Affinage

TRIM3

Tripartite motif-containing protein 3 · UniProt O75382

Length
744 aa
Mass
80.8 kDa
Annotated
2026-06-10
100 papers in source corpus 25 papers cited in narrative 25 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

TRIM3 (BERP) is a RING-type, microtubule- and vesicle-associated TRIM-family E3 ubiquitin ligase that couples substrate ubiquitination to the control of synaptic architecture, membrane trafficking, innate immune signaling, and tumor suppression (PMID:24393003, PMID:26527743, PMID:32878999). Its catalytic output depends on the RING domain, which in placental mammals is monomeric and inactive in isolation and is activated by heterodimerization with TRIM2 through their coiled-coil and filamin domains (PMID:36481767); reconstituted ligase activity uses UbcH5a as the preferred E2 (PMID:24393003). In neurons, TRIM3 ubiquitinates the postsynaptic scaffold GKAP/SAPAP1 to drive its proteasomal turnover and restrict dendritic spine head size (PMID:20352094), and polyubiquitinates synaptic γ-actin—likely cotranslationally at mRNP granules—so that its loss elevates spine density, long-term potentiation, and contextual fear memory (PMID:26527743); it also assembles into a cytoskeletal recycling (CART) complex with Hrs/actinin-4/myosin V required for transferrin receptor recycling (PMID:15772161) and binds the kinesin KIF21B to support dendritic motor motility independently of ligase activity (PMID:24086586). TRIM3 binds microtubules via its C-terminal NHL repeats and sustains acetylated tubulin levels by maintaining ATAT1 protein abundance (PMID:38149663). In innate immunity it controls TLR3: K63-linked ubiquitination at K831 directs TLR3 trafficking from Golgi to endolysosomes for dsRNA sensing (PMID:32878999), while a distinct K48-linked modification promotes TLR3 turnover within an IFN-β feedback loop (PMID:41545343). As a tumor suppressor across glioma, lung, breast, colorectal and other cancers, TRIM3 restrains proliferation by ubiquitinating p21 (PMID:24393003), suppresses glioblastoma stemness by limiting c-Myc and blocking Importin-dependent nuclear transport of the NOTCH1 intracellular domain (PMID:24947043, PMID:26893479), and promotes ferroptosis through K11-linked ubiquitination of SLC7A11/xCT at K37 via its NHL domain (PMID:37978273). Additional reported substrates and partners include p53, ERα, GRP78, FABP4, Beclin1, importin α3/ACTN4 and YAP1, with conflicting reports on the direction of p53 regulation (PMID:33292295, PMID:34508066, PMID:35392925, PMID:36894560).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 Medium

    Established the first physical partner of TRIM3, defining its N-terminal RBCC domain as a protein-interaction module that engages the actin-crosslinker α-actinin-4.

    Evidence Yeast two-hybrid with RBCC bait plus reciprocal Co-IP and co-localization in PC12 cells

    PMID:10673389

    Open questions at the time
    • No functional consequence of the interaction established
    • Ubiquitination of α-actinin-4 not tested at this stage
  2. 2005 High

    Placed TRIM3 in a defined cytoskeletal trafficking machine, showing it is a structural subunit of the CART complex required for receptor recycling rather than degradation.

    Evidence Reciprocal Co-IP, dominant-negative disruption of linear complex assembly, transferrin recycling and EGFR degradation assays

    PMID:15772161

    Open questions at the time
    • Role of TRIM3 catalytic activity within the complex not addressed
    • Whether complex assembly involves ubiquitination unknown
  3. 2010 High

    Identified TRIM3 as a functional E3 ligase in the brain that degrades a postsynaptic scaffold and shapes spine morphology, linking ubiquitination to synaptic remodeling.

    Evidence Co-IP, ubiquitination assay with proteasome rescue, RNAi in rat hippocampal neurons with spine morphology readout; separately, knockout mice with GABA-A trafficking/electrophysiology phenotype and p53-dependent expression

    PMID:20352094 PMID:20543135

    Open questions at the time
    • Direct ubiquitination site on GKAP not mapped
    • Mechanism linking p53 to TRIM3 transcription not detailed
  4. 2013 Medium

    Extended TRIM3 function into cell-cycle control and motor transport, showing a ligase-dependent tumor-suppressive role via p21 and a ligase-independent role in kinesin motility.

    Evidence Co-IP of TRIM3 with p21 and with KIF21B, mouse glioma model, neuronal motility assays

    PMID:23318451 PMID:24086586

    Open questions at the time
    • Whether p21 is ubiquitinated or merely sequestered not resolved here
    • Mechanism by which TRIM3 drives KIF21B motility unknown
  5. 2014 High

    Demonstrated that RING-dependent ligase activity is necessary for growth suppression and that TRIM3 restrains glioblastoma stemness as a human Brat ortholog.

    Evidence In vitro ubiquitination reconstitution of p21 with UbcH5a and RING mutagenesis; GBM reconstitution with stem-marker, neurosphere, and asymmetric-division readouts plus xenograft

    PMID:24393003 PMID:24947043

    Open questions at the time
    • Direct biochemical mechanism of c-Myc suppression not shown
    • Link between p21 ubiquitination and asymmetric division not established
  6. 2015 High

    Resolved how TRIM3 controls structural plasticity, showing it ubiquitinates γ-actin cotranslationally at synaptic mRNP granules to limit spine density, LTP, and memory.

