Protein:BAX |
Protein Summary |
 Gene summary |
| Gene name: BAX | ASpdb.0 ID: 581 | Gene | Gene symbol | BAX | Gene ID | 581 |
| Gene name | BCL2 associated X, apoptosis regulator |
| Synonyms | BCL2L4 |
| Cytomap | 19q13.33 |
| Type of gene | protein-coding |
| Description | apoptosis regulator BAXBCL2 associated X proteinBCL2-associated X protein omegaBaxdelta2(G8)-RFS proteinBaxdelta2G9Baxdelta2G9omegaBaxdelta2omegabcl-2-like protein 4bcl2-L-4 |
| Modification date | 20240411 |
| UniProtAcc | Q07812 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | BAX | GO:0001783 | B cell apoptotic process | 15214043|16424160 |
| Gene | BAX | GO:0001836 | release of cytochrome c from mitochondria | 9843949|16199525|17052454|25609812 |
| Gene | BAX | GO:0005634 | nucleus | 12925958 |
| Gene | BAX | GO:0005635 | nuclear envelope | 12925958 |
| Gene | BAX | GO:0005737 | cytoplasm | 16302269|29531808 |
| Gene | BAX | GO:0005739 | mitochondrion | 11912183|15102863|15705586|16199525|17823127|19767770|25609812 |
| Gene | BAX | GO:0005741 | mitochondrial outer membrane | 29531808 |
| Gene | BAX | GO:0005757 | mitochondrial permeability transition pore complex | 9843949 |
| Gene | BAX | GO:0005783 | endoplasmic reticulum | 16424160 |
| Gene | BAX | GO:0005789 | endoplasmic reticulum membrane | 16424160 |
| Gene | BAX | GO:0005829 | cytosol | 11912183|12925958|15102863|15705586|17823127|19767770 |
| Gene | BAX | GO:0006915 | apoptotic process | 9660918|17428862 |
| Gene | BAX | GO:0006919 | activation of cysteine-type endopeptidase activity involved in apoptotic process | 11912183 |
| Gene | BAX | GO:0008053 | mitochondrial fusion | 14769861 |
| Gene | BAX | GO:0008289 | lipid binding | 14522999 |
| Gene | BAX | GO:0008635 | activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c | 15214043 |
| Gene | BAX | GO:0008637 | apoptotic mitochondrial changes | 9843949 |
| Gene | BAX | GO:0009636 | response to toxic substance | 16307838 |
| Gene | BAX | GO:0010248 | establishment or maintenance of transmembrane electrochemical gradient | 9843949 |
| Gene | BAX | GO:0010917 | negative regulation of mitochondrial membrane potential | 16751333 |
| Gene | BAX | GO:0015267 | channel activity | 9219694 |
| Gene | BAX | GO:0031334 | positive regulation of protein-containing complex assembly | 9111042|19805544 |
| Gene | BAX | GO:0032091 | negative regulation of protein binding | 9388232 |
| Gene | BAX | GO:0032976 | release of matrix enzymes from mitochondria | 9843949 |
| Gene | BAX | GO:0042803 | protein homodimerization activity | 16608847 |
| Gene | BAX | GO:0042981 | regulation of apoptotic process | 25609812 |
| Gene | BAX | GO:0043065 | positive regulation of apoptotic process | 16751333|17464193 |
| Gene | BAX | GO:0043525 | positive regulation of neuron apoptotic process | 15637643 |
| Gene | BAX | GO:0043653 | mitochondrial fragmentation involved in apoptotic process | 12499352 |
| Gene | BAX | GO:0046930 | pore complex | 9219694 |
| Gene | BAX | GO:0051434 | BH3 domain binding | 21199865 |
| Gene | BAX | GO:0051881 | regulation of mitochondrial membrane potential | 9843949 |
| Gene | BAX | GO:0071944 | cell periphery | 21803450 |
| Gene | BAX | GO:0090200 | positive regulation of release of cytochrome c from mitochondria | 14963330 |
| Gene | BAX | GO:0097136 | Bcl-2 family protein complex | 21199865 |
| Gene | BAX | GO:0097144 | BAX complex | 14522999|17024184|19074440|19767770|20541605|20850011 |
| Gene | BAX | GO:0097145 | BAK complex | 16113678 |
| Gene | BAX | GO:0097190 | apoptotic signaling pathway | 16424160 |
| Gene | BAX | GO:0097191 | extrinsic apoptotic signaling pathway | 15214043 |
| Gene | BAX | GO:0097193 | intrinsic apoptotic signaling pathway | 9219694|16462759 |
| Gene | BAX | GO:0097435 | supramolecular fiber organization | 31690630 |
