isolation of HPV16 capsid with SEC24B and siRNA knockdown with pseudovirus infection assay","pmids":["40431628"],"confidence":"Low","gaps":["Single pulldown and knockdown without binding-site mapping","Mechanistic resolution limited, single lab"]},{"year":null,"claim":"How SEC24B signal-recognition specificity is deployed and regulated across its diverse cargoes (Vangl2, PCSK9, EGFR, STING) and how this connects to ferroptosis remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified structural model of SEC24B binding across distinct cargo classes","Mechanism linking SEC24B trafficking to ferroptosis undefined","Regulation of SEC24B isoform choice per cargo unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0038024","term_label":"cargo receptor activity","supporting_discovery_ids":[0,1,8,12]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,1,9]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[1,9]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[0,9]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,1,9]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[3,7,8]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[6]}],"complexes":["COPII coat"],"partners":["VANGL2","SEC23B","PCSK9","STING1","ERGIC-53","EGFR"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O95487","full_name":"Protein transport protein Sec24B","aliases":["SEC24-related protein B"],"length_aa":1268,"mass_kda":137.4,"function":"Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules for their transport to the Golgi complex (PubMed:17499046, PubMed:18843296, PubMed:20427317). Plays a central role in cargo selection within the COPII complex and together with SEC24A may have a different specificity compared to SEC24C and SEC24D. May package preferentially cargos with cytoplasmic DxE or LxxLE motifs and may also recognize conformational epitopes (PubMed:17499046, PubMed:18843296)","subcellular_location":"Cytoplasmic vesicle, COPII-coated vesicle membrane; Endoplasmic reticulum membrane; Cytoplasm, cytosol","url":"https://www.uniprot.org/uniprotkb/O95487/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SEC24B","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"SEC23A","stoichiometry":10.0},{"gene":"SEC23B","stoichiometry":10.0},{"gene":"STT3B","stoichiometry":10.0},{"gene":"CLTA","stoichiometry":0.2},{"gene":"DDOST","stoichiometry":0.2},{"gene":"OST4","stoichiometry":0.2},{"gene":"RPN1","stoichiometry":0.2},{"gene":"RPN2","stoichiometry":0.2},{"gene":"SEC13","stoichiometry":0.2},{"gene":"YIPF5","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/SEC24B","total_profiled":1310},"omim":[{"mim_id":"607186","title":"SEC24-RELATED GENE FAMILY, MEMBER D; SEC24D","url":"https://www.omim.org/entry/607186"},{"mim_id":"607185","title":"SEC24-RELATED GENE FAMILY, MEMBER C; SEC24C","url":"https://www.omim.org/entry/607185"},{"mim_id":"607184","title":"SEC24-RELATED GENE FAMILY, MEMBER B; SEC24B","url":"https://www.omim.org/entry/607184"},{"mim_id":"607183","title":"SEC24-RELATED GENE FAMILY, MEMBER A; SEC24A","url":"https://www.omim.org/entry/607183"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Vesicles","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SEC24B"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"O95487","domains":[{"cath_id":"2.30.30.380","chopping":"599-659","consensus_level":"medium","plddt":93.2943,"start":599,"end":659},{"cath_id":"3.40.50.410","chopping":"680-917","consensus_level":"high","plddt":95.6418,"start":680,"end":917},{"cath_id":"3.40.20.10","chopping":"1120-1245","consensus_level":"high","plddt":95.971,"start":1120,"end":1245}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O95487","model_url":"https://alphafold.ebi.ac.uk/files/AF-O95487-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O95487-F1-predicted_aligned_error_v6.png","plddt_mean":71.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SEC24B","jax_strain_url":"https://www.jax.org/strain/search?query=SEC24B"},"sequence":{"accession":"O95487","fasta_url":"https://rest.uniprot.org/uniprotkb/O95487.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O95487/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O95487"}},"corpus_meta":[{"pmid":"36536241","id":"PMC_36536241","title":"Microglia 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Conversely, LxxLE class transport signals and the DxE signal of VSV glycoprotein are selectively bound by SEC24A and SEC24B. This structural analysis established the molecular basis for cargo discrimination among human COPII SEC24 subunits.\",\n      \"method\": \"X-ray crystallography combined with biochemical binding assays and functional COPII vesicle packaging assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structures of all four isoforms with functional validation via vesicle packaging assays, single rigorous study with multiple orthogonal methods\",\n      \"pmids\": [\"18843296\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"SEC24B selectively sorts Vangl2 (a core planar cell polarity component) into COPII vesicles for ER-to-Golgi transport. The SEC24B Y613 mutant mouse exhibits craniorachischisis, convergent extension defects, and other PCP phenotypes. Vangl2 looptail point mutants (D255E and S464N) fail to sort into COPII vesicles and are trapped in the ER, and SEC24B Y613 genetically interacts with loss-of-function Vangl2 allele to increase spina bifida prevalence.