Affinage

SEMA6A

Semaphorin-6A · UniProt Q9H2E6

Length
1030 aa
Mass
114.4 kDa
Annotated
2026-04-28
78 papers in source corpus 20 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SEMA6A is a transmembrane class 6 semaphorin that functions as a bidirectional signaling molecule, engaging PlexinA2 and PlexinA4 as receptors in trans (forward signaling) to regulate neuronal migration, axon guidance, oligodendrocyte differentiation and myelination, osteoclastogenesis, and neuroendocrine vascular permeability, while its intracellular domain mediates reverse signaling through interactions with EVL and FADD to control actin dynamics, apoptosis, and retinal integrity (PMID:16205717, PMID:18327254, PMID:22777942, PMID:38062045, PMID:10993894, PMID:30518871, PMID:38963001). Forward signaling through PlexinA2 controls nucleus-centrosome coupling during cerebellar granule cell migration and regulates fenestrated capillary permeability in the median eminence to govern GnRH neuron innervation and puberty onset (PMID:18327254, PMID:38062045). Co-expression of SEMA6A with PlexinA4 on the same cell acts as a cis-inhibitory mechanism that attenuates responsiveness to exogenous SEMA6A in trans (PMID:20606624). SEMA6A transcription is regulated epigenetically by the C11orf46/SETDB1 repressor complex and by HIF-2α under hypoxia, and in cancer contexts SEMA6A activates a RhoA/YAP signaling axis in melanoma and stabilizes β-catenin through interaction with SEC62 in renal cell carcinoma (PMID:31511512, PMID:36739418, PMID:35440004).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2000 Medium

    The discovery that SEMA6A binds EVL via a C-terminal zyxin-like domain established that transmembrane semaphorins can engage cytoskeletal regulators intracellularly, opening the concept of semaphorin reverse signaling.

    Evidence Yeast two-hybrid and co-immunoprecipitation in heterologous systems

    PMID:10993894

    Open questions at the time
    • Binding detected by yeast two-hybrid and co-IP without reconstitution of downstream actin remodeling
    • Functional consequence of EVL binding on cell behavior not demonstrated
    • No in vivo validation
  2. 2005 High

    Knockout mouse studies demonstrated that SEMA6A is required for cerebellar granule cell migration, establishing the first in vivo developmental function for this semaphorin.

    Evidence Sema6A knockout mouse and chimera analysis of cerebellar granule cell migration

    PMID:16205717

    Open questions at the time
    • Receptor identity unknown at this point
    • Cell-autonomous vs non-cell-autonomous mechanism not fully resolved for all cell populations
  3. 2008 High

    Identification of PlexinA2 as the functional receptor for SEMA6A in granule cells, with demonstration that their interaction controls nucleus-centrosome coupling, established the molecular mechanism underlying SEMA6A-dependent neuronal migration.

    Evidence PlexinA2 KO and ENU point mutant mice, binding assays, live imaging of nucleus-centrosome dynamics

    PMID:18327254

    Open questions at the time
    • Downstream intracellular signaling cascade from PlexinA2 to centrosome positioning not identified
    • Whether other plexins contribute in this context not excluded
  4. 2010 High

    The finding that SEMA6A and PlexinA4 interact in cis on the same neuron to attenuate trans signaling revealed a novel regulatory mechanism whereby co-expression of ligand and receptor gates guidance responses.

    Evidence Heterologous cis/trans binding assays, growth cone collapse assays in Sema6A KO and PlexinA4 knockdown neurons

    PMID:20606624

    Open questions at the time
    • Structural basis of cis vs trans binding selectivity not resolved
    • Whether cis inhibition operates in non-neuronal tissues unknown
  5. 2012 High

    Parallel studies showed SEMA6A functions in oligodendrocyte biology: it promotes oligodendrocyte differentiation and myelination, while oligodendrocyte-derived SEMA6A acts via PlexinA2 to inhibit adult CNS axon regeneration after injury.

    Evidence Sema6A and PlexinA2 KO mice; oligodendrocyte differentiation assays, DRG-OL co-culture myelination, pyramidotomy model with behavioral recovery

    PMID:22564823 PMID:22777942

    Open questions at the time
    • Whether differentiation and axon inhibition roles are mechanistically coupled or independent
    • Downstream signaling in oligodendrocytes not characterized
  6. 2014 High

    Time-lapse imaging in KO cerebella and zebrafish eye vesicles refined the migratory defect to the tangential-to-radial mode-switching phase and extended the SEMA6A/PlexinA2 partnership to epithelial tissue integrity beyond the mammalian CNS.

    Evidence Cerebellar slice electroporation with live imaging in KO mice; morpholino knockdown with time-lapse in zebrafish eye progenitors

    PMID:24917502 PMID:25284064

    Open questions at the time
    • Zebrafish data relies on morpholinos rather than genetic mutants
    • Whether mode-switching signal is contact-dependent or secreted not determined
  7. 2017 Medium

    The discovery that miR-27b represses SEMA6A to promote pericyte-endothelial adhesion expanded SEMA6A's role to vascular biology, identifying it as a repulsive cue that normally limits pericyte recruitment.

    Evidence miR-27b overexpression/inhibition with SEMA6A siRNA rescue in endothelial cells, in vivo antisense oligonucleotide treatment, femoral artery explant

    PMID:28453731

    Open questions at the time
    • Which plexin receptor mediates repulsion in pericytes not identified
    • Relative contribution of SEMA6A vs SEMA6D in this context not fully resolved
  8. 2018 Medium

    Two studies established intracellular (reverse) signaling functions: the SEMA6A extracellular domain normally suppresses FADD-mediated apoptosis via its cytoplasmic tail, while SEMA6A also guides accessory optic system axons, broadening its circuit-level roles.

    Evidence Domain truncation, FADD co-IP, and tumor growth assays in lung cancer cells; Sema6A null mouse axonal tracing in midbrain

    PMID:30076594 PMID:30518871

    Open questions at the time
    • FADD interaction demonstrated by co-IP without reciprocal pull-down or structural data
    • Whether apoptotic signaling operates in normal tissues or only cancer contexts unknown
    • Downstream effectors linking FADD binding to apoptosis modulation not mapped
  9. 2019 High

    SEMA6A was placed downstream of C11orf46/SETDB1 epigenetic regulation critical for corpus callosum connectivity, and separately shown to stimulate osteoclastogenesis via PLCγ/NFATc1, revealing both transcriptional control mechanisms and a bone biology function.

    Evidence dCas9-SunTag epigenetic editing with in vivo callosal rescue; Fc-Sema6A/PlexinA2 co-IP with PLCγ inhibitor in osteoclast cultures

    PMID:30826495 PMID:31511512

    Open questions at the time
    • Whether SETDB1-mediated repression of SEMA6A operates in non-neuronal tissues not tested
    • Full signaling cascade from PlexinA2 to PLCγ activation in osteoclasts not mapped
  10. 2022 Medium

    In melanoma, SEMA6A was shown to activate a RhoA/YAP axis that mediates fibroblast-dependent resistance to BRAF/MEK inhibition, linking SEMA6A to mechanotransduction and tumor-stroma crosstalk.

    Evidence Inducible SEMA6A knockdown, RhoA and YAP activity assays, fibroblast co-culture under dabrafenib/trametinib treatment

    PMID:35440004

    Open questions at the time
    • Which plexin receptor activates RhoA in this context not identified
    • Whether RhoA/YAP axis operates downstream of SEMA6A in normal physiology unknown
  11. 2023 High

    Two studies expanded SEMA6A's physiological scope: in the median eminence, oligodendrocyte-expressed SEMA6A/PlexinA2 controls fenestrated capillary permeability to regulate GnRH neuron innervation and puberty, while in renal carcinoma, HIF-2α transcriptionally activates SEMA6A which then interacts with SEC62 to stabilize β-catenin.

    Evidence Sema6A KO mouse with vascular permeability assays and human variant identification; ChIP for HIF-2α at SEMA6A promoter, co-IP of SEMA6A–SEC62, in vivo tumor models

    PMID:36739418 PMID:38062045

    Open questions at the time
    • Mechanism by which SEMA6A/PlexinA2 alters endothelial fenestration not defined
    • Structural basis of SEMA6A–SEC62 interaction not resolved
    • Whether SEC62 interaction is cancer-specific or generalizable unknown
  12. 2024 Medium

    Domain-deletion rescue experiments in zebrafish formally dissected forward from reverse signaling: the intracellular domain of SEMA6A is specifically required for Müller glia end-feet integrity and retinal cell survival but dispensable for eye patterning, establishing non-overlapping outputs of SEMA6A's bidirectional signaling.

