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PR01212

Identifier
ASYNUCLEIN  [View Relations]  [View Alignment]  
Accession
PR01212
No. of Motifs
4
Creation Date
02-OCT-1999
Title
Alpha-synuclein signature
Database References
PRINTS; PR01211 SYNUCLEIN
INTERPRO; IPR002460
Literature References
1. LAVEDAN, C.
The synuclein family.
GENOME RES. 8 871-880 (1998).
 
2. TOBE, T., NAKAJO, S., TANAKA, A., MITOYA, A., OMATA, K., NAKAYA, K.,
TOMITA, M. AND NAKAMURA, Y.
Cloning and characterization of the cDNA encoding a novel brain-specific
14kDa protein.
J.NEUROCHEM. 59 1624-1629 (1992).
 
3. GEORGE, J.M., JIN, H., WOODS, W.S. AND CLAYTON, D.F.
Characterization of a novel protein regulated during the critical period
for song learning in the zebra finch.
NEURON 15 361-372 (1995).

Documentation
Human synuclein has been shown to belong to a gene family [1]. To date, 
three different proteins, termed alpha, beta and gamma, have been 
characterised. The amino acid sequences of synucleins share a similar
overall structure: hydropathy analysis reveals a central hydrophobic domain
of ~30 amino acids, flanked by highly hydrophilic stretches; the N-terminal
flanking region contains four repeating motifs (EKTKEGV); and the C-terminal
domain is rich in glutamic acid and proline [2]
 
Synelfin, a homologue of synuclein, is a soluble presynaptic protein that 
is predicted to form an amphipathic alpha-helical structure typical of the
lipid-binding domain in apolipoproteins [3]. This protein is believed to
serve a novel function critical to the regulation of vertebrate neural
plasticity [3]. 
 
Alpha-synuclein has been found to be mutated in several families with 
autosomal dominant Parkinson's disease (PD) [1]. A peptide of the alpha-
synuclein protein was previously characterised as a major component of 
amyloid plaques in brains of Alzheimer's disease (AD) patients. The 
mechanism by which this presynaptic protein is involved in the two most
common neurodegenerative disorders, AD and PD, remains unclear [1]. 
 
ASYNUCLEIN is a 4-element fingerprint that provides a signature for
alpha-synucleins. The fingerprint was derived from an initial alignment of
3 sequences: the motifs were drawn from short conserved regions spanning
virtually the full alignment length, focusing on those sections that
characterise the alpha-synucleins but distinguish them from the rest of the
synuclein family - motif 1 encodes a short sequence that precedes the final
EKT repeat; motif 2 lies at the C-terminus of the hydrophobic domain; and
motifs 3 and 4 lie in the C-terminal Glu-Pro-rich domain. Two iterations on 
SPTR37_10f were required to reach convergence, at which point a true set
comprising 4 sequences was identified. A single partial match was found,
SYU2_RAT, a form 2 alpha-synuclein that fails to match motifs 3 and 4. 
Summary Information
   4 codes involving  4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
44444
30000
21100
1234
True Positives
SYU1_RAT      SYUA_HUMAN    SYUA_MOUSE    SYUA_POEGU    
True Positive Partials
Codes involving 2 elements
SYU2_RAT
Sequence Titles
SYU1_RAT    ALPHA-SYNUCLEIN, FORMS 1 AND 3 - RATTUS NORVEGICUS (RAT). 
SYUA_HUMAN ALPHA-SYNUCLEIN (NON-A BETA COMPONENT OF AD AMYLOID) (NACP) - HOMO SAPIENS (HUMA
SYUA_MOUSE ALPHA-SYNUCLEIN (NON-A BETA COMPONENT OF AD AMYLOID) (NACP) - MUS MUSCULUS (MOUS
SYUA_POEGU ALPHA-SYNUCLEIN (SYNELFIN) - POEPHILA GUTTATA (ZEBRA FINCH) (TAENIOPYGIA GUTTATA

SYU2_RAT ALPHA-SYNUCLEIN, FORM 2 - RATTUS NORVEGICUS (RAT).
Scan History
SPTR37_10f 1  50   NSINGLE    
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
VTGVTAVAQK SYU1_RAT 71 71 -
VTGVTAVAQK SYUA_HUMAN 71 71 -
VTGVTAVAQK SYUA_POEGU 71 71 -

Motif 2 width=11
Element Seqn Id St Int Rpt
TGFVKKDQMGK SYU1_RAT 92 11 -
TGFVKKDQLGK SYUA_HUMAN 92 11 -
TGLVKKDQLAK SYUA_POEGU 92 11 -

Motif 3 width=15
Element Seqn Id St Int Rpt
GEEGYPQEGILEDMP SYU1_RAT 103 0 -
NEEGAPQEGILEDMP SYUA_HUMAN 103 0 -
NEEGFLQEGMVNNTG SYUA_POEGU 104 1 -

Motif 4 width=16
Element Seqn Id St Int Rpt
VDPSSEAYEMPSEEGY SYU1_RAT 118 0 -
VDPDNEAYEMPSEEGY SYUA_HUMAN 118 0 -
VDPDNEAYEMPPEEEY SYUA_POEGU 121 2 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
VTGVTAVAQK SYU1_RAT 71 71 -
VTGVTAVAQK SYUA_MOUSE 71 71 -
VTGVTAVAQK SYUA_HUMAN 71 71 -
VTGVTAVAQK SYUA_POEGU 71 71 -

Motif 2 width=11
Element Seqn Id St Int Rpt
TGFVKKDQMGK SYU1_RAT 92 11 -
TGFVKKDQMGK SYUA_MOUSE 92 11 -
TGFVKKDQLGK SYUA_HUMAN 92 11 -
TGLVKKDQLAK SYUA_POEGU 92 11 -

Motif 3 width=15
Element Seqn Id St Int Rpt
GEEGYPQEGILEDMP SYU1_RAT 103 0 -
GEEGYPQEGILEDMP SYUA_MOUSE 103 0 -
NEEGAPQEGILEDMP SYUA_HUMAN 103 0 -
NEEGFLQEGMVNNTG SYUA_POEGU 104 1 -

Motif 4 width=16
Element Seqn Id St Int Rpt
VDPSSEAYEMPSEEGY SYU1_RAT 118 0 -
VDPGSEAYEMPSEEGY SYUA_MOUSE 118 0 -
VDPDNEAYEMPSEEGY SYUA_HUMAN 118 0 -
VDPDNEAYEMPPEEEY SYUA_POEGU 121 2 -