{"gene":"SEC24B","run_date":"2026-04-28T20:42:07","timeline":{"discoveries":[{"year":2009,"finding":"SEC24B selectively sorts Vangl2 (a core PCP component) into COPII vesicles for ER-to-Golgi transport; the Vangl2 looptail point mutants D255E and S464N fail to be sorted by SEC24B and are trapped in the ER. Sec24b(Y613) mutant mice exhibit craniorachischisis and convergent extension defects, and genetically interact with Vangl2(LP) loss-of-function allele, placing SEC24B in the PCP pathway upstream of neural tube closure.","method":"Forward genetic screen in mice; COPII vesicle budding assays; genetic epistasis (Sec24b × Vangl2LP double mutants); analysis of looptail Vangl2 mutant sorting","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods (in vivo genetics, vesicle budding assays, epistasis), replicated by independent lab","pmids":["19966784"],"is_preprint":false},{"year":2010,"finding":"SEC24B deficiency in mice specifically impairs ER-to-Golgi transport of the PCP protein Vangl2, confirmed in embryos and cultured primary cells; Sec24b mutant mice exhibit craniorachischisis, cochlear disorganization, and outflow tract vessel abnormalities consistent with PCP disruption, and genetically interact with scribble.","method":"Mouse ENU mutagenesis; Vangl2 localization in Sec24b-null embryos and primary cells; genetic interaction with scribble","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 2 — independent replication of Sec24b–Vangl2 trafficking relationship with cellular and genetic evidence","pmids":["20215345"],"is_preprint":false},{"year":2008,"finding":"Crystal structures of all four human SEC24 isoforms revealed that a conserved IxM packaging signal binds a surface groove in SEC24C and SEC24D but is occluded in SEC24A and SEC24B; conversely, LxxLE class signals and the DxE signal of VSV-G are selectively bound by SEC24A and SEC24B, establishing structural determinants for cargo discrimination.","method":"X-ray crystallography of all four human SEC24 isoforms; biochemical binding assays; functional COPII vesicle packaging assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 — crystal structures combined with biochemical and functional vesicle packaging assays","pmids":["18843296"],"is_preprint":false},{"year":2007,"finding":"SEC24B participates in signal-mediated ER export of transmembrane proteins; double knockdown of SEC24B/C or SEC24B/D preferentially impairs di-leucine-mediated transport, and in vitro binding assays show isoform-selective binding preferences for cytosolic ER export signals.","method":"siRNA knockdown of individual and pairs of SEC24 isoforms; ERGIC-53 transport assays; in vitro signal-binding assays","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 2 — multiple isoform knockdowns combined with in vitro binding assays and functional transport readouts","pmids":["17255961"],"is_preprint":false},{"year":1999,"finding":"SEC24B was identified as one of four mammalian Sec24 paralogs; it forms a subclass with SEC24A (~50% identity) and co-localizes with SEC13, another COPII component, at ER-Golgi boundary membranes, indicating its incorporation into COPII structures.","method":"Molecular cloning; Northern blot; co-localization of myc-tagged SEC24 with SEC13 by fluorescence microscopy","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 3 — co-localization without functional follow-up, foundational identification paper","pmids":["10329445"],"is_preprint":false},{"year":2013,"finding":"SEC24B shows partial overlap in cargo selectivity with SEC24A; both contribute to efficient ER exit of PCSK9 (a soluble secretory protein), demonstrating that cargo selectivity among SEC24 paralogs extends to soluble as well as transmembrane proteins.","method":"Sec24a knockout mouse; epistasis with Apoe and Ldlr mutations; PCSK9 secretion assays in SEC24A-deficient cells","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 — genetic epistasis and cellular secretion assays, but SEC24B role inferred from partial overlap rather than direct SEC24B knockout","pmids":["23580231"],"is_preprint":false},{"year":2013,"finding":"Four rare missense mutations in SEC24B (p.Phe227Ser, p.Phe682Leu, p.Arg1248Gln, p.Ala1251Gly) found in human NTD cases impair protein stability, physical interaction with VANGL2, and VANGL2 subcellular localization; zebrafish overexpression and rescue studies show loss-of-function effects, confirming SEC24B–VANGL2 interaction is required for neural tube closure.","method":"Human mutation analysis; co-immunoprecipitation; VANGL2 localization assays in cultured cells; zebrafish overexpression and dosage-dependent rescue","journal":"Human mutation","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (co-IP, localization, in vivo zebrafish rescue) across human and model organism systems","pmids":["23592378"],"is_preprint":false},{"year":2018,"finding":"Upon nutrient starvation, ULK1 phosphorylates SEC23B on Ser186, preventing its degradation by FBXW5; stabilized, phosphorylated SEC23B then associates specifically with SEC24A and SEC24B (but not SEC24C or SEC24D) and this complex re-localizes to the ER-Golgi intermediate compartment to promote autophagic flux.","method":"Co-immunoprecipitation; in vitro ULK1 kinase assay; siRNA