    Evidence Full-length vs ΔC Sema6A rescue in zebrafish sema6a morphants with retinal histology and Müller glia analysis

    PMID:38963001

    Open questions at the time
    • Morpholino-based approach; genetic mutant confirmation needed
    • Intracellular effectors mediating Müller glia protection not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the structural basis of cis vs trans PlexinA binding selectivity, the identity of downstream effectors linking reverse signaling to cytoskeletal and survival outcomes, and whether SEMA6A's diverse tissue-specific functions employ a common or divergent intracellular signaling logic.
  • No crystal structure of SEMA6A in cis vs trans plexin complexes
  • Reverse signaling effectors beyond EVL and FADD not mapped
  • No unifying model connecting PlexinA2-dependent and PlexinA4-dependent pathways across tissues

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5 GO:0008092 cytoskeletal protein binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 1
Partners
EVLFADDPLXNA2PLXNA4SEC62

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 SEMA6A-1 (human and murine) directly binds EVL (Ena/VASP-like protein) via a novel carboxyl-terminal zyxin-like domain, physically linking the semaphorin and Ena/VASP protein families and suggesting a role for transmembrane semaphorins in retrograde signaling. Yeast two-hybrid, co-localization, binding assays (pulldown/co-IP) The Journal of biological chemistry Medium 10993894
2005 Sema6A controls cerebellar granule cell migration; in Sema6A-deficient mice, postmitotic granule cells fail to initiate radial migration and remain ectopic in the molecular layer, with chimera analysis indicating this function is primarily non-cell-autonomous. Knockout mouse analysis, chimera studies, cerebellar explant migration assay, neurite outgrowth assay Nature neuroscience High 16205717
2008 Plexin-A2 is the functional receptor for Sema6A in migrating cerebellar granule cells; Sema6A binds Plexin-A2, and loss of either Sema6A or Plexin-A2 disrupts nucleus-centrosome coupling and coordinated motility during migration, demonstrating semaphorin-plexin signaling controls cell migration by modulating centrosome positioning. Plexin-A2 knockout mouse (homologous recombination), ENU mutagenesis point mutant (abolishes Sema6A binding), chimera analysis, time-lapse video microscopy, binding assay Nature neuroscience High 18327254
2010 Sema6A engages in a cis interaction with its receptor Plexin-A4 in sensory neurons, which inhibits binding of exogenous Sema6A ligand in trans and suppresses responsiveness to Sema6A, revealing that co-expression of a transmembrane semaphorin with its receptor acts as a guidance response modulator. Heterologous expression (cis vs trans binding assay), sensory/sympathetic neuron collapse assay, Sema6A knockout neurons, Plexin-A4 knockdown The EMBO journal High 20606624
2012 Sema6A is highly expressed by myelinating oligodendrocytes; Sema6A-deficient mice show delayed oligodendrocyte differentiation, delayed node of Ranvier development, and impaired myelination in co-culture, establishing a role for Sema6A in oligodendrocyte differentiation. Sema6A knockout mouse, optic nerve and anterior commissure analysis, in vitro oligodendrocyte differentiation assay, dorsal root ganglion neuron/oligodendrocyte co-culture myelination assay Glia High 22777942
2012 PlexinA2 mediates the inhibitory effect of oligodendrocyte-derived Sema6A on adult sensory axon growth; PlexinA2 null mice show greater corticospinal axon sprouting and functional recovery after pyramidotomy, establishing a PlexinA2-Sema6A axis that limits adult CNS axon growth after injury. PlexinA2 knockout mouse, adult dorsal root ganglion neurite inhibition assay, unilateral pyramidotomy model, immunohistochemistry (synaptophysin), behavioral assays Molecular and cellular neurosciences High 22564823
