Affinage

CLNS1A

Methylosome subunit pICln · UniProt P54105

Round 2 corrected
Length
237 aa
Mass
26.2 kDa
Annotated
2026-04-28
65 papers in source corpus 20 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLNS1A (pICln) is a bifunctional scaffold protein that operates both as a core subunit of the methylosome complex and as a regulator of volume-sensitive chloride currents. Within the methylosome, pICln binds Sm protein folds and presents them to PRMT5 for symmetric dimethylarginine modification, thereby preventing premature Sm core assembly on snRNA and ensuring ordered transfer to the SMN complex for spliceosomal snRNP biogenesis—a function conserved from fission yeast to mammals and essential for embryonic viability (PMID:11713266, PMID:11747828, PMID:10777517, PMID:24298023). Upon hypo-osmotic cell swelling, pICln translocates from the cytosol to the plasma membrane through interaction with α-integrin cytoplasmic domains—an event regulated by O-GlcNAcylation at Ser67—where it activates IClswell currents required for regulatory volume decrease, and reconstituted pICln forms ion channels whose selectivity is modulated by calcium and lipid environment (PMID:12970357, PMID:31434921, PMID:33330510, PMID:10864003). In CD4 T cells, pICln cooperates with PRMT5 to maintain symmetric histone dimethylation at DNA repair and cell cycle genes; T cell-specific deletion causes DNA damage, cell cycle arrest, and impaired effector function, protecting mice from autoimmune disease (PMID:40540585).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1996 High

    Establishing that CLNS1A encodes an ion-conducting protein: expression cloning showed that ICln generates a nucleotide-sensitive, outwardly rectifying chloride current in Xenopus oocytes resembling IClswell, and antisense knockdown impairs regulatory volume decrease, identifying pICln as a molecular component of swelling-activated chloride conductance.

    Evidence Expression cloning, Xenopus oocyte electrophysiology, antisense knockdown with RVD assay in epithelial cells

    PMID:8939183

    Open questions at the time
    • Whether pICln is itself the pore-forming subunit or an essential accessory/regulator of a separate channel
    • Identity of in vivo regulatory partners controlling channel gating
  2. 2000 High

    Defining the intrinsic channel properties and in vivo essentiality of pICln: reconstituted pICln forms ~3 pS channels whose ion selectivity switches from cation- to anion-selective in a calcium- and lipid-dependent manner, while gene knockout in mice demonstrated embryonic lethality by E7.5, establishing that pICln is indispensable for early development.

    Evidence Reconstitution in planar lipid bilayers with site-directed mutagenesis; gene targeting in ES cells and blastocyst injection in mouse

    PMID:10777517 PMID:10825435 PMID:10864003

    Open questions at the time
    • Which pICln function (channel vs. methylosome vs. other) is responsible for embryonic lethality
    • Structural basis for calcium-dependent selectivity switch at atomic resolution
  3. 2001 High

    Discovery of the methylosome function resolved how Sm proteins are symmetrically dimethylated prior to snRNP assembly: two independent groups showed that pICln is a core scaffold of a 20S complex with PRMT5 that binds Sm folds and methylates RG-rich tails, while simultaneously blocking premature Sm–snRNA assembly.

    Evidence Biochemical fractionation, co-immunoprecipitation, in vitro methyltransferase and Sm core reconstitution assays in two independent laboratories

    PMID:11713266 PMID:11747828

    Open questions at the time
    • Structural mechanism by which pICln blocks Sm ring closure
    • How the methylated Sm–pICln intermediate is handed off to the SMN complex
  4. 2003 High

    Connecting channel activation to membrane translocation: hypotonicity triggers pICln redistribution from cytosol to plasma membrane (shown by FRET and fractionation), correlating with faster IClswell kinetics, which explained how a predominantly cytosolic protein regulates a membrane conductance.

    Evidence Cell fractionation, acceptor-photobleaching FRET in living cells, patch-clamp electrophysiology in NIH 3T3, LLC-PK1, MDCK cells

    PMID:12970357

    Open questions at the time
    • Signal that triggers translocation (osmosensor identity unknown)
    • Whether pICln inserts into the bilayer as a multimer or modulates an existing channel complex
  5. 2004 High

    Identifying α-integrin as the membrane recruitment partner for pICln: pICln binds the conserved KVGFFKR motif of αIIb with ~82 nM affinity, and disruption of this interaction blocks integrin activation and platelet aggregation, linking pICln's channel function to integrin signaling.

