Affinage

MKRN2

E3 ubiquitin-protein ligase makorin-2 · UniProt Q9H000

Length
416 aa
Mass
46.9 kDa
Annotated
2026-04-28
40 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MKRN2 is an RNA-binding RING-finger E3 ubiquitin ligase that governs inflammatory signaling, translational control, mRNA export, and cell fate decisions by targeting a broad array of substrates for ubiquitin-dependent degradation or functional modification. MKRN2 suppresses NF-κB signaling by catalyzing K48-linked polyubiquitination and proteasomal degradation of p65, acting synergistically with PDLIM2, and constrains IL-6 translation in macrophages by conjugating K29-linked ubiquitin chains to PAIP1 at Lys179, disrupting the PAIP1–eIF4A interaction required for translational initiation (PMID:28378844, PMID:40524017). Additional validated ubiquitination substrates include p53, PKM2, PPP2CA (K48-linked at K41, inactivating Wnt/β-catenin signaling), IGF2BP3, CSDE1 (four mapped sites; co-localizes with MKRN2 in liquid–liquid phase-separation condensates), LMNA, and the chemically induced neo-substrate RPS7, through which MKRN2 mediates nucleolar stress and synthetic lethality in p53-deficient cells (PMID:32194692, PMID:40959281, PMID:41757349, PMID:41991154). MKRN2 also binds mRNA 3′ UTRs and interacts with the mRNA export factor GLE1 to selectively restrain nuclear export of associated transcripts, a function co-opted by influenza A virus for viral mRNA trafficking, and is required for spermiogenesis in mice through regulation of Odf2 and the p53/PERP axis (PMID:32460013, PMID:38753876, PMID:28008940).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2008 High

    Establishing that MKRN2 functions in vertebrate neural development, acting as a neurogenesis inhibitor positioned downstream of PI3K/Akt and upstream of GSK-3β, provided the first signaling-pathway context for this gene.

    Evidence Xenopus animal cap explants with constitutively active/dominant-negative PI3K, Akt, and GSK-3β constructs; morpholino knockdown

    PMID:18198183

    Open questions at the time
    • Direct biochemical substrate in the PI3K/Akt–GSK-3β axis not identified
    • Whether the RING E3 activity is required for the anti-neurogenic function was not tested
  2. 2010 Medium

    Domain-mapping revealed that the third C3H zinc finger, Cys-His motif, and RING domain are the minimal region sufficient for anti-neurogenic activity, focusing mechanistic attention on the RING-containing C-terminus.

    Evidence Systematic N- and C-terminal truncation mutagenesis in Xenopus overexpression assay

    PMID:20167204

    Open questions at the time
    • Point mutations in the RING finger were not tested for catalytic dead activity
    • Binding partners for truncated constructs not identified
  3. 2016 High

    Genetic knockout in mice demonstrated that MKRN2 is essential for spermiogenesis and male fertility, with loss causing ectoplasmic specialization defects and reduced Odf2 expression, establishing an in vivo physiological requirement.

    Evidence Mkrn2 knockout mouse; histology, sperm analysis, Western blot for Odf2

    PMID:28008940

    Open questions at the time
    • Whether Odf2 is a direct ubiquitination substrate of MKRN2 was not tested
    • Cell-autonomous versus paracrine contributions not dissected
  4. 2017 High

    Identification of p65 as a direct MKRN2 ubiquitination substrate established MKRN2 as a bona fide E3 ligase suppressing NF-κB-driven inflammation, defining its first characterized enzymatic activity and substrate.

    Evidence Yeast two-hybrid, Co-IP, in vitro ubiquitination, RING mutagenesis, shRNA knockdown in dendritic cells

    PMID:28378844

    Open questions at the time
    • Specific lysine sites on p65 targeted by MKRN2 not mapped
    • Relative contribution of MKRN2 versus other p65 E3 ligases unclear
  5. 2020 High

    The substrate repertoire of MKRN2 was expanded to include p53 and IGF2BP3, showing that MKRN2 promotes their proteasomal degradation to regulate cancer cell proliferation, and the spermatogenesis phenotype was linked to the p53/PERP apoptotic axis.

    Evidence Co-IP, GST pulldown, in vitro ubiquitination, CRISPR p53 KO rescue in melanoma; shRNA in neuroblastoma; Mkrn2 KO mouse testis transcriptomics

    PMID:31489847 PMID:32194692 PMID:32560817

    Open questions at the time
    • Ubiquitin chain type for p53 and IGF2BP3 not determined
    • Whether p53 degradation is direct versus via an intermediate in the PERP pathway not resolved
  6. 2020 High

    Discovery that MKRN2 physically interacts with GLE1 and binds mRNA 3′ UTRs established a non-degradative, RNA-regulatory role: MKRN2 selectively restrains nuclear export of associated mRNAs, with genetic epistasis in zebrafish retinal development confirming functional partnership with GLE1.

    Evidence AP-MS, RIP-seq, zebrafish morpholino and CRISPR KO epistasis

    PMID:32460013

    Open questions at the time
    • Whether MKRN2 ubiquitinates GLE1 or another export factor was not tested
    • Determinants of mRNA selectivity not defined
  7. 2022 Medium

    PKM2 was identified as another ubiquitination substrate, linking MKRN2 to metabolic reprogramming via suppression of PKM2-ERK signaling in gastric cancer.

    Evidence Co-IP, ubiquitination assay, overexpression/knockdown, xenograft model

    PMID:35196650

    Open questions at the time
    • Ubiquitin chain type and target lysines on PKM2 not mapped
    • Single-lab finding
  8. 2024 Medium

    The GLE1–MKRN2 mRNA export axis was shown to be co-opted by influenza A virus, with MKRN2 positively regulating viral mRNA nuclear-to-cytoplasmic trafficking; this extended the mRNA export function to a pathogen context.

    Evidence RNA interactome capture, MKRN2 knockdown, fluorescence microscopy for mRNA localization, viral replication assays

    PMID:38753876

    Open questions at the time
    • Direct ubiquitination of a viral or host factor in mRNA export not demonstrated
    • Generality to other viruses unknown
  9. 2024 Medium

    MKRN2 was shown to ubiquitinate LMNA when scaffolded by the lncRNA lncCCKAR-5, introducing lncRNA-dependent substrate recruitment as a regulatory mechanism for MKRN2.

    Evidence Co-IP, ubiquitination assay, lncRNA overexpression/knockdown

    PMID:38242315

    Open questions at the time
    • Ubiquitin chain type on LMNA not determined
    • Whether other lncRNAs similarly redirect MKRN2 substrate specificity is unknown
    • Single-lab finding
  10. 2025 High

    A major mechanistic advance resolved how MKRN2 controls inflammation at the translational level: MKRN2 conjugates K29-linked ubiquitin to PAIP1-K179, disrupting PAIP1–eIF4A interaction and selectively blocking IL-6 mRNA translation in macrophages, with conditional KO mice showing exacerbated colitis.

    Evidence Macrophage-specific conditional KO, K29-linkage-specific ubiquitination assay, PAIP1 K179 mutagenesis, polysome profiling, experimental colitis model

    PMID:40524017

    Open questions at the time
    • Whether K29-linked ubiquitination is used for other MKRN2 substrates beyond PAIP1 is unknown
    • How MKRN2 achieves mRNA selectivity for IL-6 versus other transcripts is unresolved
  11. 2025 High

    PPP2CA was identified as a K48-ubiquitination substrate at K41, mechanistically connecting MKRN2 to Wnt/β-catenin pathway inactivation and apoptosis in renal cell carcinoma, and providing one of the most fully mapped substrate-site-chain type-pathway cascades for MKRN2.

    Evidence Co-IP, K48-linkage-specific ubiquitination, K41 site-directed mutagenesis, xenograft

    PMID:40959281

    Open questions at the time
    • Whether MKRN2 regulation of PP2A extends to other PP2A substrates is untested
    • Structural basis for PPP2CA recognition unknown
  12. 2025 High

    MKRN2 was shown to ubiquitinate CSDE1 at four mapped lysines and to co-localize with CSDE1 in LLPS condensates; Mkrn2 KO mice displayed sex-specific social behavioral abnormalities resembling ASD, linking MKRN2's phase-separation and ubiquitin ligase activities to neuronal function.

    Evidence Mass spectrometry, lysine mutagenesis, LLPS assays, Mkrn2 KO mouse behavioral testing

    PMID:41757349

    Open questions at the time
    • Causal chain from CSDE1 ubiquitination to behavioral phenotype not fully established
    • Whether LLPS condensate function requires catalytic activity is unclear
  13. 2026 High

    A covalent molecular glue (DPB) was shown to modify MKRN2-Cys335 and create a neo-interface recruiting the ribosomal protein RPS7 for MKRN2-mediated ubiquitination and degradation, triggering nucleolar stress and synthetic lethality in p53-null NSCLC — demonstrating that MKRN2 can be pharmacologically redirected to novel substrates.

