Affinage

MYH9

Myosin-9 · UniProt P35579

Length
1960 aa
Mass
226.5 kDa
Annotated
2026-06-10
100 papers in source corpus 43 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MYH9 encodes the heavy chain of non-muscle myosin IIA, an actin-based motor whose ATPase and filament functions underlie cytokinesis, cell migration, mechanical force generation, and specialized epithelial trafficking (PMID:33871354, PMID:30068598, PMID:33001861). Heterozygous mutations clustered in the motor head and coiled-coil rod domains cause an autosomal-dominant disorder spanning May-Hegglin anomaly, Fechtner and Sebastian syndromes, with head mutations predicted to impair ATPase activity and rod mutations destabilizing the filament, while a tailpiece-truncating allele acts via dominant-negative co-assembly into leukocyte inclusion bodies and the D1424N allele via haploinsufficiency (PMID:10973259, PMID:10973260, PMID:12533692, PMID:12649151); an SH1-helix R705H substitution causes DFNA17 hearing loss, consistent with cochlear hair-cell stereocilia localization (PMID:11023810, PMID:16862555). Knock-in models recapitulate macrothrombocytopenia by disrupting proplatelet formation and reducing agonist-induced light-chain phosphorylation, adhesion, and traction forces in platelets (PMID:21908426, PMID:35584211). Complete loss is embryonic lethal, and conditional deletion reveals tissue-autonomous requirements: hematopoietic deletion causes bone marrow failure, renal tubular deletion disrupts uromodulin transport with ER stress, and preimplantation loss causes cytokinesis failure, with MYH9 functionally dominant over MYH10 (PMID:15555549, PMID:17914179, PMID:35740994, PMID:33001861, PMID:33871354). Beyond its cytoskeletal motor role, MYH9 functions as a scaffold for ubiquitin-regulatory enzymes, binding GSK3β and promoting its ubiquitin-mediated degradation to activate Wnt/β-catenin signaling and tumor stemness, and recruiting deubiquitinases (USP22, USP14, YOD1) to stabilize HIF-1α, NAP1L1, and MYH9 itself (PMID:32296025, PMID:39300073, PMID:37770914, PMID:40041897); its own abundance is set by competition between the STUB1 E3 ligase and stabilizers such as RGS19 (PMID:38825640). Phosphorylation at Ser1943, catalyzed by RIOK1 within an SPC25/RIOK1 complex, releases MYH9 from the cytoskeleton and drives its nuclear accumulation, where it binds the CTNNB1 promoter and assembles a transcription complex with myosin light chain 9, β-actin, and RNA Pol II to directly transcribe β-catenin (PMID:32685004, PMID:39488790). NEK9 targets MYH9 for selective autophagic degradation via an LC3-interacting region to permit primary cilium formation (PMID:34078910).

Mechanistic history

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

    Establishing that MYH9 is the disease gene defined the molecular basis of a group of autosomal-dominant macrothrombocytopenia syndromes and pointed mechanism toward motor and rod-domain dysfunction.

    Evidence Mutation screening and molecular modelling in unrelated probands; independent candidate-gene sequencing for hereditary hearing loss

    PMID:10973259 PMID:10973260 PMID:11023810

    Open questions at the time
    • ATPase impairment was predicted by modelling, not measured directly
    • genotype-phenotype basis for syndromic vs. nonsyndromic presentations not resolved
  2. 2003 Medium

    Resolving how different alleles act—dominant-negative co-assembly versus haploinsufficiency—showed the disorder has more than one pathogenic mechanism.

    Evidence Immunofluorescence with epitope-mapped antibodies on patient neutrophils, plus protein/mRNA stability and localization assays for D1424N in megakaryocytes

    PMID:12533692 PMID:12649151

    Open questions at the time
    • allele-specific mechanisms generalized from limited cases
    • inclusion-body composition beyond NMMHC-IIA not defined
  3. 2004 High

    Genetic knockout established that MYH9 is essential for embryonic development, distinguishing the lethal null state from the viable heterozygous disease state.

    Evidence Targeted and gene-trap knockout mice with breeding analysis and auditory testing

    PMID:15555549 PMID:17914179

    Open questions at the time
    • the developmental process requiring MYH9 not identified at the null stage
    • tissue-specific contributions not separated
  4. 2011 High

    Knock-in alleles linked human mutations to a defined cellular defect—disrupted proplatelet formation—explaining macrothrombocytopenia mechanistically.

    Evidence R702C/D1424N/E1841K knock-in mice with live megakaryocyte imaging and hemostasis assays; separately a MYH9-USP6 oncogenic fusion in nodular fasciitis

    PMID:21826056 PMID:21908426

    Open questions at the time
    • molecular link between motor dysfunction and proplatelet branching not fully mechanized
    • fusion-driven USP6 overexpression mechanism distinct from MYH9 function
  5. 2018 High

    Cell-intrinsic requirement for MYH9 in maintaining leading-edge F-actin dynamics established its direct motor role in migration in vivo.

    Evidence Vav-iCre conditional knockdown, STED nanoscopy, 2D/3D and in vivo migration assays with Myh9-EGFP rescue

    PMID:30068598

    Open questions at the time
    • regulators coupling MYH9 to leading-edge actin not defined
    • threshold-level requirement not molecularly explained
  6. 2020 High

    Discovery of nuclear MYH9 binding the CTNNB1 promoter redefined the motor as a direct transcriptional driver of β-catenin, beyond its scaffolding of GSK3β degradation.

    Evidence Chromatin fractionation, ChIP, oligonucleotide pulldown, NLS-mutation analysis, EM, and in vivo models; parallel Co-IP/ubiquitination work defining the MYH9-GSK3β axis

    PMID:32296025 PMID:32685004

    Open questions at the time
    • how a cytoskeletal motor engages promoter DNA structurally is unresolved
    • signals controlling nuclear partitioning incompletely defined
  7. 2020 High

    Renal tubular conditional deletion connected MYH9 to specialized epithelial trafficking, showing uromodulin transport failure and ER stress as the route to progressive kidney disease.