knockdown; autophagy flux assays; subcellular fractionation","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1–2 — in vitro kinase assay plus multiple co-IPs and functional autophagy assays establishing SEC24B as a selective binding partner of phospho-SEC23B","pmids":["30596474"],"is_preprint":false},{"year":2016,"finding":"SEC23B, SEC24B, and SEC24D are specifically required for ER-to-plasma membrane transport of newly synthesized EGFR; EGF stimulation upregulates these COPII components through the endosomal transcriptional regulator RNF11, linking EGFR degradation to compensatory biosynthetic transport.","method":"siRNA knockdown of individual COPII subunits; EGFR transport assays; RNF11 localization and knockdown","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 — specific knockdown with defined transport readout, but SEC24B role assessed alongside SEC23B and SEC24D","pmids":["27872256"],"is_preprint":false},{"year":2021,"finding":"Manipulation of the cargo-binding domain of COPII SEC24B prohibits cargo accumulation in ER exit sites (ERES); live-cell and EM imaging shows the COPII coat (including SEC24B) remains bound at the ER-ERES boundary rather than coating Golgi-bound carriers, indicating SEC24B functions in concentrating cargo at ERES rather than vesicle coating.","method":"CRISPR/Cas12a tagging; live-cell microscopy (RUSH system); pharmaceutical and genetic perturbation of SEC24B cargo-binding domain; electron microscopy","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods including live imaging, genetic perturbation of active domain, and EM in same study","pmids":["33852719"],"is_preprint":false},{"year":2020,"finding":"SEC24A, SEC24B, and SEC24C (but not SEC24D) facilitate secretion of the full-length endogenous PCSK9 from cultured human hepatocytes; this facilitation is mediated by the C-terminal domain (CTD) of PCSK9, as mutant PCSK9(1-446) lacking the relevant CTD region is insensitive to knockdown of these SEC24 isoforms.","method":"siRNA knockdown of individual SEC24 isoforms; PCSK9 secretion assays in hepatocytes; PCSK9 truncation/deletion mutants","journal":"Biochimica et biophysica acta. Molecular and cell biology of lipids","confidence":"Medium","confidence_rationale":"Tier 2 — isoform-specific knockdown with domain-mapping experiments, single lab","pmids":["32058034"],"is_preprint":false},{"year":2020,"finding":"BMP2K isoforms (L and S) interact with SEC16A and differentially regulate the abundance and distribution of SEC24B at COPII assemblies in erythroid cells; SEC24B-positive COPII assemblies are linked to autophagic flux and erythroid differentiation.","method":"Co-immunoprecipitation; variant-specific siRNA depletion; fluorescence microscopy of SEC24B at COPII assemblies; autophagy flux assays","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal interactions and functional readouts, but SEC24B is a downstream effector rather than the primary subject","pmids":["32795391"],"is_preprint":false},{"year":2022,"finding":"A genome-wide CRISPR screen in human iPSC-derived microglia identified SEC24B as a novel regulator of ferroptosis; loss of SEC24B alters the iron-dependent cell death pathway in microglia, linking vesicle trafficking to iron-regulated ferroptotic susceptibility.","method":"Genome-wide CRISPR screen in iPSC-derived microglia tri-culture system; ferroptosis assays","journal":"Nature neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 — genome-wide CRISPR screen with defined phenotypic readout, but downstream mechanism of SEC24B in ferroptosis not yet resolved","pmids":["36536241"],"is_preprint":false},{"year":2025,"finding":"Linear ubiquitination of STING by LUBAC drives its trafficking from the ER to the Golgi via binding to SEC24B of the COPII complex; OTULIN removes linear ubiquitin chains to terminate this transport, establishing SEC24B as a reader of linearly ubiquitinated STING during antiviral innate immune signaling.","method":"Co-immunoprecipitation of STING with SEC24B; LUBAC/OTULIN overexpression and knockdown; STING trafficking assays","journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","confidence":"Medium","confidence_rationale":"Tier 2 — direct co-IP of STING-SEC24B interaction with functional ubiquitination and trafficking readouts, single lab","pmids":["40536345"],"is_preprint":false},{"year":2025,"finding":"SEC24B associates biochemically with HPV16 capsid proteins (L1/L2) and is required for productive HPV infection; silencing SEC24B inhibits infection, implicating COPII-dependent anterograde transport in post-Golgi HPV trafficking toward mitotic chromosomes.","method":"Co-immunoprecipitation of SEC24B with HPV capsid proteins; siRNA silencing of SEC24B; HPV pseudovirus infection assays","journal":"Viruses","confidence":"Medium","confidence_rationale":"Tier 2–3 — direct biochemical association plus functional knockdown phenotype, single study","pmids":["40431628"],"is_preprint":false},{"year":2023,"finding":"SEC24B knockdown abolishes HDAC inhibitor-induced secretion of PEDV virions via COPII-coated vesicles, demonstrating that SEC24B is required for COPII-mediated ER budding and release of PEDV coronavirus particles.","method":"siRNA knockdown of SEC24B; PEDV infection