Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

BCL2L1 (Q07817) - Overview - Molecular Target Synopsis

Protein


BCL2L1, Bcl-2-like protein 1
UniProt Q07817

Also Known as B2CL1_HUMAN, BCL2L1, BCL2L, BCLX

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. Homodimer. Isoform Bcl-X(L) forms heterodimers with BAX, BAK or BCL2. Heterodimerization with BAX does not seem to be required for anti-apoptotic activity. Interacts with BCL2L11. Interacts with BAD. Interacts (isoform Bcl-X(L)) with SIVA1 (isoform 1); the interaction inhibits the anti-apoptotic activity. Interacts with BECN1 and PGAM5. Isoform Bcl-X(L) interacts with IKZF3. Interacts with HEBP2. Isoform Bcl-X(L) interacts with RTL10/BOP. Interacts with p53/TP53 and BBC3; interaction with BBC3 disrupts the interaction with p53/TP53. Isoform Bcl-X(L) interacts with DNM1L and CLTA; DNM1L and BCL2L1 isoform BCL-X(L) may form a complex in synaptic vesicles that also contains clathrin and MFF. Interacts with ATP5F1A and ATP5F1B; the interactions mediate the association of isoform Bcl-X(L) with the mitochondrial membrane ATP synthase F(1)F(0) ATP synthase. Interacts with VDAC1 (PubMed:25296756). Isoform Bcl-X(L) 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 BCL2L11 (via BH3) (PubMed:27013495). Interacts with RNF183 (PubMed:29507230).

6IJQ
SOLUTION STRUCTURE OF BCL-XL BOUND TO P73-TAD PEPTIDE
RCSB/PDB
Inspect Structure
See all 3D Structures for BCL2L1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: BCL2L1 is active in the following subcellular-locations: centrosome, cytoplasm, cytoplasmic vesicle, cytoskeleton, cytosol, microtubule organizing center, mitochondrion inner membrane, mitochondrion matrix, mitochondrion outer membrane, nucleus membrane, secretory vesicle, synaptic vesicle membrane.
GO terms: BCL2L1 is active in the following subcellular-locations: Bcl-2 family protein complex, cell junction, centrosome, cytoplasm, cytosol, endoplasmic reticulum, integral component of membrane, mitochondrial inner membrane, mitochondrial matrix, mitochondrial outer membrane, mitochondrion, nuclear membrane, synaptic vesicle membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project BCL2L1 has gain in 12 cell-lines, loss in 0 cell-lines and no signal in 993 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MDA_MB_231, T47D, ACHN

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SW 1417, MKN-74, SW 480

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HSMM, SK-N-SH, HMEC

(see details)

3D Structures


For BCL2L1 there are:
74 structures (126 chains) solved
25 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


BCL2L1 has been screened with 1189 compounds (1860 bioactivities), 631 compounds have bioactivities that show binding affinity of <= 500nM (984 bioactivities). (see details)