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Q64373 (B2CL1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Bcl-2-like protein 1

Short name=Bcl2-L-1
Alternative name(s):
Apoptosis regulator Bcl-X
Gene names
Name:Bcl2l1
Synonyms:Bcl2l, Bclx
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length233 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4

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 F1F0 activity and regulates endocytic vesicle retrieval in hippocampal neurons through association with DMN1L and stimulation of its GTPase activity in synaptic vesicles By similarity. Ref.4

Isoform Bcl-X(S) promotes apoptosis By similarity. Ref.4

Subunit structure

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 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 ATP5A and ATP5B; the interactions mediate the association of isoform Bcl-X(L) with the mitochondrial membrane ATP synthase F1F0 ATP synthase By similarity.

Subcellular location

Mitochondrion membrane; Single-pass membrane protein. Nucleus membrane; Single-pass membrane protein; Cytoplasmic side By similarity. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Note: Localizes to the centrosome when phosphorylated at Ser-49. Ref.2

Isoform Bcl-X(L): Mitochondrion inner membrane. Mitochondrion outer membrane. Mitochondrion matrix By similarity. Cytoplasmic vesiclesecretory vesiclesynaptic vesicle membrane By similarity. Cytoplasmcytosol By similarity. Note: After neuronal stimulation, translocates from cytosol to synaptic vesicle and mitochondrion membrane in a calmodulin-dependent manner By similarity. Ref.2

Isoform Bcl-X(delta-TM): Cytoplasm Ref.2.

Tissue specificity

Widely expressed, with highest levels in the brain, thymus, bone marrow, and kidney. Bcl-X(L) and Bcl-X(delta-TM) expression is enhanced in B- and T-lymphocytes that have been activated. Ref.2

Developmental stage

Bcl-X(beta) is expressed in both embryonal and postnatal tissues, whereas Bcl-X(L) is predominantly found in postnatal tissues. Ref.2

Domain

The BH4 motif is required for anti-apoptotic activity. The BH1 and BH2 motifs are required for both heterodimerization with other Bcl-2 family members and for repression of cell death.

Post-translational modification

Proteolytically cleaved by caspases during apoptosis By similarity. The cleaved protein, lacking the BH4 motif, has pro-apoptotic activity By similarity.

Phosphorylated on Ser-62 by CDK1. This phosphorylation is partial in normal mitotic cells, but complete in G2-arrested cells upon DNA-damage, thus promoting subsequent apoptosis probably by triggering caspases-mediated proteolysis. Phosphorylated by PLK3, leading to regulate the G2 checkpoint and progression to cytokinesis during mitosis. Phosphorylation at Ser-49 appears during the S phase and G2, disappears rapidly in early mitosis during prometaphase, metaphase and early anaphase, and re-appears during telophase and cytokinesis By similarity.

Sequence similarities

Belongs to the Bcl-2 family.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentCell junction
Cytoplasm
Cytoplasmic vesicle
Cytoskeleton
Membrane
Mitochondrion
Mitochondrion inner membrane
Mitochondrion outer membrane
Nucleus
Synapse
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process in bone marrow

Inferred from mutant phenotype PubMed 10618441. Source: MGI

cell proliferation

Inferred from direct assay PubMed 9176392. Source: MGI

cellular process regulating host cell cycle in response to virus

Inferred from mutant phenotype PubMed 15231831. Source: MGI

cellular response to alkaloid

Inferred from direct assay PubMed 15231831. Source: MGI

cellular response to amino acid stimulus

Inferred from mutant phenotype PubMed 15231831. Source: MGI

cellular response to gamma radiation

Inferred from mutant phenotype PubMed 15231831. Source: MGI

cytokinesis

Inferred from sequence or structural similarity. Source: UniProtKB

extrinsic apoptotic signaling pathway in absence of ligand

Inferred from mutant phenotype PubMed 12115603. Source: MGI

fertilization

Inferred from genetic interaction PubMed 10894153. Source: MGI

germ cell development

Inferred from mutant phenotype PubMed 10894153. Source: MGI

growth

Inferred from mutant phenotype PubMed 10894153. Source: MGI

hepatocyte apoptotic process

Inferred from mutant phenotype PubMed 10618441. Source: MGI

in utero embryonic development

Inferred from mutant phenotype PubMed 10618441. Source: MGI

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from mutant phenotype PubMed 14517295. Source: MGI

