Bcl-2-like protein 1 (BCL2L1)
The protein contains 233 amino acids for an estimated molecular weight of 26049 Da.
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. (updated: Jan. 31, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is predicted to be membranous by TOPCONS.
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Biological Process
Apoptotic mitochondrial changes
Apoptotic process
Apoptotic process in bone marrow cell
Cell population proliferation
Cellular process regulating host cell cycle in response to virus
Cellular response to alkaloid
Cellular response to amino acid stimulus
Cellular response to gamma radiation
Cytokine-mediated signaling pathway
Cytokinesis
Defense response to virus
Endocytosis
Extrinsic apoptotic signaling pathway in absence of ligand
Fertilization
Germ cell development
Growth
Hepatocyte apoptotic process
In utero embryonic development
Innate immune response
Intrinsic apoptotic signaling pathway
Intrinsic apoptotic signaling pathway in response to DNA damage
Male gonad development
MAPK cascade
Mitochondrion morphogenesis
Mitotic cell cycle checkpoint signaling
Negative regulation of anoikis
Negative regulation of apoptotic process
Negative regulation of autophagy
Negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
Negative regulation of establishment of protein localization to plasma membrane
Negative regulation of execution phase of apoptosis
Negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
Negative regulation of intrinsic apoptotic signaling pathway
Negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage
Negative regulation of neuron apoptotic process
Negative regulation of protein localization to plasma membrane
Negative regulation of release of cytochrome c from mitochondria
Neuron apoptotic process
Nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
Ovarian follicle development
Positive regulation of cell population proliferation
Positive regulation of intrinsic apoptotic signaling pathway
Regulation of cytokinesis
Regulation of growth
Regulation of mitochondrial membrane permeability
Regulation of mitochondrial membrane potential
Release of cytochrome c from mitochondria
Response to cycloheximide
Response to cytokine
Response to virus
Spermatogenesis
Suppression by virus of host apoptotic process
The reference OMIM entry for this protein is 600039
Bcl2-like 1; bcl2l1
Bcl2-related gene; bclx bcl2-related protein, long isoform, included; bclxl, included
Bcl2-related protein, short isoform, included; bclxs, included
CLONING
Boise et al. (1993) isolated a BCL2 (151430)-related gene, which they designated BCLX, and showed that it can function as a BCL2-independent regulator of programmed cell death (apoptosis). Alternative splicing resulted in 2 distinct BCLX mRNAs. The protein product of the larger mRNA (BCLXL) was similar in size and predicted structure to BCL2. When stably transfected into an IL3-dependent cell line, it inhibited cell death upon growth factor withdrawal at least as well as BCL2. Unexpectedly, the smaller mRNA species (BCLXS) encodes a protein that inhibits the ability of BCL2 to enhance the survival of growth factor-deprived cells. In vivo, the smaller BCLX mRNA was expressed at high levels in cells that undergo a high rate of turnover, such as developing lymphocytes. In contrast, the large form of BCLX was found in tissues containing long-lived postmitotic cells, such as adult brain. Together these data suggested that BCLX plays an important role in both positive and negative regulation of programmed cell death. Boise et al. (1993) found that BCLX is highly conserved in vertebrate evolution. By microarray analysis, Jun et al. (2001) demonstrated expression of the BCL2L1 gene in human donor corneas.GENE FUNCTION
Vander Heiden et al. (1997) observed in Jurkat cells that a wide variety of apoptotic and necrotic stimuli induce progressive mitochondrial swelling and outer mitochondrial membrane rupture. Discontinuity of the outer mitochondrial membrane results in cytochrome c redistribution from the intermembrane space to the cytosol, followed by subsequent inner mitochondrial membrane depolarization. The mitochondrial membrane protein BCLX could inhibit these changes in cells treated with apoptotic stimuli. In addition, BCLX-expressing cells adapt to growth factor withdrawal or staurosporine treatment by maintaining a decreased mitochondrial membrane potential. BCLX expression also prevents mitochondrial swelling in response to agents that inhibit oxidative phosphorylation. These data suggested to Vander Heiden et al. (1997) that BCLX promotes cell survival by regulating the electrical and osmotic homeostasis of mitochondria. Silva et al. (1998) found that erythroid cells from patients with polycythemia vera (263300) survived in vitro without erythropoietin. This finding correlated with the expression of BCLX protein, even in mature erythroblasts that normally do not express BCLX. The large BCLX mRNA was the predominant form detected in the erythropoietin-independent erythroid cells. They concluded that deregulated expression of BCLX may contribute to the erythropoietin-independent survival of erythroid-lineage cells in polycythemia vera and thereby contribute to the pathogenesis of this disorder. Moliterno et al. (1998) simultaneously reported impaired expression of the thrombopoietin receptor (MPL; 159530) by platelets from patients with polycythemia vera. During transduction of an apoptotic signal into the cell, there is an alteration in the permeability of the membranes of the cell's mitochondria, which causes the translocation of the apoptogenic protein cytochrome c into the cytoplasm, which in turn activates death-driving proteolytic proteins known as caspases (see 147678). The BCL2 family of proteins, whose members may be antiapoptotic or proapoptotic, regulates cell death by controlling this mitochondrial membrane permeability during apoptosis. Shimizu et al. (1999) created liposomes that carried the mi ... More on the omim web site
Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600039 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed