Affinage

TAGLN

Transgelin · UniProt Q01995

Length
201 aa
Mass
22.6 kDa
Annotated
2026-04-28
83 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAGLN (SM22α/transgelin) is an actin-binding and actin-bundling protein that stabilizes the cytoskeleton, regulates smooth muscle cell contractility and phenotypic identity, and modulates inflammatory and matrix-remodeling signaling in vascular and other cell types. TAGLN binds F-actin through multiple C-terminal regions (residues ~154–186 critical) at a 1:6 molar stoichiometry, and this interaction is negatively regulated by PKC- and ROCK-mediated phosphorylation at Ser-181, which causes dissociation from actin filaments and cytoplasmic redistribution (PMID:11053353, PMID:10939458, PMID:25617350). Transcription of TAGLN is driven by SRF through CArG boxes and by NRF2 through an antioxidant response element in its promoter, while its protein stability is controlled by TRAF6-mediated ubiquitination at K89/K108 leading to proteasomal degradation (PMID:7768949, PMID:41029755, PMID:33771884). Loss of TAGLN activates NF-κB via ROS/NADPH oxidase, upregulates MMP-9 through derepression of ERK/AP-1 signaling, and promotes vascular inflammation and chondrogenic conversion of smooth muscle cells, while in cancer contexts TAGLN participates in mechanotransduction through the RhoA/ROCK pathway and interacts with HMGA2 to modulate epithelial-mesenchymal transition (PMID:20224039, PMID:16835221, PMID:21183509, PMID:34538264, PMID:33116628).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1987 High

    Identification and biophysical characterization of SM22 as a novel, abundant smooth-muscle-specific protein resolved its identity as distinct from all known muscle proteins, establishing it as a new cytoskeletal component to study.

    Evidence Purification from chicken gizzard smooth muscle with SDS-PAGE, sedimentation equilibrium, Stokes radius, CD spectroscopy; immunoblotting across bird and mammalian tissues

    PMID:3446186 PMID:3571244 PMID:3818630

    Open questions at the time
    • No binding partner or function identified at this stage
    • Expression analysis limited to immunoblotting with one polyclonal antibody
  2. 1993 High

    Establishing structural homology between SM22 and calponin placed TAGLN within the calponin family and predicted actin-binding capability, framing subsequent biochemical studies.

    Evidence cDNA cloning and sequence alignment of rat SM22 vs. calponin showing 43% identity over 181 aa

    PMID:8359698

    Open questions at the time
    • Functional similarity to calponin not yet tested
    • No direct actin-binding data at this point
  3. 1994 High

    Direct demonstration that SM22 binds F-actin with defined stoichiometry (1:6) and a Ca²⁺-sensitive membrane association answered the fundamental question of molecular function.

    Evidence F-actin cosedimentation assay with purified bovine aorta SM22 homolog, Ca²⁺-dependent membrane fractionation

    PMID:8117285

    Open questions at the time
    • Actin-binding domain not mapped
    • Physiological relevance of Ca²⁺ sensitivity unclear
  4. 1995 High

    Mapping the SM22α promoter to CArG/SRF boxes explained smooth-muscle-specific transcription and provided the regulatory logic for lineage-restricted expression.

    Evidence Transient transfection with luciferase reporters and deletion constructs in primary rat aortic SMCs and A7r5 cells

    PMID:7768949

    Open questions at the time
    • Contribution of MEF-2 and CACC elements not functionally separated
    • In vivo promoter activity not tested with transgenic models in this study
  5. 2000 High

    Systematic mutagenesis mapped the actin-binding interface to C-terminal residues 154–186 and identified PKC phosphorylation of Ser-181 as a switch that disrupts actin binding and relocalizes SM22 to the cytoplasm, establishing the first regulatory mechanism for TAGLN function.

    Evidence Site-directed mutagenesis, His-tagged mutant cosedimentation, PKC phosphorylation assay, immunofluorescence in transfected airway myocytes; in vitro PKC assay with mass spectrometry and in vivo localization in PKC-activated cells

    PMID:10939458 PMID:11053353

    Open questions at the time
    • Identity of in vivo kinase(s) not resolved (PKC isoform specificity unclear)
    • Whether phosphorylation is reversible and by which phosphatase unknown
  6. 2003 Medium

    Demonstrating that AVP-induced SM22α expression requires SRF binding to CArG boxes while PDGF suppression operates through Ras effectors independently of CArG elements revealed dual and opposing signaling inputs converging on the SM22 promoter.

    Evidence Promoter-reporter truncation/mutation analysis, dominant-negative/active signaling constructs, SRF overexpression, kinase inhibitors in VSMCs

    PMID:12829429

    Open questions at the time
    • Chromatin-level regulation not addressed
    • In vivo relevance of AVP/PDGF antagonism on SM22 not tested
  7. 2005 High

    Demonstrating that fission yeast and budding yeast SM22 orthologs crosslink/bundle F-actin and function in actin patch dynamics and endocytosis established evolutionary conservation of the actin-bundling mechanism and linked it to membrane trafficking.

