Affinage

RETREG1

Reticulophagy regulator 1 · UniProt Q9H6L5

Length
497 aa
Mass
54.7 kDa
Annotated
2026-06-10
100 papers in source corpus 34 papers cited in narrative 33 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

RETREG1 (FAM134B) is an ER-resident selective autophagy receptor that drives reticulophagy — the targeted lysosomal degradation of endoplasmic reticulum — and is essential for the long-term survival of nociceptive and autonomic neurons, with loss-of-function mutations causing hereditary sensory and autonomic neuropathy (PMID:19838196, PMID:30559329). Its reticulon homology domain (RHD) forms wedge-shaped transmembrane hairpins and amphipathic helices that induce membrane curvature, and upon clustering it amplifies membrane remodeling to fragment ER for capture by autophagosomes (PMID:31147549, PMID:31930741). A cytosolic LIR motif together with a C-terminal helix mediates binding to the autophagosomal ATG8 proteins, with selectivity for the GABARAP subfamily over LC3 (PMID:34854256, PMID:37273064). ER-phagy activity is gated by a dense post-translational and transcriptional control network: CAMK2B phosphorylation and CBP acetylation promote oligomerization and membrane scission, SIRT7 deacetylation tempers it, O-GlcNAcylation and USP20-mediated removal of K48/K63 ubiquitin chains stabilize the receptor, and TRIM21 ubiquitination at K247/K252 drives proteasomal turnover unless CKAP4 binding shields it (PMID:31930741, PMID:37043189, PMID:36056188, PMID:38705724, PMID:39689859); nutrient- and stress-responsive transcription factors TFEB/TFE3, ATF4–CEBPG, ATF6, and others induce RETREG1 expression (PMID:32716134, PMID:40437698, PMID:41874459). Functionally, RETREG1 executes selective ER quality control via a Calnexin co-receptor complex that delivers misfolded luminal procollagen for degradation, and degrades the ER Ca2+ sensor STIM1 to restrain G1-to-S cell cycle progression (PMID:30559329, PMID:39128711). Through direct cholesterol and SCAP binding it couples ER-phagy to SREBP2-driven cholesterol synthesis and STING trafficking (PMID:41083602), and it also influences mitochondrial morphology by promoting DRP1 recruitment for fission (PMID:41178515). RETREG1 is exploited or restricted at host–pathogen interfaces: flavivirus NS3 protease cleaves its RHD, Salmonella SopF blocks its oligomerization, coronavirus ORF8/p62 condensates sequester it, and retroviral glycoGag hijacks it for autophagosome-independent micro-ER-phagy of SERINC5 (PMID:28102736, PMID:40133256, PMID:36952345, PMID:41066524, PMID:40093084).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2009 High

    Established RETREG1/FAM134B as a disease gene and as essential for neuronal survival, before any molecular function was known.

    Evidence Human loss-of-function mutations and siRNA knockdown in primary dorsal root ganglion neurons with Golgi morphology and apoptosis readouts

    PMID:19838196

    Open questions at the time
    • No molecular mechanism for the survival defect
    • Golgi phenotype precedes identification of an ER-phagy role
  2. 2017 High

    Identified RETREG1 as an ER-phagy receptor and a flavivirus restriction factor by showing NS3 protease cleaves its reticulon homology domain to disable the pathway.

    Evidence RNAi viral replication assays and in vitro protease cleavage assay mapping a single RHD cleavage site

    PMID:28102736

    Open questions at the time
    • Did not resolve how the RHD remodels membranes
    • Cargo selectivity not defined
  3. 2018 High

    Defined selective ER quality control by showing Calnexin acts as a luminal co-receptor delivering misfolded procollagen to the lysosome through RETREG1–LC3 coupling.

    Evidence Reciprocal co-IP of CANX–FAM134B, LC3 binding and lysosomal procollagen degradation assays with siRNA/CRISPR/KO tools

    PMID:30559329

    Open questions at the time
    • How luminal misfolding signals across the membrane to the cytosolic receptor unresolved
    • Generality beyond procollagen clients untested
  4. 2019 High

    Provided the structural basis for membrane fragmentation, showing the RHD's transmembrane hairpins and amphipathic helices induce curvature amplified by clustering.

    Evidence Molecular dynamics simulations plus in vitro liposome remodeling validated by electron microscopy

    PMID:31147549 PMID:33591770

    Open questions at the time
    • Atomic-resolution structure of the full RHD not determined
    • Coupling of clustering to autophagosome capture in vivo not directly shown
  5. 2020 High

    Showed oligomerization is the key activating step and is regulated by CAMK2B phosphorylation, and that a hyperactive patient variant (G216R) drives excessive ER-phagy and neuron death — establishing gain-of-function pathology distinct from loss-of-function disease.

    Evidence In vitro membrane fragmentation and oligomerization assays, CAMK2B kinase assay with phospho-mapping, in vivo ER-phagy flux, G216R variant analysis

    PMID:31930741

    Open questions at the time
    • Upstream trigger of CAMK2B activation at the ER unclear
    • How G216R alters self-association at the structural level not resolved
  6. 2020 High

    Connected RETREG1 to nutrient-responsive transcriptional control via the TFEB/TFE3 axis downstream of mTORC1.

    Evidence Promoter reporter assays, transcription factor manipulation, chondrocyte epistasis, medaka FAM134B knockout

    PMID:32716134

    Open questions at the time
    • Whether TFEB/TFE3 induction occurs in neurons unaddressed
  7. 2021 High

    Resolved ATG8 selectivity, showing RETREG1 binds the GABARAP subfamily more strongly than LC3 using both LIR core and a C-terminal helix.

