Apoptosis regulator BAX (BAX)
The protein contains 192 amino acids for an estimated molecular weight of 21184 Da.
Plays a role in the mitochondrial apoptotic process. Under normal conditions, BAX is largely cytosolic via constant retrotranslocation from mitochondria to the cytosol mediated by BCL2L1/Bcl-xL, which avoids accumulation of toxic BAX levels at the mitochondrial outer membrane (MOM) (PubMed:21458670). Under stress conditions, undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis. Promotes activation of CASP3, and thereby apoptosis. (updated: March 28, 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
Activation of cysteine-type endopeptidase activity involved in apoptotic process
Activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c
Activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
Apoptotic mitochondrial changes
Apoptotic process
Apoptotic process involved in blood vessel morphogenesis
Apoptotic process involved in embryonic digit morphogenesis
Apoptotic signaling pathway
B cell apoptotic process
B cell homeostasis
B cell homeostatic proliferation
B cell negative selection
B cell receptor apoptotic signaling pathway
Blood vessel remodeling
Cellular response to organic substance
Cellular response to unfolded protein
Cellular response to UV
Cellular response to virus
Cerebral cortex development
Development of secondary sexual characteristics
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
Ectopic germ cell programmed cell death
Endoplasmic reticulum calcium ion homeostasis
Establishment or maintenance of transmembrane electrochemical gradient
Extrinsic apoptotic signaling pathway
Extrinsic apoptotic signaling pathway in absence of ligand
Extrinsic apoptotic signaling pathway via death domain receptors
Fertilization
Germ cell development
Glycosphingolipid metabolic process
Homeostasis of number of cells within a tissue
Hypothalamus development
Intrinsic apoptotic signaling pathway
Intrinsic apoptotic signaling pathway by p53 class mediator
Intrinsic apoptotic signaling pathway in response to DNA damage
Intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
Kidney development
Mitochondrial fragmentation involved in apoptotic process
Mitochondrial fusion
Mitochondrion morphogenesis
Myeloid cell homeostasis
Negative regulation of apoptotic signaling pathway
Negative regulation of endoplasmic reticulum calcium ion concentration
Negative regulation of fibroblast proliferation
Negative regulation of mitochondrial membrane potential
Negative regulation of neuron apoptotic process
Negative regulation of peptidyl-serine phosphorylation
Negative regulation of protein binding
Neuron apoptotic process
Neuron migration
Obsolete activation of signaling protein activity involved in unfolded protein response
Obsolete transformed cell apoptotic process
Odontogenesis of dentin-containing tooth
Ovarian follicle development
Positive regulation of apoptotic DNA fragmentation
Positive regulation of apoptotic process
Positive regulation of apoptotic process involved in mammary gland involution
Positive regulation of B cell apoptotic process
Positive regulation of developmental pigmentation
Positive regulation of endoplasmic reticulum unfolded protein response
Positive regulation of extrinsic apoptotic signaling pathway in absence of ligand
Positive regulation of intrinsic apoptotic signaling pathway
Positive regulation of IRE1-mediated unfolded protein response
Positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
Positive regulation of neuron apoptotic process
Positive regulation of protein oligomerization
Positive regulation of protein-containing complex assembly
Positive regulation of release of cytochrome c from mitochondria
Positive regulation of release of sequestered calcium ion into cytosol
Post-embryonic camera-type eye morphogenesis
Protein complex oligomerization
Protein homooligomerization
Protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
Regulation of apoptotic process
Regulation of cell cycle
Regulation of mammary gland epithelial cell proliferation
Regulation of mitochondrial membrane permeability involved in programmed necrotic cell death
Regulation of mitochondrial membrane potential
Regulation of nitrogen utilization
Regulation of protein heterodimerization activity
Regulation of protein homodimerization activity
Regulation of transcription initiation from RNA polymerase II promoter
Release of cytochrome c from mitochondria
Release of matrix enzymes from mitochondria
Response to axon injury
Response to gamma radiation
Response to salt stress
Response to toxic substance
Retina development in camera-type eye
Retinal cell apoptotic process
Retinal cell programmed cell death
Sertoli cell proliferation
Spermatid differentiation
T cell homeostatic proliferation
Thymocyte apoptotic process
Transcription initiation from RNA polymerase II promoter
Vagina development
Viral process
Cellular Component
BAK complex
BAX complex
Bcl-2 family protein complex
Cytoplasm
Cytosol
Endoplasmic reticulum
Endoplasmic reticulum membrane
Extracellular exosome
Membrane
Mitochondrial outer membrane
Mitochondrial permeability transition pore complex
Mitochondrion
Nuclear envelope
Nucleus
Obsolete cell
Pore complex
The reference OMIM entry for this protein is 600040
Bcl2-associated x protein; bax
DESCRIPTION
The proapoptotic BAX protein induces cell death by acting on mitochondria.CLONING
Oltvai et al. (1993) identified BAX as a protein partner of BCL2 (151430).GENE FUNCTION
Development as well as maintenance of many adult tissues is achieved by several dynamically regulated processes that include cell proliferation, differentiation, and programmed cell death. Oltvai et al. (1993) noted that, in the latter process, cells are eliminated by a highly characteristic suicide program called apoptosis. The best-defined genetic pathway of cell death exists in the nematode Caenorhabditis elegans. Two autosomal recessive death effector genes, ced-3 and ced-4, are required for the death of all 131 cells destined to die during worm development. One autosomal dominant death repressor gene, ced-9, can save those cells in its gain-of-function form. This implies that both effector and repressor genes also exist within each mammalian cell death pathway. BCL2 is one such mammalian gene that has been identified; it functions as a repressor of programmed cell death. Oltvai et al. (1993) showed that BCL2 associates in vivo with a 21-kD program partner, BAX. BAX shows extensive amino acid homology with BCL2 and forms homodimers and heterodimers with BCL2 in vivo. When BAX predominates, programmed cell death is accelerated, and the death repressor activity of BCL2 is countered. Their findings suggested to Oltvai et al. (1993) a model in which the ratio of BCL2 to BAX determines survival or death following an apoptotic stimulus. The BAX gene promoter region contains 4 motifs with homology to consensus p53-binding sites. In cotransfection assays using p53-deficient tumor cell lines, Miyashita and Reed (1995) found that wildtype but not mutant p53 expression plasmids transactivated a reporter gene plasmid that utilized the BAX gene promoter to drive transcription of chloramphenicol acetyltransferase. Introduction of mutations into the consensus p53-binding site sequences abolished p53 responsiveness of the reporter gene plasmids. Taken together, the results suggested that BAX is a primary-response gene for p53 (191170) and is involved in a p53-regulated pathway for induction of apoptosis. Apte et al. (1995) isolated a BAX cDNA clone in which the mRNA encoded by exon 3 was absent. The skipping of exon 3 predicted the existence of an interstitially truncated form of the major BAX protein (BAX-alpha), termed BAX-delta. Unlike 2 previously described variant forms, BAX-delta retains the functionally critical C-terminal membrane anchor region, as well as the BCL2 homology 1 and 2 (BH1 and BH2) domains. Cartron et al. (2002) examined the expression of BAX in 55 patients with glioblastoma multiforme (see 137800), the most common and aggressive form of brain tumors. The authors identified a novel form of BAX, designated BAX-psi, which was present in 24% of the patients. BAX-psi is an N-terminal truncated form of BAX which results from a partial deletion of exon 1 of the BAX gene. BAX-psi and the wildtype form, BAX-alpha, are encoded by distinct mRNAs, both of which are present in normal tissues. Glial tumors expressed either BAX-alpha or BAX-psi proteins, an apparent consequence of an exclusive transcription of the corresponding mRNAs. The BAX-psi protein was preferentially localized to mitochondria and was a more powerful inducer of apoptosis than BAX-alpha. BAX-psi tumors exhibited slower proliferation in Swiss nude mice, and ... More on the omim web site
April 12, 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 600040 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed