Full text data of BCL2L1
BCL2L1
(BCL2L, BCLX)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Bcl-2-like protein 1; Bcl2-L-1 (Apoptosis regulator Bcl-X)
Bcl-2-like protein 1; Bcl2-L-1 (Apoptosis regulator Bcl-X)
UniProt
Q07817
ID B2CL1_HUMAN Reviewed; 233 AA.
AC Q07817; E1P5L6; Q5CZ89; Q5TE65; Q92976;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1995, sequence version 1.
DT 22-JAN-2014, entry version 170.
DE RecName: Full=Bcl-2-like protein 1;
DE Short=Bcl2-L-1;
DE AltName: Full=Apoptosis regulator Bcl-X;
GN Name=BCL2L1; Synonyms=BCL2L, BCLX;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BCL-X(L) AND BCL-X(S)).
RX PubMed=8358789; DOI=10.1016/0092-8674(93)90508-N;
RA Boise L.H., Gonzalez-Garcia M., Postema C.E., Ding L., Lindsten T.,
RA Turka L.A., Mao X., Nunez G., Thompson C.B.;
RT "bcl-x, a bcl-2-related gene that functions as a dominant regulator of
RT apoptotic cell death.";
RL Cell 74:597-608(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BCL-X(BETA)), AND INTERACTION WITH
RP BAX.
RX PubMed=9675101; DOI=10.1006/bbrc.1998.8907;
RA Ban J., Eckhart L., Weninger W., Mildner M., Tschachler E.;
RT "Identification of a human cDNA encoding a novel Bcl-x isoform.";
RL Biochem. Biophys. Res. Commun. 248:147-152(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM BCL-X(BETA)).
RA Inohara N., Ohta S.;
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BCL-X(L)).
RC TISSUE=Colon carcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BCL-X(L)).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BCL-X(L)).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP MUTAGENESIS OF GLY-138, AND HETERODIMERIZATION.
RX PubMed=7644501; DOI=10.1073/pnas.92.17.7834;
RA Sedlak T.W., Oltvai Z.N., Yang E., Wang K., Boise L.H., Thompson C.B.,
RA Korsmeyer S.J.;
RT "Multiple Bcl-2 family members demonstrate selective dimerizations
RT with Bax.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:7834-7838(1995).
RN [10]
RP MUTAGENESIS OF BH1 AND BH2 MOTIFS.
RX PubMed=8596636; DOI=10.1038/379554a0;
RA Cheng E.H.-Y., Levine B., Boise L.H., Thompson C.B., Hardwick J.M.,
RA Korsmeyer S.J.;
RT "Bax-independent inhibition of apoptosis by Bcl-XL.";
RL Nature 379:554-556(1996).
RN [11]
RP CLEAVAGE BY CASPASES, AND MUTAGENESIS OF ASP-61.
RX PubMed=9435230; DOI=10.1073/pnas.95.2.554;
RA Clem R.J., Cheng E.H.-Y., Karp C.L., Kirsch D.G., Ueno K.,
RA Takahashi A., Kastan M.B., Griffin D.E., Earnshaw W.C., Veliuona M.A.,
RA Hardwick J.M.;
RT "Modulation of cell death by Bcl-xL through caspase interaction.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:554-559(1998).
RN [12]
RP INTERACTION WITH BAX.
RX PubMed=10772918; DOI=10.1006/bbrc.2000.2537;
RA Schmitt E., Paquet C., Beauchemin M., Dever-Bertrand J., Bertrand R.;
RT "Characterization of Bax-sigma, a cell death-inducing isoform of
RT Bax.";
RL Biochem. Biophys. Res. Commun. 270:868-879(2000).
RN [13]
RP INTERACTION WITH IKZF3.
RX PubMed=11714801;
RA Rebollo A., Ayllon V., Fleischer A., Martinez C.A., Zaballos A.;
RT "The association of Aiolos transcription factor and Bcl-xL is involved
RT in the control of apoptosis.";
RL J. Immunol. 167:6366-6373(2001).
RN [14]
RP INTERACTION WITH BCL2 AND BBC3.
RX PubMed=11463391; DOI=10.1016/S1097-2765(01)00213-1;
RA Yu J., Zhang L., Hwang P.M., Kinzler K.W., Vogelstein B.;
RT "PUMA induces the rapid apoptosis of colorectal cancer cells.";
RL Mol. Cell 7:673-682(2001).
RN [15]
RP INTERACTION WITH SIVA1.
