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PR00203

Identifier
AMYLOIDA4  [View Relations]  [View Alignment]  
Accession
PR00203
No. of Motifs
4
Creation Date
14-SEP-1993  (UPDATE 06-JUN-1999)
Title
Amyloid A4 protein precursor signature
Database References
PRINTS; PR00204 BETAAMYLOID
PROSITE; PS00319 A4_EXTRA; PS00320 A4_INTRA; PS00280 BPTI_KUNITZ

BLOCKS; BL00319
INTERPRO; IPR001868
PDB; 1AAP
SCOP; 1AAP
CATH; 1AAP
Literature References
1. HARDY, J.
Framing beta-amyloid.
NATURE GENET.(1) 233-234 (1992).
 
2. ARISPE, N., ROJAS, E. AND POLLARD, H.B.
Alzheimers disease amyloid beta-protein forms calcium channels in bilayer
membranes: blockade by tromethamine and aluminum.
PROC.NATL.ACAD.SCI.U.S.A. 90 567-571 (1993).
 
3. OTVOS, L., SZENDREI, G.I., LEE, V.M.-Y AND MANTSCH, H.H.
Human and rodent Alzheimer beta-amyloid peptides acquire distinct 
conformations in membrane-mimicking solvents.
EUR.J.BIOCHEMISTRY 211 249-257 (1993).

Documentation
Amyloid A4 protein precursor (APP) is an integral, glycosylated membrane
brain protein. APP contains a 40-residue peptide, known as beta-amyloid
protein (beta-APP), which forms the major constituent of the amyloid
deposits that characterise Alzheimers disease and aged Down's Syndrome. The
exact function of APP is unknown, but it may mediate cell-cell inter-
actions. The protein comprises a large extracellular N-terminal domain,
and a short hydrophobic membrane-spanning domain, followed by a short
C-terminal region - the beta amyloid protein both precedes and forms 
part of the transmembrane domain [1-3].
 
AMYLOIDA4 is a 4-element fingerprint that provides a signature for the
amyloid A4 protein precursor. The fingerprint was derived from an initial
alignment of 3 sequences: motif 1 includes the extracellular region encoded
by PROSITE pattern A4_EXTRA (PS00319); motif 3 corresponds to the trans-
membrane domain; and motif 4 includes the cytoplasmic region encoded by
PROSITE pattern A4_INTRA (PS00320). Two iterations on OWL21.1 were required
to reach convergence, at which point a true set comprising 10 sequences was
identified. Six partial matches were also found, most of which are
fragments: YWK2_RAT is a sperm membrane protein known to share a high
degree of similarity with the A4 amyloid protein towards its C-terminus.
 
An update on SPTR37_9f identified a true set of 18 sequences, and 3
partial matches.
Summary Information
  18 codes involving  4 elements
1 codes involving 3 elements
2 codes involving 2 elements
Composite Feature Index
418181818
31101
22101
1234
True Positives
A4_HUMAN      A4_MOUSE      A4_RAT        A4_SAISC      
APP1_HUMAN APP1_MOUSE APP2_HUMAN APP2_MOUSE
APP2_RAT O57394 O73683 O93279
P97487 Q60496 Q60709 Q61482
Q64348 Q91963
True Positive Partials
Codes involving 3 elements
Q10651
Codes involving 2 elements
A4_DROME Q13764
Sequence Titles
A4_HUMAN    ALZHEIMER'S DISEASE AMYLOID A4 PROTEIN PRECURSOR (PROTEASE NEXIN-II) (PN-II) (APPI) [CONTAINS: BETA-AMYLOID PROTEIN (BETA-APP)] - HOMO SAPIENS (HUMAN). 
A4_MOUSE ALZHEIMER'S DISEASE AMYLOID A4 PROTEIN HOMOLOG PRECURSOR (AMYLOIDOGENIC GLYCOPROTEIN) (AG) - MUS MUSCULUS (MOUSE).
A4_RAT ALZHEIMER'S DISEASE AMYLOID A4 PROTEIN HOMOLOG PRECURSOR (AMYLOIDOGENIC GLYCOPROTEIN) (AG) - RATTUS NORVEGICUS (RAT).
A4_SAISC ALZHEIMER'S DISEASE AMYLOID A4 PROTEIN PRECURSOR [CONTAINS: BETA- AMYLOID PROTEIN (BETA-APP)] - SAIMIRI SCIUREUS (COMMON SQUIRREL MONKEY).
APP1_HUMAN AMYLOID-LIKE PROTEIN 1 PRECURSOR (APLP) - HOMO SAPIENS (HUMAN).
APP1_MOUSE AMYLOID-LIKE PROTEIN 1 PRECURSOR (APLP) - MUS MUSCULUS (MOUSE).
APP2_HUMAN AMYLOID-LIKE PROTEIN 2 PRECURSOR (AMYLOID PROTEIN HOMOLOG) (APPH) (CDEI-BOX BINDING PROTEIN) (CDEBP) - HOMO SAPIENS (HUMAN).
APP2_MOUSE AMYLOID-LIKE PROTEIN 2 PRECURSOR (CDEI-BOX BINDING PROTEIN) (CDEBP) - MUS MUSCULUS (MOUSE).
APP2_RAT AMYLOID-LIKE PROTEIN 2 PRECURSOR (SPERM MEMBRANE PROTEIN YWK-II) - RATTUS NORVEGICUS (RAT).
O57394 EL AMYLOID PRECURSOR PROTEIN 699 - NARKE JAPONICA (ELECTRIC RAY).
O73683 AMYLOID PRECURSOR PROTEIN - TETRAODON FLUVIATILIS (PUFFER FISH).
O93279 BETA-AMYLOID PRECURSOR PROTEIN - FUGU RUBRIPES (JAPANESE PUFFERFISH) (TAKIFUGU RUBRIPES).
P97487 HIPPOCAMPAL AMYLOID PROTEIN - MUS MUSCULUS (MOUSE).
Q60496 ALZHEIMER'S DISEASE AMYLOID A4 PROTEIN - CAVIA PORCELLUS (GUINEA PIG).
Q60709 AMYLOID BETA (A4) PRECURSOR-LIKE PROTEIN 2 (AMYLOID-LIKE PROTEIN 2, ISOFORM 751) - MUS MUSCULUS (MOUSE).
Q61482 CDE1-BINDING PROTEIN - MUS MUSCULUS (MOUSE).
Q64348 AMYLOID BETA (A4) PRECURSOR-LIKE PROTEIN 2 (HYPOTHETICAL 79.0 KD PROTEIN) - MUS MUSCULUS (MOUSE).
Q91963 APP747 - XENOPUS LAEVIS (AFRICAN CLAWED FROG).

Q10651 BETA-AMYLOID-LIKE PROTEIN PRECURSOR - CAENORHABDITIS ELEGANS.

A4_DROME BETA-AMYLOID-LIKE PROTEIN PRECURSOR - DROSOPHILA MELANOGASTER (FRUIT FLY).
Q13764 AMYLOID-BETA PROTEIN - HOMO SAPIENS (HUMAN).
Scan History
OWL21_1    2  50   NSINGLE    
OWL25_2 1 50 NSINGLE
SPTR37_9f 2 190 NSINGLE
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
DKFRGVEFVCCPLAEESDS A4_MOUSE 176 176 -
DKFRGVEFVCCPLAEESDS A4_RAT 176 176 -
DKFRGVEFVCCPLAEESDN A4_HUMAN 176 176 -

Motif 2 width=24
Element Seqn Id St Int Rpt
PGDENEHAHFQKAKERLEAKHRER A4_MOUSE 381 186 -
PGDENEHAHFQKAKERLEAKHRER A4_RAT 381 186 -
PGDENEHAHFQKAKERLEAKHRER A4_HUMAN 381 186 -

Motif 3 width=26
Element Seqn Id St Int Rpt
KGAIIGLMVGGVVIATVIVITLVMLK A4_MOUSE 698 293 -
KGAIIGLMVGGVVIATVIVITLVMLK A4_RAT 698 293 -
KGAIIGLMVGGVVIATVIVITLVMLK A4_HUMAN 698 293 -

Motif 4 width=23
Element Seqn Id St Int Rpt
EERHLSKMQQNGYENPTYKFFEQ A4_MOUSE 744 20 -
EERHLSKMQQNGYENPTYKFFEQ A4_RAT 744 20 -
EERHLSKMQQNGYENPTYKFFEQ A4_HUMAN 744 20 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
DKFRGVEFVCCPLAEESDS A4_MOUSE 176 176 -
DKFRGVEFVCCPLAEESDS P97487 177 177 -
DKFRGVEFVCCPLAEESDS A4_RAT 176 176 -
DKFRGVEFVCCPLAEESDN A4_HUMAN 176 176 -
DKFRGVEFVCCPLAEESDN Q60496 177 177 -
DKFRGVEFVCCPLAEESDH A4_SAISC 177 177 -
DEFRGVEFVCCPIPEENDK O57394 189 189 -
DRFRGVEFVCCPAEAERDM O73683 178 178 -
DKFRGVEFVCCPSAEESES Q91963 173 173 -
DQFHGTEYVCCPQTKTVDS APP2_MOUSE 193 193 -
DQFHGTEYVCCPQTKTVDS Q64348 193 193 -
DQFHGTEYVCCPQTKTVDS Q61482 193 193 -
DQFHGTEYVCCPQTKTVDS Q60709 193 193 -
DQFHGTEYVCCPQTKVVDS APP2_RAT 193 193 -
DQFHGTEYVCCPQTKIIGS APP2_HUMAN 193 193 -
DRFRGVKFVCCPAETEQET O93279 178 178 -
DRFRGVEYVCCPPPATPNP APP1_MOUSE 199 199 -
DRFRGVEYVCCPPPGTPDP APP1_HUMAN 200 200 -