    Evidence Trim3 knockout mice, in vitro γ-actin ubiquitination, TRIM3/Actg1 mRNP co-localization, spine, LTP, and fear-conditioning assays

    PMID:26527743

    Open questions at the time
    • Cotranslational ubiquitination mechanism inferred rather than directly imaged
    • Coupling to GKAP pathway not integrated
  7. 2016 Medium

    Defined a non-degradative tumor-suppressive mechanism whereby TRIM3 blocks Notch signaling by binding the Importin complex to prevent NICD nuclear entry.

    Evidence Co-IP of TRIM3 with Importin, NICD nuclear transport assay in GBM cells, Drosophila brat-RNAi tumor model

    PMID:26893479

    Open questions at the time
    • Whether Importin binding requires ubiquitination not tested
    • Direct NICD-TRIM3 interaction not demonstrated
  8. 2018 Medium

    Connected TRIM3 to NF-κB regulation through ligase-dependent turnover of importin α3 and ACTN4, positioning it as a metastasis suppressor.

    Evidence Co-IP, ubiquitination and proteasomal degradation assays, NF-κB reporter and p65 methylation analysis, in vivo metastasis assays

    PMID:30542119

    Open questions at the time
    • Ubiquitin linkage type not specified
    • Direct cause-effect between substrate degradation and p65 methylation incomplete
  9. 2020 High

    Established a substrate-specific trafficking mechanism in innate immunity: K63-linked ubiquitination of TLR3 at K831 routes it from Golgi to endolysosomes for dsRNA sensing.

    Evidence Reconstituted K63-specific ubiquitination, K831 mutagenesis, subcellular fractionation/confocal localization, Trim3 knockout cells and mice, poly(I:C) stimulation; separate Low-confidence IRF3 phosphorylation report

    PMID:32878999 PMID:34643859

    Open questions at the time
    • IRF3 interaction (Low confidence) lacks ubiquitination or reconstitution evidence
    • How TRIM3 selects K63 versus K48 on TLR3 unresolved
  10. 2022 High

    Explained the catalytic basis of TRIM3 regulation, revealing its RING is autoinhibited in placental mammals and activated by TRIM2 heterodimerization.

    Evidence RING structural analysis, in vitro ubiquitination with mutagenesis, TRIM2-TRIM3 heterodimerization Co-IP and domain mapping

    PMID:36481767

    Open questions at the time
    • Which physiological substrates require TRIM2 partnering not delineated
    • Whether all reported substrates depend on heterodimer activation untested
  11. 2023 Medium

    Diversified TRIM3 ubiquitin-linkage output and substrate range, including K11-linked degradation of SLC7A11 promoting ferroptosis and degradation of FABP4 suppressing lipid-driven metastasis.

    Evidence NHL-domain mapping, K11- and K48-linkage-specific ubiquitination, site mutagenesis (K37), proteasome rescue, ROS/lipid and migration assays, xenografts; plus cytoplasmic-retention control of p53 with domain mapping

    PMID:36894560 PMID:37212515 PMID:37978273

    Open questions at the time
    • NHL domain used for both microtubule and SLC7A11 binding; selectivity unexplained
    • Direction of p53 regulation conflicts with other reports
  12. 2024 Medium

    Defined a ubiquitination-independent cytoskeletal function: TRIM3 binds microtubules via NHL repeats and sustains acetylated tubulin by maintaining ATAT1 protein levels.

    Evidence Differential extraction proteomics, nocodazole/taxol drug-sensitivity mass spectrometry, NHL deletion mapping, ATAT1 protein quantification independent of transcription

    PMID:38149663

    Open questions at the time
    • Whether ATAT1 is a direct TRIM3 substrate not shown
    • Mechanism stabilizing ATAT1 unknown
  13. 2026 Medium

    Revealed a second mode of TLR3 control, where K48-linked degradation of TLR3 operates within a reciprocal IFN-β negative-feedback loop suppressing lung cancer.

    Evidence Co-IP, K48-linked ubiquitination and TLR3 stability assays, IFN-β ELISA, CD8+ T cell cytotoxicity co-culture, xenograft

    PMID:41545343

    Open questions at the time
    • Reconciliation with K63-linked stabilizing modification of TLR3 not mechanistically resolved
    • Signal determining linkage choice unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TRIM3 selects among diverse substrates and ubiquitin-linkage types, and which functions require TRIM2 heterodimer activation versus ligase-independent scaffolding, remains unresolved.
  • No structural model of substrate engagement by the NHL domain
  • Conflicting reports on p53 regulation direction unreconciled
  • Determinants of K11 vs K48 vs K63 linkage selection unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0008092 cytoskeletal protein binding 4 GO:0016874 ligase activity 4 GO:0060090 molecular adaptor activity 2
Localization
GO:0005794 Golgi apparatus 2 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2 GO:0005768 endosome 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-9609507 Protein localization 3 R-HSA-112316 Neuronal System 2 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 1
Partners
ACTN4ESR1GKAP/SAPAP1IMPORTIN Α3KIF21BSLC7A11TLR3TRIM2
Complex memberships
CART complex (Hrs/actinin-4/BERP/myosin V)TRIM2-TRIM3 heterodimer