    Evidence QTRP proteomics, Cys335 mutagenesis, Co-IP-MS, genetic KO/rescue, orthotopic xenograft

    PMID:41991154

    Open questions at the time
    • Whether endogenous RPS7 is a physiological MKRN2 substrate is unknown
    • Long-term in vivo safety and selectivity of DPB not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis for MKRN2's broad substrate recognition, the rules governing its use of distinct ubiquitin chain types (K48 versus K29) on different substrates, and the relationship between its RNA-binding, phase-separation, and E3 ligase functions in an integrated cellular model.
  • No crystal or cryo-EM structure of MKRN2 or any MKRN2–substrate complex
  • Chain-type selectivity mechanism unexplored biochemically
  • Relative physiological importance of translational control versus protein degradation roles unranked

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016874 ligase activity 5 GO:0003723 RNA binding 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 7 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-9609507 Protein localization 2

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 MKRN2 is a RING finger domain-dependent E3 ubiquitin ligase that binds to the p65 subunit of NF-κB, promotes its K48-linked polyubiquitination and proteasome-dependent degradation, thereby suppressing NF-κB transactivation. MKRN2 was identified via yeast two-hybrid screening with PDLIM2, and MKRN2 and PDLIM2 synergistically promote p65 polyubiquitination and degradation. MKRN2 knockdown in dendritic cells increased nuclear p65 and augmented proinflammatory cytokine production. Yeast two-hybrid screening, Co-IP, in vitro ubiquitination assay, RING domain mutagenesis, shRNA knockdown, cytokine measurement Scientific reports High 28378844
2008 Xenopus makorin-2 (mkrn2) functions as a neurogenesis inhibitor acting downstream of PI3K and Akt and upstream of GSK-3β; overexpression suppresses PI3K/Akt-induced neural marker (NCAM) expression and upregulates GSK-3β mRNA and protein, while morpholino knockdown induces double axis in tadpoles. Xenopus animal cap explant assay, morpholino antisense knockdown, overexpression of constitutively active PI3K/Akt and dominant negative GSK-3β, Western blot, RT-PCR The Journal of biological chemistry High 18198183
2010 The third C3H zinc finger, Cys-His motif, and C3HC4 RING zinc finger of mkrn2 are essential and sufficient for its anti-neurogenic activity; a C-terminal truncation mutant containing only these domains (mkrn2(s)-7) recapitulates the full-length phenotype of dorso-posterior deficiencies in tadpoles and inhibits NCAM expression and induces GSK-3β in animal cap assays. N- and C-terminal truncation mutagenesis, Xenopus overexpression, animal cap explant assay Biochemical and biophysical research communications Medium 20167204
2016 Mkrn2 knockout in mice causes male infertility characterized by low sperm number, poor motility, aberrant morphology, spermiation failure, and misarrangement of ectoplasmic specialization in testes; mechanistically, Odf2 (a vital spermatogenesis protein) expression is significantly decreased in knockout testes. Mkrn2 knockout mouse model, histology, sperm analysis, Western blot for Odf2 Scientific reports High 28008940
2020 Mkrn2 deficiency in mice causes abnormally high testicular apoptosis through the p53/PERP signaling pathway; MKRN2 normally suppresses PERP expression, and PERP acts as a negative regulator of spermatogenesis whose ectopic expression induces male infertility. Mkrn2 knockout mouse model, digital gene expression profiling (DGE), GSEA, KEGG pathway analysis, protein expression analysis Asian journal of andrology Medium 31489847