assays; colocalization of PEDV with COPII by immunofluorescence; ultrastructural analysis by EM","journal":"Viruses","confidence":"Medium","confidence_rationale":"Tier 2–3 — knockdown with defined viral secretion phenotype and EM confirmation, single lab","pmids":["37766280"],"is_preprint":false}],"current_model":"SEC24B is a cargo-selective subunit of the COPII coat that concentrates specific transmembrane and soluble secretory proteins at ER exit sites for anterograde transport; its best-characterized cargo is the planar cell polarity protein VANGL2, whose selective ER-to-Golgi sorting by SEC24B is essential for convergent extension and neural tube closure, while structurally distinct binding grooves in SEC24B also accommodate LxxLE and DxE transport signals, and SEC24B additionally participates in COPII-dependent autophagosome biogenesis, EGFR transport, PCSK9 secretion, STING antiviral trafficking, and ferroptosis regulation in microglia."},"narrative":{"teleology":[{"year":1999,"claim":"Identification of SEC24B as one of four mammalian Sec24 paralogs, forming a subclass with SEC24A, established that COPII cargo selection in mammals involves a diversified family of Sec24 proteins rather than a single ortholog.","evidence":"Molecular cloning, Northern blot, and co-localization of tagged SEC24B with SEC13 at ER-Golgi membranes by fluorescence microscopy","pmids":["10329445"],"confidence":"Medium","gaps":["No functional transport assay performed","Cargo specificity of SEC24B unknown","Interaction with SEC23 subunits not characterized"]},{"year":2007,"claim":"Demonstration that SEC24 isoform pairs have distinct cargo signal preferences resolved how di-leucine versus other ER export motifs are partitioned, showing SEC24B contributes preferentially to di-leucine-mediated transport.","evidence":"siRNA knockdown of single and paired SEC24 isoforms with ERGIC-53 transport assays and in vitro signal-binding assays","pmids":["17255961"],"confidence":"High","gaps":["Endogenous cargo specificity beyond ERGIC-53 not defined","In vivo significance not tested"]},{"year":2008,"claim":"Crystal structures of all four human SEC24 isoforms revealed that a conserved surface groove in SEC24A/B accommodates LxxLE and DxE motifs while the IxM groove is occluded, providing a structural explanation for isoform-specific cargo discrimination.","evidence":"X-ray crystallography combined with biochemical binding and functional COPII vesicle packaging assays","pmids":["18843296"],"confidence":"High","gaps":["No structure of SEC24B bound to its physiological cargo VANGL2","Additional binding sites for non-canonical cargo signals uncharacterized"]},{"year":2009,"claim":"Forward genetic screens linked SEC24B to neural tube closure by showing it selectively sorts the PCP protein VANGL2 into COPII vesicles; this was the first demonstration that a specific SEC24 paralog controls a defined developmental signaling pathway.","evidence":"ENU mutagenesis in mice; COPII vesicle budding assays; genetic epistasis between Sec24b and Vangl2(LP) alleles","pmids":["19966784","20215345"],"confidence":"High","gaps":["Molecular details of the SEC24B–VANGL2 binding interface unknown","Whether SEC24B sorts other PCP components not resolved"]},{"year":2013,"claim":"Human NTD-associated missense mutations in SEC24B were shown to impair VANGL2 interaction and localization, translating the mouse findings to human disease and confirming the physiological requirement for SEC24B–VANGL2 sorting in neural tube closure.","evidence":"Co-immunoprecipitation; VANGL2 localization assays; zebrafish overexpression and rescue","pmids":["23592378"],"confidence":"High","gaps":["Penetrance and genetic modifiers in human NTD cohorts not defined","Structural basis for how each mutation disrupts VANGL2 binding unknown"]},{"year":2013,"claim":"Extension of SEC24B cargo repertoire to soluble secretory proteins was established through its role in PCSK9 ER exit, demonstrating that cargo selectivity extends beyond transmembrane proteins.","evidence":"Sec24a knockout mice with epistasis to Apoe/Ldlr; PCSK9 secretion assays; later confirmed by SEC24 isoform-specific knockdowns mapping the requirement to PCSK9's C-terminal domain","pmids":["23580231","32058034"],"confidence":"Medium","gaps":["SEC24B contribution inferred partly from overlap with SEC24A rather than direct SEC24B knockout","Whether SEC24B recognizes a specific sorting signal on PCSK9 CTD is unknown"]},{"year":2016,"claim":"SEC24B was identified as specifically required for biosynthetic ER-to-plasma membrane transport of EGFR, linking COPII cargo selection to receptor tyrosine kinase homeostasis.","evidence":"siRNA knockdown of individual COPII subunits with EGFR transport readouts; RNF11-dependent transcriptional upregulation","pmids":["27872256"],"confidence":"Medium","gaps":["Sorting signal on EGFR recognized by SEC24B not mapped","Redundancy with SEC24D (also required) not fully dissected"]},{"year":2018,"claim":"The discovery that ULK1-phosphorylated SEC23B selectively pairs with SEC24A/B to promote autophagy flux placed SEC24B at the intersection of COPII trafficking and autophagosome biogenesis, expanding its role beyond conventional secretory transport.","evidence":"In vitro ULK1 kinase