    Evidence Inducible Myh9/Myh10 renal cKO with immunofluorescence, EM, and UPR marker analysis

    PMID:33001861

    Open questions at the time
    • direct cargo-transport role of NM2 in this trafficking step not biochemically reconstituted
    • Myh9 vs Myh10 individual contributions not separated
  8. 2021 High

    Identifying NEK9 as a selective autophagy adaptor for MYH9 explained how degrading a cytoskeletal stabilizer permits ciliogenesis.

    Evidence Co-IP, LIR-mutant knock-in mice with kidney cilia phenotypes, and MYH9-depletion rescue of ciliogenesis

    PMID:34078910

    Open questions at the time
    • signal triggering NEK9-directed MYH9 turnover unknown
    • relationship to MYH9-related kidney disease not established
  9. 2021 High

    Maternal-zygotic deletion established MYH9 as the dominant non-muscle myosin II isoform for cytokinesis and compaction in early embryogenesis.

    Evidence Single and double Myh9/Myh10 maternal-zygotic knockouts with multiscale light-sheet and confocal imaging

    PMID:33871354

    Open questions at the time
    • basis for the MYH9 > MYH10 functional hierarchy not molecularly explained
  10. 2022 High

    Single-platelet biophysics tied reduced light-chain phosphorylation in mutant platelets to impaired force generation, providing the mechanical explanation for bleeding and a pharmacological correction.

    Evidence Single-platelet force measurements, MLC phosphorylation assays, and tranexamic acid rescue across mutant lines and patient platelets

    PMID:35584211

    Open questions at the time
    • how head/rod mutations specifically lower MLC phosphorylation not resolved
  11. 2022 High

    Hematopoietic conditional deletion demonstrated a cell-autonomous requirement for MYH9 in HSPC survival, defining bone marrow failure as a consequence of its loss.

    Evidence Mx1-cre Myh9 cKO with transplantation chimeras, RNA-seq, and apoptosis assays

    PMID:35740994

    Open questions at the time
    • pro-survival pathway downstream of MYH9 in HSPCs not defined
  12. 2023 Medium

    Reconstituting the SPC25/RIOK1/MYH9 complex identified RIOK1 as the kinase phosphorylating Ser1943 to release MYH9 from the cytoskeleton and drive nuclear CTNNB1 transcription in chemoresistance.

    Evidence Co-IP, RIOK1 kinase assay on S1943, subcellular fractionation, CTNNB1 reporter, and competitive peptide disruption in vitro and in vivo

    PMID:39488790

    Open questions at the time
    • upstream control of RIOK1 activity unclear
    • single-lab mechanism awaiting independent confirmation
  13. 2024 Medium

    Phospho-Ser1943 was shown to recruit deubiquitinases such as USP22 to stabilize signaling proteins like HIF-1α, extending the scaffold paradigm to a phosphorylation-gated ubiquitin-regulatory hub.

    Evidence IP-MS, ubiquitination and phospho-site assays, and CK2-inhibitor reversal of resistance in vivo; converging Co-IP/ubiquitination studies on YOD1, NAP1L1, RGS19, and STUB1

    PMID:37770914 PMID:38825640 PMID:39300073 PMID:40041897

    Open questions at the time
    • structural basis for phospho-dependent deubiquitinase recruitment unknown
    • most scaffold partnerships rest on single-lab Co-IP/ubiquitination data

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single actin motor coordinately switches between cytoskeletal force generation, ubiquitin-machinery scaffolding, and direct promoter binding—and what determines which role dominates in a given cell—remains unresolved.
  • no structural model of nuclear MYH9 on DNA
  • phosphorylation code partitioning MYH9 among compartments not fully mapped
  • scaffold interactions largely from individual cancer contexts not unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003774 cytoskeletal motor activity 3 GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 3 GO:0140657 ATP-dependent activity 3 GO:0001618 virus receptor activity 1 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 3 GO:0005856 cytoskeleton 3 GO:0005829 cytosol 2 GO:0005576 extracellular region 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 GO:0140110 transcription regulator activity 2 R-HSA-109582 Hemostasis 2 R-HSA-1266738 Developmental Biology 2 R-HSA-1640170 Cell Cycle 1 R-HSA-9612973 Autophagy 1
Partners
ATG9BGSK3BNEK9RIOK1STUB1TUBB4AUSP22YOD1
Complex memberships
SPC25/RIOK1/MYH9 complexnuclear MYH9/MYL9/β-actin/RNA Pol II transcription complex

