Affinage

NES

Nestin · UniProt P48681

Length
1621 aa
Mass
177.4 kDa
Annotated
2026-06-10
73 papers in source corpus 2 papers cited in narrative 2 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 2/2 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Nestin (NES) is a type VI intermediate filament protein that cannot self-assemble but instead co-assembles into filaments with partner intermediate filament proteins; a short neuronal isoform, Nes-S, identified in rat dorsal root ganglia (DRG) neurons co-assembles with vimentin in vimentin-positive cells and with peripherin and neurofilament proteins in neuronal cells and primary DRG neurons (PMID:23319587). Nes-S serves a cytoprotective role: its knockdown impairs survival of cultured DRG neurons while its exogenous expression enhances neuronal cell viability (PMID:23319587). Beyond these isoform-specific co-assembly and survival functions, no further mechanistic detail on Nes-S has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2013 Medium

    Establishing how a short nestin isoform behaves in the cytoskeleton answered whether Nes-S contributes to filament networks and to neuronal survival, defining a cytoprotective role for the isoform.

    Evidence Transfection into IF-free SW13 and N2a cells with co-assembly and immunofluorescence assays, plus siRNA knockdown with cell viability readout in primary DRG neurons

    PMID:23319587

    Open questions at the time
    • Molecular mechanism by which Nes-S promotes neuronal survival is undefined
    • Whether co-assembly with partner filaments is required for the cytoprotective effect is not resolved
    • Findings are in rat/rodent cell systems without in vivo confirmation
  2. 2013 Low

    Characterizing a rod-domain-truncated isoform addressed whether structural integrity of nestin determines its protective versus toxic behavior, showing assembly competence separates cytoprotection from cytotoxicity.

    Evidence Transfection into SW13 and N2a cells, co-assembly assays, and caspase-3 activation assay in HEK293T cells

    PMID:23994057

    Open questions at the time
    • Single lab, single paper with limited mechanistic follow-up on the cytotoxic mechanism
    • Pathway linking aggregation to caspase-3 activation is unknown
    • Physiological relevance of the truncated isoform in neurons is unestablished

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular pathway connecting Nes-S co-assembly to neuronal survival, and the determinants of the cytotoxic truncated isoform, remain unresolved.
  • No identified downstream effectors of Nes-S cytoprotection
  • No structural model of nestin co-assembly with partner filaments
  • No in vivo validation of isoform-specific functions

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 1
Localization
GO:0005856 cytoskeleton 1
Partners
PRPHVIM

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 A novel short nestin isoform, Nes-S, was identified in rat dorsal root ganglia (DRG) neurons. Nes-S cannot form filaments by itself in cytoplasmic intermediate filament-free SW13 cells, but co-assembles into filaments with vimentin in vimentin+ SW13 cells, and co-assembles with peripherin and neurofilament proteins in N2a cells and in primary DRG neurons. Knockdown of endogenous Nes-S impairs survival of DRG neurons in primary culture, and exogenous Nes-S enhances viability in N2a cells, establishing a cytoprotective function for this isoform. Transfection into SW13 (IF-free) and N2a cells, co-assembly assays, immunofluorescence, siRNA knockdown with cell viability readout The Journal of biological chemistry Medium 23319587
2013 A second nestin isoform, Nes-SΔ₁₀₇₋₂₅₄, was identified in rat DRG neurons. Unlike Nes-S, this rod domain-truncated isoform is assembly-compromised, forms aggregates, and does not exert cytoprotective effects. Expression of EGFP-Nes-SΔ₁₀₇₋₂₅₄ in HEK293T cells elevated caspase-3 activation, indicating cytotoxicity. Transfection into SW13 and N2a cells, co-assembly assays, caspase-3 activation assay Neuroscience letters Low 23994057