2013 Sema6A expressed in oligodendrocyte precursor cells (OPCs) promotes their autonomous migration through cis and trans ligand-receptor interactions with Plexin-A4; Sema6A knockdown in OPC-like FBD-102b cells represses migration, and co-culture segregation experiments confirm Sema6A/Plexin-A4 repulsive interaction. Sema6A siRNA knockdown in FBD-102b cells, in vitro migration assay, co-culture segregation assay, gradient exposure assay, Plexin-A4 knockdown Neuroscience letters Medium 23376059
2014 Sema6a and Plexin-A2 cooperate in a cell-autonomous, tissue-autonomous manner to keep zebrafish eye vesicle progenitor cells integrated within the epithelium; knockdown of either disrupts eye vesicle integrity with progenitors failing to enter or delaminating from the vesicle, as shown by time-lapse microscopy. Morpholino knockdown in zebrafish, time-lapse microscopy of eye progenitors, explant rescue experiments, double knockdown epistasis Development (Cambridge, England) Medium 24917502
2014 Time-lapse analysis of Sema6A and PlexinA2 knockout cerebella reveals that lack of Sema6A preferentially perturbs later-born granule cells and that defects in tangential migration (bipolar cell stage) precede the failure to initiate radial migration, confirming that Sema6A/PlexinA2 regulate mode-switching in granule cell migration. Cerebellar slice electroporation, time-lapse video microscopy in Sema6A and PlexinA2 KO mice Molecular and cellular neurosciences High 25284064
2015 Sema6A silencing in BRAFV600E melanoma cells causes cytoskeletal remodeling, loss of stress fibers, cell death, and loss of anchorage-independent growth; forced Sema6A overexpression promotes invasiveness, establishing Sema6A as a regulator of actin cytoskeleton and cell viability in melanoma complexed with plexins. Sema6A siRNA knockdown, overexpression in NRASQ61R clones, cytoskeletal imaging, anchorage-independent growth assay, chemotaxis/invasion assay Oncotarget Medium 25576923
2016 Sema6A/PlexinA2 signaling participates in interkinetic nuclear migration of retinal progenitor cells (RPCs) around birth; loss of either Sema6A or PlexinA2 blocks RPC migration at the apical side of the neuroblastic layer. Sema6A and PlexinA2 knockout mouse retina analysis, time-lapse videomicroscopy Development, growth & differentiation Medium 27301906
2017 Shear stress-induced miR-27b promotes pericyte recruitment to endothelial cells partly by repressing SEMA6A and SEMA6D; silencing of SEMA6A rescues reduced pericyte adhesion caused by miR-27 inhibition, identifying SEMA6A as a repulsive cue that normally inhibits pericyte-endothelial interaction. miR-27b overexpression/inhibition in endothelial cells, SEMA6A/SEMA6D siRNA knockdown, pericyte adhesion assay, in vivo locked nucleic acid antisense oligonucleotide treatment, ex vivo femoral artery explant Cardiovascular research Medium 28453731
2018 The extracellular SEMA domain of SEMA6A attenuates intracellular apoptotic signaling: truncation of the SEMA domain or the entire extracellular region causes increased apoptosis, and re-introduction of the SEMA domain rescues this. FADD binds the cytosolic region of truncated SEMA6A and mediates apoptosis induction, revealing a novel mechanism of SEMA6A intracellular signaling. Domain truncation transfection into lung cancer cells, co-immunoprecipitation (FADD–cytosolic SEMA6A), co-culture assay, gene silencing, in vivo tumor growth assay Oncogenesis Medium 30518871
2018 Sema6A is required for the formation of axonal projections from the medial terminal nucleus (MTN) to the nucleus of the optic tract (NOT) in the accessory optic system, demonstrating a role for Sema6A in establishing midbrain circuits mediating motion perception. Genetic characterization using Cre-driver lines, Sema6A null mouse analysis, axonal tracing The Journal of comparative neurology Medium 30076594
2019 Sema6A-plexin-A2 signaling stimulates RANKL-induced osteoclastogenesis through PLCγ-mediated NFATc1 activation; soluble Fc-Sema6A binds plexin-A2 from osteoclast lysates, and pharmacological inhibition of PLCγ abrogates Sema6A-stimulated NFATc1 activation. Co-immunoprecipitation (Fc-Sema6A + plexin-A2), plexin-A2 neutralization, PLCγ inhibitor (U73122), NFATc1 activation assay, osteoclastogenesis assay Life sciences Medium 30826495
2019 Multiple genes including Sema6a are hyperexpressed when C11orf46 is knocked down in neurons; in vivo epigenetic editing of the Sema6a promoter using dCas9-SunTag with C11orf46 (recruiting SETDB1 repressor complex) normalizes SEMA6A expression and rescues transcallosal dysconnectivity, placing Sema6a downstream of C11orf46/SETDB1-mediated chromatin regulation in corpus callosum axon guidance. C11orf46 shRNA knockdown, RNA-guided epigenetic editing (dCas9-SunTag-C11orf46/SETDB1), in vivo transcallosal axon tracing, rescue experiments Nature communications High 31511512
2022 In BRAF-mutant melanoma, SEMA6A coordinates actin cytoskeleton remodeling via RhoA-dependent YAP activation (SEMA6A/RhoA/YAP axis); SEMA6A depletion abrogates fibroblast-mediated protection from dual BRAF/MEK inhibition, identifying SEMA6A as a mediator of tumor-stroma interactions conferring targeted therapy resistance. Inducible SEMA6A silencing, fibroblast co-culture model, RhoA and YAP activity assays, pharmacological BRAF/MEK inhibition (dabrafenib+trametinib) Journal of experimental & clinical cancer research Medium 35440004
2023 Semaphorin-6A expressed by median eminence-resident oligodendrocytes controls GnRH neuron innervation and puberty onset via its receptor Plexin-A2 by regulating vascular permeability of fenestrated capillaries in the median eminence; in vitro and in vivo experiments establish a role in neuroendocrine homeostasis. Sema6A knockout mouse, in vivo GnRH neuron tracing, vascular permeability assays (in vitro and in vivo), Plexin-A2 receptor identification, human patient variant identification Nature communications High 38062045
2023 SEMA6A is a direct transcriptional target of HIF-2α in hypoxic ccRCC cells (VHL-HIF-2α axis); SEMA6A physically interacts with SEC62 to promote β-catenin stabilization and Wnt/β-catenin pathway activation, driving ccRCC progression. Chromatin immunoprecipitation (HIF-2α binding to SEMA6A promoter), luciferase reporter assay, co-immunoprecipitation (SEMA6A–SEC62), SEC62 knockdown, in vitro and in vivo proliferation assays Cell death & disease Medium 36739418
2024 The intracellular domain of Sema6A (reverse signaling) is required for retinal integrity, Müller glia end-feet strength, and protection against retinal cell death in zebrafish, but not for eye size or retinal patterning; rescue experiments with Sema6A-ΔC distinguish forward (PlexinA2-mediated) from reverse signaling roles. Sema6A morphant rescue experiments with full-length vs. ΔC (intracellular domain deleted) Sema6A in zebrafish, retinal histology, Müller glia analysis Journal of cell science Medium 38963001
2024 In developing hippocampal mossy fibers, Sema6A reverse signaling (via its intracellular domain) contributes to mossy fiber partitioning into suprapyramidal and infrapyramidal tracts; PlexinA2 (using GAP-independent signaling) and PlexinA4 (requiring GAP catalytic activity) mediate distinct and overlapping aspects of this guidance, with a genetic interaction identified between Plxna2 and Ncam1. Sema6A KO mouse, PlexinA2 and PlexinA4 KO and GAP-domain mutant mice, anti-PlxnA2 proximity biotinylation (BioID), genetic epistasis (double KO with Ncam1), axonal tracing bioRxivpreprint Medium

Source papers

Stage 0 corpus · 78 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Neuropilin-2, a novel member of the neuropilin family, is a high affinity receptor for the semaphorins Sema E and Sema IV but not Sema III. Neuron 572 9331348
2004 Crystal structure of the HGF beta-chain in complex with the Sema domain of the Met receptor. The EMBO journal 198 15167892
2001 Plexina1 autoinhibition by the plexin sema domain. Neuron 176 11239433
2004 The Sema domain of Met is necessary for receptor dimerization and activation. Cancer cell 175 15261143
1998 The transmembrane Semaphorin Sema I is required in Drosophila for embryonic motor and CNS axon guidance. Neuron 165 9491983
2013 Association of granulomatosis with polyangiitis (Wegener's) with HLA-DPB1*04 and SEMA6A gene variants: evidence from genome-wide analysis. Arthritis and rheumatism 133 23740775
2004 The sema domain. Current opinion in structural biology 122 15582390
2008 Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells. Nature neuroscience 117 18327254
2005 The transmembrane semaphorin Sema6A controls cerebellar granule cell migration. Nature neuroscience 109 16205717
2009 Neuropilin 1-Sema signaling regulates crossing of cingulate pioneering axons during development of the corpus callosum. Cerebral cortex (New York, N.Y. : 1991) 83 19357391
2010 Cis interaction between Semaphorin6A and Plexin-A4 modulates the repulsive response to Sema6A. The EMBO journal 74 20606624
2006 Drosophila Plexin B is a Sema-2a receptor required for axon guidance. Development (Cambridge, England) 74 16672342
2000 The orthologous human and murine semaphorin 6A-1 proteins (SEMA6A-1/Sema6A-1) bind to the enabled/vasodilator-stimulated phosphoprotein-like protein (EVL) via a novel carboxyl-terminal zyxin-like domain. The Journal of biological chemistry 66 10993894
2015 Sema6A and Mical1 control cell growth and survival of BRAFV600E human melanoma cells. Oncotarget 57 25576923
2022 SEMA: Antigen B-cell conformational epitope prediction using deep transfer learning. Frontiers in immunology 54 36189325
2013 Linking cell fate, trajectory choice, and target selection: genetic analysis of Sema-2b in olfactory axon targeting. Neuron 54 23719164
2019 In vivo epigenetic editing of Sema6a promoter reverses transcallosal dysconnectivity caused by C11orf46/Arl14ep risk gene. Nature communications 47 31511512
2012 Role of transmembrane semaphorin Sema6A in oligodendrocyte differentiation and myelination. Glia 45 22777942
1999 Growth cone neuropilin-1 mediates collapsin-1/Sema III facilitation of antero- and retrograde axoplasmic transport. Journal of neurobiology 41 10380079
2007 Comparative integromics on non-canonical WNT or planar cell polarity signaling molecules: transcriptional mechanism of PTK7 in colorectal cancer and that of SEMA6A in undifferentiated ES cells. International journal of molecular medicine 40 17671748
2003 The soluble sema domain of the RON receptor inhibits macrophage-stimulating protein-induced receptor activation. The Journal of biological chemistry 38 14597639
2017 Shear stress-regulated miR-27b controls pericyte recruitment by repressing SEMA6A and SEMA6D. Cardiovascular research 36 28453731
2012 PlexinA2 limits recovery from corticospinal axotomy by mediating oligodendrocyte-derived Sema6A growth inhibition. Molecular and cellular neurosciences 34 22564823
2012 Crystal structure of the Sema-PSI extracellular domain of human RON receptor tyrosine kinase. PloS one 32 22848655
1999 Cloning, expression, and genetic mapping of Sema W, a member of the semaphorin family. Proceedings of the National Academy of Sciences of the United States of America 32 10051670
2010 Inhibition of MSP-RON signaling pathway in cancer cells by a novel soluble form of RON comprising the entire sema sequence. International journal of oncology 30 20428780
2017 Sema-1a Reverse Signaling Promotes Midline Crossing in Response to Secreted Semaphorins. Cell reports 28 28052247
2014 Sema6a and Plxna2 mediate spatially regulated repulsion within the developing eye to promote eye vesicle cohesion. Development (Cambridge, England) 27 24917502
2005 Met activation and receptor dimerization in cancer: a role for the Sema domain. Cell cycle (Georgetown, Tex.) 27 15846105
2024 SEMA 2.0: web-platform for B-cell conformational epitopes prediction using artificial intelligence. Nucleic acids research 26 38742639
2018 Genetic access to neurons in the accessory optic system reveals a role for Sema6A in midbrain circuitry mediating motion perception. The Journal of comparative neurology 26 30076594
2023 Improvement of glycaemic control and treatment satisfaction by switching from liraglutide or dulaglutide to subcutaneous semaglutide in patients with type 2 diabetes: A multicentre, prospective, randomized, open-label, parallel-group comparison study (SWITCH-SEMA 1 study). Diabetes, obesity & metabolism 22 36722623
2017 Suppression of Oral Carcinoma Oncogenic Activity by microRNA-203 via Down-regulation of SEMA6A. Anticancer research 22 28982852
2007 Semaphorin-4D (Sema-4D), the Plexin-B1 ligand, is involved in mouse ovary follicular development. Reproductive biology and endocrinology : RB&E 22 17376242
2023 Real world effectiveness of subcutaneous semaglutide in type 2 diabetes: A retrospective, cohort study (Sema-MiDiab01). Frontiers in endocrinology 21 36743930
2018 The extracellular SEMA domain attenuates intracellular apoptotic signaling of semaphorin 6A in lung cancer cells. Oncogenesis 21 30518871
2001 Characterization and mutant analysis of the Drosophila sema 5c gene. Developmental dynamics : an official publication of the American Association of Anatomists 21 11458392
2008 Expression of the semaphorins Sema 3D and Sema 3F in the developing parathyroid and thymus. Developmental dynamics : an official publication of the American Association of Anatomists 20 18489001
2022 SEMA6A/RhoA/YAP axis mediates tumor-stroma interactions and prevents response to dual BRAF/MEK inhibition in BRAF-mutant melanoma. Journal of experimental & clinical cancer research : CR 19 35440004
2021 Giant ankyrin-B mediates transduction of axon guidance and collateral branch pruning factor sema 3A. eLife 18 34812142
2020 Correlation of Long Noncoding RNA SEMA6A-AS1 Expression with Clinical Outcome in HBV-Related Hepatocellular Carcinoma. Clinical therapeutics 18 32070484
2016 Doxorubicin-induced epithelial-mesenchymal transition through SEMA 4A in hepatocellular carcinoma. Biochemical and biophysical research communications 17 27697528
2016 PlexinA2 and Sema6A are required for retinal progenitor cell migration. Development, growth & differentiation 16 27301906
1998 Cloning and expression pattern of a murine semaphorin homologous to H-sema IV. Neuroreport 16 9875739
2021 Cortical expression of IL1-β, Bcl-2, Caspase-3 and 9, SEMA-3a, NT-3 and P-glycoprotein as biological markers of intrinsic severity in drug-resistant temporal lobe epilepsy. Brain research 15 33516813
2010 Sema-3A indirectly disrupts the regeneration process of goldfish optic nerve after controlled injury. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 15 20449604
2006 The class 6 semaphorin SEMA6A is induced by interferon-gamma and defines an activation status of langerhans cells observed in pathological situations. The American journal of pathology 15 16436660
2014 Singapore grouper iridovirus-encoded semaphorin homologue (SGIV-sema) contributes to viral replication, cytoskeleton reorganization and inhibition of cellular immune responses. The Journal of general virology 14 24535211
2014 Time-lapse analysis of tangential migration in Sema6A and PlexinA2 knockouts. Molecular and cellular neurosciences 14 25284064
2019 Impaired ligand-dependent MET activation caused by an extracellular SEMA domain missense mutation in lung cancer. Cancer science 13 31342590
2015 Breast cancer cells promote osteoblastic differentiation via Sema 3A signaling pathway in vitro. International journal of clinical and experimental pathology 13 25973043
2013 A role of Sema6A expressed in oligodendrocyte precursor cells. Neuroscience letters 13 23376059
2024 Real-world clinical evidence of oral semaglutide on metabolic abnormalities in subjects with type 2 diabetes: a multicenter retrospective observational study (the Sapporo-Oral SEMA study). Endocrine journal 12 38658349
2023 VHL-HIF-2α axis-induced SEMA6A upregulation stabilized β-catenin to drive clear cell renal cell carcinoma progression. Cell death & disease 12 36739418
