Affinage

MID1

E3 ubiquitin-protein ligase Midline-1 · UniProt O15344

Length
667 aa
Mass
75.3 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

MID1 (TRIM18) is a microtubule-associated RING-Bbox-coiled-coil E3 ubiquitin ligase that couples microtubule dynamics to phosphatase control, protein translation, and signaling, with loss-of-function disrupting epithelial and neuronal microtubule architecture during development (PMID:10077590, PMID:20534674, PMID:27367845). It binds microtubules directly through a helix-loop-helix COS domain acting in concert with the coiled-coil region, while coiled-coil-mediated dimerization is required for the assembled complex to associate with microtubules (PMID:27367845, PMID:11806752); the protein is actively transported bidirectionally along microtubules by kinesins and dyneins in a manner gated by MAP kinase and PP2A-dependent phosphorylation (PMID:18949047). The central biochemical activity of MID1 is RING-dependent ubiquitination, in which the Bbox1 domain recruits the PP2A regulatory subunit alpha4, and MID1 ubiquitinates both alpha4 and the PP2A catalytic subunit (PP2Ac) to drive their proteasomal turnover and thereby raise net PP2A activity when MID1 is lost (PMID:21296087, PMID:23740247, PMID:25207814, PMID:21555591). By limiting PP2A, MID1 sustains mTORC1 signaling and cap-dependent translation, positioning it downstream of Rac GTPases and upstream of mTORC1 in neuronal morphogenesis and axon development (PMID:21555591, PMID:28512198, PMID:24194544). MID1 also nucleates a microtubule-anchored ribonucleoprotein complex with EF-1α, RACK1, and ribosomal subunits that binds purine-rich and CAG-repeat-containing mRNAs and stimulates their translation in a PP2A/mTOR-dependent manner, including expanded CAG-repeat polyglutamine transcripts, androgen receptor mRNA, and APP mRNA (PMID:18172692, PMID:23443539, PMID:27774050, PMID:24913494, PMID:29531801). Beyond PP2A, MID1 ubiquitinates additional substrates to control distinct pathways: Fused kinase in SHH-GLI signaling (PMID:25278022), IRF3 (K48-linked) and PPM1A (K63-linked) to restrain type I interferon and TBK1-dependent antiviral signaling (PMID:33513265, PMID:35909127), and DPP4 and PTP1B in inflammatory and fibrotic disease contexts (PMID:38777113, PMID:34434118). Patient mutations in MID1 cause Opitz syndrome by abolishing microtubule association or, for Bbox1 mutations, selectively disrupting alpha4 binding and ubiquitination (PMID:10077590, PMID:25207814).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 High

    Established MID1 as a microtubule-associated protein whose disease mutations mislocalize it, defining microtubules as its primary site of action.

    Evidence GFP tagging, subcellular fractionation, and in vitro microtubule assembly with patient mutation controls

    PMID:10077590

    Open questions at the time
    • Did not identify the domain mediating microtubule binding
    • No molecular partners defined
  2. 2002 Medium

    Identified alpha4 (PP2-type phosphatase regulatory subunit) as a Bbox-binding partner and showed coiled-coil dimerization is required for microtubule association, linking MID1 to phosphatase regulation.

    Evidence Yeast two-hybrid and domain-deletion analysis

    PMID:11806752

    Open questions at the time
    • No demonstration of catalytic consequence on PP2A
    • Single-lab Y2H without reciprocal in vivo validation
  3. 2004 Medium

    Showed MID1 recruits Mig12 to stabilize and bundle microtubules, defining a functional role in microtubule stabilization.

    Evidence Yeast two-hybrid, reciprocal Co-IP, and microtubule depolymerization assays

    PMID:15070402

    Open questions at the time
    • Mechanism of bundle stabilization unresolved
    • Physiological context not established
  4. 2008 High

    Revealed MID1 assembles a microtubule-anchored ribonucleoprotein complex binding G/U-rich RNAs, extending its function from cytoskeleton to translation, with OS mutations disrupting EF-1α binding.

    Evidence Affinity purification, co-fractionation, RNA-binding, and Y2H across five orthogonal methods

    PMID:18172692

    Open questions at the time
    • Translational output of the complex not yet measured
    • RNA target specificity beyond MID1 mRNA undefined
  5. 2008 High

    Demonstrated MID1 is actively transported along microtubules by motors in a phosphorylation-gated manner, mechanistically connecting PP2A/alpha4 to MID1 trafficking.

    Evidence FRAP with pharmacological PP2A inhibition, siRNA, and phosphomimetic mutations

    PMID:18949047

    Open questions at the time
    • Kinase responsible for Ser96 phosphorylation in vivo not defined
    • Functional purpose of transport unclear
  6. 2011 High

    Defined MID1 as an E3 ligase that degrades PP2A-C to sustain mTORC1 signaling and cap-dependent translation, establishing the core MID1-PP2A-mTOR axis.