    Evidence Surface plasmon resonance, co-immunoprecipitation from platelets, competitive peptide inhibition, flow cytometry

    PMID:15075326

    Open questions at the time
    • Whether the integrin interaction is required for IClswell in non-platelet cell types
    • Structural basis of the pICln–integrin interface
  6. 2006 Medium

    Placing pICln translocation downstream of Cdc42-dependent actin remodeling: dominant-negative Cdc42 prevented both hypotonicity-induced microspike formation and IClswell generation, and pICln–actin interaction increased upon swelling, implicating the Rho-GTPase–cytoskeletal axis in channel regulation.

    Evidence Immunofluorescence, co-immunoprecipitation, dominant-negative Cdc42 expression, patch-clamp in renal CD8 cells

    PMID:17138647

    Open questions at the time
    • Whether Cdc42 acts on pICln directly or via intermediate effectors
    • Not independently confirmed outside the originating laboratory
  7. 2009 Medium

    Demonstrating pICln self-association in living cells: FRET showed C-terminus-mediated homo-oligomerization, with residues 135–159 essential, providing a structural basis for multimeric channel or scaffolding assemblies.

    Evidence Acceptor-photobleaching FRET with truncation mutants in living NIH 3T3 cells

    PMID:19471107

    Open questions at the time
    • Stoichiometry and quaternary structure of the oligomer
    • Functional consequence of preventing oligomerization on methylosome vs. channel activity
  8. 2011 Medium

    Structural characterization revealed that the N-terminal domain adopts a PH-like fold while the C-terminus is intrinsically disordered with locally preformed helical and strand elements; separately, identification of HSPC038 as a mammalian partner that directs pICln to the plasma membrane during swelling extended the C. elegans operon-partner interaction to human cells.

    Evidence NMR backbone assignment and secondary chemical shift analysis; co-immunoprecipitation and NMR of HSPC038, electrophysiology

    PMID:21917931 PMID:22179008

    Open questions at the time
    • No high-resolution structure of the pICln–HSPC038 complex
    • Whether HSPC038 interaction is required in all cell types for IClswell
  9. 2013 Medium

    Establishing evolutionary conservation of the methylosome–snRNP axis: in S. pombe, deletion of ICln impairs splicing genome-wide, and human CLNS1A rescues the growth defect; epistasis places ICln upstream of/parallel to SMN, not downstream.

    Evidence Gene deletion, cross-species complementation, RT-PCR and genome-wide splicing assays in fission yeast

    PMID:24298023

    Open questions at the time
    • Whether ICln has SMN-independent roles in splicing regulation
    • Quantitative contribution of ICln loss to individual intron retention events
  10. 2019 Medium

    Generalizing the integrin-recruitment mechanism beyond platelets: pICln binds conserved motifs in multiple α-integrin chains, and competitive peptides blocking this interaction prevent pICln membrane translocation and IClswell activation, establishing integrins as a general membrane anchor for pICln channel function.

    Evidence Co-immunoprecipitation, peptide competition, patch-clamp, live-cell imaging across multiple cell types

    PMID:31434921

    Open questions at the time
    • In vivo validation with integrin-mutant knockin animals
    • Whether other membrane proteins also recruit pICln independently of integrins
  11. 2020 Medium

    Identifying O-GlcNAcylation at Ser67 as a regulatory switch that tonically inhibits pICln–integrin interaction and IClswell: elevated O-GlcNAc suppresses current and RVD, while hypotonicity reduces global O-GlcNAcylation, creating a feed-forward activation loop.

    Evidence Ser67 mutagenesis, OGT/OGA pharmacological manipulation, patch-clamp, co-immunoprecipitation, RVD assay

    PMID:33330510

    Open questions at the time
    • Whether Ser67 is O-GlcNAcylated in vivo under physiological conditions (direct mass spectrometry evidence not provided)
    • How hypotonicity reduces O-GlcNAcylation mechanistically
  12. 2023 Medium

    Reconstituting the full Sm core assembly pathway in vitro with recombinant fission yeast proteins confirmed that ICln and the SMN complex act sequentially—ICln first—establishing the minimal biochemical sufficiency of this two-step chaperoning mechanism.

