P53563 (B2CL1_RAT) 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:	Bclx, Blc2l

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [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 › Rattus

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.3 Ref.4 Ref.6
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 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). Interacts with BCL2L11 By similarity. Isoform Bcl-X(L) interacts with IKZF3 By similarity. Interacts with HEBP2 By similarity. Isoform Bcl-X(L) interacts with BOP By similarity. 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. Ref.6
Subcellular location	Mitochondrion membrane; Single-pass membrane protein By similarity. Nucleus membrane; Single-pass membrane protein; Cytoplasmic side By similarity. Cytoplasm › cytoskeleton › centrosome By similarity. Note: Mitochondrial membranes and perinuclear envelope By similarity.
Tissue specificity	Expressed in most tissues. Bcl-X(beta) is specifically expressed in cerebellum, heart, and thymus. In the ovary, the predominant form is Bcl-X(L), with a small but detectable level of Bcl-X(S).
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. 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.
Sequence caution	The sequence AAC60701.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAC60702.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Cytoskeleton Membrane Mitochondrion Nucleus
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cytokinesis Inferred from sequence or structural similarity. Source: UniProtKB mitotic cell cycle checkpoint Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of apoptotic process Inferred from direct assay PubMed 12097494PubMed 12515824. Source: RGD ovarian follicle development Inferred from mutant phenotype PubMed 17989359. Source: RGD response to hydrogen peroxide Inferred from expression pattern PubMed 17869087. Source: RGD response to hypoxia Inferred from expression pattern PubMed 17272823. Source: RGD response to lead ion Inferred from expression pattern PubMed 17912701. Source: RGD response to organic cyclic compound Inferred from expression pattern PubMed 17805306. Source: RGD response to peptide hormone stimulus Inferred from expression pattern PubMed 17728251. Source: RGD
Cellular_component	centrosome Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial outer membrane Inferred from direct assay PubMed 12515824. Source: RGD nuclear membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	cysteine-type endopeptidase inhibitor activity involved in apoptotic process Inferred from direct assay PubMed 12097494. Source: RGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Dnm1l	O35303	2	EBI-287204,EBI-1767447

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform Bcl-X(L) (identifier: P53563-1)

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: P53563-2)

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: P53563-3)

The sequence of this isoform differs from the canonical sequence as follows:
     189-233: DTFVDLYGNN...VLLGSLFSRK → VRTTPLVCPP...DYSGDIPGLL

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_0000143065

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_000520

Alternative sequence

189 – 233

45

DTFVD…LFSRK → VRTTPLVCPPLVCLSSVEIP NCPFWSPGMVVEDIDYSGDI PGLL in isoform Bcl-X(beta).

VSP_000521

Experimental info

Sequence conflict

6

1

R → Q in CAA57886. Ref.1

Sequence conflict

6

1

R → Q in CAA57887. Ref.1

Sequence conflict

12

1

F → S in AAA19257. Ref.2

Sequence conflict

64

1

A → E in AAA19257. Ref.2

Sequence conflict

81

1

I → L in AAA77686. Ref.4

Sequence conflict

81

1

I → L in AAC60701. Ref.4

Sequence conflict

81

1

I → L in AAC60702. Ref.4

Sequence conflict

119

1

A → V in AAA77686. Ref.4

Sequence conflict

119

1

A → V in AAC60701. Ref.4

Sequence conflict

119

1

A → V in AAC60702. Ref.4

Sequence conflict

143 – 144

2

FF → SS in AAA77686. Ref.4

Sequence conflict

143 – 144

2

FF → SS in AAC60701. Ref.4

Sequence conflict

199

1

A → T in AAA77686. Ref.4

Sequence conflict

199

1

A → T in AAC60701. Ref.4

Sequence conflict

199

1

A → T in AAC60702. Ref.4

Sequence conflict

201

1

A → P in AAA77686. Ref.4

Sequence conflict

201

1

A → P in AAC60701. Ref.4

Sequence conflict

201

1

A → P in AAC60702. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

233

Helix Strand Turn

Details...

