PMID- 10656250
OWN - NLM
STAT- MEDLINE
DCOM- 20000217
LR  - 20100825
IS  - 1044-7431 (Print)
IS  - 1044-7431 (Linking)
VI  - 14
IP  - 6
DP  - 1999 Dec
TI  - Identification of a novel aspartic protease (Asp 2) as beta-secretase.
PG  - 419-27
AB  - The Alzheimer's disease beta-amyloid peptide (Abeta) is produced by excision from
      the type 1 integral membrane glycoprotein amyloid precursor protein (APP) by the 
      sequential actions of beta- and then gamma-secretases. Here we report that Asp 2,
      a novel transmembrane aspartic protease, has the key activities expected of
      beta-secretase. Transient expression of Asp 2 in cells expressing APP causes an
      increase in the secretion of the N-terminal fragment of APP and an increase in
      the cell-associated C-terminal beta-secretase APP fragment. Mutation of either of
      the putative catalytic aspartyl residues in Asp 2 abrogates the production of the
      fragments characteristic of cleavage at the beta-secretase site. The enzyme is
      present in normal and Alzheimer's disease (AD) brain and is also found in cell
      lines known to produce Abeta. Asp 2 localizes to the Golgi/endoplasmic reticulum 
      in transfected cells and shows clear colocalization with APP in cells stably
      expressing the 751-amino-acid isoform of APP.
FAU - Hussain, I
AU  - Hussain I
AD  - Department of Neurosciences, SmithKline Beecham Pharmaceuticals, Harlow, Essex,
      United Kingdom.
FAU - Powell, D
AU  - Powell D
FAU - Howlett, D R
AU  - Howlett DR
FAU - Tew, D G
AU  - Tew DG
FAU - Meek, T D
AU  - Meek TD
FAU - Chapman, C
AU  - Chapman C
FAU - Gloger, I S
AU  - Gloger IS
FAU - Murphy, K E
AU  - Murphy KE
FAU - Southan, C D
AU  - Southan CD
FAU - Ryan, D M
AU  - Ryan DM
FAU - Smith, T S
AU  - Smith TS
FAU - Simmons, D L
AU  - Simmons DL
FAU - Walsh, F S
AU  - Walsh FS
FAU - Dingwall, C
AU  - Dingwall C
FAU - Christie, G
AU  - Christie G
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.22.2 (Papain)
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
RN  - EC 3.4.23.45 (BACE2 protein, human)
RN  - EC 3.4.23.46 (BACE1 protein, human)
RN  - EC 3.4.23.5 (Cathepsin D)
SB  - IM
MH  - Alzheimer Disease/*enzymology
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Amyloid Precursor Protein Secretases
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Animals
MH  - Aspartic Acid Endopeptidases/chemistry/genetics/*metabolism
MH  - COS Cells
MH  - Cathepsin D/metabolism
MH  - Cell Line
MH  - Cell Membrane/enzymology
MH  - Endopeptidases
MH  - Female
MH  - Hippocampus/*enzymology
MH  - Humans
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Papain/chemistry
MH  - Recombinant Proteins/metabolism
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Transfection
EDAT- 1999/11/24 09:00
MHDA- 2000/02/19 09:00
CRDT- 1999/11/24 09:00
PHST- 1999/11/24 09:00 [pubmed]
PHST- 2000/02/19 09:00 [medline]
PHST- 1999/11/24 09:00 [entrez]
AID - S1044-7431(99)90811-4 [pii]
AID - 10.1006/mcne.1999.0811 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 1999 Dec;14(6):419-27. doi: 10.1006/mcne.1999.0811.