    Evidence Crystal structure of FAM134B–GABARAP complex with affinity measurements and selectivity mutagenesis

    PMID:34854256 PMID:37273064

    Open questions at the time
    • Functional consequence of GABARAP preference for cargo-specific ER-phagy not established
  8. 2023 High

    Expanded the activation code, showing CBP acetylation primes intense ER-phagy and licenses CAMKII phosphorylation, while SIRT7 deacetylation restrains over-degradation.

    Evidence In vitro acetylation/deacetylation/phosphorylation assays with site mutagenesis and ER-phagy flux readouts

    PMID:37043189

    Open questions at the time
    • Stimuli controlling the CBP/SIRT7 balance in vivo unknown
  9. 2024 High

    Established opposing ubiquitin-based stability control: USP20 (via VAP recruitment) deubiquitinates and stabilizes the receptor, whereas TRIM21 ubiquitinates K247/K252 for degradation unless CKAP4 competitively protects it.

    Evidence In vitro deubiquitination with K48/K63 specificity, DUB screen, co-IPs, WIPI2 recruitment, ubiquitination site mutagenesis and competitive binding/degradation rescue

    PMID:38705724 PMID:39689859

    Open questions at the time
    • How USP20 and TRIM21 activities are balanced under a given stress unresolved
    • O-GlcNAcylation stabilization mechanism (36056188) is Medium-confidence
  10. 2024 Medium

    Broadened the substrate repertoire and organelle reach: RETREG1 degrades STIM1 to gate the cell cycle and influences mitochondrial fission via DRP1 recruitment.

    Evidence Co-IPs (STIM1, DRP1, OPA1), ER-to-autolysosome trafficking, cell cycle analysis, mitochondrial morphology imaging

    PMID:32559118 PMID:39128711 PMID:41178515

    Open questions at the time
    • DRP1 and OPA1 links rest on single-lab co-IP plus imaging
    • Direct vs. indirect effect on mitochondrial fission not disentangled
  11. 2025 High

    Identified RETREG1 as a cholesterol/SCAP sensor that couples ER-phagy to sterol biosynthesis and STING trafficking, integrating lipid metabolism with ER turnover.

    Evidence Direct cholesterol-binding assay, FAM134B–SCAP co-IP, cholesterol manipulation, SREBP2 and STING readouts

    PMID:41083602

    Open questions at the time
    • Structural basis of cholesterol/SCAP sensing unresolved
    • Physiological tissue context of sterol coupling untested
  12. 2025 High

    Defined RETREG1 as a broadly targeted node in host–pathogen conflict, hijacked by bacteria and viruses through distinct anti-oligomerization, sequestration, and micro-ER-phagy mechanisms.

    Evidence FAM134B KO cells/mice with bacterial burden and SopF oligomerization assays, ORF8/p62 condensate assays, CRISPR KO of autophagy genes with SERINC5 degradation and interactome MS

    PMID:35239449 PMID:36952345 PMID:40093084 PMID:40133256 PMID:41066524

    Open questions at the time
    • Whether autophagosome-independent micro-ER-phagy operates outside glycoGag context unknown
    • Shared structural determinant exploited by diverse pathogens not defined
  13. 2025 Medium

    Extended transcriptional and physiological control through ER-stress factors (ATF4–CEBPG, ATF6) and immune/tissue functions, including dendritic cell antigen presentation, sepsis pyroptosis, and protection from hepatic lipotoxicity.

    Evidence ChIP/promoter reporter assays, conditional and global KO mouse models, ERGIC turnover and STING1/GSDME readouts

    PMID:40437698 PMID:41787734 PMID:41874459

    Open questions at the time
    • Tissue-specific transcriptional logic across stressors not unified
    • Several immune phenotypes from single-lab conditional KOs
  14. 2025 High

    Demonstrated isoform specialization, showing FAM134B2 replaces FAM134B1 during myogenesis to drive ER reshaping, and that FAM134B/FAM134C cooperate to maintain axonal tubular ER.

    Evidence Isoform-specific double KO with rescue, proteomics and EM in myotubes; combined FAM134b/c KO mouse neurodegeneration with EM of axonal ER