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 A leucine-rich nuclear export signal in the p53 tetramerization domain: regulation of subcellular localization and p53 activity by NES masking. The EMBO journal 613 10075936
2006 Both carboxy-terminus NES motif and mutated tryptophan(s) are crucial for aberrant nuclear export of nucleophosmin leukemic mutants in NPMc+ AML. Blood 240 16455950
2000 Influenza A virus NS2 protein mediates vRNP nuclear export through NES-independent interaction with hCRM1. The EMBO journal 214 11118210
1999 The NES-Crm1p export pathway is not a major mRNA export route in Saccharomyces cerevisiae. The EMBO journal 164 10393189
2006 Nestin-Cre transgenic mouse line Nes-Cre1 mediates highly efficient Cre/loxP mediated recombination in the nervous system, kidney, and somite-derived tissues. Genesis (New York, N.Y. : 2000) 152 16847871
2012 NESdb: a database of NES-containing CRM1 cargoes. Molecular biology of the cell 147 22833564
2012 Evidence for only oxygenative cleavage of aldehydes to alk(a/e)nes and formate by cyanobacterial aldehyde decarbonylases. Biochemistry 104 22947199
2017 Implementation of CsLIS/NES in linalool biosynthesis involves transcript splicing regulation in Camellia sinensis. Plant, cell & environment 96 28963730
2005 CDK phosphorylation of a novel NLS-NES module distributed between two subunits of the Mcm2-7 complex prevents chromosomal rereplication. Molecular biology of the cell 94 16093348
2011 Conversion of fatty aldehydes to alka(e)nes and formate by a cyanobacterial aldehyde decarbonylase: cryptic redox by an unusual dimetal oxygenase. Journal of the American Chemical Society 87 21462983
2002 A masked NES in INI1/hSNF5 mediates hCRM1-dependent nuclear export: implications for tumorigenesis. The EMBO journal 87 11782423
2003 The Drosophila nucleoporin DNup88 localizes DNup214 and CRM1 on the nuclear envelope and attenuates NES-mediated nuclear export. The Journal of cell biology 72 14638854
1999 Antagonistic effects of NES and NLS motifs determine S. cerevisiae Rna1p subcellular distribution. Journal of cell science 60 9885287
2000 Nuclear export of yeast signal recognition particle lacking Srp54p by the Xpo1p/Crm1p NES-dependent pathway. Current biology : CB 56 11069106
1996 Identification and characterization of the origin of conjugative transfer (oriT) and a gene (nes) encoding a single-stranded endonuclease on the staphylococcal plasmid pGO1. Journal of bacteriology 56 8759863
2001 The nuclear export receptor Xpo1p forms distinct complexes with NES transport substrates and the yeast Ran binding protein 1 (Yrb1p). Molecular biology of the cell 50 11251069
2018 Correlation of CRM1-NES affinity with nuclear export activity. Molecular biology of the cell 47 29927350
2013 Conversion of fatty aldehydes into alk (a/e)nes by in vitro reconstituted cyanobacterial aldehyde-deformylating oxygenase with the cognate electron transfer system. Biotechnology for biofuels 47 23759169
2017 Nuclear export of misfolded SOD1 mediated by a normally buried NES-like sequence reduces proteotoxicity in the nucleus. eLife 40 28463106
2020 Synthesis of high-titer alka(e)nes in Yarrowia lipolytica is enabled by a discovered mechanism. Nature communications 33 33273473
2010 Expression of (NES-)hTERT in cancer cells delays cell cycle progression and increases sensitivity to genotoxic stress. PloS one 24 20520826
1998 Tolerance of diverse amino acid substitutions at conserved positions in the nuclear export signal (NES) of HIV-1 Rev. Biochemical and biophysical research communications 23 9473489
2023 Cellular Proteomic Profiling Using Proximity Labeling by TurboID-NES in Microglial and Neuronal Cell Lines. Molecular & cellular proteomics : MCP 22 37061046
2004 A putative NES mediates cytoplasmic localization of Apoptin in normal cells. Acta biochimica et biophysica Sinica 20 15592649
