Protein:BCL2 |
Protein Summary |
 Gene summary |
| Gene name: BCL2 | ASpdb.0 ID: 596 | Gene | Gene symbol | BCL2 | Gene ID | 596 |
| Gene name | BCL2 apoptosis regulator |
| Synonyms | Bcl-2|PPP1R50 |
| Cytomap | 18q21.33 |
| Type of gene | protein-coding |
| Description | apoptosis regulator Bcl-2B-cell CLL/lymphoma 2protein phosphatase 1, regulatory subunit 50 |
| Modification date | 20240411 |
| UniProtAcc | P10415 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | BCL2 | GO:0000209 | protein polyubiquitination | 16717086 |
| Gene | BCL2 | GO:0002020 | protease binding | 10620603 |
| Gene | BCL2 | GO:0005634 | nucleus | 7546744|7896880 |
| Gene | BCL2 | GO:0005737 | cytoplasm | 7546744|11530860 |
| Gene | BCL2 | GO:0005739 | mitochondrion | 7896880|9027314 |
| Gene | BCL2 | GO:0005741 | mitochondrial outer membrane | 21358617 |
| Gene | BCL2 | GO:0005741 | mitochondrial outer membrane | 8402648|9027314 |
| Gene | BCL2 | GO:0005783 | endoplasmic reticulum | 8402648 |
| Gene | BCL2 | GO:0005789 | endoplasmic reticulum membrane | 21358617 |
| Gene | BCL2 | GO:0006915 | apoptotic process | 36599|8022822 |
| Gene | BCL2 | GO:0008625 | extrinsic apoptotic signaling pathway via death domain receptors | 10597216 |
| Gene | BCL2 | GO:0009410 | response to xenobiotic stimulus | 36599 |
| Gene | BCL2 | GO:0009636 | response to toxic substance | 16717086 |
| Gene | BCL2 | GO:0009636 | response to toxic substance | 16307838 |
| Gene | BCL2 | GO:0010039 | response to iron ion | 11264898 |
| Gene | BCL2 | GO:0010507 | negative regulation of autophagy | 21358617 |
| Gene | BCL2 | GO:0015267 | channel activity | 9219694 |
| Gene | BCL2 | GO:0016020 | membrane | 7896880 |
| Gene | BCL2 | GO:0016248 | channel inhibitor activity | 9219694 |
| Gene | BCL2 | GO:0022898 | regulation of transmembrane transporter activity | 9219694 |
| Gene | BCL2 | GO:0030307 | positive regulation of cell growth | 8022822 |
| Gene | BCL2 | GO:0031965 | nuclear membrane | 1502141|8402648 |
| Gene | BCL2 | GO:0032848 | negative regulation of cellular pH reduction | 10506221 |
| Gene | BCL2 | GO:0034097 | response to cytokine | 9184696 |
| Gene | BCL2 | GO:0035094 | response to nicotine | 12421819 |
| Gene | BCL2 | GO:0042100 | B cell proliferation | 1373874 |
| Gene | BCL2 | GO:0043066 | negative regulation of apoptotic process | 1373874|7650367|7772249|8050499|8080725|15776018 |
| Gene | BCL2 | GO:0043066 | negative regulation of apoptotic process | 9027314|9219694|10506221|10620603|20041405 |
| Gene | BCL2 | GO:0043524 | negative regulation of neuron apoptotic process | 7546744 |
| Gene | BCL2 | GO:0043565 | sequence-specific DNA binding | 12086670 |
| Gene | BCL2 | GO:0046930 | pore complex | 9219694 |
| Gene | BCL2 | GO:0051607 | defense response to virus | 10620603 |
| Gene | BCL2 | GO:0051924 | regulation of calcium ion transport | 8022822 |
| Gene | BCL2 | GO:0070059 | intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | 15776018 |
| Gene | BCL2 | GO:2001243 | negative regulation of intrinsic apoptotic signaling pathway | 11684014 |
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 |
| P10415-1 | P10415-1_5vau_A.pdb | 5VAU | X-ray | 1.75 | A | 1 | 206 |
| 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 |
| P10415 | BCL2 | P10415-1 | P10415-2 | 239 | 205 | 196 | 239 | Substitution | DAFVELYGPSMRPLFDFSWLSLKTLLSLALVGACITLGAYLGHK | VGALGDVSLG | 196 | 205 |
| Multiple sequence alignment of our canonical and alternatively spliced BCL2 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of BCL2 |
| UniProt-id | ENSG | ENST | ENSP |
| P10415-1 | ENSG00000171791.14 | ENST00000333681.5 | ENSP00000329623.3 |
| P10415-1 | ENSG00000171791.14 | ENST00000398117.1 | ENSP00000381185.1 |
| P10415-2 | ENSG00000171791.14 | ENST00000589955.2 | ENSP00000466417.1 |
| P10415-2 | ENSG00000171791.14 | ENST00000678349.1 | ENSP00000504190.1 |
| UniProt-id | NM ID | NP ID |
| P10415-1 | NM_000633.2 | NP_000624.2 |
| P10415-2 | NM_000657.2 | NP_000648.2 |
| Amino acid sequences of our canonical and alternatively spliced BCL2 |
| accession_id | Protein sequence |
| P10415-1 | MAHAGRTGYDNREIVMKYIHYKLSQRGYEWDAGDVGAAPPGAAPAPGIFSSQPGHTPHPAASRDPVARTSPLQTPAAPGAAAGPALSPVP PVVHLTLRQAGDDFSRRYRRDFAEMSSQLHLTPFTARGRFATVVEELFRDGVNWGRIVAFFEFGGVMCVESVNREMSPLVDNIALWMTEY |
| P10415-2 | MAHAGRTGYDNREIVMKYIHYKLSQRGYEWDAGDVGAAPPGAAPAPGIFSSQPGHTPHPAASRDPVARTSPLQTPAAPGAAAGPALSPVP PVVHLTLRQAGDDFSRRYRRDFAEMSSQLHLTPFTARGRFATVVEELFRDGVNWGRIVAFFEFGGVMCVESVNREMSPLVDNIALWMTEY |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| BCL2 (go to UniProt):P10415 |