    Evidence In vitro F-actin crosslinking, fluorescence microscopy of actin patches, overexpression phenotype in S. pombe (Stg1); live imaging, bundling assay, genetic epistasis with fimbrin in S. cerevisiae (Scp1)

    PMID:16256112 PMID:18400761

    Open questions at the time
    • Whether mammalian TAGLN similarly functions in endocytic actin patches not tested
    • Structural basis of dual actin-binding domain architecture not resolved
  8. 2006 High

    Discovery that SM22 represses MMP-9 by inhibiting ERK/AP-1 signaling, validated in SM22-null mice, established TAGLN as a signaling modulator beyond a structural actin-binding protein.

    Evidence Expression cloning, siRNA, overexpression in HT1080, MMP-9 promoter deletion/EMSA, AP-1 reporter, invasion assay, SM22-null mouse immunohistochemistry

    PMID:16835221

    Open questions at the time
    • Whether MMP-9 repression is direct or mediated through cytoskeletal changes not resolved
    • Calponin homology domain contribution to ERK inhibition not mechanistically explained
  9. 2010 High

    SM22 knockout in VSMCs revealed that TAGLN restrains NF-κB activation via suppression of ROS (NADPH oxidase/mitochondrial), and that its loss drives proinflammatory gene expression and chondrogenic transdifferentiation, expanding its role to vascular inflammation and cell fate.

    Evidence SM22 knockout mouse carotid injury model, primary Sm22−/− VSMCs, siRNA, ROS measurement, NF-κB assay, ROS scavenger rescue, immunostaining for chondrogenic markers

    PMID:20224039 PMID:21183509

    Open questions at the time
    • Direct molecular target linking SM22 to NADPH oxidase suppression unknown
    • Whether chondrogenic conversion is reversible upon SM22 restoration not shown
  10. 2014 Medium

    Identification of TAGLN as an activator of RAS-MAPK signaling in NF1-associated tumors, upregulated by promoter hypomethylation, revealed a context-dependent oncogenic role contrasting its tumor-suppressive function elsewhere.

    Evidence DNA methylation analysis, siRNA knockdown and overexpression, GTP-RAS and phospho-ERK1/2 western blot in MPNST cells

    PMID:25109740

    Open questions at the time
    • Mechanism by which TAGLN activates RAS-GTP loading not identified
    • Whether this is specific to NF1-deficient context not resolved
  11. 2015 Medium

    Establishing that ROCK (not only PKC) phosphorylates SM22 to regulate actin binding and smooth muscle basal tone added a second kinase input and linked TAGLN to RhoA/ROCK contractile signaling.

    Evidence SM22 overexpression/siRNA in IAS and RSM cells, phospho-SM22 western blot, ROCK inhibitor (Y-27632) and PKC inhibitor treatments, cell length measurement

    PMID:25617350

    Open questions at the time
    • Specific ROCK phosphorylation site on SM22 not mapped
    • In vivo contribution of ROCK vs. PKC phosphorylation not quantified
  12. 2020 Medium

    Identification of a physical TAGLN–HMGA2 interaction and TGF-β-induced nuclear translocation of TAGLN revealed a non-cytoskeletal mechanism through which TAGLN promotes EMT in colorectal cancer.

    Evidence Co-immunoprecipitation, siRNA knockdown, TGF-β treatment, EMT marker western blot, in vivo tumor growth

    PMID:33116628

    Open questions at the time
    • Single Co-IP without reciprocal validation or domain mapping
    • Mechanism of TAGLN nuclear translocation not defined
    • Whether TAGLN-HMGA2 interaction occurs in non-cancer contexts unknown
  13. 2021 Medium

    Multiple studies in 2021 expanded TAGLN regulation and function: TRAF6-mediated ubiquitination at K89/K108 was identified as the degradation pathway; ALKBH5-dependent m6A demethylation stabilizes TAGLN mRNA affecting enteric neural crest cells; TAGLN acts as a mechanosensor activating Src/RhoA/ROCK in ovarian cancer; and TAGLN negatively regulates angiogenesis in endothelial cells.

    Evidence In vitro ubiquitination reconstitution with mutagenesis (TRAF6); MeRIP-qPCR and zebrafish model (ALKBH5/m6A); AFM, hydrogels, siRNA, xenografts (mechanosensing); CRISPR disruption in HUVECs (angiogenesis)

    PMID:33771884 PMID:33961858 PMID:34338296 PMID:34538264

    Open questions at the time
    • Whether TRAF6 ubiquitination is regulated by upstream signals unknown
    • m6A regulation shown only for Hirschsprung's context; generalizability unclear
    • Mechanosensor mechanism (how stiffness upregulates TAGLN) not defined
  14. 2025 Medium

    Identification of NRF2 as a direct transcriptional activator of TAGLN via an ARE element, and discovery of the TAGLN→RhoA/ROCK2→SLC2A3 mechano-metabolic axis in fibrosis, connected TAGLN to oxidative stress responses and glycolytic metabolism.

    Evidence ChIP and dual luciferase reporter for NRF2-ARE; RNA-seq, functional assays, and bleomycin mouse model for RhoA/ROCK2/SLC2A3 axis

    PMID:39781462 PMID:41029755

    Open questions at the time
    • Relative contribution of NRF2 vs. SRF to TAGLN transcription under physiological conditions not compared
    • Whether SLC2A3-mediated metabolic reprogramming occurs in contexts beyond dermal fibrosis unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of TAGLN's dual actin-binding domains, how TAGLN switches between tumor-suppressive and oncogenic roles across cell types, the identity of the molecular target linking TAGLN to NADPH oxidase/ROS suppression, and whether TAGLN's nuclear functions (HMGA2 interaction, EMT promotion) are mechanistically separable from its cytoskeletal roles.
  • No high-resolution structure of TAGLN-actin complex available
  • No unifying model for context-dependent tumor suppressor vs. oncogene function
  • Nuclear import mechanism and nuclear interaction partners beyond HMGA2 uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 7 GO:0098772 molecular function regulator activity 3
Localization
GO:0005856 cytoskeleton 7 GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-168256 Immune System 2 R-HSA-392499 Metabolism of proteins 1
Partners
ACTA2HMGA2ROCK2SRFTRAF6

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 SM22 (TAGLN) was isolated and characterized as an abundant ~22 kDa protein from chicken gizzard smooth muscle, existing as a monomer at physiological ionic strength with a moderately asymmetric globular structure (~37% α-helix, ~31% β-sheet); it was shown not to share functional properties with myokinase, brain 23-kDa protein, or troponin I, establishing it as a novel smooth muscle protein. SDS-PAGE, sedimentation equilibrium, Stokes radius measurement, CD spectroscopy, purification The Journal of biological chemistry High 3818630
1987 SM22 (TAGLN) is widely distributed in smooth muscles of birds and mammals (chicken and bovine aorta, pig carotid, uterus, intestine, gizzard, oesophagus) with molar abundance relative to actin of ~1:6 in bovine aorta; present only in trace amounts or absent in brain, liver, heart, and skeletal muscle. Immunoblotting with polyclonal antibody, 1D and 2D gel electrophoresis, purification from bovine aorta The Biochemical journal High 3446186
1987 The complete amino acid sequence of chicken gizzard SM22α was determined: a single polypeptide of 197 residues with Mr ~21,978 and net charge of +4.5 at neutral pH; no significant similarity to any known protein at the time, confirming it as a novel protein. Automated and manual Edman degradation sequencing of chemical and proteolytic fragments The Journal of biological chemistry High 3571244
1993 Rat SM22 encodes a 201-amino acid protein (Mr 22,601) with 43% identity to calponin over a 181-aa overlap, particularly high (70%) identity at the C-terminal region of SM22 and the first repeat motif of calponin, establishing structural homology between SM22 and calponin. cDNA cloning, sequencing, sequence alignment Gene High 8359698
1994 A bovine aorta SM22 homolog (25-kDa) directly binds F-actin at a ratio of 1:6 actin monomers with a binding constant of 7.0 × 10^5 M⁻¹, and the interaction is Ca²⁺-sensitive: the protein associates with the membrane fraction in the presence of Ca²⁺ and dissociates with EGTA. Protein purification, F-actin cosedimentation assay, Ca²⁺-dependent membrane fractionation, partial sequence analysis Biochemical and biophysical research communications High 8117285
1995 The murine SM22α gene promoter (441 bp of 5'-flanking sequence) containing two CArG/SRF boxes, a CACC box, and a MEF-2 binding site is necessary and sufficient to drive high-level transcription specifically in smooth muscle cells; deletion analysis defined the core promoter elements. Transient transfection, luciferase reporter assay, deletion analysis in primary rat aortic SMCs and A7r5 cells The Journal of biological chemistry High 7768949
2000 Human SM22 (TAGLN) binds F-actin through multiple regions within its C-terminal domain: the region 170–186 is almost completely required, the segment 154–161 (KKAQEHKR) partially required, and residues beyond 151 are necessary; the N-terminal domain alone is insufficient. Phosphorylation of Ser-181 by protein kinase C greatly decreases actin binding, and a S181D phosphomimetic also reduces binding. In transfected airway myocytes, full-length SM22 colocalizes with actin filaments while truncated SM22-(1-151) does not. Site-directed mutagenesis, E. coli expression of His-tagged mutants, in vitro actin cosedimentation assay, PKC phosphorylation assay, immunofluorescence in transfected cells Journal of applied physiology High 11053353