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 MYH9 mutations (one nonsense and five missense) in the myosin head domain and coiled-coil rod domain cause May-Hegglin anomaly, Fechtner syndrome, and Sebastian syndrome; molecular modelling predicted that head-domain mutations impose electrostatic/conformational changes affecting ATPase activity, while coiled-coil mutations destabilize the rod, and the truncating mutation deletes the C-terminal tailpiece. Mutation screening, direct sequencing, molecular modelling Nature genetics High 10973259 10973260
2000 MYH9 R705H mutation within the conserved SH1 helix causes DFNA17 nonsyndromic hereditary hearing loss; previous studies established that SH1 helix modification disrupts myosin II ATPase activity in the motor domain. Candidate gene sequencing, cosegregation analysis, RT-PCR and immunohistochemistry for cochlear expression American journal of human genetics Medium 11023810
2003 Abnormal NMMHC-IIA (MYH9 protein) subcellular localization is observed in neutrophils from all individuals with MYH9 mutations; the protein colocalizes with inclusion bodies; normal NMMHC-IIA dimerizes with abnormal (truncated) NMMHC-IIA to form inclusion bodies, as shown by C-terminal antibody reactivity in heterozygotes for truncating mutations. Immunofluorescence analysis with polyclonal anti-NMMHCA antibody on blood smears from 24 patients, epitope mapping with C-terminal peptide antibody Laboratory investigation; a journal of technical methods and pathology Medium 12533692
2003 The D1424N MYH9 mutation results in a highly unstable protein without abnormalities in protein localization or mRNA stability, suggesting haploinsufficiency—rather than dominant-negative mislocalization—as the pathogenic mechanism for this allele. Protein expression analysis, mRNA stability assay, immunofluorescence in megakaryocytes Blood Medium 12649151
2004 Complete homozygous loss of Myh9 is embryonic lethal (no homozygous pups among 552 births), establishing that MYH9 expression is required for embryonic development; heterozygous mice are viable without gross hematological or nephrological abnormalities, though some show hearing loss. Targeted gene disruption (knockout mouse), breeding analysis, auditory brainstem response Biochemical and biophysical research communications High 15555549 17914179
2006 Myh9 is localized within the stereocilia of inner and outer hair cells in the mouse cochlea, raising the possibility that MYH9 mutations cause hearing loss through disruption of stereocilia structure. Confocal immunofluorescence microscopy of cochlear surface preparations with anti-Myh9 antibody Journal of neuroscience research Medium 16862555
2011 Mouse knock-in lines with R702C, D1424N, and E1841K Myh9 mutations recapitulate human MYH9-related disease; heterozygous R702C megakaryocytes form fewer, shorter proplatelets with less branching and larger buds in live-cell imaging of bone marrow, demonstrating that disrupted proplatelet formation underlies macrothrombocytopenia. Mouse knock-in models, live-cell imaging of megakaryocytes, cultured megakaryocyte analysis, bleeding time, clot retraction assay Blood High 21908426
2011 MYH9-USP6 gene fusion in nodular fasciitis places the entire USP6 coding sequence under the MYH9 promoter, driving USP6 overexpression; xenografts of USP6-overexpressing cells in nude mice recapitulate clinical and histological features of nodular fasciitis. 5'-RACE, RT-PCR/sequencing, in vivo xenograft, genomic FISH Laboratory investigation High 21826056
2015 Myh9 (nonmuscle myosin II-A) accumulates at colonic epithelial injury sites; monoallelic gut-epithelium-specific Myh9 deletion or pharmacological inhibition with blebbistatin activates Akt via Rac1 and PAK1, improving Lgr5+ stem cell survival and protecting against DSS-induced colitis, defining a Myh9–Rac1–PAK1–Akt pathway in intestinal stem cell maintenance. Conditional knockout mouse (Myh9 monoallelic deletion), blebbistatin inhibitor, Lgr5 organoid assay, live imaging, western blot for pathway components Nature communications High 25968904
2017 MYH9 binds to the lncRNA PTCSC2 and inhibits the bidirectional FOXE1/PTCSC2 promoter activity in both directions; PTCSC2 reverses this MYH9-mediated transcriptional repression, demonstrating that MYH9 acts as a transcriptional repressor at this genomic locus. RNA pulldown, co-immunoprecipitation, dual-luciferase reporter assay, RNA knockdown Proceedings of the National Academy of Sciences of the United States of America Medium 28049826
2017 SRF transcription factor binds the CArG box in the MYH9 promoter to drive MYH9 expression; miR-647 suppresses GC metastasis by directly targeting SRF mRNA, reducing MYH9 levels. ChIP for SRF at MYH9 promoter, 3'-UTR luciferase reporter, orthotopic GC xenograft model Theranostics Medium 28900514
2018 Myh9 is required for neutrophil migration: genetic downregulation of Myh9 in Vav-iCre mice significantly reduces migration velocity, transmigration, and 3D migration; STED nanoscopy showed that a threshold level of Myh9 is needed to maintain F-actin dynamics at the leading edge; Myh9-EGFP rescue restored migration defects, confirming cell-intrinsic function. Conditional knockdown (Vav-iCre), STED nanoscopy, 2D/3D migration assays, laser-induced skin injury, peritonitis model, bone marrow chimera, Myh9-EGFP rescue Journal of immunology High 30068598
2018 MYH9 C-terminal domain (PRA, aa1676–1791) directly interacts with PRRSV glycoprotein 5 (GP5); soluble recombinant PRA blocks PRRSV entry in a dose-dependent manner and inhibits both genotype 1 and 2 strains, identifying MYH9 as an essential entry co-factor for PRRSV. GST pulldown, recombinant protein blocking assay, siRNA knockdown, blebbistatin inhibition, dose-response infection assay Antiviral research Medium 29879459
2019 Angiotensin II reduces MYH9 expression in podocytes via TRPC6-mediated Ca2+ influx driven by NOX4-generated ROS; MYH9 knockdown recapitulates Ang II-induced actin cytoskeleton disruption and increased albumin permeability, while MYH9 overexpression rescues these effects, placing MYH9 downstream of the Ang II/TRPC6/NOX4 axis in maintaining the filtration barrier. siRNA knockdown, MYH9 overexpression, NOX4/ROS measurement, TRPC6 inhibition, albumin permeability assay, actin staining Scientific reports Medium 31118506