RX PubMed=12011449; DOI=10.1073/pnas.102182299;
RA Xue L., Chu F., Cheng Y., Sun X., Borthakur A., Ramarao M., Pandey P.,
RA Wu M., Schlossman S.F., Prasad K.V.S.;
RT "Siva-1 binds to and inhibits BCL-X(L)-mediated protection against UV
RT radiation-induced apoptosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:6925-6930(2002).
RN [16]
RP INTERACTION WITH PGAM5.
RX PubMed=17046835; DOI=10.1074/jbc.M606539200;
RA Lo S.-C., Hannink M.;
RT "PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the
RT redox-regulated Keap1-dependent ubiquitin ligase complex.";
RL J. Biol. Chem. 281:37893-37903(2006).
RN [17]
RP FUNCTION IN APOPTOSIS, PHOSPHORYLATION AT SER-62 BY CDK1, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19917720; DOI=10.1128/MCB.00882-09;
RA Terrano D.T., Upreti M., Chambers T.C.;
RT "Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts
RT as a functional link coupling mitotic arrest and apoptosis.";
RL Mol. Cell. Biol. 30:640-656(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-49, AND
RP MUTAGENESIS OF SER-49.
RX PubMed=21840391; DOI=10.1016/j.cellsig.2011.07.017;
RA Wang J., Beauchemin M., Bertrand R.;
RT "Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle
RT progression and checkpoints.";
RL Cell. Signal. 23:2030-2038(2011).
RN [20]
RP INTERACTION WITH DNM1L, FUNCTION, AND MUTAGENESIS OF 145-SER--GLY-147
RP AND 188-TRP--PHE-191.
RX PubMed=23792689; DOI=10.1038/ncb2791;
RA Li H., Alavian K.N., Lazrove E., Mehta N., Jones A., Zhang P.,
RA Licznerski P., Graham M., Uo T., Guo J., Rahner C., Duman R.S.,
RA Morrison R.S., Jonas E.A.;
RT "A Bcl-xL-Drp1 complex regulates synaptic vesicle membrane dynamics
RT during endocytosis.";
RL Nat. Cell Biol. 15:773-785(2013).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), AND STRUCTURE BY NMR OF 1-209.
RX PubMed=8692274; DOI=10.1038/381335a0;
RA Muchmore S.W., Sattler M., Liang H., Meadows R.P., Harlan J.E.,
RA Yoon H.S., Nettesheim D., Chang B.S., Thompson C.B., Wong S.L.,
RA Ng S.L., Fesik S.W.;
RT "X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed
RT cell death.";
RL Nature 381:335-341(1996).
RN [22]
RP STRUCTURE BY NMR OF 1-209.
RX PubMed=9020082; DOI=10.1126/science.275.5302.983;
RA Sattler M., Liang H., Nettesheim D., Meadows R.P., Harlan J.E.,
RA Eberstadt M., Yoon H.S., Shuker S.B., Chang B.S., Minn A.J.,
RA Thompson C.B., Fesik S.W.;
RT "Structure of Bcl-xL-Bak peptide complex: recognition between
RT regulators of apoptosis.";
RL Science 275:983-986(1997).
RN [23]
RP STRUCTURE BY NMR OF 1-209 IN COMPLEX WITH BAD.
RX PubMed=11206074; DOI=10.1017/S096183680000331X;
RA Petros A.M., Nettesheim D.G., Wang Y., Olejniczak E.T., Meadows R.P.,
RA Mack J., Swift K., Matayoshi E.D., Zhang H., Thompson C.B.,
RA Fesik S.W.;
RT "Rationale for Bcl-xL/Bad peptide complex formation from structure,
RT mutagenesis, and biophysical studies.";
RL Protein Sci. 9:2528-2534(2000).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 1-211.
RX PubMed=14534311; DOI=10.1074/jbc.M306021200;
RA Manion M.K., O'Neill J.W., Giedt C.D., Kim K.M., Zhang K.Y.Z.,
RA Hockenbery D.M.;
RT "Bcl-XL mutations suppress cellular sensitivity to antimycin A.";
RL J. Biol. Chem. 279:2159-2165(2004).
RN [25]
RP STRUCTURE BY NMR OF 1-209.
