| 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.
|