    Evidence In vitro reconstitution with recombinant S. pombe ICln, SMN/Gemin2/Gemin6-8, and Sm proteins

    PMID:37664592

    Open questions at the time
    • Kinetic parameters of the handoff from ICln to SMN complex
    • Whether additional factors accelerate or regulate this transfer in vivo
  13. 2025 Medium

    Two studies expanded pICln's functional repertoire: in CD4 T cells, pICln–PRMT5 cooperation maintains histone dimethylation at DNA repair/cell cycle genes, and conditional deletion causes DNA damage and cell cycle arrest protecting from autoimmunity; in lung cancer, a channel-dead mutant (3W) separated channel-dependent drug efflux from PRMT5-dependent RUVBL1 methylation that supports DNA damage response signaling.

    Evidence Conditional T cell-specific Clns1a KO with EAE/IBD models, histone methylation assays; site-directed channel-dead mutagenesis with drug accumulation, xenograft, and kinase pathway analysis in lung cancer cells

    PMID:40345428 PMID:40540585

    Open questions at the time
    • Whether CLNS1A-dependent histone dimethylation is direct or mediated entirely through PRMT5 substrate presentation
    • Specificity of the 3W mutations—whether they affect methylosome function indirectly
    • Therapeutic relevance of targeting CLNS1A vs. PRMT5 selectively

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions: whether pICln itself forms the swelling-activated channel pore or acts as an essential regulatory subunit of a distinct pore-forming entity (e.g., LRRC8/SWELL1); the atomic-resolution structure of pICln oligomers in a membrane context; and the molecular mechanism governing partitioning of pICln between its methylosome scaffold role and its membrane/channel role in the same cell.
  • Relationship to LRRC8A/SWELL1 as the bona fide VRAC pore remains unaddressed in this literature
  • No cryo-EM or crystal structure of membrane-inserted pICln oligomers
  • Regulatory logic governing dual-function partitioning is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005886 plasma membrane 5 GO:0005829 cytosol 4
Pathway
R-HSA-382551 Transport of small molecules 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-73894 DNA Repair 2 R-HSA-1640170 Cell Cycle 1
Partners
CDC42HSPC038ITGA2BPRMT5RUVBL1SMN1SNRPD1SNRPD3
Complex memberships
Methylosome (pICln–PRMT5–MEP50/WD45)