RX PubMed=15902208; DOI=10.1038/nature03579;
RA Oltersdorf T., Elmore S.W., Shoemaker A.R., Armstrong R.C.,
RA Augeri D.J., Belli B.A., Bruncko M., Deckwerth T.L., Dinges J.,
RA Hajduk P.J., Joseph M.K., Kitada S., Korsmeyer S.J., Kunzer A.R.,
RA Letai A., Li C., Mitten M.J., Nettesheim D.G., Ng S.-C., Nimmer P.M.,
RA O'Connor J.M., Oleksijew A., Petros A.M., Reed J.C., Shen W.,
RA Tahir S.K., Thompson C.B., Tomaselli K.J., Wang B., Wendt M.D.,
RA Zhang H., Fesik S.W., Rosenberg S.H.;
RT "An inhibitor of Bcl-2 family proteins induces regression of solid
RT tumours.";
RL Nature 435:677-681(2005).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (3.45 ANGSTROMS) OF 1-211, AND HOMODIMERIZATION.
RX PubMed=16368107; DOI=10.1016/j.jmb.2005.11.032;
RA O'Neill J.W., Manion M.K., Maguire B., Hockenbery D.M.;
RT "BCL-XL dimerization by three-dimensional domain swapping.";
RL J. Mol. Biol. 356:367-381(2006).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 83-209 IN COMPLEX WITH BECN1.
RX PubMed=17337444; DOI=10.1074/jbc.M700492200;
RA Oberstein A., Jeffrey P.D., Shi Y.;
RT "Crystal structure of the Bcl-XL-Beclin 1 peptide complex: Beclin 1 is
RT a novel BH3-only protein.";
RL J. Biol. Chem. 282:13123-13132(2007).
RN [28]
RP STRUCTURE BY NMR OF 1-209.
RX PubMed=17256834; DOI=10.1021/jm061152t;
RA Bruncko M., Oost T.K., Belli B.A., Ding H., Joseph M.K., Kunzer A.,
RA Martineau D., McClellan W.J., Mitten M., Ng S.-C., Nimmer P.M.,
RA Oltersdorf T., Park C.-M., Petros A.M., Shoemaker A.R., Song X.,
RA Wang X., Wendt M.D., Zhang H., Fesik S.W., Rosenberg S.H.,
RA Elmore S.W.;
RT "Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL.";
RL J. Med. Chem. 50:641-662(2007).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 1-209 IN COMPLEX WITH HEBP2,
RP AND INTERACTION WITH HEBP2.
RX PubMed=21639858; DOI=10.1042/BJ20110257;
RA Ambrosi E., Capaldi S., Bovi M., Saccomani G., Perduca M.,
RA Monaco H.L.;
RT "Structural changes in the BH3 domain of SOUL protein upon interaction
RT with the anti-apoptotic protein Bcl-xL.";
RL Biochem. J. 438:291-301(2011).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 1-209 IN COMPLEX WITH BBC3,
RP STRUCTURE BY NMR OF 1-209 IN COMPLEX WITH BBC3, AND INTERACTION WITH
RP BBC3 AND TP53.
RX PubMed=23340338; DOI=10.1038/nchembio.1166;
RA Follis A.V., Chipuk J.E., Fisher J.C., Yun M.K., Grace C.R.,
RA Nourse A., Baran K., Ou L., Min L., White S.W., Green D.R.,
RA Kriwacki R.W.;
RT "PUMA binding induces partial unfolding within BCL-xL to disrupt p53
RT binding and promote apoptosis.";
RL Nat. Chem. Biol. 9:163-168(2013).
CC -!- FUNCTION: Potent inhibitor of cell death. Inhibits activation of
CC caspases. Appears to regulate cell death by blocking the voltage-
CC dependent anion channel (VDAC) by binding to it and preventing the
CC release of the caspase activator, CYC1, from the mitochondrial
CC membrane. Also acts as a regulator of G2 checkpoint and
CC progression to cytokinesis during mitosis.
CC -!- FUNCTION: Isoform Bcl-X(L) also regulates presynaptic plasticity,
CC including neurotransmitter release and recovery, number of axonal
CC mitochondria as well as size and number of synaptic vesicle
CC clusters. During synaptic stimulation, increases ATP availability
CC from mitochondria through regulation of mitochondrial membrane ATP
CC synthase F(1)F(0) activity and regulates endocytic vesicle
CC retrieval in hippocampal neurons through association with DMN1L
CC and stimulation of its GTPase activity in synaptic vesicles.
CC -!- FUNCTION: Isoform Bcl-X(S) promotes apoptosis.
CC -!- SUBUNIT: Homodimer. Isoform Bcl-X(L) forms heterodimers with BAX,
CC BAK or BCL2. Heterodimerization with BAX does not seem to be
CC required for anti-apoptotic activity. Interacts with BCL2L11.