    PMID:39039299 PMID:39762646

    Open questions at the time
    • Functional non-equivalence of paralogs mechanistically unexplained
    • Why neurons are uniquely vulnerable not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple regulatory layers — phosphorylation, acetylation, ubiquitination, O-GlcNAcylation, lipid sensing, and transcription — are integrated to set RETREG1 activity in a given cell type and stress, and how this dictates the loss- vs. gain-of-function disease balance, remains unresolved.
  • No unified model linking the regulatory inputs
  • Cell-type-specific thresholds for protective vs. lethal ER-phagy undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0060090 molecular adaptor activity 3 GO:0008092 cytoskeletal protein binding 1 GO:0008289 lipid binding 1
Localization
GO:0005783 endoplasmic reticulum 4 GO:0005829 cytosol 3 GO:0005739 mitochondrion 2
Pathway
R-HSA-9612973 Autophagy 5 R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-168256 Immune System 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1430728 Metabolism 2
Partners
CANXCKAP4DRP1GABARAPSCAPSTIM1TRIM21USP20
Complex memberships
FAM134B–Calnexin ER-phagy co-receptor complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 Loss-of-function mutations in FAM134B cause hereditary sensory and autonomic neuropathy type II (HSAN II). FAM134B knockdown results in structural alterations of the cis-Golgi compartment and induces apoptosis in primary dorsal root ganglion neurons, establishing FAM134B as critical for long-term survival of nociceptive and autonomic ganglion neurons. siRNA knockdown in primary dorsal root ganglion neurons, morphological analysis of cis-Golgi, apoptosis assays; human loss-of-function mutations identified Nature genetics High 19838196
2017 FAM134B is an ER-localized reticulophagy receptor that acts as a host restriction factor for dengue virus (DENV) and Zika virus (ZIKV). The flavivirus NS3 protease directly cleaves FAM134B at a single site within its reticulon homology domain (RHD), blocking ER/viral protein-enriched autophagosome formation and suppressing the reticulophagy pathway to promote viral replication. RNAi depletion, viral replication assays, in vitro protease cleavage assay identifying the cleavage site within the RHD, autophagosome formation quantification Autophagy High 28102736
2018 The ER-resident lectin chaperone Calnexin (CANX) acts as a co-receptor that recognizes ER-luminal misfolded procollagens and physically interacts with the ER-phagy receptor FAM134B. FAM134B in turn binds autophagosome membrane-associated LC3 and delivers a portion of ER containing both CANX and misfolded procollagen to the lysosome for degradation, constituting selective ER-phagy-based quality control. siRNA/CRISPR-Cas9/knockout gene deletion, co-immunoprecipitation of CANX–FAM134B complex, LC3 binding assay, lysosomal degradation assay in collagen-producing cells The EMBO journal High 30559329
2019 The reticulon homology domain (RHD) of FAM134B contains two wedge-shaped transmembrane helical hairpins and two amphipathic helices that induce membrane curvature and drive membrane remodeling. FAM134B clustering amplifies membrane-shaping effects, and disruption of the RHD structure impairs selective autophagy flux and leads to disease states. Molecular dynamics simulations of RHD in flat and curved membranes, in vitro liposome remodeling assays by electron microscopy, structural modeling Nature communications High 31147549
2020 FAM134B oligomerization through its reticulon-homology domain is required for ER membrane fragmentation in vitro and ER-phagy in vivo. Under ER-stress conditions, CAMK2B phosphorylates the RHD of FAM134B, enhancing FAM134B oligomerization and membrane fragmentation activity. The HSAN patient variant FAM134B G216R exhibits gain-of-function hyperactive self-association and membrane scission, resulting in excessive ER-phagy and sensory neuron death. In vitro membrane fragmentation assays, oligomerization assays, CAMK2B kinase assay with phosphorylation mapping, ER-phagy flux assays in vivo, analysis of patient-derived G216R variant The EMBO journal High 31930741
2020 The nutrient-responsive transcription factors TFEB and TFE3 directly control ER-phagy by inducing transcription of FAM134B. The TFEB/TFE3–FAM134B axis promotes ER-phagy activation upon prolonged starvation. In chondrocytes, FGF signaling activates JNK-dependent proteasomal degradation of IRS1, which inhibits PI3K–PKB/Akt–mTORC1 and promotes TFEB/TFE3 nuclear translocation to enhance FAM134B transcription. Transcription factor overexpression/knockdown, FAM134B promoter reporter assays, genetic epistasis in chondrocytes, medaka fish FAM134B knockout for in vivo validation The EMBO journal High 32716134
2020 RETREG1/FAM134B mediates dual organelle turnover (reticulo-mito-phagy) by interacting with OPA1 (inner mitochondrial membrane protein) when AMFR-destabilized mitochondria form 'mitoplasts' that bring the inner mitochondrial membrane into ER proximity. RETREG1-dependent autophagosomal degradation of both AMFR and OPA1 occurs simultaneously. Co-immunoprecipitation of RETREG1–OPA1 interaction, structured illumination and STED microscopy, autophagosomal degradation assays, stress induction with CCCP Autophagy Medium 32559118
2021 The crystal structure of the FAM134B–GABARAP complex reveals that FAM134B binds to the GABARAP subfamily more strongly than to the LC3 subfamily. FAM134B uses both its LIR core motif and a C-terminal helix to bind GABARAP, and structural determinants for this binding selectivity were identified. Crystal structure determination of FAM134B–GABARAP complex, binding affinity measurements, mutagenesis to identify selectivity determinants FEBS open bio High 34854256
2021 FAM134B-RHD spontaneously forms clusters driven by curvature-mediated attractions. At a critical cluster size, FAM134B-RHD induces membrane bud formation. Budding kinetics depend on protein concentration and bilayer asymmetry. Molecular dynamics simulations of FAM134B-RHD clustering and membrane budding The journal of physical chemistry letters Low 33591770