    Evidence siRNA, proteasome inhibition, Co-IP, rescue with WT MID1 or activated mTOR, and OS patient fibroblasts

    PMID:21555591

    Open questions at the time
    • Ubiquitin linkage type on PP2Ac not specified here
    • Direct vs alpha4-bridged targeting not resolved
  7. 2011 High

    Reconstituted MID1 RING ligase activity in vitro, showing tandem RING-Bbox cooperation, K63 chain elongation, and Bbox1 autoubiquitination at Lys154.

    Evidence In vitro ligase assays with linkage mutants, mass spectrometry, and domain mutagenesis

    PMID:21296087

    Open questions at the time
    • Physiological substrate beyond autoubiquitination not addressed here
    • E2 enzyme partner in cells undefined
  8. 2013 High

    Identified alpha4 and PP2Ac as direct MID1 substrates, mapping alpha4 ubiquitination to Bbox1-dependent recruitment and explaining how OS Bbox1 mutations dysregulate the complex.

    Evidence In vitro ubiquitination, dominant-negative cell lines, mass spectrometry, and mutagenesis (#10, #13)

    PMID:23740247 PMID:25207814

    Open questions at the time
    • Relative in vivo contribution of alpha4 vs PP2Ac ubiquitination unresolved
    • Stoichiometry of alpha4-PP2Ac-MID1 complex undefined
  9. 2013 High

    Connected expanded CAG-repeat RNA to the MID1-PP2A-S6K complex and showed length-dependent stimulation of repeat-mRNA translation, linking MID1 to polyglutamine disease pathology.

    Evidence RNA immunoprecipitation, Co-IP, translation reporters, and siRNA

    PMID:23443539

    Open questions at the time
    • Direct RNA-binding subunit within the complex not pinpointed
    • In vivo relevance to disease onset not tested
  10. 2013 High

    Established the physiological requirement for MID1-dependent PP2Ac turnover in axon development via genetic epistasis in vivo.

    Evidence Mid1 knockout mouse, in vivo brain imaging, and Mid1/PP2Ac double-knockdown rescue

    PMID:24194544

    Open questions at the time
    • Downstream effectors of PP2A in axon growth not defined
  11. 2014 Medium

    Extended MID1 translational control to disease-relevant mRNAs (AR, APP) and to substrate Fu kinase in SHH-GLI signaling, broadening its regulatory reach.

    Evidence RNA pull-down, Co-IP-PCR, reporter assays, ChIP, and in vitro ubiquitination (#11, #12, #14)

    PMID:24913494 PMID:25025689 PMID:25278022

    Open questions at the time
    • Sequence determinants of mRNA target selection incompletely mapped
    • Single-lab evidence for each target
  12. 2016 High

    Solved the COS domain structure and demonstrated CC-COS suffices for direct microtubule binding, providing the structural basis for MID1 cytoskeletal anchoring.

    Evidence NMR structure (PDB 5IM8) with microtubule-binding domain fusion assays

    PMID:27367845

    Open questions at the time
    • Tubulin contact residues not mapped
    • Structure of full-length assembled complex unknown
  13. 2016 Medium

    Generalized the CAG-repeat translational mechanism across ataxin transcripts, establishing a common MID1 pathway for multiple polyglutamine diseases.

    Evidence RNA immunoprecipitation, translation reporters, and siRNA across ATXN2/3/7

    PMID:27774050

    Open questions at the time
    • In vivo confirmation across disease models lacking
    • Single-lab functional series
  14. 2017 Medium

    Placed Mid1 downstream of Rac GTPases and upstream of mTORC1 in neuronal development and linked MID1-PP2A-Tau regulation to Alzheimer's disease pathology.

    Evidence Rac1/Rac3 double-knockout mice, siRNA, mTORC1 immunoblot, PP2A activity and phospho-Tau assays (#17, #18)

    PMID:28512198 PMID:29062069

    Open questions at the time
    • Mechanism connecting Rac to MID1 expression undefined
    • Causal role in human AD not established
  15. 2019 Medium

    Identified TRAIL as an upstream input that signals through MID1 to deactivate PP2A, implicating the axis in pulmonary fibrosis.

    Evidence TRAIL-knockout mice, PP2A activator treatment, fibroblast assays, and human biopsies

    PMID:30732588

    Open questions at the time
    • Direct biochemical link from TRAIL receptor to MID1 not defined
    • Single-lab disease model
  16. 2022 High

    Defined MID1/TRIM18 as a negative regulator of antiviral signaling through K48 degradation of IRF3 and PPM1A-mediated TBK1 dephosphorylation, with K63 stabilization of PPM1A.