CC Interacts with BAD. Interacts (isoform Bcl-X(L)) with SIVA1
CC (isoform 1); the interaction inhibits the anti-apoptotic activity.
CC Interacts with BECN1 and PGAM5. Isoform Bcl-X(L) interacts with
CC IKZF3. Interacts with HEBP2. Isoform Bcl-X(L) interacts with
CC BOP/C22orf29. Interacts with p53/TP53 and BBC3; interaction with
CC BBC3 disrupts the interaction with p53/TP53. Isoform Bcl-X(L)
CC interacts with DNM1L and CLTA; DNM1L and BCL2L1 isoform BCL-X(L)
CC may form a complex in synaptic vesicles that also contains
CC clathrin and MFF. Interacts with ATP5A and ATP5B; the interactions
CC mediate the association of isoform Bcl-X(L) with the mitochondrial
CC membrane ATP synthase F(1)F(0) ATP synthase.
CC -!- INTERACTION:
CC Self; NbExp=2; IntAct=EBI-78035, EBI-78035;
CC Q92934:BAD; NbExp=6; IntAct=EBI-287195, EBI-700771;
CC Q61337:Bad (xeno); NbExp=2; IntAct=EBI-287195, EBI-400328;
CC Q16611:BAK1; NbExp=8; IntAct=EBI-287195, EBI-519866;
CC Q07812:BAX; NbExp=13; IntAct=EBI-287195, EBI-516580;
CC Q9BXH1:BBC3; NbExp=7; IntAct=EBI-287195, EBI-519884;
CC Q99ML1:Bbc3 (xeno); NbExp=3; IntAct=EBI-287195, EBI-727801;
CC O43521:BCL2L11; NbExp=10; IntAct=EBI-287195, EBI-526406;
CC O43521-1:BCL2L11; NbExp=2; IntAct=EBI-287195, EBI-526416;
CC Q14457:BECN1; NbExp=4; IntAct=EBI-287195, EBI-949378;
CC P55957:BID; NbExp=6; IntAct=EBI-287195, EBI-519672;
CC Q13323:BIK; NbExp=3; IntAct=EBI-287195, EBI-700794;
CC P30429:ced-4 (xeno); NbExp=3; IntAct=EBI-78035, EBI-494118;
CC P10909-4:CLU; NbExp=6; IntAct=EBI-287195, EBI-4322678;
CC O00198:HRK; NbExp=3; IntAct=EBI-287195, EBI-701322;
CC Q9C000:NLRP1; NbExp=9; IntAct=EBI-78035, EBI-1220518;
CC O15304:SIVA1; NbExp=2; IntAct=EBI-78035, EBI-520756;
CC O15304-1:SIVA1; NbExp=5; IntAct=EBI-287195, EBI-520766;
CC Q9H2V7:SPNS1; NbExp=3; IntAct=EBI-78035, EBI-1386527;
CC P04637:TP53; NbExp=18; IntAct=EBI-287195, EBI-366083;
CC P02340:Tp53 (xeno); NbExp=3; IntAct=EBI-287195, EBI-474016;
CC Q13625:TP53BP2; NbExp=4; IntAct=EBI-287195, EBI-77642;
CC Q86Y07-1:VRK2; NbExp=2; IntAct=EBI-287195, EBI-1207633;
CC -!- SUBCELLULAR LOCATION: Isoform Bcl-X(L): Mitochondrion inner
CC membrane (By similarity). Mitochondrion outer membrane (By
CC similarity). Mitochondrion matrix (By similarity). Cytoplasmic
CC vesicle, secretory vesicle, synaptic vesicle membrane (By
CC similarity). Cytoplasm, cytosol (By similarity). Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome. Nucleus
CC membrane; Single-pass membrane protein; Cytoplasmic side (By
CC similarity). Note=After neuronal stimulation, translocates from
CC cytosol to synaptic vesicle and mitochondrion membrane in a
CC calmodulin-dependent manner (By similarity). Localizes to the
CC centrosome when phosphorylated at Ser-49.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Bcl-X(L); Synonyms=Bcl-xL;
CC IsoId=Q07817-1; Sequence=Displayed;
CC Name=Bcl-X(S); Synonyms=Bcl-xS;
CC IsoId=Q07817-2; Sequence=VSP_000515;
CC Name=Bcl-X(beta);
CC IsoId=Q07817-3; Sequence=VSP_000516;
CC -!- TISSUE SPECIFICITY: Bcl-X(S) is expressed at high levels in cells
CC that undergo a high rate of turnover, such as developing
CC lymphocytes. In contrast, Bcl-X(L) is found in tissues containing
CC long-lived postmitotic cells, such as adult brain.
