- Length
- 955 aa
- Mass
- 103.7 kDa
- Annotated
- 2026-06-13
26 papers in source corpus
21 papers cited in narrative
21 extracted findings
Mechanistic narrative
Synthesis pass · prose summary of the discoveries below
Parse failed — see logs
Mechanism profile
Synthesis pass · controlled-vocabulary classification · explore literature graph →
No controlled-vocabulary terms were assigned to this entry.
Evidence
Reading pass · 21 per-paper findings extracted from the source corpus
| Year | Finding | Method | Journal | Conf | PMIDs |
|---|---|---|---|---|---|
| 2003 | MIB2 (skeletrophin) binds actin monomer, as demonstrated by yeast two-hybrid screening and co-immunoprecipitation experiments. | Yeast two-hybrid screen; co-immunoprecipitation | The American journal of pathology | Medium | 14507647 |
| 2005 | MIB2 (skeletrophin) is a RING finger-dependent E3 ubiquitin ligase that binds the intracellular region of Notch ligand Jagged-2 (but not Delta-1, -3, -4, or Jagged-1) and ubiquitinates it; RING-mutated skeletrophin lacks this activity. Exogenous skeletrophin (but not RING mutant) in Jagged-2-positive myeloma cells induced Hes-1 expression in stromal cells via Notch signaling. | In vitro autoubiquitination assay with recombinant proteins; RING domain mutagenesis; cell-based functional assay | The American journal of pathology | High | 15920166 |
| 2006 | MIB2 (skeletrophin) reduces melanoma cell invasion in vitro and in vivo and suppresses colony formation in soft agar in a RING motif-dependent manner; it also downregulates Met oncogene transcription and increases Hes1 transcription. The RING mutant lacks these activities. | Exogenous expression; RING domain mutagenesis; invasion assays; soft agar colony formation; in vivo xenograft | Oncogene | Medium | 16715130 |
| 2006 | Zebrafish Mib2 has a C-terminal-most RING finger-dependent E3 ubiquitin ligase activity; Mib and Mib2 are reciprocal E3 ubiquitin ligases and substrates of each other; they share DeltaC as a common substrate but differ in DeltaD internalization; Mib2 binds differently from Mib to extracellular and intracellular parts of DeltaA and DeltaC. | In vitro ubiquitination assay; RING domain mutagenesis; Delta internalization assay; binding assays | Journal of molecular biology | High | 17196985 |
| 2007 | Zebrafish Mib2 co-localizes with Mib in transfected cells and functions redundantly with Mib in regulating Notch signaling in embryos; dominant-negative Mib alleles compete with Mib2 in DeltaC ubiquitylation and internalization. | Co-localization in transfected cells; genetic epistasis in zebrafish embryos; ubiquitylation/internalization assay | Developmental biology | Medium | 17331493 |
| 2007 | Targeted disruption of Mib2 in mice causes failure to close the cranial neural tube (exencephaly) with variable penetrance depending on genetic background, indicating a role in neural tube closure but not complete developmental essentiality. | Targeted gene knockout in mice; developmental phenotype analysis | Genesis (New York, N.Y. : 2000) | Medium | 17987667 |
| 2011 | MIB2 is a component of the activated BCL10 signaling complex; it directly interacts with BCL10 (shown by in vitro translation and pulldown); MIB2 promotes autoubiquitination and ubiquitination of IKKγ/NEMO and recruits/activates TAK1, thereby controlling BCL10-dependent NF-κB activation. MIB2 knockdown inhibited BCL10-dependent NF-κB activation. | Proteomics identification; in vitro pulldown; overexpression; RNAi knockdown; NF-κB reporter assay | The Journal of biological chemistry | Medium | 21896478 |
| 2014 | CYLD (ubiquitin hydrolase) interacts with MIB2; co-expression of CYLD and MIB2 stabilizes MIB2 protein levels and is associated with reduced levels of JAG2; silencing CYLD increases JAG2 expression and upregulates Notch signaling. | Proteomics/co-IP interaction screen; co-expression experiments; siRNA knockdown; Notch target gene expression | Oncotarget | Medium | 25565632 |
| 2017 | A missense variant MIB2 p.V742G shows reduced ubiquitination activity in vitro; expression of MIB2 variants (p.V742G and p.V984L) affects NOTCH signaling, proliferation, and apoptosis in primary rat cardiomyocytes. | In vitro ubiquitination assay; functional cell-based assay in primary cardiomyocytes; whole exome sequencing with family segregation | Human molecular genetics | Medium | 28013292 |
| 2017 | In Drosophila, the ankyrin repeat domains (in entirety) and Mib-specific (MIB) domains of Mib2 are required for its major function in maintaining larval skeletal and visceral muscle integrity; the RING finger domain is required for adult flight muscle development. Missense mutations in the MIB domain and RING finger produce viable but flightless hypomorphic phenotypes. | Domain deletion analysis; forward genetic screen; in vivo imaging; functional dissection with novel alleles | PloS one | Medium | 28282454 |
| 2018 | MIB2 catalyzes Lys-63-linked ubiquitination of GABAB1 at multiple sites, sorting GABAB receptors to lysosomes for degradation. CaMKIIβ (but not CaMKIIα) promotes this MIB2-mediated Lys-63-linked ubiquitination; phosphorylation of GABAB1 at Ser-867 by CaMKII is required, as the phosphomimetic S867D mutant shows strongly increased Lys-63-linked ubiquitination and reduced surface expression, while inactivation of Ser-867 reduces ubiquitination. | Site-directed mutagenesis; overexpression/knockdown; ubiquitin linkage-specific assays; surface receptor quantification in cortical neurons | Molecular neurobiology | High | 29881949 |
| 2019 | MIB2 promotes proteasomal degradation of CYLD via Lys-48-linked polyubiquitination at Lys-338 and Lys-530 of CYLD; the ankyrin repeat in MIB2 interacts with the third CAP domain of CYLD. MIB2-dependent CYLD degradation activates NF-κB signaling via TNFα stimulation and LUBAC. Mib2-knockout mice show reduced IL-6, reduced arthritic inflammation, and suppressed NF-κB signaling. | AlphaScreen; pulldown assay; immunofluorescence; Mib2 KO mice; ubiquitination mapping (K48-linked, site-specific) | The Journal of biological chemistry | High | 31366726 |
| 2021 | Gm364 (a transmembrane protein) directly binds and anchors MIB2 on the membrane; membrane-localized MIB2 ubiquitinates and activates DLL3, which binds and activates Notch2; the resulting NICD2 directly activates AKT in the cytoplasm to regulate oocyte meiosis and quality. | Genetic knockout; co-IP/binding assays; ubiquitination assay; Notch pathway activation assay; oocyte developmental phenotype | Cell death and differentiation | Medium | 34635817 |
| 2023 | MIB2 is required for PD-L1 transport from the trans-Golgi network to the plasma membrane; mechanistically, MIB2 catalyzes nonproteolytic K63-linked ubiquitination of PD-L1, facilitating RAB8-mediated exocytosis to the plasma membrane. MIB2 deficiency reduces surface PD-L1 and promotes antitumor T cell immunity in mice. | MIB2 knockdown/knockout; ubiquitination assay (K63-linkage specific); RAB8 interaction/trafficking assay; mouse tumor models; surface PD-L1 quantification | The Journal of clinical investigation | High | 36719382 |
| 2023 | FAT1 (protocadherin) interacts with MIB2 E3 ubiquitin ligase; MIB2 mediates FAT1-induced ubiquitination and degradation of YAP/TAZ in endothelial cells. Loss of MIB2 reduces YAP/TAZ degradation, increases YAP/TAZ protein levels and target gene expression, and increases endothelial cell proliferation and angiogenesis in vivo. | Co-IP/interactome analysis; MIB2 knockdown in vitro and in vivo; YAP/TAZ ubiquitination assay; angiogenesis models | Nature communications | High | 37031213 |
| 2023 | MIB2 interacts with CARD6 and promotes K48-linked CARD6 polyubiquitination and proteasomal degradation; high fructose upregulates MIB2 expression, leading to CARD6 degradation and consequent ASK1/JNK1/2 activation and lipid accumulation in hepatocytes. MIB2 siRNA reverses these effects. | Immunoprecipitation; immunofluorescence; siRNA knockdown; immunoblotting | Food & function | Medium | 37186242 |
| 2024 | MIB2 expression is increased in SN (surrounded nucleolus) oocytes; specific depletion of MIB2 in SN oocytes disrupts meiotic apparatus and causes aneuploidy, impaired meiotic maturation, and defective early embryo development. Overexpression of MIB2 in NSN oocytes facilitates chromatin configuration transition from NSN to SN and reduces spindle/chromosome disorganization. | Quantitative proteomics; MIB2-specific depletion; overexpression; meiotic phenotype analysis; aneuploidy quantification | Molecular & cellular proteomics : MCP | Medium | 39019259 |
| 2025 | Ebola virus VP35 contains an NNLNS motif (residues 201–205) that serves as a direct binding site for MIB2; this motif is critical for VP35-dependent inhibition of MIB2-mediated interferon induction. MIB2 binding to VP35 also inhibits EBOV minigenome (RNA synthesis) activity. | Mutational analysis of NNLNS motif; protein-protein interaction assays; IFN induction assay; EBOV minigenome assay | Proceedings of the National Academy of Sciences of the United States of America | Medium | 40982696 |
| 2025 | MIB2 directly interacts with Runx2 transcription factor, ubiquitinating and degrading Runx2, which inhibits Hmgcs2 transcription and impedes fatty acid metabolic processes in cardiomyocytes. Cardiac-specific MIB2 overexpression in HFpEF mice worsens cardiac dysfunction and lipid accumulation. | Immunoprecipitation; dual luciferase reporter assay; proteomic analysis; AAV9-mediated cardiac overexpression in mice | Journal of cellular and molecular medicine | Medium | 40159625 |
| 2025 | MIB2 physically interacts with SUZ12 (PRC2 component) via its MIB/HERC and ZZ-type domains; MIB2 mediates ubiquitination of SUZ12, promoting its degradation. MIB2 knockdown reduces SUZ12 protein levels (despite increased ubiquitination), decreases H3K27me3, upregulates PRC2 target genes, and reduces proliferation/increases apoptosis in PNH clone cells. | Immunoprecipitation and mass spectrometry; domain mapping; RNA-seq; western blotting; flow cytometry; colony formation assay | Journal of cellular and molecular medicine | Medium | 40478202 |
| 2025 | Loss of FAT1 in tumor cells (including HNSCC) leads to decreased YAP/TAZ ubiquitination and degradation; MIB2 is identified as an interaction partner of the intracellular part of FAT1 by interactome analysis; MIB2 suppression recapitulates FAT1 loss (increased YAP/TAZ levels, target gene expression, proliferation in vitro, and tumor growth in vivo). | Interactome analysis of FAT1 cytoplasmic domain; siRNA knockdown; ubiquitination assay; in vivo xenograft | PloS one | Medium | 40478800 |
Source papers
Stage 0 corpus · 26 papers · ranked by NIH iCite citations
| Year | Title | Journal | Citations | PMID |
|---|---|---|---|---|
| 2022 | MIB2: metal ion-binding site prediction and modeling server. | Bioinformatics (Oxford, England) | 94 | 35904542 |
| 2023 | PD-L1 translocation to the plasma membrane enables tumor immune evasion through MIB2 ubiquitination. | The Journal of clinical investigation | 52 | 36719382 |
| 2005 | Skeletrophin, a novel ubiquitin ligase to the intracellular region of Jagged-2, is aberrantly expressed in multiple myeloma. | The American journal of pathology | 49 | 15920166 |
| 2007 | The characterization of zebrafish antimorphic mib alleles reveals that Mib and Mind bomb-2 (Mib2) function redundantly. | Developmental biology | 45 | 17331493 |
| 2011 | The E3 ubiquitin ligase mind bomb-2 (MIB2) protein controls B-cell CLL/lymphoma 10 (BCL10)-dependent NF-κB activation. | The Journal of biological chemistry | 41 | 21896478 |
| 2023 | Endothelial FAT1 inhibits angiogenesis by controlling YAP/TAZ protein degradation via E3 ligase MIB2. | Nature communications | 35 | 37031213 |
| 2006 | A ubiquitin ligase, skeletrophin, is a negative regulator of melanoma invasion. | Oncogene | 34 | 16715130 |
| 2006 | Zebrafish Mib and Mib2 are mutual E3 ubiquitin ligases with common and specific delta substrates. | Journal of molecular biology | 34 | 17196985 |
| 2019 | The E3 ubiquitin ligase MIB2 enhances inflammation by degrading the deubiquitinating enzyme CYLD. | The Journal of biological chemistry | 29 | 31366726 |
| 2014 | The cylindromatosis gene product, CYLD, interacts with MIB2 to regulate notch signalling. | Oncotarget | 26 | 25565632 |
| 2018 | Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII) β-Dependent Phosphorylation of GABAB1 Triggers Lysosomal Degradation of GABAB Receptors via Mind Bomb-2 (MIB2)-Mediated Lys-63-Linked Ubiquitination. | Molecular neurobiology | 24 | 29881949 |
| 2003 | Down-regulation of a novel actin-binding molecule, skeletrophin, in malignant melanoma. | The American journal of pathology | 24 | 14507647 |
| 2021 | Gm364 coordinates MIB2/DLL3/Notch2 to regulate female fertility through AKT activation. | Cell death and differentiation | 14 | 34635817 |
| 2007 | Targeted disruption of Mib2 causes exencephaly with a variable penetrance. | Genesis (New York, N.Y. : 2000) | 13 | 17987667 |
| 2023 | Nuciferine blocks MIB2-mediated CARD6 polyubiquitination and degradation in the amelioration of high fructose-induced liver lipid accumulation. | Food & function | 8 | 37186242 |
| 2017 | MIB2 variants altering NOTCH signalling result in left ventricle hypertrabeculation/non-compaction and are associated with Ménétrier-like gastropathy. | Human molecular genetics | 8 | 28013292 |
| 2017 | Identification of the essential protein domains for Mib2 function during the development of the Drosophila larval musculature and adult flight muscles. | PloS one | 7 | 28282454 |
| 2005 | Skeletrophin, a novel RING molecule controlled by the chromatin remodeling complex, is downregulated in malignant melanoma. | DNA and cell biology | 7 | 15869411 |
| 2025 | Taraxerol induces ferroptosis in breast cancer by targeting Nrf2 transcriptional activity to promote MIB2-mediated GPX4 ubiquitination. | Phytomedicine : international journal of phytotherapy and phytopharmacology | 6 | 40592077 |
| 2025 | Mib2 Regulates Lipid Metabolism in Heart Failure With Preserved Ejection Fraction via the Runx2-Hmgcs2 Axis. | Journal of cellular and molecular medicine | 3 | 40159625 |
| 2025 | The tumor suppressor FAT1 controls YAP/TAZ protein degradation and tumor cell proliferation through E3 ligase MIB2. | PloS one | 2 | 40478800 |
| 2025 | Ebola virus VP35 NNLNS motif modulates viral RNA synthesis and MIB2-mediated signaling. | Proceedings of the National Academy of Sciences of the United States of America | 2 | 40982696 |
| 2025 | Ebola virus VP35 NNLNS motif modulates viral RNA synthesis and MIB2-mediated signaling. | bioRxiv : the preprint server for biology | 1 | 40777377 |
| 2023 | MIB2 promotes the progression of non-small cell lung cancer by regulating cell cycle control pathways. | Genes & genomics | 1 | 37436668 |
| 2025 | MIB2-Mediated SUZ12 Ubiquitination Regulates Clonal Proliferation in Patients With Paroxysmal Nocturnal Haemoglobinuria. | Journal of cellular and molecular medicine | 0 | 40478202 |
| 2024 | MIB2 Functions in Oocyte Meiosis by Modulating Chromatin Configuration. | Molecular & cellular proteomics : MCP | 0 | 39019259 |
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