Affinage

CAPNS1

Calpain small subunit 1 · UniProt P04632

Length
268 aa
Mass
28.3 kDa
Annotated
2026-04-28
100 papers in source corpus 17 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CAPNS1 encodes the obligate small regulatory subunit shared by the µ-calpain and m-calpain heterodimers, and is essential for the stability and proteolytic activity of both calcium-dependent cysteine proteases. Its C-terminal EF-hand domain binds Ca²⁺ and mediates heterodimerization with the catalytic large subunits, while its N-terminal glycine-rich hydrophobic region enables phosphatidylinositol-dependent reduction of the Ca²⁺ requirement for calpain activation (PMID:3038855, PMID:3034871, PMID:3011770). Genetic ablation of CAPNS1 eliminates both calpain activities and disrupts diverse downstream processes including IκB–NF-κB inflammatory signaling, cell-cycle G1/S progression through p27Kip1 accumulation, USP1-dependent PCNA deubiquitination in the DNA damage response, FAK-Src pathway activation, and mitochondrial ATP synthase integrity (PMID:10825211, PMID:22753411, PMID:20368361, PMID:23589330, PMID:26246018). CAPNS1 transcription is driven primarily by NRF-1 and AP-1 transcription factors, and AP-1-mediated upregulation can be co-opted by viral oncoproteins such as EBV LMP1 (PMID:18234454, PMID:31691433).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1986 High

    Establishing how the small subunit modulates Ca²⁺ sensitivity: the N-terminal hydrophobic region of CAPNS1 was shown to be required for phosphatidylinositol-mediated lowering of the Ca²⁺ threshold for calpain autolysis, while hybrid reconstitution showed the large subunit N-terminus, not the small subunit, directly sets Ca²⁺ sensitivity for catalysis.

    Evidence In vitro proteolytic trimming and subunit-swap reconstitution with Ca²⁺-sensitivity autolysis assays

    PMID:3011770 PMID:3023314

    Open questions at the time
    • Precise lipid-binding residues in the N-terminal region not mapped
    • Physiological membrane context not tested
  2. 1987 High

    The C-terminal EF-hand domain of CAPNS1 was identified as the structural determinant for Ca²⁺ binding and for heterodimer assembly with the catalytic subunit, establishing CAPNS1 as a Ca²⁺-sensing scaffold essential for calpain complex integrity.

    Evidence Carboxypeptidase Y digestion destroying the EF-hand abolished complex formation; recombinant EF-hand domain bound 2–4 mol Ca²⁺ at physiologically relevant concentrations

    PMID:3034871 PMID:3038855

    Open questions at the time
    • Stoichiometry of Ca²⁺ binding per individual EF-hand not resolved
    • No crystal structure at this stage
  3. 2000 High

    Genetic proof that CAPNS1 is indispensable in vivo: homozygous Capn4 knockout eliminated both µ- and m-calpain activities, caused midgestational embryonic lethality with cardiovascular defects, and established CAPNS1 as the obligate regulatory subunit for both heterodimers.

    Evidence Knockout mouse with enzymatic activity assays, cell viability assays, and developmental phenotyping

    PMID:10825211

    Open questions at the time
    • Specific calpain substrates driving cardiovascular lethality not identified
    • Relative contribution of µ- vs. m-calpain loss to the phenotype unclear
  4. 2007 High

    The transcriptional control of CAPNS1 was defined: NRF-1 and AP-1 are the principal transcription factors driving the core promoter, with NRF-1 mutation reducing activity ~70% and double mutation ~90%.

    Evidence Promoter deletion/mutagenesis, EMSA, ChIP, and siRNA against NRF-1 in two cell lines

    PMID:18234454

    Open questions at the time
    • Epigenetic regulation and chromatin context not addressed
    • Tissue-specific transcription factor usage not explored
  5. 2008 High

    CAPNS1 was linked to specific receptor signaling and tissue homeostasis: it directly binds the PTH/PTHrP receptor tail and is required for osteoblast proliferation, differentiation, and bone mineralization; separately, it was identified as a RasGAP-SH3 interactor in oncogenic Ras cells, linking it to migration and survival.