\",\n      \"method\": \"Forward genetic screen in mice, COPII vesicle budding assays, genetic epistasis (double mutant analysis), ER retention assays in cultured cells\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal genetic interaction, direct cargo sorting assay, replicated by independent lab (PMID:20215345), multiple orthogonal methods\",\n      \"pmids\": [\"19966784\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Independent confirmation that SEC24B deficiency specifically impairs trafficking of the PCP core protein Vangl2 in vivo. SEC24B mutant mice display craniorachischisis, abnormal outflow tract vessel arrangement, and cochlear defects, and genetic interaction with the PCP gene scribble was demonstrated.\",\n      \"method\": \"ENU mutagenesis screen, analysis of Sec24b mutant mouse embryos and primary cells, genetic interaction with scribble\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — independent replication of Vangl2 trafficking by SEC24B across two labs (PMID:19966784 and PMID:20215345) with consistent cellular and in vivo phenotypes\",\n      \"pmids\": [\"20215345\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Knockdown of SEC24B alone preferentially impairs di-leucine signal-mediated ER export of ERGIC-53. Double knockdown of SEC24B with SEC24C or SEC24D preferentially affected di-leucine-mediated transport. In vitro binding preferences of transport signals correlated with isoform-selective transport effects.\",\n      \"method\": \"siRNA-mediated knockdown of individual and pairs of SEC24 isoforms; in vitro binding assays of transport signals to SEC24 isoforms\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal methods (knockdown functional assay + in vitro binding), single lab\",\n      \"pmids\": [\"17255961\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Human SEC24B mutations (p.Phe227Ser, p.Phe682Leu, p.Arg1248Gln, p.Ala1251Gly) found in NTD patients impair SEC24B protein stability and/or physical interaction with VANGL2 (co-IP), affect VANGL2 subcellular localization in cultured cells, and display loss-of-function effects in zebrafish overexpression/rescue assays.\",\n      \"method\": \"Co-immunoprecipitation, subcellular localization assays in cultured cells, zebrafish overexpression and dosage-dependent rescue\",\n      \"journal\": \"Human mutation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal functional evidence in two model systems (cell culture + zebrafish) with multiple mutant alleles, single lab\",\n      \"pmids\": [\"23592378\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"SEC24A and SEC24B show partial overlap in cargo selectivity. SEC24A-deficient mice exhibit markedly reduced plasma cholesterol due to selective dependence of PCSK9 on SEC24A for ER exit; residual secretion implies partial SEC24B redundancy for some cargoes. Mutations in Apoe and Ldlr are epistatic to Sec24a, placing PCSK9/LDLR regulation downstream of SEC24A.\",\n      \"method\": \"Genetic deficiency mouse model, epistasis with Apoe and Ldlr mutations, hepatocyte fractionation and LDLR/PCSK9 measurements\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis plus biochemical measurements of cargo, single lab, SEC24B involvement inferred from overlap rather than direct assay\",\n      \"pmids\": [\"23580231\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Upon nutrient starvation, ULK1-phosphorylated (pSer186) SEC23B associates with SEC24A and SEC24B (but not SEC24C or SEC24D) and re-localizes to the ER-Golgi intermediate compartment, promoting autophagic flux. FBXW5 targets SEC23B for proteasomal degradation in nutrient-replete conditions, limiting COPII-mediated autophagosome biogenesis.\",\n      \"method\": \"Co-immunoprecipitation of SEC23B with SEC24 isoforms, phosphorylation site mutagenesis, autophagy flux assays, ULK1 kinase assays\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP with isoform specificity and phosphorylation mutagenesis, single lab\",\n      \"pmids\": [\"30596474\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"EGF stimulation increases ER-to-plasma membrane transport of newly synthesized EGFR, coinciding with transcriptional up-regulation of SEC23B, SEC24B, and SEC24D by the endosomal transcriptional regulator RNF11. Knockdown experiments showed that SEC24B (and SEC24D) are specifically required for EGFR transport.\",\n      \"method\": \"siRNA knockdown, pulse-chase transport assays, RUSH system, transcriptional reporter assays\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — knockdown with defined transport phenotype plus transcriptional mechanism, single lab, two orthogonal methods\",\n      \"pmids\": [\"27872256\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"SEC24A, SEC24B, and SEC24C (but not SEC24D) knockdown reduces secretion of full-length PCSK9 from human hepatocytes; this reduction is not observed with a PCSK9 C-terminal deletion mutant (PCSK91-446), indicating that SEC24B (along with SEC24A/C) facilitates PCSK9 secretion through recognition of the C-terminal domain.\",\n      \"method\": \"siRNA knockdown of individual SEC24 isoforms in hepatocytes, PCSK9 secretion assays with wild-type and deletion mutants\",\n      \"journal\": \"Biochimica et biophysica acta. Molecular and cell biology of lipids\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple isoform-specific knockdowns with mutant cargo dissection, single lab\",\n      \"pmids\": [\"32058034\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Manipulation of the cargo-binding domain in COPII SEC24B prohibits cargo accumulation at ER exit sites (ERES). Live-cell and electron microscopy showed that the COPII coat (including SEC24B) remains bound to the ER-ERES boundary during protein export rather than coating Golgi-bound carriers, establishing SEC24B's role in concentrating cargo at ERES.\",\n      \"method\": \"CRISPR/Cas12a endogenous tagging, live-cell microscopy, RUSH system, pharmaceutical and genetic perturbations of ER-Golgi transport, electron microscopy\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (live imaging, EM, genetic perturbation) in single study, single lab\",\n      \"pmids\": [\"33852719\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"BMP2K splicing variants interact with SEC16A and differentially regulate distribution of SEC24B and abundance of SEC31A at COPII assemblies; SEC24B-positive assemblies are specifically affected by BMP2K isoforms, linking SEC24B to autophagy regulation in erythroid cells.\",\n      \"method\": \"Co-immunoprecipitation of BMP2K with SEC16A, variant-specific siRNA depletion, fluorescence microscopy of COPII assemblies\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP and localization data, SEC24B involvement inferred from assembly marker analysis, single lab\",\n      \"pmids\": [\"32795391\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"A genome-wide CRISPR screen in iPSC-derived microglia identified SEC24B as a novel regulator of ferroptosis. Loss of SEC24B function modifies the iron-overload-induced ferroptotic response in microglia, placing SEC24B in the vesicle trafficking pathway that controls microglial iron homeostasis.\",\n      \"method\": \"Genome-wide CRISPR screen in iPSC-derived microglia tri-culture system with iron overload/ferroptosis as phenotypic readout\",\n      \"journal\": \"Nature neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide CRISPR screen with defined cellular phenotype (ferroptosis), single lab, mechanistic follow-up limited in abstract\",\n      \"pmids\": [\"36536241\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"During DNA viral infection, LUBAC-mediated linear ubiquitination of STING promotes its trafficking from the ER to the Golgi through binding to SEC24B of the COPII complex. OTULIN subsequently removes linear ubiquitin chains to limit excessive antiviral signaling, identifying SEC24B as the COPII adaptor that recognizes linearly ubiquitinated STING for ER export.\",\n      \"method\": \"Co-immunoprecipitation of ubiquitinated STING with SEC24B, LUBAC/OTULIN gain- and loss-of-function, STING trafficking assays\",\n      \"journal\": \"Advanced science (Weinheim, Baden-Wurttemberg, Germany)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP of modified STING with SEC24B plus functional trafficking assay, single lab, two orthogonal methods\",\n      \"pmids\": [\"40536345\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SEC24B inner coat protein is biochemically isolated in association with HPV16 capsid proteins, and silencing of SEC24B inhibits HPV infection, implicating SEC24B-containing COPII vesicles in post-Golgi HPV trafficking.\",\n      \"method\": \"Biochemical pulldown/co-isolation of HPV capsid with SEC24B; siRNA knockdown with HPV pseudovirus infection assay\",\n      \"journal\": \"Viruses\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single pulldown and knockdown experiment, single lab, limited mechanistic resolution\",\n      \"pmids\": [\"40431628\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SEC24B knockdown abolishes HDAC-inhibitor (TSA/NaB)-induced secretion of PEDV virions via COPII-coated vesicles, demonstrating that SEC24B is required for COPII-mediated ER budding of PEDV particles.\",\n      \"method\": \"siRNA knockdown of SEC24B, PEDV secretion assays, colocalization by fluorescence microscopy, ultrastructural EM\",\n      \"journal\": \"Viruses\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single knockdown with viral secretion readout, single lab, no direct cargo-binding evidence\",\n      \"pmids\": [\"37766280\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SEC24B is a cargo-selective subunit of the COPII vesicle coat that preferentially binds LxxLE and DxE transport signals (but not IxM signals, whose binding site is occluded) to recruit specific transmembrane cargoes—most notably Vangl2 for planar cell polarity signaling and PCSK9—into ER-derived transport vesicles; it concentrates cargo at ER exit sites rather than coating anterograde carriers, and it also serves as the COPII adaptor recognized by linearly ubiquitinated STING during innate immune signaling, with its loss causing neural tube closure defects in mice due to impaired Vangl2 trafficking and additionally modulating ferroptosis in microglia.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SEC24B is a cargo-selective subunit of the COPII vesicle coat that recognizes specific transport signals to concentrate transmembrane cargoes at endoplasmic reticulum exit sites for anterograde transport [#0, #9]. Crystal structures of all four human SEC24 isoforms established the structural basis for cargo discrimination: SEC24B selectively binds LxxLE-class transport signals and the DxE signal, whereas the IxM-binding groove used by SEC24C/D is occluded in SEC24B [#0]. A defining function of SEC24B is the selective sorting of the planar cell polarity protein Vangl2 into COPII vesicles; loss of SEC24B activity traps Vangl2 in the ER and causes neural tube closure defects, with the Y613 mutant mouse exhibiting craniorachischisis and genetic interactions with Vangl2 and scribble [#1, #2]. Human SEC24B mutations found in neural tube defect patients impair SEC24B stability and its physical interaction with VANGL2 [#4]. Beyond Vangl2, SEC24B contributes to ER export of additional cargoes including ERGIC-53 via di-leucine signals [#3], EGFR [#7], and PCSK9 through recognition of its C-terminal domain [#8]. SEC24B also serves as the COPII adaptor that recognizes linearly ubiquitinated STING to promote its ER-to-Golgi trafficking during antiviral signaling [#12], and participates in starvation-induced autophagy through phosphorylated SEC23B association at the ER-Golgi intermediate compartment [#6]. A genome-wide CRISPR screen additionally identified SEC24B as a regulator of iron-overload-induced ferroptosis in microglia [#11].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Established that SEC24 isoforms are functionally non-redundant by showing SEC24B preferentially supports a distinct class of transport signals, defining isoform-specific cargo selectivity.\",\n      \"evidence\": \"siRNA knockdown of individual and paired SEC24 isoforms with in vitro transport-signal binding assays\",\n      \"pmids\": [\"17255961\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not resolve the structural basis of signal discrimination\", \"Single lab, limited cargo panel\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Resolved the molecular basis of cargo discrimination among SEC24 isoforms, explaining why SEC24B binds LxxLE/DxE signals but not IxM signals.\",\n      \"evidence\": \"X-ray crystallography of all four human SEC24 isoforms with biochemical binding and vesicle packaging assays\",\n      \"pmids\": [\"18843296\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structures of full coat assembly with physiological cargo not resolved\", \"Did not address in vivo cargo specificity\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Identified Vangl2 as a physiological SEC24B cargo and linked SEC24B to planar cell polarity and neural tube closure, connecting COPII cargo selection to a developmental phenotype.\",\n      \"evidence\": \"Forward genetic screen in mice, COPII budding assays, genetic epistasis with Vangl2, ER retention assays\",\n      \"pmids\": [\"19966784\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not map the exact Vangl2 signal recognized by SEC24B\", \"Full set of SEC24B-dependent PCP cargoes unknown\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Independently confirmed SEC24B-dependent Vangl2 trafficking and its developmental consequences, strengthening the in vivo cargo assignment.\",\n      \"evidence\": \"ENU mutagenesis screen with mutant mouse embryo and primary cell analysis, genetic interaction with scribble\",\n      \"pmids\": [\"20215345\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of genetic interaction with scribble not defined at molecular level\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Extended SEC24B-Vangl2 biology to human disease by showing patient mutations impair SEC24B stability and VANGL2 binding, supporting a causal role in neural tube defects.\",\n      \"evidence\": \"Co-IP, subcellular localization in cultured cells, zebrafish overexpression/rescue with multiple mutant alleles\",\n      \"pmids\": [\"23592378\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Causality in human NTD population not established by family segregation\", \"Single lab\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Demonstrated partial overlap between SEC24A and SEC24B cargo handling, with PCSK9 export revealing functional redundancy among paralogs.