Q64373 · B2CL1_MOUSE
- ProteinBcl-2-like protein 1
- GeneBcl2l1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids233 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Potent inhibitor of cell death. Inhibits activation of caspases. Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.
Isoform Bcl-X(L) also regulates presynaptic plasticity, including neurotransmitter release and recovery, number of axonal mitochondria as well as size and number of synaptic vesicle clusters. During synaptic stimulation, increases ATP availability from mitochondria through regulation of mitochondrial membrane ATP synthase F1F0 activity and regulates endocytic vesicle retrieval in hippocampal neurons through association with DMN1L and stimulation of its GTPase activity in synaptic vesicles (By similarity).
May attenuate inflammation impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (By similarity).
May attenuate inflammation impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (By similarity).
Isoform Bcl-X(S) promotes apoptosis.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameBcl-2-like protein 1
- Short namesBcl2-L-1
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ64373
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion membrane ; Single-pass membrane protein
Nucleus membrane ; Single-pass membrane protein
Note: Localizes to the centrosome when phosphorylated at Ser-49.
Isoform Bcl-X(L)
Note: After neuronal stimulation, translocates from cytosol to synaptic vesicle and mitochondrion membrane in a calmodulin-dependent manner.
Isoform Bcl-X(delta-TM)
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 210-226 | Helical | ||||
Sequence: FNRWFLTGMTVAGVVLL |
Keywords
- Cellular component
Phenotypes & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 13 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000143063 | 1-233 | Bcl-2-like protein 1 | |||
Sequence: MSQSNRELVVDFLSYKLSQKGYSWSQFSDVEENRTEAPEETEAERETPSAINGNPSWHLADSPAVNGATGHSSSLDAREVIPMAAVKQALREAGDEFELRYRRAFSDLTSQLHITPGTAYQSFEQVVNELFRDGVNWGRIVAFFSFGGALCVESVDKEMQVLVSRIASWMATYLNDHLEPWIQENGGWDTFVDLYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK | ||||||
Modified residue | 49 | Phosphoserine; by PLK3 | ||||
Sequence: S | ||||||
Modified residue | 62 | Phosphoserine; by CDK1 | ||||
Sequence: S |
Post-translational modification
Proteolytically cleaved by caspases during apoptosis. The cleaved protein, lacking the BH4 motif, has pro-apoptotic activity.
Phosphorylated on Ser-62 by CDK1. This phosphorylation is partial in normal mitotic cells, but complete in G2-arrested cells upon DNA-damage, thus promoting subsequent apoptosis probably by triggering caspases-mediated proteolysis. Phosphorylated by PLK3, leading to regulate the G2 checkpoint and progression to cytokinesis during mitosis. Phosphorylation at Ser-49 appears during the S phase and G2, disappears rapidly in early mitosis during prometaphase, metaphase and early anaphase, and re-appears during telophase and cytokinesis (By similarity).
Ubiquitinated by RNF183 during prolonged ER stress, leading to degradation by the proteosome.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Widely expressed, with highest levels in the brain, thymus, bone marrow, and kidney. Bcl-X(L) and Bcl-X(delta-TM) expression is enhanced in B- and T-lymphocytes that have been activated.
Developmental stage
Bcl-X(beta) is expressed in both embryonal and postnatal tissues, whereas Bcl-X(L) is predominantly found in postnatal tissues.
Gene expression databases
Interaction
Subunit
Homodimer. Interacts with BAD. Interacts with PGAM5. Interacts with HEBP2. Interacts with p53/TP53 and BBC3; interaction with BBC3 disrupts the interaction with p53/TP53. Interacts with ATP5F1A and ATP5F1B; the interactions mediate the association of isoform Bcl-X(L) with the mitochondrial membrane ATP synthase F1F0 ATP synthase (By similarity).
Interacts with VDAC1 (By similarity).
Interacts with BCL2L11 (via BH3) (PubMed:14499110, PubMed:27013495).
Interacts with RNF183 (By similarity).
Interacts with GIMAP3/IAN4 and GIMAP5/IAN5 (PubMed:16509771).
Interacts with GIMAP5 and HSPA8/HSC70; the interaction between HSPA8 and BCL2L1 is impaired in the absence of GIMAP5 (PubMed:21502331).
Interacts with isoform 4 of CLU; this interaction releases and activates BAX and promotes cell death (By similarity).
Interacts with VDAC1 (By similarity).
Interacts with BCL2L11 (via BH3) (PubMed:14499110, PubMed:27013495).
Interacts with RNF183 (By similarity).
Interacts with GIMAP3/IAN4 and GIMAP5/IAN5 (PubMed:16509771).
Interacts with GIMAP5 and HSPA8/HSC70; the interaction between HSPA8 and BCL2L1 is impaired in the absence of GIMAP5 (PubMed:21502331).
Interacts with isoform 4 of CLU; this interaction releases and activates BAX and promotes cell death (By similarity).
Isoform Bcl-X(L)
Forms heterodimers with BAX, BAK or BCL2; heterodimerization with BAX does not seem to be required for anti-apoptotic activity (By similarity).
