Affinage

SEC61B

Protein transport protein Sec61 subunit beta · UniProt P60468

Round 2 corrected Audit flag: rerun needed
Length
96 aa
Mass
10.0 kDa
Annotated
2026-04-28
65 papers in source corpus 14 papers cited in narrative 13 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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Mechanism profile

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Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 SEC61B (Sec61-beta) is a subunit of the mammalian Sec61p complex, the core protein translocation channel of the endoplasmic reticulum. Its gamma subunit (Sec61-gamma) is homologous to yeast SSS1p and can functionally replace it in yeast, establishing evolutionary conservation of the translocon complex across eukaryotes and bacteria. Sequence determination, functional complementation in yeast, structural homology analysis Nature High 8107851
1996 The Sec61 complex (including SEC61B as a subunit) mediates retrotranslocation of MHC class I molecules from the ER lumen to the cytosol for proteasomal degradation, a process hijacked by the HCMV US2 protein, demonstrating that the translocon can operate in reverse for ERAD. Biochemical fractionation, immunoprecipitation, proteasome inhibition, cell biology Nature High 8945469
2000 Mammalian SEC61B is part of a ribosome-free Sec61 complex that associates with mammalian SEC62 and SEC63, forming a higher-order complex at the ER membrane analogous to the yeast post-translational translocation machinery. Biochemical fractionation, co-immunoprecipitation, sequence analysis The Journal of biological chemistry High 10799540
2015 SEC61B mRNA is a tail-anchored protein whose transcript is partially localized to the ER surface in mammalian cells via both translation-dependent and translation-independent mechanisms, independent of p180/RRBP1 and TRC40/BAT3 pathway components, suggesting that Sec61β is synthesized directly on the ER to facilitate membrane insertion. Fluorescence in situ hybridization (FISH), live-cell imaging, siRNA knockdown, cell fractionation Journal of cell science Medium 26272916
2017 Loss-of-function of SEC61B in cell line models results in defective maturation and trafficking of polycystin-1, placing SEC61B in the ER protein biogenesis pathway as a regulator of polycystin-1 processing. SEC61B loss-of-function has distinct effects on polycystin-1 biogenesis compared to loss of other PCLD genes (PRKCSH, SEC63, ALG8, GANAB). Gene inactivation in cell lines, polycystin-1 maturation/trafficking assays, whole exome sequencing The Journal of clinical investigation Medium 28375157 28862642
2017 Endogenous SEC61B protein has reduced abundance in certain peripheral ER tubules compared to the ER sheet network, as revealed by dual-color endogenous tagging with split fluorescent proteins (GFP11/sfCherry211), demonstrating non-uniform distribution within ER subdomains. CRISPR endogenous tagging with split fluorescent proteins, super-resolution and confocal live-cell imaging Nature communications Medium 28851864
2017 SEC61B was identified as part of the SEC63 interactome by affinity proteomics, confirming that SEC61B is a component of the SEC63-containing translocon complex at the ER membrane in cholangiocytes. Affinity proteomics (immunoprecipitation-MS) in HEK293T cells and H69 cholangiocytes Human molecular genetics Medium 28973524
2019 DDR1 nuclear translocation requires its interaction with SEC61B (a component of the Sec61 translocon), as well as nonmuscle myosin IIA and β-actin. This interaction enables collagen-activated DDR1 to move from the ER/membrane to the nucleus where it drives collagen IV transcription. Co-immunoprecipitation, biochemical fractionation, immunofluorescence, mutant DDR1 constructs Journal of the American Society of Nephrology : JASN Medium 31383731
2021 SEC61B anchored to the ER lumen (as SEC61b-TurboID) selectively labels proteins that transit through the classical secretory pathway via proximity biotinylation, validating that SEC61B resides in the ER translocon and that transiting secretory proteins pass through its proximity. Proximity labeling (TurboID), in vivo mouse model, quantitative proteomics Nature communications High 34471136
2021 SEC61B expression is decreased in dendritic cells following LPS-induced reticulophagy (FAM134B-mediated), consistent with SEC61B being selectively degraded during ER-phagy of ER membrane subdomains. Western blotting, FAM134B siRNA knockdown, LPS stimulation time course Zhonghua shao shang yu chuang mian xiu fu za zhi Low 37805802
2021 Let-7b-5p upregulates SERP1 (stress-associated ER protein 1), which modulates its chaperone protein SEC61B during ER stress response, activating the unfolded protein response via PERK-CHOP pathway. miRNA mimic/inhibitor transfection, qPCR, Western blot, in vitro and in vivo PE models IUBMB life Low 32534478
2025 SEC61B overexpression in HEK293 cells increases calcium flux from the ER into the cytosol and decreases protein synthesis. In hyperglycemic mice and humans with diabetes, platelet SEC61B is elevated, ER stress induces SEC61B expression, and increased SEC61B causes elevated cytosolic calcium leading to platelet hyperreactivity. Pharmacological inhibition of Sec61 with anisomycin decreased platelet calcium flux and inhibited platelet aggregation in vitro and in vivo. HEK293 overexpression calcium flux assays, proteomic profiling of human/mouse platelets, pharmacological inhibition (anisomycin), in vivo thrombosis models The Journal of clinical investigation High 40829182
2025 SEC61B is required for proteolytic cleavage (by furin and furin-related enzyme SKI-1) and normal N-glycosylation of Marburg virus glycoprotein (MARV-GP) but not Ebola virus GP, revealing a virus-specific role of SEC61B in MARV-GP processing. SEC61B KO impaired SKI-1-mediated cleavage of MARV-GP and abrogated robust MARV cell entry. Blockade of the Sec61 translocon with apratoxin S4 markedly inhibited both EBOV and MARV infection. SEC61B CRISPR knockout cells, pseudovirus entry assays, Western blot for GP cleavage and glycosylation, in silico cleavage motif identification bioRxivpreprint Medium bio_10.1101_2025.06.26.660697

