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PR01817

Identifier
BACE2  [View Relations]  [View Alignment]  
Accession
PR01817
No. of Motifs
6
Creation Date
18-DEC-2002  (UPDATE 12-APR-2009)
Title
Beta-site APP cleaving enzyme 2 (BACE2) signature
Database References
PRINTS; PR00792 PEPSIN; PR01815 BACEFAMILY
MIM; 605668
Literature References
1. GLENNER, G. AND WONG, C.
Alzheimer's disease: initial report of the purification and characterization
of a novel cerebrovascular amyloid protein.
BIOCHEM.BIOPHYS.RES.COMMUN. 120 885-890 (1984).
 
2. KANG, J., LEMAIRE, H., UNTERBECK, A., SALBAUM, J., MASTERS, C., 
GRZESCHIK, K., MULTHAUP, G., BEYREUTHER, K. AND MULLER-HILL, B.
The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-
surface receptor.
NATURE 325 733-736 (1987).
 
3. VASSAR, R., BENNETT, B., BABU-KAHN, S., KAHN, S., MENDIAZ, E., DENIS, P.,
TEPLOW, D., ROSS, S., AMARANTE, P., LOELOFF, R., LUO, Y., FISHER, S., 
FULLER, J., EDENSON, S., LILE, J., JAROSINSKI, M., BIERE, A., CURRAN, E., 
BURGESS, T., LOUIS, J., COLLINS, F., TREANOR, J., ROGERS, G. AND CITRON, M.
Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the 
transmembrane aspartic protease BACE.
SCIENCE 286 735-741 (1999).
 
4. HUSSAIN, I., POWELL, D., HOWLETT, D., TEW, D., MEEK, T., CHAPMAN, C., 
GLOGER, I., MURPHY, K., SOUTHAN C., RYAN, D., SMITH, T., SIMMONS, D., 
WALSH, F., DINGWALL, C. AND CHRISTIE, G.
Identification of a novel aspartic protease (Asp 2) as beta-secretase.
MOL.CELL.NEUROSCI. 14 419-427 (1999).
 
5. YAN, R., BIENKOWSKI, M., SHUCK, M., MIAO, H., TORY, M., PAULEY, A., 
BRASHIER, J., STRATMAN, N., MATHEWS, W., BUHL, A., CARTER, D.,
TOMASSELLI, A., PARODI, L., HEINRIKSON, R. AND GURNEY, M.
Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase 
activity.
NATURE 402 533-537 (1999).
 
6. CITRON, M.
Beta-secretase as a target for the treatment of Alzheimer's disease.
J.NEUROSCI.RES. 70 373-379 (2002).
 
7. FARZAN, M., SCHNITZLER, C., VASILIEVA, N., LEUNG, D. AND CHOE, H.
BACE2, a beta -secretase homolog, cleaves at the beta site and within the 
amyloid-beta region of the amyloid-beta precursor protein.
PROC.NATL.ACAD.SCI.U.S.A. 97 9712-9717 (2000).
 
8. BENNETT, B., BABU-KHAN, S., LOELOFF, R., LOUIS, J., CURRAN, E.,
CITRON, M. AND VASSAR, R.
Expression analysis of BACE2 in brain and peripheral tissues.
J.BIOL.CHEM. 275 20647-20651 (2000).

Documentation
One of the major neuropathological hallmarks of Alzheimer's disease (AD)
is the progressive formation in the brain of insoluble amyloid plaques and 
vascular deposits consisting of beta-amyloid protein (beta-APP) [1].
Production of beta-APP requires proteolytic cleavage of the large type-1 
transmembrane (TM) protein amyloid precursor protein (APP) [2]. This process
is performed by a variety of enzymes known as secretases. To initiate 
beta-APP formation, beta-secretase cleaves APP to release a soluble 
N-terminal fragment (APPsBeta) and a C-terminal fragment that remains 
membrane bound. This fragment is subsequently cleaved by gamma-secretase 
to liberate beta-APP.
 
Several independent studies identified a novel TM aspartic protease as the
major beta-secretase [3,4,5]. This protein, termed beta-site APP cleaving
enzyme 1 (BACE1), shares 64% amino acid sequence similarity with a second
enzyme, termed BACE2. Together, BACE1 and BACE2 define a novel family of 
aspartyl proteases [6]. Both enzymes share significant sequence similarity
with other members of the pepsin family of aspartyl proteases and contain 
the two characteristic D(T/S)G(T/S) motifs that form the catalytic site.
However, by contrast with other aspartyl proteases, BACE1 and BACE2 are
type I TM proteins. Each protein comprises a large lumenal domain containing
the active centre, a single TM domain and a small cytoplasmic tail.
 