assay; co-immunoprecipitation of phospho-SEC23B with SEC24 isoforms; autophagy flux assays; subcellular fractionation","pmids":["30596474"],"confidence":"High","gaps":["What membrane cargo SEC24A/B packages for autophagosomes is unknown","Whether SEC24B has autophagy-specific post-translational modifications not tested"]},{"year":2021,"claim":"Live-cell and EM imaging resolved that SEC24B functions to concentrate cargo at ER exit sites rather than coating Golgi-bound carriers, refining the model of COPII coat dynamics.","evidence":"CRISPR/Cas12a endogenous tagging; RUSH live-cell imaging; perturbation of SEC24B cargo-binding domain; electron microscopy","pmids":["33852719"],"confidence":"High","gaps":["Whether this ERES-resident behavior applies to all SEC24 isoforms not resolved","Mechanism by which SEC24B is released from ERES membranes not defined"]},{"year":2022,"claim":"A CRISPR screen in iPSC-derived microglia identified SEC24B as a regulator of ferroptosis, revealing an unexpected connection between COPII-mediated trafficking and iron-dependent cell death.","evidence":"Genome-wide CRISPR screen in microglia tri-culture; ferroptosis phenotypic assays","pmids":["36536241"],"confidence":"Medium","gaps":["Mechanism by which SEC24B loss alters ferroptotic susceptibility is entirely unresolved","Specific cargo whose mis-sorting drives ferroptosis not identified","Not independently replicated"]},{"year":2025,"claim":"Linear ubiquitination of STING by LUBAC was shown to direct its binding to SEC24B for ER-to-Golgi trafficking, establishing SEC24B as a reader of a non-canonical cargo signal (linear ubiquitin) in innate immune signaling.","evidence":"Co-immunoprecipitation of STING with SEC24B; LUBAC/OTULIN overexpression and knockdown; STING trafficking assays","pmids":["40536345"],"confidence":"Medium","gaps":["Whether SEC24B directly binds linear ubiquitin chains or requires an adaptor not determined","Structural basis for ubiquitin-dependent recognition unknown","Not independently replicated"]},{"year":null,"claim":"Key unresolved questions include the structural basis of SEC24B–VANGL2 recognition, the full endogenous cargo repertoire of SEC24B versus other paralogs, the mechanism linking SEC24B to ferroptosis, and whether linear ubiquitin constitutes a general COPII sorting signal or is STING-specific.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structure of SEC24B bound to any physiological cargo","Comprehensive cargo profiling (e.g., proximity labeling at ERES) not performed","SEC24B post-translational regulation (beyond phospho-SEC23B pairing) unexplored"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0038024","term_label":"cargo receptor activity","supporting_discovery_ids":[0,2,3,9]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[2,4,9]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0,4,9]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[7,9]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[4]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,1,2,3,7,8,9]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0,1,3,8,9,13]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[7,11]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[0,1,6]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[13]}],"complexes":["COPII coat (SEC23-SEC24 inner coat)"],"partners":["SEC23B","SEC23A","VANGL2","SEC24A","SEC16A","STING1","EGFR"],"other_free_text":[]},"mechanistic_narrative":"SEC24B is a cargo-selective subunit of the COPII vesicle coat that concentrates specific transmembrane and soluble secretory proteins at ER exit sites for anterograde transport to the Golgi. Structural studies show that SEC24B, together with its paralog SEC24A, selectively recognizes LxxLE and DxE export signals through surface grooves distinct from those used by SEC24C/D, thereby partitioning the secretory proteome among COPII isoforms [PMID:18843296, PMID:17255961]. The best-characterized cargo of SEC24B is the planar cell polarity protein VANGL2, whose selective sorting into COPII vesicles by SEC24B is essential for convergent extension and neural tube closure; loss-of-function mutations in SEC24B cause craniorachischisis in mice and are found in human neural tube defect cases [PMID:19966784, PMID:20215345, PMID:23592378]. Beyond PCP signaling, SEC24B mediates ER-to-Golgi trafficking of EGFR, PCSK9, and linearly ubiquitinated STING, participates in autophagosome biogenesis through selective pairing with phosphorylated SEC23B, and regulates ferroptotic susceptibility in microglia [PMID:27872256, PMID:32058034, PMID:40536345, PMID:30596474, PMID:36536241]."},"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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Sec24b(Y613) mutant mice exhibit craniorachischisis and convergent extension defects, and genetically interact with Vangl2(LP) loss-of-function allele, placing SEC24B in the PCP pathway upstream of neural tube closure.