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
1996 Sec61-mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction. Nature 911 8945469
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1998 The role of assembly in insulin's biosynthesis. Current opinion in structural biology 406 9631292
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2012 Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Nature 319 22810586
2019 Intrinsically Disordered Protein TEX264 Mediates ER-phagy. Molecular cell 296 31006538
2020 The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis. Nature 292 32322062
2017 Genetic Complexity of Autosomal Dominant Polycystic Kidney and Liver Diseases. Journal of the American Society of Nephrology : JASN 273 29038287
2022 Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration. Cell 256 35063084
1994 Evolutionary conservation of components of the protein translocation complex. Nature 241 8107851
2010 A ribosome-associating factor chaperones tail-anchored membrane proteins. Nature 238 20676083
2018 Prevalence Estimates of Polycystic Kidney and Liver Disease by Population Sequencing. Journal of the American Society of Nephrology : JASN 218 30135240
2014 Proximity biotinylation and affinity purification are complementary approaches for the interactome mapping of chromatin-associated protein complexes. Journal of proteomics 215 25281560
2016 Ubiquilins Chaperone and Triage Mitochondrial Membrane Proteins for Degradation. Molecular cell 210 27345149
2009 Proteomic analysis of integrin-associated complexes identifies RCC2 as a dual regulator of Rac1 and Arf6. Science signaling 207 19738201
2017 Improved split fluorescent proteins for endogenous protein labeling. Nature communications 197 28851864
2020 Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions. Nature cell biology 194 32203420
2019 H4K20me0 recognition by BRCA1-BARD1 directs homologous recombination to sister chromatids. Nature cell biology 162 30804502
2019 A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. Nature immunology 159 30833792
2000 Mammalian Sec61 is associated with Sec62 and Sec63. The Journal of biological chemistry 158 10799540
2009 The structural basis of tail-anchored membrane protein recognition by Get3. Nature 155 19675567
2020 AMPK, a Regulator of Metabolism and Autophagy, Is Activated by Lysosomal Damage via a Novel Galectin-Directed Ubiquitin Signal Transduction System. Molecular cell 152 31995728
2017 Isolated polycystic liver disease genes define effectors of polycystin-1 function. The Journal of clinical investigation 127 28375157
2020 Insights into Autosomal Dominant Polycystic Kidney Disease from Genetic Studies. Clinical journal of the American Society of Nephrology : CJASN 101 32690722
2021 Dynamic tracking and identification of tissue-specific secretory proteins in the circulation of live mice. Nature communications 90 34471136
2014 Proteomic analysis of solid pseudopapillary tumor of the pancreas reveals dysfunction of the endoplasmic reticulum protein processing pathway. Molecular & cellular proteomics : MCP 86 24997997
2019 WDR45 contributes to neurodegeneration through regulation of ER homeostasis and neuronal death. Autophagy 81 31204559
2022 Exome Sequencing of a Clinical Population for Autosomal Dominant Polycystic Kidney Disease. JAMA 71 36573973
2022 Human T-bet governs the generation of a distinct subset of CD11chighCD21low B cells. Science immunology 65 35867801
2015 Genetic ablation of ataxin-2 increases several global translation factors in their transcript abundance but decreases translation rate. Neurogenetics 58 25721894
2018 A combination of curcumin and oligomeric proanthocyanidins offer superior anti-tumorigenic properties in colorectal cancer. Scientific reports 54 30218018