Helix

4 – 19

16

Turn

25 – 28

4

Helix

84 – 100

17

Helix

106 – 112

7

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, 1997. Version 2. Checksum: 2B62B6C63864BC8F	FASTA	233	26,158
	10 20 30 40 50 60 MSQSNRELVV DFLSYKLSQK GYSWSQFSDV EENRTEAPEE TEPERETPSA 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: D90868EC7F69ED59	FASTA	170	18,987
	10 20 30 40 50 60 MSQSNRELVV DFLSYKLSQK GYSWSQFSDV EENRTEAPEE TEPERETPSA 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: 5B44307AB9D2975E	FASTA	232	25,865
	10 20 30 40 50 60 MSQSNRELVV DFLSYKLSQK GYSWSQFSDV EENRTEAPEE TEPERETPSA 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 WIQENGGWVR TTPLVCPPLV CLSSVEIPNC PFWSPGMVVE DIDYSGDIPG LL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Michaelidis T.M. Submitted (DEC-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS BCL-X(L) AND BCL-X(S)). Tissue: Brain.
[2]	"Cloning and expression of rat bcl-x in cultured neurons." Wesselingh S.L., David G.L., Choi S., Veliuona M., Hardwick J.M. Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE (ISOFORM BCL-X(L)). Tissue: Brain.
[3]	"An additional form of rat Bcl-x, Bcl-xbeta, generated by an unspliced RNA, promotes apoptosis in promyeloid cells." Shiraiwa N., Inohara N., Okada S., Yuzaki M., Shoji S., Ohta S. J. Biol. Chem. 271:13258-13265(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BCL-X(L) AND BCL-X(BETA)), FUNCTION. Tissue: Thymus.
[4]	"Expression of members of the Bcl-2 gene family in the immature rat ovary: equine chorionic gonadotropin-mediated inhibition of granulosa cell apoptosis is associated with decreased Bax and constitutive Bcl-2 and Bcl-xlong messenger ribonucleic acid levels." Tilly J.L., Tilly K.I., Kenton M.L., Johnson A.L. Endocrinology 136:232-241(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BCL-X(L) AND BCL-X(S)), FUNCTION. Strain: Sprague-Dawley. Tissue: Ovary.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BCL-X(L)). Tissue: Brain.
[6]	"Bcl-xL induces Drp1-dependent synapse formation in cultured hippocampal neurons." Li H., Chen Y., Jones A.F., Sanger R.H., Collis L.P., Flannery R., McNay E.C., Yu T., Schwarzenbacher R., Bossy B., Bossy-Wetzel E., Bennett M.V., Pypaert M., Hickman J.A., Smith P.J., Hardwick J.M., Jonas E.A. Proc. Natl. Acad. Sci. U.S.A. 105:2169-2174(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DNM1L, FUNCTION.
[7]	"Crystal structure of rat Bcl-xL. Implications for the function of the Bcl-2 protein family." Aritomi M., Kunishima N., Inohara N., Ishibashi Y., Ohta S., Morikawa K. J. Biol. Chem. 272:27886-27892(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X82537 Genomic DNA. Translation: CAA57886.1.
X82537 Genomic DNA. Translation: CAA57887.1.
U10579 Unassigned DNA. Translation: AAA19257.1.
U72350 mRNA. Translation: AAB17353.1.
U72349 mRNA. Translation: AAB17352.1.
U34963 mRNA. Translation: AAA77686.1.
S76513 mRNA. Translation: AAC60701.2. Different initiation.
S78284 mRNA. Translation: AAC60702.1. Different initiation.
BC094213 mRNA. Translation: AAH94213.1.

IPI

IPI00211135.
IPI00231893.
IPI00231894.

PIR

I67431.
I67435.
S51761.

RefSeq

NP_001028842.1. NM_001033670.1.
NP_001028843.1. NM_001033671.1.
NP_113723.2. NM_031535.2.

UniGene

Rn.10323.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AF3	X-ray	2.50	A	1-196	[»]

DisProt

DP00449.

ProteinModelPortal

P53563.

SMR

P53563. Positions 1-210.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29698N.

IntAct

P53563. 2 interactions.

PTM databases

PhosphoSite

P53563.

Proteomic databases

PRIDE

P53563.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000010762; ENSRNOP00000010762; ENSRNOG00000007946.

GeneID

24888.

KEGG

rno:24888.

UCSC

RGD:2200. rat.

Organism-specific databases

CTD

598.

RGD

2200. Bcl2l1.

Phylogenomic databases

eggNOG

NOG300479.

GeneTree

ENSGT00530000062935.

KO

K04570.

OMA

NGSPSWH.

OrthoDB

EOG47PX6Z.

Gene expression databases

ArrayExpress

P53563.

Genevestigator

P53563.

GermOnline

ENSRNOG00000007946. Rattus norvegicus.

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

ChEMBL

CHEMBL1075182.

EvolutionaryTrace

P53563.

NextBio

604742.

Entry information

Entry name

B2CL1_RAT

Accession

Primary (citable) accession number: P53563
Secondary accession number(s): P70613 , P70614, Q52KS0, Q62678, Q62836, Q64087, Q64128

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 129 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program