BCL2L1

The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The proteins encoded by this gene are located at the outer mitochondrial membrane, and have been shown to regulate outer mitochondrial membrane channel (VDAC) opening. VDAC regulates mitochondrial membrane potential, and thus controls the production of reactive oxygen species and release of cytochrome C by mitochondria, both of which are the potent inducers of cell apoptosis. Alternative splicing results in multiple transcript variants encoding two different isoforms. The longer isoform acts as an apoptotic inhibitor and the shorter isoform acts as an apoptotic activator. [provided by RefSeq, Dec 2015]

BCL2 Like 1

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. May attenuate inflammation impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785).
Isoform Bcl-X(S) promotes apoptosis.

Apoptotic mitochondrial changes Source: ProtInc
Cytokine-mediated signaling pathway Source: Reactome
Defense response to virus Source: DIBU
Endocytosis Source: UniProtKB-KW
Extrinsic apoptotic signaling pathway in absence of ligand Source: GO_Central
Intrinsic apoptotic signaling pathway in response to DNA damage Source: GO_Central
MAPK cascade Source: Reactome
Mitotic cell cycle checkpoint Source: UniProtKB
Negative regulation of anoikis Source: UniProtKB
Negative regulation of apoptotic process Source: UniProtKB
Negative regulation of autophagy Source: UniProtKB
Negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: UniProtKB
Negative regulation of execution phase of apoptosis Source: UniProtKB
Negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: MGI
Negative regulation of intrinsic apoptotic signaling pathway Source: BHF-UCL
Negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage Source: BHF-UCL
Negative regulation of protein localization to plasma membrane Source: BHF-UCL
Negative regulation of release of cytochrome c from mitochondria Source: BHF-UCL
Positive regulation of intrinsic apoptotic signaling pathway Source: Reactome
Regulation of cytokinesis Source: UniProtKB
Regulation of mitochondrial membrane permeability Source: HGNC-UCL
Regulation of mitochondrial membrane potential Source: HGNC-UCL
Release of cytochrome c from mitochondria Source: HGNC-UCL
Response to cytokine Source: MGI
Suppression by virus of host apoptotic process Source: MGI

Isoform Bcl-X(L): Centrosome; Mitochondrion inner membrane; Mitochondrion outer membrane; Mitochondrion matrix; Cytosol; Nucleus membrane; Synaptic vesicle membrane. 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.

Helical: 210-226 aa

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.