Q64373 (B2CL1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	233 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Potent inhibitor of cell death. Inhibits activation of caspases By similarity. 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(S) promotes apoptosis By similarity. Ref.4
Subunit structure	Homodimer By similarity. 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 DMN1L; the interaction stimulates the GTPase activity of DMN1L in synapses and increases the number of axonal mitochondria and the size and number of synaptic vesicle clusters. Interacts with BAD. Interacts with P53/TP53 and BBC3; interaction with BBC3 disrupts the interaction with P53/TP53. Interacts (isoform Bcl-X(L)) with SIVA1 (isoform 1); the interaction inhibits the anti-apoptotic activity. Interacts with BECN1 and PGAM5. Interacts (isoform Bcl-X(L)) with BAX (isoform Sigma) By similarity. Interacts with BCL2L11. Isoform Bcl-X(L) interacts with IKZF3. Interacts with HEBP2 By similarity. Isoform Bcl-X(L) interacts with BOP By similarity.
Subcellular location	Isoform Bcl-X(L): Mitochondrion membrane. Cytoplasm › cytoskeleton › centrosome By similarity. Note: Mitochondrial membranes and perinuclear envelope. 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 process	Apoptosis
Cellular component	Cytoplasm Cytoskeleton Membrane Mitochondrion
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from direct assay PubMed 12115603. 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 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 in utero embryonic development Inferred from mutant phenotype PubMed 10618441. Source: MGI male gonad development Inferred from mutant phenotype PubMed 10894153. Source: MGI mitotic cell cycle checkpoint Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of anoikis Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from mutant phenotype PubMed 15901672. Source: UniProtKB negative regulation of establishment of protein localization to plasma membrane Inferred from electronic annotation. Source: Compara negative regulation of intrinsic apoptotic signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of neuron apoptotic process Inferred from direct assay PubMed 15231831PubMed 7753802PubMed 8625820. 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: Compara regulation of mitochondrial membrane potential Inferred from electronic annotation. Source: Compara 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 stimulus Inferred from electronic annotation. Source: Compara spermatogenesis Inferred from genetic interaction PubMed 10894153. Source: MGI
Cellular_component	Bcl-2 family protein complex Inferred from electronic annotation. Source: Compara centrosome Inferred from sequence or structural similarity. Source: UniProtKB cytosol Inferred from direct assay PubMed 11980919. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial membrane Inferred from direct assay PubMed 11980919. Source: MGI
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 233

233

Bcl-2-like protein 1

PRO_0000143063

Regions

Transmembrane

210 – 226

17

Helical; Potential

Motif

4 – 24

21

BH4

Motif

86 – 100

15

BH3

Motif

129 – 148

20

BH1

Motif

180 – 195

16

BH2

Amino acid modifications

Modified residue

49

1

Phosphoserine; by PLK3 By similarity

Modified residue

62

1

Phosphoserine; by CDK1 By similarity

Natural variations

Alternative sequence

126 – 188

63

Missing in isoform Bcl-X(S).

VSP_000517

Alternative sequence

189 – 233

45

DTFVD…LFSRK → VRTTPLVCPPLACVSLLCEH P in isoform Bcl-X(beta).

VSP_000518

Alternative sequence

194 – 233

40

LYGNN…LFSRK → GHDCGWCGSAGLTLQSEVTR H in isoform Bcl-X(delta-TM).

VSP_000519

Experimental info

Sequence conflict

207 – 209

3

QER → KEG in AAC53459. Ref.4

Secondary structure

1

.

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.

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.

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.

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233

Helix Strand Turn

Details...

Helix

1 – 20

20

Helix

24 – 26

3

Helix

83 – 101

19

Helix

102 – 105

4

Helix

106 – 112

7

Turn

116 – 118

3

Helix

120 – 127

8

Helix

128 – 131

4

Helix

137 – 156

20

Helix

162 – 177

16

Helix

179 – 184

6

Helix

187 – 195

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform Bcl-X(L) (Bcl-xL) [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 24D2AC79887E072E	FASTA	233	26,132
	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
	Isoform Bcl-X(S) (Bcl-xS) [UniParc]. Checksum: 2C12D8EC7F735D52	FASTA	170	18,961
	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 QSFEQDTFVD LYGNNAAAES RKGQERFNRW FLTGMTVAGV VLLGSLFSRK
	Isoform Bcl-X(beta) [UniParc]. Checksum: DC53895D8014B5DD	FASTA	209	23,357
	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 WIQENGGWVR TTPLVCPPLA CVSLLCEHP
	Isoform Bcl-X(delta-TM) [UniParc]. Checksum: 4FAECDC42B064B4A	FASTA	214	23,900
	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 WIQENGGWDT FVDGHDCGWC GSAGLTLQSE VTRH

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.

IPI

IPI00133454.
IPI00227922.
IPI00227924.
IPI00406354.

PIR

I49055.
I49056.
I49057.

RefSeq

NP_033873.3. NM_009743.4.

UniGene

Mm.238213.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PQ0	X-ray	2.20	A	1-196	[»]
1PQ1	X-ray	1.65	A	1-196	[»]
2BZW	X-ray	2.30	A	1-211	[»]
3IHC	X-ray	1.85	A	1-196	[»]
3IHD	X-ray	1.88	A	1-196	[»]
3IHE	X-ray	3.00	A	1-196	[»]
3IHF	X-ray	2.28	A/B/C/D	1-196	[»]
3IIG	X-ray	2.30	A	1-196	[»]
3IIH	X-ray	2.75	A	1-196	[»]
3ILB	X-ray	2.38	A/N	1-196	[»]
3ILC	X-ray	1.64	A	1-196	[»]

ProteinModelPortal

Q64373.

SMR

Q64373. Positions 1-210.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q64373. 7 interactions.

MINT

MINT-87027.

PTM databases

PhosphoSite

Q64373.

Proteomic databases

PaxDb

Q64373.

PRIDE

Q64373.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000007803; ENSMUSP00000007803; ENSMUSG00000007659.
ENSMUST00000109820; ENSMUSP00000105445; ENSMUSG00000007659.
ENSMUST00000134902; ENSMUSP00000134614; ENSMUSG00000007659.
ENSMUST00000140436; ENSMUSP00000134596; ENSMUSG00000007659.

GeneID

12048.

KEGG

mmu:12048.

UCSC

uc008ngi.1. mouse.
uc008ngn.1. mouse.

Organism-specific databases

CTD

598.

MGI

MGI:88139. Bcl2l1.

Phylogenomic databases

eggNOG

NOG300479.

GeneTree

ENSGT00530000062935.

HOGENOM

HOG000056452.

KO

K04570.

OMA

NGSPSWH.

OrthoDB

EOG47PX6Z.

Gene expression databases

ArrayExpress

Q64373.

Bgee

Q64373.

CleanEx

MM_BCL2L1.

Genevestigator

Q64373.

GermOnline

ENSMUSG00000007659. Mus musculus.

Family and domain databases

InterPro

IPR013279. 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]

PANTHER

PTHR11256. PTHR11256. 1 hit.
PTHR11256:SF12. PTHR11256:SF12. 1 hit.

Pfam

PF00452. Bcl-2. 1 hit.
PF02180. BH4. 1 hit.
[Graphical view]

PRINTS

PR01864. APOPREGBCLX.
PR01862. BCL2FAMILY.

SMART

SM00265. BH4. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00865. bcl-2. 1 hit.

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.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

BCL2L1. mouse.

EvolutionaryTrace

Q64373.

NextBio

280335.

PMAP-CutDB

Q64373.

SOURCE

Search...

Entry information

Entry name

B2CL1_MOUSE

Accession

Primary (citable) accession number: Q64373
Secondary accession number(s): O35844 , Q60657, Q60658, Q61338

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 132 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program