Affinage

MTSS1

Protein MTSS 1 · UniProt O43312

Length
755 aa
Mass
82.3 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: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MTSS1 (MIM) is a membrane-deforming, actin-regulatory scaffold that couples the plasma membrane to the actin cytoskeleton to build and stabilize cellular protrusions, junctions, and receptor-trafficking machinery across epithelial, neuronal, and hematopoietic cells (PMID:26051541, PMID:21406566). Its I-BAR (IMD) domain binds PIP2-rich membrane and deforms it outward into nascent protrusions while also bundling F-actin and binding/activating Rac1, whereas its C-terminal WH2 domain sequesters ATP-actin monomers and modulates nucleation (PMID:12482861, PMID:15684034, PMID:26051541). Through these activities MTSS1 promotes Arp2/3-dependent actin assembly at adherens junctions and dendritic spines while restraining opposing actin machinery—directly binding and pausing the formin DAAM1 and suppressing Src family kinase activity (and downstream cortactin phosphorylation) in Purkinje and ciliated cells (PMID:29972794, PMID:30530649, PMID:20708589, PMID:21406566). By regulating endocytic internalization, MTSS1 controls the surface levels and signaling output of multiple receptors including CXCR4/CXCR5 and EGFR (PMID:26965284, PMID:22081072, PMID:21927027). MTSS1 abundance is tightly controlled: it is degraded via CKIδ-primed phosphorylation of a DSGXXS degron that recruits the SCFβ-TRCP ubiquitin ligase (PMID:24318128), and it acts as a tumor and lymphoma suppressor, with loss producing renal junction failure, B-cell lymphoma, and dysregulated NF-κB signaling through its scaffolding of the RBCK1 E3 ligase that ubiquitinates p65 (PMID:21406566, PMID:22081072, PMID:35122005). In neurons, reduced MTSS1 with elevated Src activity links it mechanistically to spinocerebellar ataxia models (PMID:30530649).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2002 High

    Established the biochemical basis of MTSS1's actin engagement, defining the C-terminal WH2 domain as an ATP-actin-monomer-binding module that regulates filament nucleation.

    Evidence In vitro actin binding/sedimentation with Kd measurements, WH2 mutagenesis, and NIH 3T3 overexpression

    PMID:12482861

    Open questions at the time
    • Did not address membrane-deforming activity
    • Cellular consequence shown only by overexpression phenotype
  2. 2003 Medium

    Linked MTSS1's actin function to membrane targeting and a receptor partner, showing the N-terminus localizes to membranes and the protein binds the phosphatase PTPδ while inducing actin-rich protrusions.

    Evidence Pulldown with purified proteins and cell extracts, truncation-construct localization

    PMID:12570871

    Open questions at the time
    • PTPδ interaction shown by single pulldown without reciprocal validation
    • Functional consequence of PTPδ binding unresolved
  3. 2004 Medium

    Identified a transcriptional/signaling role distinct from actin, placing MTSS1 in a Gli/SUFU complex that potentiates Hedgehog-dependent transcription.

    Evidence Co-IP of Gli/SUFU complex, luciferase reporter assays, regenerated skin model

    PMID:15545630

    Open questions at the time
    • Mechanism of Gli potentiation unclear
    • Later in vivo work found MTSS1 dispensable for Shh signaling in some contexts
  4. 2005 High

    Defined MTSS1 as a bifunctional actin/membrane regulator: the IMD/I-BAR domain bundles F-actin and binds/activates Rac, while the protein modulates cortactin- and N-WASP-driven Arp2/3 polymerization and cell motility.

    Evidence In vitro actin polymerization and bundling assays, direct binding assays, domain-deletion motility experiments, RPTPδ co-IP and Rac pulldown

    PMID:15684034 PMID:15688017 PMID:16280553

    Open questions at the time
    • How Rac binding and actin bundling are mechanistically coupled within the IMD remains unresolved
    • Directionality of motility effects context-dependent
  5. 2006 Medium

    Showed MTSS1 expression is epigenetically controlled, with CpG-island methylation silencing the promoter in low-expressing cells.

    Evidence Bisulfite sequencing, luciferase reporter, 5-Aza-2'-deoxycytidine treatment

    PMID:16921485

    Open questions at the time
    • Upstream signals controlling methylation not identified
  6. 2010 High

    Revealed MTSS1 as a ciliogenesis factor that acts by antagonizing Src-dependent cortactin phosphorylation at the basal body.

    Evidence siRNA knockdown, Src activity assays, phospho-cortactin immunoblotting, epistatic rescue by Src inhibition or cortactin depletion, cilia immunofluorescence

    PMID:20708589

    Open questions at the time
    • How MTSS1 restrains Src is not established
    • Direct Src interaction not demonstrated
  7. 2011 High

    Established physiological in vivo functions through knockout phenotypes—renal epithelial junction integrity and B-cell lymphoma suppression with defective CXCR5 chemotaxis/internalization—and defined MTSS1's role in receptor endocytosis and Rho-GTPase-dependent polarity.