2020 MKRN2 ubiquitinates IGF2BP3 (an RNA-binding protein) to promote its degradation, thereby regulating CD44 and PDPN expression; MKRN2 knockdown in neuroblastoma SHSY5Y cells promotes proliferation and migration in an IGF2BP3-dependent manner. shRNA knockdown, Co-IP, pulldown, in vitro ubiquitination assay, Western blot Biochemical and biophysical research communications Medium 32560817
2020 MKRN2 interacts with and ubiquitinates p53 to promote its degradation, thereby regulating melanoma cell proliferation; MKRN2 downregulation inhibits melanoma cell growth in a p53-dependent manner (confirmed by p53 CRISPR knockout rescue). Co-IP, GST pulldown, in vitro ubiquitination assay, CRISPR-Cas9 p53 knockout, MTT and colony formation assays Oncology letters High 32194692
2020 MKRN2 physically interacts with GLE1 (a DEAD-box helicase activator involved in mRNA export termination) as identified by affinity-purification mass spectrometry; MKRN2 binds selectively to the 3' UTR of a diverse subset of mRNAs; morpholino knockdown or CRISPR/Cas9 knockout of MKRN2 partially rescues retinal developmental defects upon GLE1 depletion in zebrafish, establishing epistasis; knockdown of MKRN2 enhances nuclear export of MKRN2-associated mRNAs. Affinity purification–mass spectrometry, zebrafish morpholino knockdown, CRISPR/Cas9 knockout, genetic epistasis, ribonomic (RIP-seq) approaches Cell reports High 32460013
2018 MKRN2 inhibits migration and invasion of non-small-cell lung cancer cells through downregulation of the PI3K/Akt pathway, as demonstrated by MKRN2 silencing and overexpression experiments in NSCLC cell lines. MKRN2 siRNA knockdown and overexpression, migration and invasion assays, Western blot for PI3K/Akt pathway components Journal of experimental & clinical cancer research Medium 30103781
2022 MKRN2 promotes ubiquitination-mediated degradation of PKM2 (pyruvate kinase M2) and attenuates PKM2's effect on ERK signaling, thereby inhibiting gastric cancer cell proliferation. Co-IP, ubiquitination assay, overexpression and knockdown, CCK-8, in vivo xenograft Aging Medium 35196650
2023 MKRN2 interacts with STAT1; Co-IP assays show a direct MKRN2–STAT1 interaction in testis and MEF cells, and STAT1 expression is significantly decreased in MKRN2 knockout testes. MKRN2 also regulates SIX4 and tenascin C (TNC) expression via EBF transcription factor 2 (EBF2). Mkrn2 knockout mouse model, Co-IP, Western blot, qRT-PCR Frontiers in endocrinology Medium 36967804
2024 MKRN2 associates with influenza A virus (IAV) mRNA and positively regulates IAV mRNA nuclear-cytoplasmic trafficking, potentially through an association with the RNA export mediator GLE1; in the absence of MKRN2, IAV mRNAs accumulate in the nucleus and may be degraded by the nuclear RNA exosome complex. RNA interactome capture (RIC), MKRN2 knockdown, fluorescence microscopy for mRNA localization, functional viral replication assays PLoS pathogens Medium 38753876
2025 MKRN2 selectively inhibits IL-6 translation (not transcription) in LPS-activated macrophages by binding Il6 mRNA and attaching K29-linked polyubiquitin chains to Lys179 of PAIP1 (a translation initiation coactivator), blocking PAIP1–eIF4A interaction and reducing translational efficiency of Il6 mRNA; LysM-Cre+Mkrn2fl/fl mice showed increased serum IL-6 after LPS and increased severity of experimental colitis. Conditional macrophage-specific Mkrn2 knockout, RNA-binding assays, ubiquitination assay with K29-linkage specificity, Co-IP for PAIP1–eIF4A interaction, polysome profiling, experimental colitis model Nature immunology High 40524017