    Evidence Osteoblast-specific conditional KO with functional assays; yeast two-hybrid, co-IP, and siRNA in K-Ras(V12) cells

    PMID:18515801 PMID:18761085

    Open questions at the time
    • Structural basis of CAPNS1–PTH1R interaction unknown
    • RasGAP interaction confirmed in single lab; reciprocal validation limited
  6. 2010 High

    CAPNS1 was placed upstream of G1/S cell-cycle control: chondrocyte-specific Capn4 deletion caused p27Kip1 accumulation and reduced cyclin D transcription, and p27 silencing rescued growth, demonstrating calpain-dependent cell-cycle regulation.

    Evidence Chondrocyte-specific Capn4 KO, cell-cycle analysis, siRNA rescue, dose-dependent small-subunit reintroduction

    PMID:20368361

    Open questions at the time
    • Whether calpain directly cleaves p27Kip1 or acts indirectly not definitively resolved
    • Generalizability beyond chondrocytes not tested
  7. 2012 High

    CAPNS1-dependent calpain activity was shown to drive inflammatory signaling via IκB degradation and NF-κB activation in cardiomyocytes after myocardial infarction, establishing calpain as a proximal activator of the NF-κB–cytokine axis in cardiac injury.

    Evidence Cardiomyocyte-specific Capn4 KO, MI model, NF-κB/IκB western blot, histology

    PMID:22753411

    Open questions at the time
    • Whether IκB is a direct calpain substrate or an indirect target not resolved
    • Contribution of non-calpain pathways to residual NF-κB signaling unclear
  8. 2013 High

    A non-canonical pathway was uncovered: CAPNS1 stabilizes the deubiquitinase USP1 via Cdk5 activation, preventing APC/C(Cdh1)-mediated USP1 degradation and thereby controlling PCNA ubiquitination and translesion synthesis fidelity.

    Evidence CAPNS1 siRNA in U2OS cells and MEFs, co-IP, ubiquitinated PCNA detection, rescue with Cdk5/p25

    PMID:23589330

    Open questions at the time
    • Whether calpain directly cleaves a Cdk5 inhibitor or activates Cdk5 through another intermediate unknown
    • In vivo mutagenesis phenotype not tested
  9. 2014 Medium

    CAPNS1 was shown to physically associate with FAK and promote FAK-Src-p130Cas hyperphosphorylation, linking calpain activity to MMP2-dependent invasion in hepatocellular carcinoma.

    Evidence Co-IP, protein microarray, phosphorylation assays, siRNA, in vivo metastasis models

    PMID:24962955

    Open questions at the time
    • Direct versus calpain-mediated nature of FAK interaction not distinguished
    • Single lab; independent replication lacking
  10. 2015 High

    Mitochondria-localized calpain-1 (dependent on CAPNS1) was shown to cleave ATP synthase-α during endotoxemia, disrupting oxidative phosphorylation and generating mitochondrial superoxide that drives inflammatory signaling.

    Evidence Capn4 cardiomyocyte-specific KO, endotoxemia model, mitochondrial fractionation, ATP5A1 overexpression rescue, mitochondria-targeted calpastatin

    PMID:26246018

    Open questions at the time
    • Mechanism of calpain-1 import into mitochondria not defined
    • Cleavage site on ATP5A1 not mapped
  11. 2016 Medium

    miRNA-mediated silencing of CAPNS1 (via miR-99a/miR-491) was shown to destabilize calpain-1/2 catalytic subunits, reduce caspase-3/PARP1 cleavage, and confer cisplatin resistance, linking CAPNS1 expression level to apoptotic threshold in cancer.

    Evidence miRNA mimics/inhibitors, siRNA, western blot, dual-luciferase reporter assay in gastric cancer cells

    PMID:27994509

    Open questions at the time
    • Apoptosis readout in single cancer cell model; generalizability unclear
    • Relative contribution of calpain-1 vs. calpain-2 loss not dissected
  12. 2019 Medium

    EBV oncoprotein LMP1 was shown to upregulate CAPNS1 transcription via AP-1, activated through ERK/JNK phosphorylation, thereby promoting cytoskeletal rearrangement and migration in nasopharyngeal carcinoma cells.

    Evidence Luciferase promoter assay, ERK/JNK phosphorylation, siRNA, migration assays

    PMID:31691433

    Open questions at the time
    • Whether LMP1 regulation of CAPNS1 occurs in primary NPC tissue not confirmed
    • Contribution of NRF-1 in LMP1-driven upregulation not examined
  13. 2021 Medium

    CAPNS1 was implicated in innate immune polarization and additional substrate regulation: macrophage-specific KO reduced NLRP3 inflammasome activation and M1 polarization via CHOP-STAT1/3 during viral myocarditis, while CAPNS1 was shown to interact with and promote degradation of CNOT3 in renal cancer.

