Affinage

TRIM13

E3 ubiquitin-protein ligase TRIM13 · UniProt O60858

Length
407 aa
Mass
47.0 kDa
Annotated
2026-06-10
100 papers in source corpus 13 papers cited in narrative 13 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRIM13 is an endoplasmic reticulum-anchored RING-type E3 ubiquitin ligase that operates at the intersection of protein quality control, innate immune signaling, inflammatory regulation, and lipid metabolism (PMID:17314412, PMID:35080984). Its C-terminal transmembrane domain confers ER localization, and an intact RING domain is required for its auto-polyubiquitination and substrate ubiquitination activity; it physically associates with the VCP/p97 ERAD machinery and routes ERAD substrates such as CD3-delta and, in the absence of the Cavβ subunit, Cav1.2 L-type calcium channels to proteasomal degradation via derlin-1 and p97 (PMID:17314412, PMID:21186355). Beyond canonical ERAD, TRIM13 controls innate antiviral and inflammatory signaling through linkage-specific ubiquitination: it interacts with MDA5 and RIG-I to differentially tune type I IFN output (PMID:25008915), catalyzes K6-linked ubiquitination of STING to accelerate its ER-initiated degradation and restrain DNA-triggered inflammation (PMID:35080984), catalyzes K29-linked ubiquitination of TRAF6 to potentiate TLR2-driven NF-κB activation (PMID:28087809), and modulates NEMO ubiquitination and turnover to suppress TNF-induced NF-κB activity in a manner dependent on its RING domain and ER localization but independent of autophagy (PMID:25152375). During ER stress TRIM13 is stabilized, induces autophagy through its coiled-coil domain together with p62/SQSTM1, and drives K63-linked ubiquitination of caspase-8 to couple autophagosomal translocation to ER stress-induced cell death (PMID:22178386, PMID:24021263). It additionally degrades a panel of substrates—Nur77, CHOP, LXRα/β and SOCS1/3—linking it to cytokine production, collagen synthesis in diabetic nephropathy, and cholesterol efflux and foam-cell formation in atherosclerosis (PMID:30224829, PMID:31901873, PMID:38537695). The gene was originally identified within the minimally deleted 13q14.3 region in B-CLL (PMID:9599022).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 Low

    Established the gene's existence and a candidate disease context by mapping LEU5/RFP2/TRIM13 to a B-CLL deletion region, but left its function entirely unknown.

    Evidence Cosmid contig construction, cDNA cloning and sequencing within the 13q14 deletion region

    PMID:9599022

    Open questions at the time
    • No functional experiment performed on the protein
    • RING-domain enzymatic activity inferred only from sequence homology
    • No causal link between TRIM13 loss and B-CLL demonstrated
  2. 2007 High

    Answered what biochemical activity TRIM13 has by showing it is a RING-dependent ER-resident E3 ligase that engages the ERAD machinery, defining its core molecular identity.

    Evidence In vitro/in vivo ubiquitination assays, RING mutagenesis, immunopurification + mass spectrometry, ER co-localization, CD3-delta degradation assay

    PMID:17314412

    Open questions at the time
    • Direct substrate beyond CD3-delta not defined
    • Mechanism of substrate selection within ERAD unclear
    • Ubiquitin linkage type for ERAD substrates not resolved
  3. 2010 High

    Extended the ERAD role to a physiological client by showing TRIM13 ubiquitinates Cav1.2 channels to control their surface expression, demonstrating regulatory rather than purely degradative function.

    Evidence Reciprocal Co-IP with derlin-1/p97, ubiquitination assay, MG132 rescue, RFP2 overexpression/knockdown

    PMID:21186355

    Open questions at the time
    • Linkage type on Cav1.2 not specified
    • How Cavβ blocks ubiquitination structurally unknown
    • Physiological consequence in native excitable cells not tested
  4. 2011 Medium

    Connected TRIM13 to autophagy by mapping autophagy induction to its coiled-coil domain and showing ER-stress stabilization and p62 interaction, broadening its role beyond ubiquitin transfer.