2024 MKRN2 is a substrate of lncCCKAR-5; lncCCKAR-5 acts as a scaffold facilitating interaction between MKRN2 and LMNA, promoting ubiquitin-mediated degradation of LMNA, with this effect augmented by N6-adenosine methylation of lncCCKAR-5. Co-IP, ubiquitination assay, lncRNA overexpression/knockdown, Western blot The Journal of investigative dermatology Medium 38242315
2025 MKRN2 directly targets PPP2CA (Protein Phosphatase 2 Catalytic Subunit Alpha) for K48-linked ubiquitination at its K41 residue, leading to proteasomal degradation of PPP2CA; this results in increased β-catenin phosphorylation and decreased β-catenin protein levels, causing inactivation of Wnt signaling and apoptosis in clear cell renal cell carcinoma cells. Co-IP, immunofluorescence, K48-linkage-specific ubiquitination assay, site-directed mutagenesis (K41), in vivo xenograft International journal of biological sciences High 40959281
2025 MKRN2 mediates ubiquitination of CSDE1 at four specific lysine residues (K81, K91, K208, K727); MKRN2 and CSDE1 co-localize in liquid-liquid phase separation (LLPS) condensates, and disruption of either protein impairs condensate formation; Mkrn2 knockout mice exhibit sex-specific social abnormalities resembling ASD; MARK1 and HNRNPUL2 mRNAs are identified as ubiquitination-dependent targets of CSDE1. Mass spectrometry substrate identification, lysine mutagenesis, LLPS assays in HEK293 and SH-SY5Y cells, Mkrn2 knockout mice, behavioral assays Frontiers in cellular neuroscience High 41757349
2025 MKRN2 is recruited to stress granules (SGs) in a manner dependent on active ubiquitination (UBA1 activity); MKRN2 promotes SG formation and disassembly following stress recovery by preventing accumulation of defective ribosomal products (DRiPs) within SGs. Proximity proteomics (BioID), UBA1 inhibition, MKRN2 localization imaging, stress granule formation and dissolution assays bioRxivpreprint Medium bio_10.1101_2025.10.15.682570
2026 The covalent molecular glue DPB directly modifies Cys335 of MKRN2's E3 ligase domain and creates a neo-interface that recruits the ribosomal protein RPS7 to MKRN2, inducing ubiquitination and proteasomal degradation of RPS7, triggering nucleolar stress and apoptosis selectively in p53-deficient NSCLC cells; this synthetic lethal effect depends on a functional MKRN2–RPS7 axis. Quantitative thiol-reactivity proteomics (QTRP), biophysical assays, site-directed mutagenesis (Cys335), Co-IP-mass spectrometry, genetic KO/rescue, in vivo orthotopic mouse model British journal of pharmacology High 41991154
2025 MKRN2 promotes ubiquitination-mediated degradation of p53 in lung epithelial cells; Co-IP confirms direct MKRN2–p53 interaction; MKRN2 overexpression reduces LPS-induced apoptosis and lung injury through p53 downregulation. Co-IP, ubiquitination assay, transcriptome sequencing, adenovirus-mediated overexpression, siRNA knockdown, in vivo LPS ARDS model Biochemical and biophysical research communications Medium 40885043
2025 MKRN2 directly targets NF-κB p65 for proteasomal degradation via its E3 ubiquitin ligase activity, constraining NF-κB/COX2-mediated inflammatory signaling in the tumor microenvironment; MKRN2 deficiency promotes M1-to-M2 macrophage polarization switch and tumor growth acceleration in MKRN2 knockout mice. MKRN2 knockout mice, tumor implantation models, immune cell composition analysis (flow cytometry), Western blot for p65/COX2 Cancer letters Medium 40925500
2026 MKRN2 promotes HCC cell proliferation through activation of the p38 MAPK signaling pathway; MKRN2 depletion arrests the cell cycle at G1/S and reduces c-Myc activation; RNA-seq analysis placed MKRN2 in cell cycle regulation and p38 MAPK signaling. MKRN2 knockdown, RNA-seq, flow cytometry, CCK-8/colony/EdU assays, in vivo xenograft Human cell Medium 41741886