BACE2, also termed Asp1 and memapsin 2, was initially identified though
Expressed Sequence Tag (EST) database searching [5]. In vitro enzymatic
assays with peptide substrates have demonstrated that BACE2 cleaves beta-
secretase substrates in a similar fashion to BACE1 [7]. The BACE2 mRNA is
expressed in the central nervous system and many peripheral tissues,
although its expression level in neurons is substantially lower than that
of BACE1 [8].
 
BACE2 is a 6-element fingerprint that provides a signature for beta-site APP
cleaving enzyme 2 (BACE2). The fingerprint was derived from an initial
alignment of 10 sequences: the motifs were drawn from conserved regions 
spanning virtually the full alignment length, focusing on those sections
that characterise BACE2 but distinguish it from other BACE family members.
Two iterations on SPTR55_38f were required to reach convergence, at which 
point a true set comprising 12 sequences was identified. A single partial
match was also found, a human aspartyl protease that matches motifs 1-3.
Summary Information
  12 codes involving  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
1 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
6121212121212
5000000
4000000
3111000
2000000
123456
True Positives
A8K7P1_HUMAN  BAE2_HUMAN    Q3TNS7_MOUSE  Q6IE75_RAT    
Q6PB20_XENLA Q7T0Y2_XENLA Q8C5E9_MOUSE Q8C793_MOUSE
Q8N2D4_HUMAN Q9H2V8 Q9JL18 Q9NZL2
True Positive Partials
Codes involving 3 elements
Q9NZL1
Sequence Titles
A8K7P1_HUMAN cDNA FLJ77581, highly similar to Homo sapiens beta-site APP-cleaving enzyme 2 (BACE2), transcript variant a, mRNA (Beta-site APP-cleaving enzyme 2, isoform CRA_c) - Homo sapiens (Human). 
BAE2_HUMAN Beta secretase 2 precursor (EC 3.4.23.-) (Beta-site APP-cleaving enzyme 2) (Aspartyl protease 1) (Asp 1) (ASP1) (Membrane-associated aspartic protease 1) (Memapsin-1) - Homo sapiens (Human).
Q3TNS7_MOUSE 0 day neonate eyeball cDNA, RIKEN full-length enriched library, clone:E130311K05 product:beta-site APP-cleaving enzyme 2, full insert sequence - Mus musculus (Mouse).
Q6IE75_RAT Beta-site APP-cleaving enzyme 2 (EC 3.4.23.45) - Rattus norvegicus (Rat).
Q6PB20_XENLA MGC68482 protein - Xenopus laevis (African clawed frog).
Q7T0Y2_XENLA Bace2-prov protein - Xenopus laevis (African clawed frog).
Q8C5E9_MOUSE 15 days embryo male testis cDNA, RIKEN full-length enriched library, clone:8030470O09 product:beta-site APP-cleaving enzyme 2, full insert sequence - Mus musculus (Mouse).
Q8C793_MOUSE 13 days embryo heart cDNA, RIKEN full-length enriched library, clone:D330025D14 product:beta-site APP-cleaving enzyme 2, full insert sequence - Mus musculus (Mouse).
Q8N2D4_HUMAN cDNA PSEC0239 fis, clone OVARC1000363, highly similar to Homo sapiens aspartyl protease mRNA - Homo sapiens (Human).
Q9H2V8 CDA13 - Homo sapiens (Human).
Q9JL18 ASPARTYL PROTEASE 1 - Mus musculus (Mouse).
Q9NZL2 ASPARTYL PROTEASE - Homo sapiens (Human).

Q9NZL1 ASPARTYL PROTEASE - Homo sapiens (Human).
Scan History
SPTR55_38f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
AGAPHSYIDTYFDSESS Q6IE75_RAT 115 115 -
AGAPHSYIDTYFDSESS Q3TNS7_MOUSE 115 115 -
AGAPHSYIDTYFDSESS Q9JL18 115 115 -
AGAPHSYIDTYFDSESS Q8C793_MOUSE 115 115 -
AGAPHSYIDTYFDSESS Q8C5E9_MOUSE 115 115 -
AGTPHSYIDTYFDTERS A8K7P1_HUMAN 119 119 -
AGTPHSYIDTYFDTERS Q9H2V8 40 40 -
AGTPHSYIDTYFDTERS BAE2_HUMAN 119 119 -
AGSPNPDVNTFFDSKLS Q7T0Y2_XENLA 103 103 -
AGSPNPDVKTFYDSKLS Q6PB20_XENLA 102 102 -

