Affinage

SEC24B

Protein transport protein Sec24B · UniProt O95487

Length
1268 aa
Mass
137.4 kDa
Annotated
2026-06-10
36 papers in source corpus 15 papers cited in narrative 15 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2007 Medium

    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

    PMID:17255961

    Open questions at the time
    • Did not resolve the structural basis of signal discrimination
    • Single lab, limited cargo panel
  2. 2008 High

    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

    PMID:18843296

    Open questions at the time
    • Structures of full coat assembly with physiological cargo not resolved
    • Did not address in vivo cargo specificity
  3. 2009 High

    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

    PMID:19966784

    Open questions at the time
    • Did not map the exact Vangl2 signal recognized by SEC24B
    • Full set of SEC24B-dependent PCP cargoes unknown
  4. 2010 High

    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

    PMID:20215345

    Open questions at the time
    • Mechanism of genetic interaction with scribble not defined at molecular level
  5. 2013 Medium

    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

    PMID:23592378

    Open questions at the time
    • Causality in human NTD population not established by family segregation
    • Single lab
  6. 2013 Medium

    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

    PMID:23580231

    Open questions at the time
    • SEC24B contribution inferred from residual secretion rather than direct assay
    • Extent of redundancy per cargo undefined
  7. 2016 Medium

    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

    PMID:27872256

    Open questions at the time
    • Direct EGFR-SEC24B binding not demonstrated
    • Signal recognized on EGFR unidentified
  8. 2018 Medium

    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

    PMID:30596474

    Open questions at the time
    • Specific cargo carried by SEC24B in autophagy not identified
    • Single lab
  9. 2020 Medium

    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

    PMID:32058034

    Open questions at the time
    • Direct binding of SEC24B to the PCSK9 C-terminus not shown
    • Relative isoform contribution not quantified
  10. 2020 Low

    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

    PMID:32795391

    Open questions at the time
    • SEC24B involvement inferred from assembly markers rather than direct interaction
    • Single Co-IP, single lab
  11. 2021 Medium

    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

    PMID:33852719

    Open questions at the time
    • Generalizability across all cargo classes not established
    • Single lab
  12. 2022 Medium

    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

    PMID:36536241

    Open questions at the time
    • Cargo or trafficking event mediating ferroptosis effect unknown
    • Mechanistic follow-up limited
  13. 2025 Medium

    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

    PMID:40536345

    Open questions at the time
    • Structural basis for recognition of linear ubiquitin by SEC24B not resolved
    • Single lab
  14. 2025 Low

    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

    PMID:40431628

    Open questions at the time
    • Single pulldown and knockdown without binding-site mapping
    • Mechanistic resolution limited, single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • 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.
  • 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

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005783 endoplasmic reticulum 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9609507 Protein localization 3 R-HSA-9612973 Autophagy 1
Partners
EGFRERGIC-53PCSK9SEC23BSTING1VANGL2
Complex memberships
COPII coat

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 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. X-ray crystallography combined with biochemical binding assays and functional COPII vesicle packaging assays The EMBO journal High 18843296
2009 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. Forward genetic screen in mice, COPII vesicle budding assays, genetic epistasis (double mutant analysis), ER retention assays in cultured cells Nature cell biology High 19966784
2010 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. ENU mutagenesis screen, analysis of Sec24b mutant mouse embryos and primary cells, genetic interaction with scribble Development (Cambridge, England) High 20215345
2007 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. siRNA-mediated knockdown of individual and pairs of SEC24 isoforms; in vitro binding assays of transport signals to SEC24 isoforms EMBO reports Medium 17255961
2013 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. Co-immunoprecipitation, subcellular localization assays in cultured cells, zebrafish overexpression and dosage-dependent rescue Human mutation Medium 23592378
2013 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. Genetic deficiency mouse model, epistasis with Apoe and Ldlr mutations, hepatocyte fractionation and LDLR/PCSK9 measurements eLife Medium 23580231
2018 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. Co-immunoprecipitation of SEC23B with SEC24 isoforms, phosphorylation site mutagenesis, autophagy flux assays, ULK1 kinase assays eLife Medium 30596474
2016 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. siRNA knockdown, pulse-chase transport assays, RUSH system, transcriptional reporter assays The Journal of cell biology Medium 27872256
2020 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. siRNA knockdown of individual SEC24 isoforms in hepatocytes, PCSK9 secretion assays with wild-type and deletion mutants Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 32058034
2021 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. CRISPR/Cas12a endogenous tagging, live-cell microscopy, RUSH system, pharmaceutical and genetic perturbations of ER-Golgi transport, electron microscopy The Journal of cell biology Medium 33852719
2020 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. Co-immunoprecipitation of BMP2K with SEC16A, variant-specific siRNA depletion, fluorescence microscopy of COPII assemblies eLife Low 32795391
2022 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. Genome-wide CRISPR screen in iPSC-derived microglia tri-culture system with iron overload/ferroptosis as phenotypic readout Nature neuroscience Medium 36536241
2025 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. Co-immunoprecipitation of ubiquitinated STING with SEC24B, LUBAC/OTULIN gain- and loss-of-function, STING trafficking assays Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 40536345
2025 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. Biochemical pulldown/co-isolation of HPV capsid with SEC24B; siRNA knockdown with HPV pseudovirus infection assay Viruses Low 40431628
2023 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. siRNA knockdown of SEC24B, PEDV secretion assays, colocalization by fluorescence microscopy, ultrastructural EM Viruses Low 37766280

Source papers

Stage 0 corpus · 36 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2022 Microglia ferroptosis is regulated by SEC24B and contributes to neurodegeneration. Nature neuroscience 296 36536241
2008 Structural basis of cargo membrane protein discrimination by the human COPII coat machinery. The EMBO journal 179 18843296
2009 Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closure. Nature cell biology 178 19966784
2007 Role of Sec24 isoforms in selective export of membrane proteins from the endoplasmic reticulum. EMBO reports 165 17255961
2010 Selective export of human GPI-anchored proteins from the endoplasmic reticulum. Journal of cell science 124 20427317
2021 Iron status influences non-alcoholic fatty liver disease in obesity through the gut microbiome. Microbiome 114 33962692
2013 SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion. eLife 105 23580231
2010 Planar cell polarity defects and defective Vangl2 trafficking in mutants for the COPII gene Sec24b. Development (Cambridge, England) 78 20215345
2021 COPII collar defines the boundary between ER and ER exit site and does not coat cargo containers. The Journal of cell biology 76 33852719
2018 The ULK1-FBXW5-SEC23B nexus controls autophagy. eLife 71 30596474
1999 A family of mammalian proteins homologous to yeast Sec24p. Biochemical and biophysical research communications 63 10329445
2013 Disruption of the Sec24d gene results in early embryonic lethality in the mouse. PloS one 51 23596517
2016 The endosomal transcriptional regulator RNF11 integrates degradation and transport of EGFR. The Journal of cell biology 43 27872256
2013 Mutations in the COPII vesicle component gene SEC24B are associated with human neural tube defects. Human mutation 42 23592378
2018 The COPII cargo adapter SEC24C is essential for neuronal homeostasis. The Journal of clinical investigation 37 29939162
2014 Mammalian COPII coat component SEC24C is required for embryonic development in mice. The Journal of biological chemistry 34 24876386
2011 An ENU-mutagenesis screen in the mouse: identification of novel developmental gene functions. PloS one 27 21559415
2020 The role of the C-terminal domain of PCSK9 and SEC24 isoforms in PCSK9 secretion. Biochimica et biophysica acta. Molecular and cell biology of lipids 25 32058034
2009 Proline-rich sequence recognition: II. Proteomics analysis of Tsg101 ubiquitin-E2-like variant (UEV) interactions. Molecular & cellular proteomics : MCP 22 19542561
2019 Exome sequencing in 51 early onset non-familial CRC cases. Molecular genetics & genomic medicine 21 30809968
2018 Rare variants and de novo variants in mesial temporal lobe epilepsy with hippocampal sclerosis. Neurology. Genetics 18 29904720
2018 A novel NCSTN gene mutation in a Chinese family with acne inversa. Molecular genetics and genomics : MGG 15 30030622
2024 Unraveling the genetic architecture of congenital vertebral malformation with reference to the developing spine. Nature communications 13 38321032
2020 Splicing variation of BMP2K balances abundance of COPII assemblies and autophagic degradation in erythroid cells. eLife 10 32795391
2025 Spatiotemporal Regulation of STING Activity by Linear Ubiquitination Governs Antiviral Immunity. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 8 40536345
2020 The Integrated Analyses of Driver Genes Identify Key Biomarkers in Thyroid Cancer. Technology in cancer research & treatment 7 32812852
2021 SEC24A facilitates colocalization and Ca2+ flux between the endoplasmic reticulum and mitochondria. Journal of cell science 6 33622772
2025 Experimentally verified flexible molecular docking and dynamic simulation of aptamer with intracellular proteins based on direct DNA 3D structure prediction. International journal of biological macromolecules 4 40383336
2025 The COPII Transport Complex Participates in HPV16 Infection. Viruses 3 40431628
2023 HDAC-Specific Inhibitors Induce the Release of Porcine Epidemic Diarrhea Virus via the COPII-Coated Vesicles. Viruses 2 37766280
2020 Splicing variants of an endocytic regulator, BMP2K, differentially control autophagic degradation in erythroid cells. Autophagy 2 33025853
2025 Bioinformatics-based Mechanisms of Lipid Metabolism and Endoplasmic Reticulum Stress in Coronary Artery Disease. Endocrine, metabolic & immune disorders drug targets 1 41185499
2023 Proteome Analysis of Bevacizumab Intervention in Experimental Central Retinal Vein Occlusion. Journal of personalized medicine 1 38003895
2026 TCOF1 affects Golgi secretory pathway contributing to the angiogenesis in renal cancer. Cell communication and signaling : CCS 0 41840584
2025 Identification and validation of feature genes in hepatocellular carcinoma based on bioinformatics and machine learning: An observational study. Medicine 0 41137296
2025 Positive Selection in Aggression-Linked Genes and Their Protein Interaction Networks. Life (Basel, Switzerland) 0 41598173

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