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 TRIM3 (BERP) is a subunit of the CART (cytoskeleton-associated recycling or transport) complex containing Hrs/actinin-4/BERP/myosin V, which assembles in a linear manner and is required for efficient transferrin receptor recycling to the plasma membrane but not for EGFR degradation. Disrupting any binding interaction within the complex inhibits recycling rate and shunts receptors to a slower recycling endosome pathway. Co-immunoprecipitation, dominant-negative disruption of complex assembly, transferrin recycling assay, EGFR degradation assay Molecular biology of the cell High 15772161
2000 TRIM3 (BERP) binds alpha-actinin-4 via its RBCC domain (N-terminus). Alpha-actinin-4 can be co-immunoprecipitated with BERP from HEK293 cells, and the two proteins co-localize in the cytoplasm of differentiated PC12 cells. Yeast two-hybrid screen with RBCC domain as bait, co-immunoprecipitation from transfected HEK293 cells, immunohistochemistry co-localization Biochemical and biophysical research communications Medium 10673389
2010 TRIM3 functions as an E3 ubiquitin ligase for the postsynaptic density scaffold protein GKAP/SAPAP1. TRIM3 is present in PSD fractions from rat brain, stimulates ubiquitination and proteasome-dependent degradation of GKAP, induces loss of GKAP and Shank1 from postsynaptic sites, and RNAi knockdown of TRIM3 increases GKAP/Shank1 at synapses and enlarges dendritic spine heads. TRIM3 RNAi also prevented activity-dependent GKAP loss. Co-immunoprecipitation, ubiquitination assay, proteasome inhibitor rescue, RNAi knockdown in rat hippocampal neurons, immunofluorescence quantification of spine morphology PloS one High 20352094
2010 TRIM3 (BERP) expression is upregulated in a p53-dependent manner. BERP-deficient mice show increased resistance to pentylenetetrazol-induced seizures, decreased amplitude of GABA-A receptor-mediated miniature inhibitory postsynaptic currents, and reduced surface expression of GABA-A receptors containing the gamma2-subunit, suggesting BERP regulates intracellular trafficking of GABA-A receptors at a posttranscriptional level. Gene targeting (knockout mice), electrophysiology (mIPSC recording), surface protein expression by biochemical fractionation, p53-dependent transcriptional regulation assay Proceedings of the National Academy of Sciences of the United States of America High 20543135
2013 TRIM3 interacts with KIF21B (a neuronal kinesin enriched in dendrites) via its RBCC domain. TRIM3 is found at intracellular and Golgi-derived vesicles and co-localizes with KIF21B in neurons. TRIM3 depletion reduces KIF21B motor motility, while its E3 ligase function is not involved in KIF21B degradation. Co-immunoprecipitation, Trim3 gene deletion in mice, TRIM3 overexpression in cultured neurons, co-localization imaging, motility assays PloS one Medium 24086586
2013 TRIM3 can bind to the CDK inhibitor p21(WAF1/CIP1). Reducing TRIM3 expression accelerated platelet-derived growth factor-induced glioma development in mice, consistent with a tumor suppressor role. TRIM3 binding to p21 may sequester p21 and prevent it from facilitating cyclin D1-CDK4 accumulation. Co-immunoprecipitation (TRIM3-p21 binding), mouse glioma model with reduced TRIM3 expression Oncogene Medium 23318451
2014 TRIM3 suppresses c-Myc expression and activity in human glioma cell lines and attenuates stem-like properties of primary GBM cultures (neurosphere formation, CD133/Nestin/Nanog expression). TRIM3 expression increases the proportion of glioblastoma stem cells dividing asymmetrically rather than symmetrically, functioning as a human ortholog of Drosophila Brat. TRIM3 reconstitution in GBM cell lines and neurospheres, neurosphere formation assay, flow cytometry for stem markers, asymmetric division quantification, in vivo xenograft Cancer research Medium 24947043
2014 The RING domain E3 ligase activity of TRIM3 is required for its growth-suppressive function. In a reconstituted in vitro ubiquitination system, TRIM3 promotes ubiquitination of p21 with UbcH5a as the preferred E2 enzyme. RING domain mutations abolish both E3 ligase activity and growth suppression. In vitro ubiquitination reconstitution with UbcH5a as E2, RING domain mutagenesis, cell proliferation assay The Biochemical journal High 24393003
2015 TRIM3 E3 ubiquitin ligase regulates synaptic γ-actin levels by polyubiquitylating γ-actin, most likely cotranslationally at synaptic sites. TRIM3 protein and Actg1 transcript co-localize in messenger ribonucleoprotein (mRNP) granules responsible for dendritic mRNA targeting. Trim3(-/-) mice have increased γ-actin at hippocampal synapses, higher spine densities, increased long-term potentiation, and enhanced short-term contextual fear memory. Trim3 knockout mice, co-localization of TRIM3 protein and Actg1 mRNA in mRNP granules, in vitro ubiquitination of γ-actin, spine density quantification, LTP electrophysiology, fear conditioning behavioral assay The Journal of cell biology High 26527743
2016 TRIM3 (human ortholog of Drosophila Brat) suppresses nuclear transport of active NOTCH1 intracellular domain (NICD) in glioblastoma by directly binding to the Importin complex. This attenuates Notch signaling and the stem cell component, maintaining stem cell equilibrium. Co-immunoprecipitation of TRIM3 with Importin complex, NICD nuclear transport assay, TRIM3 knockdown/overexpression in GBM cells, Drosophila brat-RNAi brain tumor model Cancer research Medium 26893479
2020 TRIM3 mediates K63-linked polyubiquitination of TLR3 at K831, promoting TLR3 trafficking from the Golgi apparatus to endolysosomes via ESCRT complexes, which is required for dsRNA sensing and antiviral innate immune response. TRIM3 is mainly localized in the Golgi apparatus and translocates to early endosomes upon poly(I:C) stimulation. TRIM3 deficiency impairs TLR3 trafficking and reduces antiviral gene expression. Co-immunoprecipitation, ubiquitination assay with K63 linkage-specific analysis, site-directed mutagenesis (K831), subcellular fractionation, confocal localization, Trim3 knockout cells and mice, poly(I:C) stimulation assay Proceedings of the National Academy of Sciences of the United States of America High 32878999
2023 TRIM3 directly interacts with SLC7A11/xCT through its NHL domain and promotes K11-linked ubiquitination of SLC7A11 at K37, leading to proteasome-mediated degradation of SLC7A11. This reduces cystine import, increases ROS and lipid peroxidation, and promotes ferroptosis in non-small cell lung cancer cells. Co-immunoprecipitation, ubiquitination assay with K11 linkage-specific analysis, NHL domain deletion analysis, site-directed mutagenesis (K37), proteasome inhibitor rescue, ROS/lipid peroxidation measurement, in vivo xenograft Cell death and differentiation High 37978273
2018 TRIM3 directly interacts with and induces E3 ligase-dependent proteasomal turnover of importin α3 and α-Actinin-4 (ACTN4), controlling NF-κB activity. TRIM3 downregulation leads to constitutive NF-κB activation through disruption of the NF-κB–IκB-α negative feedback loop and enhanced p65 DNA-binding via symmetrical dimethylarginine modification of NF-κB/p65 at Arg30 and Arg35. Co-immunoprecipitation, ubiquitination assay, proteasomal degradation assay, NF-κB reporter assay, NF-κB/p65 methylation analysis, in vitro and in vivo metastasis assays Oncogene Medium 30542119
2020 TRIM3 interacts with IRF3 and inhibits its phosphorylation, thereby suppressing the IRF3 signaling pathway and NLRP3 inflammasome activation in LPS-treated renal tubular cells. Co-immunoprecipitation, Western blot for IRF3 phosphorylation, TRIM3 overexpression/knockdown in HK-2 cells and LPS-treated rat model International urology and nephrology Low 34643859
2019 TRIM3 directly interacts with Beclin1 and promotes its K48-linked polyubiquitination, leading to Beclin1 degradation and consequent inhibition of autophagy in Ewing sarcoma cells. Co-immunoprecipitation, ubiquitination assay with K48 linkage-specific analysis, Western blot, immunofluorescence for autophagy markers OncoTargets and therapy Medium 32021240
2020 TRIM3 associates with p53 and promotes p53 K48-linked ubiquitination and degradation. TRIM3 depletion in breast cancer cells increases p53 protein levels, inhibits cell proliferation, and promotes apoptosis. Co-immunoprecipitation, K48-specific ubiquitination assay, protein stability assay, Western blot, TRIM3 knockdown with apoptosis readout Cancer cell international Medium 33292295
2021 TRIM3 acts as a SUMO E3 ligase by binding UBC9 and promoting SUMOylation of estrogen receptor alpha (ESR1/ERα), thereby activating the ER signaling pathway and conferring tamoxifen resistance. Silencing UBC9 abolishes TRIM3's effect on tamoxifen resistance. Co-immunoprecipitation of TRIM3-UBC9, SUMOylation assay for ERα, TRIM3 knockdown/overexpression with ERα pathway reporter, cell viability assay Oncogenesis Medium 34508066
