Primary Information
BoMiProt ID	Bomi22
Protein Name	Cathepsin D
Organism	Bos taurus
Uniprot ID	P80209
Milk Fraction	Whey
Aminoacid Length	390
Molecular Weight	42491
FASTA Sequence	Download
Gene Name	CTSD
Protein Existence Status	Reviewed: Experimental evidence at protein level
Secondary Information
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) N-glycosylation, O-glycosylation, Phosphorylation
Predicted Disorder Regions	NA
DisProt Annotation
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.