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PR01865

Identifier
APOPREGBCLW  [View Relations]  [View Alignment]  
Accession
PR01865
No. of Motifs
5
Creation Date
08-APR-2003
Title
Bcl-W apoptosis regulator protein signature
Database References
PRINTS; PR01862 BCL2FAMILY
MIM; 601931
Literature References
1. HUNOT, S. AND FLAVELL, R.A.
Apoptosis: death of a monopoly?
SCIENCE 292 865-866 (2001).
 
2. GERMAIN, M. AND SHORE, G.C.
Cellular distribution of Bcl-2 family proteins.
SCI.STKE 173 PE10 (2003).
 
3. ADAMS, J.M. AND CORY, S.
The Bcl-2 protein family: arbiters of cell survival.
SCIENCE 281 1322-1326 (1998).
 
4. CORY, S. AND ADAMS, J.M.
The Bcl2 family: regulators of the cellular life-or-death switch.
NAT.REV.CANCER 2 647-656 (2002).

Documentation
Apoptosis, or programmed cell death (PCD), is a common and evolutionarily 
conserved property of all metazoans [1]. In many biological processes, 
apoptosis is required to eliminate supernumerary or dangerous (e.g., pre-
cancerous) cells and to promote normal development. Thus, dysregulation  
of apoptosis can contribute to the development of many major diseases, 
including cancer, autoimmunity and neurodegenerative disorders. In most
cases, proteins of the caspase family execute the genetic programme that
leads to cell death. Bcl-2 proteins are central regulators of caspase
activation, and play a key role in cell death by regulating the integrity
of the mitochondrial and endoplasmic reticulum (ER) membranes [2]. At 
least 20 Bcl-2 proteins have been reported in mammals, and several
others have been identified in viruses.
 
Bcl-2 family proteins fall roughly into three subtypes, which either promote 
cell survival (anti-apoptotic) or trigger cell death (pro-apoptotic). All 
members contain at least one of four conserved motifs, termed Bcl-2 Homology
(BH) domains. Bcl-2 subfamily proteins, which contain at least BH1 and BH2,
promote cell survival by inhibiting the adapters needed for the activation
of caspases. Pro-apoptotic members potentially exert their effects by dis-
placing the adapters from the pro-survival proteins; these proteins belong
either to the Bax subfamily, which contain BH1-BH3, or to the BH3 subfamily,
which mostly only feature BH3 [3]. Thus, the balance between antagonistic
family members is believed to play a role in determining cell fate.
 
Members of the wider Bcl-2 family, which also includes Bcl-x, Bcl-w and 
Mcl-1, are described by their similarity to Bcl-2 protein, a member of
the pro-survival Bcl-2 subfamily [3]. The C-terminal transmembrane domain
of Bcl-w targets the protein to the outer mitochondrial membrane, the ER
and the nuclear envelope. In healthy cells, Bcl-w resides in the cytoplasm,
and becomes membrane-associated in response to cytotoxic insults. Its 3D 
structure comprises a bundle of five amphipathic alpha-helices surrounding
two central hydrophobic helical regions. A hydrophobic groove, formed by
residues from BH1-BH3, is capable of binding the BH3 alpha-helix from a
pro-apoptotic BH3-only family member [4].
 
APOPREGBCLW is a 5-element fingerprint that provides a signature for Bcl-W 
apoptosis regulator protein. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved regions 
spanning virtually the full alignment length, focusing on those sections 
that characterise Bcl-W proteins but distinguish them from closely-related 
Bcl-2 family members - motif 1 lies at the N-terminus, and includes part of 
BH4; motif 2 spans the C-terminal portion of BH4; motifs 3 and 4 are located 
between BH4 and BH1; and motif 5 spans the N-terminal portion of BH2. Two
iterations on SPTR40_22f were required to reach convergence, at which
point a true set comprising 4 sequences was identified.
Summary Information
4 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
544444
400000
300000
200000
12345
True Positives
BCLW_HUMAN    BCLW_MOUSE    O88996        Q9CYW5        
Sequence Titles
BCLW_HUMAN  Apoptosis regulator Bcl-W (BCL2-like 2 protein) - Homo sapiens (Human). 
BCLW_MOUSE Apoptosis regulator Bcl-W (BCL2-like 2 protein) - Mus musculus (Mouse).
O88996 Bcl-w - Rattus norvegicus (Rat).
Q9CYW5 Bcl2-like 2 - Mus musculus (Mouse).
Scan History
SPTR40_22f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
MATPASTPDTRALVADF BCLW_MOUSE 1 1 -
MATPASTPDTRALVADF O88996 1 1 -
MATPASAPDTRALVADF BCLW_HUMAN 1 1 -

Motif 2 width=11
Element Seqn Id St Int Rpt
RQKGYVCGAGP BCLW_MOUSE 23 5 -
RQKGYVCGAGP O88996 23 5 -
RQKGYVCGAGP BCLW_HUMAN 23 5 -

Motif 3 width=15
Element Seqn Id St Int Rpt
EGPAADPLHQAMRAA BCLW_MOUSE 35 1 -
EGPAADPLHQAMRAA O88996 35 1 -
EGPAADPLHQAMRAA BCLW_HUMAN 35 1 -

Motif 4 width=11
Element Seqn Id St Int Rpt
VTPGSAQQRFT BCLW_MOUSE 70 20 -
VTPGSAQQRFT O88996 70 20 -
VTPGSAQQRFT BCLW_HUMAN 70 20 -

Motif 5 width=16
Element Seqn Id St Int Rpt
LETRLADWIHSSGGWA BCLW_MOUSE 130 49 -
LETRLADWIHSSGGWA O88996 130 49 -
LETRLADWIHSSGGWA BCLW_HUMAN 130 49 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
MATPASTPDTRALVADF BCLW_MOUSE 1 1 -
MATPASTPDTRALVADF O88996 1 1 -
MATPASAPDTRALVADF BCLW_HUMAN 1 1 -
MATPASTPDTRALVADF Q9CYW5 1 1 -

Motif 2 width=11
Element Seqn Id St Int Rpt
RQKGYVCGAGP BCLW_MOUSE 23 5 -
RQKGYVCGAGP O88996 23 5 -
RQKGYVCGAGP BCLW_HUMAN 23 5 -
RQKGYVCGAGP Q9CYW5 23 5 -

Motif 3 width=15
Element Seqn Id St Int Rpt
EGPAADPLHQAMRAA BCLW_MOUSE 35 1 -
EGPAADPLHQAMRAA O88996 35 1 -
EGPAADPLHQAMRAA BCLW_HUMAN 35 1 -
EGPAADPLHQAMRAA Q9CYW5 35 1 -

Motif 4 width=11
Element Seqn Id St Int Rpt
VTPGSAQQRFT BCLW_MOUSE 70 20 -
VTPGSAQQRFT O88996 70 20 -
VTPGSAQQRFT BCLW_HUMAN 70 20 -
VTPGSAQQRFT Q9CYW5 70 20 -

Motif 5 width=16
Element Seqn Id St Int Rpt
LETRLADWIHSSGGWA BCLW_MOUSE 130 49 -
LETRLADWIHSSGGWA O88996 130 49 -
LETRLADWIHSSGGWA BCLW_HUMAN 130 49 -
LETRLADWIHSSGGWV Q9CYW5 130 49 -