    Evidence Macrophage-specific Capn4 conditional KO with CVB3 infection model; co-IP and xenograft studies for CNOT3 interaction

    PMID:34733662 PMID:37660839

    Open questions at the time
    • CHOP as a direct calpain substrate not demonstrated
    • CNOT3 interaction from single lab; cleavage site and directness not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how CAPNS1-containing calpain heterodimers are targeted to distinct subcellular compartments (e.g., mitochondria, membrane protrusions), the structural basis for CAPNS1's non-catalytic interactions with partners like FAK and PTH1R, and whether CAPNS1 has calpain-independent functions.
  • Mechanism of mitochondrial calpain import unknown
  • No high-resolution structure of full-length heterodimer with membrane lipids
  • Calpain-independent roles of CAPNS1 not tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0008289 lipid binding 1
Localization
GO:0005829 cytosol 3 GO:0005886 plasma membrane 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 2 R-HSA-1640170 Cell Cycle 1 R-HSA-5357801 Programmed Cell Death 1 R-HSA-73894 DNA Repair 1
Partners
CAPN1CAPN2CNOT3FAKPTH1RRASA1USP1
Complex memberships
m-calpain (CAPN2–CAPNS1 heterodimer)µ-calpain (CAPN1–CAPNS1 heterodimer)