2018 Sema 3A as a biomarker of the activated mTOR pathway during hexavalent chromium-induced acute kidney injury. Toxicology letters 12 30236763
2023 SEMA6A drives GnRH neuron-dependent puberty onset by tuning median eminence vascular permeability. Nature communications 11 38062045
2023 Effect of Switching to Once-Weekly Semaglutide on Non-Alcoholic Fatty Liver Disease: The SWITCH-SEMA 1 Subanalysis. Pharmaceutics 9 37631377
2022 Secondary Metabolite Transcriptomic Pipeline (SeMa-Trap), an expression-based exploration tool for increased secondary metabolite production in bacteria. Nucleic acids research 9 35580059
2021 Effects of Switching from Liraglutide or Dulaglutide to Subcutaneous Semaglutide on Glucose Metabolism and Treatment Satisfaction in Patients with Type 2 Diabetes: Protocol for a Multicenter, Prospective, Randomized, Open-Label, Blinded-Endpoint, Parallel-Group Comparison Study (The SWITCH-SEMA 1 Study). Diabetes therapy : research, treatment and education of diabetes and related disorders 8 33491111
2006 c-Met Mutational Analysis in the Sema and Juxtamembrane Domains in Small-Cell-Lung-Cancer. Translational oncogenomics 8 23662036
2024 Real-World Evaluation of Once-Weekly Subcutaneous Semaglutide in Patients with Type 2 Diabetes Mellitus in Spain (SEMA-RW Study). Nutrients 6 39125424
2025 Real-world retrospective study in elderly patients aged 65 years and older with type 2 diabetes mellitus treated with daily oral semaglutide (SEMA-elderly). Diabetes, obesity & metabolism 5 39789997
2023 LINC00312 Inhibits Lung Cancer Progression through the miR-3175/SEMA6A Axis. Critical reviews in eukaryotic gene expression 5 36734856
2021 Inhibition of Sema-3A Promotes Cell Migration, Axonal Growth, and Retinal Ganglion Cell Survival. Translational vision science & technology 5 34817617
2019 Sema6A-plexin-A2 axis stimulates RANKL-induced osteoclastogenesis through PLCγ-mediated NFATc1 activation. Life sciences 5 30826495
2024 Efficacy and safety of oral semaglutide in older patients with type 2 diabetes: a retrospective observational study (the OTARU-SEMA study). BMC endocrine disorders 4 39049060
2022 Effects of switching from a dipeptidyl peptidase-4 inhibitor to oral semaglutide on glucose metabolism in patients with type 2 diabetes: protocol for a multicentre, prospective, randomised, open-label, parallel-group comparison study (the SWITCH-SEMA 2 study). BMJ open 3 35584872
2019 Graphical data mining of cancer mechanisms with SEMA. Bioinformatics (Oxford, England) 3 31070723
2026 Semaglutide promotes bone marrow-derived progenitor cell flux towards an anti-inflammatory and pro-regenerative profile in high-risk patients: the SEMA-VR CardioLink-15 trial. European heart journal 2 40886061
2025 The Effects of Oral Semaglutide on Hepatic Fibrosis in Subjects with Type 2 Diabetes in Real-World Clinical Practice: A Post Hoc Analysis of the Sapporo-Oral SEMA Study. Pharmaceuticals (Basel, Switzerland) 2 39861190
2025 O-SEMA-FAST: A Prospective, Non-interventional Study Investigating Oral Semaglutide Use in Adults with Type 2 Diabetes Mellitus During Ramadan. Diabetes therapy : research, treatment and education of diabetes and related disorders 2 40016571
2024 The intracellular domain of Sema6A is essential for development of the zebrafish retina. Journal of cell science 2 38963001
2020 Finally on Track: Interactions of Off-Track with Plex-Sema Pathway and Glycosaminoglycans. Structure (London, England : 1993) 2 32375057
2020 Crizotinib inhibits activation of MET pathway caused by MET extracellular SEMA domain duplication. Lung cancer (Amsterdam, Netherlands) 2 32673828
2025 Real-world evaluation of the efficacy and safety of switching from weekly dulaglutide to weekly semaglutide: The SEMA-SWITCH study. Endocrinologia, diabetes y nutricion 0 40450456
2025 SEMA6A overexpression inhibited tumor growth and metastasis in colorectal cancer. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 0 41259456
2024 Sema-3E/PlexinD1 axis modulates dendritic cell phenotypes and functions: Current status and future implications. Human immunology 0 38772051
2023 Comprehensive Analysis to Identify LINC00511-hsa-miR-625-5p-SEMA6A Pathway Fuels Progression of Skin Cutaneous Melanoma. International journal of genomics 0 37434634