2019 PTP1B dephosphorylates MYH9 at Y1408; this dephosphorylation event upregulates EGFR expression and promotes cell migration and invasion in esophageal squamous cell carcinoma, defining a PTP1B–MYH9–EGFR signaling axis. GST pulldown combined with LC/MS/MS to identify MYH9 as PTP1B substrate, site-specific phosphorylation analysis, migration/invasion assays Biochemical and biophysical research communications Medium 31735331
2020 MYH9 interacts with GSK3β and promotes its ubiquitin-mediated degradation, thereby dysregulating the β-catenin destruction complex and activating downstream Wnt/β-catenin signaling and tumor stemness in hepatocellular carcinoma; HBx protein interacts with MYH9 and induces its expression, while c-Jun transcriptionally stimulates MYH9 to form a feedback loop. Co-immunoprecipitation, siRNA knockdown, ubiquitination assay, luciferase reporter, in vivo mouse model, ChIP for c-Jun at MYH9 promoter Signal transduction and targeted therapy Medium 32296025
2020 Nuclear MYH9 binds directly to the CTNNB1 (β-catenin) promoter through its DNA-binding domain, and forms a transcriptional complex with myosin light chain 9, β-actin, and RNA Pol II to drive CTNNB1 transcription; nuclear translocation is enabled by potential NLS sequences; S1943 phosphorylation promotes nuclear accumulation, while staurosporine reduces S1943 phosphorylation to inhibit this activity. Immunofluorescence, immune transmission electron microscopy, chromatin fractionation, Co-IP, ChIP, dual luciferase reporter, agarose-oligonucleotide pulldown, nuclear localization signal mutation analysis, in vivo transgenic and xenograft models Theranostics High 32685004
2020 Conditional inactivation of Myh9 (and Myh10) in adult mouse renal tubular epithelia causes progressive kidney disease preceded by intracellular accumulation of uromodulin (UMOD), loss of NKCC2 from the apical membrane, expansion of ER tubules, and activation of ER stress/UPR pathways, demonstrating that NM2 proteins are required for UMOD transport and specialized renal epithelial trafficking. Inducible conditional knockout mouse (Myh9/Myh10 cKO), immunofluorescence, electron microscopy, ER stress marker analysis JCI insight High 33001861
2021 NEK9 acts as a selective autophagy adaptor for MYH9: NEK9 interacts with MYH9 and its LC3-interacting region (LIR) directs autophagic degradation of MYH9, which otherwise stabilizes the actin network and inhibits primary cilia formation; MYH9 depletion restores ciliogenesis in NEK9 LIR-mutant cells. Co-IP, LIR mutation knock-in mice (in vivo cilia analysis in kidneys), MYH9 accumulation measurement, MYH9 siRNA rescue of ciliogenesis Nature communications High 34078910
2021 Myh9 is the major nonmuscle myosin II heavy chain during mouse preimplantation development: maternal-zygotic loss of Myh9 causes failed cytokinesis, prolonged cell cycle, weaker compaction, and reduced differentiation; double Myh9/Myh10 maternal-zygotic mutants show near-complete cytokinesis failure, while Myh10 single mutants are much less severely affected. Maternal-zygotic knockout mouse models, multiscale live imaging (light-sheet and confocal), morphometric analysis eLife High 33871354
2021 MYH9 promotes lung cancer stem cell-like features by activating the mTOR signaling pathway; MYH9 knockdown or blebbistatin treatment reduces stemness markers (CD44, SOX2, Nanog, CD133, OCT4), sphere formation, and mTOR pathway activity. MYH9 overexpression/knockout, western blot for mTOR pathway, sphere formation assay, rapamycin inhibitor, in vivo blebbistatin treatment Cell death discovery Low 34635641
2021 MYH9 directly binds cytoplasmic segments aa368–411 of ATG9B via its head domain; ATG9B–MYH9 interaction decreases each protein's binding to E3 ubiquitin ligase STUB1, mutually stabilizing both proteins; during invasion, MYH9 transports ATG9B to the cell edge, where ATG9B promotes focal adhesion assembly by mediating interaction of endocytosed integrin β1 with Talin-1. Co-IP, peptide-domain mapping, STUB1 ubiquitination assay, live-cell imaging of ATG9B polarization, integrin β1-Talin-1 interaction assay Cell death and differentiation Medium 34131310
2021 TGF-β1 increases MYH9 expression via the ALK5/Smad2/3 pathway (but not p38 MAPK or Akt); siRNA-mediated knockdown or pharmacological inhibition of MYH9 ATPase activity suppresses TGF-β1-induced lung fibroblast-to-myofibroblast differentiation. siRNA knockdown, MYH9 ATPase inhibitor, pathway inhibitors (ALK5, p38, Akt), western blot for differentiation markers Frontiers in pharmacology Medium 33519439
2022 Reduced myosin light chain phosphorylation after agonist stimulation in Myh9 mutant platelets (R702C, D1424N, E1841K) leads to altered biophysical properties and lower adhesion, interaction, and traction forces, directly underlying the increased bleeding tendency in MYH9-related disease; tranexamic acid restores clot retraction and reduces bleeding. Single-platelet force measurement, myosin light chain phosphorylation assay, clot retraction assay, patient platelet analysis, tranexamic acid treatment in mutant mice Science advances High 35584211
2022 TUBB4A interacts with MYH9 to protect the nucleus during constricted cell migration; TUBB4A knockout or MYH9 knockdown causes severe nuclear DNA damage (increased γH2AX, 53BP1) and reduces NF-κB signaling; TUBB4A/GSK3β binds the N-terminal domain of MYH9 and TUBB4A KO reduces MYH9-mediated GSK3β ubiquitination and degradation, decreasing β-catenin signaling. Co-IP, domain-mapping (N-terminal MYH9), MYH9 knockdown, TUBB4A KO, nuclear damage quantification (γH2AX/53BP1), ubiquitination assay, constricted migration assay Nature communications Medium 35589707
2022 TPRG1-AS1 lncRNA directly interacts with MYH9 protein in HASMCs and promotes MYH9 protein degradation through the proteasome pathway, thereby hindering F-actin stress fiber formation and inhibiting smooth muscle cell migration; VSM-specific TPRG1-AS1 overexpression reduces neointima formation and atherosclerosis in vivo. RNA-protein interaction assay, Co-IP, proteasome inhibitor (MG132) rescue, F-actin staining, migration assay, transgenic/KO mouse vascular injury and atherosclerosis models Arteriosclerosis, thrombosis, and vascular biology Medium 36172865
2022 OVGP1 interacts with MYH9 (shown by pulldown-MS and Co-IP); inhibition of MYH9 attenuates OVGP1-induced hypertension and vascular remodeling in transgenic mice, placing MYH9 downstream of OVGP1 in this pathway. Pulldown/mass spectrometry, Co-IP, MYH9 inhibitor in OVGP1 transgenic mice, blood pressure measurement Circulation Medium 36172862