    Evidence Reciprocal Co-IP, linkage-specific ubiquitination assays, lysine mutagenesis, IFN reporters, and TRIM18-knockout mice with viral challenge (#21, #22)

    PMID:33513265 PMID:35909127

    Open questions at the time
    • Integration with microtubule/PP2A functions unclear
    • Cell-type specificity of immune restriction not mapped
  17. 2024 High

    Demonstrated MID1-driven degradation of DPP4 (and PTP1B/STAT3 in kidney disease) as a mechanism in inflammatory and fibrotic pathology, validated by in vivo double-knockout epistasis.

    Evidence Co-IP, proteomics, ubiquitination assays, and Mid1-/-Dpp4-/- collagen-induced arthritis mice with DPP4 reconstitution (#23, #24)

    PMID:34434118 PMID:38777113

    Open questions at the time
    • Whether DPP4/PTP1B targeting depends on the alpha4/PP2A machinery unknown
    • Substrate recognition determinants undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how MID1 selects among its diverse substrates (PP2Ac, alpha4, IRF3, PPM1A, DPP4, PTP1B, Fu) and target mRNAs, and how microtubule anchoring, motor transport, ubiquitination, and translational control are integrated within a single complex.
  • No unified structural model of the assembled MID1 complex
  • Substrate-selection code unknown
  • Mechanism coupling RNA binding to ligase activity undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 8 GO:0140096 catalytic activity, acting on a protein 7 GO:0003723 RNA binding 5 GO:0045182 translation regulator activity 4 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005856 cytoskeleton 4 GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 7 R-HSA-162582 Signal Transduction 6 R-HSA-8953854 Metabolism of RNA 5 R-HSA-1266738 Developmental Biology 3 R-HSA-168256 Immune System 2
Partners
EEF1AIGBP1IRF3MID2MIG12PPM1APPP2CARACK1
Complex memberships
MID1 microtubule-associated ribonucleoprotein complexMID1-alpha4-PP2A complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 MID1 protein associates with microtubules and influences microtubule dynamics in overexpressing cells; endogenous MID1 co-localizes with tubulin in subcellular fractions and associates with microtubules in an in vitro assembly assay. OS patient mutations abolish microtubule association, causing cytoplasmic aggregation instead. GFP tagging, subcellular fractionation, in vitro microtubule assembly assay, immunofluorescence Proceedings of the National Academy of Sciences of the United States of America High 10077590
2002 MID1 and MID2 interact with Alpha 4 (regulatory subunit of PP2-type phosphatases) via their B-box domains; the coiled-coil motifs mediate homo- and heterodimerization, and dimerization is required for association of the MID1/Alpha4 complex with microtubules. Yeast two-hybrid screening, domain-deletion analysis BMC cell biology Medium 11806752
2004 MID1 interacts with Mig12 via its coiled-coil domain; when co-expressed, Mig12 is recruited to thick microtubule bundles by MID1. The MID1-Mig12 complex stabilizes microtubules (bundles are resistant to depolymerizing agents and composed of acetylated tubulin). Yeast two-hybrid, co-immunoprecipitation, co-transfection with immunofluorescence, microtubule depolymerization assay BMC cell biology Medium 15070402
2008 MID1 assembles a microtubule-associated ribonucleoprotein complex that includes elongation factor 1α (EF-1α), RACK1, Annexin A2, Nucleophosmin, and small ribosomal subunit proteins; the complex specifically associates with G- and U-rich RNAs and incorporates MID1 mRNA. OS patient mutations in MID1 abolish its interaction with EF-1α. Yeast two-hybrid, immunofluorescence, affinity purification, microtubule assembly co-fractionation, immunoprecipitation, RNA binding assay Human genetics High 18172692
2008 MID1 undergoes active, bi-directional transport along microtubules dependent on both kinesins and dyneins. Transport is regulated by MAP kinase and PP2A-mediated phosphorylation (simulating permanent phosphorylation at Ser96 stops migration). Knockdown of alpha4, inhibition of PP2A by okadaic acid/fostriecin, or OS patient B-box1 missense mutations block active transport while preserving microtubule association. FRAP (fluorescence recovery after photobleaching), pharmacological inhibition (colcemide, okadaic acid, fostriecin), siRNA knockdown, phosphomimetic mutations PloS one High 18949047
2010 MID1 and its paralog MID2 are required for neural tube closure in Xenopus; MID knockdown destabilizes and disorganizes apicobasally polarized microtubules in the neural plate, disrupting epithelial morphology. MIDs and their interactor Mig12 cooperate for microtubule stabilization during neural plate remodeling. Morpholino-mediated knockdown, immunofluorescence, live imaging of microtubule dynamics Development (Cambridge, England) Medium 20534674
2011 MID1 functions as an E3 ligase targeting the catalytic subunit of PP2A (PP2A-C) for ubiquitin-mediated degradation. Elevated PP2A resulting from MID1 depletion or proteasome inhibition disrupts the mTOR/Raptor complex and down-regulates mTORC1 signaling (reduced S6K1 phosphorylation, cell size, cap-dependent translation). This is rescued by wild-type MID1 re-expression or constitutively active mTOR. siRNA knockdown, proteasome inhibition, co-immunoprecipitation, phosphorylation assays, rescue experiments with WT MID1 or activated mTOR, OS patient-derived fibroblasts Proceedings of the National Academy of Sciences of the United States of America High 21555591
2011 Human MID1 RING domain exhibits E3 ubiquitin ligase activity in vitro, catalyzing auto-polyubiquitination; tandem RING-Bbox1 and RING-Bbox1-Bbox2 constructs show greater activity than individual domains. MID1 facilitates Lys63-linked ubiquitin chain elongation and polyubiquitinates its Bbox1 domain at Lys154. A C-terminal peptide of alpha4 that binds Bbox1 is monoubiquitinated and inhibits polyubiquitin product formation. In vitro E3 ligase assay, ubiquitin linkage mutants, mass spectrometry, domain mutagenesis Journal of molecular biology High 21296087
2013 Expanded CAG repeat RNA (from huntingtin and other polyglutamine disease genes) binds to a complex containing MID1, PP2A, and 40S ribosomal S6 kinase. Binding increases with CAG repeat length and stimulates translation of the repeat-containing mRNA in a MID1-, PP2A-, and mTOR-dependent manner. RNA immunoprecipitation, co-immunoprecipitation, translation reporter assays, siRNA knockdown Nature communications High 23443539
2013 MID1-dependent PP2Ac turnover is required for normal axon development; silencing Mid1 increases PP2Ac levels, promoting axon growth and branching and disrupting callosal projections in vivo. Further knockdown of PP2Ac rescues the axonal phenotype in Mid1-depleted neurons. In vitro knockdown, Mid1 knockout mouse, in vivo brain imaging, genetic epistasis (double knockdown of Mid1 and PP2Ac) Proceedings of the National Academy of Sciences of the United States of America High 24194544
2013 MID1 E3 ligase catalyzes polyubiquitination of alpha4 (regulatory subunit of PP2A); direct binding of alpha4 to the Bbox1 domain is required (a L146Q mutation abolishes alpha4 interaction and its polyubiquitination without affecting RING autoubiquitination). Full-length MID1 and RING-Bbox1 constructs catalyze alpha4 polyubiquitination; ubiquitination of alpha4 occurs within its last 105 amino acids. In vitro ubiquitination assay, dominant-negative MID1 stable cells, proteasome inhibition, mass spectrometry, mutagenesis The Journal of biological chemistry High 23740247
2014 MID1 protein complex associates with androgen receptor (AR) mRNA via purine-rich trinucleotide repeats and increases AR protein levels through enhanced translation (without changing mRNA levels or AR protein stability). Conversely, AR exerts a negative transcriptional feedback on MID1 via AR binding sites in the MID1 gene. Co-immunoprecipitation followed by PCR, RNA pull-down followed by western blot, siRNA knockdown, overexpression, reporter gene assays, chromatin immunoprecipitation Molecular cancer Medium 24913494
2014 MID1 E3 ligase catalyzes ubiquitination and proteasomal cleavage of Fu (Fused kinase), a regulator of GLI3 transcriptional activity in the SHH-GLI signaling pathway, linking the MID1-PP2A complex to GLI3 activity control. In vitro ubiquitination assay, co-immunoprecipitation, proteasome inhibition, cell-based reporter assays The Journal of biological chemistry Medium 25278022
2014 MID1 catalyzes in vitro ubiquitination of the PP2A catalytic subunit (PP2Ac) directly, in the absence of alpha4. In the presence of alpha4, PP2Ac ubiquitination is reduced. OS patient Bbox1 domain mutations (C142S, C145T, A130V/T) abolish polyubiquitination of alpha4 but not of PP2Ac, suggesting alpha4 dysregulation as the direct molecular consequence of these mutations. In vitro ubiquitination assay, domain mutagenesis, western blot PloS one Medium 25207814
2014 Metformin decreases BACE1 protein expression by interfering with the MID1 mRNA-protein complex, reducing BACE1 activity in primary neurons, human cell lines, and in vivo in mice. Western blot, pharmacological treatment, siRNA knockdown, in vivo mouse studies PloS one Medium 25025689
2016 NMR solution structure of the MID1 COS (C-terminal subgroup One Signature) domain reveals a helix-loop-helix fold with a hydrophobic core and a basic patch of positively charged residues. Fusion of the COS domain to the coiled-coil (CC) domain confers microtubule binding; CC-COS constructs directly bind microtubules, establishing the structural basis for MID1 microtubule association. NMR structure determination (PDB: 5IM8), microtubule binding assay, domain fusion experiments The FEBS journal High 27367845
2016 MID1 protein complex binds to ATXN2, ATXN3, and ATXN7 mRNAs in a CAG repeat length-dependent manner and induces protein synthesis of the cognate polyglutamine proteins in a repeat length-dependent manner, indicating a common translational regulatory mechanism for expanded CAG repeat mRNAs. RNA immunoprecipitation, translation reporter assays, western blot, siRNA knockdown Frontiers in cellular neuroscience Medium 27774050
2017 Resveratrol decreases MID1 ubiquitin ligase expression, which reduces MID1-mediated ubiquitination and degradation of PP2A-C on microtubules, thereby increasing PP2A activity and reducing Tau phosphorylation at PP2A-dependent epitopes. MID1 expression is elevated in Alzheimer's disease tissue. Western blot, PP2A activity assay, phospho-tau immunoblot, pharmacological treatment with resveratrol Scientific reports Medium 29062069
2017 Mid1 levels are reduced in Rac1/Rac3 double-knockout cerebellar granule neurons, and Mid1 depletion impairs neuritogenesis and reduces mTORC1 signaling, placing Mid1 downstream of Rac GTPases and upstream of mTORC1 in a Rac1-Mid1-mTORC1 pathway in cerebellar development. Conditional double knockout mouse, Mid1 siRNA depletion in primary neurons, mTORC1 signaling western blot, neurite morphology assay Development (Cambridge, England) Medium 28512198
2018 MID1 protein complex binds to and regulates translation of APP mRNA via the mTOR pathway; inhibition of the MID1 complex by metformin reduces APP protein levels and Aβ in an AD mouse model when treatment is initiated in an already-advanced disease state. RNA immunoprecipitation, western blot, mTOR pathway inhibition, primary neuron cultures, in vivo mouse treatment, behavioral phenotype Cell death discovery Medium 29531801
2019 TRAIL signals through the MID1 ubiquitin ligase to deactivate PP2A, promoting pulmonary fibrosis; TRAIL-deficient mice and PP2A activator-treated mice are protected from bleomycin-induced fibrosis. Recombinant TRAIL increases collagen production in fibroblasts, reversible by PP2A activation. Genetic TRAIL-knockout mouse, pharmacological PP2A activation, in vitro fibroblast treatment, lung function measurement, human biopsy analysis BMC pulmonary medicine Medium 30732588
2021 MID1 physically interacts with IRF3, induces K48-linked polyubiquitination of IRF3 at Lys313, and promotes proteasomal degradation of IRF3, thereby restricting type I interferon production and cellular antiviral response. Co-immunoprecipitation, in vitro/cellular ubiquitination assay, site-directed mutagenesis of ubiquitin acceptor site, IFN reporter assay, antiviral assay Immunology High 33513265
2022 TRIM18 (MID1) recruits protein phosphatase PPM1A to dephosphorylate TBK1, inactivating TBK1 and blocking its interaction with MAVS and STING adaptors, thereby dampening antiviral interferon signaling. TRIM18 also stabilizes PPM1A by inducing K63-linked ubiquitination of PPM1A. Co-immunoprecipitation, immunoblot, siRNA knockdown, TRIM18 knockout mice with viral challenge, luciferase assay, ubiquitination assay Journal of biomedical science High 35909127
2021 TRIM18 (MID1) promotes ubiquitin-mediated proteasomal degradation of PTP1B, which activates STAT3 signaling to promote renal epithelial-mesenchymal transition, inflammation, and fibrosis in diabetic kidney disease. Co-immunoprecipitation, ubiquitination assay, western blot, siRNA knockdown, overexpression in HK-2 cells, pharmacological STAT3 inhibition Frontiers in physiology Medium 34434118
2024 MID1 promotes synoviocyte proliferation and migration by inducing ubiquitin-mediated proteasomal degradation of DPP4; DPP4 deficiency phenocopies MID1 overexpression and DPP4 reconstitution abolishes MID1-induced synoviocyte activation. In a collagen-induced arthritis model, Mid1 knockout completely protects mice from arthritis, and this protection is abolished by concurrent DPP4 knockout. Co-immunoprecipitation, proteomic analysis, ubiquitination assay, overexpression/knockdown in synoviocytes, collagen-induced arthritis in Mid1-/- and Mid1-/-Dpp4-/- double-knockout mice Pharmacological research High 38777113