male gonad development

Inferred from mutant phenotype PubMed 10894153. Source: MGI

mitochondrion morphogenesis

Inferred from genetic interaction PubMed 20671748. Source: MGI

mitotic cell cycle checkpoint

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of anoikis

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from direct assay PubMed 11717309PubMed 17267035Ref.2PubMed 8798158PubMed 9867803. Source: MGI

negative regulation of establishment of protein localization to plasma membrane

Inferred from electronic annotation. Source: Ensembl

negative regulation of execution phase of apoptosis

Inferred from electronic annotation. Source: Ensembl

negative regulation of intrinsic apoptotic signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron apoptotic process

Inferred from direct assay PubMed 15231831PubMed 7753802PubMed 8625820. Source: MGI

negative regulation of release of cytochrome c from mitochondria

Inferred from electronic annotation. Source: Ensembl

neuron apoptotic process

Inferred from mutant phenotype PubMed 10618441. Source: MGI

ovarian follicle development

Inferred from mutant phenotype PubMed 10894153. Source: MGI

positive regulation of apoptotic process

Inferred from direct assay PubMed 8798158. Source: MGI

positive regulation of cell proliferation

Inferred from direct assay PubMed 17267035. Source: MGI

regulation of mitochondrial membrane permeability

Inferred from electronic annotation. Source: Ensembl

regulation of mitochondrial membrane potential

Inferred from electronic annotation. Source: Ensembl

release of cytochrome c from mitochondria

Inferred from genetic interaction PubMed 17052454. Source: MGI

response to cycloheximide

Inferred from direct assay PubMed 9176392. Source: MGI

response to cytokine

Inferred from sequence orthology PubMed 9184696. Source: MGI

response to radiation

Inferred from mutant phenotype PubMed 14517295. Source: MGI

response to virus

Inferred from direct assay PubMed 15231831. Source: MGI

spermatogenesis

Inferred from genetic interaction PubMed 10894153. Source: MGI

suppression by virus of host apoptotic process

Inferred from sequence orthology PubMed 15231831. Source: MGI

   Cellular_componentBcl-2 family protein complex

Inferred from electronic annotation. Source: Ensembl

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

centrosome

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 11980919. Source: MGI

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular

Inferred from direct assay PubMed 11146504. Source: MGI

mitochondrial inner membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrial matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrial membrane

Inferred from direct assay PubMed 11980919. Source: MGI

mitochondrial outer membrane

Inferred from direct assay PubMed 23530063. Source: MGI

mitochondrion

Inferred from direct assay PubMed 12931191PubMed 14651853PubMed 20671748Ref.2. Source: MGI

nuclear membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

synaptic vesicle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 18223655PubMed 21095239. Source: UniProtKB

protein heterodimerization activity

Inferred from physical interaction PubMed 7650488PubMed 7834748PubMed 8798452. Source: MGI

protein homodimerization activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

BadQ613372EBI-526380,EBI-400328

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform Bcl-X(L) (identifier: Q64373-1)

Also known as: Bcl-xL;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Bcl-X(S) (identifier: Q64373-2)

Also known as: Bcl-xS;

The sequence of this isoform differs from the canonical sequence as follows:
     126-188: Missing.
Isoform Bcl-X(beta) (identifier: Q64373-3)

The sequence of this isoform differs from the canonical sequence as follows:
     189-233: DTFVDLYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK → VRTTPLVCPPLACVSLLCEHP
Isoform Bcl-X(delta-TM) (identifier: Q64373-4)

The sequence of this isoform differs from the canonical sequence as follows:
     194-233: LYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK → GHDCGWCGSAGLTLQSEVTRH

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 233233Bcl-2-like protein 1
PRO_0000143063