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 pICln (CLNS1A) is a core component of the methylosome, a 20S complex also containing PRMT5 (JBP1), that produces symmetrical dimethylarginine (sDMA) modifications on Sm proteins (SmD1, SmD3). pICln binds Sm domains while PRMT5 methylates RG-rich domains, and the pICln complex inhibits spontaneous Sm protein assembly onto snRNA by occupying the Sm fold, thereby preventing premature snRNP core formation before transfer to the SMN complex. Biochemical fractionation, co-immunoprecipitation, in vitro methyltransferase assay, reconstitution experiments Molecular and cellular biology / Current biology High 11713266 11747828
1996 ICln functions as a chloride channel essential for regulatory volume decrease (RVD) after cell swelling; its expression in Xenopus oocytes generates a nucleotide-sensitive, outwardly rectifying chloride current resembling IClswell, and knockdown impairs RVD in epithelial cells. Expression cloning, Xenopus oocyte electrophysiology, antisense knockdown with RVD assay The Journal of allergy and clinical immunology High 8939183
2000 Purified ICln reconstituted in lipid bilayers forms functional ion channels with ~3 pS conductance whose open probability is sensitive to nucleoside analogues. Ion selectivity (cation vs. anion) depends on calcium concentration, with a specific calcium-binding site identified by mutagenesis. A histidine in the predicted pore region has access to the ion-conducting tunnel, established by site-directed mutagenesis. Reconstitution in artificial lipid bilayer, site-directed mutagenesis, single-channel electrophysiology Pflugers Archiv : European journal of physiology High 10864003
2000 ICln is essential for embryonic viability: homozygous ICln knockout mice die between E3.5 and E7.5, and ICln-null embryonic stem cells are non-viable. ICln also forms a complex with spliceosomal proteins, suggesting roles in spliceosomal biogenesis and cell cycle regulation. Gene targeting in embryonic stem cells, blastocyst injection, genetic complementation The Journal of biological chemistry High 10777517
2003 Cell swelling (hypotonicity) triggers translocation of ICln from the cytosol to the plasma membrane in multiple cell types (NIH 3T3, LLC-PK1, MDCK). This redistribution correlates with faster activation kinetics of swelling-dependent Cl− currents (RVDC) and increased anion permeability. Addition of purified ICln to extracellular solution or farnesylated ICln overexpression increases anion permeability. Cell fractionation, FRET in living cells, patch-clamp electrophysiology, overexpression of farnesylated ICln The Journal of biological chemistry High 12970357
2004 ICln directly interacts with the conserved cytoplasmic KVGFFKR motif of the platelet integrin αIIb subunit with an affinity of ~82 nM (surface plasmon resonance). This interaction is physiologically relevant as ICln co-immunoprecipitates with αIIbβ3 from platelet lysates. Pharmacological inhibition of ICln chloride channel activity (acyclovir) or a cell-permeable peptide blocking the ICln–integrin interaction inhibits integrin activation (PAC-1 binding) and platelet aggregation. Protein expression array probing, surface plasmon resonance, co-immunoprecipitation, peptide-affinity pull-down, platelet aggregation assay, flow cytometry The Journal of biological chemistry High 15075326
2000 ICln channels reconstituted in synthetic lipid bilayers are potassium-selective by default but become chloride-selective in the presence of calcium; ion selectivity also depends on the lipid environment (heart lipid extract vs. synthetic Diph-PC), with near-native chloride selectivity achieved in heart lipid at acidic pH and calcium. Reconstitution in planar lipid bilayers using different lipid compositions, ion permeability measurements Pflugers Archiv : European journal of physiology / Cellular physiology and biochemistry Medium 10825435 11889572
2001 In C. elegans, two splice variants of ICln (IClnN1, IClnN2) differ in voltage-dependent inactivation: IClnN2 fully inactivates at positive potentials due to a cluster of positively charged amino acids encoded by exon 2a (absent in IClnN1), consistent with a 'ball and chain' mechanism. Synthetic peptides matching this positive cluster convert IClnN1 current to IClnN2-like current. Co-reconstitution with the operon partner protein Nx abolishes voltage sensitivity of IClnN2, demonstrating a functional protein–protein interaction. Lipid bilayer reconstitution, site-directed analysis, synthetic peptide experiments, co-reconstitution The Journal of biological chemistry Medium 11706026
2006 Hypotonicity in renal CD8 cells causes ICln to relocate from cytosol to plasma membrane and increases ICln–actin interaction, coinciding with Cdc42-dependent actin remodeling (loss of stress fibers, microspike formation). Expression of dominant-negative Cdc42 (N17-Cdc42) prevents both microspike formation and hypotonicity-induced Cl− current generation. Immunofluorescence, co-immunoprecipitation, dominant-negative overexpression, FRET (cAMP dynamics), patch-clamp Endocrinology Medium 17138647