2022 Dlc1 (RhoGAP) interacts with MYH9 in multiprotein complexes; Dlc1 overexpression increases phosphorylation of MYH9 and activates Rac1 GTPase, linking MYH9 to Rac1-mediated cytoskeletal changes. Co-immunoprecipitation, mass spectrometry, western blot for MYH9 phosphorylation, Rac1 activation assay Biology open Low 26977077
2022 MYH9 promotes microglial homeostasis; YOD1 deubiquitinase binds MYH9 and removes K48-linked ubiquitin chains, stabilizing MYH9 protein; YOD1 knockout reduces MYH9 levels, impairs microglial migration, phagocytosis, and inflammatory response, and improves cognition in AD model mice. LC-MS/MS, Co-IP, ubiquitination assay (K48-chain specificity), YOD1 KO mouse, behavioral tests Acta pharmaceutica Sinica. B Medium 40041897
2023 MYH9 is identified as a key secreted/extracellular regulator of rheumatoid arthritis fibroblast-like synoviocyte migration and invasion; IL-1β, TNF-α, TLR ligation, and ER stress induce MYH9 secretion; blebbistatin (MYH9 ATPase inhibitor) substantially inhibits RA-FLS migration/invasion in vitro and in a humanized synovitis mouse model. LC-MS/MS secretome analysis, western blot, ELISA, siRNA/blebbistatin functional assays, humanized synovitis mouse model Annals of the rheumatic diseases Medium 37188496
2023 DNAJA4 facilitates MYH9 protein degradation via the ubiquitin-proteasome pathway by recruiting PSMD2; overexpression of MYH9 reverses the suppressive effects of DNAJA4 on NPC cell migration, invasion, and EMT, placing MYH9 downstream of the DNAJA4-PSMD2 complex. Co-IP, ubiquitination assay, MYH9 overexpression rescue, in vitro migration/invasion assay, in vivo metastasis model Cell death & disease Medium 37875476
2023 SPC25 scaffolds a trimeric SPC25/RIOK1/MYH9 complex; RIOK1 phosphorylates MYH9 at Ser1943 within this complex, causing MYH9 to disengage from the cytoskeleton and accumulate in the nucleus, where it drives CTNNB1 transcription and Wnt/β-catenin signaling to promote cancer stemness and platinum resistance in ovarian cancer. Co-IP (trimeric complex), kinase assay (RIOK1-mediated MYH9 S1943 phosphorylation), subcellular fractionation, luciferase reporter for CTNNB1, competitive peptide (CBP1) disruption in vitro/in vivo/organoids Advanced science Medium 39488790
2023 MYH9 binds NAP1L1 and recruits USP14 deubiquitinase to prevent NAP1L1 ubiquitination and degradation; stabilized NAP1L1 binds c-Myc and activates CCND1/CDK4 expression, promoting glioma proliferation and temozolomide resistance. Co-IP, ubiquitination assay, MYH9 knockdown, rescue experiments, western blot Cancer cell international Low 37770914
2023 SAMD9 stimulates GSK3β ubiquitin-mediated degradation by interacting with both MYH9 and TRAF6; silencing MYH9 or β-catenin blocks SAMD9-driven tumor stemness, EMT, and metastasis, placing MYH9 as the key intermediary in the SAMD9/MYH9/GSK3β/β-catenin axis. Co-IP, ubiquitination assay, MYH9/β-catenin siRNA rescue, in vivo tumor and metastasis models Advanced science Medium 36757050
2024 Phosphorylated MYH9 at Ser1943 (p-MYH9 S1943) recruits deubiquitinase USP22 to deubiquitinate and stabilize HIF-1α in lenvatinib-resistant HCC cells, promoting cancer stemness; CK2 inhibitor reduces MYH9 S1943 phosphorylation and reverses resistance in vivo. Immunoprecipitation, mass spectrometry, ubiquitination assay, site-specific phosphorylation analysis, CK2 inhibitor treatment, in vivo models Signal transduction and targeted therapy Medium 39300073
2024 MafG physically interacts with MYH9 to transcriptionally activate LCN2 expression; MARE motif site-directed mutation blocks MafG binding to the LCN2 promoter; LCN2 re-expression in MafG-knockdown HSCs restores resistance to ferroptosis, defining MafG/MYH9 as a transcriptional activator complex suppressing HSC ferroptosis. Co-IP, ChIP, site-directed mutagenesis of MARE motif, LCN2 rescue experiment, AAV6-mediated HSC-specific MafG KD in BDL mouse model Cell death and differentiation Medium 38871948
2024 HMBA binds directly to MYH9 (and ACTG1) in hypothalamic neurons; this binding is required for HMBA's anti-obesity effects on NPY and POMC expression; MYH9 binding by HMBA elevates HEXIM1 expression and enhances HEXIM1-MDM2 interaction, causing free HEXIM1 and p53 to translocate to the nucleus and modulate neuropeptide transcription. Direct binding assay (HMBA-MYH9), co-IP (HEXIM1-MDM2), nuclear fractionation, NPY/POMC reporter/ChIP assays, in vivo central/peripheral HMBA administration to DIO mice, MYH9-KD in NPY/POMC neurons EMBO molecular medicine Medium 37984341
2022 MYH9 head domain directly binds the cytoplasmic segment aa368–411 of ATG9B; their interaction mutually prevents binding to STUB1 E3 ubiquitin ligase, stabilizing both proteins and promoting CRC invasion. Co-IP, domain-mapping, ubiquitination assay, STUB1 interaction competition Cell death and differentiation Medium 34131310
2022 ENKUR recruits E3 ligase FBXW7 to form a ubiquitinated degradation complex with MYH9; downregulated MYH9 reduces recruitment of deubiquitinase USP2, promoting β-catenin degradation and suppressing EMT and GC metastasis. Co-IP, ubiquitination assay, MYH9 overexpression rescue, migration/invasion assays, in vivo metastasis MedComm Low 36448053
2023 MYH10 protein functional domain combines with MYH9 to recruit deubiquitinase USP45, which deubiquitinates Snail to prevent its degradation, promoting ovarian cancer tumorigenesis and cisplatin resistance. Co-IP, GST pulldown, deubiquitination assay, confocal colocalization, MYH10/MYH9 knockdown Advanced science Low 36929633
2024 RGS19 stabilizes MYH9 protein by directly competing with STUB1 (E3 ligase) for MYH9 binding via its RGS domain, reducing MYH9 ubiquitination; stabilized MYH9 activates β-catenin/c-Myc signaling; RGS19 is in turn a transcriptional target of c-Myc, forming a positive feedback loop. Co-IP, domain competition assay (RGS domain), ubiquitination assay, STUB1 identified as E3 ligase for MYH9, c-Myc ChIP Experimental & molecular medicine Medium 38825640
2022 Myh9 is essential for hematopoietic stem/progenitor cell (HSPC) survival and maintenance: Mx1-cre conditional Myh9 deletion causes pancytopenia, drastic reduction of HSPCs, bone marrow failure, impaired repopulation capacity, increased apoptosis, and early lethality; the defect is cell-autonomous. Inducible conditional knockout (Mx1-cre Myh9 flox), bone marrow transplantation chimera, RNA-seq, apoptosis assay Cells High 35740994