| Gene | BAX | GO:0098586 | cellular response to virus | 25609812 |
| Gene | BAX | GO:1990117 | B cell receptor apoptotic signaling pathway | 15214043 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| Q07812-1 | Q07812-1_4s0o_A.pdb | 4S0O | X-ray | 1.9 | A | 13 | 192 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| Q07812 | BAX | Q07812-1 | Q07812-2 | 192 | 218 | 159 | 192 | Substitution | DGLLSYFGTPTWQTVTIFVAGVLTASLTIWKKMG | VRLLKPPHPHHRALTTAPAPPSLPPATPLGPWAFWSRSQWCPLPIFRSSDVVYNAFSLRV | 159 | 218 |
| Q07812 | BAX | Q07812-1 | Q07812-3 | 192 | 41 | 12 | 41 | Substitution | GPTSSEQIMKTGALLLQGFIQDRAGRMGGE | VSSRIEQGEWGGRHPSWPWTRCLRMRPPRS | 12 | 41 |
| Q07812 | BAX | Q07812-1 | Q07812-3 | 192 | 41 | 42 | 192 | Deletion | none | none | 41 | 41 |
| Q07812 | BAX | Q07812-1 | Q07812-4 | 192 | 143 | 30 | 78 | Deletion | none | none | 29 | 29 |
| Q07812 | BAX | Q07812-1 | Q07812-5 | 192 | 164 | 125 | 192 | Substitution | LCTKVPELIRTIMGWTLDFLRERLLGWIQDQGGWDGLLSYFGTPTWQTVTIFVAGVLTASLTIWKKMG | GVKWRDLGSLQPLPPGFKRFTCLSIPRSWDYRPCAPRCRN | 125 | 164 |
| Q07812 | BAX | Q07812-1 | Q07812-6 | 192 | 114 | 1 | 78 | Deletion | none | none | 0 | 0 |
| Q07812 | BAX | Q07812-1 | Q07812-7 | 192 | 173 | 1 | 19 | Deletion | none | none | 0 | 0 |
| Q07812 | BAX | Q07812-1 | Q07812-8 | 192 | 179 | 159 | 171 | Deletion | none | none | 158 | 158 |
| Multiple sequence alignment of our canonical and alternatively spliced BAX |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of BAX |
| UniProt-id | ENSG | ENST | ENSP |
| Q07812-1 | ENSG00000087088.21 | ENST00000345358.12 | ENSP00000263262.9 |
| Q07812-2 | ENSG00000087088.21 | ENST00000293288.12 | ENSP00000293288.8 |
| Q07812-3 | ENSG00000087088.21 | ENST00000515540.5 | ENSP00000426328.1 |
| Q07812-4 | ENSG00000087088.21 | ENST00000354470.7 | ENSP00000346461.3 |
| Q07812-5 | ENSG00000087088.21 | ENST00000356483.8 | ENSP00000348871.4 |
| Q07812-8 | ENSG00000087088.21 | ENST00000415969.6 | ENSP00000389971.2 |
| UniProt-id | NM ID | NP ID |
| Q07812-1 | NM_138761.3 | NP_620116.1 |
| Q07812-2 | NM_004324.3 | NP_004315.1 |
| Q07812-4 | NM_138763.3 | NP_620118.1 |
| Q07812-6 | NM_001291431.1 | NP_001278360.1 |
| Q07812-8 | NM_138764.4 | NP_620119.2 |
| Amino acid sequences of our canonical and alternatively spliced BAX |
| accession_id | Protein sequence |
| Q07812-1 | MDGSGEQPRGGGPTSSEQIMKTGALLLQGFIQDRAGRMGGEAPELALDPVPQDASTKKLSECLKRIGDELDSNMELQRMIAAVDTDSPRE VFFRVAADMFSDGNFNWGRVVALFYFASKLVLKALCTKVPELIRTIMGWTLDFLRERLLGWIQDQGGWDGLLSYFGTPTWQTVTIFVAGV |
| Q07812-2 | MDGSGEQPRGGGPTSSEQIMKTGALLLQGFIQDRAGRMGGEAPELALDPVPQDASTKKLSECLKRIGDELDSNMELQRMIAAVDTDSPRE VFFRVAADMFSDGNFNWGRVVALFYFASKLVLKALCTKVPELIRTIMGWTLDFLRERLLGWIQDQGGWVRLLKPPHPHHRALTTAPAPPS |
| Q07812-3 | |
| Q07812-4 | MDGSGEQPRGGGPTSSEQIMKTGALLLQGMIAAVDTDSPREVFFRVAADMFSDGNFNWGRVVALFYFASKLVLKALCTKVPELIRTIMGW |
| Q07812-5 | MDGSGEQPRGGGPTSSEQIMKTGALLLQGFIQDRAGRMGGEAPELALDPVPQDASTKKLSECLKRIGDELDSNMELQRMIAAVDTDSPRE |
| Q07812-6 | MIAAVDTDSPREVFFRVAADMFSDGNFNWGRVVALFYFASKLVLKALCTKVPELIRTIMGWTLDFLRERLLGWIQDQGGWDGLLSYFGTP |
| Q07812-7 | MKTGALLLQGFIQDRAGRMGGEAPELALDPVPQDASTKKLSECLKRIGDELDSNMELQRMIAAVDTDSPREVFFRVAADMFSDGNFNWGR |
| Q07812-8 | MDGSGEQPRGGGPTSSEQIMKTGALLLQGFIQDRAGRMGGEAPELALDPVPQDASTKKLSECLKRIGDELDSNMELQRMIAAVDTDSPRE |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| BAX (go to UniProt):Q07812 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Q07812 | Transmembrane | 172 | 192 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=159;End=192 |
| Q07812 | Transmembrane | 172 | 192 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=42;End=192 |
| Q07812 | Transmembrane | 172 | 192 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=125;End=192 |
| Q07812 | Motif | 59 | 73 | Note=BH3;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8521816;Dbxref=PMID:8521816 | Type=Deletion;Start=42;End=192 |
| Q07812 | Motif | 59 | 73 | Note=BH3;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8521816;Dbxref=PMID:8521816 | Type=Deletion;Start=30;End=78 |
| Q07812 | Motif | 59 | 73 | Note=BH3;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8521816;Dbxref=PMID:8521816 | Type=Deletion;Start=1;End=78 |
| Q07812 | Motif | 98 | 118 | Note=BH1 | Type=Deletion;Start=42;End=192 |
| Q07812 | Motif | 150 | 165 | Note=BH2 | Type=Substitution;Start=159;End=192 |
| Q07812 | Motif | 150 | 165 | Note=BH2 | Type=Deletion;Start=42;End=192 |
| Q07812 | Motif | 150 | 165 | Note=BH2 | Type=Substitution;Start=125;End=192 |
| Q07812 | Motif | 150 | 165 | Note=BH2 | Type=Deletion;Start=159;End=171 |
Gene Isoform Structures and Expression Levels for BAX |
| Gene structures of our canonical and alternative spliced genes of BAX * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of Q07812-1 |
| 3D view using mol* of Q07812-2 |
| 3D view using mol* of Q07812-3 |
| 3D view using mol* of Q07812-4 |
| 3D view using mol* of Q07812-5 |
| 3D view using mol* of Q07812-6 |
| 3D view using mol* of Q07812-7 |
| 3D view using mol* of Q07812-8 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of Q07812-1 |
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| pLDDT distribution across the protein length of Q07812-2 |
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| pLDDT distribution across the protein length of Q07812-4 |
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| pLDDT distribution across the protein length of Q07812-5 |
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| pLDDT distribution across the protein length of Q07812-6 |
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| pLDDT distribution across the protein length of Q07812-7 |
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| pLDDT distribution across the protein length of Q07812-8 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of Q07812-1 |
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| Ramachandran plot of Q07812-4 |
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| Ramachandran plot of Q07812-6 |
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| Ramachandran plot of Q07812-7 |
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| Ramachandran plot of Q07812-8 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| Q07812-1 | 0.705 | 32 | 0.479 | 83.692 | 0.579 | 0.732 | 1.023 | 0.054 | 1.509 | 0.036 | 0.984 | 13,18,19,21,22,25,53,55,56,59,157,158,159
|
| Q07812-2 | 0.998 | 198 | 1.04 | 457.219 | 0.618 | 0.651 | 0.862 | 0.53 | 0.89 | 0.596 | 1.175 | 62,65,66,69,70,72,73,74,76,79,190,193,194,195,196, 197,198,199,200,201,202,204,205,206,207,208,209,21 0,211 |
| Q07812-4 | 0.674 | 18 | 0.639 | 69.286 | 0.571 | 0.702 | 0.99 | 1.627 | 0.555 | 2.93 | 2.948 | 37,39,42,43,71,74,75,78,83,87,90
|
| Q07812-5 | 1.074 | 456 | 1.157 | 1341.473 | 0.578 | 0.675 | 0.859 | 1.582 | 0.577 | 2.74 | 1.173 | 13,14,16,18,19,20,21,22,23,24,25,26,27,31,50,51,52 ,53,55,56,58,59,61,62,63,65,66,88,89,92,93,96,97,1 00,105,106,107,110,111,113,114,117,120,121,124,126 ,128,130,131,132,133,134,135,136,137,138,139,141,1 42,143,144,145,146,147,149,150,153,155 |
| Q07812-6 | 0.774 | 19 | 0.796 | 62.769 | 0.513 | 0.72 | 1.09 | 3.237 | 0.14 | 23.119 | 0.404 | 10,13,14,38,42,54,58,61
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| Q07812-7 | 0.694 | 33 | 0.663 | 95.011 | 0.711 | 0.636 | 0.847 | 0.375 | 0.793 | 0.473 | 0.567 | 6,9,10,11,13,30,31,32,33,38,41,45
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| Q07812-8 | 1.037 | 105 | 1.092 | 193.109 | 0.483 | 0.68 | 0.874 | 1.404 | 0.786 | 1.786 | 1.609 | 76,79,80,83,94,95,98,99,100,101,102,109,112,115,11 6,173,174,175,177,178 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of Q07812-1_Q07812-1_4s0o_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q07812-1_4s0o_A_Q07812-2.pdb |