    Evidence MIM knockout mice (renal, lymphoma), MDCK domain-mutant junction assays, CXCL13 chemotaxis and CXCR5 internalization assays, knockout MEF endocytosis and Rho-GTPase assays, EGFR localization in HNSCC

    PMID:21406566 PMID:21695258 PMID:21927027 PMID:22081072

    Open questions at the time
    • Molecular machinery coupling MTSS1 to receptor internalization not fully defined
    • Tissue-specific contributions of I-BAR vs WH2 incompletely separated
  8. 2011 Medium

    Connected MTSS1 to developmental Wnt signaling and additional transcriptional silencing, showing it binds DAAM1 to drive neural fold closure and is repressed by DNMT3B in hepatocellular carcinoma.

    Evidence Co-IP of MIM-Daam1, Xenopus morpholino knockdown with domain rescue; ChIP, reporter, methylation assays, cell-cycle analysis in HCC

    PMID:21471152 PMID:21909138

    Open questions at the time
    • DAAM1 functional consequence not yet mechanistically resolved at this stage
    • DNMT3B silencing mechanism methylation-independent but undefined
  9. 2012 Medium

    Demonstrated MTSS1 stabilizes cell-cell junctions by elevating Rac1-GTP and recruiting F-actin, conferring resistance to scatter-inducing signals.

    Evidence siRNA knockdown, HGF scatter and wound-healing assays, Rac-GTP pulldown, junctional F-actin imaging

    PMID:22479308

    Open questions at the time
    • Mechanism of Rac1 activation at junctions not detailed
  10. 2013 Medium

    Positioned MTSS1 within a RhoA-suppressing, anti-metastatic axis regulated by miR-182.

    Evidence 3'UTR luciferase reporter, RhoA activity assay, rescue experiments, xenograft

    PMID:23474751

    Open questions at the time
    • How MTSS1 suppresses RhoA mechanistically unresolved
    • Context-dependence vs pro-metastatic roles unexplained
  11. 2013 High

    Defined the degradation pathway controlling MTSS1 levels: CKIδ phosphorylation of Ser322 in a DSGXXS degron recruits SCFβ-TRCP for ubiquitin-proteasome turnover.

    Evidence Co-IP, ubiquitination assay, S322A mutagenesis, Cullin1/β-TRCP knockdown, proliferation/migration assays

    PMID:24318128

    Open questions at the time
    • Signals triggering CKIδ phosphorylation not identified
    • Structural basis of degron recognition not determined
  12. 2014 Medium

    Showed MTSS1 can also promote metastasis in a subset of melanomas through Rho-GTPase and cofilin-mediated actin dynamics, highlighting context-dependent function.

    Evidence Loss/gain-of-function, invasion assays, xenograft, Rho-GTPase and cofilin pathway analysis

    PMID:24632752

    Open questions at the time
    • Determinants of pro- vs anti-metastatic switch not defined
  13. 2015 High

    Resolved the temporal mechanics of protrusion initiation, showing the I-BAR domain deforms PIP2 membrane outward independent of actin to nucleate dendritic spines, with Arp2/3 actin assembly driving subsequent elongation; identified ΔNp63 as a transcriptional activator.

    Evidence Live imaging, PIP2 manipulation, Arp2/3 inhibition, MIM knockout mice with electrophysiology and behavior; ChIP and reporter for ΔNp63

    PMID:26051541 PMID:26119942

    Open questions at the time
    • Trigger localizing MTSS1 to spine initiation sites unknown
    • Coordination between membrane deformation and actin handoff incompletely mapped
  14. 2016 High

    Established MTSS1 as a controller of CXCR4 surface expression and internalization in hematopoietic cells, with loss causing constitutive Rac/Cdc42/p38 activation and enhanced bone marrow homing.

    Evidence Knockout bone marrow transplantation, CXCR4 flow cytometry and internalization assays, GTPase activity assays, p38 pharmacological inhibition

    PMID:26965284

    Open questions at the time
    • Direct link between MTSS1 and CXCR4 endocytic machinery undefined
  15. 2018 High

    Revealed MTSS1's dual balancing role in neuronal protrusion morphology—directly binding and pausing the formin DAAM1 while activating Arp2/3—and as a suppressor of Src family kinases relevant to spinocerebellar ataxia.

    Evidence Single-molecule speckle microscopy, co-IP, conditional knockout mice, SCA1/SCA2 models, Src activity assays, electrophysiology, Src-inhibitor rescue

    PMID:29972794 PMID:30530649

    Open questions at the time
    • Mechanism by which MTSS1 inhibits SFK activity not molecularly defined
    • Whether MTSS1 directly binds Src unresolved
  16. 2020 High

    Identified a scaffolding role in NF-κB control, with MTSS1 promoting RBCK1-mediated ubiquitination of p65 to restrain tumor-initiating-cell expansion, antagonized by ACTBL2 competition.

    Evidence Co-IP (MTSS1-RBCK1, MTSS1-ACTBL2), p65 ubiquitination assay, knockout mammary tumor models, patient-derived organoid/xenograft

    PMID:35122005

    Open questions at the time
    • How MTSS1's actin/membrane domains relate to its E3-scaffolding function unclear
  17. 2021 High

    Demonstrated MTSS1 generates filopodia-derived extracellular vesicles by membrane scission, enabling intercellular signaling that promotes recipient-cell migration.

    Evidence Live imaging, electron microscopy, FDV proteomics/lipidomics, recipient-cell Rac1 assays, ALIX suppression, force application

    PMID:33756122

    Open questions at the time
    • Physiological contexts and in vivo relevance of FDVs not established
    • Mechanism of force-promoted scission not detailed

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular basis for how MTSS1 simultaneously coordinates its membrane-deforming, actin-regulating, receptor-trafficking, and ubiquitin-ligase-scaffolding activities—and what dictates its context-dependent tumor-suppressive versus pro-metastatic behavior—remains unresolved.
  • No unified structural model integrating I-BAR, WH2, and protein-scaffolding regions
  • Determinants of opposing cancer roles undefined
  • Direct mechanism of Src kinase suppression unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0098772 molecular function regulator activity 3 GO:0005198 structural molecule activity 2 GO:0060090 molecular adaptor activity 2 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 3 GO:0005856 cytoskeleton 2 GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1
Pathway
R-HSA-9609507 Protein localization 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 2
Partners
ACTB (ACTIN)ACTBL2BTRC (Β-TRCP)CTTN (CORTACTIN)DAAM1PTPRD (PTPΔ)RAC1RBCK1
Complex memberships
Gli/SUFU complexSCFβ-TRCP ubiquitin ligase complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 MIM/MTSS1 C-terminal WH2 domain binds ATP-actin monomers with higher affinity (Kd ~0.06 µM) than ADP-actin monomers (Kd ~0.3 µM), inhibits actin filament nucleation in vitro, but allows barbed-end assembly; inhibits nucleotide exchange on actin monomers. Overexpression in NIH 3T3 cells causes disappearance of stress fibers and abnormal actin structures. In vitro actin binding/sedimentation assays, site-directed mutagenesis of WH2 domain, Northern blot, overexpression in NIH 3T3 cells The Journal of biological chemistry High 12482861
2003 MIM-B (long isoform of MIM/MTSS1) binds actin via a C-terminal WH2 domain and also binds the cytoplasmic domain of receptor protein tyrosine phosphatase delta (PTPδ), as shown by pulldown with purified proteins and cell extracts. The N-terminal portion of MIM-B localizes to internal vesicles and likely targets the protein to membranes; the C-terminal portion is cytoplasmic and does not affect the actin cytoskeleton. Full-length MIM-B induces actin-rich protrusions at the plasma membrane and promotes disassembly of stress fibers. Pulldown with purified proteins and cell extracts, subcellular localization by expression of truncated constructs The Biochemical journal Medium 12570871
2004 MIM/MTSS1 is a Sonic hedgehog (Shh)-responsive gene that is part of a Gli/Suppressor of Fused complex and potentiates Gli-dependent transcription. MIM uses domains distinct from those required for actin monomer binding to enhance Gli activity. Together with Gli1, MIM recapitulates Shh-mediated epidermal proliferation and invasion. Co-immunoprecipitation (Gli/SUFU complex), cotransfection luciferase assays, regenerated human skin model Genes & development Medium 15545630
2005 MIM/MTSS1 directly binds the SH3 domain of cortactin and promotes cortactin/Arp2/3-mediated actin polymerization in vitro. Full-length MIM binds G-actin with affinity similar to N-WASP-VCA and inhibits N-WASP-VCA-mediated actin polymerization in vitro. Overexpression of full-length MIM inhibits PDGF-induced cell motility, while deletion of the WH2 domain (abrogating G-actin binding) enhances motility; deletion of the proline-rich domain (required for cortactin binding) strengthens MIM-mediated motility inhibition. In vitro actin polymerization assays, direct binding assays, GFP colocalization, cell motility assays with domain-deletion mutants Oncogene High 15688017
2005 MIM-B induces lamellipodia-like actin-rich protrusions dependent on both the IRSp53/MIM (IMD/I-BAR) domain and Rac activity, but not the WH2 motif. MIM-B binds and activates Rac GTPase via its IMD domain, though Rac binding alone is insufficient to induce lamellipodia. Actin-bundling and Rac-binding properties of the IMD are inseparable. Expression of domain mutants, dominant-negative Rac experiments, actin bundling assays, Rac activation assays (pull-down) Journal of cell science Medium 16280553
2005 MIM/MTSS1 bundles F-actin via its IMD/I-BAR domain; this self-association-dependent bundling is independent of G-actin binding. MIM's cytoskeletal remodeling in cells requires a domain that associates with RPTPδ, which in turn enhances RPTPδ membrane localization. MIM is induced in a patched1-dependent manner (downstream of Shh signaling). F-actin bundling assays, domain mutagenesis, RPTPδ co-immunoprecipitation, membrane localization assay, patched1 dependency by genetic manipulation The Journal of cell biology Medium 15684034
2006 MIM/MTSS1 promoter expression is regulated by DNA methylation of a CpG island in its 5' region; treatment with demethylation agent 5-Aza-2'-deoxycytidine upregulates MIM expression in low-expressing cell lines. The non-methylated promoter has similar activity regardless of endogenous MIM expression level. Bisulfite sequencing, luciferase reporter assay, 5-Aza-2'-deoxycytidine treatment International journal of cancer Medium 16921485
2010 MIM/MTSS1 is required at the basal body of mesenchymal cells for cilia maintenance and Shh responsiveness. MIM knockdown results in increased Src kinase activity and hyperphosphorylation of cortactin. Inhibition of Src or depletion of cortactin compensates for the ciliogenesis defect in MIM knockdown cells; overexpression of Src or phospho-mimetic cortactin is sufficient to inhibit ciliogenesis. Thus, MIM promotes ciliogenesis by antagonizing Src-dependent phosphorylation of cortactin. siRNA knockdown, Src kinase activity assays, phospho-cortactin immunoblotting, Src inhibitor treatment, cortactin depletion, cilia immunofluorescence, hair follicle regeneration assay Developmental cell High 20708589
2011 MIM/MTSS1 promotes Arp2/3-mediated actin assembly at adherens junctions in kidney epithelial (MDCK) cells; this requires both membrane binding (I-BAR domain) and actin monomer interaction (WH2 domain). MIM-deficient mice develop severe urinary concentration defects due to compromised kidney epithelial junction integrity, leading to end-stage renal failure. MIM is dispensable for embryonic development and, in this in vivo context, is not required for Shh signaling. Knockout mouse phenotyping, MDCK cell culture with domain mutants, actin assembly assays, junction integrity assays Journal of cell science High 21406566
2011 MIM-deficient mice develop B-cell lymphomas (~78% incidence by 1–2 years). MIM-deficient B-cells fail to undergo chemotaxis or morphological changes in response to CXCL13 and fail to internalize CXCR5. MIM is the only I-BAR family member highly expressed in human B cells. MIM knockout mouse autopsy/histology, CXCL13 chemotaxis assays, CXCR5 internalization assays, microarray gene expression Oncogene High 22081072
2011 MIM/MTSS1 specifically binds Daam1 (through a conserved domain in Daam1) and couples non-canonical Wnt signaling to neural tube closure in Xenopus. This interaction is positively regulated by Wnt stimulation. MIM depletion inhibits anterior neural fold closure but not convergent extension; the function requires both the membrane-remodeling (I-BAR) and actin-binding (WH2) domains. Co-immunoprecipitation of MIM and Daam1, Xenopus morpholino knockdown, domain rescue experiments, in situ hybridization Development (Cambridge, England) Medium 21471152
2011 MIM/MTSS1 expression in hepatocellular carcinoma is silenced by DNMT3B binding directly to the MTSS1 5'-flanking region (-865/-645), independently of DNA methylation. MTSS1 overexpression arrests HCC cells in G2/M phase. Methylation inhibitors fail to restore DNMT3B-mediated MTSS1 silencing. Chromatin immunoprecipitation (ChIP), luciferase reporter assay, methylation-specific PCR, bisulfite sequencing, cell cycle analysis Oncogene Medium 21909138
2012 Mtss1 promotes cell-cell junction assembly and stability by elevating Rac1-GTP levels and driving actin recruitment to junctions. Mtss1 depletion reduces F-actin at cell-cell junctions, and Mtss1 makes cells resistant to HGF-induced junction disassembly and scatter. siRNA knockdown, wound healing and HGF scatter assays, Rac-GTP pulldown, F-actin immunofluorescence at junctions PloS one Medium 22479308
2013 MIM/MTSS1 suppresses RhoA activity and stress fiber formation in breast cancer cells. miR-182 targets MIM directly (3'UTR luciferase assay), and restoring MIM expression blocks the pro-metastasis function of miR-182; RhoA inhibition reverses the phenotypes of both miR-182 overexpression and MIM knockdown. 3'UTR luciferase reporter assay, RhoA activity assay, rescue experiments, in vivo xenograft Oncogene Medium 23474751
2013 SCFβ-TRCP E3 ubiquitin ligase targets MTSS1 for ubiquitination and proteasomal degradation. Casein Kinase Iδ (CKIδ) phosphorylates Ser322 within a DSGXXS degron in MTSS1, triggering interaction with β-TRCP. Depletion of Cullin1 or β-TRCP1 increases MTSS1 levels. A non-degradable S322A mutant more strongly inhibits cancer cell proliferation and migration than wild-type MTSS1. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (S322A), shRNA knockdown of Cullin1/β-TRCP, cell proliferation and migration assays Oncotarget High 24318128
2014 High MTSS1 expression in a subset of primary melanomas promotes metastatic ability via engagement of actin dynamics through Rho-GTPases and cofilin, demonstrated by loss- and gain-of-function approaches in vitro and in vivo. Loss/gain-of-function assays, in vitro invasion assays, in vivo xenograft, Rho-GTPase activation assay, cofilin pathway analysis Nature communications Medium 24632752
2015 MIM/MTSS1 I-BAR domain accumulates at future dendritic spine initiation sites in a PIP2-dependent manner and deforms the plasma membrane outward into a proto-protrusion, initiating spine formation independent of actin polymerization. Subsequent elongation requires PIP2-dependent Arp2/3-mediated actin assembly. MIM-deficient mice show decreased spine density, larger spine heads, altered glutamatergic transmission, and compatible behavioral defects. Live imaging of MIM accumulation, PIP2 manipulation, Arp2/3 inhibition, MIM knockout mice, electrophysiology, behavioral tests Developmental cell High 26051541
2015 ΔNp63 transcription factor drives MTSS1 expression by binding to a p63-responsive element in the MTSS1 locus, and this axis promotes migration of breast tumor cells. ChIP, luciferase reporter assay, siRNA knockdown, migration assays Oncogene Medium 26119942
2016 MIM/MTSS1 regulates CXCR4 surface expression and internalization in bone marrow cells. MIM-deficient cells show increased surface CXCR4, impaired CXCR4 internalization, constitutive activation of Rac, Cdc42, and p38, and enhanced homing to bone marrow. This enhanced homing is abolished by p38 antagonist treatment. MIM knockout mouse bone marrow transplantation, CXCR4 surface expression by flow cytometry, CXCR4 internalization assay, Rac/Cdc42/p38 activity assays, pharmacological p38 inhibition Leukemia High 26965284
2018 MTSS1 inhibits the actin-nucleating formin DAAM1 in Purkinje cell dendritic filopodia by directly binding DAAM1 through its C-terminus, pausing DAAM1-mediated F-actin polymerization as shown by single-molecule speckle microscopy. MTSS1 plays a dual role: inhibiting formin DAAM1 and activating ARP2/3, thus balancing filopodia morphology and determining final neuronal morphology. Co-immunoprecipitation, single-molecule speckle microscopy, conditional knockout mice, overactivation of DAAM1 phenocopy, domain-binding assays Cell reports High 29972794
2018 MTSS1 is a suppressor of Src family kinase (SFK) activity in Purkinje neurons. MTSS1 loss results in increased SFK activity, reduced Purkinje neuron arborization, low basal firing, and subsequent cell death. Mouse models of SCA1 and SCA2 show elevated SFK activity and dramatically reduced MTSS1 protein levels (SCA1 via reduced gene expression; SCA2 via reduced protein translation). Treatment with a clinically approved Src inhibitor corrects Purkinje neuron basal firing and delays ataxia progression. MTSS1 knockout mice, Src kinase activity assays, electrophysiology, SCA1/SCA2/SCA5 mouse models, Src inhibitor pharmacological rescue, protein expression analysis Proceedings of the National Academy of Sciences of the United States of America High 30530649
2020 MTSS1 interacts with the E3 ubiquitin ligase RBCK1 to facilitate RBCK1-mediated ubiquitination and degradation of NF-κB p65, thereby suppressing NF-κB signaling and tumor-initiating cell (TIC) expansion. ACTBL2 competes with RBCK1 for MTSS1 binding, leading to p65 stabilization when ACTBL2 is present. Co-immunoprecipitation (MTSS1-RBCK1 and MTSS1-ACTBL2), ubiquitination assay for p65, knockout mouse mammary tumor models, patient-derived organoid and xenograft experiments Nature cancer High 35122005
2021 MIM/MTSS1 I-BAR protein generates large extracellular vesicles (filopodia-derived vesicles, FDVs) by scission of filopodia. MIM-containing FDV production is promoted by external forces and by suppression of ALIX. These FDVs contain lysophospholipids, IRS4, and Rac1, and stimulate migration of recipient cells through lamellipodia formation. Live imaging, electron microscopy, FDV isolation and proteomics/lipidomics, Rac1 activity assay in recipient cells, ALIX suppression, force application experiments Developmental cell High 33756122
2011 Mtss1 enhances EGF receptor localization to the plasma membrane in head and neck squamous cell carcinoma cells, prolongs EGF signaling, and results in enhanced Erk1/2 and Akt phosphorylation. Depletion of Mtss1 decreases EGF receptor levels and reduces Erk1/2 and Akt phosphorylation. siRNA knockdown, EGF receptor localization by immunofluorescence, phospho-Erk1/2 and phospho-Akt immunoblotting, proliferation assays, organotypic assay, xenograft Oncogene Medium 21927027
2011 MIM/MTSS1 regulates cell polarity, Rho GTPase activity, and endocytosis in mouse embryonic fibroblasts. MIM-deficient MEFs show impaired stress fiber and focal adhesion assembly with reduced Rho GTPase activity; this is rescued by constitutively active RhoA. MIM-null cells show attenuated internalization of transferrin, PDGF receptor, and foreign DNAs, and elevated PDGF receptor tyrosine phosphorylation upon PDGF treatment. MIM gene-trap knockout MEFs, Rho GTPase activity assays, constitutively active RhoA rescue, internalization assays, PDGF receptor phosphorylation immunoblotting, cell migration assays PloS one Medium 21695258