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis. Nature genetics 552 18794856
2000 Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Heggllin/Fechtner Syndrome Consortium. Nature genetics 344 10973259
2011 Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Laboratory investigation; a journal of technical methods and pathology 258 21826056
2018 MYH9: Structure, functions and role of non-muscle myosin IIA in human disease. Gene 252 29679756
2000 Mutation of MYH9, encoding non-muscle myosin heavy chain A, in May-Hegglin anomaly. Nature genetics 203 10973260
2000 Human nonsyndromic hereditary deafness DFNA17 is due to a mutation in nonmuscle myosin MYH9. American journal of human genetics 186 11023810
2011 Recent advances in the understanding and management of MYH9-related inherited thrombocytopenias. British journal of haematology 183 21542825
2009 MYH9-related platelet disorders. Seminars in thrombosis and hemostasis 165 19408192
2020 Silencing MYH9 blocks HBx-induced GSK3β ubiquitination and degradation to inhibit tumor stemness in hepatocellular carcinoma. Signal transduction and targeted therapy 159 32296025
2020 Nuclear MYH9-induced CTNNB1 transcription, targeted by staurosporin, promotes gastric cancer cell anoikis resistance and metastasis. Theranostics 154 32685004
2021 circ-EIF6 encodes EIF6-224aa to promote TNBC progression via stabilizing MYH9 and activating the Wnt/beta-catenin pathway. Molecular therapy : the journal of the American Society of Gene Therapy 148 34450253
2011 Mouse models of MYH9-related disease: mutations in nonmuscle myosin II-A. Blood 142 21908426
2003 Immunofluorescence analysis of neutrophil nonmuscle myosin heavy chain-A in MYH9 disorders: association of subcellular localization with MYH9 mutations. Laboratory investigation; a journal of technical methods and pathology 134 12533692
2011 MYH9 and APOL1 are both associated with sickle cell disease nephropathy. British journal of haematology 133 21910715
2010 Patients with Epstein-Fechtner syndromes owing to MYH9 R702 mutations develop progressive proteinuric renal disease. Kidney international 93 20200500
2021 Glycoprotein PTGDS promotes tumorigenesis of diffuse large B-cell lymphoma by MYH9-mediated regulation of Wnt-β-catenin-STAT3 signaling. Cell death and differentiation 88 34743203
2010 Advances in the understanding of MYH9 disorders. Current opinion in hematology 87 20601875
2014 Mutation spectrum and genotype-phenotype correlations in a large French cohort of MYH9-Related Disorders. Molecular genetics & genomic medicine 86 25077172
2017 MicroRNA-647 Targets SRF-MYH9 Axis to Suppress Invasion and Metastasis of Gastric Cancer. Theranostics 85 28900514
2017 MYH9 binds to lncRNA gene PTCSC2 and regulates FOXE1 in the 9q22 thyroid cancer risk locus. Proceedings of the National Academy of Sciences of the United States of America 80 28049826
2019 MYH9 Promotes Growth and Metastasis via Activation of MAPK/AKT Signaling in Colorectal Cancer. Journal of Cancer 77 30854093
2005 Genotype-phenotype correlation in MYH9-related thrombocytopenia. British journal of haematology 76 16098078
2011 The MYH9/APOL1 region and chronic kidney disease in European-Americans. Human molecular genetics 74 21429915
2021 MYH9-dependent polarization of ATG9B promotes colorectal cancer metastasis by accelerating focal adhesion assembly. Cell death and differentiation 69 34131310
2010 The spectrum of MYH9-associated nephropathy. Clinical journal of the American Society of Nephrology : CJASN 68 20299374
2022 TUBB4A interacts with MYH9 to protect the nucleus during cell migration and promotes prostate cancer via GSK3β/β-catenin signalling. Nature communications 67 35589707
2020 Linking the Landscape of MYH9-Related Diseases to the Molecular Mechanisms that Control Non-Muscle Myosin II-A Function in Cells. Cells 57 32545517
2019 Angiotensin II-mediated MYH9 downregulation causes structural and functional podocyte injury in diabetic kidney disease. Scientific reports 55 31118506
2020 miR-6089/MYH9/β-catenin/c-Jun negative feedback loop inhibits ovarian cancer carcinogenesis and progression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 52 32058212
2015 The non-muscle-myosin-II heavy chain Myh9 mediates colitis-induced epithelium injury by restricting Lgr5+ stem cells. Nature communications 51 25968904
2021 NEK9 regulates primary cilia formation by acting as a selective autophagy adaptor for MYH9/myosin IIA. Nature communications 48 34078910
2024 The p-MYH9/USP22/HIF-1α axis promotes lenvatinib resistance and cancer stemness in hepatocellular carcinoma. Signal transduction and targeted therapy 45 39300073
2004 Targeted disruption of mouse ortholog of the human MYH9 responsible for macrothrombocytopenia with different organ involvement: hematological, nephrological, and otological studies of heterozygous KO mice. Biochemical and biophysical research communications 45 15555549
2009 CKD in MYH9-related disorders. American journal of kidney diseases : the official journal of the National Kidney Foundation 44 19726116
