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BCL2L1

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.

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 F(1)F(0) activity and regulates endocytic vesicle retrieval in hippocampal neurons through association with DMN1L and stimulation of its GTPase activity in synaptic vesicles. May attenuate inflammation impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785).

Isoform Bcl-X(S) promotes apoptosis.

Post-translational modifications

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.

Ubiquitinated by RNF183 during prolonged ER stress, leading to degradation by the proteosome.

Sequence similarities

Belongs to the Bcl-2 family.

Tissue specificity

Bcl-X(S) is expressed at high levels in cells that undergo a high rate of turnover, such as developing lymphocytes. In contrast, Bcl-X(L) is found in tissues containing long-lived postmitotic cells, such as adult brain.

Cellular localization

  • Isoform Bcl-X(L)
  • Mitochondrion inner membrane
  • Mitochondrion outer membrane
  • Mitochondrion matrix
  • Cytoplasmic vesicle
  • Secretory vesicle
  • Synaptic vesicle membrane
  • Cytoplasm
  • Cytosol
  • Cytoplasm
  • Cytoskeleton
  • Microtubule organizing center
  • Centrosome
  • Nucleus membrane
  • Single-pass membrane protein
  • Cytoplasmic side
  • After neuronal stimulation, translocates from cytosol to synaptic vesicle and mitochondrion membrane in a calmodulin-dependent manner (By similarity). Localizes to the centrosome when phosphorylated at Ser-49.

Alternative names

  • Bcl-2-like protein 1
  • Bcl2-L-1
  • Apoptosis regulator Bcl-X
  • BCL2L
  • BCLX
  • BCL2L1

Target type

Proteins

Molecular weight

26049Da