CC -!- DOMAIN: The BH4 motif is required for anti-apoptotic activity. The
CC BH1 and BH2 motifs are required for both heterodimerization with
CC other Bcl-2 family members and for repression of cell death.
CC -!- PTM: Proteolytically cleaved by caspases during apoptosis. The
CC cleaved protein, lacking the BH4 motif, has pro-apoptotic
CC activity.
CC -!- PTM: Phosphorylated on Ser-62 by CDK1. This phosphorylation is
CC partial in normal mitotic cells, but complete in G2-arrested cells
CC upon DNA-damage, thus promoting subsequent apoptosis probably by
CC triggering caspases-mediated proteolysis. Phosphorylated by PLK3,
CC leading to regulate the G2 checkpoint and progression to
CC cytokinesis during mitosis. Phosphorylation at Ser-49 appears
CC during the S phase and G2, disappears rapidly in early mitosis
CC during prometaphase, metaphase and early anaphase, and re-appears
CC during telophase and cytokinesis.
CC -!- SIMILARITY: Belongs to the Bcl-2 family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/BCL2L1ID129ch20q11.html";
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DR EMBL; Z23115; CAA80661.1; -; mRNA.
DR EMBL; Z23116; CAA80662.1; -; mRNA.
DR EMBL; U72398; AAB17354.1; -; Genomic_DNA.
DR EMBL; CR936637; CAI56777.1; -; mRNA.
DR EMBL; BT007208; AAP35872.1; -; mRNA.
DR EMBL; AL160175; CAI12811.1; -; Genomic_DNA.
DR EMBL; AL117381; CAI12811.1; JOINED; Genomic_DNA.
DR EMBL; AL117381; CAI23025.1; -; Genomic_DNA.
DR EMBL; AL160175; CAI23025.1; JOINED; Genomic_DNA.
DR EMBL; CH471077; EAW76424.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76425.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76429.1; -; Genomic_DNA.
DR EMBL; BC019307; AAH19307.1; -; mRNA.
DR PIR; B47537; B47537.
DR PIR; JE0203; JE0203.
DR RefSeq; NP_001182.1; NM_001191.2.
DR RefSeq; NP_612815.1; NM_138578.1.
DR RefSeq; XP_005260543.1; XM_005260486.1.
DR RefSeq; XP_005260544.1; XM_005260487.1.
DR UniGene; Hs.516966; -.
DR PDB; 1BXL; NMR; -; A=1-209.
DR PDB; 1G5J; NMR; -; A=1-209.
DR PDB; 1LXL; NMR; -; A=1-209.
DR PDB; 1MAZ; X-ray; 2.20 A; A=1-209.
DR PDB; 1R2D; X-ray; 1.95 A; A=1-211.
DR PDB; 1R2E; X-ray; 2.10 A; A=1-211.
DR PDB; 1R2G; X-ray; 2.70 A; A=1-211.
DR PDB; 1R2H; X-ray; 2.20 A; A=1-211.
DR PDB; 1R2I; X-ray; 2.00 A; A=1-211.
DR PDB; 1YSG; NMR; -; A=1-209.
DR PDB; 1YSI; NMR; -; A=1-209.
DR PDB; 1YSN; NMR; -; A=1-209.
DR PDB; 2B48; X-ray; 3.45 A; A=1-211.
DR PDB; 2LP8; NMR; -; A=1-209.
DR PDB; 2LPC; NMR; -; A=1-209.
DR PDB; 2M03; NMR; -; A=1-209.
DR PDB; 2M04; NMR; -; A=1-209.
DR PDB; 2O1Y; NMR; -; A=1-209.
DR PDB; 2O2M; NMR; -; A=2-196.
DR PDB; 2O2N; NMR; -; A=2-196.
DR PDB; 2P1L; X-ray; 2.50 A; A/C/E/G=1-209.
DR PDB; 2PON; NMR; -; B=1-196.
DR PDB; 2YJ1; X-ray; 2.24 A; A/C=1-209.
DR PDB; 2YQ6; X-ray; 1.80 A; A=1-209.
DR PDB; 2YQ7; X-ray; 1.90 A; A=1-209.
DR PDB; 2YXJ; X-ray; 2.20 A; A/B=1-209.
DR PDB; 3CVA; X-ray; 2.70 A; X=1-211.