    Evidence Ectopic expression, CC-domain deletion mapping, Co-IP with p62, DFCP1 co-localization, clonogenic assay

    PMID:22178386

    Open questions at the time
    • Single lab
    • Whether autophagy induction requires ligase activity not established
    • Direct autophagy machinery target not identified
  5. 2013 Medium

    Linked TRIM13's ubiquitin and autophagy activities to cell fate by showing K63-linked ubiquitination of caspase-8 drives its autophagosomal translocation and ER stress-induced death.

    Evidence K63-linkage-specific ubiquitination assay, caspase-8 activation and translocation assays, lysosome fusion assay, overexpression/knockdown

    PMID:24021263

    Open questions at the time
    • Single lab
    • Direct vs indirect caspase-8 ubiquitination not fully resolved
    • Physiological stress contexts beyond model systems untested
  6. 2014 High

    Defined opposing roles in RNA-sensing innate immunity, with TRIM13 negatively regulating MDA5-driven IFN while interacting with RIG-I, using genetic knockout for in vivo validation.

    Evidence Reciprocal Co-IP with MDA5/RIG-I, Trim13-/- mice and MEFs, IFN-β ELISA, EMCV and Sendai virus challenge

    PMID:25008915

    Open questions at the time
    • Whether TRIM13 ubiquitinates MDA5/RIG-I directly not shown
    • Mechanism of opposite RIG-I vs MDA5 effects unresolved
    • Linkage type not defined
  7. 2014 Medium

    Showed TRIM13 restrains TNF-induced NF-κB by modulating NEMO ubiquitination and turnover, requiring RING activity and ER localization but not autophagy.

    Evidence Co-IP with NEMO, ubiquitination assay, NF-κB reporter, RING and ER-localization mutants

    PMID:25152375

    Open questions at the time
    • Single lab
    • Ubiquitin linkage on NEMO not specified
    • Reconciliation with TRAF6-potentiating role not addressed
  8. 2017 Medium

    Revealed a context-dependent positive arm of inflammatory signaling, with K29-linked ubiquitination of TRAF6 potentiating TLR2-driven NF-κB activation.

    Evidence Co-IP with TRAF6, K29-linkage-specific ubiquitination assay, C10/13A catalytic mutagenesis, NF-κB reporter, knockdown

    PMID:28087809

    Open questions at the time
    • Single lab
    • How TRIM13 toggles between suppressing (NEMO) and activating (TRAF6) NF-κB unclear
    • In vivo relevance not established
  9. 2018 Medium

    Identified a phosphodegron-controlled substrate by showing CK2α phosphorylation of Nur77 promotes TRIM13-mediated degradation, controlling TNFα-driven IL-6.

    Evidence Co-IP with Nur77, ubiquitination assay with E2 panel (UbcH5), Lys539 mutagenesis, CK2 inhibition/mutant, IL-6 measurement

    PMID:30224829

    Open questions at the time
    • Single lab
    • Generality of CK2-priming for other TRIM13 substrates unknown
    • In vivo confirmation lacking
  10. 2020 Medium

    Placed TRIM13 in a disease pathway by showing it degrades CHOP to suppress collagen synthesis, with promoter methylation silencing TRIM13 in diabetic nephropathy.

    Evidence Ubiquitination assay, overexpression in mesangial cells and diabetic mice, promoter methylation analysis, collagen synthesis assay

    PMID:31901873

    Open questions at the time
    • Single lab
    • Ubiquitin linkage on CHOP not specified
    • Direct vs indirect CHOP regulation not fully separated
  11. 2022 High

    Resolved a precise mechanism in DNA-sensing immunity by showing TM-domain-mediated, K6-linked ubiquitination of STING decelerates ER exit and accelerates its degradation, with epistasis confirming the STING axis in vivo.

    Evidence Co-IP via TRIM13 TM domain, K6-linkage-specific ubiquitination assay, Trim13-/- mice, STING double-knockout epistasis, ER exit/degradation and cytokine assays

    PMID:35080984

    Open questions at the time
    • Structural basis of TM-domain STING engagement unknown
    • Relationship to other innate substrates not integrated
    • Human relevance of age-related autoinflammation not tested
  12. 2023 Medium

    Connected TRIM13 to redox and tumor biology by showing RING-dependent ubiquitination of p62 dampens Nrf2 signaling and suppresses lung adenocarcinoma growth.

    Evidence Co-IP with p62, ubiquitination assay, RING deletion mutant, Nrf2 pathway readouts, xenograft model

    PMID:37245083

    Open questions at the time
    • Single lab
    • Reconciliation with p62 acting as autophagy partner (idx 2) unaddressed
    • Ubiquitin linkage on p62 not specified
  13. 2024 High

    Established a metabolic-vascular role by showing TRIM13 degrades LXRα/β and SOCS1/3 to impair cholesterol efflux and promote foam-cell formation, with knockout protecting against atherosclerosis.

    Evidence Ubiquitination assays for multiple substrates, Trim13 KO in ApoE-/- mice, cholesterol efflux and foam cell assays, human coronary tissue analysis

    PMID:38537695

    Open questions at the time
    • Linkage types on LXR/SOCS not specified
    • Which substrate dominates the atherosclerosis phenotype unclear
    • Upstream regulation of TRIM13 in macrophages undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single ER-anchored ligase coordinates its opposing roles (NF-κB suppression vs potentiation, RIG-I vs MDA5, autophagy partner vs degrader of p62) and how substrate selection is governed remain unresolved.
  • No structural model of substrate recognition
  • Ubiquitin linkage codes across substrates not systematically compared
  • Mechanism switching TRIM13 between activating and inhibitory outputs unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016874 ligase activity 5
Localization
GO:0005783 endoplasmic reticulum 3
Pathway
R-HSA-168256 Immune System 3 R-HSA-162582 Signal Transduction 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-9612973 Autophagy 2 R-HSA-1430728 Metabolism 1
Partners
MDA5NEMONUR77RIG-ISQSTM1STINGTRAF6VCP

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 RFP2 (TRIM13) is an ER-resident E3 ubiquitin ligase: it exhibits auto-polyubiquitination activity in vivo and in vitro dependent on an intact RING domain; RING-deficient mutants fail to drive polyubiquitination in vitro and are stabilized in vivo. RFP2 co-immunopurifies with VCP/p97 (an ERAD component) and regulates degradation of the ERAD substrate CD3-delta but not an N-end rule substrate. A C-terminal transmembrane domain is required for ER localization. In vitro ubiquitination assay, in vivo ubiquitination assay, RING domain mutagenesis, immunopurification + tandem mass spectrometry, co-localization with ER markers, CD3-delta degradation assay Molecular biology of the cell High 17314412
2010 TRIM13 (RFP2) ubiquitinates Cav1.2 L-type calcium channels in the absence of the Cavβ subunit, targeting them to the ERAD complex (via derlin-1 and p97) and proteasomal degradation. Cavβ co-expression interferes with TRIM13-mediated ubiquitination, thereby preventing ER-associated degradation and promoting channel surface expression. Co-immunoprecipitation of channel with ERAD components (derlin-1, p97), ubiquitination assay, proteasome inhibitor (MG132) rescue experiment, overexpression/knockdown of RFP2 Nature neuroscience High 21186355
2011 TRIM13 induces autophagy when ectopically expressed in HEK-293 cells; the coiled-coil (CC) domain is required for autophagy induction. TRIM13 is stabilized during ER stress, interacts with p62/SQSTM1, and co-localizes with the autophagosome marker DFCP1. TRIM13 regulates initiation of autophagy during ER stress and decreases clonogenic ability of cells. Ectopic expression, domain deletion mapping (CC domain mutants), co-immunoprecipitation with p62/SQSTM1, co-localization with DFCP1 by fluorescence microscopy, clonogenic assay Biochimica et biophysica acta Medium 22178386
2013 TRIM13 induces K63-linked polyubiquitination of caspase-8, resulting in caspase-8 stabilization and activation during ER stress. TRIM13-induced autophagy is essential for caspase-8 translocation to autophagosomes and lysosomal fusion, linking TRIM13-mediated ubiquitination to ER stress-induced cell death. Ubiquitination assay (K63-linkage specific), caspase-8 activation assay, autophagosome translocation assay (co-localization), lysosome fusion assay, TRIM13 overexpression and knockdown Biochimica et biophysica acta Medium 24021263
2014 TRIM13 interacts with MDA5 and negatively regulates MDA5-mediated type I IFN production, acting upstream of IRF3. Trim13-/- mice and MEFs challenged with EMCV (sensed by MDA5) produce increased IFN-β. TRIM13 also interacts with RIG-I, and Trim13-/- MEFs show diminished IFN-β responses to RIG-I-activating Sendai virus, suggesting TRIM13 may positively regulate RIG-I signaling. Co-immunoprecipitation (TRIM13 with MDA5 and RIG-I), TRIM13 knockout mouse generation, IFN-β ELISA in MEFs and in vivo, viral challenge (EMCV, Sendai virus), poly(I:C) stimulation Journal of virology High 25008915
2014 TRIM13 interacts with NEMO (NF-κB essential modulator), modulates NEMO ubiquitination and turnover, and thereby suppresses TNF-induced NF-κB activation. E3 ligase activity (RING domain) and ER localization are required for NF-κB suppression; TRIM13-regulated autophagy is not required for this function. Co-immunoprecipitation (TRIM13 with NEMO), ubiquitination assay, TRIM13 knockdown/overexpression, NF-κB reporter assay, RING domain mutant and ER-localization mutant analysis Cellular signalling Medium 25152375