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Homozygous disruption of murine Capn4 (the common small regulatory subunit) eliminates both µ-calpain and m-calpain proteolytic activities, demonstrating that CAPNS1 is essential for the activity of both calpain heterodimers. Loss of Capn4 does not affect ES cell or fibroblast proliferation but causes embryonic lethality at midgestation with cardiovascular defects. Knockout mouse (homozygous gene disruption), enzymatic activity assays, cell viability assays Molecular and cellular biology High 10825211
1986 The amino-terminal hydrophobic, glycine-rich region of the CANP small subunit (CAPNS1) is required for phosphatidylinositol-mediated reduction of the Ca²⁺ requirement for calpain autolysis; trimming this region abolishes the phosphatidylinositol effect, implicating CAPNS1 in membrane-dependent regulation of calpain Ca²⁺ sensitivity. Proteolytic trimming of small subunit followed by in vitro autolysis assay with phosphatidylinositol Journal of biochemistry High 3011770
1986 The Ca²⁺ sensitivity of calpain is determined by the structural state of the large subunit N-terminus after autolysis, not by the small subunit (CAPNS1). Hybrid reconstitution experiments showed that swapping autolyzed vs. intact large subunits changed Ca²⁺ requirements, while swapping small subunits did not. Subunit dissociation and hybrid reconstitution in vitro; enzymatic activity assays Journal of biochemistry High 3023314
1987 The COOH-terminal E-F hand structure of the calpain small subunit (CAPNS1) is essential for subunit association and resulting proteolytic activity. Carboxypeptidase Y digestion destroying the C-terminal E-F hand helical region of both subunits abolished complex formation and enzyme activity. Carboxypeptidase Y limited digestion of calpain subunits, subunit reassociation assay, enzymatic activity assay Journal of biochemistry High 3034871
1987 The E-F hand domain of the calpain small subunit (CAPNS1) binds Ca²⁺ ions; expressed E-F hand domains from rabbit small subunit bound 2–4 mol Ca²⁺, and the Ca²⁺-binding affinity roughly corresponds to the Ca²⁺ concentration required for calpain activity. Bacterial expression of E-F hand domain fragments, microscale filter Ca²⁺-binding assay Journal of biochemistry High 3038855
2013 CAPNS1 is required for stability of the deubiquitinating enzyme USP1. In CAPNS1-depleted cells, APC/C(Cdh1)-mediated destruction of USP1 is upregulated, leading to accumulation of ubiquitinated PCNA, increased loading of polymerase-η on chromatin, and elevated mutagenesis. Calpain stabilizes USP1 by activating Cdk5, which represses Cdh1. siRNA knockdown of CAPNS1 in U2OS cells and MEFs, co-immunoprecipitation, western blot for ubiquitinated PCNA, rescue with Cdk5/p25 forced expression Molecular and cellular biology High 23589330
2008 The calpain small subunit (CAPNS1/Capn4) directly binds to the intracellular C-terminal tail of the PTH/PTHrP receptor and is required for proper osteoblast proliferation, differentiation, and matrix mineralization. Osteoblast-specific Capn4 knockout mice show reduced trabecular bone and decreased osteoblast number. Osteoblast-specific Cre-LoxP conditional knockout, in vitro osteoblast function assays (proliferation, differentiation, mineralization) The Journal of biological chemistry High 18515801
2010 Chondrocyte-specific deletion of Capn4 impairs cell cycle G1/S progression, reduces cyclin D gene transcription, and causes accumulation of calpain substrate cell-cycle proteins (e.g., p27Kip1). Silencing p27Kip1 rescues impaired growth, and reintroduction of the small subunit normalizes cyclin D levels dose-dependently. Chondrocyte-specific Capn4 knockout (Cre-LoxP), cell cycle analysis, siRNA rescue experiments, western blot Molecular and cellular biology High 20368361
2012 Cardiomyocyte-specific deletion of Capn4 eliminates calpain-1 and calpain-2 activities, prevents IκB degradation and NF-κB activation after myocardial infarction, thereby suppressing proinflammatory cytokines, limiting infarct expansion, and reducing adverse cardiac remodeling. Cardiomyocyte-specific Capn4 knockout mouse, myocardial infarction model, calpain activity assay, NF-κB/IκB western blot, histology The Journal of biological chemistry High 22753411
2015 Mitochondrial calpain-1 (dependent on Capn4) cleaves ATP synthase-α (ATP5A1) during endotoxemia, disrupting ATP synthase and generating mitochondrial superoxide that drives proinflammatory signaling. Capn4 cardiomyocyte-specific KO or ATP5A1 overexpression prevents this cascade. Capn4 cardiomyocyte-specific KO, lipopolysaccharide endotoxemia model, mitochondrial fractionation, co-localization and cleavage assays, mitochondria-targeted calpastatin overexpression Circulation. Heart failure High 26246018
2008 CAPNS1 (Capns1) was identified as a binding partner of the RasGAP-SH3 domain in K-Ras(V12) oncogenic cells. The interaction, confirmed by co-immunoprecipitation, occurs specifically in oncogenic Ras-expressing cells and co-localizes to cell protrusions. Capns1 knockdown increases apoptosis and reduces migration speed. Yeast two-hybrid screening, co-immunoprecipitation, confocal co-localization, siRNA knockdown with migration and apoptosis assays Cellular signalling Medium 18761085
2014 Capn4 physically associates with FAK and promotes hyperphosphorylation of FAK, Src, and p130Cas, activating the FAK-Src signaling pathway. This leads to upregulation of MMP2 and increased invasion/metastasis of hepatocellular carcinoma cells. Co-immunoprecipitation, protein microarray, phosphorylation assays, siRNA knockdown, in vivo tumor/metastasis models The Journal of pathology Medium 24962955
2007 The human CAPNS1 promoter is regulated by transcription factors NRF-1 and AP-1. The core promoter maps to -187/+174; NRF-1 mutation reduces promoter activity by 70%, AP-1 by 50%, and double mutation by 90%. NRF-1 binding to the natural promoter was confirmed by ChIP. Promoter deletion analysis, site-directed mutagenesis, EMSA, supershift assay, ChIP, siRNA against NRF-1 Gene High 18234454
2016 CAPNS1 positively regulates calpain-1 and calpain-2 (the catalytic subunits), and loss of CAPNS1 via miR-99a/miR-491-mediated silencing reduces cleaved caspase-3 and PARP1 cleavage, thereby reducing apoptosis and conferring cisplatin resistance in gastric cancer cells. miRNA mimics/inhibitors, siRNA knockdown of CAPNS1, western blot for calpain-1/2 and cleaved caspase-3/PARP1, dual-luciferase reporter assay International journal of biological sciences Medium 27994509
2019 Epstein-Barr virus LMP1 upregulates Capn4 transcription through its CTAR1 and CTAR2 domains by activating AP-1 via ERK/JNK phosphorylation. Capn4 in turn promotes actin rearrangement and NPC cell migration. Luciferase promoter assay, western blot, siRNA, ERK/JNK phosphorylation assays, migration assays Cancer science Medium 31691433
2021 CAPN4 promotes macrophage M1 polarization and NLRP3 inflammasome activation during CVB3 infection through upregulation of CHOP, which activates STAT1 and STAT3 phosphorylation. Macrophage-specific CAPN4 conditional KO reduces M1 transformation and myocardial injury in vivo. Macrophage-specific conditional KO (LYZ2-Cre), CVB3 infection model, NLRP3 and cytokine assays, STAT1/STAT3 phosphorylation western blot, CHOP modulation Free radical biology & medicine Medium 37660839
2021 CAPN4 directly interacts with CNOT3 and promotes its degradation. In renal cancer cells, CAPN4 loss (via miR-124) stabilizes CNOT3 and enhances cisplatin-induced necroptosis; this was confirmed by co-immunoprecipitation. Co-immunoprecipitation, qPCR, western blot, flow cytometry for necroptosis, in vivo xenograft Translational andrology and urology Medium 34733662

