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Gene Review

CAPNS1  -  calpain, small subunit 1

Homo sapiens

Synonyms: 30K, CALPAIN4, CANP, CANP small subunit, CANPS, ...
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Disease relevance of CAPNS1

  • Increased levels of the calpain small subunit were also observed in breast tumors, and significant amounts of its proteolyzed forms indicated increased calpain activity [1].
  • Association of mitochondrial calpain activation with increased expression and autolysis of calpain small subunit in an early stage of apoptosis [2].
  • 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 [3].
  • In normal subjects and pancreatectomized patients, plasma IRG levels were 2- to 3-fold higher with the C-terminus-directed antibody X4 than with either 30K or P7, but in glucagonoma and uremic patients, this discrepancy was smaller [4].
  • These data show that the 30K protein in stool is produced by specific cleavage of the NV capsid protein in vivo [5].

High impact information on CAPNS1

  • Proteasomes have several proteolytically active sites and are complexes of high relative molecular mass (Mr about 600K), consisting of about 20-30 subunits with Mrs between 15 and 30K [6].
  • Here we report that two-dimensional peptide maps of the clathrin light chains and of all chromaffin granule membrane binding proteins in the 30K range are distinct, and therefore fail to support this hypothesis [7].
  • Immunostaining of the endogenous autophagosome marker LC3 and electron microscopy experiments demonstrate that autophagy is impaired in CAPNS1-deficient cells [8].
  • Utilizing transformed fibroblasts from calpain small subunit knock-out (Capns1(-/-)) mouse embryos, we now show that the heterodimeric, typical subclass of calpains is required for calcium-mediated survival after plasma membrane damage caused by scraping a cell monolayer [9].
  • The alphaPIX triple domain SH3-DH-PH was found to be required for calpain 4 binding [10].

Chemical compound and disease context of CAPNS1

  • The soybean allergenic protein, Gly m Bd 30K [Ogawa et al., J. Nutr. Sci. Vitaminol., 37, 555-565 (1991)] which is most strongly and frequently recognized by the IgE antibodies in sera of soybean-sensitive patients with atopic dermatitis, has been characterized [11].

Biological context of CAPNS1

  • Depletion of calpain small subunit after 5 or more days of treatment led to inhibition of cell proliferation that could be reversed by removal of antisense oligodeoxyribonucleotide from the culture medium [12].
  • In CAPNS1-depleted cells, ectopic LC3 accumulates in early endosome-like vesicles that may represent a salvage pathway for protein degradation when autophagy is defective [8].
  • The deduced amino acid sequences of the three isolated clones showed a high degree of similarity to the large subunit of calcium-activated neutral proteinase (CANP) from humans and chicken [13].
  • Upstream of the promoter region are tandemly reiterated multiple regulatory regions (-2.5k to -690, -690 to -460, -460 to -260, and -260 to -202), each of which negatively regulates the CANP mL gene promoter as well as heterologous promoters in an orientation-independent manner [14].
  • In order to explore the binding sites for calcium-activated neutral protease (CANP) with high calcium sensitivity (muCANP) on the inner surface of human erythrocyte membranes, we analyzed the binding of muCANP to two kinds of membranes modified by treatment with phospholipase C or Triton X-100 [15].

Anatomical context of CAPNS1

  • Based on a knowledge of calpain metabolic stability, a protocol was devised for chronic exposure of WI-38 cells and HeLa cells to a calpain small subunit antisense oligodeoxyribonucleotide [12].
  • The location of calcium-activated neutral proteinase (CANP) was determined in human erythrocytes by crosslinking CANP to co-localizing proteins using a photolabeling bifunctional reagent, 4,4'-dithiobisphenylazide (DTBPA) [16].
  • Since the mRNA for p94 is five times more abundant than that for the CANP small subunit in skeletal muscle, it is possible that p94 does not associate with the small subunit in vivo [17].
  • With both extraction procedures the immunoreactive glucagon (IRG) content in the submaxillary glands was greater than in parotid glands as determined with a C-terminal reactive glucagon antiserum (30K) [18].
  • We find that an immortalized Capn4(-/-) fibroblast line displays an altered morphology, characterized by numerous thin membrane projections and increased transient membrane activity [19].

Associations of CAPNS1 with chemical compounds

  • AlphaPIX associates with calpain 4, the small subunit of calpain, and has a dual role in integrin-mediated cell spreading [10].
  • After oral glucose, plasma IRG (with the COOH-terminal-specific 30K glucagon antibody) rose from 59 +/- 7 to a peak of 113 +/- 17 pg/ml at 60-120 min [20].
  • Mutational analysis of the IgE-binding epitopes of P34/Gly m Bd 30K [21].
  • Chromatography of plasma from one pancreatectomized dog on Sephadex G-50 after arginine stimulation revealed that much of the material cross-reacting with antibody 30K was eluted from the column earlier than either 125I-insulin or 125I-glucagon [22].
  • VP84, the large glycoprotein, contains a protein backbone of only 26K to 30K which is modified by N-linked and probable O-linked glycosylation [23].

Physical interactions of CAPNS1


Other interactions of CAPNS1


Analytical, diagnostic and therapeutic context of CAPNS1

  • Using Sephacryl S-200 gel filtration, BCGF activity was demonstrated in the 20 to 30K m.w. fractions of mitogen-stimulated peripheral blood mononuclear cells [27].
  • An "interference factor" has been shown to be present in human plasma, which can cause artifactual elevation of pancreatic glucagon values as conventionally determined by radioimmunoassay using antiserum 30K [28].
  • With immunoblotting, the anti-IGF-BP-3 antibody, which specifically recognizes the 41.5 and 38.5K species, cross-reacted with this 30K material [29].
  • These results suggest that some of the material that reacted with 30K antibody and which increased after pancreatectomy in response to arginine has a molecular weight greater than pancreatic glucagon [22].
  • Western blot analysis of the BPs revealed a predominant 30K form and 24K and 20K forms which appeared inconsistently and in small quantities [30].


  1. Cyclin E in breast tumors is cleaved into its low molecular weight forms by calpain. Wang, X.D., Rosales, J.L., Magliocco, A., Gnanakumar, R., Lee, K.Y. Oncogene (2003) [Pubmed]
  2. Association of mitochondrial calpain activation with increased expression and autolysis of calpain small subunit in an early stage of apoptosis. Daniel, K.G., Anderson, J.S., Zhong, Q., Kazi, A., Gupta, P., Dou, Q.P. Int. J. Mol. Med. (2003) [Pubmed]
  3. 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. Grodzicker, T., Lewis, J.B., Anderson, C.W. J. Virol. (1976) [Pubmed]
  4. Differential immunoreactivity of plasma glucagon components in man: studies with different glucagon antibodies. Soybel, D., Jaspan, J., Polonsky, K., Goldberg, I., Rayfield, E., Tager, H. J. Clin. Endocrinol. Metab. (1983) [Pubmed]
  5. Specific proteolytic cleavage of recombinant Norwalk virus capsid protein. Hardy, M.E., White, L.J., Ball, J.M., Estes, M.K. J. Virol. (1995) [Pubmed]
  6. Subunit of the '20S' proteasome (multicatalytic proteinase) encoded by the major histocompatibility complex. Ortiz-Navarrete, V., Seelig, A., Gernold, M., Frentzel, S., Kloetzel, P.M., Hämmerling, G.J. Nature (1991) [Pubmed]
  7. Clathrin light chains and secretory vesicle binding proteins are distinct. Creutz, C.E., Harrison, J.R. Nature (1984) [Pubmed]
  8. Calpain is required for macroautophagy in mammalian cells. Demarchi, F., Bertoli, C., Copetti, T., Tanida, I., Brancolini, C., Eskelinen, E.L., Schneider, C. J. Cell Biol. (2006) [Pubmed]
  9. Calpain Is Required for the Rapid, Calcium-dependent Repair of Wounded Plasma Membrane. Mellgren, R.L., Zhang, W., Miyake, K., McNeil, P.L. J. Biol. Chem. (2007) [Pubmed]
  10. AlphaPIX associates with calpain 4, the small subunit of calpain, and has a dual role in integrin-mediated cell spreading. Rosenberger, G., Gal, A., Kutsche, K. J. Biol. Chem. (2005) [Pubmed]
  11. Identification of the soybean allergenic protein, Gly m Bd 30K, with the soybean seed 34-kDa oil-body-associated protein. Ogawa, T., Tsuji, H., Bando, N., Kitamura, K., Zhu, Y.L., Hirano, H., Nishikawa, K. Biosci. Biotechnol. Biochem. (1993) [Pubmed]
  12. The major calpain isozymes are long-lived proteins. Design of an antisense strategy for calpain depletion in cultured cells. Zhang, W., Lane, R.D., Mellgren, R.L. J. Biol. Chem. (1996) [Pubmed]
  13. Characterization of cDNA clones encoding a novel calcium-activated neutral proteinase from Schistosoma mansoni. Andresen, K., Tom, T.D., Strand, M. J. Biol. Chem. (1991) [Pubmed]
  14. Tandemly reiterated negative enhancer-like elements regulate transcription of a human gene for the large subunit of calcium-dependent protease. Hata, A., Ohno, S., Akita, Y., Suzuki, K. J. Biol. Chem. (1989) [Pubmed]
  15. Binding sites for calcium-activated neutral protease on erythrocyte membranes are not membrane phospholipids. Inomata, M., Saito, Y., Kon, K., Kawashima, S. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  16. Calcium-induced localization of calcium-activated neutral proteinase on plasma membranes. Sakai, K., Hayashi, M., Kawashima, S., Akanuma, H. Biochim. Biophys. Acta (1989) [Pubmed]
  17. A novel member of the calcium-dependent cysteine protease family. Sorimachi, H., Ohmi, S., Emori, Y., Kawasaki, H., Saido, T.C., Ohno, S., Minami, Y., Suzuki, K. Biol. Chem. Hoppe-Seyler (1990) [Pubmed]
  18. Synthesis and release of glucagon by human salivary glands. Pérez-Castillo, A., Blázquez, E. Diabetologia (1980) [Pubmed]
  19. Isoform specific function of calpain 2 in regulating membrane protrusion. Franco, S., Perrin, B., Huttenlocher, A. Exp. Cell Res. (2004) [Pubmed]
  20. Glucagon immunoreactivity and chromatographic profiles in pancreatectomized humans. Paradoxical response to oral glucose. Bajorunas, D.R., Fortner, J.G., Jaspan, J.B. Diabetes (1986) [Pubmed]
  21. Mutational analysis of the IgE-binding epitopes of P34/Gly m Bd 30K. Helm, R.M., Cockrell, G., Connaughton, C., West, C.M., Herman, E., Sampson, H.A., Bannon, G.A., Burks, A.W. J. Allergy Clin. Immunol. (2000) [Pubmed]
  22. Persistent pancreatic glucagon but not insulin response to arginine in pancreatectomized dogs. Mashiter, K., Harding, P.E., Chou, M., Mashiter, G.D., Stout, J., Diamond, D., Field, J.B. Endocrinology (1975) [Pubmed]
  23. Kinetics of synthesis of respiratory syncytial virus glycoproteins. Fernie, B.F., Dapolito, G., Cote, P.J., Gerin, J.L. J. Gen. Virol. (1985) [Pubmed]
  24. The receptor for parathyroid hormone and parathyroid hormone-related peptide is hydrolyzed and its signaling properties are altered by directly binding the calpain small subunit. Shimada, M., Mahon, M.J., Greer, P.A., Segre, G.V. Endocrinology (2005) [Pubmed]
  25. Characterization of a human digestive tract-specific calpain, nCL-4, expressed in the baculovirus system. Lee, H.J., Tomioka, S., Kinbara, K., Masumoto, H., Jeong, S.Y., Sorimachi, H., Ishiura, S., Suzuki, K. Arch. Biochem. Biophys. (1999) [Pubmed]
  26. Constitutive expression of cytotoxic proteases and down-regulation of protease inhibitors in LGL leukemia. Kothapalli, R., Bailey, R.D., Kusmartseva, I., Mane, S., Epling-Burnette, P.K., Loughran, T.P. Int. J. Oncol. (2003) [Pubmed]
  27. B cell growth factor and T cell growth factor produced by mitogen-stimulated normal human peripheral blood T lymphocytes are distinct molecules. Muraguchi, A., Kasahara, T., Oppenheim, J.J., Fauci, A.S. J. Immunol. (1982) [Pubmed]
  28. High molecular weight glucagon-like immunoreactivity in plasma. Weir, G.C., Knowlton, S.D., Martin, D.B. J. Clin. Endocrinol. Metab. (1975) [Pubmed]
  29. Evidence of enzymatic degradation of insulin-like growth factor-binding proteins in the 150K complex during pregnancy. Hossenlopp, P., Segovia, B., Lassarre, C., Roghani, M., Bredon, M., Binoux, M. J. Clin. Endocrinol. Metab. (1990) [Pubmed]
  30. Production of insulin-like growth factors and their binding proteins by rabbit articular chondrocytes: relationships with cell multiplication. Froger-Gaillard, B., Hossenlopp, P., Adolphe, M., Binoux, M. Endocrinology (1989) [Pubmed]
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