2018 A Fundamental Role of Myh9 for Neutrophil Migration in Innate Immunity. Journal of immunology (Baltimore, Md. : 1950) 41 30068598
2003 Asp1424Asn MYH9 mutation results in an unstable protein responsible for the phenotypes in May-Hegglin anomaly/Fechtner syndrome. Blood 41 12649151
2024 MafG/MYH9-LCN2 axis promotes liver fibrosis through inhibiting ferroptosis of hepatic stellate cells. Cell death and differentiation 38 38871948
2023 SAMD9 Promotes Postoperative Recurrence of Esophageal Squamous Cell Carcinoma by Stimulating MYH9-Mediated GSK3β/β-Catenin Signaling. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 38 36757050
2022 MYH9 Facilitates Cell Invasion and Radioresistance in Head and Neck Cancer via Modulation of Cellular ROS Levels by Activating the MAPK-Nrf2-GCLC Pathway. Cells 38 36139430
2017 MYH9 E1841K Mutation Augments Proteinuria and Podocyte Injury and Migration. Journal of the American Society of Nephrology : JASN 37 28993503
2018 Recombinant MYH9 protein C-terminal domain blocks porcine reproductive and respiratory syndrome virus internalization by direct interaction with viral glycoprotein 5. Antiviral research 36 29879459
2020 Cisplatin-Mediated Upregulation of APE2 Binding to MYH9 Provokes Mitochondrial Fragmentation and Acute Kidney Injury. Cancer research 35 33288657
2020 MYH9 promotes cell metastasis via inducing Angiogenesis and Epithelial Mesenchymal Transition in Esophageal Squamous Cell Carcinoma. International journal of medical sciences 34 32788880
2023 MHA, an interactive website for scRNA-seq data of male genitourinary development and disease. Andrology 32 36710661
2023 TM4SF1 upregulates MYH9 to activate the NOTCH pathway to promote cancer stemness and lenvatinib resistance in HCC. Biology direct 32 37069693
2021 MYH9 is crucial for stem cell-like properties in non-small cell lung cancer by activating mTOR signaling. Cell death discovery 32 34635641
2023 ACTN1 promotes HNSCC tumorigenesis and cisplatin resistance by enhancing MYH9-dependent degradation of GSK-3β and integrin β1-mediated phosphorylation of FAK. Journal of experimental & clinical cancer research : CR 31 38057867
2022 Oviductal Glycoprotein 1 Promotes Hypertension by Inducing Vascular Remodeling Through an Interaction With MYH9. Circulation 30 36172862
2020 CRLF1-MYH9 Interaction Regulates Proliferation and Metastasis of Papillary Thyroid Carcinoma Through the ERK/ETV4 Axis. Frontiers in endocrinology 29 32982961
2018 MYH9-related disorders display heterogeneous kidney involvement and outcome. Clinical kidney journal 29 31384440
2024 OLFM4 promotes the progression of intestinal metaplasia through activation of the MYH9/GSK3β/β-catenin pathway. Molecular cancer 28 38849840
2023 MYH10 Combines with MYH9 to Recruit USP45 by Deubiquitinating Snail and Promotes Serous Ovarian Cancer Carcinogenesis, Progression, and Cisplatin Resistance. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 28 36929633
2022 Reduced platelet forces underlie impaired hemostasis in mouse models of MYH9-related disease. Science advances 28 35584211
2023 Identification of MYH9 as a key regulator for synoviocyte migration and invasion through secretome profiling. Annals of the rheumatic diseases 27 37188496
2022 Long Noncoding RNA TPRG1-AS1 Suppresses Migration of Vascular Smooth Muscle Cells and Attenuates Atherogenesis via Interacting With MYH9 Protein. Arteriosclerosis, thrombosis, and vascular biology 27 36172865
2022 Single-cell RNA-sequencing analysis reveals MYH9 promotes renal cell carcinoma development and sunitinib resistance via AKT signaling pathway. Cell death discovery 26 35318312
2007 Generation and characterization of mice with Myh9 deficiency. Neuromolecular medicine 26 17914179
2024 MYH9: A key protein involved in tumor progression and virus-related diseases. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 25 38181716
2006 Expression of Myh9 in the mammalian cochlea: localization within the stereocilia. Journal of neuroscience research 24 16862555
2022 Identification of MYH9 Key Domain Involved in the Entry of PRRSV Into Permissive Cells. Frontiers in microbiology 23 35694306
2004 Cloning and developmental expression of nonmuscle myosin IIA (Myh9) in the mammalian inner ear. Journal of neuroscience research 23 15079858
2014 MYH9 and APOL1 gene polymorphisms and the risk of CKD in patients with lupus nephritis from an admixture population. PloS one 22 24658608
2024 TMEM120B strengthens breast cancer cell stemness and accelerates chemotherapy resistance via β1-integrin/FAK-TAZ-mTOR signaling axis by binding to MYH9. Breast cancer research : BCR 21 38504374
2022 NAP1L5 targeting combined with MYH9 Inhibit HCC progression through PI3K/AKT/mTOR signaling pathway. Aging 21 36374212
2021 Knockdown of circ_NEK6 Decreased 131I Resistance of Differentiated Thyroid Carcinoma via Regulating miR-370-3p/MYH9 Axis. Technology in cancer research & treatment 21 33759638
