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PR01211

Identifier
SYNUCLEIN  [View Relations]  [View Alignment]  
Accession
PR01211
No. of Motifs
5
Creation Date
02-OCT-1999
Title
Synuclein signature 
Database References
PRINTS; PR01212 ASYNUCLEIN; PR01213 BSYNUCLEIN; PR01214 GSYNUCLEIN

PFAM; PF01387 Synuclein
INTERPRO; IPR001058
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]. 
 
The synuclein gene family recently hit the headlines when one of its 
members, alpha-synuclein, was found to be mutated in several families with 
autosomal dominant Parkinson's disease (PD) [1]. A peptide of the alpha-
synuclein protein had been characterised previously 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]. Another
member of the gene family, gamma-synuclein, has been shown to be over-
expressed in breast carcinomas and may also be overexpressed in ovarian
cancer [1].
 
SYNUCLEIN is a 5-element fingerprint that provides a signature for
synucleins. The fingerprint was derived from an initial alignment of 8
sequences: the motifs were drawn from short conserved regions spanning
virtually the full alignment length - motif 1 lies at the N-terminus;
motif 2 includes the first EKT repeat; motif 3 encodes the second and 
third repeats; motif 4 spans the final repeat, leading into the hydrophobic
domain; and motif 5 spans the C-terminus of the hydrophobic domain, leading 
into the Glu-Pro-rich C-terminal domain. Two iterations on SPTR37_10f were
required to reach convergence, at which point a true set comprising 12
sequences was identified.
Summary Information
12 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
51212121212
400000
300000
200000
12345
True Positives
Q9Z0F7        SYU1_RAT      SYU2_RAT      SYUA_HUMAN    
SYUA_MOUSE SYUA_POEGU SYUB_BOVIN SYUB_HUMAN
SYUB_RAT SYUG_HUMAN SYUG_RAT SYU_TORCA
Sequence Titles
Q9Z0F7      PERSYN - MUS MUSCULUS (MOUSE).                
SYU1_RAT ALPHA-SYNUCLEIN, FORMS 1 AND 3 - RATTUS NORVEGICUS (RAT).
SYU2_RAT ALPHA-SYNUCLEIN, FORM 2 - 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
SYUB_BOVIN BETA-SYNUCLEIN (PHOSPHONEUROPROTEIN 14) (PNP 14) (14 KD BRAIN- SPECIFIC PROTEIN)
SYUB_HUMAN BETA-SYNUCLEIN - HOMO SAPIENS (HUMAN).
SYUB_RAT BETA-SYNUCLEIN (PHOSPHONEUROPROTEIN 14) (PNP 14) - RATTUS NORVEGICUS (RAT).
SYUG_HUMAN GAMMA-SYNUCLEIN (PERSYN) (BREAST CANCER-SPECIFIC GENE 1 PROTEIN) - HOMO SAPIENS
SYUG_RAT GAMMA-SYNUCLEIN (SENSORY NEURON SYNUCLEIN) - RATTUS NORVEGICUS (RAT).
SYU_TORCA SYNUCLEIN - TORPEDO CALIFORNICA (PACIFIC ELECTRIC RAY).
Scan History
SPTR37_10f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
DVFMKGLSKAKEG SYU1_RAT 2 2 -
DVFMKGLSKAKEG SYU2_RAT 2 2 -
DVFMKGLSKAKEG SYUA_POEGU 2 2 -
DVFMKGLSKAKEG SYUA_HUMAN 2 2 -
DVFMKGLSMAKEG SYUB_BOVIN 2 2 -
DVFMKGLSMAKEG SYUB_RAT 2 2 -
DVFMKGLSMAKEG SYUB_HUMAN 2 2 -
DVLKKGFSFAKEG SYU_TORCA 2 2 -

Motif 2 width=15
Element Seqn Id St Int Rpt
GVVAAAEKTKQGVAE SYU1_RAT 14 -1 -
GVVAAAEKTKQGVAE SYU2_RAT 14 -1 -
GVVAAAEKTKQGVAE SYUA_POEGU 14 -1 -
GVVAAAEKTKQGVAE SYUA_HUMAN 14 -1 -
GVVAAAEKTKQGVTE SYUB_BOVIN 14 -1 -
GVVAAAEKTKQGVTE SYUB_RAT 14 -1 -
GVVAAAEKTKQGVTE SYUB_HUMAN 14 -1 -
GVVAAAEKTKQGVQD SYU_TORCA 14 -1 -

Motif 3 width=20
Element Seqn Id St Int Rpt
AAGKTKEGVLYVGSKTKEGV SYU1_RAT 29 0 -
AAGKTKEGVLYVGSKTKEGV SYU2_RAT 29 0 -
AAGKTKEGVLYVGSRTKEGV SYUA_POEGU 29 0 -
AAGKTKEGVLYVGSKTKEGV SYUA_HUMAN 29 0 -
AAEKTKEGVLYVGSKTKEGV SYUB_BOVIN 29 0 -
AAEKTKEGVLYVGSKTKEGV SYUB_RAT 29 0 -
AAEKTKEGVLYVGSKTREGV SYUB_HUMAN 29 0 -
AAEKTKEGVMYVGTKTKEGV SYU_TORCA 40 11 -

Motif 4 width=24
Element Seqn Id St Int Rpt
VHGVTTVAEKTKEQVTNVGGAVVT SYU1_RAT 49 0 -
VHGVTTVAEKTKEQVTNVGGAVVT SYU2_RAT 49 0 -
VHGVTTVAEKTKEQVSNVGGAVVT SYUA_POEGU 49 0 -
VHGVATVAEKTKEQVTNVGGAVVT SYUA_HUMAN 49 0 -
VQGVASVAEKTKEQASHLGGAVFS SYUB_BOVIN 49 0 -
VQGVASVAEKTKEQASHLGGAVFS SYUB_RAT 49 0 -
VQGVASVAEKTKEQASHLGGAVFS SYUB_HUMAN 49 0 -
VQSVNTVTEKTKEQANVVGGAVVA SYU_TORCA 60 0 -

Motif 5 width=16
Element Seqn Id St Int Rpt
GAGNIAAATGFVKKDQ SYU1_RAT 84 11 -
GAGNIAAATGFVKKDQ SYU2_RAT 84 11 -
GAGNIAAATGLVKKDQ SYUA_POEGU 84 11 -
GAGSIAAATGFVKKDQ SYUA_HUMAN 84 11 -
GAGNIAAATGLVKKEE SYUB_BOVIN 73 0 -
GAGNIAAATGLVKKEE SYUB_RAT 73 0 -
GAGNIAAATGLVKREE SYUB_HUMAN 73 0 -
GVENVAAASGVVKLDE SYU_TORCA 95 11 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
DVFMKGLSKAKEG SYU1_RAT 2 2 -
DVFMKGLSKAKEG SYU2_RAT 2 2 -
DVFMKGLSKAKEG SYUA_MOUSE 2 2 -
DVFMKGLSKAKEG SYUA_POEGU 2 2 -
DVFMKGLSKAKEG SYUA_HUMAN 2 2 -
DVFMKGLSMAKEG SYUB_BOVIN 2 2 -
DVFMKGLSMAKEG SYUB_RAT 2 2 -
DVFMKGLSMAKEG SYUB_HUMAN 2 2 -
DVLKKGFSFAKEG SYU_TORCA 2 2 -
DVFKKGFSIAKEG SYUG_HUMAN 2 2 -
DVFKKGFSIAKEG Q9Z0F7 2 2 -
DVFKKGFSIAREG SYUG_RAT 2 2 -

Motif 2 width=15
Element Seqn Id St Int Rpt
GVVAAAEKTKQGVAE SYU1_RAT 14 -1 -
GVVAAAEKTKQGVAE SYU2_RAT 14 -1 -
GVVAAAEKTKQGVAE SYUA_MOUSE 14 -1 -
GVVAAAEKTKQGVAE SYUA_POEGU 14 -1 -
GVVAAAEKTKQGVAE SYUA_HUMAN 14 -1 -
GVVAAAEKTKQGVTE SYUB_BOVIN 14 -1 -
GVVAAAEKTKQGVTE SYUB_RAT 14 -1 -
GVVAAAEKTKQGVTE SYUB_HUMAN 14 -1 -
GVVAAAEKTKQGVQD SYU_TORCA 14 -1 -
GVVGAVEKTKQGVTE SYUG_HUMAN 14 -1 -
GVVGAVEKTKQGVTE Q9Z0F7 14 -1 -
GVVGAVEKTTQGVTE SYUG_RAT 14 -1 -

Motif 3 width=20
Element Seqn Id St Int Rpt
AAGKTKEGVLYVGSKTKEGV SYU1_RAT 29 0 -
AAGKTKEGVLYVGSKTKEGV SYU2_RAT 29 0 -
AAGKTKEGVLYVGSKTKEGV SYUA_MOUSE 29 0 -
AAGKTKEGVLYVGSRTKEGV SYUA_POEGU 29 0 -
AAGKTKEGVLYVGSKTKEGV SYUA_HUMAN 29 0 -
AAEKTKEGVLYVGSKTKEGV SYUB_BOVIN 29 0 -
AAEKTKEGVLYVGSKTKEGV SYUB_RAT 29 0 -
AAEKTKEGVLYVGSKTREGV SYUB_HUMAN 29 0 -
AAEKTKEGVMYVGTKTKEGV SYU_TORCA 40 11 -
AAEKTKEGVMYVGAKTKENV SYUG_HUMAN 29 0 -
AAEKTKEGVMYVGTKTKENV Q9Z0F7 29 0 -
AAEKTKEGVMYVGAKTKGER SYUG_RAT 29 0 -

Motif 4 width=24
Element Seqn Id St Int Rpt
VHGVTTVAEKTKEQVTNVGGAVVT SYU1_RAT 49 0 -
VHGVTTVAEKTKEQVTNVGGAVVT SYU2_RAT 49 0 -
VHGVTTVAETTKEQVTNVGGAVVT SYUA_MOUSE 49 0 -
VHGVTTVAEKTKEQVSNVGGAVVT SYUA_POEGU 49 0 -
VHGVATVAEKTKEQVTNVGGAVVT SYUA_HUMAN 49 0 -
VQGVASVAEKTKEQASHLGGAVFS SYUB_BOVIN 49 0 -
VQGVASVAEKTKEQASHLGGAVFS SYUB_RAT 49 0 -
VQGVASVAEKTKEQASHLGGAVFS SYUB_HUMAN 49 0 -
VQSVNTVTEKTKEQANVVGGAVVA SYU_TORCA 60 0 -
VQSVTSVAEKTKEQANAVSEAVVS SYUG_HUMAN 49 0 -
VQSVTSVAEKTKEQANAVSEAVVS Q9Z0F7 49 0 -
GTSVTSVAEKTKEQANAVSEAVVS SYUG_RAT 49 0 -

Motif 5 width=16
Element Seqn Id St Int Rpt
GAGNIAAATGFVKKDQ SYU1_RAT 84 11 -
GAGNIAAATGFVKKDQ SYU2_RAT 84 11 -
GAGNIAAATGFVKKDQ SYUA_MOUSE 84 11 -
GAGNIAAATGLVKKDQ SYUA_POEGU 84 11 -
GAGSIAAATGFVKKDQ SYUA_HUMAN 84 11 -
GAGNIAAATGLVKKEE SYUB_BOVIN 73 0 -
GAGNIAAATGLVKKEE SYUB_RAT 73 0 -
GAGNIAAATGLVKREE SYUB_HUMAN 73 0 -
GVENVAAASGVVKLDE SYU_TORCA 95 11 -
EAENIAVTSGVVRKED SYUG_HUMAN 84 11 -
EAENIVVTTGVVRKED Q9Z0F7 84 11 -
EAENIVVTTGVVRKED SYUG_RAT 84 11 -