2000 SM22 (TAGLN) is identified as a novel protein kinase C (PKC) substrate in smooth muscle cells; phosphorylation by PKC in vitro was confirmed and, upon PKC activation in vivo, SM22 dissociates from the actin cytoskeleton and redistributes diffusely in the cytoplasm, demonstrating that PKC-mediated phosphorylation controls SM22 intracellular localization. In vitro PKC kinase assay, 2D gel electrophoresis, mass spectrometry identification, immunofluorescence in PKC-activated cells Electrophoresis High 10939458
2006 SM22 (transgelin/TAGLN) represses MMP-9 expression by targeting the ERK/MAPK signaling pathway, leading to reduced AP-1 (c-Fos) binding to the proximal MMP-9 promoter AP-1 motif; this requires an intact N-terminal calponin homology domain. SM22 knockdown by siRNA elevates MMP-9 synthesis and invasion, while SM22 null mouse uterus shows strong MMP-9 immunoreactivity. Expression cloning, siRNA knockdown, overexpression in HT1080 cells, MMP-9 promoter deletion/mutation analysis, AP-1 reporter assay, nuclear extract EMSA for c-Fos binding, in vitro invasion assay, immunohistochemistry in SM22-null mice The Journal of biological chemistry High 16835221
2008 Yeast SM22 homolog Scp1 (ortholog of mammalian TAGLN) contains two distinct actin-binding domains that allow it to both bind and bundle F-actin without dimerization; live cell imaging showed Scp1 localizes to cortical actin patches during endocytosis and is required for movement of patches away from the plasma membrane. Loss of both Scp1 and fimbrin Sac6 dramatically increases patch lifetime, demonstrating that actin-bundling activity is critical for endocytosis. Live cell imaging of GFP-tagged mutants, in vitro actin bundling assays, genetic deletion and epistasis (scp1Δ sac6Δ double mutant), Western blot The Journal of biological chemistry High 18400761
2010 SM22 (TAGLN) disruption in vascular smooth muscle cells (VSMCs) promotes NF-κB pathway activation via increased reactive oxygen species (ROS) production involving NADPH oxidase (p47phox activation) and mitochondria (increased Sod2), leading to upregulation of proinflammatory genes (Vcam1, Icam1, Cx3cl1, Ccl2, Ptgs2) after arterial injury; ROS scavengers blocked NF-κB activation and gene induction. SM22 knockout mouse carotid denudation model, primary Sm22⁻/⁻ VSMCs, siRNA knockdown in PAC1 cells, ROS measurement, NF-κB activation assay, ROS scavenger rescue experiments Circulation research High 20224039
2010 SM22 deficiency promotes chondrogenic conversion of VSMCs: loss of SM22 alters VSMC morphology with compromised stress fiber formation and increased actin dynamics, upregulates Sox9 mRNA and chondrogenic markers (type II collagen, aggrecan, BMP2), and downregulates myocardin and VSMC markers; this chondrogenic switch is mediated via ROS-NF-κB pathway activation. SM22 knockout mouse carotid denudation model, primary Sm22⁻/⁻ VSMCs, SM22 siRNA knockdown, immunostaining for chondrogenic markers, actin dynamics assay Cardiovascular research High 21183509
2012 Depletion of SM22 (TAGLN) in REF52 fibroblasts disrupts normal actin organization, increases cell motility, increases spontaneous podosome formation, and enhances Matrigel invasion; conversely, re-expression of SM22 in SM22-negative PC3 prostate cancer cells reduces Matrigel invasion. SM22-depleted cells also have reduced ROS under serum starvation stress. siRNA knockdown in REF52 fibroblasts, SM22 re-expression in PC3 cells, actin organization imaging, podosome quantification, Matrigel invasion assay, ROS measurement BMC cell biology Medium 22257561
2015 SM22 (TAGLN) phosphorylation by Rho kinase (ROCK), but not PKC, inversely correlates with SM22-actin binding in smooth muscle cells; SM22 overexpression (pFLAG-SM22) causes relaxation in tonic IAS smooth muscle cells greater than in phasic RSM cells, while SM22 siRNA causes contraction in both cell types, indicating SM22 regulates basal tone via ROCK-induced phosphorylation affecting its actin binding. SM22 overexpression (pFLAG-SM22 transfection), siRNA knockdown, measurement of SMC length, phospho-SM22 western blot, Y-27632 (ROCK inhibitor) and Gö-6850 (PKC inhibitor) treatment American journal of physiology. Gastrointestinal and liver physiology Medium 25617350
2021 TAGLN acts as a mechanosensitive gene in ovarian cancer cells: matrix stiffness upregulates TAGLN expression, TAGLN activates Src, and Src in turn feeds back on TAGLN in a regulation loop mediating stiffness-induced OC progression through the RhoA/ROCK pathway. Atomic force microscopy for stiffness measurement, polyacrylamide hydrogel system (soft vs. stiff), siRNA knockdown, western blot, immunofluorescence, in vivo xenograft Journal of experimental & clinical cancer research Medium 34538264
2021 TAGLN is expressed in endothelial cells (ECs) and functions as a negative regulator of angiogenesis: TAGLN expression is activated during EC elongation in response to VEGF-A; genetic disruption of TAGLN in HUVECs augments angiogenic behaviors (tube formation, sprouting); similar results were obtained with TAGLN2 and TAGLN3 knockouts. Mouse ESC Tagln promoter-fluorescence reporter, VEGF-A stimulation, PI3K-Akt/mTORC1 inhibition, CRISPR genetic disruption in HUVECs, angiogenesis assay Journal of cell science Medium 34338296
2021 TRAF6 mediates mono-ubiquitination of TAGLN at K89 or K108 residues via the E2A-TRAF6 pair, leading to proteasomal degradation of TAGLN in prostate cancer cells. Loss of TAGLN activates NF-κB and Myc signaling pathways, promoting cancer cell proliferation and suppressing migration. In vitro ubiquitination assay screening >20 E2-E3 pairs, site-directed mutagenesis of ubiquitination sites, proteasome inhibitor rescue, western blot, siRNA/overexpression functional assays Molecular cancer research High 33771884
2021 ALKBH5, an m6A demethylase, binds to m6A sites in TAGLN mRNA and reduces m6A methylation of TAGLN mRNA, thereby inhibiting its degradation and increasing TAGLN protein expression; elevated TAGLN then inhibits proliferation and migration of enteric neural crest cells, contributing to Hirschsprung's disease. MeRIP-qPCR, dual-luciferase reporter assay, ALKBH5 overexpression/knockdown, cell proliferation and migration assays, zebrafish overexpression model Life sciences Medium 33961858
2020 TAGLN physically interacts with HMGA2, and TGF-β-induced TAGLN undergoes nuclear translocation; knockdown of TAGLN reverses TGF-β-induced EMT markers (E-cadherin loss, vimentin, fibronectin upregulation) and MMP2/MMP9 elevation in colorectal cancer cells; HMGA2 overexpression restores TGF-β effects suppressed by TAGLN inhibition in vitro and in vivo. Co-immunoprecipitation, siRNA knockdown, TGF-β treatment, western blot for EMT markers, migration/invasion assays, in vivo tumor growth experiment OncoTargets and therapy Medium 33116628
2007 The C-terminal domain of SM22α (TAGLN) directly interacts with F-actin to participate in cytoskeleton reorganization in VSMCs: GST pull-down and co-immunoprecipitation confirmed SM22-actin interaction; immunofluorescence showed SM22α colocalizes with F-actin during VSMC redifferentiation, and SM22α distributes predominantly in F-actin fractions (not G-actin) during the contractile phenotype. GST pull-down assay, co-immunoprecipitation, western blot of F-actin/G-actin fractions, immunofluorescence in VSMCs undergoing phenotypic modulation Chinese journal of applied physiology Medium 21162287
2025 TAGLN regulates skin fibroblast motility and secretory function (invasion, migration, contraction, collagen secretion) through a mechano-metabolic axis: TAGLN activates the RhoA/ROCK2 pathway, which upregulates the glucose transporter SLC2A3, thereby affecting glycolysis in dermal fibroblasts. Targeting TAGLN reduced fibrosis in a bleomycin-induced mouse model. Transwell, wound healing, collagen gel contraction assay, immunofluorescence, RNA-seq, siRNA knockdown/overexpression, western blot, bleomycin mouse model International journal of biological sciences Medium 39781462
2025 NRF2 directly transcriptionally activates TAGLN: a functional antioxidant response element (ARE) was identified in the TAGLN promoter; ChIP confirmed NRF2 binding; TAGLN mediates NRF2-promoted ovarian cancer cell migration and EMT (E-cadherin down, N-cadherin up), as TAGLN siRNA reversed NRF2 overexpression effects on migration and EMT markers. Dual luciferase reporter assay, ChIP assay, siRNA knockdown, wound-healing and Transwell assays, western blot for EMT markers Journal of ovarian research Medium 41029755
2014 TAGLN upregulation in NF1-associated MPNSTs is caused by hypomethylation of its promoter and subpromoter regions; TAGLN knockdown in MPNST cells decreases RAS-GTP and phospho-ERK1/2 activation, while TAGLN overexpression in normal NF1-deficient cells increases RAS and ERK1/2 activation, placing TAGLN as an activator of the RAS-MAPK pathway. DNA methylation analysis, siRNA knockdown, TAGLN overexpression, western blot for GTP-RAS and phospho-ERK1/2, immunohistochemistry Oncology reports Medium 25109740
2005 Fission yeast Stg1, an SM22/transgelin-like protein (ortholog of mammalian TAGLN), crosslinks F-actin in vitro and localizes to actin patches; Stg1 overexpression causes cytokinesis defects by suppressing contractile ring formation and generating abnormal F-actin aggregates, implicating TAGLN orthologs in actin cytoskeleton organization and cytokinesis. In vitro F-actin crosslinking assay, fluorescence microscopy of actin patches, Stg1 overexpression phenotype analysis in fission yeast FEBS letters Medium 16256112
2003 AVP induces and PDGF-BB suppresses SM22α expression in VSMCs through distinct signaling pathways: AVP activates both JNK and p38 MAPK and requires the proximal CArG boxes in the SM22α promoter and serum response factor (SRF) binding; PDGF suppression involves Raf, Ral-GDS, and PI3K activation downstream of Ras, independently of CArG boxes. Promoter-reporter assays, truncation analysis, CArG box mutagenesis, dominant-active and dominant-negative signaling constructs, SRF overexpression, kinase inhibitor experiments American journal of physiology. Heart and circulatory physiology Medium 12829429