\",\n      \"method\": \"Forward genetic screen in mice; COPII vesicle budding assays; genetic epistasis (Sec24b × Vangl2LP double mutants); analysis of looptail Vangl2 mutant sorting\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods (in vivo genetics, vesicle budding assays, epistasis), replicated by independent lab\",\n      \"pmids\": [\"19966784\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"SEC24B deficiency in mice specifically impairs ER-to-Golgi transport of the PCP protein Vangl2, confirmed in embryos and cultured primary cells; Sec24b mutant mice exhibit craniorachischisis, cochlear disorganization, and outflow tract vessel abnormalities consistent with PCP disruption, and genetically interact with scribble.\",\n      \"method\": \"Mouse ENU mutagenesis; Vangl2 localization in Sec24b-null embryos and primary cells; genetic interaction with scribble\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — independent replication of Sec24b–Vangl2 trafficking relationship with cellular and genetic evidence\",\n      \"pmids\": [\"20215345\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Crystal structures of all four human SEC24 isoforms revealed that a conserved IxM packaging signal binds a surface groove in SEC24C and SEC24D but is occluded in SEC24A and SEC24B; conversely, LxxLE class signals and the DxE signal of VSV-G are selectively bound by SEC24A and SEC24B, establishing structural determinants for cargo discrimination.\",\n      \"method\": \"X-ray crystallography of all four human SEC24 isoforms; biochemical binding assays; functional COPII vesicle packaging assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structures combined with biochemical and functional vesicle packaging assays\",\n      \"pmids\": [\"18843296\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"SEC24B participates in signal-mediated ER export of transmembrane proteins; double knockdown of SEC24B/C or SEC24B/D preferentially impairs di-leucine-mediated transport, and in vitro binding assays show isoform-selective binding preferences for cytosolic ER export signals.\",\n      \"method\": \"siRNA knockdown of individual and pairs of SEC24 isoforms; ERGIC-53 transport assays; in vitro signal-binding assays\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple isoform knockdowns combined with in vitro binding assays and functional transport readouts\",\n      \"pmids\": [\"17255961\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"SEC24B was identified as one of four mammalian Sec24 paralogs; it forms a subclass with SEC24A (~50% identity) and co-localizes with SEC13, another COPII component, at ER-Golgi boundary membranes, indicating its incorporation into COPII structures.\",\n      \"method\": \"Molecular cloning; Northern blot; co-localization of myc-tagged SEC24 with SEC13 by fluorescence microscopy\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — co-localization without functional follow-up, foundational identification paper\",\n      \"pmids\": [\"10329445\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"SEC24B shows partial overlap in cargo selectivity with SEC24A; both contribute to efficient ER exit of PCSK9 (a soluble secretory protein), demonstrating that cargo selectivity among SEC24 paralogs extends to soluble as well as transmembrane proteins.\",\n      \"method\": \"Sec24a knockout mouse; epistasis with Apoe and Ldlr mutations; PCSK9 secretion assays in SEC24A-deficient cells\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis and cellular secretion assays, but SEC24B role inferred from partial overlap rather than direct SEC24B knockout\",\n      \"pmids\": [\"23580231\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Four rare missense mutations in SEC24B (p.Phe227Ser, p.Phe682Leu, p.Arg1248Gln, p.Ala1251Gly) found in human NTD cases impair protein stability, physical interaction with VANGL2, and VANGL2 subcellular localization; zebrafish overexpression and rescue studies show loss-of-function effects, confirming SEC24B–VANGL2 interaction is required for neural tube closure.\",\n      \"method\": \"Human mutation analysis; co-immunoprecipitation; VANGL2 localization assays in cultured cells; zebrafish overexpression and dosage-dependent rescue\",\n      \"journal\": \"Human mutation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (co-IP, localization, in vivo zebrafish rescue) across human and model organism systems\",\n      \"pmids\": [\"23592378\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Upon nutrient starvation, ULK1 phosphorylates SEC23B on Ser186, preventing its degradation by FBXW5; stabilized, phosphorylated SEC23B then associates specifically with SEC24A and SEC24B (but not SEC24C or SEC24D) and this complex re-localizes to the ER-Golgi intermediate compartment to promote autophagic flux.\",\n      \"method\": \"Co-immunoprecipitation; in vitro ULK1 kinase assay; siRNA knockdown; autophagy flux assays; subcellular fractionation\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — in vitro kinase assay plus multiple co-IPs and functional autophagy assays establishing SEC24B as a selective binding partner of phospho-SEC23B\",\n      \"pmids\": [\"30596474\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"SEC23B, SEC24B, and SEC24D are specifically required for ER-to-plasma membrane transport of newly synthesized EGFR; EGF stimulation upregulates these COPII components through the endosomal transcriptional regulator RNF11, linking EGFR degradation to compensatory biosynthetic transport.