| 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 |
| P10415 | Transmembrane | 212 | 233 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=196;End=239 |
| P10415 | Motif | 187 | 202 | Note=BH2;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=196;End=239 |
Gene Isoform Structures and Expression Levels for BCL2 |
| Gene structures of our canonical and alternative spliced genes of BCL2 * 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 P10415-1 |
| 3D view using mol* of P10415-2 |
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 P10415-1 |
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| pLDDT distribution across the protein length of P10415-2 |
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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 P10415-1 |
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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 |
| P10415-1 | 0.918 | 76 | 0.893 | 192.08 | 0.528 | 0.716 | 0.899 | 0.523 | 1.093 | 0.479 | 0.511 | 22,25,26,102,105,106,109,112,113,116,152,155,156,1 59,160,163 |
| P10415-2 | 0.869 | 45 | 0.595 | 80.948 | 0.451 | 0.862 | 1.151 | 1.089 | 1.697 | 0.641 | 0.515 | 45,47,48,49,127,128,130,131,176,179,180,183,184
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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 P10415-1_P10415-1_5vau_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 P10415-1_5vau_A_P10415-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P10415-1_P10415-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P10415-1_vs_P10415-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P10415-1_vs_P10415-2.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 BCL2 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P10415 | BCL2 | DB01229 | Paclitaxel | approved, vet_approved | inhibitor |
| P10415 | BCL2 | DB12816 | Terpinen-4-ol | investigational | regulator |
| P10415 | BCL2 | DB12843 | Oleandrin | experimental, investigational | downregulator |
| P10415 | BCL2 | DB06307 | Apoptone | investigational | |
| P10415 | BCL2 | DB08871 | Eribulin | approved, investigational | |
| P10415 | BCL2 | DB01050 | Ibuprofen | approved | modulator |
| P10415 | BCL2 | DB09213 | Dexibuprofen | approved, investigational | negative modulator |
| P10415 | BCL2 | DB12340 | Navitoclax | investigational | inhibitor |
| P10415 | BCL2 | DB01367 | Rasagiline | approved | activator |
| P10415 | BCL2 | DB05103 | AN-9 | investigational | downregulator |
| P10415 | BCL2 | DB11581 | Venetoclax | approved, investigational | antagonist, inhibitor |
| P10415 | BCL2 | DB12191 | Obatoclax | investigational | |
| P10415 | BCL2 | DB01248 | Docetaxel | approved, investigational | |
| P10415 | BCL2 | DB05297 | Paclitaxel docosahexaenoic acid | investigational |
Related Diseases to BCL2 |
| Previous studies relating to the alternative splicing of BCL2 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| BCL2 | 15231831 | BAD is a pro-survival factor prior to activation of its pro-apoptotic function. | The mammalian BAD protein belongs to the BH3-only subgroup of the BCL-2 family. In contrast to its known pro-apoptotic function, we found that endogenous and overexpressed BAD(L) can inhibit cell death in neurons and other cell types. Several mechanisms regulate the conversion of BAD from an anti-death to a pro-death factor, including alternative splicing that produces the N-terminally truncated BAD(S). In addition, caspases convert BAD(L) into a pro-death fragment that resembles the short splice variant. The caspase site that is selectively cleaved during cell death following growth factor (interleukin-3) withdrawal is conserved between human and murine BAD. A second cleavage site that is required for murine BAD to promote death following Sindbis virus infection, gamma-irradiation, and staurosporine treatment is not conserved in human BAD, consistent with the inability of human BAD to promote death with these stimuli. However, loss of the BAD N terminus by any mechanism is not always sufficient to activate its pro-death activity, suggesting that the N terminus is a regulatory domain rather than an anti-death domain. These findings suggest that BAD is more than an inert death factor in healthy cells; it is also a pro-survival factor, prior to its role in promoting cell death. | D018354 | Alphavirus Infections |
Clinically important variants in BCL2 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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