Regions

Transmembrane210 – 22617Helical; Potential
Motif4 – 2421BH4
Motif86 – 10015BH3
Motif129 – 14820BH1
Motif180 – 19516BH2

Amino acid modifications

Modified residue491Phosphoserine; by PLK3 By similarity
Modified residue621Phosphoserine; by CDK1 By similarity

Natural variations

Alternative sequence126 – 18863Missing in isoform Bcl-X(S).
VSP_000517
Alternative sequence189 – 23345DTFVD…LFSRK → VRTTPLVCPPLACVSLLCEH P in isoform Bcl-X(beta).
VSP_000518
Alternative sequence194 – 23340LYGNN…LFSRK → GHDCGWCGSAGLTLQSEVTR H in isoform Bcl-X(delta-TM).
VSP_000519

Experimental info

Sequence conflict207 – 2093QER → KEG in AAC53459. Ref.4

Secondary structure

..................... 233
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Bcl-X(L) (Bcl-xL) [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 24D2AC79887E072E

FASTA23326,132
        10         20         30         40         50         60 
MSQSNRELVV DFLSYKLSQK GYSWSQFSDV EENRTEAPEE TEAERETPSA INGNPSWHLA 

        70         80         90        100        110        120 
DSPAVNGATG HSSSLDAREV IPMAAVKQAL REAGDEFELR YRRAFSDLTS QLHITPGTAY 

       130        140        150        160        170        180 
QSFEQVVNEL FRDGVNWGRI VAFFSFGGAL CVESVDKEMQ VLVSRIASWM ATYLNDHLEP 

       190        200        210        220        230 
WIQENGGWDT FVDLYGNNAA AESRKGQERF NRWFLTGMTV AGVVLLGSLF SRK 

« Hide

Isoform Bcl-X(S) (Bcl-xS) [UniParc].

Checksum: 2C12D8EC7F735D52
Show »

FASTA17018,961
Isoform Bcl-X(beta) [UniParc].

Checksum: DC53895D8014B5DD
Show »

FASTA20923,357
Isoform Bcl-X(delta-TM) [UniParc].

Checksum: 4FAECDC42B064B4A
Show »

FASTA21423,900

References

[1]"IL-5 inhibits anti-IgM-induced apoptosis in an immature B cell line through inductin of bcl-Xl."
Kamesaki H., Michaud G.Y., Takatsu K., Okuma M.
Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BCL-X(L)).
Strain: 2A4B.
[2]"bcl-XL is the major bcl-x mRNA form expressed during murine development and its product localizes to mitochondria."
Gonzalez-Garcia M., Perez-Ballestero R., Ding L., Duan L., Boise L.H., Thompson C.B., Nunez G.
Development 120:3033-3042(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BCL-X(L) AND BCL-X(BETA)), DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Strain: C57BL/6.
Tissue: Brain.
[3]"Cloning and molecular characterization of mouse bcl-x in B and T lymphocytes."
Fang W., Rivard J.J., Mueller D.L., Behrens T.W.
J. Immunol. 153:4388-4398(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BCL-X(L); BCL-X(S) AND BCL-X(DELTA-TM)).
Tissue: Pre-B cell.
[4]"A novel Bcl-x isoform connected to the T cell receptor regulates apoptosis in T cells."
Yang X.-F., Weber G.F., Cantor H.
Immunity 7:629-639(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BCL-X(L) AND BCL-X(BETA)), FUNCTION.
Strain: C57BL/6 X CBA.
Tissue: Thymus.
[5]"Genomic organization, promoter region analysis, and chromosome localization of the mouse bcl-x gene."
Grillot D.A., Gonzalez-Garcia M., Ekhterae D., Duan L., Inohara N., Ohta S., Seldin M.F., Nunez G.
J. Immunol. 158:4750-4757(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"The structure of a Bcl-xL/Bim fragment complex: implications for Bim function."
Liu X., Dai S., Zhu Y., Marrack P., Kappler J.W.
Immunity 19:341-352(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 1-196 IN COMPLEX WITH BCL2L11.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X83574 mRNA. Translation: CAA58557.1.
L35049 mRNA. Translation: AAA51039.1.
L35048 mRNA. Translation: AAA51040.1.
U10102 mRNA. Translation: AAA82174.1.
U10101 mRNA. Translation: AAA82173.1.
U10100 mRNA. Translation: AAA82172.1.
U51278 mRNA. Translation: AAC53459.1.
U51279 mRNA. Translation: AAC53460.1.
U78031, U78030 Genomic DNA. Translation: AAB96881.1.
CCDSCCDS16899.1. [Q64373-1]
PIRI49055.
I49056.
I49057.
RefSeqNP_001276645.1. NM_001289716.1. [Q64373-1]
NP_001276646.1. NM_001289717.1. [Q64373-1]
NP_033873.3. NM_009743.5. [Q64373-1]
XP_006498672.1. XM_006498609.1. [Q64373-1]
XP_006498674.1. XM_006498611.1. [Q64373-1]
XP_006498675.1. XM_006498612.1. [Q64373-1]
UniGeneMm.238213.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1PQ0X-ray2.20A1-196[»]
1PQ1X-ray1.65A1-196[»]
2BZWX-ray2.30A1-211[»]
3IHCX-ray1.85A1-196[»]
3IHDX-ray1.88A1-196[»]
3IHEX-ray3.00A1-196[»]
3IHFX-ray2.28A/B/C/D1-196[»]
3IIGX-ray2.30A1-196[»]
3IIHX-ray2.75A1-196[»]
3ILBX-ray2.38A/N1-196[»]
3ILCX-ray1.64A1-196[»]
ProteinModelPortalQ64373.
SMRQ64373. Positions 1-210.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198323. 6 interactions.
IntActQ64373. 8 interactions.
MINTMINT-87027.

