Affinage

CLMN

Calmin · UniProt Q96JQ2

Length
1002 aa
Mass
111.7 kDa
Annotated
2026-06-09
28 papers in source corpus 5 papers cited in narrative 4 extracted findings
Cross-family judge faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLMN (calmin) is a membrane-associated actin-binding protein that couples the actin cytoskeleton to cellular membranes to control adhesion, calcium signaling, and cell movement (PMID:40184252, PMID:38328045). At the endoplasmic reticulum it is enriched in ER tubules that contact focal adhesions, where it acts as an ER-actin tether: its depletion perturbs focal adhesion disassembly and actin dynamics, reduces polarization of ER-plasma membrane contacts and of the calcium sensor STIM1, and alters calcium signaling near ER-actin interfaces, impairing cell migration (PMID:40184252, PMID:38328045). A membrane-linking role is corroborated in kidney collecting duct cells, where CLMN behaves as an integral membrane protein bridging F-actin to the apical plasma membrane within a vasopressin-regulated actin network associated with aquaporin-2 trafficking (PMID:24085853). In the nervous system CLMN is a retinoic-acid-responsive effector of cell-cycle exit and differentiation: its expression is induced by all-trans retinoic acid (atRA) and restricted to postmitotic neurons, and it is required for atRA-driven cell-cycle arrest and neurite outgrowth, with CLMN overexpression alone raising p21(Cip1), lowering cyclin D1, and increasing hypophosphorylated Rb to enforce G1/S arrest (PMID:22001116, PMID:20014094).

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2010 Medium

    Established CLMN as a retinoid-regulated gene with neuron-restricted expression, defining a developmental context for its function before any molecular activity was known.

    Evidence subtracted cDNA library plus in situ/immunodetection in vitamin A-deficient and atRA-rescued embryos and adult brain

    PMID:20014094

    Open questions at the time
    • Did not define a molecular activity or binding partner for CLMN
    • Correlative expression — no functional manipulation of CLMN itself
    • Mechanism linking atRA signaling to CLMN transcription not resolved
  2. 2011 High

    Showed CLMN is a functional effector of atRA-induced cell-cycle exit and neurite outgrowth, connecting it to the p21/cyclin D1/Rb axis governing G1/S arrest.

    Evidence shRNA knockdown, overexpression, rescue, and western blots for p21, cyclin D1, Rb phosphorylation in neuroblastoma cells

    PMID:22001116

    Open questions at the time
    • Molecular mechanism by which CLMN modulates p21/cyclin D1/Rb is unknown
    • Direct binding partners mediating the cell-cycle effect not identified
    • Relationship between this nuclear/cell-cycle role and its cytoskeletal role unclear
  3. 2013 Medium

    Identified CLMN as an integral membrane protein linking F-actin to the plasma membrane, placing it in a vasopressin-regulated, aquaporin-2-associated actin network.

    Evidence quantitative apical membrane proteomics with surface biotinylation in mouse cortical collecting duct cells

    PMID:24085853

    Open questions at the time
    • No direct functional manipulation of CLMN in this system
    • Whether CLMN directly binds actin versus associating indirectly not tested
    • Role in aquaporin-2 trafficking inferred from network membership, not demonstrated
  4. 2025 High

    Defined CLMN as an ER-actin tether at focal adhesions that coordinates adhesion turnover, STIM1 polarization, and calcium signaling to drive cell migration.