\",\n      \"method\": \"siRNA knockdown of individual COPII subunits; EGFR transport assays; RNF11 localization and knockdown\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — specific knockdown with defined transport readout, but SEC24B role assessed alongside SEC23B and SEC24D\",\n      \"pmids\": [\"27872256\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Manipulation of the cargo-binding domain of COPII SEC24B prohibits cargo accumulation in ER exit sites (ERES); live-cell and EM imaging shows the COPII coat (including SEC24B) remains bound at the ER-ERES boundary rather than coating Golgi-bound carriers, indicating SEC24B functions in concentrating cargo at ERES rather than vesicle coating.\",\n      \"method\": \"CRISPR/Cas12a tagging; live-cell microscopy (RUSH system); pharmaceutical and genetic perturbation of SEC24B cargo-binding domain; electron microscopy\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods including live imaging, genetic perturbation of active domain, and EM in same study\",\n      \"pmids\": [\"33852719\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"SEC24A, SEC24B, and SEC24C (but not SEC24D) facilitate secretion of the full-length endogenous PCSK9 from cultured human hepatocytes; this facilitation is mediated by the C-terminal domain (CTD) of PCSK9, as mutant PCSK9(1-446) lacking the relevant CTD region is insensitive to knockdown of these SEC24 isoforms.\",\n      \"method\": \"siRNA knockdown of individual SEC24 isoforms; PCSK9 secretion assays in hepatocytes; PCSK9 truncation/deletion mutants\",\n      \"journal\": \"Biochimica et biophysica acta. Molecular and cell biology of lipids\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — isoform-specific knockdown with domain-mapping experiments, single lab\",\n      \"pmids\": [\"32058034\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"BMP2K isoforms (L and S) interact with SEC16A and differentially regulate the abundance and distribution of SEC24B at COPII assemblies in erythroid cells; SEC24B-positive COPII assemblies are linked to autophagic flux and erythroid differentiation.\",\n      \"method\": \"Co-immunoprecipitation; variant-specific siRNA depletion; fluorescence microscopy of SEC24B at COPII assemblies; autophagy flux assays\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal interactions and functional readouts, but SEC24B is a downstream effector rather than the primary subject\",\n      \"pmids\": [\"32795391\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"A genome-wide CRISPR screen in human iPSC-derived microglia identified SEC24B as a novel regulator of ferroptosis; loss of SEC24B alters the iron-dependent cell death pathway in microglia, linking vesicle trafficking to iron-regulated ferroptotic susceptibility.\",\n      \"method\": \"Genome-wide CRISPR screen in iPSC-derived microglia tri-culture system; ferroptosis assays\",\n      \"journal\": \"Nature neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genome-wide CRISPR screen with defined phenotypic readout, but downstream mechanism of SEC24B in ferroptosis not yet resolved\",\n      \"pmids\": [\"36536241\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Linear ubiquitination of STING by LUBAC drives its trafficking from the ER to the Golgi via binding to SEC24B of the COPII complex; OTULIN removes linear ubiquitin chains to terminate this transport, establishing SEC24B as a reader of linearly ubiquitinated STING during antiviral innate immune signaling.\",\n      \"method\": \"Co-immunoprecipitation of STING with SEC24B; LUBAC/OTULIN overexpression and knockdown; STING trafficking assays\",\n      \"journal\": \"Advanced science (Weinheim, Baden-Wurttemberg, Germany)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct co-IP of STING-SEC24B interaction with functional ubiquitination and trafficking readouts, single lab\",\n      \"pmids\": [\"40536345\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SEC24B associates biochemically with HPV16 capsid proteins (L1/L2) and is required for productive HPV infection; silencing SEC24B inhibits infection, implicating COPII-dependent anterograde transport in post-Golgi HPV trafficking toward mitotic chromosomes.\",\n      \"method\": \"Co-immunoprecipitation of SEC24B with HPV capsid proteins; siRNA silencing of SEC24B; HPV pseudovirus infection assays\",\n      \"journal\": \"Viruses\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — direct biochemical association plus functional knockdown phenotype, single study\",\n      \"pmids\": [\"40431628\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SEC24B knockdown abolishes HDAC inhibitor-induced secretion of PEDV virions via COPII-coated vesicles, demonstrating that SEC24B is required for COPII-mediated ER budding and release of PEDV coronavirus particles.