PTM databases

PhosphoSiteQ64373.

Proteomic databases

MaxQBQ64373.
PaxDbQ64373.
PRIDEQ64373.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000007803; ENSMUSP00000007803; ENSMUSG00000007659. [Q64373-1]
ENSMUST00000109820; ENSMUSP00000105445; ENSMUSG00000007659. [Q64373-1]
ENSMUST00000134902; ENSMUSP00000134614; ENSMUSG00000007659. [Q64373-3]
ENSMUST00000140436; ENSMUSP00000134596; ENSMUSG00000007659. [Q64373-3]
GeneID12048.
KEGGmmu:12048.
UCSCuc008ngi.1. mouse. [Q64373-2]
uc008ngj.1. mouse. [Q64373-1]
uc008ngn.1. mouse. [Q64373-3]

Organism-specific databases

CTD598.
MGIMGI:88139. Bcl2l1.

Phylogenomic databases

eggNOGNOG300479.
GeneTreeENSGT00530000062935.
HOGENOMHOG000056452.
KOK04570.
OMANGSPSWH.
OrthoDBEOG70GMGD.
TreeFamTF315834.

Gene expression databases

ArrayExpressQ64373.
BgeeQ64373.
CleanExMM_BCL2L1.
GenevestigatorQ64373.

Family and domain databases

InterProIPR013279. Apop_reg_BclX.
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.
IPR026298. Blc2_fam.
[Graphical view]
PANTHERPTHR11256. PTHR11256. 1 hit.
PTHR11256:SF12. PTHR11256:SF12. 1 hit.
PfamPF00452. Bcl-2. 1 hit.
PF02180. BH4. 1 hit.
[Graphical view]
PRINTSPR01864. APOPREGBCLX.
PR01862. BCL2FAMILY.
SMARTSM00265. BH4. 1 hit.
[Graphical view]
TIGRFAMsTIGR00865. bcl-2. 1 hit.
PROSITEPS50062. 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.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSBCL2L1. mouse.
EvolutionaryTraceQ64373.
NextBio280335.
PMAP-CutDBQ64373.
PROQ64373.
SOURCESearch...

Entry information

Entry nameB2CL1_MOUSE
AccessionPrimary (citable) accession number: Q64373
Secondary accession number(s): O35844 expand/collapse secondary AC list , Q60657, Q60658, Q61338
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot