UniProtKB - P10415 (BCL2_HUMAN)
Protein
Apoptosis regulator Bcl-2
Gene
BCL2
Organism
Homo sapiens (Human)
Status
Functioni
Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785).2 Publications
GO - Molecular functioni
- BH3 domain binding Source: UniProtKB
- channel activity Source: BHF-UCL
- channel inhibitor activity Source: BHF-UCL
- identical protein binding Source: UniProtKB
- protease binding Source: UniProtKB
- protein heterodimerization activity Source: UniProtKB
- protein homodimerization activity Source: GO_Central
- protein phosphatase 2A binding Source: Ensembl
- repressing transcription factor binding Source: ARUK-UCL
- sequence-specific DNA binding Source: MGI
- ubiquitin protein ligase binding Source: UniProtKB
GO - Biological processi
- actin filament organization Source: Ensembl
- apoptotic process Source: MGI
- axonogenesis Source: Ensembl
- axon regeneration Source: Ensembl
- B cell homeostasis Source: Ensembl
- B cell lineage commitment Source: Ensembl
- B cell proliferation Source: MGI
- B cell receptor signaling pathway Source: UniProtKB
- behavioral fear response Source: Ensembl
- branching involved in ureteric bud morphogenesis Source: Ensembl
- CD8-positive, alpha-beta T cell lineage commitment Source: Ensembl
- cell aging Source: Ensembl
- cell-cell adhesion Source: Ensembl
- cellular response to DNA damage stimulus Source: UniProtKB
- cellular response to glucose starvation Source: Ensembl
- cellular response to hypoxia Source: Ensembl
- cochlear nucleus development Source: Ensembl
- cytokine-mediated signaling pathway Source: Reactome
- defense response to virus Source: UniProtKB
- digestive tract morphogenesis Source: Ensembl
- ear development Source: Ensembl
- endoplasmic reticulum calcium ion homeostasis Source: UniProtKB
- extrinsic apoptotic signaling pathway in absence of ligand Source: GO_Central
- extrinsic apoptotic signaling pathway via death domain receptors Source: MGI
- female pregnancy Source: UniProtKB
- focal adhesion assembly Source: Ensembl
- gland morphogenesis Source: Ensembl
- glomerulus development Source: Ensembl
- hair follicle morphogenesis Source: Ensembl
- homeostasis of number of cells within a tissue Source: Ensembl
- humoral immune response Source: UniProtKB
- intrinsic apoptotic signaling pathway in response to DNA damage Source: GO_Central
- intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: MGI
- intrinsic apoptotic signaling pathway in response to oxidative stress Source: Ensembl
- lymphoid progenitor cell differentiation Source: Ensembl
- male gonad development Source: Ensembl
- melanin metabolic process Source: Ensembl
- melanocyte differentiation Source: Ensembl
- mesenchymal cell development Source: Ensembl
- metanephros development Source: Ensembl
- negative regulation of anoikis Source: UniProtKB
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of apoptotic signaling pathway Source: UniProtKB
- negative regulation of autophagy Source: UniProtKB
- negative regulation of calcium ion transport into cytosol Source: Ensembl
- negative regulation of cell growth Source: Ensembl
- negative regulation of cell migration Source: Ensembl
- negative regulation of cellular pH reduction Source: UniProtKB
- negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: MGI
- negative regulation of G1/S transition of mitotic cell cycle Source: Ensembl
- negative regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
- negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: BHF-UCL
- negative regulation of mitochondrial depolarization Source: UniProtKB
- negative regulation of myeloid cell apoptotic process Source: Ensembl
- negative regulation of neuron apoptotic process Source: MGI
- negative regulation of ossification Source: Ensembl
- negative regulation of osteoblast proliferation Source: Ensembl
- negative regulation of reactive oxygen species metabolic process Source: Ensembl
- negative regulation of retinal cell programmed cell death Source: Ensembl
- neuron apoptotic process Source: HGNC-UCL
- oocyte development Source: Ensembl
- organ growth Source: Ensembl
- ossification Source: Ensembl
- ovarian follicle development Source: Ensembl
- peptidyl-serine phosphorylation Source: Ensembl
- peptidyl-threonine phosphorylation Source: Ensembl
- pigment granule organization Source: Ensembl
- positive regulation of B cell proliferation Source: UniProtKB
- positive regulation of catalytic activity Source: Ensembl
- positive regulation of cell growth Source: MGI