2017 TRIM13 potentiates TLR2-mediated NF-κB activation by interacting with TRAF6 and catalyzing K29-linked polyubiquitination of TRAF6. RING domain mutants (C10/13A or RING deletion) abolish TRAF6 ubiquitination and NF-κB activation, confirming dependence on E3 ligase activity. TRIM13 is upregulated in macrophages upon TLR2 ligand stimulation. Co-immunoprecipitation (TRIM13 with TRAF6), K29-linkage-specific ubiquitination assay, RING domain active-site mutagenesis (C10/13A), NF-κB reporter assay, TRIM13 knockdown Molecular pharmacology Medium 28087809
2018 TRIM13 ubiquitinates the nuclear receptor Nur77 at Lys539, leading to its proteasomal degradation; optimal ubiquitination requires the E2 enzyme UbcH5. TRIM13–Nur77 interaction was confirmed by co-immunoprecipitation. CK2α phosphorylates Nur77 at Ser154 to promote TRIM13-mediated ubiquitination and degradation, and this CK2α–TRIM13 axis controls TNFα-mediated IL-6 production. Co-immunoprecipitation (TRIM13 with Nur77), ubiquitination assay with E2 enzyme panel, site-directed mutagenesis (Lys539), CK2 pharmacological inhibition and CK2α overexpression/inactive mutant, IL-6 cytokine measurement Scientific reports Medium 30224829
2020 TRIM13 promotes ubiquitination and degradation of CHOP in renal mesangial cells, thereby suppressing collagen synthesis. TRIM13 promoter methylation is increased in diabetic nephropathy, correlating with reduced TRIM13 expression and elevated CHOP. Restoring TRIM13 expression attenuated DN-induced collagen synthesis and improved renal function in vitro and in vivo. Ubiquitination assay (TRIM13 ubiquitinates CHOP), TRIM13 overexpression in mesangial cells and diabetic mouse model, promoter methylation analysis, collagen synthesis assay EBioMedicine Medium 31901873
2022 TRIM13 interacts with STING via its transmembrane domain and catalyzes Lys6-linked polyubiquitination of STING, leading to decelerated ER exit and accelerated ER-initiated degradation of STING. TRIM13 deficiency enhances pathogenic-DNA-triggered inflammatory cytokine production and causes age-related autoinflammation; STING deficiency reverses enhanced innate responses in TRIM13-knockout mice. Co-immunoprecipitation (TRIM13 TM domain with STING), K6-linkage-specific ubiquitination assay, TRIM13 knockout mice, STING double-knockout epistasis, STING ER exit/degradation assay, cytokine measurement Science advances High 35080984
2024 TRIM13 ubiquitinates and degrades LXRα/β, downregulating ABCA1/G1 expression and inhibiting cholesterol efflux in macrophages and smooth muscle cells. TRIM13 also ubiquitinates and degrades SOCS1/3, leading to STAT1 activation, CD36 upregulation, and foam cell formation. Genetic deletion of TRIM13 rescues cholesterol efflux and protects against diet-induced atherosclerosis in ApoE-/- mice. Ubiquitination assay (TRIM13 ubiquitinates LXRα/β and SOCS1/3), TRIM13 knockout mouse model, cholesterol efflux assay, foam cell assay, Western blot for ABCA1/G1/CD36/STAT1, human coronary artery tissue analysis The Journal of biological chemistry High 38537695
2023 TRIM13 interacts with p62/SQSTM1 and mediates its ubiquitination and degradation via the RING finger domain in lung adenocarcinoma cells, negatively regulating Nrf2 signaling and downstream antioxidants. This suppresses tumor cell proliferation and activates autophagy. Co-immunoprecipitation (TRIM13 with p62), ubiquitination assay, RING domain deletion mutant, Nrf2 pathway reporter/Western blot, xenograft in vivo model Cell cycle (Georgetown, Tex.) Medium 37245083
1998 The LEU5 (RFP2/TRIM13) gene was identified within the minimally deleted 13q14.3 region in B-CLL; its cDNA encodes a RING-type zinc-finger domain with homology to other RING proteins involved in tumorigenesis and embryogenesis (RET finger protein, BRCA1, MID1). Cosmid contig construction, cDNA cloning and sequencing, mapping to 13q14 deletion region FEBS letters Low 9599022