2011 ICln interacts with HSPC038 (the human ortholog of the C. elegans operon partner Nx), and this interaction directs ICln to the plasma membrane after hypotonic cell swelling, facilitating IClswell activation. NMR structure of HSPC038 revealed a zinc finger motif, and NMR plus biochemical assays identified the ICln/HSPC038 interacting sites. Co-immunoprecipitation, NMR structure determination, cell volume regulation assay, electrophysiology The Journal of biological chemistry Medium 21917931
2009 ICln forms homo-oligomers in living NIH 3T3 cells, with the C-terminus mediating intermolecular interactions. FRET between C-terminally tagged ICln molecules is detected; truncation mutant ICln(134) lacking residues P135–Q159 abolishes oligomerization, identifying this region as essential for self-association. FRET (acceptor photobleaching) with fluorescently tagged ICln constructs and C-terminal truncation mutants in living cells Cellular physiology and biochemistry Medium 19471107
2011 The C-terminus of ICln (residues Q159–H235) is intrinsically disordered but displays local structural preformation: residues E170–E187 preferentially adopt α-helical conformation and residues D161–Y168 and E217–T223 adopt extended β-strand-like conformations, as determined by NMR chemical shift analysis. The N-terminal domain (residues 1–159) folds into a PH-like domain. NMR spectroscopy (backbone resonance assignment, 13Cα–13Cβ secondary chemical shifts) Cellular physiology and biochemistry Medium 22179008
2019 ICln directly binds the intracellular domain of α-integrin chains (not only αIIb in platelets) through conserved amino acid motifs. Integrin α recruits ICln to the plasma membrane, facilitating IClswell activation during hypotonicity; perturbation of this interaction by competitive peptides prevents ICln membrane transposition and blocks IClswell. Co-immunoprecipitation, peptide competition, electrophysiology (patch-clamp), live-cell imaging Scientific reports Medium 31434921
2020 O-GlcNAcylation of ICln at Ser67 (a YinOYang site) suppresses IClswell and impairs RVD by preventing ICln binding to the intracellular domain of α-integrin. Elevated O-GlcNAcylation inhibits IClswell and RVD, whereas reduced O-GlcNAcylation augments current. Hypotonicity itself reduces O-GlcNAcylation of cellular proteins, proposing a feed-forward mechanism for IClswell activation. Site-directed mutagenesis (Ser67), OGT/OGA pharmacological manipulation, patch-clamp electrophysiology, co-immunoprecipitation, RVD assay Frontiers in cell and developmental biology Medium 33330510
2013 In fission yeast (S. pombe), ICln (SpICln) is required for optimal snRNP production and efficient splicing in vivo. Human ICLN complements the Δicln slow-growth phenotype, confirming conservation of function. Genetic interaction analysis shows that ICln activity modulation cannot compensate for SMN-deficiency, placing ICln upstream of or parallel to SMN in snRNP biogenesis. Gene deletion in S. pombe, genetic complementation with human ICLN, RT-PCR splicing assays, genome-wide splicing analysis Molecular and cellular biology Medium 24298023
2023 In S. pombe, ICln and the SMN complex (SMN/Gemin2/Gemin6-8) are necessary and sufficient for Sm core assembly in vitro using recombinant proteins. ICln and the SMN complex act sequentially (ICln first), paralleling the human system. Key differences from human: Sp_F/E/G only forms heterohexamers (not trimers), and Sp_Gemin2 alone cannot bind D1/D2/F/E/G unlike human Gemin2. Reconstitution of chaperone machinery with recombinant proteins, genetic analysis (Gemin2 essentiality) iScience Medium 37664592
2025 CLNS1A interacts with PRMT5 and regulates symmetric histone dimethylation and expression of genes involved in DNA repair, replication, and cell cycle progression in CD4 T cells. T cell-specific deletion of Clns1a causes DNA damage, cell cycle arrest, and impaired proliferation and effector function, protecting mice from EAE and IBD. Forward genetic screen (EAE model), conditional T cell-specific knockout, co-immunoprecipitation (CLNS1A–PRMT5), histone methylation assays, proliferation/cell cycle assays Science immunology Medium 40540585
2025 CLNS1A promotes drug efflux via its chloride channel activity and activates the FAK-SRC-RAC1 signaling pathway to enhance migration and clonogenicity in lung cancer cells. A chloride channel-defective triple mutant (3W) with steric hindrance at pore residues reduces drug resistance and motility. CLNS1A also facilitates PRMT5-mediated RUVBL1 methylation to support anti-apoptotic DNA damage response signaling. Site-directed mutagenesis (3W channel-dead variant), drug accumulation assays, knockdown/overexpression, kinase pathway analysis, in vivo xenograft Cancer letters Medium 40345428
2024 Knockdown of CLNS1A (pICln), which specifically enables PRMT5-mediated Sm protein methylation, causes widespread retention of detained introns and gross chromatin detention of mRNA, SNRPB, and SNRPD3 proteins—phenocopying PRMT5 inhibition. This places CLNS1A specifically in the PRMT5–Sm protein methylation axis controlling transcript processing and chromatin escape. Nascent and total transcriptomics, spike-in controlled fractionated transcriptomics, fractionated proteomics, siRNA knockdown of CLNS1A bioRxiv (preprint)preprint Low

