CTSV

CTSV Background

Cathepsin V (CTSV) is a cysteine endopeptidase with a preference for hydrophobic residues such as Trp, Tyr, Phe, Leu, and Val in its S2 binding pocket. CTSV shares high homolog with cathepsin L in the protein sequence. Different from the ubiquitously expressed cathepsin L, CTSV' expression is restricted to the thymus and testis ^[1][2]. And it is uniquely high expressed in the corneal epithelium ^[3]. So cathepsin V is also named cathepsin L2. CTSV has optimal activity between pH 5.5 and 6.0. CTSV exhibits a potent elastolytic activity, whereas CTSL has only a minimal proteolytic activity toward insoluble elastin. Xin Du et al. revealed two exosites contributing to the elastolytic activity of cathepsin V that is distant from the active cleft of the protease and are located in surface loop regions ^[4]. Like most other cathepsins, cathepsin V cleaves in the telopeptide region of type I collagen, but it is incapable of cleaving within the triple-helical region of native collagens. Studies found that recombinant CTSV can efficiently convert MHC/class II-associated invariant chain Ii into CLIP, suggesting that CTSV is the protease that controls the generation of antigen-presentable αβ-CLIP complexes in the human thymus ^[5]. Comparison of CTSV expression between thymi from patients with myasthenia gravis and healthy controls revealed a significantly higher expression level in the pathological samples, suggesting a potential involvement of this protease in the immunopathogenesis of myasthenia gravis, an autoimmune disease almost invariably associated with thymic pathology ^[5]. CTSV is efficiently inhibited by classical cysteine protease inhibitors. Human CTSV is involved in the production of enkephalin and neuropeptide Y, which are required for neurotransmission in health and neurological diseases ^[6].

[1] I. Santamaria, G. Velasco, et al. Cathepsin L2, a novel human cysteine proteinase produced by breast and colorectal carcinomas [J]. Cancer Res., 58 (1998), pp. 1624-1630.
[2] D. Bromme, Z. Li, et al. Human cathepsin V functional expression, tissue distribution, electrostatic surface potential, enzymatic characterization, and chromosomal localization [J]. Biochemistry, 38 (1999), pp. 2377-2385.
[3] Adachi W, Kawamoto S, et al. Isolation and characterization of human cathepsin V: a major proteinase in corneal epithelium [J]. Invest Ophthalmol Vis Sci. 1998 Sep; 39(10):1789-96.
[4] Xin Du, Nelson L H Chen, et al. Elastin Degradation by Cathepsin V Requires Two Exosites [J]. J Biol Chem, 2013, 288 (48), 34871-81.
[5] Eva Tolosa, Weijie Li, et al. Cathepsin V Is Involved in the Degradation of Invariant Chain in Human Thymus and Is Overexpressed in Myasthenia Gravis [J]. J Clin Invest, 2003, 112 (4), 517-26.
[6] Funkelstein L, Lu WD, et al. Human cathepsin V protease participates in production of enkephalin and NPY neuropeptide neurotransmitters [J]. J Biol Chem. 2012 May 4; 287(19):15232-41.