Skip Header

 
Contribute Send feedback

Reviewed, UniProtKB/Swiss-Prot Q07817 (BCLX_HUMAN)

Last modified November 25, 2008. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Apoptosis regulator Bcl-X
Alternative name(s):
    Bcl-2-like 1 protein
Gene names
Name: BCL2L1
Synonyms: BCL2L, BCLX
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length233 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Potent inhibitor of cell death. Isoform Bcl-X(L) anti-apoptotic activity is inhibited by association with SIVA isoform 1. Inhibits activation of caspases By similarity. Appears to regulate cell death by blocking the voltage-dependent anion channnel (VDAC) by binding to it and preventing the release of the caspase activator, cytochrome c, from the mitochondrial membrane. The Bcl-X(S) isoform promotes apoptosis.

Subunit structure

Bcl-X(L) forms homodimers, and heterodimers with BAX, BAK and BCL2. Heterodimerization with BAX does not seem to be required for anti-apoptotic activity. Also interacts with BAD and BBC3. Isoform Bcl-X(L) binds to Siva isoform 1. Interacts with BCL2L11 By similarity. Interacts with BECN1 and PGAM5.

Subcellular location

Mitochondrion membrane; Single-pass membrane proteinBy similarity. Nucleus membrane; Single-pass membrane protein; Cytoplasmic sideBy similarity. Note= Mitochondrial membranes and perinuclear envelope By similarity.

Tissue specificity

Bcl-X(S) is expressed at high levels in cells that undergo a high rate of turnover, such as developing lymphocytes. In contrast, Bcl-X(L) is found in tissues containing long-lived postmitotic cells, such as adult brain.

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.

Sequence similarities

Belongs to the Bcl-2 family.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform Bcl-X(L) (identifier: Q07817-1)

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: Q07817-2)

The sequence of this isoform differs from the canonical sequence as follows:
     126-188: Missing.
Isoform Bcl-X(beta) (identifier: Q07817-3)

The sequence of this isoform differs from the canonical sequence as follows:
     189-233: DTFVELYGNN...VLLGSLFSRK → VRTKPLVCPF...CWVIVGDVDS

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 233233Apoptosis regulator Bcl-X
PRO_0000143062

Regions

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

Sites

Site61 – 622Cleavage; by caspase-1

Natural variations

Alternative sequence126 – 18863Missing in isoform Bcl-X(S).
VSP_000515
Alternative sequence189 – 23345DTFVE…LFSRK → VRTKPLVCPFSLASGQRSPT ALLLYLFLLCWVIVGDVDS in isoform Bcl-X(beta).
VSP_000516

Experimental info

Mutagenesis611D → A: No cleavage by caspase-1 nor by caspase-3
Mutagenesis131 – 1333FRD → VRA: No heterodimerization with BAX
Mutagenesis135 – 1373VNW → AIL: Loss of anti-apoptotic activity
Mutagenesis138 – 1403GRI → ELN: Loss of anti-apoptotic activity
Mutagenesis1381G → A: No heterodimerization with BAX
Mutagenesis1481G → E: No heterodimerization with BAX
Mutagenesis1561D → A: No effect on caspase-1 cleavage
Mutagenesis1761D → A: No effect on caspase-1 cleavage
Mutagenesis188 – 1892WD → GA: Reduces anti-apoptotic activity by about half
Mutagenesis1891D → A: No effect on caspase-1 cleavage
Sequence conflict701G → A in CAA80661. Ref.1

Secondary structure

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

Details...

Sequences

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

Last modified February 1, 1995. Version 1.
Checksum: E09D3CDD851AE9BE

FASTA23326,049
        10         20         30         40         50         60 
MSQSNRELVV DFLSYKLSQK GYSWSQFSDV EENRTEAPEG TESEMETPSA INGNPSWHLA 

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

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

       190        200        210        220        230 
WIQENGGWDT FVELYGNNAA AESRKGQERF NRWFLTGMTV AGVVLLGSLF SRK 

« Hide

Isoform Bcl-X(S) [UniParc].

Checksum: 75D1FC01EC06AD47
Show »

17018,894
Isoform Bcl-X(beta) [UniParc].

Checksum: 1EF621E5D0744E4E
Show »