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD. Nature cell biology 420 18264092
1996 The dmf1/mid1 gene is essential for correct positioning of the division septum in fission yeast. Genes & development 233 8946912
2002 Osmoregulation and fungicide resistance: the Neurospora crassa os-2 gene encodes a HOG1 mitogen-activated protein kinase homologue. Applied and environmental microbiology 171 11823187
2011 Os-GIGANTEA confers robust diurnal rhythms on the global transcriptome of rice in the field. The Plant cell 159 21571948
2004 Analysis of the insect os-d-like gene family. Journal of chemical ecology 130 15274438
1999 The Opitz syndrome gene product, MID1, associates with microtubules. Proceedings of the National Academy of Sciences of the United States of America 115 10077590
2002 MID1 and MID2 homo- and heterodimerise to tether the rapamycin-sensitive PP2A regulatory subunit, alpha 4, to microtubules: implications for the clinical variability of X-linked Opitz GBBB syndrome and other developmental disorders. BMC cell biology 114 11806752
2015 Mechanistic insights into the anchorage of the contractile ring by anillin and Mid1. Developmental cell 105 25959226
2021 circPDE4B prevents articular cartilage degeneration and promotes repair by acting as a scaffold for RIC8A and MID1. Annals of the rheumatic diseases 89 34039624
2002 The Opitz syndrome gene Mid1 is transcribed from a human endogenous retroviral promoter. Molecular biology and evolution 87 12411602
2009 Spatial control of cytokinesis by Cdr2 kinase and Mid1/anillin nuclear export. Current biology : CB 81 19427212
2003 X-linked Opitz syndrome: novel mutations in the MID1 gene and redefinition of the clinical spectrum. American journal of medical genetics. Part A 79 12833403
2013 Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1-PP2A protein complex. Nature communications 75 23443539
2017 Resveratrol induces dephosphorylation of Tau by interfering with the MID1-PP2A complex. Scientific reports 73 29062069
2011 Control of mTORC1 signaling by the Opitz syndrome protein MID1. Proceedings of the National Academy of Sciences of the United States of America 73 21555591
2014 The anti-diabetic drug metformin reduces BACE1 protein level by interfering with the MID1 complex. PloS one 67 25025689
2003 Putative homologs of SSK22 MAPKK kinase and PBS2 MAPK kinase of Saccharomyces cerevisiae encoded by os-4 and os-5 genes for osmotic sensitivity and fungicide resistance in Neurospora crassa. Bioscience, biotechnology, and biochemistry 67 12619694
2010 MID1 and MID2 are required for Xenopus neural tube closure through the regulation of microtubule organization. Development (Cambridge, England) 66 20534674
2007 OS-9 regulates the transit and polyubiquitination of TRPV4 in the endoplasmic reticulum. The Journal of biological chemistry 65 17932042
1998 The mouse Mid1 gene: implications for the pathogenesis of Opitz syndrome and the evolution of the mammalian pseudoautosomal region. Human molecular genetics 64 9467009
2016 Quality control of glycoprotein folding and ERAD: the role of N-glycan handling, EDEM1 and OS-9. Histochemistry and cell biology 63 27803995
2022 TRIM18 is a critical regulator of viral myocarditis and organ inflammation. Journal of biomedical science 61 35909127
2013 miR-135b coordinates progression of ErbB2-driven mammary carcinomas through suppression of MID1 and MTCH2. The American journal of pathology 57 23623609
2004 Mig12, a novel Opitz syndrome gene product partner, is expressed in the embryonic ventral midline and co-operates with Mid1 to bundle and stabilize microtubules. BMC cell biology 57 15070402
2008 The Opitz syndrome gene product MID1 assembles a microtubule-associated ribonucleoprotein complex. Human genetics 56 18172692
1999 MID2, a homologue of the Opitz syndrome gene MID1: similarities in subcellular localization and differences in expression during development. Human molecular genetics 56 10400986
2008 MID1 mutations in patients with X-linked Opitz G/BBB syndrome. Human mutation 52 18360914
2002 Ru(II) and Os(II) nucleosides and oligonucleotides: synthesis and properties. Journal of the American Chemical Society 52 11929265
2000 Molecular evolution of odorant-binding protein genes OS-E and OS-F in Drosophila. Genetics 52 10790388
2022 Exosomes derived from myeloid-derived suppressor cells facilitate castration-resistant prostate cancer progression via S100A9/circMID1/miR-506-3p/MID1. Journal of translational medicine 51 35918733
2020 Circular RNA PVT1 promotes metastasis via regulating of miR-526b/FOXC2 signals in OS cells. Journal of cellular and molecular medicine 51 32249539
2009 The sugar-binding ability of human OS-9 and its involvement in ER-associated degradation. Glycobiology 51 19914915
2021 End-of-treatment PET/CT predicts PFS and OS in DLBCL after first-line treatment: results from GOYA. Blood advances 50 33651099
2018 An Advanced View on Baculovirus per Os Infectivity Factors. Insects 47 30018247
2016 Effect of fulvic acid induction on the physiology, metabolism, and lipid biosynthesis-related gene transcription of Monoraphidium sp. FXY-10. Bioresource technology 45 28042988
2014 Pom1 regulates the assembly of Cdr2-Mid1 cortical nodes for robust spatial control of cytokinesis. The Journal of cell biology 45 24982431
2016 MID1 plays an important role in response to drought stress during reproductive development. The Plant journal : for cell and molecular biology 44 27337541
2007 MID1 mutation screening in a large cohort of Opitz G/BBB syndrome patients: twenty-nine novel mutations identified. Human mutation 44 17221865
2014 The involvement of the Mid1/Cch1/Yvc1 calcium channels in Aspergillus fumigatus virulence. PloS one 41 25083783
2012 Characterization of Mid1 domains for targeting and scaffolding in fission yeast cytokinesis. Journal of cell science 40 22427686
2012 Mid1/anillin and the spatial regulation of cytokinesis in fission yeast. Cytoskeleton (Hoboken, N.J.) 40 22888038
2004 Subcellular localization and oligomeric structure of the yeast putative stretch-activated Ca2+ channel component Mid1. Experimental cell research 39 14729456
2014 A hormone-dependent feedback-loop controls androgen receptor levels by limiting MID1, a novel translation enhancer and promoter of oncogenic signaling. Molecular cancer 38 24913494
2011 Detection and characterization of the in vitro e3 ligase activity of the human MID1 protein. Journal of molecular biology 37 21296087
2020 Overexpression of Os-microRNA408 enhances drought tolerance in perennial ryegrass. Physiologia plantarum 36 33215699
1998 Cloning and characterization of three isoforms of OS-9 cDNA and expression of the OS-9 gene in various human tumor cell lines. Journal of biochemistry 36 9562620
2012 Roles of Cch1 and Mid1 in morphogenesis, oxidative stress response and virulence in Candida albicans. Mycopathologia 35 22886468
2008 Active transport of the ubiquitin ligase MID1 along the microtubules is regulated by protein phosphatase 2A. PloS one 35 18949047
2016 The MID1 protein is a central player during development and in disease. Frontiers in bioscience (Landmark edition) 34 26709798
2012 The N's and O's of Drosophila glycoprotein glycobiology. Glycoconjugate journal 34 22936173
2019 Baculovirus Per Os Infectivity Factor Complex: Components and Assembly. Journal of virology 33 30602603
2013 X-linked microtubule-associated protein, Mid1, regulates axon development. Proceedings of the National Academy of Sciences of the United States of America 33 24194544
2021 Ubiquitin E3 ligase MID1 inhibits the innate immune response by ubiquitinating IRF3. Immunology 32 33513265
2020 The MID1 gene product in physiology and disease. Gene 32 32283114
2021 TRIM18-Regulated STAT3 Signaling Pathway via PTP1B Promotes Renal Epithelial-Mesenchymal Transition, Inflammation, and Fibrosis in Diabetic Kidney Disease. Frontiers in physiology 30 34434118
2018 Inhibition of the MID1 protein complex: a novel approach targeting APP protein synthesis. Cell death discovery 30 29531801
2012 Blt1 and Mid1 provide overlapping membrane anchors to position the division plane in fission yeast. Molecular and cellular biology 30 23149940
1999 FXY2/MID2, a gene related to the X-linked Opitz syndrome gene FXY/MID1, maps to Xq22 and encodes a FNIII domain-containing protein that associates with microtubules. Genomics 30 10644436
2019 TRAIL signals through the ubiquitin ligase MID1 to promote pulmonary fibrosis. BMC pulmonary medicine 29 30732588
2005 OS-D-like genes and their expression in aphids (Hemiptera: Aphididae). Insect molecular biology 29 16033435
2006 A structure-function study of MID1 mutations associated with a mild Opitz phenotype. Molecular genetics and metabolism 28 16378742
2004 Heterologous expression of G protein-coupled receptors in U-2 OS osteosarcoma cells. Receptors & channels 28 15512846
2013 Cch1 and Mid1 are functionally required for vegetative growth under low-calcium conditions in the phytopathogenic ascomycete Botrytis cinerea. Eukaryotic cell 27 23475703
2013 The MID1 E3 ligase catalyzes the polyubiquitination of Alpha4 (α4), a regulatory subunit of protein phosphatase 2A (PP2A): novel insights into MID1-mediated regulation of PP2A. The Journal of biological chemistry 27 23740247
2019 Emerging Roles of the TRIM E3 Ubiquitin Ligases MID1 and MID2 in Cytokinesis. Frontiers in physiology 26 30941058
2019 lncRNA CEBPA-AS1 Overexpression Inhibits Proliferation and Migration and Stimulates Apoptosis of OS Cells via Notch Signaling. Molecular therapy. Nucleic acids 26 32160715
2017 Per os infectivity factors: a complicated and evolutionarily conserved entry machinery of baculovirus. Science China. Life sciences 26 28755302
2020 Fission yeast Pak1 phosphorylates anillin-like Mid1 for spatial control of cytokinesis. The Journal of cell biology 25 32421151
2003 Molecular dissection of the hydrophobic segments H3 and H4 of the yeast Ca2+ channel component Mid1. The Journal of biological chemistry 25 12514173
2008 Hepatic expression of the SPOT 14 (S14) paralog S14-related (Mid1 interacting protein) is regulated by dietary carbohydrate. Endocrinology 24 18556348
2014 EDEM2 and OS-9 are required for ER-associated degradation of non-glycosylated sonic hedgehog. PloS one 23 24910992
2002 Widely spaced alternative promoters, conserved between human and rodent, control expression of the Opitz syndrome gene MID1. Genomics 23 12408967
2016 Regulation of mRNA Translation by MID1: A Common Mechanism of Expanded CAG Repeat RNAs. Frontiers in cellular neuroscience 22 27774050
2014 The E3 ubiquitin ligase MID1 catalyzes ubiquitination and cleavage of Fu. The Journal of biological chemistry 22 25278022
2002 Isolation and characterisation of the chick orthologue of the Opitz syndrome gene, Mid1, supports a conserved role in vertebrate development. The International journal of developmental biology 22 12141430
2017 Novel role of Rac-Mid1 signaling in medial cerebellar development. Development (Cambridge, England) 21 28512198
2024 Edaravone Maintains AQP4 Polarity Via OS/MMP9/β-DG Pathway in an Experimental Intracerebral Hemorrhage Mouse Model. Molecular neurobiology 20 38421470
2019 NDR Kinase Sid2 Drives Anillin-like Mid1 from the Membrane to Promote Cytokinesis and Medial Division Site Placement. Current biology : CB 20 30853434
2019 Decreased expression of femXAB genes and fnbp mediated biofilm pathways in OS-MRSA clinical isolates. Scientific reports 20 31690794
2024 Collagen type X expression and chondrocyte hypertrophic differentiation during OA and OS development. American journal of cancer research 18 38726262
2002 Essential hydrophilic carboxyl-terminal regions including cysteine residues of the yeast stretch-activated calcium-permeable channel Mid1. The Journal of biological chemistry 18 11796727
1998 The human FXY gene is located within Xp22.3: implications for evolution of the mammalian X chromosome. Human molecular genetics 18 9425238
2022 HOXA11-OS participates in lupus nephritis by targeting miR-124-3p mediating Cyr61 to regulate podocyte autophagy. Molecular medicine (Cambridge, Mass.) 17 36418932
2015 Mid1/Mid2 expression in craniofacial development and a literature review of X-linked opitz syndrome. Molecular genetics & genomic medicine 17 26788540
2019 MiR-362-3p is downregulated by promoter methylation and independently predicts shorter OS of cervical squamous cell carcinoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 16 31082771
2018 MID1-PP2A complex functions as new insights in human lung adenocarcinoma. Journal of cancer research and clinical oncology 16 29450633
2014 MID1 catalyzes the ubiquitination of protein phosphatase 2A and mutations within its Bbox1 domain disrupt polyubiquitination of alpha4 but not of PP2Ac. PloS one 16 25207814
2012 Regulation of PP2A activity by Mid1 controls cranial neural crest speed and gangliogenesis. Mechanisms of development 16 22285438
2024 High-Throughput Transcriptomics Screen of ToxCast Chemicals in U-2 OS Cells. Toxicology and applied pharmacology 15 39159848
2022 Tanshinol suppresses osteosarcoma by specifically inducing apoptosis of U2-OS cells through p53-mediated mechanism. Journal of ethnopharmacology 15 35331874
2022 Os(II) complexes for catalytic anticancer therapy: recent update. Chemical communications (Cambridge, England) 15 35348152
2021 Reactivity of N-Heterocyclic Carbene Half-Sandwich Ru-, Os-, Rh-, and Ir-Based Complexes with Cysteine and Selenocysteine: A Computational Study. Inorganic chemistry 15 34894670
2024 Mid1 promotes synovitis in rheumatoid arthritis via ubiquitin-dependent post-translational modification. Pharmacological research 14 38777113
2016 Biological evaluation of 2-arylidene-4, 7-dimethyl indan-1-one (FXY-1): a novel Akt inhibitor with potent activity in lung cancer. Cancer chemotherapy and pharmacology 14 26781309
2016 Solution structure of the microtubule-targeting COS domain of MID1. The FEBS journal 14 27367845
2012 A MID1 gene mutation in a patient with Opitz G/BBB syndrome that altered the 3D structure of SPRY domain. American journal of medical genetics. Part A 14 22407675
2008 Clinical and molecular studies of patients with characteristics of Opitz G/BBB syndrome shows a novel MID1 mutation. American journal of medical genetics. Part A 14 18697196
2000 yam8(+), a Schizosaccharomyces pombe gene, is a potential homologue of the Saccharomyces cerevisiae MID1 gene encoding a stretch-activated Ca(2+)-permeable channel. Biochemical and biophysical research communications 14 10694511
2017 Protein-protein interactions of the baculovirus per os infectivity factors (PIFs) in the PIF complex. The Journal of general virology 13 28141488
2014 Characterization of the Grp94/OS-9 chaperone-lectin complex. Journal of molecular biology 13 25193139

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