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PR01867

Identifier
BCL2RLATEDA1  [View Relations]  [View Alignment]  
Accession
PR01867
No. of Motifs
4
Creation Date
08-APR-2003
Title
Bcl-2-related protein A1 signature
Database References
PRINTS; PR01862 BCL2FAMILY
MIM; 601056
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. HAMASAKI, A., SENDO, F., NAKAYAMA, K., ISHIDA, N., NEGISHI, I.,
NAKAYAMA, K. AND HATAKEYAMA, S.
Accelerated neutrophil apoptosis in mice lacking A1-a, a subtype of
the Bcl-2-related A1 gene.
J.EXP.MED. 188 1985-1992 (1998).

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 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 A1 subtype appears to have weaker
survival activity than Bcl-2, Bcl-x and Bcl-w, and is more divergent in 
sequence, which may indicate additional functionality. Gene knockout 
experiments in mice have shown the A1 gene to be required for survival of 
peripheral blood neutrophils [4].
 
BCL2RLATEDA1 is a 4-element fingerprint that provides a signature for Bcl-2-
related protein A1. The fingerprint was derived from an initial alignment of
6 sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length, focusing on those sections that characterise 
Bcl-A1 proteins but distinguish them from closely-related Bcl-2 family 
members - motif 1 lies at the N-terminus; motif 2 resides at the N-terminal 
end of BH1; motif 3 is located at the C-terminal end of BH1; and motif 4 
is C-terminal to BH2. Two iterations on SPTR40_22f were required to reach 
convergence, at which point a true set comprising 8 sequences was identified.
Summary Information
8 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
48888
30000
20000
1234
True Positives
BFL1_HUMAN    BFL1_MOUSE    O55177        O55178        
O55179 Q8K164 Q925A9 Q9W6F2
Sequence Titles
BFL1_HUMAN  Bcl-2-related protein A1 (BFL-1 protein) (Hemopoietic-specific early response protein) (GRS protein) - Homo sapiens (Human). 
BFL1_MOUSE Bcl-2-related protein A1 (BFL-1 protein) (Hemopoietic-specific early response protein) (A1-A) - Mus musculus (Mouse).
O55177 A1-b protein - Mus musculus (Mouse).
O55178 A1-c protein - Mus musculus (Mouse).
O55179 B-cell leukemia/lymphoma 2 related protein A1d - Mus musculus (Mouse).
Q8K164 B-cell leukemia/lymphoma 2 related protein A1b - Mus musculus (Mouse).
Q925A9 BCL2-related protein A1 - Rattus norvegicus (Rat).
Q9W6F2 Protein A1 - Gallus gallus (Chicken).
Scan History
SPTR40_22f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
EYEFMYIHSLAEH O55177 3 3 -
EYEFMYIHSLAEH O55179 3 3 -
DCEFMYIHSLAEN Q925A9 3 3 -
ESELMHIHSLAEH BFL1_MOUSE 3 3 -
EYELMHIHSLAEH O55178 3 3 -
DCEFGYIYRLAQD BFL1_HUMAN 3 3 -

Motif 2 width=14
Element Seqn Id St Int Rpt
IDTARIIFNQVMEK O55177 64 48 -
IDTARIIFNQVMEK O55179 64 48 -
IDTARIIFNQVMEK Q925A9 64 48 -
IDTARIIFNQVMEK BFL1_MOUSE 64 48 -
IDTTRIIFNQVMEK O55178 64 48 -
VDTARTLFNQVMEK BFL1_HUMAN 64 48 -

Motif 3 width=10
Element Seqn Id St Int Rpt
FEDGIINWGR O55177 79 1 -
FEDGIINWGR O55179 79 1 -
FEDGIINWGR Q925A9 79 1 -
FEDGIINWGR BFL1_MOUSE 79 1 -
FEDGIINWGR O55178 79 1 -
FEDGIINWGR BFL1_HUMAN 79 1 -

Motif 4 width=12
Element Seqn Id St Int Rpt
TIFAFGGVLLKK O55177 91 2 -
TIFAFGGVLLKK O55179 91 2 -
TIFAFGGVLLKK Q925A9 91 2 -
TIFAFGGVLLKK BFL1_MOUSE 91 2 -
TIFAFGGVLLKK O55178 91 2 -
TIFAFEGILIKK BFL1_HUMAN 91 2 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
EYEFMYIHSLAEH O55177 3 3 -
EYEFMYIHSLAEH Q8K164 3 3 -
EYEFMYIHSLAEH O55179 3 3 -
DCEFMYIHSLAEN Q925A9 3 3 -
ESELMHIHSLAEH BFL1_MOUSE 3 3 -
EYELMHIHSLAEH O55178 3 3 -
DCEFGYIYRLAQD BFL1_HUMAN 3 3 -
TAEFYYVYYLAQD Q9W6F2 3 3 -

Motif 2 width=14
Element Seqn Id St Int Rpt
IDTARIIFNQVMEK O55177 64 48 -
IDTARIIFNQVMEK Q8K164 64 48 -
IDTARIIFNQVMEK O55179 64 48 -
IDTARIIFNQVMEK Q925A9 64 48 -
IDTARIIFNQVMEK BFL1_MOUSE 64 48 -
IDTTRIIFNQVMEK O55178 64 48 -
VDTARTLFNQVMEK BFL1_HUMAN 64 48 -
VDVAKRIFNGVMEE Q9W6F2 64 48 -

Motif 3 width=10
Element Seqn Id St Int Rpt
FEDGIINWGR O55177 79 1 -
FEDGIINWGR Q8K164 79 1 -
FEDGIINWGR O55179 79 1 -
FEDGIINWGR Q925A9 79 1 -
FEDGIINWGR BFL1_MOUSE 79 1 -
FEDGIINWGR O55178 79 1 -
FEDGIINWGR BFL1_HUMAN 79 1 -
FADGNTNWGR Q9W6F2 79 1 -

Motif 4 width=12
Element Seqn Id St Int Rpt
TIFAFGGVLLKK O55177 91 2 -
TIFAFGGVLLKK Q8K164 91 2 -
TIFAFGGVLLKK O55179 91 2 -
TIFAFGGVLLKK Q925A9 91 2 -
TIFAFGGVLLKK BFL1_MOUSE 91 2 -
TIFAFGGVLLKK O55178 91 2 -
TIFAFEGILIKK BFL1_HUMAN 91 2 -
TIFTFGGLLTKK Q9W6F2 91 2 -