| 3D view using mol* of Q07812-1_4s0o_A_Q07812-3.pdb |
| 3D view using mol* of Q07812-1_4s0o_A_Q07812-4.pdb |
| 3D view using mol* of Q07812-1_4s0o_A_Q07812-5.pdb |
| 3D view using mol* of Q07812-1_4s0o_A_Q07812-6.pdb |
| 3D view using mol* of Q07812-1_4s0o_A_Q07812-7.pdb |
| 3D view using mol* of Q07812-1_4s0o_A_Q07812-8.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q07812-1_Q07812-2.pdb |
| 3D view using mol* of Q07812-1_Q07812-3.pdb |
| 3D view using mol* of Q07812-1_Q07812-4.pdb |
| 3D view using mol* of Q07812-1_Q07812-5.pdb |
| 3D view using mol* of Q07812-1_Q07812-6.pdb |
| 3D view using mol* of Q07812-1_Q07812-7.pdb |
| 3D view using mol* of Q07812-1_Q07812-8.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/Q07812-1_vs_Q07812-2.png |
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| ./stats/secondary_structure/figure/Q07812-1_vs_Q07812-3.png |
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| ./stats/secondary_structure/figure/Q07812-1_vs_Q07812-4.png |
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| ./stats/secondary_structure/figure/Q07812-1_vs_Q07812-5.png |
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| ./stats/secondary_structure/figure/Q07812-1_vs_Q07812-6.png |
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| ./stats/secondary_structure/figure/Q07812-1_vs_Q07812-7.png |
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| ./stats/secondary_structure/figure/Q07812-1_vs_Q07812-8.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/Q07812-1_vs_Q07812-2.png |
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| ./stats/relative_asa/Q07812-1_vs_Q07812-3.png |
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| ./stats/relative_asa/Q07812-1_vs_Q07812-4.png |
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| ./stats/relative_asa/Q07812-1_vs_Q07812-5.png |
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| ./stats/relative_asa/Q07812-1_vs_Q07812-6.png |
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| ./stats/relative_asa/Q07812-1_vs_Q07812-7.png |
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| ./stats/relative_asa/Q07812-1_vs_Q07812-8.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to BAX |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| Q07812 | BAX | DB12756 | TAK-901 | investigational | activator |
Related Diseases to BAX |
| Previous studies relating to the alternative splicing of BAX and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| BAX | 22910913 | BaxΔ2 is a novel bax isoform unique to microsatellite unstable tumors. | "The pro-death Bcl-2 family protein and tumor suppressor Bax is frequently mutated in tumors with microsatellite instability (MSI). The mutation often results in a ""Bax negative"" phenotype and therefore is generally thought to be beneficial to the development of the tumor. Here, we report the identification of a novel Bax isoform, BaxΔ2, which is unique to microsatellite unstable tumors. BaxΔ2 is generated by a unique combination of a microsatellite deletion in Bax exon 3 and alternative splicing of Bax exon 2. Consistently, BaxΔ2 is only detected in MSI cell lines and primary tumors. BaxΔ2 is a potent cell death inducer but does not directly target mitochondria. In addition, BaxΔ2 sensitizes certain MSI tumor cells to a subset of chemotherapeutic agents, such as adriamycin. Thus, our data provide evidence that mutation and alternative splicing of tumor suppressors such as Bax are not always beneficial to tumor development but can be detrimental instead." | D053842 | Microsatellite Instability |
| BAX | 22910913 | BaxΔ2 is a novel bax isoform unique to microsatellite unstable tumors. | "The pro-death Bcl-2 family protein and tumor suppressor Bax is frequently mutated in tumors with microsatellite instability (MSI). The mutation often results in a ""Bax negative"" phenotype and therefore is generally thought to be beneficial to the development of the tumor. Here, we report the identification of a novel Bax isoform, BaxΔ2, which is unique to microsatellite unstable tumors. BaxΔ2 is generated by a unique combination of a microsatellite deletion in Bax exon 3 and alternative splicing of Bax exon 2. Consistently, BaxΔ2 is only detected in MSI cell lines and primary tumors. BaxΔ2 is a potent cell death inducer but does not directly target mitochondria. In addition, BaxΔ2 sensitizes certain MSI tumor cells to a subset of chemotherapeutic agents, such as adriamycin. Thus, our data provide evidence that mutation and alternative splicing of tumor suppressors such as Bax are not always beneficial to tumor development but can be detrimental instead." | D009369 | Neoplasms |
| BAX | 24842234 | BaxΔ2 promotes apoptosis through caspase-8 activation in microsatellite-unstable colon cancer. | Loss of apoptotic Bax due to microsatellite mutation contributes to tumor development and chemoresistance. Recently, a Bax microsatellite mutation was uncovered in combination with a specific alternative splicing event that could generate a unique Bax isoform (BaxΔ2) in otherwise Bax-negative cells. Like the prototype Baxα, BaxΔ2 is a potent proapoptotic molecule. However, the proapoptotic mechanism and therapeutic implication of BaxΔ2 remain elusive. Here, the isolation and analysis of isogenic subcell lines are described that represent different Bax microsatellite statuses from colorectal cancer. Colon cancer cells harboring Bax microsatellite G7/G7 alleles are capable of producing low levels of endogenous BaxΔ2 transcripts and proteins. Interestingly, BaxΔ2-positive cells are selectively sensitive to a subgroup of chemotherapeutics compared with BaxΔ2-negative cells. Unlike other Bax isoforms, BaxΔ2 recruits caspase-8 into the proximity for activation, and the latter, in turn, activates caspase-3 and apoptosis independent of the mitochondrial pathway. These data suggest that the expression of BaxΔ2 may provide alternative apoptotic and chemotherapeutic advantages for Bax-negative tumors. | D015179 | Colorectal Neoplasms |
| BAX | 24842234 | BaxΔ2 promotes apoptosis through caspase-8 activation in microsatellite-unstable colon cancer. | Loss of apoptotic Bax due to microsatellite mutation contributes to tumor development and chemoresistance. Recently, a Bax microsatellite mutation was uncovered in combination with a specific alternative splicing event that could generate a unique Bax isoform (BaxΔ2) in otherwise Bax-negative cells. Like the prototype Baxα, BaxΔ2 is a potent proapoptotic molecule. However, the proapoptotic mechanism and therapeutic implication of BaxΔ2 remain elusive. Here, the isolation and analysis of isogenic subcell lines are described that represent different Bax microsatellite statuses from colorectal cancer. Colon cancer cells harboring Bax microsatellite G7/G7 alleles are capable of producing low levels of endogenous BaxΔ2 transcripts and proteins. Interestingly, BaxΔ2-positive cells are selectively sensitive to a subgroup of chemotherapeutics compared with BaxΔ2-negative cells. Unlike other Bax isoforms, BaxΔ2 recruits caspase-8 into the proximity for activation, and the latter, in turn, activates caspase-3 and apoptosis independent of the mitochondrial pathway. These data suggest that the expression of BaxΔ2 may provide alternative apoptotic and chemotherapeutic advantages for Bax-negative tumors. | D053842 | Microsatellite Instability |
Clinically important variants in BAX |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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