\",\n      \"method\": \"siRNA knockdown of SEC24B; PEDV infection assays; colocalization of PEDV with COPII by immunofluorescence; ultrastructural analysis by EM\",\n      \"journal\": \"Viruses\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — knockdown with defined viral secretion phenotype and EM confirmation, single lab\",\n      \"pmids\": [\"37766280\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SEC24B is a cargo-selective subunit of the COPII coat that concentrates specific transmembrane and soluble secretory proteins at ER exit sites for anterograde transport; its best-characterized cargo is the planar cell polarity protein VANGL2, whose selective ER-to-Golgi sorting by SEC24B is essential for convergent extension and neural tube closure, while structurally distinct binding grooves in SEC24B also accommodate LxxLE and DxE transport signals, and SEC24B additionally participates in COPII-dependent autophagosome biogenesis, EGFR transport, PCSK9 secretion, STING antiviral trafficking, and ferroptosis regulation in microglia.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"SEC24B is a cargo-selective subunit of the COPII vesicle coat that concentrates specific transmembrane and soluble secretory proteins at ER exit sites for anterograde transport to the Golgi. Structural studies show that SEC24B, together with its paralog SEC24A, selectively recognizes LxxLE and DxE export signals through surface grooves distinct from those used by SEC24C/D, thereby partitioning the secretory proteome among COPII isoforms [PMID:18843296, PMID:17255961]. The best-characterized cargo of SEC24B is the planar cell polarity protein VANGL2, whose selective sorting into COPII vesicles by SEC24B is essential for convergent extension and neural tube closure; loss-of-function mutations in SEC24B cause craniorachischisis in mice and are found in human neural tube defect cases [PMID:19966784, PMID:20215345, PMID:23592378]. Beyond PCP signaling, SEC24B mediates ER-to-Golgi trafficking of EGFR, PCSK9, and linearly ubiquitinated STING, participates in autophagosome biogenesis through selective pairing with phosphorylated SEC23B, and regulates ferroptotic susceptibility in microglia [PMID:27872256, PMID:32058034, PMID:40536345, PMID:30596474, PMID:36536241].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Identification of SEC24B as one of four mammalian Sec24 paralogs, forming a subclass with SEC24A, established that COPII cargo selection in mammals involves a diversified family of Sec24 proteins rather than a single ortholog.\",\n      \"evidence\": \"Molecular cloning, Northern blot, and co-localization of tagged SEC24B with SEC13 at ER-Golgi membranes by fluorescence microscopy\",\n      \"pmids\": [\"10329445\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional transport assay performed\", \"Cargo specificity of SEC24B unknown\", \"Interaction with SEC23 subunits not characterized\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Demonstration that SEC24 isoform pairs have distinct cargo signal preferences resolved how di-leucine versus other ER export motifs are partitioned, showing SEC24B contributes preferentially to di-leucine-mediated transport.\",\n      \"evidence\": \"siRNA knockdown of single and paired SEC24 isoforms with ERGIC-53 transport assays and in vitro signal-binding assays\",\n      \"pmids\": [\"17255961\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Endogenous cargo specificity beyond ERGIC-53 not defined\", \"In vivo significance not tested\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Crystal structures of all four human SEC24 isoforms revealed that a conserved surface groove in SEC24A/B accommodates LxxLE and DxE motifs while the IxM groove is occluded, providing a structural explanation for isoform-specific cargo discrimination.\",\n      \"evidence\": \"X-ray crystallography combined with biochemical binding and functional COPII vesicle packaging assays\",\n      \"pmids\": [\"18843296\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structure of SEC24B bound to its physiological cargo VANGL2\", \"Additional binding sites for non-canonical cargo signals uncharacterized\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Forward genetic screens linked SEC24B to neural tube closure by showing it selectively sorts the PCP protein VANGL2 into COPII vesicles; this was the first demonstration that a specific SEC24 paralog controls a defined developmental signaling pathway.\",\n      \"evidence\": \"ENU mutagenesis in mice; COPII vesicle budding assays; genetic epistasis between Sec24b and Vangl2(LP) alleles\",\n      \"pmids\": [\"19966784\", \"20215345\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular details of the SEC24B–VANGL2 binding interface unknown\", \"Whether SEC24B sorts other PCP components not resolved\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Human NTD-associated missense mutations in SEC24B were shown to impair VANGL2 interaction and localization, translating the mouse findings to human disease and confirming the physiological requirement for SEC24B–VANGL2 sorting in neural tube closure.\",\n      \"evidence\": \"Co-immunoprecipitation; VANGL2 localization assays; zebrafish overexpression and rescue\",\n      \"pmids\": [\"23592378\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Penetrance and genetic modifiers in human NTD cohorts not defined\", \"Structural basis for how each mutation disrupts VANGL2 binding unknown\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Extension of SEC24B cargo repertoire to soluble secretory proteins was established through its role in PCSK9 ER exit, demonstrating that cargo selectivity extends beyond transmembrane proteins.