2022 O-GlcNAc transferase (OGT) directly associates with FAM134B and O-GlcNAcylates it, which reduces FAM134B ubiquitination-mediated degradation, thereby stabilizing FAM134B and enhancing FAM134B-mediated ER-phagy under nutrient deprivation. Co-IP of OGT–FAM134B complex, O-GlcNAcylation site mapping, ubiquitination assays comparing wild-type vs. O-GlcNAc-mutant FAM134B, genetic manipulation in cells and rat IDD model Experimental & molecular medicine Medium 36056188
2022 SARS-CoV-2 ORF3a localizes to the ER and induces RETREG1/FAM134B-dependent reticulophagy through the HMGB1–BECN1 (beclin 1) pathway, leading to ER stress and inflammatory responses that facilitate SARS-CoV-2 infection. ORF3a overexpression/localization studies, FAM134B knockdown combined with reticulophagy flux assays, HMGB1–BECN1 pathway epistasis experiments Autophagy Medium 35239449
2022 GSDMD promotes autophagy and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity by forming pores on the ER membrane via its N-terminus, thereby activating FAM134B-mediated ER stress. FAM134B then interacts with autophagic protein LC3 to induce cardiac autophagy. GSDMD overexpression/knockdown in cardiomyocytes, ER membrane pore formation assay, co-IP of FAM134B–LC3, autophagy flux assays, in vivo mouse model Cell death & disease Medium 36289195
2023 FAM134B is acetylated by the acetyltransferase CBP, which elicits intense ER-phagy. FAM134B acetylation subsequently promotes CAMKII-mediated phosphorylation for sustained ER-phagy. Conversely, the deacetylase SIRT7 deacetylates FAM134B to temper its ER-phagy activity and prevent excessive ER degradation. In vitro acetylation assay with CBP, deacetylation assay with SIRT7, phosphorylation assay with CAMKII, ER-phagy flux measurements, mutagenesis of acetylation sites The Journal of cell biology High 37043189
2023 Coronavirus ORF8 binds FAM134B and ATL3 and undergoes condensation with p62, sequestering FAM134B and ATL3 into ORF8/p62 liquid droplets. This disrupts ER-phagy, facilitates viral double-membrane vesicle (DMV) formation, and activates ER stress. Co-IP of ORF8–FAM134B and ORF8–ATL3 interactions, phase separation/condensate assays, ER-phagy flux assays, DMV formation by EM, FAM134B knockdown/overexpression Cell reports Medium 36952345
2024 USP20 deubiquitinates FAM134B/RETREG1 by specifically cleaving K48- and K63-linked ubiquitin chains, thereby stabilizing RETREG1 and promoting reticulophagy under starvation. USP20 is recruited to the ER through its interaction with VAPs (VAMP-associated proteins), which also facilitate recruitment of WIPI2 to ER subdomains enriched in USP20 and RETREG1. DUB screen, in vitro deubiquitination assay with USP20, K48/K63 ubiquitin chain specificity assays, co-IP of USP20–VAP and USP20–RETREG1 interactions, WIPI2 recruitment assay, reticulophagy flux measurement Autophagy High 38705724
2024 TRIM21 ubiquitinates RETREG1 at K247 and K252, facilitating its proteasomal degradation. CKAP4 competitively binds RETREG1 and shields it from TRIM21-mediated degradation, thereby stabilizing RETREG1 and modulating reticulophagy. Stress-induced TRIM21 upregulation reduces RETREG1 to restore ER stress equilibrium. Co-IP of CKAP4–RETREG1 and TRIM21–RETREG1 interactions, ubiquitination site mapping (K247/K252) by mutagenesis, proteasomal degradation assays, competitive binding assay Autophagy High 39689859
2024 FAM134B interacts with DDX3X and prevents its proteasomal degradation by reducing K48-linked polyubiquitination and enhancing K63-linked polyubiquitination of DDX3X. DDX3X stabilization promotes transcription of Rac1, activating AKT signaling in hepatocellular carcinoma. DDX3X also reciprocally increases FAM134B transcriptional activity, forming a positive feedback loop. Co-IP of FAM134B–DDX3X, ubiquitin linkage assays (K48/K63), Rac1 transcription reporter, AKT signaling readouts, FAM134B knockdown in vivo/in vitro Cell death & disease Medium 41198618
2024 FAM134B interacts with the canonical mitochondrial fission-promoting protein DRP1. Functional depletion of FAM134B leads to local actin rearrangement and reduced DRP1 recruitment onto mitochondria, resulting in mitochondrial hyperfusion. FAM134B levels decrease with aging in rat brains and in Parkinson's disease models. Co-IP of FAM134B–DRP1, fluorescence microscopy of mitochondrial morphology, actin staining, DRP1 recruitment assay upon FAM134B knockdown/KO Journal of cell science Medium 41178515
2024 FAM134B degrades STIM1 (an ER Ca2+ sensor) via ER-phagy. FAM134B binds STIM1 through its C-terminal cytosolic region; FAM134B knockdown increases STIM1 protein levels by reducing its transport from ER to autolysosomes, accelerates G1-to-S phase transition, and promotes cell proliferation. Co-IP of FAM134B–STIM1, ER-to-autolysosome trafficking assay, cell cycle analysis (G1/S), cell proliferation assay upon FAM134B knockdown The Journal of biological chemistry Medium 39128711
2025 FAM134B directly interacts with both cholesterol and SCAP (a key regulator of cholesterol biosynthesis). When ER cholesterol is high, FAM134B and SCAP are sequestered by cholesterol-tightened interactions, halting ER-phagy, STING activation, and cholesterol synthesis. Under low cholesterol, FAM134B dissociates from SCAP, allowing SCAP to activate SREBP2 and upregulate cholesterol synthesis, while free FAM134B facilitates ER-phagy through oligomerization or aids STING trafficking. Direct cholesterol-binding assay, co-IP of FAM134B–SCAP complex, cholesterol manipulation experiments, SREBP2 activation assay, ER-phagy and STING trafficking readouts Nature cell biology High 41083602
2025 ATF4 forms a heterodimer with CEBPG/C/EBPγ and binds directly to the promoter and enhancer regions of the RETREG1 gene to transcriptionally upregulate RETREG1-mediated reticulophagy in response to lipotoxic stress. RETREG1 knockout mice exhibit more severe hepatic lipotoxicity, confirming protective function. ChIP identifying ATF4 and CEBPG binding sites in RETREG1 promoter/enhancer, co-IP of ATF4–CEBPG heterodimer, RETREG1 promoter reporter assay, retreg1 KO mouse model Autophagy High 40437698
2025 Salmonella Typhimurium inhibits ER-phagy by targeting FAM134B through the bacterial effector protein SopF, preventing FAM134B oligomerization required for efficient ER-phagy. FAM134B knockout raises intracellular Salmonella numbers, while FAM134B activation reduces bacterial burden. FAM134B knockout cells/mice infected with Salmonella, bacterial burden quantification, FAM134B oligomerization assay in presence/absence of SopF, FAM134B activation experiments Nature communications Medium 40133256
2025 MLV glycoGag exploits RETREG1/FAM134B to downregulate SERINC5 at the ER via micro-ER-phagy through an autophagosome-independent process that bypasses ATG3, ATG5, ATG7, BECN1, LC3 lipidation, and PIK3C3. RETREG1 knockout abolishes degradation of ER-retained SERINC5. CRISPR/Cas9 knockout of RETREG1 and autophagy genes (ATG3, ATG5, ATG7, BECN1, PIK3C3), affinity-purified mass spectrometry, SERINC5 degradation assays, co-localization studies PLoS pathogens High 40093084 41066524
2025 During myogenesis, FAM134B1 is degraded and replaced by FAM134B2. FAM134B2, with its partial reticulon homology domain, drives ER reshaping and reticulophagy during the active differentiation phase. Knockout of both FAM134B isoforms results in aberrant proteome landscape and dilated ER structures, rescued by FAM134B2 re-expression but only partially by FAM134B1. FAM134B double-isoform knockout in myotubes, isoform-specific re-expression rescue experiments, proteomics of ER proteome, EM for ER morphology, ER-phagy flux assays during differentiation The EMBO journal High 39762646
2025 ATF6 directly transcriptionally regulates RETREG1 expression in response to LPS-induced ER stress. RETREG1-mediated reticulophagy reduces excessive ER stress via the EIF2AK3 signaling pathway and inhibits MARCH8-dependent MHC-II ubiquitination to maintain antigen presentation in dendritic cells. ATF6 knockout mice, RETREG1 promoter analysis, Cd11ccreRetreg1fl/fl conditional KO mice, MHC-II ubiquitination assay, EIF2AK3 pathway epistasis, DC function assays Advanced science Medium 41874459
2025 RETREG1-deficiency in dendritic cells activates CASP3–GSDME-dependent pyroptosis during sepsis by inhibiting autophagic degradation of the ERGIC (ER-Golgi intermediate compartment), resulting in abnormal STING1 activation. Genetic downregulation of TMED9 prevents STING1 activation and GSDME-mediated pyroptosis by disrupting ERGIC structure. Cd11ccreRetreg1fl/fl KO mice, ERGIC turnover assays, STING1 activation assays, CASP3/GSDME cleavage readouts, Tmed9 siRNA epistasis, sepsis CLP model Autophagy Medium 41787734
2025 FAM134B interacts with GSTK1 (glutathione S-transferase kappa 1), and silencing GSTK1 further aggravates reduction in reticulophagy and tubular injury that can be partially blocked by RETREG1 overexpression, establishing GSTK1 as a functional partner of RETREG1 in ER homeostasis. Immunoprecipitation coupled with mass spectrometry (IP-MS) identifying GSTK1, co-IP validation, GSTK1 siRNA in proximal tubule-specific Retreg1 KO mice and HK-2 cells, reticulophagy flux assays Autophagy Medium 40778749
2019 FAM134B overexpression in HeLa cells is sufficient to impair ER homeostasis, accelerate ER degradation, and cause ER stress, the unfolded protein response (UPR), and ER-phagy-dependent cell death. This demonstrates that excessive FAM134B-driven ER-phagy can itself be lethal. FAM134B overexpression in HeLa cells, ER stress markers (UPR), autophagosome number/size quantification, cell death assays, autophagy inhibitor controls The Journal of biological chemistry Medium 31748416
2019 In hepatocellular carcinoma, FAM134B induces tumorigenesis and epithelial-to-mesenchymal transition (EMT) via the Akt signaling pathway, with subsequent glycogen synthase kinase-3β phosphorylation, β-catenin accumulation, and Snail stabilization. FAM134B gain- and loss-of-function experiments, Akt pathway activator/inhibitor pharmacological rescue, nude mouse xenograft and lung metastasis models, Western blot for pathway components Molecular oncology Medium 30556279
2018 FAM134B physically interacts with CAP1, EB1, CYPB/PPIB, and KDELR2 in colon cancer cells. Exogenous suppression of FAM134B leads to upregulation of EB1 and reduction of KDELR2 expression; elevated EB1 promotes WNT/β-catenin signaling by inactivating the tumor suppressor APC. LC-MS/MS on anti-FAM134B co-immunoprecipitate, Western blot and confocal microscopy validation of FAM134B–EB1, FAM134B–CYPB, FAM134B–KDELR2 interactions, shRNA-mediated FAM134B silencing Molecular carcinogenesis Medium 29964340
2018 m6A modification of FAM134B mRNA is recognized by the m6A reader protein YTHDF2, which binds FAM134B mRNA and reduces its protein level by decreasing mRNA lifetime. A non-m6A FAM134B coding sequence (FAM134B-MUT) is expressed at higher levels, promotes porcine preadipocyte adipogenic differentiation more effectively, and upregulates PPARγ and C/EBPα. m6A site mapping on FAM134B CDS, YTHDF2 RNA immunoprecipitation, wild-type vs. m6A-mutant FAM134B transfection, mRNA stability assay, adipogenic differentiation assays IUBMB life Medium 30506811
2023 FAM134B (wild-type and HSAN2B-linked mutants) interact with LC3/GABARAPL1 in cells, as shown by NanoBiT reporter assay. C-terminal truncated FAM134B mutants show lower protein–protein interaction with LC3 and lower ER-phagy activity. The G216R variant retains LC3/GABARAPL1 interaction to the same extent as wild-type FAM134B. NanoBiT split-luciferase protein–protein interaction reporter assay for FAM134B–LC3/GABARAPL1 interaction, GFP-tagged ER-phagy reporter flux assay, transfection into FAM134B-deficient Neuro2a cells Molecular biology reports Medium 37273064
2024 FAM134B and FAM134C cooperate in shaping tubular ER architecture in peripheral axons. Combined Fam134b/Fam134c double knockout (but not Fam134a combinations) in mice causes rapid neuromuscular and somatosensory degeneration, loss of motor and sensory axons, and expanded tubular ER with a transverse ladder-like appearance in long axons, without obvious cortical ER abnormalities. Single and combined FAM134 protein knockout mice, neuromuscular phenotyping, transmission electron microscopy of axonal ER morphology, peripheral nerve histopathology EMBO reports High 39039299

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 A selective ER-phagy exerts procollagen quality control via a Calnexin-FAM134B complex. The EMBO journal 217 30559329
2009 Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe sensory and autonomic neuropathy. Nature genetics 214 19838196
2019 Curvature induction and membrane remodeling by FAM134B reticulon homology domain assist selective ER-phagy. Nature communications 176 31147549
2017 Dengue and Zika viruses subvert reticulophagy by NS2B3-mediated cleavage of FAM134B. Autophagy 174 28102736
2020 FAM134B oligomerization drives endoplasmic reticulum membrane scission for ER-phagy. The EMBO journal 130 31930741
2020 MiT/TFE factors control ER-phagy via transcriptional regulation of FAM134B. The EMBO journal 91 32716134
2016 FAM134B, the Selective Autophagy Receptor for Endoplasmic Reticulum Turnover, Inhibits Replication of Ebola Virus Strains Makona and Mayinga. The Journal of infectious diseases 81 27511895
2019 Excessive ER-phagy mediated by the autophagy receptor FAM134B results in ER stress, the unfolded protein response, and cell death in HeLa cells. The Journal of biological chemistry 71 31748416
2022 Gasdermin D mediates endoplasmic reticulum stress via FAM134B to regulate cardiomyocyte autophagy and apoptosis in doxorubicin-induced cardiotoxicity. Cell death & disease 62 36289195
2020 Critical roles of FAM134B in ER-phagy and diseases. Cell death & disease 59 33199694
2017 MicroRNA-186-5p overexpression modulates colon cancer growth by repressing the expression of the FAM134B tumour inhibitor. Experimental cell research 57 28549913
2022 SARS-CoV-2 ORF3a induces RETREG1/FAM134B-dependent reticulophagy and triggers sequential ER stress and inflammatory responses during SARS-CoV-2 infection. Autophagy 55 35239449
2010 Mutation in FAM134B causing severe hereditary sensory neuropathy. Journal of neurology, neurosurgery, and psychiatry 53 21115472
2007 Oncogenic properties of a novel gene JK-1 located in chromosome 5p and its overexpression in human esophageal squamous cell carcinoma. International journal of molecular medicine 53 17487424
2022 Cancer cells adapt FAM134B/BiP mediated ER-phagy to survive hypoxic stress. Cell death & disease 52 35436985
2018 RETREG1 (FAM134B): A new player in human diseases: 15 years after the discovery in cancer. Journal of cellular physiology 51 29226326
2023 Coronavirus subverts ER-phagy by hijacking FAM134B and ATL3 into p62 condensates to facilitate viral replication. Cell reports 50 36952345
2016 Stage dependent expression and tumor suppressive function of FAM134B (JK1) in colon cancer. Molecular carcinogenesis 46 27120410
2022 O-GlcNAc transferase regulates intervertebral disc degeneration by targeting FAM134B-mediated ER-phagy. Experimental & molecular medicine 40 36056188
2014 The roles of JK-1 (FAM134B) expressions in colorectal cancer. Experimental cell research 40 24973512
2019 FAM134B induces tumorigenesis and epithelial-to-mesenchymal transition via Akt signaling in hepatocellular carcinoma. Molecular oncology 39 30556279
2020 RETREG1/FAM134B mediated autophagosomal degradation of AMFR/GP78 and OPA1 -a dual organellar turnover mechanism. Autophagy 38 32559118
2016 Identification of Novel FAM134B (JK1) Mutations in Oesophageal Squamous Cell Carcinoma. Scientific reports 37 27373372
1989 A novel germ-line JK transcript starting immediately upstream of JK1. Nucleic acids research 34 2506531
2021 Targeting FAM134B-mediated reticulophagy activates sorafenib-induced ferroptosis in hepatocellular carcinoma. Biochemical and biophysical research communications 33 34929448
2018 Loss of m6 A on FAM134B promotes adipogenesis in porcine adipocytes through m6 A-YTHDF2-dependent way. IUBMB life 33 30506811
2011 A strong synergistic epistasis between FAM134B and TNFRSF19 on the susceptibility to vascular dementia. Psychiatric genetics 33 21127458
2014 JK1 (FAM134B) represses cell migration in colon cancer: a functional study of a novel gene. Experimental and molecular pathology 32 24927874
2014 Genetic analysis of an allergic rhinitis cohort reveals an intercellular epistasis between FAM134B and CD39. BMC medical genetics 32 24970562
2021 FAM134B-RHD Protein Clustering Drives Spontaneous Budding of Asymmetric Membranes. The journal of physical chemistry letters 31 33591770
2024 USP20 deubiquitinates and stabilizes the reticulophagy receptor RETREG1/FAM134B to drive reticulophagy. Autophagy 30 38705724
2021 FAM134B-mediated endoplasmic reticulum autophagy protects against sepsis myocardial injury in mice. Aging 30 33819192
2018 Protein interactions of FAM134B with EB1 and APC/beta-catenin in vitro in colon carcinoma. Molecular carcinogenesis 30 29964340
2014 JK1 (FAM134B) gene and colorectal cancer: a pilot study on the gene copy number alterations and correlations with clinicopathological parameters. Experimental and molecular pathology 30 24825067
2019 FAM134B promotes esophageal squamous cell carcinoma in vitro and its correlations with clinicopathologic features. Human pathology 27 30794892
