Cathepsin E

Cathepsin E is an enzyme (EC 3.4.23.34) that in humans is encoded by the CTSE gene.[5][6][7] The enzyme is also known as slow-moving proteinase, erythrocyte membrane aspartic proteinase, SMP, EMAP, non-pepsin proteinase, cathepsin D-like acid proteinase, cathepsin E-like acid proteinase, cathepsin D-type proteinase) is an enzyme.[8][9][10][6]

CTSE
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCTSE, Ctse, A430072O03Rik, C920004C08Rik, CE, CatE, cathepsin E
External IDsOMIM: 116890 MGI: 107361 HomoloGene: 37551 GeneCards: CTSE
Orthologs
SpeciesHumanMouse
Entrez

1510

13034

Ensembl

ENSG00000196188

ENSMUSG00000004552

UniProt

P14091

P70269

RefSeq (mRNA)

NM_001910
NM_148964
NM_001317331

NM_007799

RefSeq (protein)

NP_001304260
NP_001901
NP_683865

NP_031825

Location (UCSC)Chr 1: 206.01 – 206.02 MbChr 1: 131.57 – 131.6 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Cathepsin E
Identifiers
EC no.3.4.23.34
CAS no.110910-42-4
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Search
PMCarticles
PubMedarticles
NCBIproteins

Cathepsin E is a protease found in animals, as well as various other organisms, that belongs to the aspartic protease group. In humans it is encoded by the CTSE gene located at 1q32 on chromosome 1.[11][12][6][13] It is an intracellular non-lysosomal glycoprotein that is mainly found in the skin and in immune cells.[14] The protein is an aspartyl protease that functions as a disulfide-linked homodimer, and has an oligosaccharide chain of the high-mannose type.[15] It is a member of the peptidase A1 family, and therefore observes specificity similar to that of Pepsin A and Cathepsin D. Cathepsin E is an intracellular enzyme and does not appear to be involved in dietary protein digestion. It is found at highest abundance on the stomach’s epithelial mucus producing cell surfaces. It is the first aspartic protease present in the fetal stomach and is found in more than half of gastric cancers, leading to it appearing to be an oncofetal antigen. Transcript variants utilizing alternative polyadenylation signals and two transcript variants encoding different isoforms exist for this gene.[13][14]

A deficiency in the levels of Cathepsin E in the body may play a part in inflammatory skin diseases such as atopic dermatitis, for which treatment would rely on fixing functionality and levels of the protein in the body.[16] Along with renin and Cathepsin D, Cathepsin E is one of the only few aspartic proteases known to be made in human tissues other than those of gastrointestinal and reproductive tracts.[17]

Structure

The structure of Cathepsin E is very similar to those of Cathepsin D and BACE1, and all 3 have almost identical active site regions. The differences between them lie in the microenvironments that surround their active sites. Residues DTG 96-98 and DTG 281-283 contribute to the formation of the enzyme’s active site. There are also two pairs of disulfide bonds at residues Cys 272-276 and Cys 314-351. Two other Cys residues at positions 109 and 114 on the amino acid chain reside close to teach other in three dimensional space, however the distance between their sulfur atoms is 3.53 Å which is too large for the formation of a proper disulfide bond. The structure also has four hydrogen bonds between the Asp residues of the active site and the surrounding residues. A distinguishing factor of Cathepsin E in comparison with the structure of Cathepsin D and BACE1 can be seen at the formation of an extra hydrogen bond between the Asp 96 and Ser 99 residues, and absence of a hydrogen bond with Leu/Met at Asp 281.[16]

Location

The enzyme is distributed in cells of the gastrointestinal tracts, lymphoid tissues, blood cells, urinary organs and microglia. Its intracellular localization in different mammalian cells is different to that of its analog Cathepsin D. Cathepsin E associates with the membrane tissue in the intracellular canaliculi of gastric parietal cells, bile canaliculi of hepatic cells, cells of the rinal proximal tubule in the kidney, epithelial cells in the intestine, trachea and bronchi, osteoclasts and even in erythrocytes. Its localization in the endosome structures can be seen in many different cell types such as antigen-presenting B cell lymphoblasts, gastric cells and microglia. Its presence is also detected in the cisternae of the cell’s endoplasmic reticulum.[15][18]

Function

Cathepsin E plays a vital role in protein degradation, antigen processing via the MHC class II pathway[13] and bioactive protein generation. The enzyme is also thought to be involved in age induced neuronal death pathway execution as well as the excessive stimulation of glutamate receptors with excitotoxins and transient forebrain ischemia. In an experiment carried out on rats, Cathepsin E was barely detected in the brain tissues of young rats, however in older rats its level was greatly increased in the neostriatum and cerebral cortex. The enzyme was also expressed at high levels in the activated microglia of the hippocampal CA1 region and in degenerating neurons for a week after transient forebrain ischemia.[18] Cathepsin E has a possible role in the development of well differentiated adenocarcinoma from intestinal metaplasia.[15] The enzyme also plays a part in association with dendritic cells where it generates the CD4 repertoire in response to self and foreign proteins.[19]