Source papers

Stage 0 corpus · 40 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. Genome research 161 11042152
2015 Genetic Variations in MicroRNA-Binding Sites Affect MicroRNA-Mediated Regulation of Several Genes Associated With Cardio-metabolic Phenotypes. Circulation. Cardiovascular genetics 59 25814643
2017 MKRN2 is a novel ubiquitin E3 ligase for the p65 subunit of NF-κB and negatively regulates inflammatory responses. Scientific reports 58 28378844
2018 MKRN2 inhibits migration and invasion of non-small-cell lung cancer by negatively regulating the PI3K/Akt pathway. Journal of experimental & clinical cancer research : CR 46 30103781
2010 The vertebrate makorin ubiquitin ligase gene family has been shaped by large-scale duplication and retroposition from an ancestral gonad-specific, maternal-effect gene. BMC genomics 40 21172006
2001 Phylogenetic conservation of the makorin-2 gene, encoding a multiple zinc-finger protein, antisense to the RAF1 proto-oncogene. Genomics 40 11597136
2008 Makorin-2 is a neurogenesis inhibitor downstream of phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signal. The Journal of biological chemistry 31 18198183
2020 Ubiquitination of IGF2BP3 by E3 ligase MKRN2 regulates the proliferation and migration of human neuroblastoma SHSY5Y cells. Biochemical and biophysical research communications 26 32560817
2016 Deficiency of Mkrn2 causes abnormal spermiogenesis and spermiation, and impairs male fertility. Scientific reports 26 28008940
2020 Mkrn2 deficiency induces teratozoospermia and male infertility through p53/PERP-mediated apoptosis in testis. Asian journal of andrology 17 31489847
2020 Ubiquitination of P53 by E3 ligase MKRN2 promotes melanoma cell proliferation. Oncology letters 17 32194692
2020 Altered mechanisms of genital development identified through integration of DNA methylation and genomic measures in hypospadias. Scientific reports 17 32728162
2014 Ubiquitous expression of MAKORIN-2 in normal and malignant hematopoietic cells and its growth promoting activity. PloS one 15 24675897
2022 MRKNs: Gene, Functions, and Role in Disease and Infection. Frontiers in oncology 14 35463379
2020 MKRN2 Physically Interacts with GLE1 to Regulate mRNA Export and Zebrafish Retinal Development. Cell reports 14 32460013
2010 Identification of protein domains required for makorin-2-mediated neurogenesis inhibition in Xenopus embryos. Biochemical and biophysical research communications 13 20167204
2024 Human Genetics of Ventricular Septal Defect. Advances in experimental medicine and biology 12 38884729
2020 Evolutionary Conservation of MKRN3 and Other Makorins and Their Roles in Puberty Initiation and Endocrine Functions. Seminars in reproductive medicine 12 31972861
2024 N6-Methyladenosine Modification of lncCCKAR-5 Regulates Autophagy in Human Umbilical Cord Mesenchymal Stem Cells by Destabilizing LMNA and Inhibits Diabetic Wound Healing. The Journal of investigative dermatology 10 38242315
2019 Differential expression of innate immunity regulation genes in chronic HIV-1 infected adults. Cytokine 10 31629104
2023 MKRN1/2 serve as tumor suppressors in renal clear cell carcinoma by regulating the expression of p53. Cancer biomarkers : section A of Disease markers 9 36938725
2023 LINC00294/miR-620/MKRN2 axis provides biomarkers and negatively regulates malignant progression in colorectal carcinoma. Human & experimental toxicology 8 37218161
2022 MKRN2 inhibits the proliferation of gastric cancer by downregulating PKM2. Aging 8 35196650
2024 Identifying cellular RNA-binding proteins during infection uncovers a role for MKRN2 in influenza mRNA trafficking. PLoS pathogens 7 38753876
2024 Diversity of Molecular Functions of RNA-Binding Ubiquitin Ligases from the MKRN Protein Family. Biochemistry. Biokhimiia 6 39418515
2020 Identification and Characterization of the Copy Number Dosage-Sensitive Genes in Colorectal Cancer. Molecular therapy. Methods & clinical development 6 32775488
2025 The RNA-binding E3 ligase MKRN2 selectively disrupts Il6 translation to restrain inflammation. Nature immunology 5 40524017
2021 The identification of novel gene mutations for degenerative lumbar spinal stenosis using whole-exome sequencing in a Chinese cohort. BMC medical genomics 5 34020649
2025 E3 ligase MKRN2 destabilizes PPP2CA proteins to inactivate canonical Wnt pathway and mitigates tumorigenesis of clear cell renal cell carcinoma. International journal of biological sciences 3 40959281
2023 MKRN2 knockout causes male infertility through decreasing STAT1, SIX4, and TNC expression. Frontiers in endocrinology 3 36967804
2026 Genetic regulation of fatty acid content in adipose tissue. American journal of human genetics 2 41534528
2023 A genetic locus complements resistance to Bordetella pertussis-induced histamine sensitization. Communications biology 2 36879097
2025 Novel role of MKRN2 in regulating tumor growth through host microenvironment and macrophage M1 to M2 switch. Cancer letters 1 40925500
2023 [Overexpression of MKRN2 Inhibits the Growth of Ovarian Cancer Cells]. Molekuliarnaia biologiia 1 37528788
2026 Poliumoside attenuates endothelial senescence and atherosclerosis by regulating MKRN2-mediated autophagy via the PI3K/AKT/ mTOR pathway. International immunopharmacology 0 41587514
2026 Circ_Mkrn2 facilitates the progression of atrial fibrillation via sponging miR-10b-5p. Cellular signalling 0 41619923
2026 MKRN2 enhances hepatocellular carcinoma proliferation through the p38 MAPK pathway. Human cell 0 41741886
2026 Liquid-liquid phase separation couples MKRN2-mediated ubiquitination of CSDE1 with neurodevelopmental disorders. Frontiers in cellular neuroscience 0 41757349
2026 A covalent molecular glue hijacks the E3 ligase MKRN2 to degrade the ribosomal protein RPS7 and induce synthetic lethality in p53-deficient NSCLC cells. British journal of pharmacology 0 41991154
2025 MKRN2 attenuates LPS-induced apoptosis in lung epithelial cells via ubiquitination-mediated p53 degradation. Biochemical and biophysical research communications 0 40885043