Motif 2 width=8
Element Seqn Id St Int Rpt
YQIEILKL Q6IE75_RAT 270 138 -
YQIEILKL Q3TNS7_MOUSE 270 138 -
YQIEILKL Q9JL18 270 138 -
YQIEILKL Q8C793_MOUSE 270 138 -
YQIEILKL Q8C5E9_MOUSE 270 138 -
YQIEILKL A8K7P1_HUMAN 274 138 -
YQIEILKL Q9H2V8 195 138 -
YQIEILKL BAE2_HUMAN 274 138 -
YQVEVLKF Q7T0Y2_XENLA 258 138 -
YQVEVLKF Q6PB20_XENLA 257 138 -

Motif 3 width=13
Element Seqn Id St Int Rpt
EAVARTSLIPEFS Q6IE75_RAT 317 39 -
EAVARTSLIPEFS Q3TNS7_MOUSE 317 39 -
EAVARTSLIPEFS Q9JL18 317 39 -
EAVARTSLIPEFS Q8C793_MOUSE 317 39 -
EAVARTSLIPEFS Q8C5E9_MOUSE 317 39 -
EAVARASLIPEFS A8K7P1_HUMAN 321 39 -
EAVARASLIPEFS Q9H2V8 242 39 -
EAVARASLIPEFS BAE2_HUMAN 321 39 -
DAIVQTSLIQNFN Q7T0Y2_XENLA 305 39 -
DAIVQTSLIQNFN Q6PB20_XENLA 304 39 -

Motif 4 width=13
Element Seqn Id St Int Rpt
AEIAGTTVSEISG Q6IE75_RAT 430 100 -
AEIEGTTVSEISG Q3TNS7_MOUSE 430 100 -
AEIEGTTVSEISG Q9JL18 430 100 -
AEIEGTTVSEISG Q8C793_MOUSE 430 100 -
AEIEGTTVSEISG Q8C5E9_MOUSE 430 100 -
AEIAGAAVSEISG A8K7P1_HUMAN 434 100 -
AEIAGAAVSEISG Q9H2V8 355 100 -
AEIAGAAVSEISG BAE2_HUMAN 434 100 -
AEVSGITVSEIAG Q7T0Y2_XENLA 418 100 -
AEVSGITVSEIAG Q6PB20_XENLA 417 100 -

Motif 5 width=14
Element Seqn Id St Int Rpt
DIASNCVPAQALNE Q6IE75_RAT 448 5 -
DIASNCVPAQALNE Q3TNS7_MOUSE 448 5 -
DIASNCVPAQALNE Q9JL18 448 5 -
DIASNCVPAQALNE Q8C793_MOUSE 448 5 -
DIASNCVPAQALNE Q8C5E9_MOUSE 448 5 -
DVASNCVPAQSLSE A8K7P1_HUMAN 452 5 -
DVASNCVPAQSLSE Q9H2V8 373 5 -
DVASNCVPAQSLSE BAE2_HUMAN 452 5 -
DVSSNCIARNPLRE Q7T0Y2_XENLA 436 5 -
DVSSNCIVRNPLRE Q6PB20_XENLA 435 5 -

Motif 6 width=13
Element Seqn Id St Int Rpt
PILWIVSYALMSV Q6IE75_RAT 462 0 -
PILWIVSYALMSV Q3TNS7_MOUSE 462 0 -
PILWIVSYALMSV Q9JL18 462 0 -
PILWIVSYALMSV Q8C793_MOUSE 462 0 -
PILWIVSYALMSV Q8C5E9_MOUSE 462 0 -
PILWIVSYALMSV A8K7P1_HUMAN 466 0 -
PILWIVSYALMSV Q9H2V8 387 0 -
PILWIVSYALMSV BAE2_HUMAN 466 0 -
PIMWIISYSLMSL Q7T0Y2_XENLA 450 0 -
PIMWIISYSLMSL Q6PB20_XENLA 449 0 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
AGAPHSYIDTYFDSESS Q6IE75_RAT 115 115 -
AGAPHSYIDTYFDSESS Q3TNS7_MOUSE 115 115 -
AGAPHSYIDTYFDSESS Q9JL18 115 115 -
AGAPHSYIDTYFDSESS Q8C793_MOUSE 115 115 -
AGAPHSYIDTYFDSESS Q8C5E9_MOUSE 115 115 -
AGTPHSYIDTYFDTERS A8K7P1_HUMAN 119 119 -
AGTPHSYIDTYFDTERS Q9H2V8 40 40 -
AGTPHSYIDTYFDTERS Q8N2D4_HUMAN 24 24 -
AGTPHSYIDTYFDTERS BAE2_HUMAN 119 119 -
AGTPHSYIDTYFDTERS Q9NZL2 119 119 -
AGSPNPDVNTFFDSKLS Q7T0Y2_XENLA 103 103 -
AGSPNPDVKTFYDSKLS Q6PB20_XENLA 102 102 -