2022 TRIM3 associates with ERα and promotes its stability via K63-linked polyubiquitination, thereby enhancing estrogen signaling and breast cancer cell proliferation and migration on a genome-wide scale. Co-immunoprecipitation, K63-specific ubiquitination assay, protein stability assay, RNA sequencing, luciferase reporter for ERα activity, TRIM3 depletion with proliferation/migration readout Cell communication and signaling : CCS Medium 35392925
2022 The isolated RING domain of human TRIM3 is monomeric and inactive as an E3 ligase due to placental mammal-specific amino acid changes adjacent to the core RING domain that prevent self-association but not E2 recognition. TRIM3 RING activity can be restored by substitution with the corresponding TRIM2 region or by heterodimerization with TRIM2. TRIM2 and TRIM3 interact in cells via their filamin and coiled-coil domains, respectively. Structural analysis of RING domain, in vitro ubiquitination assays, RING domain mutagenesis, co-immunoprecipitation of TRIM2-TRIM3 heterodimerization, biochemical dimerization analysis Nature communications High 36481767
2024 TRIM3 binds to microtubules via its C-terminal NHL-repeat region. TRIM3 is required for accumulation of acetylated tubulin following taxol treatment, and TRIM3 loss partially recapitulates the reduction in nocodazole-resistant microtubules seen with ATAT1 depletion. Loss of TRIM3 decreases ATAT1 protein levels independently of transcription. Differential extraction proteomics, nocodazole/taxol drug sensitivity assay quantitated by mass spectrometry, TRIM3 deletion mapping to NHL repeats, ATAT1 protein quantification after TRIM3 depletion, transcription-independent protein level analysis Journal of cell science Medium 38149663
2023 TRIM3 directly interacts with FABP4 and decreases FABP4 protein levels through ubiquitination-mediated degradation. TRIM3-mediated FABP4 degradation suppresses colorectal cancer cell migration, invasion, and lipid droplet formation. Overexpressed FABP4 reverses the effect of TRIM3 upregulation. Co-immunoprecipitation, ubiquitination assay, TRIM3/FABP4 overexpression and knockdown, migration/invasion assays, lipid droplet quantification, in vivo liver metastasis model Histology and histopathology Medium 37212515
2023 TRIM3 directly interacts with the C-terminus of p53 (residues 320–393) and retains p53 in the cytoplasm to decrease its nuclear expression. In wild-type p53 CRC cells, cytoplasmic retention reduces p53 tumor-suppressive nuclear activity. In mutant p53 CRC cells, TRIM3 degrades nuclear mutant p53, reversing oxaliplatin chemotherapy resistance by downregulating multidrug resistance genes. Co-immunoprecipitation with p53 domain mapping, subcellular fractionation, immunostaining for p53 localization, TRIM3 overexpression/knockdown, drug resistance assays Cell death discovery Medium 36894560
2025 TRIM3 promotes K48-linked ubiquitination and degradation of GRP78, a key ER stress protein. TRIM3 directly interacts with GRP78, and its overexpression in cisplatin-resistant cervical cancer cells suppresses drug resistance by promoting PERK activation and apoptosis downstream of GRP78 inhibition. Co-immunoprecipitation, ubiquitination assay, TRIM3 overexpression with GRP78 rescue, apoptosis assay, drug resistance assay Biochemistry and cell biology Low 39620445
2025 TRIM3 directly interacts with YAP1 and reduces YAP1 protein stability through ubiquitination, without affecting YAP1 mRNA levels. TRIM3 depletion increases YAP1 levels and promotes proliferation and mobility of melanoma cells; knockdown of YAP1 rescues the pro-tumorigenic effects of TRIM3 depletion. Co-immunoprecipitation, ubiquitination assay, TRIM3/YAP1 overexpression/knockdown, rescue assay, qPCR for mRNA levels Scientific reports Low 40715334
2026 TRIM3 interacts with TLR3 and promotes its K48-linked ubiquitination and degradation. Activation of the TRIM3/TLR3 axis induces IFN-β secretion and overrides feedback inhibition of IFN-β. Conversely, excess IFN-β inhibits TRIM3 expression, creating a reciprocal negative feedback loop. This mechanism suppresses NSCLC progression and reprograms the tumor microenvironment. Co-immunoprecipitation, Western blot for K48-linked ubiquitination, TLR3 protein stability assay, TRIM3 overexpression/knockdown, IFN-β ELISA, CD8+ T cell co-culture cytotoxicity assay, in vivo xenograft Cell death & disease Medium 41545343

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Block of HAC1 mRNA translation by long-range base pairing is released by cytoplasmic splicing upon induction of the unfolded protein response. Cell 244 11595189
2005 ER stress signaling by regulated splicing: IRE1/HAC1/XBP1. Methods (San Diego, Calif.) 184 15804613
1999 HAC-1, a Drosophila homolog of APAF-1 and CED-4 functions in developmental and radiation-induced apoptosis. Molecular cell 173 10619022
2004 Tomato heat stress transcription factor HsfB1 represents a novel type of general transcription coactivator with a histone-like motif interacting with the plant CREB binding protein ortholog HAC1. The Plant cell 169 15131252
2014 Ire1 has distinct catalytic mechanisms for XBP1/HAC1 splicing and RIDD. Cell reports 154 25437541
2010 The HAC1 gene from Pichia pastoris: characterization and effect of its overexpression on the production of secreted, surface displayed and membrane proteins. Microbial cell factories 154 20591165
2023 TRIM3 facilitates ferroptosis in non-small cell lung cancer through promoting SLC7A11/xCT K11-linked ubiquitination and degradation. Cell death and differentiation 108 37978273
2018 Exosomal TRIM3 is a novel marker and therapy target for gastric cancer. Journal of experimental & clinical cancer research : CR 105 30031392
2005 CART: an Hrs/actinin-4/BERP/myosin V protein complex required for efficient receptor recycling. Molecular biology of the cell 104 15772161
2003 Activation mechanisms of the HAC1-mediated unfolded protein response in filamentous fungi. Molecular microbiology 103 12581366
2008 Impact of the unfolded protein response upon genome-wide expression patterns, and the role of Hac1 in the polarized growth, of Candida albicans. Fungal genetics and biology : FG & B 95 18602013
2011 RtcB, a novel RNA ligase, can catalyze tRNA splicing and HAC1 mRNA splicing in vivo. The Journal of biological chemistry 92 21757685
2010 Degradation of postsynaptic scaffold GKAP and regulation of dendritic spine morphology by the TRIM3 ubiquitin ligase in rat hippocampal neurons. PloS one 90 20352094
1996 Saccharomyces cerevisiae IRE2/HAC1 is involved in IRE1-mediated KAR2 expression. Nucleic acids research 87 8932376
1998 Unconventional splicing of HAC1/ERN4 mRNA required for the unfolded protein response. Sequence-specific and non-sequential cleavage of the splice sites. The Journal of biological chemistry 82 9430730
2014 Human Brat ortholog TRIM3 is a tumor suppressor that regulates asymmetric cell division in glioblastoma. Cancer research 81 24947043
2019 LEUNIG_HOMOLOG Mediates MYC2-Dependent Transcriptional Activation in Cooperation with the Coactivators HAC1 and MED25. The Plant cell 64 31320481
2011 Conserved RNA structures in the non-canonical Hac1/Xbp1 intron. RNA biology 61 21593604
1994 Hac1: a novel yeast bZIP protein binding to the CRE motif is a multicopy suppressor for cdc10 mutant of Schizosaccharomyces pombe. Nucleic acids research 58 7816617
2012 Basic leucine zipper transcription factor Hac1 binds DNA in two distinct modes as revealed by microfluidic analyses. Proceedings of the National Academy of Sciences of the United States of America 55 23054834
2013 Quantitative iTRAQ LC-MS/MS proteomics reveals the cellular response to heterologous protein overexpression and the regulation of HAC1 in Pichia pastoris. Journal of proteomics 54 23851310
2013 TRIM3, a tumor suppressor linked to regulation of p21(Waf1/Cip1.). Oncogene 49 23318451
2009 Loss of heterozygosity of TRIM3 in malignant gliomas. BMC cancer 47 19250537
2016 Drosophila Brat and Human Ortholog TRIM3 Maintain Stem Cell Equilibrium and Suppress Brain Tumorigenesis by Attenuating Notch Nuclear Transport. Cancer research 44 26893479
2000 The transcriptional co-activator ADA5 is required for HAC1 mRNA processing in vivo. The Journal of biological chemistry 43 10652329
1999 Conservation and divergence of the yeast and mammalian unfolded protein response. Activation of specific mammalian endoplasmic reticulum stress element of the grp78/BiP promoter by yeast Hac1. The Journal of biological chemistry 43 10521417
2004 Autoregulation of the HAC1 gene is required for sustained activation of the yeast unfolded protein response. Genes to cells : devoted to molecular & cellular mechanisms 41 15009095
2003 IRE1- and HAC1-independent transcriptional regulation in the unfolded protein response of yeast. Molecular microbiology 40 12864846
2020 TRIM3 attenuates apoptosis in Parkinson's disease via activating PI3K/AKT signal pathway. Aging 39 33253119
2018 Global Proteome Remodeling during ER Stress Involves Hac1-Driven Expression of Long Undecoded Transcript Isoforms. Developmental cell 37 30016623
2019 miR-454-3p promotes proliferation and induces apoptosis in human cervical cancer cells by targeting TRIM3. Biochemical and biophysical research communications 36 31270028
2014 Specificity in endoplasmic reticulum-stress signaling in yeast entails a step-wise engagement of HAC1 mRNA to clusters of the stress sensor Ire1. eLife 35 25549299
2015 Ubiquitin ligase TRIM3 controls hippocampal plasticity and learning by regulating synaptic γ-actin levels. The Journal of cell biology 34 26527743
2013 TRIM3 regulates the motility of the kinesin motor protein KIF21B. PloS one 34 24086586
2000 BERP, a novel ring finger protein, binds to alpha-actinin-4. Biochemical and biophysical research communications 34 10673389
2010 Dual functions of yeast tRNA ligase in the unfolded protein response: unconventional cytoplasmic splicing of HAC1 pre-mRNA is not sufficient to release translational attenuation. Molecular biology of the cell 33 20844078
2010 Identification of BERP (brain-expressed RING finger protein) as a p53 target gene that modulates seizure susceptibility through interacting with GABA(A) receptors. Proceedings of the National Academy of Sciences of the United States of America 32 20543135
2015 The bZIP Transcription Factor HAC-1 Is Involved in the Unfolded Protein Response and Is Necessary for Growth on Cellulose in Neurospora crassa. PloS one 31 26132395
2020 Ubiquitination of TLR3 by TRIM3 signals its ESCRT-mediated trafficking to the endolysosomes for innate antiviral response. Proceedings of the National Academy of Sciences of the United States of America 30 32878999
2014 The ability of TRIM3 to induce growth arrest depends on RING-dependent E3 ligase activity. The Biochemical journal 30 24393003
2019 The HAC1 histone acetyltransferase promotes leaf senescence and regulates the expression of ERF022. Plant direct 29 31468026
2017 Tripartite motif-containing 3 (TRIM3) inhibits tumor growth and metastasis of liver cancer. Chinese journal of cancer 29 28950898
2016 The fail-safe mechanism of post-transcriptional silencing of unspliced HAC1 mRNA. eLife 29 27692069
2015 Potential role of TRIM3 as a novel tumour suppressor in colorectal cancer (CRC) development. Scandinavian journal of gastroenterology 29 26691157
2008 Ricin inhibits activation of the unfolded protein response by preventing splicing of the HAC1 mRNA. The Journal of biological chemistry 27 18180297
2019 Translation Control of HAC1 by Regulation of Splicing in Saccharomyces cerevisiae. International journal of molecular sciences 25 31212749
2012 The yeast Rab GTPase Ypt1 modulates unfolded protein response dynamics by regulating the stability of HAC1 RNA. PLoS genetics 24 22844259
2011 Activation of the unfolded protein response in Pichia pastoris requires splicing of a HAC1 mRNA intron and retention of the C-terminal tail of Hac1p. FEBS letters 24 21376719
2010 Functional characterization of the unconventional splicing of Yarrowia lipolytica HAC1 mRNA induced by unfolded protein response. Yeast (Chichester, England) 24 20162530
2001 Cloning and characterization of a gene (RNF22) encoding a novel brain expressed ring finger protein (BERP) that maps to human chromosome 11p15.5. Genomics 24 11170753
2022 The protein kinase Ire1 has a Hac1-independent essential role in iron uptake and virulence of Candida albicans. PLoS pathogens 23 35108336
2019 Multiple decay events target HAC1 mRNA during splicing to regulate the unfolded protein response. eLife 21 30874502
2019 Overexpression of the transcription factor HAC1 improves nerolidol production in engineered yeast. Enzyme and microbial technology 21 32044032
2019 miR-4513 promotes breast cancer progression through targeting TRIM3. American journal of translational research 20 31105849
2015 Evidence That Base-pairing Interaction between Intron and mRNA Leader Sequences Inhibits Initiation of HAC1 mRNA Translation in Yeast. The Journal of biological chemistry 20 26175153
2018 Targeting TRIM3 deletion-induced tumor-associated lymphangiogenesis prohibits lymphatic metastasis in esophageal squamous cell carcinoma. Oncogene 19 30542119
2022 Divergent self-association properties of paralogous proteins TRIM2 and TRIM3 regulate their E3 ligase activity. Nature communications 18 36481767
2020 TRIM3 inhibits P53 signaling in breast cancer cells. Cancer cell international 16 33292295
2014 A novel role for protein kinase Kin2 in regulating HAC1 mRNA translocation, splicing, and translation. Molecular and cellular biology 16 25348718
2021 Targeted expression of the arsenate reductase HAC1 identifies cell type specificity of arsenic metabolism and transport in plant roots. Journal of experimental botany 15 33038235
2020 Expression and function of an Hac1-regulated multi-copy xylanase gene in Saccharomyces cerevisiae. Scientific reports 15 32669586
2013 Mutual cross talk between the regulators Hac1 of the unfolded protein response and Gcn4 of the general amino acid control of Saccharomyces cerevisiae. Eukaryotic cell 15 23794510
2022 TRIM3 facilitates estrogen signaling and modulates breast cancer cell progression. Cell communication and signaling : CCS 14 35392925
2022 Heavy metal exposure induces Yap1 and Hac1 mediated derepression of GSH1 and KAR2 by Tup1-Cyc8 complex. Journal of hazardous materials 13 35123133
2021 Tripartite motif-containing 3 (TRIM3) enhances ER signaling and confers tamoxifen resistance in breast cancer. Oncogenesis 13 34508066
2018 Identification of an Exceptionally Long Intron in the HAC1 Gene of Candida parapsilosis. mSphere 12 30404939
2022 TRIM3 and TRIM16 as potential tumor suppressors in breast cancer patients. BMC research notes 11 36180926
2017 Optimized expression of the Starmerella bombicola lactone esterase in Pichia pastoris through temperature adaptation, codon-optimization and co-expression with HAC1. Protein expression and purification 11 29108944
2023 TRIM3 inhibits colorectal cancer cell migration and lipid droplet formation by promoting FABP4 degradation. Histology and histopathology 10 37212515
2022 Termination of the unfolded protein response is guided by ER stress-induced HAC1 mRNA nuclear retention. Nature communications 10 36284099
2001 Differences in HAC1 mRNA processing and translation between yeast and mammalian cells indicate divergence of the eukaryotic ER stress response. Biochemical and biophysical research communications 10 11563865
2019 TRIM3 Negatively Regulates Autophagy Through Promoting Degradation of Beclin1 in Ewing Sarcoma Cells. OncoTargets and therapy 9 32021240
2012 Bax induces activation of the unfolded protein response by inducing HAC1 mRNA splicing in Saccharomyces cerevisiae. Yeast (Chichester, England) 9 22903551
2023 Endoplasmic stress sensor Ire1 is involved in cytosolic/nuclear protein quality control in Pichia pastoris cells independent of HAC1. Frontiers in microbiology 8 37415818
2021 Overexpression of TRIM3 protects against LPS-induced acute kidney injury via repressing IRF3 pathway and NLRP3 inflammasome. International urology and nephrology 8 34643859
2015 A novel HAC1-based dual-luciferase reporter vector for detecting endoplasmic reticulum stress and unfolded protein response in yeast Saccharomyces cerevisiae. Plasmid 8 25907266
2023 Molecular background of HAC1-driven improvement in the secretion of recombinant protein in Yarrowia lipolytica based on comparative transcriptomics. Biotechnology reports (Amsterdam, Netherlands) 7 37234569
2023 TRIM3 attenuates cytokine storm caused by Dabie bandavirus via promoting Toll-like receptor 3 degradation. Frontiers in microbiology 7 37520369
2021 Vps34 and TOR Kinases Coordinate HAC1 mRNA Translation in the Presence or Absence of Ire1-Dependent Splicing. Molecular and cellular biology 7 33972394
2021 Phosphorylation of Pal2 by the protein kinases Kin1 and Kin2 modulates HAC1 mRNA splicing in the unfolded protein response in yeast. Science signaling 7 34035143
1997 Suppression of the Saccharomyces cerevisiae hac1/ire15 mutation by yeast genes and human cDNAs. Gene 6 9409765
2024 Microtubule association of TRIM3 revealed by differential extraction proteomics. Journal of cell science 4 38149663
2023 Dual roles of TRIM3 in colorectal cancer by retaining p53 in the cytoplasm to decrease its nuclear expression. Cell death discovery 4 36894560
2019 Ribosome depurination by ricin leads to inhibition of endoplasmic reticulum stress-induced HAC1 mRNA splicing on the ribosome. The Journal of biological chemistry 4 31624149
2025 Artificial induction of the UPR by Tet-off system-dependent expression of Hac1 and its application in Saccharomyces cerevisiae cells. Bioscience, biotechnology, and biochemistry 3 39953902
2025 TRIM3 suppressed the tumorigenicity of melanoma cells by ubiquitinating YAP1. Scientific reports 3 40715334
2024 Selenium increases antimony uptake in As-hyperaccumulators Pteris vittata and Pteris cretica by promoting antimonate reduction: GSH-GSSG cycle and arsenate reductases HAC1/ACR2. Journal of hazardous materials 3 39303610
2022 The cap-proximal RNA secondary structure inhibits preinitiation complex formation on HAC1 mRNA. The Journal of biological chemistry 3 35101452
2025 Crucial roles of Grr1 in splicing and translation of HAC1 mRNA upon unfolded stress response. Nature communications 2 40038285
2025 FORKHEAD BOX1 promotes leaf senescence via the histone acetyltransferase HAC1 and the transcription factors TGA7 and ABF2/3. The Plant cell 2 40591739
2022 Detection of HAC1 mRNA Splicing by RT-PCR in Saccharomyces cerevisiae. Methods in molecular biology (Clifton, N.J.) 2 34985696
2022 Detecting the Non-conventional mRNA Splicing and Translational Activation of HAC1 in Budding Yeast. Methods in molecular biology (Clifton, N.J.) 2 34985697
2023 The Sequential Recruitments of Rab-GTPase Ypt1p and the NNS Complex onto pre-HAC1 mRNA Promote Its Nuclear Degradation in Baker's Yeast. Molecular and cellular biology 1 37533322
2022 Determination of the Stability and Intracellular (Intra-Nuclear) Targeting and Recruitment of Pre-HAC1 mRNA in the Saccharomyces cerevisiae During the Activation of UPR. Methods in molecular biology (Clifton, N.J.) 1 34985698
2022 TRIM3 Inhibits H2O2-Induced Apoptosis in Human Lens Epithelial Cells by Decreasing p53 via Ubiquitination. Current eye research 1 35317686
2026 The TRIM3/TLR3 axis overrides IFN-β feedback inhibition to suppress NSCLC progression. Cell death & disease 0 41545343
2026 TRIM3 Suppresses Tumor Progression in Non-small-Cell Lung Cancer by Promoting PD-L1 Ubiquitination and Degradation. Annals of surgical oncology 0 41870861
2025 Impairment in global protein synthesis uncouples UPR gene induction from HAC1 mRNA splicing in Saccharomyces cerevisiae. Frontiers in microbiology 0 40959222
2025 TRIM3 exacerbates chondrocyte apoptosis through suppression of AKT/mTOR signaling pathway in osteoarthritis. Journal of orthopaedic surgery and research 0 41437076
2024 TRIM3 modulates cisplmatin-resistant of cervical squamous cell carcinoma via endoplasmic reticulum stress signaling in vitro. Biochemistry and cell biology = Biochimie et biologie cellulaire 0 39620445

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