2017 Novel FAM134B mutations and their clinicopathological significance in colorectal cancer. Human genetics 27 28144752
2020 FAM134B Attenuates Seizure-Induced Apoptosis and Endoplasmic Reticulum Stress in Hippocampal Neurons by Promoting Autophagy. Cellular and molecular neurobiology 25 32086669
1990 Establishment of an erythroid cell line (JK-1) that spontaneously differentiates to red cells. Cancer 25 2169992
1993 DNA replication of parvovirus B 19 in a human erythroid leukemia cell line (JK-1) in vitro. Archives of virology 24 8328914
2023 A regulatory circuit comprising the CBP and SIRT7 regulates FAM134B-mediated ER-phagy. The Journal of cell biology 23 37043189
2021 FAM134B-Mediated ER-Phagy in Mg2+-Free Solution-Induced Mitochondrial Calcium Homeostasis and Cell Death in Epileptic Hippocampal Neurons. Neurochemical research 21 34212292
2021 FAM134B-Mediated ER-phagy Upregulation Attenuates AGEs-Induced Apoptosis and Senescence in Human Nucleus Pulposus Cells. Oxidative medicine and cellular longevity 20 34394825
2022 MiR-142-5p/FAM134B Axis Manipulates ER-Phagy to Control PRRSV Replication. Frontiers in immunology 19 35795666
2018 Exome Sequencing: Mutilating Sensory Neuropathy with Spastic Paraplegia due to a Mutation in FAM134B Gene. Case reports in genetics 19 30643655
2016 An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed. G3 (Bethesda, Md.) 19 27527794
2019 FAM134B improves preadipocytes differentiation by enhancing mitophagy. Biochimica et biophysica acta. Molecular and cell biology of lipids 18 31446166
2020 Differential expression of full-length and NH2 terminally truncated FAM134B isoforms in normal physiology and cancer. American journal of physiology. Gastrointestinal and liver physiology 17 33052704
2017 An electrochemical method for sensitive and rapid detection of FAM134B protein in colon cancer samples. Scientific reports 17 28273937
2021 ATG9A regulates proteostasis through reticulophagy receptors FAM134B and SEC62 and folding chaperones CALR and HSPB1. iScience 15 33870132
2019 MicroRNA-186 promotes cell proliferation and inhibits cell apoptosis in cutaneous squamous cell carcinoma by targeting RETREG1. Experimental and therapeutic medicine 15 30867688
2022 Apelin-13/APJ induces cardiomyocyte hypertrophy by activating the Pannexin-1/P2X7 axis and FAM134B-dependent reticulophagy. Journal of cellular physiology 14 35128666
2022 Piperine alleviates acute pancreatitis: A possible role for FAM134B and CCPG1 dependent ER-phagy. Phytomedicine : international journal of phytotherapy and phytopharmacology 14 35963197
2021 Roles of FAM134B in diseases from the perspectives of organelle membrane morphogenesis and cellular homeostasis. Journal of cellular physiology 13 33843059
2019 Hereditary sensory autonomic neuropathy type II: Report of two novel mutations in the FAM134B gene. Journal of the peripheral nervous system : JPNS 13 31596031
2025 Two FAM134B isoforms differentially regulate ER dynamics during myogenesis. The EMBO journal 12 39762646
2024 PRRSV non-structural protein 5 inhibits antiviral innate immunity by degrading multiple proteins of RLR signaling pathway through FAM134B-mediated ER-phagy. Journal of virology 12 39264156
2012 Characterization of the novel xylanase from the thermophilic Geobacillus thermodenitrificans JK1. Mikrobiologiia 12 23156689
2020 Overexpression of family with sequence similarity 134, member B (FAM134B) in colon cancers and its tumor suppressive properties in vitro. Cancer biology & therapy 11 32857678
2023 FAM134B-induced endoplasmic reticulum (ER)-phagy exacerbates cisplatin-insulted hair cell apoptosis ：Possible relation to excessive ER stress. Archives of biochemistry and biophysics 10 37813237
2021 The crystal structure of the FAM134B-GABARAP complex provides mechanistic insights into the selective binding of FAM134 to the GABARAP subfamily. FEBS open bio 10 34854256
2020 Beating the ER: novel insights into FAM134B function and regulation. The EMBO journal 10 32073155
2019 Hereditary Sensory and Autonomic Neuropathy 2B Caused by a Novel RETREG1 Mutation (c.765dupT) and Paternal Uniparental Isodisomy of Chromosome 5. Frontiers in genetics 9 31737055
2024 FAM134B deletion exacerbates apoptosis and epithelial-to-mesenchymal transition in rat lungs exposed to hyperoxia. iScience 8 39092177
2022 RETREG1-mediated ER-phagy activation induced by glucose deprivation alleviates nucleus pulposus cell damage via ER stress pathway. Acta biochimica et biophysica Sinica 8 35607959
2021 Hereditary sensory and autonomic neuropathy in a family of mixed breed dogs associated with a novel RETREG1 variant. Journal of veterinary internal medicine 8 34387380
2020 Molecular dynamics simulations reveal how the reticulon-homology domain of the autophagy receptor RETREG1/FAM134B remodels membranes for efficient selective reticulophagy. Autophagy 8 31996076
2018 Two mixed breed dogs with sensory neuropathy are homozygous for an inversion disrupting FAM134B previously identified in Border Collies. Journal of veterinary internal medicine 8 30307654
