CAPN2 Research Reagents

CAPN2 Background

The CAPN2 encodes calpain-2, one type of isozymic calcium-dependent protease calpain that belongs to the cysteine protease family ^[1]. Calpain is ubiquitously expressed in the central nervous system CNS) of mammalian cells. Calpain exists as an inactive proenzyme in the cytosol and migrates to membranes in response to the increase of cellular calcium ion concentration ^[2]. At the membrane, Calpain is activated in the presence of calcium ion and phospholipids ^[3]. Calpain-2 is activated by millimolar concentrations of calcium. Inactive calpain-2 is associated with the ER (endoplasmic reticulum) membrane at the cytosolic side. Upon activation, calpain-2 is released and rapidly degraded. Opposite to the neuroprotective role of calpain-1, calpain-2 is neurodegenerative. Chang-jiang Huang et al. demonstrated that either increased cytosolic calcium ion concentration or hyperactivation of calpain-2 mediates beta-cell dysfunction and apoptosis in type 2 diabetes mellitus (T2DM) ^[4]. Experimental and clinical evidence indicates that CAPN2 is aberrantly expressed in various tumors. It plays a crucial role in tumorigenesis, disease progression, and therapy resistance ^[5][6][7]. Extrasynaptic Nmethyl- D-asparate receptors (NMDARs) specifically activate calpain-2, which degrades STEP, ultimately resulting in neurotoxicity ^[8].

[1] Ohno S, Minoshima S, et al. Four genes for the calpain family locate on four distinct human chromosomes [J]. Cytogenet Cell Genet. 1990, 53 (4): 225-9.
[2] Wingrave JM, Schaecher KE, et al. Early induction of secondary injury factors causing activation of calpain and mitochondria-mediated neuronal apoptosis following spinal cord injury in rats [J]. J Neurosci Res. 2003 Jul 1; 73(1):95-104.
[3] Suzuki K, Sorimachi H. A novel aspect of calpain activation [J]. FEBS Lett. 1998 Aug 14; 433(1-2):1-4.
[4] Chang-jiang Huang, Tatyana Gurlo, et al. Calcium-activated Calpain-2 Is a Mediator of Beta Cell Dysfunction and Apoptosis in Type 2 Diabetes [J]. The Journal of Biological Chemistry, 2010, 285, 339-348.
[5] Ho WC, Pikor L, et al. Calpain 2 regulates Akt-FoxO-p27(Kip1) protein signaling pathway in mammary carcinoma [J]. J Biol Chem. 287:15458-15465. 2012.
[6] Li P, Miao C, Liang C, et al. Silencing CAPN2 expression inhibited castration-resistant prostate cancer cells proliferation and invasion via AKT/mTOR signal pathway [J]. Biomed Res Int.
2017:25936742017.  
[7] Liu B, Zhou Y, et al. Comparison of the protein expression of calpain-1, calpain-2, calpastatin and calmodulin between gastric cancer and normal gastric mucosa [J]. Oncol Lett. 14:3705-3710.2017.
[8] Xu J, et al. Extrasynaptic NMDA receptors couple preferentially to excitotoxicity via calpain-mediated cleavage of STEP [J]. J Neurosci. 2009;29(29):9330-43.