2017 Functional characterization of NES and GES responsible for the biosynthesis of (E)-nerolidol and (E,E)-geranyllinalool in Tripterygium wilfordii. Scientific reports 19 28128232
2016 Identification of CASZ1 NES reveals potential mechanisms for loss of CASZ1 tumor suppressor activity in neuroblastoma. Oncogene 19 27270431
2000 A rev-like NES mediates cytoplasmic localization of HERV-K cORF. FEBS letters 19 10683442
2009 Non-Epileptic Seizures (NES) are predicted by depressive and dissociative symptoms. Epilepsy research 17 19201163
2015 Splicing Factor Prp8 Interacts With NES(AR) and Regulates Androgen Receptor in Prostate Cancer Cells. Molecular endocrinology (Baltimore, Md.) 16 26371515
2014 Comparative analysis of seven viral nuclear export signals (NESs) reveals the crucial role of nuclear export mediated by the third NES consensus sequence of nucleoprotein (NP) in influenza A virus replication. PloS one 16 25119991
2013 The USP21 short variant (USP21SV) lacking NES, located mostly in the nucleus in vivo, activates transcription by deubiquitylating ubH2A in vitro. PloS one 16 24278184
2004 Efficient NES-dependent protein nuclear export requires ongoing synthesis and export of mRNAs. Experimental cell research 16 15212955
2001 Alpha-2 and beta-adrenergic receptors mediate NE's biphasic effects on rat thick ascending limb chloride flux. American journal of physiology. Regulatory, integrative and comparative physiology 16 11507016
2021 Molecular weight determination of adeno-associate virus serotype 8 virus-like particle either carrying or lacking genome via native nES gas-phase electrophoretic molecular mobility analysis and nESI QRTOF mass spectrometry. Journal of mass spectrometry : JMS 15 34608711
2013 Identification and cytoprotective function of a novel nestin isoform, Nes-S, in dorsal root ganglia neurons. The Journal of biological chemistry 15 23319587
2020 A newly identified NES sequence present in spastin regulates its subcellular localization and microtubule severing activity. Biochimica et biophysica acta. Molecular cell research 10 32979422
2016 Varicus lacerta, a new species of goby (Teleostei, Gobiidae, Gobiosomatini, Nes subgroup) from a mesophotic reef in the southern Caribbean. ZooKeys 10 27408581
2012 Human cytomegalovirus UL94 is a nucleocytoplasmic shuttling protein containing two NLSs and one NES. Virus research 10 22414299
2022 A synthetic biology approach reveals diverse and dynamic CDK response profiles via multisite phosphorylation of NLS-NES modules. Science advances 9 35977012
2012 Identification of the NLS and NES motifs of VP2 from chicken anemia virus and the interaction of VP2 with mini-chromosome maintenance protein 3. BMC veterinary research 9 22309683
2004 CRM1 and Ran are present but a NES-CRM1-RanGTP complex is not required in Balbiani ring mRNP particles from the gene to the cytoplasm. Journal of cell science 9 15020682
2020 pCRM1exportome: database of predicted CRM1-dependent Nuclear Export Signal (NES) motifs in cancer-related genes. Bioinformatics (Oxford, England) 8 31504173
2020 Using a Simple Cellular Assay to Map NES Motifs in Cancer-Related Proteins, Gain Insight into CRM1-Mediated NES Export, and Search for NES-Harboring Micropeptides. International journal of molecular sciences 8 32882917
2021 Novel Mechanistic Observations and NES-Binding Groove Features Revealed by the CRM1 Inhibitors Plumbagin and Oridonin. Journal of natural products 7 33890470
2018 A novel overlapping NLS/NES region within the PH domain of Rho Guanine Nucleotide Exchange Factor (RGNEF) regulates its nuclear-cytoplasmic localization. European journal of cell biology 7 30482479
2002 A trans-dominant negative HIV type 1 Rev with intact domains of NLS/NOS and NES. AIDS research and human retroviruses 7 12167277
2001 Northern epilepsy syndrome (NES, CLN8)--MRI and electrophysiological studies. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 7 11588991
1999 A potential NES of the Epstein-Barr virus nuclear antigen 1 (EBNA1) does not confer shuttling. FEBS letters 7 10214968
