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PR01864

Identifier
APOPREGBCLX  [View Relations]  [View Alignment]  
Accession
PR01864
No. of Motifs
5
Creation Date
08-APR-2003
Title
Bcl-X apoptosis regulator protein signature
Database References
PRINTS; PR01862 BCL2FAMILY
MIM; 600039
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 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]. In healthy cells, Bcl-xl 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 hydro-
phobic groove, formed by residues from BH1-BH3, is capable of binding
the BH3 alpha-helix from a pro-apoptotic BH3-only family member [4].
 
APOPREGBCLX is a 5-element fingerprint that provides a signature for Bcl-x
apoptosis regulator protein. The fingerprint was derived from an initial
alignment of 5 sequences: the motifs were drawn from conserved regions 
spanning virtually the full alignment length, focusing on those sections
that characterise Bcl-x proteins but distinguish them from closely-related
Bcl-2 family members - motif 1 lies at the N-terminus, including part of 
BH4; motifs 2 and 3 reside between BH4 and BH3, motif 3 including a portion 
of BH3; and motifs 4 and 5 are located between BH3 and BH1. Three iterations 
on SPTR40_22f were required to reach convergence, at which point a true set
comprising 15 sequences was identified.  
Summary Information
15 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
51515151515
400000
300000
200000
12345
True Positives
AR11_XENLA    BCLX_CHICK    BCLX_HUMAN    BCLX_MOUSE    
BCLX_PIG BCLX_RAT O35843 O35844
Q8SQ42 Q90Z98 Q90ZH2 Q9MYW4
Q9MZS7 Q9N1A2 Q9WUI5
Sequence Titles
AR11_XENLA  Apoptosis regulator R11 (XR11) - Xenopus laevis (African clawed frog). 
BCLX_CHICK Apoptosis regulator Bcl-X (BCL2-like 1 protein) - Gallus gallus (Chicken).
BCLX_HUMAN Apoptosis regulator Bcl-X (BCL2-like 1 protein) - Homo sapiens (Human).
BCLX_MOUSE Apoptosis regulator Bcl-X (BCL2-like 1 protein) - Mus musculus (Mouse).
BCLX_PIG Apoptosis regulator Bcl-X (BCL2-like 1 protein) - Sus scrofa (Pig).
BCLX_RAT Apoptosis regulator Bcl-X (BCL2-like 1 protein) - Rattus norvegicus (Rat).
O35843 Bcl-x-gamma - Mus musculus (Mouse).
O35844 Bcl-xL - Mus musculus (Mouse).
Q8SQ42 Bcl-xl protein - Felis silvestris catus (Cat).
Q90Z98 Bcl-XL-like protein 1 - Brachydanio rerio (Zebrafish) (Danio rerio).
Q90ZH2 Bcl-XL - Xenopus laevis (African clawed frog).
Q9MYW4 Bcl-X - Oryctolagus cuniculus (Rabbit).
Q9MZS7 Bcl-x long protein - Ovis aries (Sheep).
Q9N1A2 Anti-apoptotic regulator Bcl-xL - Sus scrofa (Pig).
Q9WUI5 Bcl-x short - Rattus norvegicus (Rat).
Scan History
SPTR40_22f 3  100  NSINGLE    
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
MSQSNRELVVDFLSYK O35844 1 1 -
MSQSNRELVVDFLSYK Q9N1A2 1 1 -
MSQSNRELVVDFLSYK Q8SQ42 1 1 -
MEGSSRDLVEKFVSKK Q90ZH2 1 1 -
MSYYNRELVVFFIKYK Q90Z98 1 1 -

Motif 2 width=16
Element Seqn Id St Int Rpt
LSQKGYSWSQFSDVEE O35844 17 0 -
LSQKGYSWSQFTDVEE Q9N1A2 17 0 -
LSQKGYSWSRFSDVEE Q8SQ42 17 0 -
LSQNEACRKFSNNPQP Q90ZH2 17 0 -
LSQRNYPCNHIGLTED Q90Z98 17 0 -

Motif 3 width=17
Element Seqn Id St Int Rpt
VIPMAAVKQALREAGDE O35844 80 47 -
VIPMAAVKQALREAGDE Q9N1A2 80 47 -
VIPMAAVKQALREAGDE Q8SQ42 80 47 -
GIVEEEVLQALLEATEE Q90ZH2 52 19 -
SGGLDAVKEALRDSANE Q90Z98 83 50 -

Motif 4 width=12
Element Seqn Id St Int Rpt
LRYRRAFSDLTS O35844 99 2 -
LRYRRAFSDLTS Q9N1A2 99 2 -
LRYRRAFSDLTS Q8SQ42 99 2 -
LRYQRAFSDLTS Q90ZH2 71 2 -
LRYSRAFNDLSS Q90Z98 102 2 -