\",\n      \"evidence\": \"SEC24A-deficient mouse model, epistasis with Apoe and Ldlr, hepatocyte fractionation and cargo measurements\",\n      \"pmids\": [\"23580231\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"SEC24B contribution inferred from residual secretion rather than direct assay\", \"Extent of redundancy per cargo undefined\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Placed SEC24B in regulated receptor trafficking by showing it is transcriptionally induced and required for EGFR ER export upon EGF stimulation.\",\n      \"evidence\": \"siRNA knockdown, pulse-chase transport assays, RUSH system, transcriptional reporters\",\n      \"pmids\": [\"27872256\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct EGFR-SEC24B binding not demonstrated\", \"Signal recognized on EGFR unidentified\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Connected SEC24B to autophagy through nutrient-regulated, ULK1-phosphorylated SEC23B association at the ERGIC, defining a context where COPII components support autophagosome biogenesis.\",\n      \"evidence\": \"Reciprocal Co-IP with isoform specificity, phosphorylation site mutagenesis, autophagy flux and ULK1 kinase assays\",\n      \"pmids\": [\"30596474\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Specific cargo carried by SEC24B in autophagy not identified\", \"Single lab\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Dissected the PCSK9 secretion requirement, showing SEC24B (with SEC24A/C) acts through the PCSK9 C-terminal domain.\",\n      \"evidence\": \"Isoform-specific siRNA knockdowns in hepatocytes with wild-type and C-terminal deletion cargo\",\n      \"pmids\": [\"32058034\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct binding of SEC24B to the PCSK9 C-terminus not shown\", \"Relative isoform contribution not quantified\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Linked SEC24B-positive COPII assemblies to autophagy regulation in erythroid cells via BMP2K and SEC16A.\",\n      \"evidence\": \"Co-IP of BMP2K with SEC16A, variant-specific siRNA, fluorescence microscopy of COPII assemblies\",\n      \"pmids\": [\"32795391\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"SEC24B involvement inferred from assembly markers rather than direct interaction\", \"Single Co-IP, single lab\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Refined the spatial model of SEC24B function, showing the coat concentrates cargo at the ER-ERES boundary rather than coating Golgi-bound carriers.\",\n      \"evidence\": \"CRISPR endogenous tagging, live-cell and electron microscopy, RUSH system, genetic and pharmacological perturbation\",\n      \"pmids\": [\"33852719\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Generalizability across all cargo classes not established\", \"Single lab\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified SEC24B as a regulator of microglial ferroptosis, implicating its trafficking activity in iron homeostasis.\",\n      \"evidence\": \"Genome-wide CRISPR screen in iPSC-derived microglia tri-culture with iron overload/ferroptosis readout\",\n      \"pmids\": [\"36536241\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cargo or trafficking event mediating ferroptosis effect unknown\", \"Mechanistic follow-up limited\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined SEC24B as the COPII adaptor recognizing linearly ubiquitinated STING, coupling a ubiquitin mark to ER export in antiviral signaling.\",\n      \"evidence\": \"Co-IP of ubiquitinated STING with SEC24B, LUBAC/OTULIN gain- and loss-of-function, STING trafficking assays\",\n      \"pmids\": [\"40536345\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis for recognition of linear ubiquitin by SEC24B not resolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Implicated SEC24B-containing COPII vesicles in viral trafficking, extending its cargo repertoire to pathogen components.\",\n      \"evidence\": \"Biochemical co-isolation of HPV16 capsid with SEC24B and siRNA knockdown with pseudovirus infection assay\",\n      \"pmids\": [\"40431628\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single pulldown and knockdown without binding-site mapping\", \"Mechanistic resolution limited, single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SEC24B signal-recognition specificity is deployed and regulated across its diverse cargoes (Vangl2, PCSK9, EGFR, STING) and how this connects to ferroptosis remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified structural model of SEC24B binding across distinct cargo classes\", \"Mechanism linking SEC24B trafficking to ferroptosis undefined\", \"Regulation of SEC24B isoform choice per cargo unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0038024\", \"supporting_discovery_ids\": [0, 1, 8, 12]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 1, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [1, 9]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [0, 9]},\n      {\"term_id\": \"GO:0005793\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 1, 9]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [3, 7, 8]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"complexes\": [\"COPII coat\"],\n    \"partners\": [\"VANGL2\", \"SEC23B\", \"PCSK9\", \"STING1\", \"ERGIC-53\", \"EGFR\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}