Motif 2 width=8
Element Seqn Id St Int Rpt
YQIEILKL Q6IE75_RAT 270 138 -
YQIEILKL Q3TNS7_MOUSE 270 138 -
YQIEILKL Q9JL18 270 138 -
YQIEILKL Q8C793_MOUSE 270 138 -
YQIEILKL Q8C5E9_MOUSE 270 138 -
YQIEILKL A8K7P1_HUMAN 274 138 -
YQIEILKL Q9H2V8 195 138 -
YQIEILKL Q8N2D4_HUMAN 179 138 -
YQIEILKL BAE2_HUMAN 274 138 -
YQIEILKL Q9NZL2 274 138 -
YQVEVLKF Q7T0Y2_XENLA 258 138 -
YQVEVLKF Q6PB20_XENLA 257 138 -

Motif 3 width=13
Element Seqn Id St Int Rpt
EAVARTSLIPEFS Q6IE75_RAT 317 39 -
EAVARTSLIPEFS Q3TNS7_MOUSE 317 39 -
EAVARTSLIPEFS Q9JL18 317 39 -
EAVARTSLIPEFS Q8C793_MOUSE 317 39 -
EAVARTSLIPEFS Q8C5E9_MOUSE 317 39 -
EAVARASLIPEFS A8K7P1_HUMAN 321 39 -
EAVARASLIPEFS Q9H2V8 242 39 -
EAVARASLIPEFS Q8N2D4_HUMAN 226 39 -
EAVARASLIPEFS BAE2_HUMAN 321 39 -
EAVARASLLYIQP Q9NZL2 321 39 -
DAIVQTSLIQNFN Q7T0Y2_XENLA 305 39 -
DAIVQTSLIQNFN Q6PB20_XENLA 304 39 -

Motif 4 width=13
Element Seqn Id St Int Rpt
AEIAGTTVSEISG Q6IE75_RAT 430 100 -
AEIEGTTVSEISG Q3TNS7_MOUSE 430 100 -
AEIEGTTVSEISG Q9JL18 430 100 -
AEIEGTTVSEISG Q8C793_MOUSE 430 100 -
AEIEGTTVSEISG Q8C5E9_MOUSE 430 100 -
AEIAGAAVSEISG A8K7P1_HUMAN 434 100 -
AEIAGAAVSEISG Q9H2V8 355 100 -
AEIAGAAVSEISG Q8N2D4_HUMAN 339 100 -
AEIAGAAVSEISG BAE2_HUMAN 434 100 -
AEIAGAAVSEISG Q9NZL2 384 50 -
AEVSGITVSEIAG Q7T0Y2_XENLA 418 100 -
AEVSGITVSEIAG Q6PB20_XENLA 417 100 -

Motif 5 width=14
Element Seqn Id St Int Rpt
DIASNCVPAQALNE Q6IE75_RAT 448 5 -
DIASNCVPAQALNE Q3TNS7_MOUSE 448 5 -
DIASNCVPAQALNE Q9JL18 448 5 -
DIASNCVPAQALNE Q8C793_MOUSE 448 5 -
DIASNCVPAQALNE Q8C5E9_MOUSE 448 5 -
DVASNCVPAQSLSE A8K7P1_HUMAN 452 5 -
DVASNCVPAQSLSE Q9H2V8 373 5 -
DVASNCVPAQSLSE Q8N2D4_HUMAN 357 5 -
DVASNCVPAQSLSE BAE2_HUMAN 452 5 -
DVASNCVPAQSLSE Q9NZL2 402 5 -
DVSSNCIARNPLRE Q7T0Y2_XENLA 436 5 -
DVSSNCIVRNPLRE Q6PB20_XENLA 435 5 -

Motif 6 width=13
Element Seqn Id St Int Rpt
PILWIVSYALMSV Q6IE75_RAT 462 0 -
PILWIVSYALMSV Q3TNS7_MOUSE 462 0 -
PILWIVSYALMSV Q9JL18 462 0 -
PILWIVSYALMSV Q8C793_MOUSE 462 0 -
PILWIVSYALMSV Q8C5E9_MOUSE 462 0 -
PILWIVSYALMSV A8K7P1_HUMAN 466 0 -
PILWIVSYALMSV Q9H2V8 387 0 -
PILWIVSYALMSV Q8N2D4_HUMAN 371 0 -
PILWIVSYALMSV BAE2_HUMAN 466 0 -
PILWIVSYALMSV Q9NZL2 416 0 -
PIMWIISYSLMSL Q7T0Y2_XENLA 450 0 -
PIMWIISYSLMSL Q6PB20_XENLA 449 0 -