Abstract
We applied cDNA selection methods to a genomic clone (YAC 761B5) from chromosome 21 located in the so‐called ‘Down critical region’ in 21q22.3. Starting from human fetal heart and brain mRNAs we obtained and sequenced several cDNA clones. One of these clones (Down region aspartic protease (DRAP), named also BACE2 according to the gene nomenclature) revealed a striking nucleotide and amino acid sequence identity with several motifs present in members of the aspartic protease family. In particular the amino acid sequences comprising the two catalytic sites found in all mammalian aspartic proteases are perfectly conserved. Interestingly, the predicted protein shows a typical membrane spanning region; this is at variance with most other known aspartic proteases, which are soluble molecules. We present preliminary evidence, on the basis of in vitro translation studies and cell transfection, that this gene encodes a glycosylated protein which localizes mainly intracellularly but to some extent also to the plasma membrane. Furthermore DRAP/BACE2 shares a high homology with a newly described β‐secretase enzyme (BACE‐1) which is a transmembrane aspartic protease. The implications of this finding for Down syndrome are discussed.
References
34
Referenced
94
10.1016/0076-6879(95)48009-9
10.1080/00365519209104650
10.1002/jcb.240330106
-
Dunn (1991) Structure and function of the aspartic proteases: genetics structure and mechanisms pp. 1–296 Plenum Press New York.
(
10.1007/978-1-4684-6012-4
) 10.1126/science.2493678
10.1016/0022-2836(90)90153-D
10.1002/prot.340080110
10.1016/S0021-9258(18)99785-1
10.1016/S0021-9258(19)45463-X
10.1126/science.286.5440.735
10.1093/nar/20.19.5173
- Monaco A. Larin Z. and Lehrach H. (1992) Pulsed Field Gel Electrophoresis Methods in Molecular Biology vol 12. pp. 225–234 The Humana Press Totowa NJ.
10.1093/nar/12.18.7035
10.1016/S0091-679X(08)61038-9
-
Matthews G.M. and Colman A. (1995) in: Methods in Molecular Biology Vol 37: In Vitro Transcription and Translation Protocols (Tymms M.J. Ed.) The Xenopus egg extract translation system pp 199–213 Humana Press Totowa NJ.
(
10.1385/0-89603-288-4:199
) 10.1093/nar/22.22.4673
{'key': 'e_1_2_6_18_1', 'first-page': '543', 'volume': '12', 'author': 'Galtier N.', 'year': '1996', 'journal-title': 'Comp. Appl. Biosci.'}
/ Comp. Appl. Biosci. by Galtier N. (1996)10.1002/(SICI)1097-0134(199703)27:3<329::AID-PROT1>3.0.CO;2-8
10.1002/prot.340190108
10.1006/jmbi.1997.1019
10.1002/pro.5560050516
- Rost B. (1995) TOPITS: threading one-dimensional predictions into three-dimensional structures (Rawlings C. Clark D. Altman R. Hunter L. Lengauer T. and Wodak S. Eds.) The third international conference on Intelligent Systems for Molecular Biology (ISMB) pp. 314–321 AIAA Press New York.
{'key': 'e_1_2_6_24_1', 'first-page': '166', 'volume': '374', 'author': 'Hoffmann K.', 'year': '1993', 'journal-title': 'Biol. Chem. Hoppe-Seyler'}
/ Biol. Chem. Hoppe-Seyler by Hoffmann K. (1993)10.1016/0955-0674(92)90075-N
10.1016/0968-0004(90)90047-F
- Epstein C. (1997) in: The Metabolic and Molecular Bases of Inherited Diseases (Sciver Cbeaudet A. Sly W. Valle D. Stanbury J. Wyngaarden J. Fredrickson D. Eds.) Down syndrome (trisomy 21) vol I pp. 749–794 McGraw-Hill New York.
10.1016/S0962-8924(98)01363-4
{'key': 'e_1_2_6_29_1', 'first-page': '22908', 'volume': '271', 'author': 'Ida N.', 'year': '1996', 'journal-title': 'Proc. Natl. Acad. Sci. USA'}
/ Proc. Natl. Acad. Sci. USA by Ida N. (1996)10.1016/0896-6273(95)90301-1
10.1016/S0021-9258(19)78080-6
10.1016/S0021-9258(20)30050-8
10.1016/S0014-5793(97)00564-4
10.1126/science.286.5443.1255a
{'key': 'e_1_2_6_35_1', 'first-page': '1256', 'volume': '286', 'author': 'Louis J.C.', 'year': '1999', 'journal-title': 'Science'}
/ Science by Louis J.C. (1999)
Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 25, 2002, 1:52 p.m.) |
Deposited | 1 year, 11 months ago (Sept. 16, 2023, 4:41 p.m.) |
Indexed | 2 days, 12 hours ago (Sept. 3, 2025, 6:56 a.m.) |
Issued | 25 years, 6 months ago (Feb. 14, 2000) |
Published | 25 years, 6 months ago (Feb. 14, 2000) |
Published Online | 25 years, 6 months ago (Feb. 14, 2000) |
Published Print | 25 years, 6 months ago (Feb. 18, 2000) |
@article{Acquati_2000, title={The gene encoding DRAP (BACE2), a glycosylated transmembrane protein of the aspartic protease family, maps to the Down critical region}, volume={468}, ISSN={1873-3468}, url={http://dx.doi.org/10.1016/s0014-5793(00)01192-3}, DOI={10.1016/s0014-5793(00)01192-3}, number={1}, journal={FEBS Letters}, publisher={Wiley}, author={Acquati, F. and Accarino, M. and Nucci, C. and Fumagalli, P. and Jovine, L. and Ottolenghi, S. and Taramelli, R.}, year={2000}, month=feb, pages={59–64} }