2024 iPSC-derived cells stimulate ABCG2+/NES+ endogenous trabecular meshwork cell proliferation and tissue regeneration. Cell proliferation 5 38356373
2024 Expression of LOXL3, NES, and SNAI1 in Melanoma Genesis and Progression. Cells 5 39273022
2023 Adeno-Associated Virus-like Particles' Response to pH Changes as Revealed by nES-DMA. Viruses 5 37376661
2019 Nuclear export signal (NES) of transposases affects the transposition activity of mariner-like elements Ppmar1 and Ppmar2 of moso bamboo. Mobile DNA 5 31452694
2023 Discovery of a Hidden Pocket beneath the NES Groove by Novel Noncovalent CRM1 Inhibitors. Journal of medicinal chemistry 4 38105606
2022 Generation of a NES-mScarlet Red Fluorescent Reporter Human iPSC Line for Live Cell Imaging and Flow Cytometric Analysis and Sorting Using CRISPR-Cas9-Mediated Gene Editing. Cells 4 35053384
2021 Profiling Glioblastoma Cases with an Expression of DCX, OLIG2 and NES. International journal of molecular sciences 4 34948016
2024 Exploring the manganese-dependent interaction between a transcription factor and its corresponding DNA: insights from gas-phase electrophoresis on a nES GEMMA instrument. Analytical and bioanalytical chemistry 3 39172237
2021 A possible role of gas-phase electrophoretic mobility molecular analysis (nES GEMMA) in extracellular vesicle research. Analytical and bioanalytical chemistry 3 34622320
2013 Identification of a rod domain-truncated isoform of nestin, Nes-SΔ₁₀₇₋₂₅₄, in rat dorsal root ganglia. Neuroscience letters 3 23994057
2025 Phosphate-dependent nuclear export via a non-classical NES class recognized by exportin Msn5. Nature communications 2 40089503
2023 Human LUHMES and NES cells as models for studying primary cilia in neurons. Methods in cell biology 2 37164541
2023 Experience-dependent Tip60 nucleocytoplasmic transport is regulated by its NLS/NES sequences for neuroplasticity gene control. Molecular and cellular neurosciences 2 37598897
2025 The CRM1-dependent NES257-266 motif in the matrix protein: another factor influencing Newcastle disease virus propagation and virulence. Veterinary research 1 40598613
2025 Strong Immune Privileges of MSC and Other Nes-GFP+ Progenitors in Bone Marrow of Transgenic Mice. Immune network 1 40620418
2025 Application of Gas-Phase Electrophoresis (nES GEMMA Instrumentation) in Molecular Weight Determination. Journal of mass spectrometry : JMS 1 41060775
2022 TERT silencing alters the expression of ARG1, GLUL, VIM, NES genes and hsa-miR-29b-3p in the T98G cell line. Nucleosides, nucleotides & nucleic acids 1 36533634
2021 nES-DMA with Charge-reduction based on Soft X-ray Radiation: Analysis of a Recombinant Monoclonal Antibody. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 1 34543886
2016 NES-REBS: A novel nuclear export signal prediction method using regular expressions and biochemical properties. Journal of bioinformatics and computational biology 1 27225342
2006 Antiviral properties of combination peptides of HIV-1 Rev NLS and NES. Protein and peptide letters 1 17168825
2002 The nuclear export signal (NES) found in the amino-terminal region of carp MEK1 and MKK6 is lacking in carp MKK4. Biochimica et biophysica acta 1 12020830
1988 Pharmacological nature of newer imidazoli(di)nes on rat anococcygeus muscle. Pharmacological research communications 1 3387458
2025 Immunomodulatory Effects of Lactobacillus brevis NES-428 in a Hyperthyroidism Mouse Model: Potential Applications for Graves' Disease. Nutrients 0 41010493
2025 Gas-Phase Electrophoresis (nES GEMMA Instrumentation) of SARS-CoV-2-Based Virus-like Particles. ACS omega 0 41322519
2024 Phosphate-dependent nuclear export via a novel NES class recognized by exportin Msn5. bioRxiv : the preprint server for biology 0 39211127

Missed literature

Know a paper Affinage missed for NES? Flag it for the maintainers and the community.

No submissions yet.