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Differential antagonism of opioid delta antinociception by [D-Ala2,Leu5,Cys6]enkephalin and naltrindole 5'-isothiocyanate: evidence for delta receptor subtypes. The Journal of pharmacology and experimental therapeutics 304 1646319
2010 The Cavβ subunit prevents RFP2-mediated ubiquitination and proteasomal degradation of L-type channels. Nature neuroscience 215 21186355
1978 Conformation of [Leu5]enkephalin from X-ray diffraction: features important for recognition at opiate receptor. Science (New York, N.Y.) 188 204006
1979 Specific protection of the binding sites of D-Ala2-D-Leu5-enkephalin (delta-receptors) and dihydromorphine (mu-receptors). Proceedings of the Royal Society of London. Series B, Biological sciences 132 41257
1982 Repeated electroconvulsive shock or chronic morphine treatment increases the number of 3H-D-Ala2,D-Leu5-enkephalin binding sites in rat brain membranes. Life sciences 111 6761529
1990 Modulation of morphine antinociception by peripheral [Leu5]enkephalin: a synergistic interaction. European journal of pharmacology 105 2364995
2007 The RBCC gene RFP2 (Leu5) encodes a novel transmembrane E3 ubiquitin ligase involved in ERAD. Molecular biology of the cell 96 17314412
1996 Ultrastructural immunocytochemical localization of mu-opioid receptors in rat nucleus accumbens: extrasynaptic plasmalemmal distribution and association with Leu5-enkephalin. The Journal of neuroscience : the official journal of the Society for Neuroscience 90 8753878
1985 A quantitative study of [3H]D-Ala2-D-Leu5-enkephalin binding to rat brain membranes. Evidence that oxymorphone is a noncompetitive inhibitor of the lower affinity delta-binding site. Molecular pharmacology 89 2579319
1983 Effect of intrahypothalamic injection of [D-Ala2,D-Leu5]enkephalin on feeding and temperature in the rat. European journal of pharmacology 86 6373308
2014 TRIM13 is a negative regulator of MDA5-mediated type I interferon production. Journal of virology 82 25008915
2011 TRIM13 regulates ER stress induced autophagy and clonogenic ability of the cells. Biochimica et biophysica acta 82 22178386
1985 The analgesic efficacy of intrathecal D-Ala2-D-Leu5-enkephalin in cancer patients with chronic pain. Pain 67 3906516
1996 Ultrastructural immunocytochemical localization of mu opioid receptors and Leu5-enkephalin in the patch compartment of the rat caudate-putamen nucleus. The Journal of comparative neurology 64 8930791
2002 Antiapoptotic and cytotoxic properties of delta opioid peptide [D-Ala(2),D-Leu(5)]enkephalin in PC12 cells. Synapse (New York, N.Y.) 61 11746737
2000 Delta opioid peptide[D- Ala(2),D-Leu(5)]enkephalin promotes cell survival. Journal of biomedical science 55 10810237
1998 A cosmid and cDNA fine physical map of a human chromosome 13q14 region frequently lost in B-cell chronic lymphocytic leukemia and identification of a new putative tumor suppressor gene, Leu5. FEBS letters 55 9599022
1996 Ultrastructural localization of mu-opioid receptors in the superficial layers of the rat cervical spinal cord: extrasynaptic localization and proximity to Leu5-enkephalin. Brain research 55 8883864
1990 Conformational preferences of [Leu5]enkephalin in biomimetic media. Investigation by 1H NMR. European journal of biochemistry 55 2209598
2013 TRIM13 regulates caspase-8 ubiquitination, translocation to autophagosomes and activation during ER stress induced cell death. Biochimica et biophysica acta 52 24021263
2007 Dose-dependent neuroprotection of delta opioid peptide [D-Ala2, D-Leu5] enkephalin in neuronal death and retarded behavior induced by forebrain ischemia in rats. Neuroscience letters 52 17689189
1983 Chronic ethanol alters the receptor binding characteristics of the delta opioid receptor ligand, D-Ala2-D-Leu5 enkephalin in mouse brain. Life sciences 52 6316062
1991 Ingestive behavior following central [D-Ala2, Leu5, Cys6]-enkephalin (DALCE), a short-acting agonist and long-acting antagonist at the delta opioid receptor. Pharmacology, biochemistry, and behavior 48 1658817
1982 Tolerance and cross tolerance to morphine after chronic spinal D-Ala2-D-Leu5-enkephalin infusion. Life sciences 48 6752616
1996 Immunolabeling of Mu opioid receptors in the rat nucleus of the solitary tract: extrasynaptic plasmalemmal localization and association with Leu5-enkephalin. The Journal of comparative neurology 47 8841907
2022 The transmembrane endoplasmic reticulum-associated E3 ubiquitin ligase TRIM13 restrains the pathogenic-DNA-triggered inflammatory response. Science advances 46 35080984