Interacts with isoform 1 of SIVA1; the interaction inhibits the anti-apoptotic activity (By similarity).
Interacts with IKZF3 (By similarity).
Interacts with RTL10/BOP (By similarity).
Interacts with DNM1L and CLTA; DNM1L and BCL2L1 isoform BCL-X(L) may form a complex in synaptic vesicles that also contains clathrin and MFF (By similarity).
Interacts (via the loop between motifs BH4 and BH3) with NLRP1 (via LRR repeats), but not with NLRP2, NLRP3, NLRP4, PYCARD, nor MEFV (By similarity).
Interacts with BECN1 (By similarity).
Interacts with isoform 1 of SIVA1; the interaction inhibits the anti-apoptotic activity (By similarity).
Interacts with IKZF3 (By similarity).
Interacts with RTL10/BOP (By similarity).
Interacts with DNM1L and CLTA; DNM1L and BCL2L1 isoform BCL-X(L) may form a complex in synaptic vesicles that also contains clathrin and MFF (By similarity).
Interacts (via the loop between motifs BH4 and BH3) with NLRP1 (via LRR repeats), but not with NLRP2, NLRP3, NLRP4, PYCARD, nor MEFV (By similarity).
Interacts with BECN1 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | Q64373 | E P59637 | 2 | EBI-526361, EBI-25487741 | |
BINARY | Q64373-1 | Bad Q61337 | 2 | EBI-526380, EBI-400328 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 4-24 | BH4 | ||||
Sequence: SNRELVVDFLSYKLSQKGYSW | ||||||
Region | 27-73 | Disordered | ||||
Sequence: FSDVEENRTEAPEETEAERETPSAINGNPSWHLADSPAVNGATGHSS | ||||||
Compositional bias | 32-46 | Basic and acidic residues | ||||
Sequence: ENRTEAPEETEAERE | ||||||
Motif | 86-100 | BH3 | ||||
Sequence: VKQALREAGDEFELR | ||||||
Motif | 129-148 | BH1 | ||||
Sequence: ELFRDGVNWGRIVAFFSFGG | ||||||
Motif | 180-195 | BH2 | ||||
Sequence: PWIQENGGWDTFVDLY |
Domain
The BH4 motif is required for anti-apoptotic activity. The BH1 and BH2 motifs are required for both heterodimerization with other Bcl-2 family members and for repression of cell death.
The loop between motifs BH4 and BH3 is required for the interaction with NLRP1.
Sequence similarities
Belongs to the Bcl-2 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 4 isoforms produced by Alternative splicing.
Q64373-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- NameBcl-X(L)
- SynonymsBcl-xL
- Length233
- Mass (Da)26,132
- Last updated1996-11-01 v1
- Checksum24D2AC79887E072E
Q64373-2
- NameBcl-X(S)
- SynonymsBcl-xS
- Differences from canonical
- 126-188: Missing
Q64373-3
- NameBcl-X(beta)
- Differences from canonical
- 189-233: DTFVDLYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK → VRTTPLVCPPLACVSLLCEHP
Q64373-4
- NameBcl-X(delta-TM)
- Differences from canonical
- 194-233: LYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK → GHDCGWCGSAGLTLQSEVTRH
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Features
Showing features for compositional bias, alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 32-46 | Basic and acidic residues | ||||
Sequence: ENRTEAPEETEAERE | ||||||
Alternative sequence | VSP_000517 | 126-188 | in isoform Bcl-X(S) | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_000518 | 189-233 | in isoform Bcl-X(beta) | |||
Sequence: DTFVDLYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK → VRTTPLVCPPLACVSLLCEHP | ||||||
Alternative sequence | VSP_000519 | 194-233 | in isoform Bcl-X(delta-TM) | |||
Sequence: LYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK → GHDCGWCGSAGLTLQSEVTRH | ||||||
Sequence conflict | 207-209 | in Ref. 4; AAC53459 | ||||
Sequence: QER → KEG |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X83574 EMBL· GenBank· DDBJ | CAA58557.1 EMBL· GenBank· DDBJ | mRNA | ||
L35049 EMBL· GenBank· DDBJ | AAA51039.1 EMBL· GenBank· DDBJ | mRNA | ||
L35048 EMBL· GenBank· DDBJ | AAA51040.1 EMBL· GenBank· DDBJ | mRNA | ||
U10102 EMBL· GenBank· DDBJ | AAA82174.1 EMBL· GenBank· DDBJ | mRNA | ||
U10101 EMBL· GenBank· DDBJ | AAA82173.1 EMBL· GenBank· DDBJ | mRNA | ||
U10100 EMBL· GenBank· DDBJ | AAA82172.1 EMBL· GenBank· DDBJ | mRNA | ||
U51278 EMBL· GenBank· DDBJ | AAC53459.1 EMBL· GenBank· DDBJ | mRNA | ||
U51279 EMBL· GenBank· DDBJ | AAC53460.1 EMBL· GenBank· DDBJ | mRNA | ||
U78031 EMBL· GenBank· DDBJ | AAB96881.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U78030 EMBL· GenBank· DDBJ | AAB96881.1 EMBL· GenBank· DDBJ | Genomic DNA |