2022 Upregulation of ribosome complexes at the blood-brain barrier in Alzheimer's disease patients. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 53 35766008
2019 The Extracellular Matrix Receptor Discoidin Domain Receptor 1 Regulates Collagen Transcription by Translocating to the Nucleus. Journal of the American Society of Nephrology : JASN 41 31383731
2017 Isolated polycystic liver disease genes define effectors of polycystin-1 function. The Journal of clinical investigation 35 28862642
2024 USP20 deubiquitinates and stabilizes the reticulophagy receptor RETREG1/FAM134B to drive reticulophagy. Autophagy 29 38705724
2017 3,4-dihydroxybenzalacetone and caffeic acid phenethyl ester induce preconditioning ER stress and autophagy in SH-SY5Y cells. Journal of cellular physiology 28 28681934
2011 Identification of candidate genes linking systemic inflammation to atherosclerosis; results of a human in vivo LPS infusion study. BMC medical genomics 25 21827714
2019 Genetics of polycystic liver diseases. Current opinion in gastroenterology 24 30652979
2015 mRNA encoding Sec61β, a tail-anchored protein, is localized on the endoplasmic reticulum. Journal of cell science 18 26272916
2020 Let-7b-5p is involved in the response of endoplasmic reticulum stress in acute pulmonary embolism through upregulating the expression of stress-associated endoplasmic reticulum protein 1. IUBMB life 13 32534478
2017 Liver cyst gene knockout in cholangiocytes inhibits cilium formation and Wnt signaling. Human molecular genetics 11 28973524
2024 Clinical manifestation, epidemiology, genetic basis, potential molecular targets, and current treatment of polycystic liver disease. Orphanet journal of rare diseases 9 38671465
2021 Autophagy-mediated reduction of miR-345 contributes to hepatic cystogenesis in polycystic liver disease. JHEP reports : innovation in hepatology 8 34568801
2025 SEC61B regulates calcium flux and platelet hyperreactivity in diabetes. The Journal of clinical investigation 6 40829182
2020 cDNA expression library screening revealed novel functional genes involved in clear cell carcinogenesis of the ovary in vitro. Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 4 32157937
2024 Identification of novel endoplasmic reticulum-related genes and their association with immune cell infiltration in major depressive disorder. Journal of affective disorders 3 38604455
2025 The Mechanism of Xuanyu Tongjing Decoction Regulating NOD/NFκB Pathway to Inhibit Ectopic Tissue Inflammation to Reduce Ovarian Damage in Rats with Ovarian Endometriosis. Drug design, development and therapy 2 40231194
2025 Autosomal Dominant Polycystic Kidney Disease-Related Multifocal Renal Cell Carcinoma: A Narrative Iconographic Review. International journal of molecular sciences 2 40362206
2025 Chronic diseases alter the platelet rheostat to promote hyperreactivity and thrombosis. The Journal of clinical investigation 2 40829178
2024 Identification of differentially expressed ER stress-related genes and their association with pulmonary arterial hypertension. Respiratory research 2 38789967
2022 Comparative proteomics analysis of human stem cells from dental gingival and periodontal ligament. Proteomics 2 35297194
2023 [Influence of family with sequence similarity 134, member B-mediated reticulophagy on lipopolysaccharide-induced apoptosis of mouse dendritic cells]. Zhonghua shao shang yu chuang mian xiu fu za zhi 1 37805802
2025 ER stress-driven unfolded protein response fuels aging-related tumor aggressiveness in gliomas. Frontiers in molecular biosciences 0 40718795
2025 TIPE2-Regulated ER-Phagy in Dendritic Cell Function Following Hemorrhagic Shock. Shock (Augusta, Ga.) 0 41697115