Source papers

Stage 0 corpus · 83 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 SM22 alpha, a marker of adult smooth muscle, is expressed in multiple myogenic lineages during embryogenesis. Circulation research 371 8575061
1999 Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators. Molecular cell 353 10198638
2000 Involvement of the TRAP220 component of the TRAP/SMCC coactivator complex in embryonic development and thyroid hormone action. Molecular cell 250 10882104
1995 Structure and expression of a smooth muscle cell-specific gene, SM22 alpha. The Journal of biological chemistry 233 7768949
1999 A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation. Molecular cell 232 10024883
2001 The TRAP/SMCC/Mediator complex and thyroid hormone receptor function. Trends in endocrinology and metabolism: TEM 209 11306338
2000 The USA-derived transcriptional coactivator PC2 is a submodule of TRAP/SMCC and acts synergistically with other PCs. Molecular cell 111 10882111
2000 Mutagenesis analysis of human SM22: characterization of actin binding. Journal of applied physiology (Bethesda, Md. : 1985) 105 11053353
2006 Expression cloning identifies transgelin (SM22) as a novel repressor of 92-kDa type IV collagenase (MMP-9) expression. The Journal of biological chemistry 101 16835221
1987 Isolation and characterization of an abundant and novel 22-kDa protein (SM22) from chicken gizzard smooth muscle. The Journal of biological chemistry 99 3818630
1987 An abundant and novel protein of 22 kDa (SM22) is widely distributed in smooth muscles. Purification from bovine aorta. The Biochemical journal 98 3446186
2002 TRAP/SMCC/mediator-dependent transcriptional activation from DNA and chromatin templates by orphan nuclear receptor hepatocyte nuclear factor 4. Molecular and cellular biology 89 12101254
2010 Disruption of SM22 promotes inflammation after artery injury via nuclear factor kappaB activation. Circulation research 88 20224039
1998 Expression and cytogenetic localization of the human SM22 gene (TAGLN). Genomics 78 9615232
1993 cDNA cloning and mRNA expression of calponin and SM22 in rat aorta smooth muscle cells. Gene 74 8359698
2021 TAGLN mediated stiffness-regulated ovarian cancer progression via RhoA/ROCK pathway. Journal of experimental & clinical cancer research : CR 71 34538264
1999 Smooth muscle-specific SM22 protein is expressed in the adventitial cells of balloon-injured rabbit carotid artery. Arteriosclerosis, thrombosis, and vascular biology 70 10364069
2021 The canonical smooth muscle cell marker TAGLN is present in endothelial cells and is involved in angiogenesis. Journal of cell science 54 34338296
2013 Stromal fibroblasts in the microenvironment of gastric carcinomas promote tumor metastasis via upregulating TAGLN expression. BMC cell biology 53 23510049
2012 Depletion of the actin bundling protein SM22/transgelin increases actin dynamics and enhances the tumourigenic phenotypes of cells. BMC cell biology 50 22257561
2006 A critical developmental role for tgfbr2 in myogenic cell lineages is revealed in mice expressing SM22-Cre, not SMMHC-Cre. Journal of molecular and cellular cardiology 49 16887142
1987 Amino acid sequence of chicken gizzard smooth muscle SM22 alpha. The Journal of biological chemistry 46 3571244
2015 Cardiomyopathy and Worsened Ischemic Heart Failure in SM22-α Cre-Mediated Neuropilin-1 Null Mice: Dysregulation of PGC1α and Mitochondrial Homeostasis. Arteriosclerosis, thrombosis, and vascular biology 45 25882068
2014 The downregulation of miR-144 is associated with the growth and invasion of osteosarcoma cells through the regulation of TAGLN expression. International journal of molecular medicine 44 25318625
1995 Cloning and analysis of the promoter region of the rat SM22 alpha gene. The Biochemical journal 40 7575400
2008 Interactions between the yeast SM22 homologue Scp1 and actin demonstrate the importance of actin bundling in endocytosis. The Journal of biological chemistry 37 18400761
2010 Arterial injury promotes medial chondrogenesis in Sm22 knockout mice. Cardiovascular research 36 21183509
2009 Expression of the actin-associated protein transgelin (SM22) is decreased in prostate cancer. Cell and tissue research 35 20012321
1997 Tissue distribution and metabolism of the [32P]-labeled oligodeoxynucleoside methylphosphonate-neoglycopeptide conjugate, [YEE(ah-GalNAc)3]-SMCC-AET-pUmpT7, in the mouse. Antisense & nucleic acid drug development 34 9212904
2012 TAGLN suppresses proliferation and invasion, and induces apoptosis of colorectal carcinoma cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 31 23138394
2011 TAGLN expression is deregulated in endometriosis and may be involved in cell invasion, migration, and differentiation. Fertility and sterility 31 21763649
1994 Purification, characterization, and partial sequence analysis of a new 25-kDa actin-binding protein from bovine aorta: a SM22 homolog. Biochemical and biophysical research communications 29 8117285
2003 Regulation of SM22 alpha expression by arginine vasopressin and PDGF-BB in vascular smooth muscle cells. American journal of physiology. Heart and circulatory physiology 28 12829429
2010 Loss of SM22 is a characteristic signature of colon carcinogenesis and its restoration suppresses colon tumorigenicity in vivo and in vitro. Cancer 27 20336793
1999 Differential expression of SM22 isoforms in myofibroblasts and smooth muscle cells from rabbit bladder. Journal of muscle research and cell motility 26 10412085
2006 Sm22.6 antigen is an inhibitor to human thrombin. Molecular and biochemical parasitology 25 16499980
1998 Paralogous sm22alpha (Tagln) genes map to mouse chromosomes 1 and 9: further evidence for a paralogous relationship. Genomics 25 9693045
2015 Delivery of PUMA Apoptosis Gene Using Polyethyleneimine-SMCC-TAT/DNA Nanoparticles: Biophysical Characterization and In Vitro Transfection Into Malignant Melanoma Cells. Journal of biomedical nanotechnology 24 26502640
2020 Long non-coding RNA GAS5 overexpression inhibits M2-like polarization of tumour-associated macrophages in SMCC-7721 cells by promoting PTEN expression. International journal of experimental pathology 23 33146930
2018 SM22 a Plasma Biomarker for Human Transmural Intestinal Ischemia. Annals of surgery 22 28525410
2003 Human SM22 alpha BAC encompasses regulatory sequences for expression in vascular and visceral smooth muscles at fetal and adult stages. American journal of physiology. Heart and circulatory physiology 21 12521938
2014 The glomerular parietal epithelial cell's responses are influenced by SM22 alpha levels. BMC nephrology 17 25376243
2014 AFM-based study of fullerenol (C60(OH)24)-induced changes of elasticity in living SMCC-7721 cells. Journal of the mechanical behavior of biomedical materials 16 25682196
1991 Gene cloning and nucleotide sequence of SM22 alpha from the chicken gizzard smooth muscle. Biochemistry international 16 1872880
2021 m6A demethylase ALKBH5 suppresses proliferation and migration of enteric neural crest cells by regulating TAGLN in Hirschsprung's disease. Life sciences 15 33961858
2015 Establishment of N-succinimidyl 4-(maleimidomethyl) cyclohexanecarboxylate (SMCC) modified biochip enabling concurrent detection of serum infectious antibodies in neuroborreliosis. Biosensors & bioelectronics 15 26655180
2021 TAGLN Is Downregulated by TRAF6-Mediated Proteasomal Degradation in Prostate Cancer Cells. Molecular cancer research : MCR 14 33771884
2020 TAGLN and High-mobility Group AT-Hook 2 (HMGA2) Complex Regulates TGF-β-induced Colorectal Cancer Metastasis. OncoTargets and therapy 14 33116628
2014 TAGLN expression is upregulated in NF1-associated malignant peripheral nerve sheath tumors by hypomethylation in its promoter and subpromoter regions. Oncology reports 14 25109740
2005 Stg 1 is a novel SM22/transgelin-like actin-modulating protein in fission yeast. FEBS letters 13 16256112
2000 Identification of the smooth muscle-specific protein, sm22, as a novel protein kinase C substrate using two-dimensional gel electrophoresis and mass spectrometry. Electrophoresis 13 10939458
2020 Functional loss of TAGLN inhibits tumor growth and increases chemosensitivity of non-small cell lung cancer. Biochemical and biophysical research communications 12 32819569
1996 Expression of senescence-induced protein WS3-10 in vivo and in vitro. Experimental gerontology 12 8706785
2022 Comparative proteomics identify HSP90A, STIP1 and TAGLN-2 in serum extracellular vesicles as potential circulating biomarkers for human adenomyosis. Experimental and therapeutic medicine 11 35495589
2022 RNA-sequencing of human aortic valves identifies that miR-629-3p and TAGLN miRNA-mRNA pair involving in calcified aortic valve disease. Journal of physiology and biochemistry 11 35776288
2018 Abrogation of TGF-beta signalling in TAGLN expressing cells recapitulates Pentalogy of Cantrell in the mouse. Scientific reports 11 29483576
2022 Colonic healing requires Wnt produced by epithelium as well as Tagln+ and Acta2+ stromal cells. Development (Cambridge, England) 10 34910127
2017 Improved performance of collagen scaffolds crosslinked by Traut's reagent and Sulfo-SMCC. Journal of biomaterials science. Polymer edition 10 28277011
2013 Reduced expression of SM22 is correlated with low autophagy activity in human colorectal cancer. Pathology, research and practice 10 23538046
2012 Single-walled carbon nanotubes promote rat vascular adventitial fibroblasts to transform into myofibroblasts by SM22-α expression. International journal of nanomedicine 10 22904629
2024 Involvement of TGFBI-TAGLN axis in cancer stem cell property of head and neck squamous cell carcinoma. Scientific reports 9 38514830
2023 CHRDL1, NEFH, TAGLN and SYNM as novel diagnostic biomarkers of benign prostatic hyperplasia and prostate cancer. Cancer biomarkers : section A of Disease markers 8 37781794
2014 [Effect of miR-30a-5p on the proliferation, apoptosis, invasion and migration of SMCC-7721 human hepatocellular carcinoma cells]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 8 25654285
1996 Presence of Ca(2+)-sensitive and -insensitive SM22 alpha isoproteins in bovine aorta. Biochemical and biophysical research communications 8 8954110
2015 Role of SM22 in the differential regulation of phasic vs. tonic smooth muscle. American journal of physiology. Gastrointestinal and liver physiology 7 25617350
2015 Potent antigen-specific immune response induced by infusion of spleen cells coupled with succinimidyl-4-(N-maleimidomethyl cyclohexane)-1-carboxylate (SMCC) conjugated antigens. International immunopharmacology 7 26735611
2006 Development of a cell-isolation method for human prostatic smooth muscle cells based on cell type-specific activation of the SM22 gene promoter. BJU international 7 17034489
2023 LZTS3/TAGLN Suppresses Cancer Progression in Human Colorectal Adenocarcinoma Through Regulating Cell Proliferation, Migration, and Actin Cytoskeleton. Archives of medical research 6 37806182
2025 Comprehensive analysis of the critical role of the epithelial mesenchymal transition subtype - TAGLN-positive fibroblasts in colorectal cancer progression and immunosuppression. Cell & bioscience 5 40413514
2021 Simple and Rapid LC-MS/MS Methods for Quantifying Catabolites of Antibody-Drug Conjugates with SMCC Linker. Journal of chromatographic science 5 33420505
2021 Effect of trypsin concentration on living SMCC-7721 cells studied by atomic force microscopy. Journal of microscopy 5 34350998
2006 [The role of SM22 alpha in cytoskeleton organization and vascular remodeling]. Sheng li ke xue jin zhan [Progress in physiology] 4 17009727
2026 SMCC: A Novel Clustering Method for Single- and Multi-Omics Data Based on Co-Regularized Network Fusion. IEEE transactions on computational biology and bioinformatics 3 38215334
2025 TAGLN-RhoA/ROCK2-SLC2A3-mediated Mechano-metabolic Axis Promotes Skin Fibrosis. International journal of biological sciences 3 39781462
2022 Bombyx batryticatus Cocoonase Inhibitor Separation, Purification, and Inhibitory Effect on the Proliferation of SMCC-7721 HeLa-Derived Cells. Evidence-based complementary and alternative medicine : eCAM 3 35747381
2010 [A study of the single nucleotide polymorphism in seven genes (GHR, IGFBP3, IGFR1, IRS1, FMN1, ANXA2, TaGLN) in ethnic Russians and in patients with prostate cancer]. Molekuliarnaia genetika, mikrobiologiia i virusologiia 3 20540360
2019 c[RGDyk]-coated liposomes loaded with adriamycin and miR-21 mimics inhibit the growth of hepatoma cell line SMCC-7721 via up-regulating Bax and p53. Translational cancer research 1 35116873
2015 [Effect of IFN-α on hepatic cancer SMCC-7721 cell via PI3K/Akt signaling pathway and related mechanism research]. Zhonghua yi xue za zhi 1 26814075
2026 5'-NucA-SMCC-DM1 and 5'-NucA-SPDMV-DM1 are Potent Aptamer-Drug Conjugates against Pancreatic Cancer. ACS omega 0 41768714
2025 NRF2 promotes the migration of ovarian cancer cell lines by targeting TAGLN mediated epithelial-mesenchymal transition. Journal of ovarian research 0 41029755
2024 Exosomal microRNA let-7c-5p enhances cell malignant characteristics by inhibiting TAGLN in oral cancer. Oncology research 0 39308508
2010 [Construction of pGL3-SM22-SCAP (D443N) eukaryotic expression vector and its expression in CHO cells]. Sheng wu gong cheng xue bao = Chinese journal of biotechnology 0 20353101
2007 [Recombinant C-terminal fragment of SM22 induces cytoskeleton reorganization]. Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 0 21162287