2017 Diagnosis and treatment of MYH9-RD in an Australasian cohort with thrombocytopenia. Platelets 21 29090586
2016 Dlc1 interaction with non-muscle myosin heavy chain II-A (Myh9) and Rac1 activation. Biology open 21 26977077
2021 Multiscale analysis of single and double maternal-zygotic Myh9 and Myh10 mutants during mouse preimplantation development. eLife 20 33871354
2011 MYH9 related platelet disorders - often unknown and misdiagnosed. Klinische Padiatrie 19 21567368
2010 The association of the MYH9 gene and kidney outcomes in American Indians: the Strong Heart Family Study. Human genetics 19 19921264
2007 Of mice and men: Relevance of cellular and molecular characterizations of myosin IIA to MYH9-related human disease. Cell adhesion & migration 19 19262128
2005 First description of somatic mosaicism in MYH9 disorders. British journal of haematology 19 15667538
2023 DNAJA4 suppresses epithelial-mesenchymal transition and metastasis in nasopharyngeal carcinoma via PSMD2-mediated MYH9 degradation. Cell death & disease 18 37875476
2021 MYH9 Inhibition Suppresses TGF-β1-Stimulated Lung Fibroblast-to-Myofibroblast Differentiation. Frontiers in pharmacology 18 33519439
2020 Conditional Myh9 and Myh10 inactivation in adult mouse renal epithelium results in progressive kidney disease. JCI insight 18 33001861
2022 PI3K-activated MSC proteomes inhibit mammary tumors via Hsp90ab1 and Myh9. Molecular therapy oncolytics 17 36090473
2013 Association between a MYH9 polymorphism (rs3752462) and renal function in the Spanish RENASTUR cohort. Gene 17 23470845
2024 YOD1 regulates microglial homeostasis by deubiquitinating MYH9 to promote the pathogenesis of Alzheimer's disease. Acta pharmaceutica Sinica. B 16 40041897
2022 Circ_0000395 Promoted CRC Progression via Elevating MYH9 Expression by Sequestering miR-432-5p. Biochemical genetics 16 35759156
2020 MYH9 suppresses melanoma tumorigenesis, metastasis and regulates tumor microenvironment. Medical oncology (Northwood, London, England) 16 32902730
2022 MAP7D2 reduces CD8+ cytotoxic T lymphocyte infiltration through MYH9-HMGB1 axis in colorectal cancer. Molecular therapy : the journal of the American Society of Gene Therapy 15 36081350
2014 MYH9 nephropathy. Kidney research and clinical practice 15 26484020
2008 Alternative splice variants of MYH9. DNA and cell biology 15 17997715
2022 Myh9 Plays an Essential Role in the Survival and Maintenance of Hematopoietic Stem/Progenitor Cells. Cells 14 35740994
2019 PTP1B up-regulates EGFR expression by dephosphorylating MYH9 at Y1408 to promote cell migration and invasion in esophageal squamous cell carcinoma. Biochemical and biophysical research communications 14 31735331
2012 Glomerular MYH9 expression is reduced by HIV-1. AIDS (London, England) 14 22313957
2005 Detection of unique neutrophil non-muscle myosin heavy chain-A localization by immunofluorescence analysis in MYH9 disorder presented with macrothrombocytopenia without leukocyte inclusions and deafness. European journal of haematology 14 15613099
2003 Macrothrombocytopenia and progressive deafness is due to a mutation in MYH9. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 14 12621333
2024 Quercetin promotes the proportion and maturation of NK cells by binding to MYH9 and improves cognitive functions in aged mice. Immunity & ageing : I & A 13 38730291
2024 MYH9-related inherited thrombocytopenia: the genetic spectrum, underlying mechanisms, clinical phenotypes, diagnosis, and management approaches. Research and practice in thrombosis and haemostasis 13 39309229
2023 Targeting MYH9 represses USP14-mediated NAP1L1 deubiquitination and cell proliferation in glioma. Cancer cell international 13 37770914
2024 RGS19 activates the MYH9/β-catenin/c-Myc positive feedback loop in hepatocellular carcinoma. Experimental & molecular medicine 12 38825640
2024 Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 12 39488790
2022 A familial case of MYH9 gene mutation associated with multiple functional and structural platelet abnormalities. Scientific reports 12 36404341
2022 ENKUR recruits FBXW7 to ubiquitinate and degrade MYH9 and further suppress MYH9-induced deubiquitination of β-catenin to block gastric cancer metastasis. MedComm 12 36448053
2024 Sesamolin serves as an MYH14 inhibitor to sensitize endometrial cancer to chemotherapy and endocrine therapy via suppressing MYH9/GSK3β/β-catenin signaling. Cellular & molecular biology letters 11 38698330
2018 MYH9 Associated nephropathy. Nefrologia 11 30471777
2024 Oncogenic GALNT5 confers FOLFIRINOX resistance via activating the MYH9/ NOTCH/ DDR axis in pancreatic ductal adenocarcinoma. Cell death & disease 10 39433745
2023 LAMC2 mitigates ER stress by enhancing ER-mitochondria interaction via binding to MYH9 and MYH10. Cancer gene therapy 10 37891404
2023 HMBA ameliorates obesity by MYH9- and ACTG1-dependent regulation of hypothalamic neuropeptides. EMBO molecular medicine 10 37984341

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