Cathepsin A Explained

Cathepsin A is an enzyme that is classified both as a cathepsin and a carboxypeptidase. In humans, it is encoded by the CTSA gene.^[1]

Function

This gene encodes a glycoprotein that associates with lysosomal enzymes beta-galactosidase and neuraminidase to form a complex of high-molecular-weight multimers. The formation of this complex provides a protective role for stability and activity. It is protective for β-galactosidase and neuraminidase.^[2]

Clinical significance

Deficiencies in this gene are linked to multiple forms of galactosialidosis.^[1]

Interactions

Cathepsin A has been shown to interact with NEU1.^[3]

Further reading

• Morreau H, Galjart NJ, Willemsen R . Human lysosomal protective protein. Glycosylation, intracellular transport, and association with beta-galactosidase in the endoplasmic reticulum. . J. Biol. Chem. . 267 . 25 . 17949–56 . 1992 . 10.1016/S0021-9258(19)37135-2 . 1387645 . etal. free .
• Halal F, Chitayat D, Parikh H . Ring chromosome 20 and possible assignment of the structural gene encoding human carboxypeptidase-L to the distal segment of the long arm of chromosome 20. . Am. J. Med. Genet. . 43 . 3 . 576–9 . 1992 . 1605251 . 10.1002/ajmg.1320430314 . etal.
• Jackman HL, Tan FL, Tamei H . A peptidase in human platelets that deamidates tachykinins. Probable identity with the lysosomal "protective protein". . J. Biol. Chem. . 265 . 19 . 11265–72 . 1990 . 10.1016/S0021-9258(19)38586-2 . 1694176 . etal. free .
• Zhou XY, Galjart NJ, Willemsen R . A mutation in a mild form of galactosialidosis impairs dimerization of the protective protein and renders it unstable. . EMBO J. . 10 . 13 . 4041–8 . 1992 . 1756715 . 10.1002/j.1460-2075.1991.tb04980.x. 453152 . etal.
• Galjart NJ, Morreau H, Willemsen R . Human lysosomal protective protein has cathepsin A-like activity distinct from its protective function. . J. Biol. Chem. . 266 . 22 . 14754–62 . 1991 . 10.1016/S0021-9258(18)98751-X . 1907282 . etal. free .
• Yoshida K, Oshima A, Shimmoto M . Human beta-galactosidase gene mutations in GM1-gangliosidosis: a common mutation among Japanese adult/chronic cases. . Am. J. Hum. Genet. . 49 . 2 . 435–42 . 1991 . 1907800 . 1683306 . etal.
• Wiegant J, Galjart NJ, Raap AK, d'Azzo A . The gene encoding human protective protein (PPGB) is on chromosome 20. . Genomics . 10 . 2 . 345–9 . 1991 . 2071143 . 10.1016/0888-7543(91)90318-9 .
• Strisciuglio P, Sly WS, Dodson WE . Combined deficiency of beta-galactosidase and neuraminidase: natural history of the disease in the first 18 years of an American patient with late infantile onset form. . Am. J. Med. Genet. . 37 . 4 . 573–7 . 1991 . 2148053 . 10.1002/ajmg.1320370431 . etal.
• Kase R, Itoh K, Takiyama N . Galactosialidosis: simultaneous deficiency of esterase, carboxy-terminal deamidase and acid carboxypeptidase activities. . Biochem. Biophys. Res. Commun. . 172 . 3 . 1175–9 . 1990 . 2244901 . 10.1016/0006-291X(90)91572-A . etal.
• Willemsen R, Hoogeveen AT, Sips HJ . Immunoelectron microscopical localization of lysosomal beta-galactosidase and its precursor forms in normal and mutant human fibroblasts. . Eur. J. Cell Biol. . 40 . 1 . 9–15 . 1986 . 3084261 . etal.
• Verheijen FW, Palmeri S, Galjaard H . Purification and partial characterization of lysosomal neuraminidase from human placenta. . Eur. J. Biochem. . 162 . 1 . 63–7 . 1987 . 3102233 . 10.1111/j.1432-1033.1987.tb10542.x .
• Nanba E, Tsuji A, Omura K, Suzuki Y . Galactosialidosis: a direct evidence that a 46-kilodalton protein restores deficient enzyme activities in fibroblasts. . Biochem. Biophys. Res. Commun. . 144 . 1 . 138–42 . 1987 . 3107551 . 10.1016/S0006-291X(87)80486-2 .
• Galjart NJ, Gillemans N, Harris A . Expression of cDNA encoding the human "protective protein" associated with lysosomal beta-galactosidase and neuraminidase: homology to yeast proteases. . Cell . 54 . 6 . 755–64 . 1988 . 3136930 . 10.1016/S0092-8674(88)90999-3 . 21504892 . etal.
• Chitayat D, Applegarth DA, Lewis J . Juvenile galactosialidosis in a white male: a new variant. . Am. J. Med. Genet. . 31 . 4 . 887–901 . 1989 . 3149149 . 10.1002/ajmg.1320310423 . etal.
• Verheijen FW, Palmeri S, Hoogeveen AT, Galjaard H . Human placental neuraminidase. Activation, stabilization and association with beta-galactosidase and its protective protein. . Eur. J. Biochem. . 149 . 2 . 315–21 . 1985 . 3922758 . 10.1111/j.1432-1033.1985.tb08928.x .
• van der Horst GT, Kleijer WJ, Hoogeveen AT . Morquio B syndrome: a primary defect in beta-galactosidase. . Am. J. Med. Genet. . 16 . 2 . 261–75 . 1984 . 6418007 . 10.1002/ajmg.1320160215 . etal.
• Maire I, Nivelon-Chevallier AR . Combined deficiency of beta-galactosidase and neuraminidase: three affected siblings in a French family. . J. Inherit. Metab. Dis. . 4 . 4 . 221–3 . 1982 . 6796775 . 10.1007/BF02263656 . 38676707 .
• Pshezhetsky AV, Potier M . Direct affinity purification and supramolecular organization of human lysosomal cathepsin A. . Arch. Biochem. Biophys. . 313 . 1 . 64–70 . 1994 . 8053688 . 10.1006/abbi.1994.1359 .
• Ishii N, Oshima A, Sakuraba H . Normal serum beta-galactosidase in juvenile GM1 gangliosidosis. . Pediatr. Neurol. . 10 . 4 . 317–9 . 1994 . 8068159 . 10.1016/0887-8994(94)90129-5 . etal.
• Chakraborty S, Rafi MA, Wenger DA . Mutations in the lysosomal beta-galactosidase gene that cause the adult form of GM1 gangliosidosis. . Am. J. Hum. Genet. . 54 . 6 . 1004–13 . 1994 . 8198123 . 1918177 .

Notes and References

1. Web site: Entrez Gene: CTSA cathepsin A.
2. Book: Mitchell, Richard Sheppard . Kumar, Vinay . Robbins, Stanley L. . Abbas, Abul K. . Fausto, Nelson . Robbins basic pathology . 8th . Saunders/Elsevier . 2007 . Table 7-6 . 978-1-4160-2973-1 .
3. van der Spoel . A . Bonten E. d'Azzo A . Mar 1998 . Transport of human lysosomal neuraminidase to mature lysosomes requires protective protein/cathepsin A . EMBO J. . 17 . 6 . 1588–97 . ENGLAND. 0261-4189. 9501080 . 10.1093/emboj/17.6.1588 . 1170506 .