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Disruption of the murine calpain small subunit gene, Capn4: calpain is essential for embryonic development but not for cell growth and division. Molecular and cellular biology 291 10825211
2000 The '30K' superfamily of viral movement proteins. The Journal of general virology 221 10640565
1987 Localization by immunogold cytochemistry of the virus-coded 30K protein in plasmodesmata of leaves infected with tobacco mosaic virus. Virology 174 18644574
1981 Limited autolysis of Ca2+-activated neutral protease (CANP) changes its sensitivity to Ca2+ ions. Journal of biochemistry 168 6270080
1986 The amino-terminal hydrophobic region of the small subunit of calcium-activated neutral protease (CANP) is essential for its activation by phosphatidylinositol. Journal of biochemistry 120 3011770
1993 Identification of the soybean allergenic protein, Gly m Bd 30K, with the soybean seed 34-kDa oil-body-associated protein. Bioscience, biotechnology, and biochemistry 118 7763872
1986 Limited autolysis of calcium-activated neutral protease (CANP): reduction of the Ca2+-requirement is due to the NH2-terminal processing of the large subunit. Journal of biochemistry 100 3023314
1991 The tobacco mosaic virus 30K movement protein in transgenic tobacco plants is localized to plasmodesmata. The Journal of general virology 99 1990065
1984 Synthesis of TMV-specific RNAs and proteins at the early stage of infection in tobacco protoplasts: transient expression of the 30K protein and its mRNA. Virology 91 18639805
1984 Comparison of low and high calcium requiring forms of the calcium-activated neutral protease (CANP) from rabbit skeletal muscle. Journal of biochemistry 86 6088474
2009 Capn4 overexpression underlies tumor invasion and metastasis after liver transplantation for hepatocellular carcinoma. Hepatology (Baltimore, Md.) 77 19053044
1986 Fodrin degradation by calcium-activated neutral proteinase (CANP) in retinal ganglion cell neurons and optic glia: preferential localization of CANP activities in neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 68 3012012
1976 Conditional lethal mutants of adenovirus type 2-simian virus 40 hybrids. II. Ad2+ND1 host-range mutants that synthesize fragments of the Ad2+ND1 30K protein. Journal of virology 64 183014
2016 MiR-99a and MiR-491 Regulate Cisplatin Resistance in Human Gastric Cancer Cells by Targeting CAPNS1. International journal of biological sciences 61 27994509
1983 Single amino acid substitution in 30K protein of TMV defective in virus transport function. Virology 59 6316652
2015 Evolution of plant virus movement proteins from the 30K superfamily and of their homologs integrated in plant genomes. Virology 58 25576984
1986 Multiple calcium-activated neutral proteinases (CANP) in mouse retinal ganglion cell neurons: specificities for endogenous neuronal substrates and comparison to purified brain CANP. The Journal of neuroscience : the official journal of the Society for Neuroscience 57 3012011
2017 MALAT1/miR-124/Capn4 axis regulates proliferation, invasion and EMT in nasopharyngeal carcinoma cells. Cancer biology & therapy 55 28857668
2012 Deficiency of Capn4 gene inhibits nuclear factor-κB (NF-κB) protein signaling/inflammation and reduces remodeling after myocardial infarction. The Journal of biological chemistry 55 22753411
2003 Inhibition of apoptosis by recombinant 30K protein originating from silkworm hemolymph. Biochemical and biophysical research communications 54 12914782
2013 Characterization of Capsicum annuum genetic diversity and population structure based on parallel polymorphism discovery with a 30K unigene Pepper GeneChip. PloS one 53 23409153
2014 The oncoprotein HBXIP enhances migration of breast cancer cells through increasing filopodia formation involving MEKK2/ERK1/2/Capn4 signaling. Cancer letters 52 25304384
1984 Conversion of myelin-associated glycoprotein (MAG) to a smaller derivative by calcium activated neutral protease (CANP)-like enzyme in myelin and inhibition by E-64 analogue. Neurochemical research 52 6206410
1990 Immunohistochemical distribution of calcium-activated neutral proteinases and endogenous CANP inhibitor in the rabbit hippocampus. The Journal of comparative neurology 51 2086609
1985 Hydrolytic and autolytic behavior of two forms of calcium-activated neutral protease (CANP). Journal of biochemistry 51 2999095
2000 Mutational analysis of the IgE-binding epitopes of P34/Gly m Bd 30K. The Journal of allergy and clinical immunology 49 10669862
1983 Molecular cloning and nucleotide sequence of the 30K and the coat protein cistron of TMV (tomato strain) genome. Nucleic acids research 49 6304642
1995 Measurement of Gly m Bd 30K, a major soybean allergen, in soybean products by a sandwich enzyme-linked immunosorbent assay. Bioscience, biotechnology, and biochemistry 48 7765969
1988 Interviral homologies of the 30K proteins of tobamoviruses. Virology 48 3201760
2014 Capn4 contributes to tumour growth and metastasis of hepatocellular carcinoma by activation of the FAK-Src signalling pathways. The Journal of pathology 46 24962955
1987 E-F hand structure-domain of calcium-activated neutral protease (CANP) can bind Ca2+ ions. Journal of biochemistry 46 3038855
2015 miR-124 suppresses the migration and invasion of glioma cells in vitro via Capn4. Oncology reports 43 26530859
1990 Time course of TMV 30K protein accumulation in intact leaves. Virology 42 2294644
2022 Calcium nanoparticles (Ca-NPs) improve drought stress tolerance in Brassica napus by modulating the photosystem II, nutrient acquisition and antioxidant performance. NanoImpact 40 36084849
2013 Experimental and bioinformatic evidence that raspberry leaf blotch emaravirus P4 is a movement protein of the 30K superfamily. The Journal of general virology 40 23761405
1986 Calcium activated neutral proteases (milli- and micro-CANP) and endogenous CANP inhibitor of muscle in Duchenne muscular dystrophy (DMD). Clinica chimica acta; international journal of clinical chemistry 40 3024865
1983 Reaction of calcium-activated neutral protease (CANP) with an epoxysuccinyl derivative (E64c) and iodoacetic acid. Journal of biochemistry 40 6309757
1983 Point mutation in the 30-K open reading frame of TMV implicated in temperature-sensitive assembly and local lesion spreading of mutant Ni 2519. The EMBO journal 39 16453478
1982 Nucleotide sequence of the 30K protein cistron of cowpea strain of tobacco mosaic virus. Nucleic acids research 39 6292867
2014 Capn4 is a marker of poor clinical outcomes and promotes nasopharyngeal carcinoma metastasis via nuclear factor-κB-induced matrix metalloproteinase 2 expression. Cancer science 38 24703594
1990 Insertion of sequences containing the coat protein subgenomic RNA promoter and leader in front of the tobacco mosaic virus 30K ORF delays its expression and causes defective cell-to-cell movement. Virology 38 2294638
2008 In vivo targeted deletion of calpain small subunit, Capn4, in cells of the osteoblast lineage impairs cell proliferation, differentiation, and bone formation. The Journal of biological chemistry 37 18515801
2005 Possible effect of 30K proteins in embryonic development of silkworm Bombyx mori. Acta biochimica et biophysica Sinica 37 15880265
1987 The COOH-terminal E-F hand structure of calcium-activated neutral protease (CANP) is important for the association of subunits and resulting proteolytic activity. Journal of biochemistry 37 3034871
1987 Localization and inhibition of calcium-activated neutral protease (CANP) in primate skeletal muscle and peripheral nerve. Experimental neurology 35 2822459
1987 Distribution of calcium activated neutral proteinase (mM CANP) in myelin and cytosolic fractions in bovine brain white matter. Life sciences 35 3039281
2015 Deletion of capn4 Protects the Heart Against Endotoxemic Injury by Preventing ATP Synthase Disruption and Inhibiting Mitochondrial Superoxide Generation. Circulation. Heart failure 32 26246018
1983 Degradation of myelin basic protein by calcium-activated neutral protease (CANP) in human brain and inhibition by E-64 analogue. Neurochemical research 32 6197665
2015 Cytorhabdovirus P3 genes encode 30K-like cell-to-cell movement proteins. Virology 30 26700068
1998 Drosophila clipper/CPSF 30K is a post-transcriptionally regulated nuclear protein that binds RNA containing GC clusters. Nucleic acids research 30 9512528
2012 Hepatitis B virus X protein drives multiple cross-talk cascade loops involving NF-κB, 5-LOX, OPN and Capn4 to promote cell migration. PloS one 29 22355367
2015 Capn4 promotes non-small cell lung cancer progression via upregulation of matrix metalloproteinase 2. Medical oncology (Northwood, London, England) 27 25636510
2010 Targeted deletion of Capn4 in cells of the chondrocyte lineage impairs chondrocyte proliferation and differentiation. Molecular and cellular biology 27 20368361
1984 Identification of the 30K protein of TMV by immunoprecipitation with antibodies directed against a synthetic peptide. Virology 26 18639799
2013 CAPNS1 regulates USP1 stability and maintenance of genome integrity. Molecular and cellular biology 25 23589330
2007 NRF-1, and AP-1 regulate the promoter of the human calpain small subunit 1 (CAPNS1) gene. Gene 25 18234454
1993 Preparation and application of monoclonal antibodies for a sandwich enzyme-linked immunosorbent assay of the major soybean allergen, Gly m Bd 30K. Journal of nutritional science and vitaminology 25 7506767
1988 Purification of calcium-activated neutral proteinase (CANP) from purified myelin of bovine brain white matter. Neurochemical research 25 2834658
2017 miR-124 suppresses proliferation and invasion of nasopharyngeal carcinoma cells through the Wnt/β-catenin signaling pathway by targeting Capn4. OncoTargets and therapy 24 28579809
1991 Calcium-activated neutral proteinase (CANP; calpain) activity in Schwann cells: immunofluorescence localization and compartmentation of mu- and mCANP. Journal of neuroscience research 24 1656060
2012 The synthesis, transportation and degradation of BmLP3 and BmLP7, two highly homologous Bombyx mori 30K proteins. Insect biochemistry and molecular biology 22 23213653
2009 An integrated expression phenotype mapping approach defines common variants in LEP, ALOX15 and CAPNS1 associated with induction of IL-6. Human molecular genetics 22 19942621
2021 Circular RNA ABCB10 promotes cell proliferation and invasion, but inhibits apoptosis via regulating the microRNA‑1271‑mediated Capn4/Wnt/β‑catenin signaling pathway in epithelial ovarian cancer. Molecular medicine reports 21 33760208
2018 Suppression of Capn4 by microRNA-1271 impedes the proliferation and invasion of colorectal cancer cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 21 29331762
2018 MiR-337-3p suppresses the proliferation and metastasis of clear cell renal cell carcinoma cells via modulating Capn4. Cancer biomarkers : section A of Disease markers 21 30452399
2014 Increased expression of Capn4 is associated with the malignancy of human glioma. CNS neuroscience & therapeutics 21 24628706
1990 Regulation of the calcium-activated neutral proteinase (CANP) of bovine brain by myelin lipids. Biochimica et biophysica acta 21 2331482
1989 The regional and subcellular distribution of calcium activated neutral proteinase (CANP) in the bovine central nervous system. Neurochemical research 21 2542823
2020 Capn4 contributes to tumor invasion and metastasis in gastric cancer via activation of the Wnt/β-catenin/MMP9 signalling pathways. Experimental cell research 20 32777225
2011 Association of PPARGC1A and CAPNS1 gene polymorphisms and expression with meat quality traits in pigs. Meat science 20 21680104
2016 Capn4 promotes epithelial-mesenchymal transition in human melanoma cells through activation of the Wnt/β-catenin pathway. Oncology reports 19 27878263
2014 Capn4 mRNA level is correlated with tumour progression and clinical outcome in clear cell renal cell carcinoma. The Journal of international medical research 18 24514433
2012 Systemic transport of Alfalfa mosaic virus can be mediated by the movement proteins of several viruses assigned to five genera of the 30K family. The Journal of general virology 18 23136366
2023 Macrophage CAPN4 regulates CVB3-induced cardiac inflammation and injury by promoting NLRP3 inflammasome activation and phenotypic transformation to the inflammatory subtype. Free radical biology & medicine 17 37660839
2018 Capn4 promotes colorectal cancer cell proliferation by increasing MAPK7 through activation of the Wnt/β-Catenin pathway. Experimental cell research 17 29331389
2016 Bioinformatic and mutational analysis of ophiovirus movement proteins, belonging to the 30K superfamily. Virology 17 27596536
