Literature References | 1. KITADA, T., ASAKAWA, S., HATTORI, N., MATSUMINE, H., YAMAMURA, Y.,
MINOSHIMA, S., YOKOCHI, M., MIZUNO, Y. AND SHIMIZU, N.
Mutations in the parkin gene cause autosomal recessive juvenile
parkinsonism.
NATURE 392 605-608 (1998).
2. ZHANG, Y., GAO, J., CHUNG, K.K.K., HUANG, H., DAWSON, V.L. AND
DAWSON, T.M.
Parkin functions as an E2-dependent ubiquitin-protein ligase and promotes
the degradation of the synaptic vesicle-associated protein.
PROC.NATL.ACAD.SCI.U.S.A. 97 13354-13359 (2000).
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Documentation | Parkinson's disease (PD) is a common neurodegenerative disorder with complex
clinical features and a poorly understood aetiology. PD is accompanied by a
progressive loss of dopamine-containing neurons in the substantia nigra,
with patients suffering from rigidity, slowness of movement, tremour and
disturbances of balance. Autosomal recessive juvenile parkinsonism (AR-JP)
is a rare form of familial PD mapped to chromosome 6 and linked strongly to
a pair of markers. One of these markers has been cloned, yielding a sequence
that encodes a protein, 465 amino acids long [1]. The protein sequence,
named parkin, shows moderate similarity with ubiquitin at the N-terminus and
a ring-finger domain at the C-terminus.
In normal individuals, parkin binds to the E2 ubiquitin-conjugating human
enzyme 8 (UbcH8) through the C-terminal ring-finger domain. In the presence
of UbcH8, parkin has ubiquitin-protein ligase activity and even catalyses
its own ubiquitination. Furthermore, parkin appears to target the synaptic
vesicle-associated protein CDCrel-1 for ubiquitination and thus promotes its
degradation. The mutated forms of parkin implicated in AR-JP appear to be
defective in terms of UbcH8 binding, E3 ubiquitin protein-ligase activity,
self-ubiquitination, and CDCrel-1 binding and ubiquitination [2].
PARKIN is a 9-element fingerprint that provides a signature for parkin and
parkin-like proteins. The fingerprint was derived from an initial alignment
of 6 sequences: the motifs were drawn from conserved regions spanning
virtually the full alignment length, but largely avoiding the N- and
C-terminal ubiquitin-like and ring-finger domains respectively. A single
iteration on SPTR39_15f was required to reach convergence, no further
sequences being identified beyond the starting set.
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