| Literature References | 1. RAWLINGS, N.D. AND BARRETT, A.J.
Families of cysteine peptidases.
METHODS ENZYMOL. 244 461-486 (1994).
2. PICKART, C.M. AND ROSE, I.A.
Mechanism of ubiquitin carboxyl-terminal hydrolase. Borohydride and
hydroxylamine inactivate in the presence of ubiquitin.
J.BIOL.CHEM. 261 10210-10217 (1986).
3. HERSHKO, A. AND ROSE, I.A.
Ubiquitin-aldehyde: a general inhibitor of ubiquitin-recycling processes.
PROC.NATL.ACAD.SCI.U.S.A. 84 1829-1833 (1987).
|
| Documentation | Cysteine protease activity is dependent on an active dyad of cysteine and
histidine, the order and spacing of these residues varying in the 20 or so
known families. Families C1, C2 and C10 are loosely termed papain-like, and
nearly half of all cysteine proteases are found exclusively in viruses [1].
Ubiquitin is highly conserved, commonly found conjugated to proteins in
eukaryotic cells, where it may act as a marker for rapid degradation, or
it may have a chaperone function in protein assembly [1]. The ubiquitin is
released by cleavage from the bound protein by a protease [1]. A number of
deubiquitinising proteases are known: all are activated by thiol compounds
[1,2], and inhibited by thiol-blocking agents and ubiquitin aldehyde [1,3],
and as such have the properties of cysteine proteases [1].
The deubiquitinsing proteases can be split into 2 size ranges (20-30 kDa
and 100-200 kDa) [1]: the yuh1 family of proteases fall into the first group.
Yeast yuh1 protease is known to be active only against small ubiquitin
conjugates, being inactive against conjugated beta-galactosidase [1]. A
mammalian homologue, UCH (ubiquitin conjugate hydrolase), is one of the most
abundant proteins in the brain [1]. Only one conserved cysteine can be
identified, along with two conserved histidines. The spacing between the
cysteine and the second histidine is thought to be more representative of
the cysteine/histidine spacing of a cysteine protease catalytic dyad [1].
UBCTHYDRLASE is a 5-element fingerprint that provides a signature for the
yuh1 family of deubiquitinising proteases (C12). The fingerprint was derived
from an initial alignment of 6 sequences: the motifs were drawn from
conserved regions spanning virtually the full alignment length: motif 3
includes the region encoded by PROSITE pattern PS00140 (UCH_1), which
contains the catalytic Cys and the first of the conserved His residues;
and motif 4 contains the second of the conserved histidines. Two iterations
on OWL29.3 were required to reach convergence, at which point a true set
comprising 7 sequences was identified.
An update on SPTR37_9f identified a true set of 7 sequences, and 5
partial matches.
|