|Protein Name||Cathepsin D|
|Protein Existence Status||Reviewed: Experimental evidence at protein level|
|Presence in other biological fluids/tissue/cells||Serum, ecrine sweat, urine, major secretions of numerous types of cancer cells, ECM and synovial fluid of cartilage during pathological conditions, macrophage-rich regions of atherosclerotic lesions, human keratinocytes|
|Protein Function||soluble lysosomal aspartic endopeptidases; role in cancer development; independent tumor marker; regulation of blood vessel formation;|
|Biochemical Properties||Four forms of cathepsin D, pro-, pseudo-, single-chained and two chained cathepsin D are identified in bovine milk; cathepsin D shows proteolyric activity at acidic pH; Mature bovine cathepsin D consists of approximately equal amounts of single-chained and two-chained forms; when exposed to acid pH in vitro, procathepsin D undergoes autoproteolytic cleavage between residues 26 and 27 of the propeptide, resulting in a proteolytically active intermediate form called pseudocathepsin D, which has an N-terminal extension of 18 residues compared with mature cathepsin D; acid proteinase of bovine milk was reported to be heat inactivated after 10 min at 70 °C, but retained some proteolytic activity after heating at lower temperatures;|
|Significance in milk||aspartic proteinase; activate neutrophils and lymphocytes as reported in human milk; regulation of surface receptirs; activation of immune systems in breast-fed infants; degardes αs1, ß- and κ-casein;|
|PTMs||glycoprotein with two N-linked oligosaccharides modified with mannose 6-phosphate residues at asparagine residues 70 and 199|
| Site(s) of PTM(s) |
|Predicted Disorder Regions||NA|
|TM Helix Prediction||No TM helices|
|Significance of PTMs||Lysosomal targeting|
|Additional Comments||Failure of protein degradation resulted in acumulation of lipofuscin in variety of cell types, neurodegeneration, developmental regression and visual loss|
|Bibliography||1. Hasilik, A., & Neufeldg, E. F. (1984). Biosynthesis of Lysosomal Enzymes in Fibroblasts. The Journal of Biological Chemistry, 25(10), 4937–4945. |
2. Larsen, L. B., Benfeldt, C., Rasmussen, L. K., & Petersen, T. E. (1996). Bovine milk procathepsin D and cathepsin D: coagulation and milk protein degradation. The Journal of Dairy Research, 63(1), 119–130. https://doi.org/10.1017/s0022029900031599.
3. Zühlsdorf, M., Imort, M., Hasilik, A., & von Figura, K. (1983). Molecular forms of beta-hexosaminidase and cathepsin D in serum and urine of healthy subjects and patients with elevated activity of lysosomal enzymes. The Biochemical Journal, 213(3), 733–740. https://doi.org/10.1042/bj2130733.
4. Fortenberry, S. C., Schorey, J. S., & Chirgwin, J. M. (1995). Role of glycosylation in the expression of human procathepsin D. Journal of Cell Science, 108 ( Pt 5), 2001–2006. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/7657720.
5. Hasilik, A., & Neufeld, E. F. (1980). Biosynthesis of lysosomal enzymes in fibroblasts. Phosphorylation of mannose residues. The Journal of Biological Chemistry, 255(10), 4946–4950. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/6989822.
6. Baechle, D., Flad, T., Cansier, A., Steffen, H., Schittek, B., Tolson, J., … Kalbacher, H. (2006). Cathepsin D is present in human eccrine sweat and involved in the postsecretory processing of the antimicrobial peptide DCD-1L. The Journal of Biological Chemistry, 281(9), 5406–5415. https://doi.org/10.1074/jbc.M504670200.
7. Leto, G., Tumminello, F. M., Crescimanno, M., Flandina, C., & Gebbia, N. (2004). Cathepsin D expression levels in nongynecological solid tumors: clinical and therapeutic implications. Clinical & Experimental Metastasis, 21(2), 91–106. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15168727.
8. Hakala, J. K., Oksjoki, R., Laine, P., Du, H., Grabowski, G. A., Kovanen, P. T., & Pentikäinen, M. O. (2003). Lysosomal enzymes are released from cultured human macrophages, hydrolyze LDL in vitro, and are present extracellularly in human atherosclerotic lesions. Arteriosclerosis, Thrombosis, and Vascular Biology, 23(8), 1430–1436. https://doi.org/10.1161/01.ATV.0000077207.49221.06.
9. Vashishta, A., Saraswat Ohri, S., Vetvickova, J., Fusek, M., Ulrichova, J., & Vetvicka, V. (2007). Procathepsin D secreted by HaCaT keratinocyte cells - A novel regulator of keratinocyte growth. European Journal of Cell Biology, 86(6), 303–313. https://doi.org/10.1016/j.ejcb.2007.03.008.