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 The v-myb oncogene product binds to and activates the promyelocyte-specific mim-1 gene. Cell 492 2688896
2005 Structural basis of filopodia formation induced by the IRSp53/MIM homology domain of human IRSp53. The EMBO journal 198 15635447
1993 Synergistic activation of the chicken mim-1 gene by v-myb and C/EBP transcription factors. The EMBO journal 193 8491193
2021 High-resolution quantitative profiling of tRNA abundance and modification status in eukaryotes by mim-tRNAseq. Molecular cell 191 33581077
2003 LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090). Journal of human genetics 166 12768443
2002 MIM, a potential metastasis suppressor gene in bladder cancer. Neoplasia (New York, N.Y.) 149 12082544
2006 The RAC binding domain/IRSp53-MIM homology domain of IRSp53 induces RAC-dependent membrane deformation. The Journal of biological chemistry 146 17003044
2002 Mouse MIM, a tissue-specific regulator of cytoskeletal dynamics, interacts with ATP-actin monomers through its C-terminal WH2 domain. The Journal of biological chemistry 140 12482861
1993 Deletion of mitochondrial DNA in a case of early-onset diabetes mellitus, optic atrophy, and deafness (Wolfram syndrome, MIM 222300). The Journal of clinical investigation 139 8383698
2004 MIM/BEG4, a Sonic hedgehog-responsive gene that potentiates Gli-dependent transcription. Genes & development 134 15545630
2013 MicroRNA-182-5p promotes cell invasion and proliferation by down regulating FOXF2, RECK and MTSS1 genes in human prostate cancer. PloS one 131 23383207
1992 Myb and Ets proteins cooperate in transcriptional activation of the mim-1 promoter. Proceedings of the National Academy of Sciences of the United States of America 126 1741383
2010 MIM and cortactin antagonism regulates ciliogenesis and hedgehog signaling. Developmental cell 119 20708589
1999 X-linked cardioskeletal myopathy and neutropenia (Barth syndrome) (MIM 302060). Journal of inherited metabolic disease 112 10407787
2008 Heterozygous CAV1 frameshift mutations (MIM 601047) in patients with atypical partial lipodystrophy and hypertriglyceridemia. Lipids in health and disease 111 18237401
2013 Suppression of MIM by microRNA-182 activates RhoA and promotes breast cancer metastasis. Oncogene 110 23474751
2003 MIM-B, a putative metastasis suppressor protein, binds to actin and to protein tyrosine phosphatase delta. The Biochemical journal 101 12570871
2000 A connexin 26 mutation causes a syndrome of sensorineural hearing loss and palmoplantar hyperkeratosis (MIM 148350). Journal of medical genetics 100 10633135
2005 Involvement of Rac in actin cytoskeleton rearrangements induced by MIM-B. Journal of cell science 99 16280553
2007 Resequencing genomic DNA of patients with severe hypertriglyceridemia (MIM 144650). Arteriosclerosis, thrombosis, and vascular biology 88 17717288
2005 Differential regulation of cortactin and N-WASP-mediated actin polymerization by missing in metastasis (MIM) protein. Oncogene 87 15688017
1996 Interaction of C/EBPbeta and v-Myb is required for synergistic activation of the mim-1 gene. Molecular and cellular biology 87 8657104
2015 Fucoidan Elevates MicroRNA-29b to Regulate DNMT3B-MTSS1 Axis and Inhibit EMT in Human Hepatocellular Carcinoma Cells. Marine drugs 86 26404322
2010 Downregulation of metastasis suppressor 1(MTSS1) is associated with nodal metastasis and poor outcome in Chinese patients with gastric cancer. BMC cancer 77 20712855
2007 Characterisation of IRTKS, a novel IRSp53/MIM family actin regulator with distinct filament bundling properties. Journal of cell science 71 17430976
2020 The Mitochondrial Import Complex MIM Functions as Main Translocase for α-Helical Outer Membrane Proteins. Cell reports 70 32348752
2015 MIM-Induced Membrane Bending Promotes Dendritic Spine Initiation. Developmental cell 69 26051541
2011 Missing-in-metastasis MIM/MTSS1 promotes actin assembly at intercellular junctions and is required for integrity of kidney epithelia. Journal of cell science 68 21406566
2009 Angelman syndrome (AS, MIM 105830). European journal of human genetics : EJHG 63 19455185
2003 Genomic basis of cystathioninuria (MIM 219500) revealed by multiple mutations in cystathionine gamma-lyase (CTH). Human genetics 63 12574942
2007 MIM: a multifunctional scaffold protein. Journal of molecular medicine (Berlin, Germany) 62 17497115
2007 Homozygous missense mutation (G56R) in glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPI-HBP1) in two siblings with fasting chylomicronemia (MIM 144650). Lipids in health and disease 62 17883852
1992 Expression patterns of c-myb and of v-myb induced myeloid-1 (mim-1) gene during the development of the chick embryo. Development (Cambridge, England) 62 1576954
2011 MTSS1: a multifunctional protein and its role in cancer invasion and metastasis. Frontiers in bioscience (Scholar edition) 57 21196400
2015 EGF induces microRNAs that target suppressors of cell migration: miR-15b targets MTSS1 in breast cancer. Science signaling 54 25783158
