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PR01863

Identifier
APOPREGBCL2  [View Relations]  [View Alignment]  
Accession
PR01863
No. of Motifs
4
Creation Date
07-MAY-2003
Title
Bcl-2 apoptosis regulator protein signature
Database References
PRINTS; PR01862 BCL2FAMILY
MIM; 151430
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).

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]. Full-length Bcl-2 proteins feature
all four BH domains, seven alpha-helices, and a C-terminal hydrophobic
motif that targets the protein to the outer mitochondrial membrane, ER
and nuclear envelope.
 
APOPREGBCL2 is a 4-element fingerprint that provides a signature for Bcl-2
apoptosis regulator protein. 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-2 proteins but distinguish them from closely-related
Bcl-2 family members - motif 1 lies at the N-terminus, and includes part
of BH4; motifs 2 and 3 lie between BH3 and BH1; and motif 4 resides within
BH2. Two iterations on SPTR40_22f were required to reach convergence,
at which point a true set comprising 7 sequences was identified.
Summary Information
7 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
47777
30000
20000
1234
True Positives
BCL2_BOVIN    BCL2_CHICK    BCL2_CRILO    BCL2_HUMAN    
BCL2_MOUSE BCL2_RAT Q923R6
Sequence Titles
BCL2_BOVIN  Apoptosis regulator Bcl-2 - Bos taurus (Bovine). 
BCL2_CHICK Apoptosis regulator Bcl-2 - Gallus gallus (Chicken).
BCL2_CRILO Apoptosis regulator Bcl-2 - Cricetulus longicaudatus (Long-tailed hamster) (Chinese hamster).
BCL2_HUMAN Apoptosis regulator Bcl-2 - Homo sapiens (Human).
BCL2_MOUSE Apoptosis regulator Bcl-2 - Mus musculus (Mouse).
BCL2_RAT Apoptosis regulator Bcl-2 - Rattus norvegicus (Rat).
Q923R6 B-cell lymphoma protein 2 - Cricetulus longicaudatus (Long-tailed hamster) (Chinese hamster).
Scan History
SPTR40_22f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
MAQAGRTGYDNREIVMKY BCL2_MOUSE 1 1 -
MAQAGRTGYDNREIVMKY BCL2_CRILO 1 1 -
MAQAGRTGYDNREIVMKY BCL2_RAT 1 1 -
MAHAGRTGYDNREIVMKY BCL2_HUMAN 1 1 -
MAHAGGTGYDNREIVMKY BCL2_BOVIN 1 1 -
MAHPGRRGYDNREIVLKY BCL2_CHICK 1 1 -

Motif 2 width=25
Element Seqn Id St Int Rpt
DAAPLGAAPTPGIFSFQPESNPMPA BCL2_MOUSE 36 17 -
DAAPLGAAPTPGIFSFQPESNPTPA BCL2_CRILO 36 17 -
DSAPLRAAPTPGIFSFQPESNRTPA BCL2_RAT 36 17 -
GAAPPGAAPAPGIFSSQPGHTPHPA BCL2_HUMAN 36 17 -
GAAPPGAAPAPGILSSQPGRTPAPS BCL2_BOVIN 36 17 -
DRPPVPPAPAPAAAPAAVAAAGASS BCL2_CHICK 35 16 -

Motif 3 width=18
Element Seqn Id St Int Rpt
TAGPALSPVPPCVHLTLR BCL2_MOUSE 78 17 -
TTGPTLSPVPPVVHLTLR BCL2_CRILO 78 17 -
NAGPALSPVPPVVHLTLR BCL2_RAT 78 17 -
AAGPALSPVPPVVHLTLR BCL2_HUMAN 81 20 -
AAGPAPSPVPPVVHLTLR BCL2_BOVIN 71 10 -
PPAEGLRPAPPGVHLALR BCL2_CHICK 75 15 -

Motif 4 width=18
Element Seqn Id St Int Rpt
PSMRPLFDFSWLSLKTLL BCL2_MOUSE 201 105 -
PSVRPLFDFSWLSLKTLL BCL2_CRILO 201 105 -
PSMRPLFDFSWLSLKTLL BCL2_RAT 201 105 -
PSMRPLFDFSWLSLKTLL BCL2_HUMAN 204 105 -
PSMRPLFDFSWLSLKALL BCL2_BOVIN 194 105 -
NSMRPLFDFSWISLKTIL BCL2_CHICK 198 105 -
Final Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
MAQAGRTGYDNREIVMKY BCL2_MOUSE 1 1 -
MAQAGRTGYDNREIVMKY BCL2_CRILO 1 1 -
MAQAGRTGYDNREIVMKY Q923R6 1 1 -
MAQAGRTGYDNREIVMKY BCL2_RAT 1 1 -
MAHAGRTGYDNREIVMKY BCL2_HUMAN 1 1 -
MAHAGGTGYDNREIVMKY BCL2_BOVIN 1 1 -
MAHPGRRGYDNREIVLKY BCL2_CHICK 1 1 -

Motif 2 width=25
Element Seqn Id St Int Rpt
DAAPLGAAPTPGIFSFQPESNPMPA BCL2_MOUSE 36 17 -
DAAPLGAAPTPGIFSFQPESNPTPA BCL2_CRILO 36 17 -
DAAPLGAAPTPGIFSFQPESNPTPA Q923R6 36 17 -
DSAPLRAAPTPGIFSFQPESNRTPA BCL2_RAT 36 17 -
GAAPPGAAPAPGIFSSQPGHTPHPA BCL2_HUMAN 36 17 -
GAAPPGAAPAPGILSSQPGRTPAPS BCL2_BOVIN 36 17 -
DRPPVPPAPAPAAAPAAVAAAGASS BCL2_CHICK 35 16 -

Motif 3 width=18
Element Seqn Id St Int Rpt
TAGPALSPVPPCVHLTLR BCL2_MOUSE 78 17 -
TTGPTLSPVPPVVHLTLR BCL2_CRILO 78 17 -
TTGPTLSPVPPVVHLTLR Q923R6 78 17 -
NAGPALSPVPPVVHLTLR BCL2_RAT 78 17 -
AAGPALSPVPPVVHLTLR BCL2_HUMAN 81 20 -
AAGPAPSPVPPVVHLTLR BCL2_BOVIN 71 10 -
PPAEGLRPAPPGVHLALR BCL2_CHICK 75 15 -

Motif 4 width=18
Element Seqn Id St Int Rpt
PSMRPLFDFSWLSLKTLL BCL2_MOUSE 201 105 -
PSVRPLFDFSWLSLKTLL BCL2_CRILO 201 105 -
PSVRPLFDFSWLSLXTLL Q923R6 201 105 -
PSMRPLFDFSWLSLKTLL BCL2_RAT 201 105 -
PSMRPLFDFSWLSLKTLL BCL2_HUMAN 204 105 -
PSMRPLFDFSWLSLKALL BCL2_BOVIN 194 105 -
NSMRPLFDFSWISLKTIL BCL2_CHICK 198 105 -