    Evidence TurboID proximity labeling, CRISPR knock-in spatial proteomics, siRNA depletion, and live-cell imaging of actin and focal adhesion dynamics with calcium measurements

    PMID:38328045 PMID:40184252

    Open questions at the time
    • Direct molecular bridge between CLMN and STIM1/calcium machinery not resolved
    • Structural basis of the ER-actin tethering not determined
    • Reconciliation with the neuronal cell-cycle role of CLMN remains open

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CLMN's membrane/actin-tethering activity mechanistically connects to its retinoic-acid-dependent control of the cell cycle remains unresolved.
  • No unifying mechanism linking ER-actin tethering to p21/cyclin D1/Rb regulation
  • No structural model of CLMN domains mediating actin versus membrane binding
  • Direct interaction partners at focal adhesions and the ER not enumerated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 2 GO:0060090 molecular adaptor activity 1 GO:0140110 transcription regulator activity 1
Localization
GO:0005783 endoplasmic reticulum 1 GO:0005856 cytoskeleton 1 GO:0005886 plasma membrane 1
Partners
STIM1

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2025 CLMN (calmin) is an ER-enriched actin-binding protein that localizes to focal adhesions adjacent to ER tubules and functions as an ER-actin tether. CLMN depletion perturbs focal adhesion disassembly, actin dynamics, and cell movement. CLMN-depleted cells display decreased polarization of ER-plasma membrane contacts and calcium signaling factor STIM1, and altered calcium signaling near ER-actin interfaces, suggesting CLMN influences calcium signaling to facilitate F-actin/adhesion dynamics and cell migration. TurboID-based proximity labeling, CRISPR knock-in spatial proteomics, siRNA depletion, live-cell imaging of actin dynamics and focal adhesion disassembly, calcium signaling measurements near ER-actin interfaces Cell reports High 38328045 40184252
2011 CLMN (calmin) promotes G1/S cell cycle arrest and is required for atRA-induced cell cycle exit and neurite outgrowth in neuroblastoma cells. Clmn knockdown nearly eliminates atRA-mediated reduction in cell proliferation (phosphohistone H3, BrdU). Clmn overexpression alone increases p21(Cip1), decreases cyclin D1, and increases hypophosphorylated Rb. Both Clmn and atRA are required for neurite outgrowth, but Clmn overexpression alone suffices to inhibit proliferation. shRNA knockdown, ectopic overexpression, rescue experiment (reintroduction of Clmn sequence), immunostaining for phosphohistone H3, BrdU incorporation, western blot for p21(Cip1), cyclin D1, and Rb phosphorylation Experimental cell research High 22001116
2010 CLMN expression is regulated by all-trans retinoic acid (atRA) during nervous system development. In vitamin A-deficient embryos, Clmn mRNA is dramatically down-regulated in neuroepithelium adjacent to somites and is rescued by atRA addition. In embryonic day 18.5 embryos and adult brain, CLMN protein is detected specifically in postmitotic neuronal cells (neural retina, cortical plate, hippocampus, cerebellum, olfactory bulb). Subtracted cDNA library, in situ hybridization/immunodetection in vitamin A-deficient and atRA-rescued embryos, adult brain localization by immunohistochemistry Developmental dynamics Medium 20014094
2013 CLMN (Clmn) was identified as an integral membrane protein that links filamentous actin (F-actin) to the plasma membrane in kidney collecting duct cells. Quantitative apical membrane proteomics showed Clmn abundance changes in the apical plasma membrane in response to vasopressin, placing it in a vasopressin-regulated actin network involved in aquaporin-2 trafficking. Stable isotope-based quantitative protein mass spectrometry, surface biotinylation, apical membrane fractionation in mouse cortical collecting duct cells Proceedings of the National Academy of Sciences of the United States of America Medium 24085853