Motif 2 width=24
Element Seqn Id St Int Rpt
PGDENEHAHFQKAKERLEAKHRER A4_MOUSE 381 186 -
PGDENEHAHFQKAKERLEAKHRER P97487 307 111 -
PGDENEHAHFQKAKERLEAKHRER A4_RAT 381 186 -
PGDENEHAHFQKAKERLEAKHRER A4_HUMAN 381 186 -
PGDENEHAHFQKAKERLEAKHRER Q60496 307 111 -
PGDENEHAHFQKAKERLEAKHRER A4_SAISC 363 167 -
PGDENEHAYFQKAKERLEAKHRER O57394 311 103 -
PADENEHAHFQKAKESLEAKHRER O73683 400 203 -
PNDENEHDRFLKAKERLEGKHREK Q91963 359 167 -
SADDNEHARFQKAKEQLEIRHRNR APP2_MOUSE 325 113 -
SADDNEHARFQKAKEQLEIRHRNR Q64348 325 113 -
SADDNEHARFQKAKEQLEIRHRNR Q61482 381 169 -
SADDNEHARFQKAKEQLEIRHRNR Q60709 381 169 -
SADDNEHARFQKAKEQLEIRHRSR APP2_RAT 383 171 -
SADDNEHARFQKAKEQLEIRHRNR APP2_HUMAN 381 169 -
PGDDNEHADFRKAKESLEAKHRER O93279 362 165 -
PGEIGEHEGFLRAKMDLEERRMRQ APP1_MOUSE 304 86 -
PGEISEHEGFLRAKMDLEERRMRQ APP1_HUMAN 301 82 -

Motif 3 width=26
Element Seqn Id St Int Rpt
KGAIIGLMVGGVVIATVIVITLVMLK A4_MOUSE 698 293 -
KGAIIGLMVGGVVIATVIVITLVMLK P97487 624 293 -
KGAIIGLMVGGVVIATVIVITLVMLK A4_RAT 698 293 -
KGAIIGLMVGGVVIATVIVITLVMLK A4_HUMAN 698 293 -
KGAIIGLMVGGVVIATVIVITLVMLK Q60496 624 293 -
KGAIIGLMVGGVVIATVIVITLVMLK A4_SAISC 680 293 -
KGAIIGLMVGGVVIATVIVITLVMLK O57394 628 293 -
KGAIIGLMVGGVVIATVIVITLVMLR O73683 709 285 -
KGAIIGLMVGGVVIATVIVITLVMLK Q91963 676 293 -
SNALIGLLVIAVAIATVIVISLVMLR APP2_MOUSE 624 275 -
SNALIGLLVIAVAIATVIVISLVMLR Q64348 624 275 -
SNALIGLLVIAVAIATVIVISLVMLR Q61482 692 287 -
SNALIGLLVIAVAIATVIVISLVMLR Q60709 680 275 -
SSALIGLLVIAVAIATVIVISLVMLR APP2_RAT 694 287 -
SSALIGLLVIAVAIATVIVISLVMLR APP2_HUMAN 692 287 -
KGAIIGLMVGGVVIATVIVITLVMLR O93279 666 280 -
REALSGLLIMGAGGGSLIVLSLLLLR APP1_MOUSE 582 254 -
REAVSGLLIMGAGGGSLIVLSMLLLR APP1_HUMAN 579 254 -

Motif 4 width=23
Element Seqn Id St Int Rpt
EERHLSKMQQNGYENPTYKFFEQ A4_MOUSE 744 20 -
EERHLSKMQQNGYENPTYKFFEQ P97487 670 20 -
EERHLSKMQQNGYENPTYKFFEQ A4_RAT 744 20 -
EERHLSKMQQNGYENPTYKFFEQ A4_HUMAN 744 20 -
EERHLSKMQQNGYENPTYKFFEQ Q60496 670 20 -
EERHLSKMQQNGYENPTYKFFEQ A4_SAISC 726 20 -
EERHLSKMQQNGYENPTYKFFEQ O57394 674 20 -
EERHLSKMQQNGYENPTYKFFEQ O73683 755 20 -
EERHLTKMQQNGYENPTYKFFEQ Q91963 722 20 -
EERHLNKMQNHGYENPTYKYLEQ APP2_MOUSE 670 20 -
EERHLNKMQNHGYENPTYKYLEQ Q64348 670 20 -
EERHLNKMQNHGYENPTYKYLEQ Q61482 738 20 -
EERHLNKMQNHGYENPTYKYLEQ Q60709 726 20 -
EERHLNKMQNHGYENPTYKYLEQ APP2_RAT 740 20 -
EERHLNKMQNHGYENPTYKYLEQ APP2_HUMAN 738 20 -
EERHLARMQQNGYENPTYKFFEQ O93279 712 20 -
EEQQLRELQRHGYENPTYRFLEE APP1_MOUSE 629 21 -
EEQQLRELQRHGYENPTYRFLEE APP1_HUMAN 626 21 -