1990 Ganglioside-modulated proteolysis by Ca2(+)-activated neutral proteinase (CANP): a role of glycoconjugates in CANP regulation. Journal of neurochemistry 17 2182778
1990 Purification of an endogenous 68 kD inhibitor of calcium-activated neutral proteinase (CANP) from bovine brain: immunoblot identification and characterization. Journal of neuroscience research 17 2319618
2017 Capn4 Enhances Osteopontin Expression through Activation of the Wnt/β-Catenin Pathway to Promote Epithelial Ovarian Carcinoma Metastasis. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 16 28535511
2008 Capns1, a new binding partner of RasGAP-SH3 domain in K-Ras(V12) oncogenic cells: modulation of cell survival and migration. Cellular signalling 16 18761085
2006 Molecular properties and tissue distribution of 30K proteins as ommin-binding proteins from diapause eggs of the silkworm, Bombyx mori. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 16 17134929
1996 Specific binding of allergenic soybean protein Gly m Bd 30K with alpha'- and alpha-subunits of conglycinin in soy milk. Bioscience, biotechnology, and biochemistry 16 8695899
1992 Response to atrial natriuretic peptide, endopeptidase 24.11 inhibitor and C-ANP receptor ligand in the rat. British journal of pharmacology 16 1330165
2013 Functional analysis of 30K proteins during silk gland degeneration by a caspase-dependent pathway in Bombyx. Insect molecular biology 15 23496335
1997 Substantially Complete Removal of Three Major Allergenic Soybean Proteins (Gly m Bd 30K, Gly m Bd 28K, and the α-Subunit of Conglycinin) from Soy Protein by Using a Mutant Soybean, Tohoku 124. Bioscience, biotechnology, and biochemistry 14 27396895
1988 Calcium-activated neutral protease (CANP), a putative processing enzyme of the neuropeptide, kyotorphin, in the brain. Biochemical and biophysical research communications 14 2844173
1985 Characterization of calcium-activated neutral protease (CANP)-associated protein kinase from bovine brain and its phosphorylation of neurofilaments. Biochemical and biophysical research communications 14 2990469
2021 Five Silkworm 30K Proteins Are Involved in the Cellular Immunity against Fungi. Insects 12 33513667
2010 Pivotal roles of three conserved carboxyl residues of the NuoC (30k) segment in the structural integrity of proton-translocating NADH-quinone oxidoreductase from Escherichia coli. Biochemistry 12 20979355
2000 Identification and characterization of a 30K protein (Ad4E3-30K) encoded by the E3 region of human adenovirus type 4. Virology 12 10891415
1992 Reinvestigation of intracellular localization of the 30K protein in tobacco protoplasts infected with tobacco mosaic virus RNA. Virology 12 1546469
1986 Subcellular localization of the 30K protein in TMV-inoculated tobacco protoplasts. Virology 12 3727401
2019 Capn4 is induced by and required for Epstein-Barr virus latent membrane protein 1 promotion of nasopharyngeal carcinoma metastasis through ERK/AP-1 signaling. Cancer science 11 31691433
2018 Capn4 expression is modulated by microRNA-520b and exerts an oncogenic role in prostate cancer cells by promoting Wnt/β-catenin signaling. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 11 30241050
2013 Two Novel 30K Proteins Overexpressed in Baculovirus System and Their Antiapoptotic Effect in Insect and Mammalian Cells. International journal of genomics 11 23862133
1990 Changing the start codon context of the 30K gene of tobacco mosaic virus from "weak" to "strong" does not increase expression. Virology 11 2294639
2021 MiRNA-124 regulates the sensitivity of renal cancer cells to cisplatin-induced necroptosis by targeting the CAPN4-CNOT3 axis. Translational andrology and urology 10 34733662
2016 Identification of Ourmiavirus 30K movement protein amino acid residues involved in symptomatology, viral movement, subcellular localization and tubule formation. Molecular plant pathology 10 26637973
1992 Calcium-activated neutral protease (CANP) in normal and dysmyelinating mutant paralytic tremor rabbit myelin. Molecular and chemical neuropathology 10 1418220
2018 Capn4 regulates migration and invasion of ovarian carcinoma cells via targeting osteopontin-mediated PI3K/AKT signaling pathway. Oncology letters 9 30655802