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2008 Identification of host proteins required for HIV infection through a functional genomic screen. Science (New York, N.Y.) 1165 18187620
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2007 Functional specialization of beta-arrestin interactions revealed by proteomic analysis. Proceedings of the National Academy of Sciences of the United States of America 360 17620599
2001 The methylosome, a 20S complex containing JBP1 and pICln, produces dimethylarginine-modified Sm proteins. Molecular and cellular biology 354 11713266
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2001 Methylation of Sm proteins by a complex containing PRMT5 and the putative U snRNP assembly factor pICln. Current biology : CB 323 11747828
2012 Dynamic protein-protein interaction wiring of the human spliceosome. Molecular cell 318 22365833
2009 Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs. Cell 281 19167051
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2012 The cellular EJC interactome reveals higher-order mRNP structure and an EJC-SR protein nexus. Cell 272 23084401
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2009 Proteomic analysis of integrin-associated complexes identifies RCC2 as a dual regulator of Rac1 and Arf6. Science signaling 207 19738201
2006 Hypotonicity induces aquaporin-2 internalization and cytosol-to-membrane translocation of ICln in renal cells. Endocrinology 66 17138647
2004 ICln, a novel integrin alphaIIbbeta3-associated protein, functionally regulates platelet activation. The Journal of biological chemistry 58 15075326
2003 Cell swelling stimulates cytosol to membrane transposition of ICln. The Journal of biological chemistry 47 12970357
2000 Functional reconstitution of ICln in lipid bilayers. Pflugers Archiv : European journal of physiology 36 10864003
2000 ICln is essential for cellular and early embryonic viability. The Journal of biological chemistry 30 10777517
1998 Hypotonicity stimulates translocation of ICln in neonatal rat cardiac myocytes. Pflugers Archiv : European journal of physiology 29 9644224
1996 ICln: a chloride channel paramount for cell volume regulation. The Journal of allergy and clinical immunology 26 8939183
2006 Glucose induces anion conductance and cytosol-to-membrane transposition of ICln in INS-1E rat insulinoma cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 24 16914887
2000 Structure and function of the ion channel ICln. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 24 11125213
2006 The ICln interactome. Acta physiologica (Oxford, England) 22 16734741
2001 ICln ion channel splice variants in Caenorhabditis elegans: voltage dependence and interaction with an operon partner protein. The Journal of biological chemistry 21 11706026
2020 O-GlcNAcylation Suppresses the Ion Current IClswell by Preventing the Binding of the Protein ICln to α-Integrin. Frontiers in cell and developmental biology 20 33330510
2000 Modulation of volume regulated anion current by I(Cln). Biochimica et biophysica acta 17 10825435
2002 ICln channels reconstituted in heart-lipid bilayer are selective to chloride. Pflugers Archiv : European journal of physiology 15 11889572
2011 The molecular and functional interaction between ICln and HSPC038 proteins modulates the regulation of cell volume. The Journal of biological chemistry 14 21917931
2013 Characterization and in vivo functional analysis of the Schizosaccharomyces pombe ICLN gene. Molecular and cellular biology 13 24298023
2021 Genomic Mapping of Splicing-Related Genes Identify Amplifications in LSM1, CLNS1A, and ILF2 in Luminal Breast Cancer. Cancers 11 34439272
2011 The C-terminus of ICln is natively disordered but displays local structural preformation. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 9 22179008
2008 Compartmentalization regulates the interaction between the platelet integrin alpha IIb beta 3 and ICln. British journal of haematology 9 19055659
1996 Chromosomal localization of the genes (CLNS1A and CLNS1B) coding for the swelling-dependent chloride channel ICln. Genomics 9 8975725
1999 ICln, an ion channel-forming protein associated with cell volume regulation. Experimental physiology 8 10564699
1998 Chloride channels ClC-2 and ICln mRNA expression differs in renal epithelial ontogeny. Kidney international. Supplement 7 9736273
2023 Mechanism of assembly of snRNP cores assisted by ICln and the SMN complex in fission yeast. iScience 6 37664592
2009 Differential binding of ICln in platelets to integrin-derived activating and inhibitory peptides. Biochemical and biophysical research communications 6 20034469
1997 Partial structure, chromosome localization, and expression of the mouse Icln gene. Genomics 6 9073507
2014 ICln: a new regulator of non-erythroid 4.1R localisation and function. PloS one 5 25295618
1998 Characterization of the human gene coding for the swelling-dependent chloride channel ICln at position 11q13.5-14.1 (CLNS1A) and further characterization of the chromosome 6 (CLNS1B) localization. Gene 5 9524223
2021 An ICln homolog contributes to osmotic and low-nitrate tolerance by enhancing nitrate accumulation in Arabidopsis. Plant, cell & environment 4 33495993
2025 CLNS1A regulates genome stability and cell cycle progression to control CD4 T cell function and autoimmunity. Science immunology 3 40540585
2019 Binding of the protein ICln to α-integrin contributes to the activation of IClswell current. Scientific reports 3 31434921
2009 Quaternary structure assessment of ICln by fluorescence resonance energy transfer (FRET) in vivo. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 3 19471107
2000 The promoter for constitutive expression of the human ICln gene CLNS1A. The Journal of biological chemistry 3 10821842
2025 Mechanistic insights into CLNS1A-mediated chemoresistance and tumor progression in non-small cell lung cancer. Cancer letters 1 40345428
2019 Conditions of limited calcium influx (CLCI) inhibits IL2 induction and favors expression of anergy-related genes in TCR/CD3 and CD28 costimulated primary human T cells. Molecular immunology 1 31344552
2019 Author Correction: Binding of the protein ICln to α-integrin contributes to the activation of IClswell current. Scientific reports 0 31728022