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PR00707

Identifier
UBCTHYDRLASE  [View Relations]  [View Alignment]  
Accession
PR00707
No. of Motifs
5
Creation Date
24-MAY-1997  (UPDATE 04-JUL-1999)
Title
Ubiquitin C-terminal hydrolase (C12) family signature
Database References

PROSITE; PS00140 UCH_1
BLOCKS; BL00140
INTERPRO; IPR001578
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.
Summary Information
   7 codes involving  5 elements
0 codes involving 4 elements
1 codes involving 3 elements
4 codes involving 2 elements
Composite Feature Index
577777
400000
311100
200314
12345
True Positives
UBL1_HUMAN    UBL1_RAT      UBL1_YEAST    UBL3_HUMAN    
UBLH_SCHPO UBL_APLCA UBL_DROME
True Positive Partials
Codes involving 3 elements
O23592
Codes involving 2 elements
O04482 Q23071 Q92560 YP87_CAEEL
Sequence Titles
UBL1_HUMAN  UBIQUITIN CARBOXYL-TERMINAL HYDROLASE ISOZYME L1 (EC 3.1.2.15) (UCH- L1) (UBIQUITIN THIOLESTERASE L1) (NEURON CYTOPLASMIC PROTEIN 9.5) (PGP 9.5) - HOMO SAPIENS (HUMAN). 
UBL1_RAT UBIQUITIN CARBOXYL-TERMINAL HYDROLASE ISOZYME L1 (EC 3.1.2.15) (UCH- L1) (UBIQUITIN THIOLESTERASE L1) - RATTUS NORVEGICUS (RAT).
UBL1_YEAST UBIQUITIN CARBOXYL-TERMINAL HYDROLASE YUH1 (EC 3.1.2.15) (UBIQUITIN THIOLESTERASE) - SACCHAROMYCES CEREVISIAE (BAKER'S YEAST).
UBL3_HUMAN UBIQUITIN CARBOXYL-TERMINAL HYDROLASE ISOZYME L3 (EC 3.1.2.15) (UCH- L3) (UBIQUITIN THIOLESTERASE L3) - HOMO SAPIENS (HUMAN).
UBLH_SCHPO PUTATIVE UBIQUITIN CARBOXYL-TERMINAL HYDROLASE C27F1.03C (EC 3.1.2.15) - SCHIZOSACCHAROMYCES POMBE (FISSION YEAST).
UBL_APLCA UBIQUITIN CARBOXYL-TERMINAL HYDROLASE (EC 3.1.2.15) (UBIQUITIN THIOLESTERASE) - APLYSIA CALIFORNICA (CALIFORNIA SEA HARE).
UBL_DROME UBIQUITIN CARBOXYL-TERMINAL HYDROLASE (EC 3.1.2.15) (UBIQUITIN THIOLESTERASE) - DROSOPHILA MELANOGASTER (FRUIT FLY).

O23592 CARBOXYL-TERMINAL PROTEINASE HOMOLOG - ARABIDOPSIS THALIANA (MOUSE-EAR CRESS).

O04482 ESTS GB|T45673 - ARABIDOPSIS THALIANA (MOUSE-EAR CRESS).
Q23071 SIMILARITY TO FAMILY 1 OF UBIQUITIN CARBOXYL-TERMINAL HYDROLASES - CAENORHABDITIS ELEGANS.
Q92560 BRCA1 ASSOCIATED PROTEIN 1 (MYELOBLAST KIAA0272) - HOMO SAPIENS (HUMAN).
YP87_CAEEL HYPOTHETICAL 37.7 KD PROTEIN C08B11.7 IN CHROMOSOME II - CAENORHABDITIS ELEGANS.
Scan History
OWL29_3    2  100  NSINGLE    
SPTR37_9f 2 200 NSINGLE
Initial Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
PLEANPEVTNQFLKQLGL UBL3_HUMAN 8 8 -
PMEINPEMLNKVLAKLGV UBL1_RAT 5 5 -
PMEINPEMLNKVLSRLGV UBL1_HUMAN 5 5 -
PLESNPEVLTKYIHKLAV UBL_DROME 6 6 -
PLENTPEVLEPYLQKIGV UBLH_SCHPO 4 4 -
PIESNPEVFTNFAHKLGL UBL1_YEAST 10 10 -

Motif 2 width=13
Element Seqn Id St Int Rpt
VPRPVCAVLLLFP UBL3_HUMAN 45 19 -
VPSPACALLLLFP UBL1_RAT 42 19 -
VPAPACALLLLFP UBL1_HUMAN 42 19 -
IPRPVKAFILLFP UBL_DROME 43 19 -
IPRPVHALLFVFP UBLH_SCHPO 39 17 -
LPRPVKAIVLLFP UBL1_YEAST 48 20 -

Motif 3 width=18
Element Seqn Id St Int Rpt
QTISNACGTIGLIHAIAN UBL3_HUMAN 89 31 -
QTIGNSCGTIGLMHAVAN UBL1_RAT 84 29 -
QTIGNSCGTIGLIHAVAN UBL1_HUMAN 84 29 -
QFTHNACGTVALIHSVAN UBL_DROME 87 31 -
QTIPNACGTIGLLHAVSN UBLH_SCHPO 77 25 -
QSVKNACGLYAILHSLSN UBL1_YEAST 84 23 -

Motif 4 width=12
Element Seqn Id St Int Rpt
EKVDLHFIALVH UBL3_HUMAN 164 57 -
DKVNFHFILFNN UBL1_RAT 156 54 -
DKVNFHFILFNN UBL1_HUMAN 156 54 -
EKVIHHFIALVN UBL_DROME 159 54 -
VETDLHFICFVK UBLH_SCHPO 153 58 -
ADTNLHYITYVE UBL1_YEAST 161 59 -

Motif 5 width=11
Element Seqn Id St Int Rpt
LYELDGRKPFP UBL3_HUMAN 180 4 -
LYELDGRMPFP UBL1_RAT 172 4 -
LYELDGRMPFP UBL1_HUMAN 172 4 -
LYELDGRKSFP UBL_DROME 175 4 -
FYELDGRQEGP UBLH_SCHPO 173 8 -
IFELDGRNLSG UBL1_YEAST 177 4 -
Final Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
PLEANPEVTNQFLKQLGL UBL3_HUMAN 8 8 -
PMEINPEMLNKVLAKLGV UBL1_RAT 5 5 -
PMEINPEMLNKVLSRLGV UBL1_HUMAN 5 5 -
PLESNPEVLTKYIHKLAV UBL_DROME 6 6 -
PLESNPKVLNKYVHNLGM UBL_APLCA 9 9 -
PLENTPEVLEPYLQKIGV UBLH_SCHPO 4 4 -
PIESNPEVFTNFAHKLGL UBL1_YEAST 10 10 -

Motif 2 width=13
Element Seqn Id St Int Rpt
VPRPVCAVLLLFP UBL3_HUMAN 45 19 -
VPSPACALLLLFP UBL1_RAT 42 19 -
VPAPACALLLLFP UBL1_HUMAN 42 19 -
IPRPVKAFILLFP UBL_DROME 43 19 -
VPRPAAALVLLFP UBL_APLCA 46 19 -
IPRPVHALLFVFP UBLH_SCHPO 39 17 -
LPRPVKAIVLLFP UBL1_YEAST 48 20 -

Motif 3 width=18
Element Seqn Id St Int Rpt
QTISNACGTIGLIHAIAN UBL3_HUMAN 89 31 -
QTIGNSCGTIGLMHAVAN UBL1_RAT 84 29 -
QTIGNSCGTIGLIHAVAN UBL1_HUMAN 84 29 -
QFTHNACGTVALIHSVAN UBL_DROME 87 31 -
QTIGNACGTVAIVHALAN UBL_APLCA 84 25 -
QTIPNACGTIGLLHAVSN UBLH_SCHPO 77 25 -
QSVKNACGLYAILHSLSN UBL1_YEAST 84 23 -

Motif 4 width=12
Element Seqn Id St Int Rpt
EKVDLHFIALVH UBL3_HUMAN 164 57 -
DKVNFHFILFNN UBL1_RAT 156 54 -
DKVNFHFILFNN UBL1_HUMAN 156 54 -
EKVIHHFIALVN UBL_DROME 159 54 -
EHVKSHFVALVH UBL_APLCA 159 57 -
VETDLHFICFVK UBLH_SCHPO 153 58 -
ADTNLHYITYVE UBL1_YEAST 161 59 -

Motif 5 width=11
Element Seqn Id St Int Rpt
LYELDGRKPFP UBL3_HUMAN 180 4 -
LYELDGRMPFP UBL1_RAT 172 4 -
LYELDGRMPFP UBL1_HUMAN 172 4 -
LYELDGRKSFP UBL_DROME 175 4 -
LYELDGRKEAP UBL_APLCA 175 4 -
FYELDGRQEGP UBLH_SCHPO 173 8 -
IFELDGRNLSG UBL1_YEAST 177 4 -