General information | DisProt: | DP00518 | Name: | Bcl-2-like protein 11 [Isoform BimL] | Synonym(s): | B2L11_MOUSE
Bcl2-L-11
Bcl2-interacting mediator of cell death
UniProt alt product: O54918-2
| First appeared in release: | Release 3.5 (12/22/2006) | UniProt: | O54918 | UniGene: | Mm.141083 | SwissProt: | B2L11_MOUSE | TrEMBL: | | NCBI (GI): | 18202064 | Source organism: | Mus musculus (Mouse) | Sequence length: | 140 | Percent disordered: | 81% | Homologues: | |
Native sequence |
10 20 30 40 50 60 | | | | | | MAKQPSDVSS ECDREGGQLQ PAERPPQLRP GAPTSLQTEP QDRSPAPMSC DKSTQTPSPP - 60 CQAFNHYLSA MASIRQSQEE PEDLRPEIRI AQELRRIGDE FNETYTRRVF ANDYREAEDH - 120 PQMVILQLLR FIFRLVWRRH
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Functional narrative |
Bcl-2 family proteins are important regulators of cell fate. The opposing factions of this family integrate diverse death and survival signals, and regulate initiation of apoptosis in response to various stimuli. Family members that promote cell survival (Bcl-2, Bcl-xL, Bcl-w, A1 and Mcl-1) contain up to four Bcl-2 homology (BH) domains in addition to a C-terminal hydrophobic sequence that targets them to the cytoplasmic face of intracellular membranes, particularly the mitochondria. The proapoptotic family members are more diverse. Those with multiple BH domains such as Bax and Bak (often referred to as Bax-like) have a critical nonredundant role that results in mitochondrial membrane disruption, whereas those with a single BH domain, referred to as BH3-only molecules, appear to function as the key initiators of death. In a healthy cell, the BH3-only molecules are either repressed (e.g. Noxa, Puma) or are present in an inactive state (e.g. Bim, Bmf, Bad and Bid). Upon receipt of a death stimulus, BH3-only molecules are activated, allowing them to engage and inactivate prosurvival Bcl-2 proteins. Interaction of BH3-only proteins with their prosurvival partners ultimately leads to oligomerization of Bax and Bak, and release of apoptogenic factors from the mitochondria. Initiation of apoptosis is thus intimately associated with the ability of BH3-only proteins to bind their prosurvival counterparts. This interaction depends on the integrity of both the BH3 domain of BH3-only proteins and their binding site, a surface exposed hydrophobic groove on prosurvival proteins. Induces apoptosis. The isoforms vary in cytotoxicity with isoform BimS being the most potent and isoform BimEL being the least potent.
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Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
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Region 1 | Type: | Disordered | Name: | deltaC27 | Location: | 1 - 113 | Length: | 113 | Region sequence: |
MAKQPSDVSSECDREGGQLQPAERPPQLRPGAPTSLQTEPQDRSPAPMSCDKSTQTPSPP CQAFNHYLSAMASIRQSQEEPEDLRPEIRIAQELRRIGDEFNETYTRRVFAND | Modification type: | Fragment
Native
| PDB: | | Structural/functional type: | Function arises from the disordered state Function arises via a disorder to order transition | Functional classes: | Molecular recognition effectors
Molecular assembly
| Functional subclasses: | Apoptosis Regulation
Protein-protein binding
| Detection methods:
- Circular dichroism (CD) spectroscopy, far-UV (298 K; pH: 6.7; microM protein (10-50); Sodium Phosphate 5 mM)
- Size exclusion/gel filtration chromatography (pH: 7.4; )
- Nuclear magnetic resonance (NMR) (298 K; pH: 6.7; 2H2O (95:5); H2O; NaCl 70 mM; NaN3 0.04 %; Sodium Phosphate 50 mM; TCEP 2 mM)
- Sensitivity to proteolysis (298 K; Microg Protein 26 ; Trypsin 70 ng)
| References:
- Hinds MG, Smits C, Fredericks-Short R, Risk JM, Bailey M, Huang DC, Day CL. "Bim, Bad and Bmf: intrinsically unstructured BH3-only proteins that undergo a localized conformational change upon binding to prosurvival Bcl-2 targets." Cell Death Differ. 2006. PubMed: 16645638
| Comments:To obtain soluble protein, it was necessary to delete the 27 C-terminal hydrophobic residues, creating the deltaC27 isoform. The deleted C-terminal residues are predicted to form a TM helix.
Bim is a member of the
intrinsically unstructured class of proteins that undergo a
localized conformational change, involving helix formation of
the contact residues (residues 85–113) in the BH3 domain, upon binding to its
partner protein. Residues outside the BH3 domain contribute
little to binding and have the same conformation in the
presence and absence of prosurvival proteins.
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References |
- O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC. "Bim: a novel member of the Bcl-2 family that promotes apoptosis." Embo J. 1998; 17(2): 384-95. PubMed: 9430630
- Shibue T, Taniguchi T. "BH3-only proteins: Integrated control point of apoptosis." Int J Cancer. 2006; 119(9): 2036-43. PubMed: 16572413
- Willis SN, Adams JM. "Life in the balance: how BH3-only proteins induce apoptosis." Curr Opin Cell Biol. 2005; 17(6): 617-25. PubMed: 16243507
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Comments |
Additional UniGene ID, Mm.453214
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