Motif 5 width=12
Element Seqn Id St Int Rpt
TAYQSFEQVVNE O35844 118 7 -
TAYQSFEQVVNE Q9N1A2 118 7 -
TAYQSFEQVVNE Q8SQ42 118 7 -
TAQQSFQQVMGE Q90ZH2 90 7 -
TAYQSFESVMDE Q90Z98 121 7 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
MSQSNRELVVDFLSYK BCLX_HUMAN 1 1 -
MSQSNRELVVDFLSYK BCLX_MOUSE 1 1 -
MSQSNRELVVDFLSYK BCLX_RAT 1 1 -
MSQSNRELVVDFLSYK O35843 1 1 -
MSQSNRELVVDFLSYK O35844 1 1 -
MSQSNRELVVDFLSYK Q9MZS7 1 1 -
MSQSNRELVVDFLSYK Q9N1A2 1 1 -
MSQSNRELVVDFLSYK Q9MYW4 1 1 -
MSQSNRELVVDFLSYK BCLX_PIG 1 1 -
MSQSNRELVVDFLSYK Q9WUI5 1 1 -
MSQSNRELVVDFLSYK Q8SQ42 1 1 -
MSSSNRELVIDFVSYK BCLX_CHICK 1 1 -
MEGSSRDLVEKFVSKK AR11_XENLA 1 1 -
MEGSSRDLVEKFVSKK Q90ZH2 1 1 -
MSYYNRELVVFFIKYK Q90Z98 1 1 -

Motif 2 width=16
Element Seqn Id St Int Rpt
LSQKGYSWSQFSDVEE BCLX_HUMAN 17 0 -
LSQKGYSWSQFSDVEE BCLX_MOUSE 17 0 -
LSQKGYSWSQFSDVEE BCLX_RAT 17 0 -
LSQKGYSWSQFSDVEE O35843 17 0 -
LSQKGYSWSQFSDVEE O35844 17 0 -
LSQKGYSWSQFSDVEE Q9MZS7 17 0 -
LSQKGYSWSQFTDVEE Q9N1A2 17 0 -
LSQKGYSWSQFSDVEE Q9MYW4 17 0 -
LSQKGYSWSQFTDVEE BCLX_PIG 17 0 -
LSQKGYSWSQFSDVEE Q9WUI5 17 0 -
LSQKGYSWSRFSDVEE Q8SQ42 17 0 -
LSQRGHCWSELEEEDE BCLX_CHICK 17 0 -
LSQNEACRKFSNNPNP AR11_XENLA 17 0 -
LSQNEACRKFSNNPQP Q90ZH2 17 0 -
LSQRNYPCNHIGLTED Q90Z98 17 0 -

Motif 3 width=17
Element Seqn Id St Int Rpt
VIPMAAVKQALREAGDE BCLX_HUMAN 80 47 -
VIPMAAVKQALREAGDE BCLX_MOUSE 80 47 -
VIPMAAVKQALREAGDE BCLX_RAT 80 47 -
VIPMAAVKQALREAGDE O35843 80 47 -
VIPMAAVKQALREAGDE O35844 80 47 -
VIPMAAVKQALREAGDE Q9MZS7 80 47 -
VIPMAAVKQALREAGDE Q9N1A2 80 47 -
VIPMTAVKQALREAGDE Q9MYW4 80 47 -
VIPMAAVKQALREAGDE BCLX_PIG 80 47 -
VIPMAAVKQALREAGDE Q9WUI5 80 47 -
VIPMAAVKQALREAGDE Q8SQ42 80 47 -
IVRASDVRQALRDAGDE BCLX_CHICK 76 43 -
GIVEEEVLQALLEATEE AR11_XENLA 52 19 -
GIVEEEVLQALLEATEE Q90ZH2 52 19 -
SGGLDAVKEALRDSANE Q90Z98 83 50 -

Motif 4 width=12
Element Seqn Id St Int Rpt
LRYRRAFSDLTS BCLX_HUMAN 99 2 -
LRYRRAFSDLTS BCLX_MOUSE 99 2 -
LRYRRAFSDLTS BCLX_RAT 99 2 -
LRYRRAFSDLTS O35843 99 2 -
LRYRRAFSDLTS O35844 99 2 -
LRYRRAFSDLTS Q9MZS7 99 2 -
LRYRRAFSDLTS Q9N1A2 99 2 -
LRYRRAFSDLTS Q9MYW4 99 2 -
LRYRRAFSDLTS BCLX_PIG 99 2 -
LRYRRAFSDLTS Q9WUI5 99 2 -
LRYRRAFSDLTS Q8SQ42 99 2 -
LRYRRAFSDLTS BCLX_CHICK 95 2 -
LRYQRAFSDLTS AR11_XENLA 71 2 -
LRYQRAFSDLTS Q90ZH2 71 2 -
LRYSRAFNDLSS Q90Z98 102 2 -

Motif 5 width=12
Element Seqn Id St Int Rpt
TAYQSFEQVVNE BCLX_HUMAN 118 7 -
TAYQSFEQVVNE BCLX_MOUSE 118 7 -
TAYQSFEQVVNE BCLX_RAT 118 7 -
TAYQSFEQVVNE O35843 118 7 -
TAYQSFEQVVNE O35844 118 7 -
TAYQSFEQVVNE Q9MZS7 118 7 -
TAYQSFEQVVNE Q9N1A2 118 7 -
TAYQSFEQVVNE Q9MYW4 118 7 -
TAYQSFEQVLNE BCLX_PIG 118 7 -
TAYQSFEQDSFV Q9WUI5 118 7 -
TAYQSFEQVVNE Q8SQ42 118 7 -
TAYQSFEQVVNE BCLX_CHICK 114 7 -
TAQQSFQQVMGE AR11_XENLA 90 7 -
TAQQSFQQVMGE Q90ZH2 90 7 -
TAYQSFESVMDE Q90Z98 121 7 -