1994 Antisense oligodeoxynucleotide to the CCKB receptor produces naltrindole- and [Leu5]enkephalin antiserum-sensitive enhancement of morphine antinociception. Neuroreport 46 7696612
1983 Unmasking of magnesium-dependent high-affinity binding sites for [dAla2, dLeu5]enkephalin after pretreatment of brain membranes with guanine nucleotides. Proceedings of the National Academy of Sciences of the United States of America 45 6302675
1988 Decrease in delta-opioid receptor density in rat brain after chronic [D-Ala2,D-Leu5]enkephalin treatment. Brain research 43 2847851
2014 TRIM13 regulates ubiquitination and turnover of NEMO to suppress TNF induced NF-κB activation. Cellular signalling 42 25152375
1988 Isolation of endopeptidase-24.11 (EC 3.4.24.11, "enkephalinase") from the pig stomach. Hydrolysis of substance P, gastrin-releasing peptide 10, [Leu5] enkephalin, and [Met5] enkephalin. Gastroenterology 42 2457534
2000 Combined effect of oleic acid and polyethylene glycol 200 on buccal permeation of [D-ala2, D-leu5]enkephalin from a cubic phase of glyceryl monooleate. International journal of pharmaceutics 41 11011997
2020 Altered DNA methylation of TRIM13 in diabetic nephropathy suppresses mesangial collagen synthesis by promoting ubiquitination of CHOP. EBioMedicine 40 31901873
2017 Trim13 Potentiates Toll-Like Receptor 2-Mediated Nuclear Factor κB Activation via K29-Linked Polyubiquitination of Tumor Necrosis Factor Receptor-Associated Factor 6. Molecular pharmacology 40 28087809
2019 TRIM13 inhibited cell proliferation and induced cell apoptosis by regulating NF-κB pathway in non-small-cell lung carcinoma cells. Gene 39 31357025
2011 Delta opioid peptide [D-Ala2, D-Leu5] enkephalin (DADLE) triggers postconditioning against transient forebrain ischemia. European journal of pharmacology 39 21349267
1986 Effects of opioid peptides containing the sequence of Met5-enkephalin or Leu5-enkephalin on nicotine-induced secretion from bovine adrenal chromaffin cells. Journal of neurochemistry 39 2866231
2016 Grouper TRIM13 exerts negative regulation of antiviral immune response against nodavirus. Fish & shellfish immunology 38 27235367
2009 Processing of the Escherichia coli leuX tRNA transcript, encoding tRNA(Leu5), requires either the 3'-->5' exoribonuclease polynucleotide phosphorylase or RNase P to remove the Rho-independent transcription terminator. Nucleic acids research 38 19906695
2004 DLEU2 encodes an antisense RNA for the putative bicistronic RFP2/LEU5 gene in humans and mouse. Genes, chromosomes & cancer 38 15188451
2011 Astroglial reaction to delta opioid peptide [D-Ala2, D-Leu5] enkephalin confers neuroprotection against global ischemia in the adult rat hippocampus. Neuroscience 37 21745540
1983 Plasma catecholamine and cardiovascular responses to morphine and D-ala2-d-leu5-enkephalin in conscious rats. Archives internationales de pharmacodynamie et de therapie 37 6360061
1989 [D-Ala2,Leu5,Cys6]enkephalin: short-term agonist effects and long-term antagonism at delta opioid receptors. Peptides 36 2547203
2009 Delta opioid agonist [D-Ala2, D-Leu5] enkephalin (DADLE) reduced oxygen-glucose deprivation caused neuronal injury through the MAPK pathway. Brain research 34 19619518
2000 Buccal permeation of [D-Ala(2), D-Leu(5)]enkephalin from liquid crystalline phases of glyceryl monooleate. International journal of pharmaceutics 34 10675680
1988 Morphine-like discriminative stimulus effects of opioid peptides: possible modulatory role of D-Ala2-D-Leu5-enkephalin (DADL) and dynorphin A (1-13). Psychopharmacology 34 2894701
2010 Effects of intracerebroventricular application of the delta opioid receptor agonist [D-Ala2, D-Leu5] enkephalin on neurological recovery following asphyxial cardiac arrest in rats. Neuroscience 33 20167252
1994 An 1H NMR determination of the three-dimensional structures of mirror-image forms of a Leu-5 variant of the trypsin inhibitor from Ecballium elaterium (EETI-II). Protein science : a publication of the Protein Society 32 8003965
1991 Effect of chronic D-Ala,2 D-Leu5-enkephalin or pertussis toxin treatment on the high-affinity state of delta opioid receptor in neuroblastoma x glioma NG108-15 hybrid cells. The Journal of pharmacology and experimental therapeutics 32 1847209
2018 The E3 ubiquitin ligase Trim13 regulates Nur77 stability via casein kinase 2α. Scientific reports 31 30224829
2003 Distinct organization of the candidate tumor suppressor gene RFP2 in human and mouse: multiple mRNA isoforms in both species- and human-specific antisense transcript RFP2OS. Gene 31 14636997
1985 Effect of [D-Ala2,Met5]enkephalinamide and [D-Ala2,D-Leu5]enkephalin on cholinergic and noradrenergic neurotransmission in isolated atria. European journal of pharmacology 30 2990945
1986 Intrathecal D-Ala2-D-Leu5-enkephalin (DADL) restores analgesia in a patient analgetically tolerant to intrathecal morphine sulfate. Pain 28 3008062
1983 Partial cross tolerance to D-Ala2-D-Leu5-enkephalin after chronic spinal morphine infusion. Life sciences 28 6304439
1991 Human mast cell proteases hydrolyze neurotensin, kinetensin and Leu5-enkephalin. Peptides 27 1800960
1991 Isobolographic analysis of analgesic interactions between intrathecally and intracerebroventricularly administered fentanyl, morphine and D-Ala2-D-Leu5-enkephalin in morphine-tolerant and nontolerant mice. The Journal of pharmacology and experimental therapeutics 26 1646321
1983 Induction of differentiation increases Met5-enkephalin and Leu5-enkephalin content in NG108-15 hybrid cells: an immunocytochemical and biochemical analysis. The Journal of neuroscience : the official journal of the Society for Neuroscience 26 6193253
1991 In vitro biosynthesis of [Thr2,Leu5,D-Hiv8,Leu10]-cyclosporin, a cyclosporin-related peptolide, with immunosuppressive activity by a multienzyme polypeptide. The Journal of biological chemistry 25 1874714
1990 Formation of [Leu5]enkephalin from dynorphin A(1-8) by rat central nervous tissue in vitro. Journal of neurochemistry 25 1968961
1988 Photoaffinity labeling of opioid delta receptors with an iodinated azido-ligand: [125I][D-Thr2,pN3Phe4,Leu5]enkephalyl-Thr6. Molecular pharmacology 25 2845246
1987 Covalent labeling of opioid receptors with 3H-D-Ala2-Leu5-enkephalin chloromethyl ketone. I. Binding characteristics in rat brain membranes. Life sciences 25 3037220
1985 Conformational states of Leu5- and Met5-enkephalins in solution. Biochemical and biophysical research communications 25 3977900
1983 The synthesis, bioactivity and enzyme stability of D-Ala2, EPhe4, Leu5-enkephalins. Biochemical and biophysical research communications 25 6615520
1982 Comparative structure-function studies with analogs of dynorphin-(1-13) and [Leu5]enkephalin. Life sciences 25 6130438
2001 Hibernation-induction peptide and cell death: [D-Ala2,D-Leu5]enkephalin blocks Bax-related apoptotic processes. European journal of pharmacology 24 11779032
1991 Acute effects of D-1 and D-2 dopamine receptor agonist and antagonist drugs on basal ganglia [Met5]- and [Leu5]-enkephalin and neurotensin content in the rat. Biochemical pharmacology 24 1673340
2013 TRIM13 (RFP2) downregulation decreases tumour cell growth in multiple myeloma through inhibition of NF Kappa B pathway and proteasome activity. British journal of haematology 23 23647456
1985 Comparative binding properties of linear and cyclic delta-selective enkephalin analogues: [3H]-[D-Thr2, Leu5] enkephalyl-Thr6 and [3H]-[D-Pen2, D-Pen5] enkephalin. FEBS letters 23 2985440
2020 Delta opioid peptide [d-Ala2, d-Leu5] enkephalin confers neuroprotection by activating delta opioid receptor-AMPK-autophagy axis against global ischemia. Cell & bioscience 22 32549974
2019 [D-Ala2, D-Leu5] Enkephalin Improves Liver Preservation During Normothermic Ex Vivo Perfusion. The Journal of surgical research 22 31071481
2003 RFP2, c13ORF1, and FAM10A4 are the most likely tumor suppressor gene candidates for B-cell chronic lymphocytic leukemia. Cancer genetics and cytogenetics 22 14499696
1983 Binding characteristics and analgesic activity of D-ALA2-Leu5-enkephalin chloromethyl ketone. Life sciences 22 6304443
2019 TRIM13 inhibits cell migration and invasion in clear-cell renal cell carcinoma. Nutrition and cancer 21 31762344
1989 Multi-dimensional analysis of behavior in mice treated with the delta opioid agonists DADL (D-Ala2-D-Leu5-enkephalin) and DPLPE (D-Pen2-L-Pen5-enkephalin). Neuropharmacology 21 2554179
2012 Protective effects of the delta opioid peptide [D-Ala2, D-Leu5]enkephalin in an ex vivo model of ischemia/reperfusion in brain slices. CNS neuroscience & therapeutics 20 22943142
2006 Delta opioid receptors stimulation with [D-Ala2, D-Leu5] enkephalin does not provide neuroprotection in the hippocampus in rats subjected to forebrain ischemia. Neuroscience letters 20 17207574
1990 Opioid agonist and antagonist antinociceptive properties of [D-Ala2,Leu5,Cys6]enkephalin: selective actions at the deltanoncomplexed site. The Journal of pharmacology and experimental therapeutics 20 2173752
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2023 TRIM13 inhibits cell proliferation and induces autophagy in lung adenocarcinoma by regulating KEAP1/NRF2 pathway. Cell cycle (Georgetown, Tex.) 17 37245083
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