- positive regulation of cell population proliferation Source: ARUK-UCL
- positive regulation of intrinsic apoptotic signaling pathway Source: Reactome
- positive regulation of melanocyte differentiation Source: Ensembl
- positive regulation of multicellular organism growth Source: Ensembl
- positive regulation of neuron maturation Source: Ensembl
- positive regulation of peptidyl-serine phosphorylation Source: Ensembl
- positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: Reactome
- positive regulation of skeletal muscle fiber development Source: Ensembl
- positive regulation of smooth muscle cell migration Source: Ensembl
- post-embryonic development Source: Ensembl
- protein dephosphorylation Source: Ensembl
- protein polyubiquitination Source: MGI
- reactive oxygen species metabolic process Source: Ensembl
- regulation of calcium ion transport Source: MGI
- regulation of cell-matrix adhesion Source: Ensembl
- regulation of gene expression Source: Ensembl
- regulation of glycoprotein biosynthetic process Source: Ensembl
- regulation of mitochondrial membrane permeability Source: HGNC-UCL
- regulation of mitochondrial membrane potential Source: HGNC-UCL
- regulation of nitrogen utilization Source: Ensembl
- regulation of protein stability Source: Ensembl
- regulation of transmembrane transporter activity Source: BHF-UCL
- regulation of viral genome replication Source: Ensembl
- release of cytochrome c from mitochondria Source: HGNC-UCL
- renal system process Source: Ensembl
- response to cytokine Source: MGI
- response to drug Source: MGI
- response to gamma radiation Source: Ensembl
- response to glucocorticoid Source: Ensembl
- response to hydrogen peroxide Source: Ensembl
- response to iron ion Source: UniProtKB
- response to ischemia Source: Ensembl
- response to nicotine Source: UniProtKB
- response to radiation Source: UniProtKB
- response to toxic substance Source: HGNC-UCL
- response to UV-B Source: Ensembl
- spleen development Source: Ensembl
- T cell differentiation in thymus Source: Ensembl
- T cell homeostasis Source: Ensembl
- thymus development Source: Ensembl
Keywordsi
| Biological process | Apoptosis |
Enzyme and pathway databases
| PathwayCommonsi | P10415 |
| Reactomei | R-HSA-111447, Activation of BAD and translocation to mitochondria R-HSA-111453, BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members R-HSA-6785807, Interleukin-4 and Interleukin-13 signaling R-HSA-844455, The NLRP1 inflammasome R-HSA-9018519, Estrogen-dependent gene expression R-HSA-9634638, Estrogen-dependent nuclear events downstream of ESR-membrane signaling |
| SIGNORi | P10415 |
Protein family/group databases
| TCDBi | 1.A.21.1.10, the bcl-2 (bcl-2) family |
Names & Taxonomyi
| Protein namesi | Recommended name: Apoptosis regulator Bcl-2 |
| Gene namesi | Name:BCL2 |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| EuPathDBi | HostDB:ENSG00000171791.12 |
| HGNCi | HGNC:990, BCL2 |
| MIMi | 151430, gene+phenotype |
| neXtProti | NX_P10415 |
Subcellular locationi
Mitochondrion
- Mitochondrion outer membrane 1 Publication; Single-pass membrane protein 1 Publication
Nucleus
- Nucleus membrane 1 Publication; Single-pass membrane protein 1 Publication
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Single-pass membrane protein 1 Publication
Cytosol
- cytosol Source: Ensembl
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Mitochondrion
- mitochondrial outer membrane Source: UniProtKB
- mitochondrion Source: UniProtKB
Nucleus
- nuclear membrane Source: UniProtKB
- nucleoplasm Source: HPA
- nucleus Source: MGI
Other locations
- cytoplasm Source: UniProtKB
- membrane Source: MGI
- myelin sheath Source: Ensembl
- pore complex Source: BHF-UCL
- protein-containing complex Source: CAFA
Topology
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Transmembranei | 212 – 233 | HelicalSequence analysisAdd BLAST | 22 |
Keywords - Cellular componenti
Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion outer membrane, NucleusPathology & Biotechi
Involvement in diseasei
A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.2 Publications
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 34 | D → A: Abolishes cleavage by caspase-3. | 1 | |
| Mutagenesisi | 64 | D → A: No effect on cleavage by caspase-3. | 1 | |
| Mutagenesisi | 138 – 141 | FRDG → AAAA: Loss of BAX-binding and of anti-apoptotic activity. 1 Publication | 4 | |
| Mutagenesisi | 144 | W → A: Loss of BAX-binding and of anti-apoptotic activity; when associated with A-145 and A146. 1 Publication | 1 | |
| Mutagenesisi | 145 | G → A: Loss of BAX-binding and of anti-apoptotic activity. No effect on NLRP1-induced IL1B release, nor on homodimerization. Loss of BAX-binding and of anti-apoptotic activity; when associated with A-145 and A146. 2 Publications | 1 | |
| Mutagenesisi | 145 | G → E: Loss of BAX-binding and of anti-apoptotic activity. No effect on homodimerization. 2 Publications | 1 | |
| Mutagenesisi | 146 | R → A: Loss of BAX-binding and of anti-apoptotic activity; when associated with A-144 and A145. 1 Publication | 1 | |
| Mutagenesisi | 188 | W → A: Loss of BAX-binding and of anti-apoptotic activity. No effect on homodimerization. 1 Publication | 1 | |
| Mutagenesisi | 190 | Q → L: Partial loss of BAX-binding and 50% decrease in anti-apoptotic activity; when associated with A-191 and A-192. No effect on homodimerization; when associated with L-190 and A-191. 1 Publication | 1 | |
| Mutagenesisi | 191 | D → A: No effect on BAX-binding, nor on anti-apoptotic activity. Partial loss of BAX-binding and 50% decrease in anti-apoptotic activity; when associated with L-190 and A-192. No effect on homodimerization; when associated with L-190 and A-191. 1 Publication | 1 | |
| Mutagenesisi | 192 | N → A: Partial loss of BAX-binding and 50% decrease in anti-apoptotic activity; when associated with L-190 and A-191. No effect on homodimerization; when associated with L-190 and A-191. 1 Publication | 1 | |
| Mutagenesisi | 194 – 197 | Missing : Loss of BAX-binding and of anti-apoptotic activity. May also affect protein stability. 1 Publication | 4 | |
| Mutagenesisi | 200 | E → A: Partial loss of BAX-binding and 50% decrease in anti-apoptotic activity. 1 Publication | 1 |
Keywords - Diseasei
Disease mutation, Proto-oncogeneOrganism-specific databases
| DisGeNETi | 596 |
| MalaCardsi | BCL2 |
| MIMi | 151430, gene+phenotype |
| OpenTargetsi | ENSG00000171791 |
| Orphaneti | 545, Follicular lymphoma 480541, High grade B-cell lymphoma with MYC and/ or BCL2 and/or BCL6 rearrangement 98839, Intravascular large B-cell lymphoma |
| PharmGKBi | PA25302 |
Miscellaneous databases
| Pharosi | P10415, Tclin |
Chemistry databases
| ChEMBLi | CHEMBL4860 |
| DrugBanki | DB06307, Apoptone DB09213, Dexibuprofen DB01248, Docetaxel DB08871, Eribulin DB06756, Glycine betaine DB01050, Ibuprofen DB09401, Isosorbide DB12340, Navitoclax DB12191, Obatoclax DB01229, Paclitaxel DB05297, Paclitaxel docosahexaenoic acid DB01367, Rasagiline DB11581, Venetoclax |
| DrugCentrali | P10415 |
| GuidetoPHARMACOLOGYi | 2844 |
Polymorphism and mutation databases
| BioMutai | BCL2 |
| DMDMi | 231632 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000143048 | 1 – 239 | Apoptosis regulator Bcl-2Add BLAST | 239 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 69 | Phosphothreonine; by MAPK81 Publication | 1 | |
| Modified residuei | 70 | Phosphoserine; by MAPK8 and PKC1 Publication | 1 | |
| Modified residuei | 87 | Phosphoserine; by MAPK81 Publication | 1 |
Post-translational modificationi
Phosphorylation/dephosphorylation on Ser-70 regulates anti-apoptotic activity. Growth factor-stimulated phosphorylation on Ser-70 by PKC is required for the anti-apoptosis activity and occurs during the G2/M phase of the cell cycle. In the absence of growth factors, BCL2 appears to be phosphorylated by other protein kinases such as ERKs and stress-activated kinases. Phosphorylated by MAPK8/JNK1 at Thr-69, Ser-70 and Ser-87, wich stimulates starvation-induced autophagy. Dephosphorylated by protein phosphatase 2A (PP2A) (By similarity).By similarity
Proteolytically cleaved by caspases during apoptosis. The cleaved protein, lacking the BH4 motif, has pro-apoptotic activity, causes the release of cytochrome c into the cytosol promoting further caspase activity.1 Publication
Monoubiquitinated by PRKN, leading to increase its stability. Ubiquitinated by SCF(FBXO10), leading to its degradation by the proteasome.2 Publications
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sitei | 34 – 35 | Cleavage; by caspase-3 | 2 |
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
| EPDi | P10415 |
| jPOSTi | P10415 |
| MassIVEi | P10415 |
| MaxQBi | P10415 |
| PaxDbi | P10415 |
| PeptideAtlasi | P10415 |
| PRIDEi | P10415 |
| ProteomicsDBi | 10203 52603 [P10415-1] 52604 [P10415-2] |
PTM databases
| iPTMneti | P10415 |
| PhosphoSitePlusi | P10415 |
Expressioni
Tissue specificityi
Expressed in a variety of tissues.