22725,290

References

« Hide 'large scale' references
[1]"bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death."
Boise L.H., Gonzalez-Garcia M., Postema C.E., Ding L., Lindsten T., Turka L.A., Mao X., Nunez G., Thompson C.B.
Cell 74:597-608(1993) [PubMed: 8358789] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BCL-X(L) AND BCL-X(S)).
[2]Inohara N., Ohta S.
Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM BCL-X(BETA)).
[3]"Identification of a human cDNA encoding a novel Bcl-x isoform."
Ban J., Eckhart L., Weninger W., Mildner M., Tschachler E.
Biochem. Biophys. Res. Commun. 248:147-152(1998) [PubMed: 9675101] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BCL-X(BETA)).
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BCL-X(L)).
[5]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed: 11780052] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BCL-X(L)).
Tissue: Lung.
[7]"Multiple Bcl-2 family members demonstrate selective dimerizations with Bax."
Sedlak T.W., Oltvai Z.N., Yang E., Wang K., Boise L.H., Thompson C.B., Korsmeyer S.J.
Proc. Natl. Acad. Sci. U.S.A. 92:7834-7838(1995) [PubMed: 7644501] [Abstract]
Cited for: MUTAGENESIS OF GLY-138, HETERODIMERIZATION.
[8]"Bax-independent inhibition of apoptosis by Bcl-XL."
Cheng E.H.-Y., Levine B., Boise L.H., Thompson C.B., Hardwick J.M., Korsmeyer S.J.
Nature 379:554-556(1996) [PubMed: 8596636] [Abstract]
Cited for: MUTAGENESIS OF BH1 AND BH2 MOTIFS.
[9]"Modulation of cell death by Bcl-xL through caspase interaction."
Clem R.J., Cheng E.H.-Y., Karp C.L., Kirsch D.G., Ueno K., Takahashi A., Kastan M.B., Griffin D.E., Earnshaw W.C., Veliuona M.A., Hardwick J.M.
Proc. Natl. Acad. Sci. U.S.A. 95:554-559(1998) [PubMed: 9435230] [Abstract]
Cited for: CLEAVAGE BY CASPASES, MUTAGENESIS OF ASP-61.
[10]"PUMA induces the rapid apoptosis of colorectal cancer cells."
Yu J., Zhang L., Hwang P.M., Kinzler K.W., Vogelstein B.
Mol. Cell 7:673-682(2001) [PubMed: 11463391] [Abstract]
Cited for: INTERACTION WITH BCL2 AND BBC3.
[11]"Siva-1 binds to and inhibits BCL-X(L)-mediated protection against UV radiation-induced apoptosis."
Xue L., Chu F., Cheng Y., Sun X., Borthakur A., Ramarao M., Pandey P., Wu M., Schlossman S.F., Prasad K.V.S.
Proc. Natl. Acad. Sci. U.S.A. 99:6925-6930(2002) [PubMed: 12011449] [Abstract]
Cited for: INTERACTION WITH SIVA.
[12]"PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the redox-regulated Keap1-dependent ubiquitin ligase complex."
Lo S.-C., Hannink M.
J. Biol. Chem. 281:37893-37903(2006) [PubMed: 17046835] [Abstract]
Cited for: INTERACTION WITH PGAM5.
[13]"X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death."
Muchmore S.W., Sattler M., Liang H., Meadows R.P., Harlan J.E., Yoon H.S., Nettesheim D., Chang B.S., Thompson C.B., Wong S.L., Ng S.L., Fesik S.W.
Nature 381:335-341(1996) [PubMed: 8692274] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), STRUCTURE BY NMR OF 1-209.
[14]"Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis."
Sattler M., Liang H., Nettesheim D., Meadows R.P., Harlan J.E., Eberstadt M., Yoon H.S., Shuker S.B., Chang B.S., Minn A.J., Thompson C.B., Fesik S.W.
Science 275:983-986(1997) [PubMed: 9020082] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-209.
[15]"Rationale for Bcl-xL/Bad peptide complex formation from structure, mutagenesis, and biophysical studies."
Petros A.M., Nettesheim D.G., Wang Y., Olejniczak E.T., Meadows R.P., Mack J., Swift K., Matayoshi E.D., Zhang H., Thompson C.B., Fesik S.W.
Protein Sci. 9:2528-2534(2000) [PubMed: 11206074] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-209 IN COMPLEX WITH BAD.
[16]"Bcl-XL mutations suppress cellular sensitivity to antimycin A."
Manion M.K., O'Neill J.W., Giedt C.D., Kim K.M., Zhang K.Y.Z., Hockenbery D.M.
J. Biol. Chem. 279:2159-2165(2004) [PubMed: 14534311] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 1-211.
[17]"An inhibitor of Bcl-2 family proteins induces regression of solid tumours."
Oltersdorf T., Elmore S.W., Shoemaker A.R., Armstrong R.C., Augeri D.J., Belli B.A., Bruncko M., Deckwerth T.L., Dinges J., Hajduk P.J., Joseph M.K., Kitada S., Korsmeyer S.J., Kunzer A.R., Letai A., Li C., Mitten M.J., Nettesheim D.G. expand/collapse author list , Ng S.-C., Nimmer P.M., O'Connor J.M., Oleksijew A., Petros A.M., Reed J.C., Shen W., Tahir S.K., Thompson C.B., Tomaselli K.J., Wang B., Wendt M.D., Zhang H., Fesik S.W., Rosenberg S.H.
Nature 435:677-681(2005) [PubMed: 15902208] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-209.
[18]"BCL-XL dimerization by three-dimensional domain swapping."
O'Neill J.W., Manion M.K., Maguire B., Hockenbery D.M.
J. Mol. Biol. 356:367-381(2006) [PubMed: 16368107] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.45 ANGSTROMS) OF 1-211, SUBUNIT.
[19]"Crystal structure of the Bcl-XL-Beclin 1 peptide complex: Beclin 1 is a novel BH3-only protein."
Oberstein A., Jeffrey P.D., Shi Y.
J. Biol. Chem. 282:13123-13132(2007) [PubMed: 17337444] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 83-209 IN COMPLEX WITH BECN1.
[20]"Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL."
Bruncko M., Oost T.K., Belli B.A., Ding H., Joseph M.K., Kunzer A., Martineau D., McClellan W.J., Mitten M., Ng S.-C., Nimmer P.M., Oltersdorf T., Park C.-M., Petros A.M., Shoemaker A.R., Song X., Wang X., Wendt M.D. expand/collapse author list , Zhang H., Fesik S.W., Rosenberg S.H., Elmore S.W.
J. Med. Chem. 50:641-662(2007) [PubMed: 17256834] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-209.
+Additional computationally mapped references.

Cross-references

Sequence databases

Z23116<