Source papers

Stage 0 corpus · 28 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders. JAMA psychiatry 202 28097321
2010 Genome-wide association of lipid-lowering response to statins in combined study populations. PloS one 190 20339536
2013 Quantitative apical membrane proteomics reveals vasopressin-induced actin dynamics in collecting duct cells. Proceedings of the National Academy of Sciences of the United States of America 60 24085853
2013 More targets, more pathways and more clues for mutant p53. Oncogenesis 55 23817466
2007 Promoter hypermethylation of CCNA1, RARRES1, and HRASLS3 in nasopharyngeal carcinoma. Oral oncology 45 17689134
2011 The all-trans retinoic acid (atRA)-regulated gene Calmin (Clmn) regulates cell cycle exit and neurite outgrowth in murine neuroblastoma (Neuro2a) cells. Experimental cell research 40 22001116
2015 Gene Signatures of 1,25-Dihydroxyvitamin D3 Exposure in Normal and Transformed Mammary Cells. Journal of cellular biochemistry 30 25736056
2015 Identification of vitamin D3 target genes in human breast cancer tissue. The Journal of steroid biochemistry and molecular biology 28 26485663
2020 Whole-exome and RNA sequencing of pulmonary carcinoid reveals chromosomal rearrangements associated with recurrence. Lung cancer (Amsterdam, Netherlands) 27 32417679
2013 Expanding role of pharmacogenomics in the management of cardiovascular disorders. American journal of cardiovascular drugs : drugs, devices, and other interventions 27 23579966
2019 Study of the mechanism underlying therapeutic effect of Compound Longmaining on myocardial infarction using a network pharmacology-based approach. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 17 31377468
2023 Development and Validation of a Computed Tomography-Based Radiomics Nomogram for the Preoperative Prediction of Central Lymph Node Metastasis in Papillary Thyroid Microcarcinoma. Academic radiology 13 38071100
2010 Calmin expression in embryos and the adult brain, and its regulation by all-trans retinoic acid. Developmental dynamics : an official publication of the American Association of Anatomists 12 20014094
2004 Synthesis and properties of dimetallic M1[Pz]-M2[Schiff base] complexes. Inorganic chemistry 10 15154799
2025 Spatial proteomics of ER tubules reveals CLMN, an ER-actin tether at focal adhesions that promotes cell migration. Cell reports 9 40184252
2018 RNA-seq based transcriptome analysis of the protective effect of compound longmaining decoction on acute myocardial infarction. Journal of pharmaceutical and biomedical analysis 9 29933226
2021 Dissecting the Pathogenesis of Diabetic Retinopathy Based on the Biological ceRNA Network and Genome Variation Disturbance. Computational and mathematical methods in medicine 6 34707685
2024 Whole-exome Sequencing of Atypical Parathyroid Tumors Detects Novel and Common Genes Linked to Parathyroid Tumorigenesis. The Journal of clinical endocrinology and metabolism 5 38940486
1996 Ferromagnetic Mn(II).Cu(II) Exchange in the New Bimetallic Quasi-2-D Compound Cu(op)(2)MnCl(4) (op = 1,4-Diazacycloheptane). Inorganic chemistry 4 11666937
1984 Correlation between the in vivo metabolism of hexobarbital and antipyrine in rats with a portacaval shunt. Pharmacology 4 6473507
2018 Identification of candidate genes and long non-coding RNAs associated with the effect of ATP5J in colorectal cancer. International journal of oncology 3 29484395
2024 Spatial proteomics of ER tubules reveals CLMN, an ER-actin tether at focal adhesions that promotes cell migration. bioRxiv : the preprint server for biology 2 38328045
2021 Potential Significance and Clinical Value Explorations of Calmin (CLMN) in Breast Invasive Carcinoma. International journal of general medicine 1 34531680
2021 Exploration of the active components and pharmacological mechanism of Compound Longmaining for the treatment of myocardial infarction. Frontiers in bioscience (Landmark edition) 1 34719208
2025 Changes in transcriptional regulation in the temporal lobe in patients with Alzheimer's disease. Journal of Alzheimer's disease : JAD 0 40095520
2025 Genome-wide association and fine-mapping analyses identify novel candidate genes affecting serum cortisol levels using imputed whole-genome sequencing data in pigs. Journal of animal science and technology 0 40874003
2025 GWAS for Periodontitis Phenotypes Using Multi-Ancestry All of Us Research Platform. medRxiv : the preprint server for health sciences 0 40963761
2025 Upregulation of PLAU in granulosa cells disrupts steroid hormone synthesis and promotes apoptosis by activating NF-κB signaling pathway in PCOS. Journal of ovarian research 0 41462288

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