Gene expression databases
| Bgeei | ENSG00000171791, Expressed in thyroid gland and 238 other tissues |
| ExpressionAtlasi | P10415, baseline and differential |
| Genevisiblei | P10415, HS |
Organism-specific databases
| HPAi | ENSG00000171791, Low tissue specificity |
Interactioni
Subunit structurei
Forms homodimers, and heterodimers with BAX, BAD, BAK and Bcl-X(L). Heterodimerization with BAX requires intact BH1 and BH2 motifs, and is necessary for anti-apoptotic activity (PubMed:8183370).
Interacts with EI24 (By similarity).
Also interacts with APAF1, BBC3, BCL2L1, BNIPL, MRPL41 and TP53BP2. Binding to FKBP8 seems to target BCL2 to the mitochondria and probably interferes with the binding of BCL2 to its targets.
Interacts with BAG1 in an ATP-dependent manner.
Interacts with RAF1 (the 'Ser-338' and 'Ser-339' phosphorylated form).
Interacts (via the BH4 domain) with EGLN3; the interaction prevents the formation of the BAX-BCL2 complex and inhibits the anti-apoptotic activity of BCL2.
Interacts with G0S2; this interaction also prevents the formation of the anti-apoptotic BAX-BCL2 complex.
Interacts with RTL10/BOP.
Interacts with the SCF(FBXO10) complex.
Interacts (via the loop between motifs BH4 and BH3) with NLRP1 (via LRR repeats), but not with NLRP2, NLRP3, NLRP4, PYCARD, nor MEFV (PubMed:17418785).
Interacts with GIMAP3/IAN4, GIMAP4/IAN1 and GIMAP5/IAN5 (By similarity).
By similarity15 PublicationsBinary interactionsi
Hide detailsP10415
Isoform Alpha [P10415-1]
| With | #Exp. | IntAct |
|---|---|---|
| LRRK2 [Q5S007] | 2 | EBI-4370304,EBI-5323863 |
| PMAIP1 [Q13794] | 3 | EBI-4370304,EBI-707392 |
GO - Molecular functioni
- BH3 domain binding Source: UniProtKB
- identical protein binding Source: UniProtKB
- protease binding Source: UniProtKB
- protein heterodimerization activity Source: UniProtKB
- protein homodimerization activity Source: GO_Central
- protein phosphatase 2A binding Source: Ensembl
- repressing transcription factor binding Source: ARUK-UCL
- ubiquitin protein ligase binding Source: UniProtKB
Protein-protein interaction databases
| BioGRIDi | 107068, 110 interactors |
| ComplexPortali | CPX-1981, BCL-2 dimer CPX-1982, BAD:BCL-2 complex CPX-1984, BID:BCL-2 complex CPX-1986, PUMA:BCL-2 complex CPX-1990, BIM:BCL-2 complex |
| CORUMi | P10415 |
| DIPi | DIP-1043N |
| ELMi | P10415 |
| IntActi | P10415, 51 interactors |
| MINTi | P10415 |
| STRINGi | 9606.ENSP00000381185 |
Chemistry databases
| BindingDBi | P10415 |
Miscellaneous databases
| RNActi | P10415, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
| SMRi | P10415 |
| ModBasei | Search... |
| PDBe-KBi | Search... |
Miscellaneous databases
| EvolutionaryTracei | P10415 |
Family & Domainsi
Motif
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Motifi | 10 – 30 | BH4Add BLAST | 21 | |
| Motifi | 93 – 107 | BH3Add BLAST | 15 | |
| Motifi | 136 – 155 | BH1Add BLAST | 20 | |
| Motifi | 187 – 202 | BH2Add BLAST | 16 |
Domaini
BH1 and BH2 domains are required for the interaction with BAX and for anti-apoptotic activity.1 Publication
The BH4 motif is required for anti-apoptotic activity and for interaction with RAF1 and EGLN3.
The loop between motifs BH4 and BH3 is required for the interaction with NLRP1.1 Publication
Sequence similaritiesi
Belongs to the Bcl-2 family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
| eggNOGi | KOG4728, Eukaryota |
| GeneTreei | ENSGT01000000214544 |
| HOGENOMi | CLU_085401_0_0_1 |
| InParanoidi | P10415 |
| KOi | K02161 |
| OMAi | QRGYDWA |
| OrthoDBi | 80538at2759 |
| PhylomeDBi | P10415 |
| TreeFami | TF315834 |
Family and domain databases
| DisProti | DP00297 |
| InterProi | View protein in InterPro IPR013278, Apop_reg_Bcl2 IPR002475, Bcl2-like IPR004725, Bcl2/BclX IPR020717, Bcl2_BH1_motif_CS IPR020726, Bcl2_BH2_motif_CS IPR020728, Bcl2_BH3_motif_CS IPR003093, Bcl2_BH4 IPR020731, Bcl2_BH4_motif_CS IPR036834, Blc2-like_sf IPR026298, Blc2_fam |
| PANTHERi | PTHR11256, PTHR11256, 1 hit PTHR11256:SF11, PTHR11256:SF11, 1 hit |
| Pfami | View protein in Pfam PF00452, Bcl-2, 1 hit PF02180, BH4, 1 hit |
| PRINTSi | PR01863, APOPREGBCL2 PR01862, BCL2FAMILY |
| SMARTi | View protein in SMART SM00265, BH4, 1 hit |
| SUPFAMi | SSF56854, SSF56854, 1 hit |
| TIGRFAMsi | TIGR00865, bcl-2, 1 hit |
| PROSITEi | View protein in PROSITE PS50062, BCL2_FAMILY, 1 hit PS01080, BH1, 1 hit PS01258, BH2, 1 hit PS01259, BH3, 1 hit PS01260, BH4_1, 1 hit PS50063, BH4_2, 1 hit |
Sequences (2)i
Sequence statusi: Complete.
This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basketIsoform Alpha (identifier: P10415-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MAHAGRTGYD NREIVMKYIH YKLSQRGYEW DAGDVGAAPP GAAPAPGIFS
60 70 80 90 100
SQPGHTPHPA ASRDPVARTS PLQTPAAPGA AAGPALSPVP PVVHLTLRQA
110 120 130 140 150
GDDFSRRYRR DFAEMSSQLH LTPFTARGRF ATVVEELFRD GVNWGRIVAF
160 170 180 190 200
FEFGGVMCVE SVNREMSPLV DNIALWMTEY LNRHLHTWIQ DNGGWDAFVE
210 220 230
LYGPSMRPLF DFSWLSLKTL LSLALVGACI TLGAYLGHK
Isoform Beta (identifier: P10415-2) [UniParc]FASTAAdd to basket
The sequence of this isoform differs from the canonical sequence as follows:
196-239: DAFVELYGPSMRPLFDFSWLSLKTLLSLALVGACITLGAYLGHK → VGALGDVSLG
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
|---|---|---|---|---|---|
| Sequence conflicti | 48 | I → F in CAA29778 (PubMed:2834197).Curated | 1 | ||
| Sequence conflicti | 59 | P → T in AAA35591 (PubMed:2875799).Curated | 1 | ||
| Sequence conflicti | 96 | T → A in AAD14111 (PubMed:1339299).Curated | 1 | ||
| Sequence conflicti | 110 | R → G in AAD14111 (PubMed:1339299).Curated | 1 | ||
| Sequence conflicti | 117 | S → R in AAA35591 (PubMed:2875799).Curated | 1 | ||
| Sequence conflicti | 129 | R → C in CAA29778 (PubMed:2834197).Curated | 1 | ||
| Isoform Beta (identifier: P10415-2) | |||||
| Sequence conflicti | 199 | L → S in AAA51814 (PubMed:3523487).Curated | 1 | ||
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_000827 | 7 | T → S2 Publications | 1 | |
| Natural variantiVAR_014716 | 43 | A → T1 PublicationCorresponds to variant dbSNP:rs1800477Ensembl. | 1 | |
| Natural variantiVAR_000828 | 59 | P → S in non-Hodgkin lymphoma; somatic mutation. 1 Publication | 1 | |
| Natural variantiVAR_000829 | 93 | V → I in non-Hodgkin lymphoma; somatic mutation. 1 Publication | 1 |
Alternative sequence
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Alternative sequenceiVSP_000512 | 196 – 239 | DAFVE…YLGHK → VGALGDVSLG in isoform Beta. 1 PublicationAdd BLAST | 44 |
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M13994 mRNA Translation: AAA51813.1 Sequence problems. M13995 mRNA Translation: AAA51814.1 Sequence problems. M14745 mRNA Translation: AAA35591.1 X06487 mRNA Translation: CAA29778.1 AY220759 Genomic DNA Translation: AAO26045.1 AC021803 Genomic DNA No translation available. AC022726 Genomic DNA No translation available. CH471096 Genomic DNA Translation: EAW63137.1 BC027258 mRNA Translation: AAH27258.1 S72602 Genomic DNA Translation: AAD14111.1 Sequence problems. |
| CCDSi | CCDS11981.1 [P10415-1] CCDS45882.1 [P10415-2] |
| PIRi | B29409, TVHUB1 C37332, TVHUA1 |
| RefSeqi | NP_000624.2, NM_000633.2 [P10415-1] NP_000648.2, NM_000657.2 [P10415-2] |
Genome annotation databases
| Ensembli | ENST00000333681; ENSP00000329623; ENSG00000171791 [P10415-1] ENST00000398117; ENSP00000381185; ENSG00000171791 [P10415-1] ENST00000589955; ENSP00000466417; ENSG00000171791 [P10415-2] |
| GeneIDi | 596 |
| KEGGi | hsa:596 |
| UCSCi | uc002lit.2, human [P10415-1] |
Keywords - Coding sequence diversityi
Alternative splicing, Chromosomal rearrangement, PolymorphismSimilar proteinsi
Cross-referencesi
Web resourcesi
| Atlas of Genetics and Cytogenetics in Oncology and Haematology |
| NIEHS-SNPs |
| Wikipedia Bcl-2 entry |
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M13994 mRNA Translation: AAA51813.1 Sequence problems. M13995 mRNA Translation: AAA51814.1 Sequence problems. M14745 mRNA Translation: AAA35591.1 X06487 mRNA Translation: CAA29778.1 AY220759 Genomic DNA Translation: AAO26045.1 AC021803 Genomic DNA No translation available. AC022726 Genomic DNA No translation available. CH471096 Genomic DNA Translation: EAW63137.1 BC027258 mRNA Translation: AAH27258.1 S72602 Genomic DNA Translation: AAD14111.1 Sequence problems. |
| CCDSi | CCDS11981.1 [P10415-1] CCDS45882.1 [P10415-2] |
| PIRi | B29409, TVHUB1 C37332, TVHUA1 |
| RefSeqi | NP_000624.2, NM_000633.2 [P10415-1] NP_000648.2, NM_000657.2 [P10415-2] |
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 1G5M | NMR | - | A | 1-34 | [»] | |
| A | 92-207 | [»] | ||||
| 1GJH | NMR | - | A | 1-34 | [»] | |
| A | 92-207 | [»] | ||||
| 1YSW | NMR | - | A | 3-33 | [»] | |
| A | 92-206 | [»] | ||||
| 2O21 | NMR | - | A | 3-34 | [»] | |
| A | 92-207 | [»] | ||||
| 2O22 | NMR | - | A | 3-34 | [»] | |
| A | 92-207 | [»] | ||||
| 2O2F | NMR | - | A | 8-31 | [»] | |
| A | 92-204 | [»] | ||||
| 2W3L | X-ray | 2.10 | A/B | 92-206 | [»] | |
| 2XA0 | X-ray | 2.70 | A/B | 1-207 | [»] | |
| 4AQ3 | X-ray | 2.40 | A/B/C/D/E/F | 1-33 | [»] | |
| A/B/C/D/E/F | 92-207 | [»] | ||||
| 4IEH | X-ray | 2.10 | A | 1-34 | [»] | |
| A | 92-207 | [»] | ||||
| 4LVT | X-ray | 2.05 | A/B | 1-34 | [»] | |
| A/B | 92-207 | [»] | ||||
| 4LXD | X-ray | 1.90 | A | 1-34 | [»] | |
| A | 92-207 | [»] | ||||
| 4MAN | X-ray | 2.07 | A/B | 1-34 | [»] | |
| A/B | 92-207 | [»] | ||||
| 5AGW | X-ray | 2.69 | A/B | 1-34 | [»] | |
| A/B | 92-207 | [»] | ||||
| 5AGX | X-ray | 2.24 | A/B | 1-34 | [»] | |
| A/B | 92-207 | [»] | ||||
| 5FCG | X-ray | 2.10 | A | 1-207 | [»] | |
| 5JSN | X-ray | 2.10 | A/C | 1-207 | [»] | |
| 5VAU | X-ray | 1.75 | A/B/C/D | 1-207 | [»] | |
| 5VAX | X-ray | 2.00 | A/B/C/D | 1-207 | [»] | |
| 5VAY | X-ray | 1.80 | A/B/C/D | 1-34 | [»] | |
| A/B/C/D | 66-207 | [»] | ||||
| 6GL8 | X-ray | 1.40 | A | 9-206 | [»] | |
| 6IWB | X-ray | 2.50 | B/D | 1-34 | [»] | |
| B/D | 92-207 | [»] | ||||
| 6O0K | X-ray | 1.62 | A | 1-34 | [»] | |
| A | 66-207 | [»] | ||||
| 6O0L | X-ray | 2.20 | A/C | 1-34 | [»] | |
| A/C | 66-207 | [»] | ||||
| 6O0M | X-ray | 1.75 | A | 1-34 | [»] | |
| A | 66-207 | [»] | ||||
| 6O0O | X-ray | 2.00 | A/C | 1-34 | [»] | |
| A/C | 66-207 | [»] | ||||
| 6O0P | X-ray | 1.80 | A | 1-34 | [»] | |
| A | 66-207 | [»] | ||||
| SMRi | P10415 | |||||
| ModBasei | Search... | |||||
| PDBe-KBi | Search... | |||||
Protein-protein interaction databases
| BioGRIDi | 107068, 110 interactors |
| ComplexPortali | CPX-1981, BCL-2 dimer CPX-1982, BAD:BCL-2 complex CPX-1984, BID:BCL-2 complex CPX-1986, PUMA:BCL-2 complex CPX-1990, BIM:BCL-2 complex |
| CORUMi | P10415 |
| DIPi | DIP-1043N |
| ELMi | P10415 |
| IntActi | P10415, 51 interactors |
| MINTi | P10415 |
| STRINGi | 9606.ENSP00000381185 |
Chemistry databases
| BindingDBi | P10415 |
| ChEMBLi | CHEMBL4860 |
| DrugBanki | DB06307, Apoptone DB09213, Dexibuprofen DB01248, Docetaxel DB08871, Eribulin DB06756, Glycine betaine DB01050, Ibuprofen DB09401, Isosorbide DB12340, Navitoclax DB12191, Obatoclax DB01229, Paclitaxel DB05297, Paclitaxel docosahexaenoic acid DB01367, Rasagiline DB11581, Venetoclax |
| DrugCentrali | P10415 |
| GuidetoPHARMACOLOGYi | 2844 |
Protein family/group databases
| TCDBi | 1.A.21.1.10, the bcl-2 (bcl-2) family |
PTM databases
| iPTMneti | P10415 |
| PhosphoSitePlusi | P10415 |
Polymorphism and mutation databases
| BioMutai | BCL2 |
| DMDMi | 231632 |
Proteomic databases
| EPDi | P10415 |
| jPOSTi | P10415 |
| MassIVEi | P10415 |
| MaxQBi | P10415 |
| PaxDbi | P10415 |
| PeptideAtlasi | P10415 |
| PRIDEi | P10415 |
| ProteomicsDBi | 10203 52603 [P10415-1] 52604 [P10415-2] |
Protocols and materials databases
| ABCDi | P10415, 1 sequenced antibody |
| Antibodypediai | 3491, 3710 antibodies |
| DNASUi | 596 |
Genome annotation databases
| Ensembli | ENST00000333681; ENSP00000329623; ENSG00000171791 [P10415-1] ENST00000398117; ENSP00000381185; ENSG00000171791 [P10415-1] ENST00000589955; ENSP00000466417; ENSG00000171791 [P10415-2] |
| GeneIDi | 596 |
| KEGGi | hsa:596 |
| UCSCi | uc002lit.2, human [P10415-1] |
Organism-specific databases
| CTDi | 596 |
| DisGeNETi | 596 |
| EuPathDBi | HostDB:ENSG00000171791.12 |
| GeneCardsi | BCL2 |
| HGNCi | HGNC:990, BCL2 |
| HPAi | ENSG00000171791, Low tissue specificity |
| MalaCardsi | BCL2 |
| MIMi | 151430, gene+phenotype |
| neXtProti | NX_P10415 |
| OpenTargetsi | ENSG00000171791 |
| Orphaneti | 545, Follicular lymphoma 480541, High grade B-cell lymphoma with MYC and/ or BCL2 and/or BCL6 rearrangement 98839, Intravascular large B-cell lymphoma |
| PharmGKBi | PA25302 |
| GenAtlasi | Search... |
Phylogenomic databases
| eggNOGi | KOG4728, Eukaryota |
| GeneTreei | ENSGT01000000214544 |
| HOGENOMi | CLU_085401_0_0_1 |
| InParanoidi | P10415 |
| KOi | K02161 |
| OMAi | QRGYDWA |
| OrthoDBi | 80538at2759 |
| PhylomeDBi | P10415 |
| TreeFami | TF315834 |
Enzyme and pathway databases
| PathwayCommonsi | P10415 |
| Reactomei | R-HSA-111447, Activation of BAD and translocation to mitochondria R-HSA-111453, BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members R-HSA-6785807, Interleukin-4 and Interleukin-13 signaling R-HSA-844455, The NLRP1 inflammasome R-HSA-9018519, Estrogen-dependent gene expression R-HSA-9634638, Estrogen-dependent nuclear events downstream of ESR-membrane signaling |
| SIGNORi | P10415 |
Miscellaneous databases
| BioGRID-ORCSi | 596, 52 hits in 879 CRISPR screens |
| ChiTaRSi | BCL2, human |
| EvolutionaryTracei | P10415 |
| GeneWikii | Bcl-2 |
| GenomeRNAii | 596 |
| Pharosi | P10415, Tclin |
| PROi | PR:P10415 |
| RNActi | P10415, protein |
| SOURCEi | Search... |
Gene expression databases
| Bgeei | ENSG00000171791, Expressed in thyroid gland and 238 other tissues |
| ExpressionAtlasi | P10415, baseline and differential |
| Genevisiblei | P10415, HS |
Family and domain databases
| DisProti | DP00297 |
| InterProi | View protein in InterPro IPR013278, Apop_reg_Bcl2 IPR002475, Bcl2-like IPR004725, Bcl2/BclX IPR020717, Bcl2_BH1_motif_CS IPR020726, Bcl2_BH2_motif_CS IPR020728, Bcl2_BH3_motif_CS IPR003093, Bcl2_BH4 IPR020731, Bcl2_BH4_motif_CS IPR036834, Blc2-like_sf IPR026298, Blc2_fam |
| PANTHERi | PTHR11256, PTHR11256, 1 hit PTHR11256:SF11, PTHR11256:SF11, 1 hit |
| Pfami | View protein in Pfam PF00452, Bcl-2, 1 hit PF02180, BH4, 1 hit |
| PRINTSi | PR01863, APOPREGBCL2 PR01862, BCL2FAMILY |
| SMARTi | View protein in SMART SM00265, BH4, 1 hit |
| SUPFAMi | SSF56854, SSF56854, 1 hit |
| TIGRFAMsi | TIGR00865, bcl-2, 1 hit |
| PROSITEi | View protein in PROSITE PS50062, BCL2_FAMILY, 1 hit PS01080, BH1, 1 hit PS01258, BH2, 1 hit PS01259, BH3, 1 hit PS01260, BH4_1, 1 hit PS50063, BH4_2, 1 hit |
| ProtoNeti | Search... |
| MobiDBi | Search... |
Entry informationi
| Entry namei | BCL2_HUMAN | |
| Accessioni | P10415Primary (citable) accession number: P10415 Secondary accession number(s): C9JHD5 Q16197 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 1, 1989 |
| Last sequence update: | April 1, 1993 | |
| Last modified: | August 12, 2020 | |
| This is version 251 of the entry and version 2 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 18
Human chromosome 18: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families
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