2024 Excessive ER-phagy mediated by FAM134B contributes to trophoblast cell mitochondrial dysfunction in preeclampsia. Acta biochimica et biophysica Sinica 7 38774969
2024 Fam134c and Fam134b shape axonal endoplasmic reticulum architecture in vivo. EMBO reports 7 39039299
2024 CKAP4 in hepatocellular carcinoma: competitive RETREG1/FAM134B binding, reticulophagy regulation, and cancer progression. Autophagy 7 39689859
2023 Phenobarbital, a hepatic metabolic enzyme inducer, inhibits preneoplastic hepatic lesions with expression of selective autophagy receptor p62 and ER-phagy receptor FAM134B in high-fat diet-fed rats through the inhibition of ER stress. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 7 36657701
2022 FAM134B-mediated ER-phagy alleviates endoplasmic reticulum stress of rat soleus muscle in response to acute exercise. General physiology and biophysics 7 35253652
2025 GSTK1 and RETREG1/FAM134B-mediated reticulophagy attenuates tubular injury in diabetic nephropathy through endoplasmic reticulum stress and apoptosis. Autophagy 6 40778749
2019 FAM134B promotes adipogenesis by increasing vesicular activity in porcine and 3T3-L1 adipocytes. Biological chemistry 6 30291780
2025 The ER-phagy receptor FAM134B is targeted by Salmonella Typhimurium to promote infection. Nature communications 5 40133256
2025 Dendrobine attenuates lipopolysaccharide-induced acute lung injury by modulating FAM134B-mediated endoplasmic reticulum autophagy and mitochondrial function. Phytomedicine : international journal of phytotherapy and phytopharmacology 5 40532488
2016 Cis-vaccenic acid induces differentiation and up-regulates gamma globin synthesis in K562, JK1 and transgenic mice erythroid progenitor stem cells. European journal of pharmacology 5 26879870
2025 FAM134B-mediated endoplasmic reticulum autophagy protects against cisplatin-induced spiral ganglion neuron damage. Frontiers in pharmacology 4 39949397
2025 RETREG1-mediated reticulophagy is activated by an ATF4-CEBPG/C/EBPγ heterodimer and confers protection against lipotoxicity. Autophagy 4 40437698
2025 Murine leukemia virus glycoGag antagonizes SERINC5 via ER-phagy receptor RETREG1. PLoS pathogens 4 41066524
2025 Cholesterol sensing by the SCAP-FAM134B complex regulates ER-phagy and STING innate immunity. Nature cell biology 4 41083602
2023 Elevated FAM134B expression induces radiation-sensitive in hepatocellular carcinoma. BMC cancer 4 37460952
2025 Maresin1 ameliorates osseointegration in type 2 diabetes mellitus by promoting FAM134B-mediated ER-phagy in osteoblasts. Biochemical pharmacology 3 40619017
2024 Degradation of STIM1 through FAM134B-mediated ER-phagy is potentially involved in cell proliferation. The Journal of biological chemistry 3 39128711
2024 Qingre Huoxue decoction attenuates myocardial ischemia‒reperfusion injury by regulating the autophagy‒endoplasmic reticulum stress axis via FAM134B-mediated ER-phagy. Frontiers in pharmacology 3 39664523
2025 FAM134B-mediated ER-phagy alleviates alcohol-related liver fibrosis by reducing endoplasmic reticulum stress. International journal of biological macromolecules 2 40154686
2025 FAM134B in Cellular Homeostasis: Bridging Endoplasmic Reticulum-Phagy to Human Diseases. International journal of biological sciences 2 40959290
2023 Phenotypic features of RETREG1-related hereditary sensory autonomic neuropathy. Journal of the peripheral nervous system : JPNS 2 37448294
2022 Identification of sensory dysfunction and nervous structure changes in Fam134b knockout mice. Neurological research 2 36302074
2025 Murine Leukemia Virus GlycoGag Antagonizes SERINC5 via ER-phagy Receptor RETREG1. bioRxiv : the preprint server for biology 1 40093084
2025 A RETREG1/FAM134B isoform switch regulates reticulophagy during myogenesis. Autophagy 1 40277456
2025 The immune regulation and signaling transduction of FAM134B-mediated endoplasmic reticulum-phagy in ferroptosis of dendritic cells after sepsis. Journal of advanced research 1 40816353
2025 Targeting FAM134B-DDX3X axis inhibiting AKT signaling in hepatocellular carcinoma. Cell death & disease 1 41198618
2025 Loss of FAM134B increased endoplasmic reticulum stress and induced cell autophagy in breast cancer. Frontiers in immunology 1 41293153
2025 RETREG1/FAM134B-mediated micro-ER-phagy in the retrovirus-SERINC5 arms race. Autophagy reports 1 41438769
2022 [Dithiothreitol promotes apoptosis in rat hepatocytes by inhibiting family with sequence similarity 134 member B (FAM134B)-mediated endoplasmic reticulophagy]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 1 36585233
2026 RETREG1/FAM134B-mediated ERGICphagy regulates GSDME-dependent dendritic cell pyroptosis during sepsis. Autophagy 0 41787734
2026 RETREG1-Mediated Reticulophagy is Essential for Dendritic Cell Maturation and Function in Sepsis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41874459
2025 The endoplasmic reticulum protein FAM134B acts as a regulator of mitochondrial morphology. Journal of cell science 0 41178515
2023 Molecular characterization of wild-type and HSAN2B-linked FAM134B. Molecular biology reports 0 37273064

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