Post-translational modification

The enzyme is glycosylated. Different cell types contribute to the differences in the nature of the carbohydrate chain. A high mannose-type oligosaccharide is observed in the proenzyme in fibroblasts, however the mature enzyme can be seen with a complex-type oligosaccharide. In the membranes of erythrocytes, the mature enzyme and the pro-enzyme both have a complex-type oligosaccharide. Auto catalytic cleavage produces two forms of the enzyme, with Form 1 beginning at residue Ile 54 and Form 2 at Thr 57.[20]

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000196188 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000004552 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Couvreur JM, Azuma T, Miller DA, Rocchi M, Mohandas TK, Boudi FA, Taggart RT (Aug 1990). "Assignment of cathepsin E (CTSE) to human chromosome region 1q31 by in situ hybridization and analysis of somatic cell hybrids". Cytogenetics and Cell Genetics. 53 (2–3): 137–9. doi:10.1159/000132914. PMID 2369841.
  6. Azuma T, Pals G, Mohandas TK, Couvreur JM, Taggart RT (October 1989). "Human gastric cathepsin E. Predicted sequence, localization to chromosome 1, and sequence homology with other aspartic proteinases". The Journal of Biological Chemistry. 264 (28): 16748–53. doi:10.1016/S0021-9258(19)84768-3. PMID 2674141.
  7. "Entrez Gene: CTSE cathepsin E".
  8. Lapresle C, Puizdar V, Porchon-Bertolotto C, Joukoff E, Turk V (June 1986). "Structural differences between rabbit cathepsin E and cathepsin D". Biological Chemistry Hoppe-Seyler. 367 (6): 523–6. doi:10.1515/bchm3.1986.367.1.523. PMID 3741628.
  9. Yonezawa S, Fujii K, Maejima Y, Tamoto K, Mori Y, Muto N (November 1988). "Further studies on rat cathepsin E: subcellular localization and existence of the active subunit form". Archives of Biochemistry and Biophysics. 267 (1): 176–83. doi:10.1016/0003-9861(88)90021-5. PMID 3058036.
  10. Jupp RA, Richards AD, Kay J, Dunn BM, Wyckoff JB, Samloff IM, Yamamoto K (September 1988). "Identification of the aspartic proteinases from human erythrocyte membranes and gastric mucosa (slow-moving proteinase) as catalytically equivalent to cathepsin E". The Biochemical Journal. 254 (3): 895–8. doi:10.1042/bj2540895. PMC 1135167. PMID 3058118.
  11. "CTSE cathepsin E [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-10-16.
  12. Couvreur JM, Azuma T, Miller DA, Rocchi M, Mohandas TK, Boudi FA, Taggart RT (1990). "Assignment of cathepsin E (CTSE) to human chromosome region 1q31 by in situ hybridization and analysis of somatic cell hybrids". Cytogenetics and Cell Genetics. 53 (2–3): 137–9. doi:10.1159/000132914. PMID 2369841.
  13. Zaidi N, Kalbacher H (March 2008). "Cathepsin E: a mini review". Biochemical and Biophysical Research Communications. 367 (3): 517–22. doi:10.1016/j.bbrc.2007.12.163. PMID 18178150.
  14. Yasuda Y, Kageyama T, Akamine A, Shibata M, Kominami E, Uchiyama Y, Yamamoto K (June 1999). "Characterization of new fluorogenic substrates for the rapid and sensitive assay of cathepsin E and cathepsin D". Journal of Biochemistry. 125 (6): 1137–43. doi:10.1093/oxfordjournals.jbchem.a022396. PMID 10348917.
  15. Saku T, Sakai H, Shibata Y, Kato Y, Yamamoto K (December 1991). "An immunocytochemical study on distinct intracellular localization of cathepsin E and cathepsin D in human gastric cells and various rat cells". Journal of Biochemistry. 110 (6): 956–64. doi:10.1093/oxfordjournals.jbchem.a123696. PMID 1794985.
  16. Chou KC (May 2005). "Modeling the tertiary structure of human cathepsin-E". Biochemical and Biophysical Research Communications. 331 (1): 56–60. doi:10.1016/j.bbrc.2005.03.123. PMID 15845357.
  17. Lees WE, Kalinka S, Meech J, Capper SJ, Cook ND, Kay J (October 1990). "Generation of human endothelin by cathepsin E". FEBS Letters. 273 (1–2): 99–102. doi:10.1016/0014-5793(90)81060-2. PMID 2226872.
  18. Tsukuba T, Okamoto K, Yasuda Y, Morikawa W, Nakanishi H, Yamamoto K (December 2000). "New functional aspects of cathepsin D and cathepsin E". Molecules and Cells. 10 (6): 601–11. doi:10.1007/s10059-000-0601-8. PMID 11211863. S2CID 20761872.
  19. Chain BM, Free P, Medd P, Swetman C, Tabor AB, Terrazzini N (February 2005). "The expression and function of cathepsin E in dendritic cells". Journal of Immunology. 174 (4): 1791–800. doi:10.4049/jimmunol.174.4.1791. PMID 15699105.
  20. "CTSE - Cathepsin E precursor - Homo sapiens (Human) - CTSE gene & protein". www.uniprot.org. Retrieved 2016-10-16.

Further reading
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