\",\n      \"evidence\": \"Sec24a knockout mice with epistasis to Apoe/Ldlr; PCSK9 secretion assays; later confirmed by SEC24 isoform-specific knockdowns mapping the requirement to PCSK9's C-terminal domain\",\n      \"pmids\": [\"23580231\", \"32058034\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"SEC24B contribution inferred partly from overlap with SEC24A rather than direct SEC24B knockout\", \"Whether SEC24B recognizes a specific sorting signal on PCSK9 CTD is unknown\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"SEC24B was identified as specifically required for biosynthetic ER-to-plasma membrane transport of EGFR, linking COPII cargo selection to receptor tyrosine kinase homeostasis.\",\n      \"evidence\": \"siRNA knockdown of individual COPII subunits with EGFR transport readouts; RNF11-dependent transcriptional upregulation\",\n      \"pmids\": [\"27872256\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Sorting signal on EGFR recognized by SEC24B not mapped\", \"Redundancy with SEC24D (also required) not fully dissected\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"The discovery that ULK1-phosphorylated SEC23B selectively pairs with SEC24A/B to promote autophagy flux placed SEC24B at the intersection of COPII trafficking and autophagosome biogenesis, expanding its role beyond conventional secretory transport.\",\n      \"evidence\": \"In vitro ULK1 kinase assay; co-immunoprecipitation of phospho-SEC23B with SEC24 isoforms; autophagy flux assays; subcellular fractionation\",\n      \"pmids\": [\"30596474\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"What membrane cargo SEC24A/B packages for autophagosomes is unknown\", \"Whether SEC24B has autophagy-specific post-translational modifications not tested\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Live-cell and EM imaging resolved that SEC24B functions to concentrate cargo at ER exit sites rather than coating Golgi-bound carriers, refining the model of COPII coat dynamics.\",\n      \"evidence\": \"CRISPR/Cas12a endogenous tagging; RUSH live-cell imaging; perturbation of SEC24B cargo-binding domain; electron microscopy\",\n      \"pmids\": [\"33852719\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether this ERES-resident behavior applies to all SEC24 isoforms not resolved\", \"Mechanism by which SEC24B is released from ERES membranes not defined\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"A CRISPR screen in iPSC-derived microglia identified SEC24B as a regulator of ferroptosis, revealing an unexpected connection between COPII-mediated trafficking and iron-dependent cell death.\",\n      \"evidence\": \"Genome-wide CRISPR screen in microglia tri-culture; ferroptosis phenotypic assays\",\n      \"pmids\": [\"36536241\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which SEC24B loss alters ferroptotic susceptibility is entirely unresolved\", \"Specific cargo whose mis-sorting drives ferroptosis not identified\", \"Not independently replicated\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Linear ubiquitination of STING by LUBAC was shown to direct its binding to SEC24B for ER-to-Golgi trafficking, establishing SEC24B as a reader of a non-canonical cargo signal (linear ubiquitin) in innate immune signaling.\",\n      \"evidence\": \"Co-immunoprecipitation of STING with SEC24B; LUBAC/OTULIN overexpression and knockdown; STING trafficking assays\",\n      \"pmids\": [\"40536345\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether SEC24B directly binds linear ubiquitin chains or requires an adaptor not determined\", \"Structural basis for ubiquitin-dependent recognition unknown\", \"Not independently replicated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include the structural basis of SEC24B–VANGL2 recognition, the full endogenous cargo repertoire of SEC24B versus other paralogs, the mechanism linking SEC24B to ferroptosis, and whether linear ubiquitin constitutes a general COPII sorting signal or is STING-specific.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structure of SEC24B bound to any physiological cargo\", \"Comprehensive cargo profiling (e.g., proximity labeling at ERES) not performed\", \"SEC24B post-translational regulation (beyond phospho-SEC23B pairing) unexplored\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0038024\", \"supporting_discovery_ids\": [0, 2, 3, 9]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [2, 4, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0, 4, 9]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [7, 9]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 1, 2, 3, 7, 8, 9]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 1, 3, 8, 9, 13]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [7, 11]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [0, 1, 6]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [13]}\n    ],\n    \"complexes\": [\n      \"COPII coat (SEC23-SEC24 inner coat)\"\n    ],\n    \"partners\": [\n      \"SEC23B\",\n      \"SEC23A\",\n      \"VANGL2\",\n      \"SEC24A\",\n      \"SEC16A\",\n      \"STING1\",\n      \"EGFR\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}