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PR01866

Identifier
APOPREGMCL1  [View Relations]  [View Alignment]  
Accession
PR01866
No. of Motifs
5
Creation Date
08-APR-2003
Title
MCL1 (myeloid cell leukaemia 1) apoptosis regulator protein signature
Database References
PRINTS; PR01862 BCL2FAMILY
MIM; 159552
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. RINKENBERGER, J.L., HORNING, S., KLOCKE, B., ROTH, K. AND
KORSMEYER, S.J.
Mcl-1 deficiency results in peri-implantation embryonic lethality.
GENES DEV. 14 23-27 (2000).

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 Mcl-1 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. Disruption of 
Mcl-1 in mice revealed that the gene may be required for zygote 
implantation, suggesting that its role extends beyond apoptosis [4].
 
APOPREGMCL1 is a 5-element fingerprint that provides a signature for Mcl-1
(myeloid cell leukaemia 1) apoptosis regulator protein. The fingerprint was 
derived from an initial alignment of 4 sequences: the motifs were drawn from
conserved regions spanning virtually the full alignment length, focusing on
those sections that characterise Mcl-1 proteins but distinguish them from
closely-related Bcl-2 family members - motif 1 lies immediately before BH1;
motif 2 resides within BH1; motif 3 spans the C-terminal portion of BH1, and
the succeeding sequence; and motifs 4 and 5 are located towards the C-
terminus. Two iterations on SPTR40_22f were required to reach convergence, 
at which point a true set comprising 6 sequences was identified.
Summary Information
6 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
566666
400000
300000
200000
12345
True Positives
MCL1_HUMAN    P97287        Q95KR3        Q9I9N3        
Q9UNJ1 Q9Z1P3
Sequence Titles
MCL1_HUMAN  Induced myeloid leukemia cell differentiation protein Mcl-1 - Homo sapiens (Human). 
P97287 EAT/MCL-1 PROTEIN (MCL1) (MYELOID CELL LEUKEMIA SEQUENCE 1) - Mus musculus (Mouse).
Q95KR3 MYELOID CELL LEUKEMIA PROTEIN 1 - Sus scrofa (Pig).
Q9I9N3 MCL-1A (CELL DEATH REGULATOR MCL-1A) - Brachydanio rerio (Zebrafish) (Zebra danio).
Q9UNJ1 MYELOID CELL DIFFERENTIATION PROTEIN (MYELOID CELL LEUKEMIA PROTEIN 1) (MYELOID CELL LEUKEMIA SEQUENCE 1) (BCL2-RELATED) - Homo sapiens (Human).
Q9Z1P3 MCL-1 PROTEIN - Rattus norvegicus (Rat).
Scan History
SPTR40_20f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
DIKNEDDVKSLSRVMIH MCL1_HUMAN 236 236 -
DIKNEDDVKSFSRVMTH Q9Z1P3 216 216 -
DIKNEGDVKSFSRVMVH P97287 217 217 -
QLDSQPASLDFIRCIAS Q9I9N3 140 140 -

Motif 2 width=14
Element Seqn Id St Int Rpt
VFSDGVTNWGRIVT MCL1_HUMAN 253 0 -
VFKDGVTNWGRIVT Q9Z1P3 233 0 -
VFKDGVTNWGRIVT P97287 234 0 -
MFKDGVTNWGRIAS Q9I9N3 158 1 -

Motif 3 width=16
Element Seqn Id St Int Rpt
ISFGAFVAKHLKTINQ MCL1_HUMAN 268 1 -
ISFGAFVAKHLKSINQ Q9Z1P3 248 1 -
ISFGAFVAKHLKSVNQ P97287 249 1 -
VAFGAVVCSRLKELQQ Q9I9N3 173 1 -

Motif 4 width=14
Element Seqn Id St Int Rpt
EDLEGGIRNVLLAF MCL1_HUMAN 322 38 -
QDLEGGIRNVLLAF Q9Z1P3 302 38 -
QDLEGGIRNVLLAF P97287 303 38 -
EDVESVVRHGLLAL Q9I9N3 227 38 -

Motif 5 width=14
Element Seqn Id St Int Rpt
GVAGVGAGLAYLIR MCL1_HUMAN 337 1 -
GVAGVGAGLAYLIR Q9Z1P3 317 1 -
GVAGVGAGLAYLIR P97287 318 1 -
GCAGIGAGLAFLIR Q9I9N3 242 1 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
DIKNEDDVKSLSRVMIH MCL1_HUMAN 236 236 -
DIKNEDDVKSLSRVMIH Q9UNJ1 236 236 -
DIKNEDDVKSFSRVMTH Q9Z1P3 216 216 -
DIKNEGDVKSFSRVMVH P97287 217 217 -
DIKNEDDVKSLSRVMVH Q95KR3 38 38 -
QLDSQPASLDFIRCIAS Q9I9N3 140 140 -

Motif 2 width=14
Element Seqn Id St Int Rpt
VFSDGVTNWGRIVT MCL1_HUMAN 253 0 -
VFSDGVTNWGRIVT Q9UNJ1 253 0 -
VFKDGVTNWGRIVT Q9Z1P3 233 0 -
VFKDGVTNWGRIVT P97287 234 0 -
VLSDGVTNWGRIVT Q95KR3 55 0 -
MFKDGVTNWGRIAS Q9I9N3 158 1 -

Motif 3 width=16
Element Seqn Id St Int Rpt
ISFGAFVAKHLKTINQ MCL1_HUMAN 268 1 -
ISFGAFVAKHLKTINQ Q9UNJ1 268 1 -
ISFGAFVAKHLKSINQ Q9Z1P3 248 1 -
ISFGAFVAKHLKSVNQ P97287 249 1 -
ISFGAFVAKHLKSINQ Q95KR3 70 1 -
VAFGAVVCSRLKELQQ Q9I9N3 173 1 -

Motif 4 width=14
Element Seqn Id St Int Rpt
EDLEGGIRNVLLAF MCL1_HUMAN 322 38 -
EDLEGGIRNVLLAF Q9UNJ1 322 38 -
QDLEGGIRNVLLAF Q9Z1P3 302 38 -
QDLEGGIRNVLLAF P97287 303 38 -
EDLEGGIRNVLLAF Q95KR3 124 38 -
EDVESVVRHGLLAL Q9I9N3 227 38 -

Motif 5 width=14
Element Seqn Id St Int Rpt
GVAGVGAGLAYLIR MCL1_HUMAN 337 1 -
GVAGVGAGLAYLIR Q9UNJ1 337 1 -
GVAGVGAGLAYLIR Q9Z1P3 317 1 -
GVAGVGAGLAYLIR P97287 318 1 -
GVAGVGAGLAYLIR Q95KR3 139 1 -
GCAGIGAGLAFLIR Q9I9N3 242 1 -