2021 Filopodium-derived vesicles produced by MIM enhance the migration of recipient cells. Developmental cell 53 33756122
2014 MTSS1 is a metastasis driver in a subset of human melanomas. Nature communications 53 24632752
2011 MTSS1, a novel target of DNA methyltransferase 3B, functions as a tumor suppressor in hepatocellular carcinoma. Oncogene 53 21909138
2005 Receptor tyrosine phosphatase-dependent cytoskeletal remodeling by the hedgehog-responsive gene MIM/BEG4. The Journal of cell biology 53 15684034
2013 Safety and efficacy of MIM-D3 ophthalmic solutions in a randomized, placebo-controlled Phase 2 clinical trial in patients with dry eye. Clinical ophthalmology (Auckland, N.Z.) 52 23836957
2005 v-Myb mediates cooperation of a cell-specific enhancer with the mim-1 promoter. Molecular and cellular biology 50 15601869
2005 Differential expression analysis of MIM (MTSS1) splice variants and a functional role of MIM in prostate cancer cell biology. International journal of oncology 50 15870888
2004 Autosomal dominant polycystic kidney disease (ADPKD, MIM 173900, PKD1 and PKD2 genes, protein products known as polycystin-1 and polycystin-2). European journal of human genetics : EJHG 49 14872199
1995 Functional and physical interactions of components of the yeast mitochondrial inner-membrane import machinery (MIM). European journal of biochemistry 49 7556166
2004 Expression and regulation of MIM (Missing In Metastasis), a novel putative metastasis suppressor gene, and MIM-B, in bladder cancer cell lines. Cancer letters 48 15488640
2020 Acute toxicity, oxidative stress and DNA damage of three task-specific ionic liquids ([C2NH2MIm]BF4, [MOEMIm]BF4, and [HOEMIm]BF4) to zebrafish (Danio rerio). Chemosphere 47 32044610
2012 Mtss1 promotes cell-cell junction assembly and stability through the small GTPase Rac1. PloS one 47 22479308
2006 The Börjeson-Forssman-Lehman syndrome (BFLS, MIM #301900). European journal of human genetics : EJHG 45 16912705
2019 Long non‑coding RNA MEG3 suppresses the growth of glioma cells by regulating the miR‑96‑5p/MTSS1 signaling pathway. Molecular medicine reports 44 31545491
2006 The expression of metastasis suppressor MIM/MTSS1 is regulated by DNA methylation. International journal of cancer 44 16921485
1998 Missense mutation and hexanucleotide duplication in the PAX2 gene in two unrelated families with renal-coloboma syndrome (MIM 120330). Human genetics 44 9760197
2013 SCF β-TRCP targets MTSS1 for ubiquitination-mediated destruction to regulate cancer cell proliferation and migration. Oncotarget 42 24318128
2018 MTSS1 Regulation of Actin-Nucleating Formin DAAM1 in Dendritic Filopodia Determines Final Dendritic Configuration of Purkinje Cells. Cell reports 40 29972794
2018 Chronic exposure to the ionic liquid [C8mim]Br induces inflammation in silver carp spleen: Involvement of oxidative stress-mediated p38MAPK/NF-κB signalling and microRNAs. Fish & shellfish immunology 40 30343007
2022 circFBXO7/miR-96-5p/MTSS1 axis is an important regulator in the Wnt signaling pathway in ovarian cancer. Molecular cancer 38 35768865
2011 Mtss1 regulates epidermal growth factor signaling in head and neck squamous carcinoma cells. Oncogene 37 21927027
2015 p63 controls cell migration and invasion by transcriptional regulation of MTSS1. Oncogene 36 26119942
2011 The impact of Metastasis Suppressor-1, MTSS1, on oesophageal squamous cell carcinoma and its clinical significance. Journal of translational medicine 36 21696600
2020 lncRNA Mtss1 promotes inflammatory responses and secondary brain injury after intracerebral hemorrhage by targeting miR-709 in mice. Brain research bulletin 35 32442560
2010 Autolytic activity of human calpain 7 is enhanced by ESCRT-III-related protein IST1 through MIT-MIM interaction. The FEBS journal 34 20849418
2002 Phage-displayed Bet mim 1, a mimotope of the major birch pollen allergen Bet v 1, induces B cell responses to the natural antigen using bystander T cell help. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 34 12569978
2011 An NGF mimetic, MIM-D3, stimulates conjunctival cell glycoconjugate secretion and demonstrates therapeutic efficacy in a rat model of dry eye. Experimental eye research 33 21726552
1964 SEROLOGY OF THE MIMA-HERELLEA GROUP AND THE GENUS MORAXELLA. Journal of bacteriology 33 14137629
2018 MTSS1 and SCAMP1 cooperate to prevent invasion in breast cancer. Cell death & disease 32 29497041
2017 Potential toxicity of ionic liquid ([C12mim]BF4) on the growth and biochemical characteristics of a marine diatom Phaeodactylum tricornutum. The Science of the total environment 32 28202243
2016 Overexpression of maelstrom promotes bladder urothelial carcinoma cell aggressiveness by epigenetically downregulating MTSS1 through DNMT3B. Oncogene 32 27181205
2019 Toxicity Evaluation of Three Imidazolium-based ionic liquids ([C6mim]R) on Vicia faba Seedlings Using an integrated biomarker response (IBR) index. Chemosphere 31 31726585
2015 Mtss1 is a critical epigenetically regulated tumor suppressor in CML. Leukemia 31 26621336
2007 Downregulation of missing in metastasis gene (MIM) is associated with the progression of bladder transitional carcinomas. Cancer investigation 31 17453818
2001 Osteoclasts secrete the chemotactic cytokine mim-1. Biochemical and biophysical research communications 30 11178977
1993 Incontinentia pigmenti achromians (hypomelanosis of ITO, MIM 146150): further evidence of localization at Xp11. American journal of medical genetics 30 8322815
2018 miR-96 promotes breast cancer metastasis by suppressing MTSS1. Oncology letters 29 29456723
2011 Mice deficient in MIM expression are predisposed to lymphomagenesis. Oncogene 29 22081072
2018 Negative impact of the imidazolium-based ionic liquid [C8mim]Br on silver carp (Hypophthalmichthys molitrix): Long-term and low-level exposure. Chemosphere 28 30241080
2011 Metastasis suppressor-1, MTSS1, acts as a putative tumour suppressor in human bladder cancer. Anticancer research 28 21965727
2016 miR-96 promotes the growth of prostate carcinoma cells by suppressing MTSS1. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 27 27164937
2003 Genomic basis of mucopolysaccharidosis type IIID (MIM 252940) revealed by sequencing of GNS encoding N-acetylglucosamine-6-sulfatase. Genomics 27 12573255
2018 MicroRNA-411 promoted the osteosarcoma progression by suppressing MTSS1 expression. Environmental science and pollution research international 26 29453719
2014 MTSS1 suppresses cell migration and invasion by targeting CTTN in glioblastoma. Journal of neuro-oncology 26 25385572
2018 Toxicity of imidazoles ionic liquid [C16mim]Cl to HepG2 cells. Toxicology in vitro : an international journal published in association with BIBRA 25 29842889
2017 Growth and physiological responses of a marine diatom (Phaeodactylum tricornutum) against two imidazolium-based ionic liquids ([C4mim]BF4 and [C8mim]BF4). Aquatic toxicology (Amsterdam, Netherlands) 25 28618302
2020 A reciprocal feedback of Myc and lncRNA MTSS1-AS contributes to extracellular acidity-promoted metastasis of pancreatic cancer. Theranostics 24 32929338
2020 MTSS1 suppresses mammary tumor-initiating cells by enhancing RBCK1-mediated p65 ubiquitination. Nature cancer 24 35122005
2018 MTSS1/Src family kinase dysregulation underlies multiple inherited ataxias. Proceedings of the National Academy of Sciences of the United States of America 24 30530649
2015 Identification of the Adapter Molecule MTSS1 as a Potential Oncogene-Specific Tumor Suppressor in Acute Myeloid Leukemia. PloS one 24 25996952
2012 The tumour suppressive role of metastasis suppressor-1, MTSS1, in human kidney cancer, a possible connection with the SHH pathway. Journal of experimental therapeutics & oncology 23 23350348
2010 The association of the Clock 3111 T/C SNP with lipids and lipoproteins including small dense low-density lipoprotein: results from the Mima study. BMC medical genetics 23 20961464
2003 CKN1 (MIM 216400): mutations in Cockayne syndrome type A and a new common polymorphism. Journal of human genetics 23 14661080
2016 Differential effects of MTSS1 on invasion and proliferation in subtypes of non-small cell lung cancer cells. Experimental and therapeutic medicine 22 27446348
2002 Four novel mutations associated with autosomal recessive inclusion body myopathy (MIM: 600737). Molecular genetics and metabolism 22 12409274
2015 MTSS1 gene regulated by miR-96 inhibits cell proliferation and metastasis in tongue squamous cellular carcinoma Tca8113 cell line. International journal of clinical and experimental medicine 21 26629033
2011 MIM regulates vertebrate neural tube closure. Development (Cambridge, England) 21 21471152
2002 X-linked Coffin-Lowry syndrome (CLS, MIM 303600, RPS6KA3 gene, protein product known under various names: pp90(rsk2), RSK2, ISPK, MAPKAP1). European journal of human genetics : EJHG 21 11896450
2022 Experimental and computational workflow for the analysis of tRNA pools from eukaryotic cells by mim-tRNAseq. STAR protocols 20 35942339
2020 New insight into the negative impact of imidazolium-based ionic liquid [C10mim]Cl on Hela cells: From membrane damage to biochemical alterations. Ecotoxicology and environmental safety 20 33396149
2018 MIM through MOM: the awakening of Bax and Bak pores. The EMBO journal 20 30135068
2016 MIM regulates the trafficking of bone marrow cells via modulating surface expression of CXCR4. Leukemia 20 26965284
2011 Murine missing in metastasis (MIM) mediates cell polarity and regulates the motility response to growth factors. PloS one 20 21695258
2011 The relationship between adiponectin, an adiponectin gene polymorphism, and high-density lipoprotein particle size: from the Mima study. Metabolism: clinical and experimental 20 21820140
2015 Promiscuous metallo-β-lactamases: MIM-1 and MIM-2 may play an essential role in quorum sensing networks. Journal of inorganic biochemistry 19 26775612

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