DR PDB; 3FDL; X-ray; 1.78 A; A=1-209.
DR PDB; 3FDM; X-ray; 2.26 A; A/B/C=1-209.
DR PDB; 3INQ; X-ray; 2.00 A; A/B=1-209.
DR PDB; 3IO8; X-ray; 2.30 A; A/C=1-209.
DR PDB; 3PL7; X-ray; 2.61 A; A/B=1-209.
DR PDB; 3QKD; X-ray; 2.02 A; A/B=1-209.
DR PDB; 3R85; X-ray; 1.95 A; A/B/C/D=1-209.
DR PDB; 3SP7; X-ray; 1.40 A; A=1-209.
DR PDB; 3SPF; X-ray; 1.70 A; A=1-200.
DR PDB; 3ZK6; X-ray; 2.48 A; A/B=1-209.
DR PDB; 3ZLN; X-ray; 2.29 A; A=1-209.
DR PDB; 3ZLO; X-ray; 2.60 A; A=1-209.
DR PDB; 3ZLR; X-ray; 2.03 A; A/B=1-209.
DR PDB; 4A1U; X-ray; 1.54 A; A=1-209.
DR PDB; 4A1W; X-ray; 2.50 A; A/B/C/D=1-209.
DR PDB; 4AQ3; X-ray; 2.40 A; A/B/C/D/E/F=15-44.
DR PDB; 4EHR; X-ray; 2.09 A; A=1-209.
DR PDB; 4HNJ; X-ray; 2.90 A; A/B=1-209.
DR PDB; 4IEH; X-ray; 2.10 A; A=15-44.
DR PDBsum; 1BXL; -.
DR PDBsum; 1G5J; -.
DR PDBsum; 1LXL; -.
DR PDBsum; 1MAZ; -.
DR PDBsum; 1R2D; -.
DR PDBsum; 1R2E; -.
DR PDBsum; 1R2G; -.
DR PDBsum; 1R2H; -.
DR PDBsum; 1R2I; -.
DR PDBsum; 1YSG; -.
DR PDBsum; 1YSI; -.
DR PDBsum; 1YSN; -.
DR PDBsum; 2B48; -.
DR PDBsum; 2LP8; -.
DR PDBsum; 2LPC; -.
DR PDBsum; 2M03; -.
DR PDBsum; 2M04; -.
DR PDBsum; 2O1Y; -.
DR PDBsum; 2O2M; -.
DR PDBsum; 2O2N; -.
DR PDBsum; 2P1L; -.
DR PDBsum; 2PON; -.
DR PDBsum; 2YJ1; -.
DR PDBsum; 2YQ6; -.
DR PDBsum; 2YQ7; -.
DR PDBsum; 2YXJ; -.
DR PDBsum; 3CVA; -.
DR PDBsum; 3FDL; -.
DR PDBsum; 3FDM; -.
DR PDBsum; 3INQ; -.
DR PDBsum; 3IO8; -.
DR PDBsum; 3PL7; -.
DR PDBsum; 3QKD; -.
DR PDBsum; 3R85; -.
DR PDBsum; 3SP7; -.
DR PDBsum; 3SPF; -.
DR PDBsum; 3ZK6; -.
DR PDBsum; 3ZLN; -.
DR PDBsum; 3ZLO; -.
DR PDBsum; 3ZLR; -.
DR PDBsum; 4A1U; -.
DR PDBsum; 4A1W; -.
DR PDBsum; 4AQ3; -.
DR PDBsum; 4EHR; -.
DR PDBsum; 4HNJ; -.
DR PDBsum; 4IEH; -.
DR DisProt; DP00298; -.
DR ProteinModelPortal; Q07817; -.
DR SMR; Q07817; 1-210.
DR DIP; DIP-30916N; -.
DR IntAct; Q07817; 54.
DR MINT; MINT-89538; -.
DR STRING; 9606.ENSP00000302564; -.
DR BindingDB; Q07817; -.
DR ChEMBL; CHEMBL4625; -.
DR TCDB; 1.A.21.1.1; the bcl-2 (bcl-2) family.
DR PhosphoSite; Q07817; -.
DR DMDM; 728955; -.
DR PaxDb; Q07817; -.
DR PRIDE; Q07817; -.
DR DNASU; 598; -.
DR Ensembl; ENST00000307677; ENSP00000302564; ENSG00000171552.
DR Ensembl; ENST00000376055; ENSP00000365223; ENSG00000171552.
DR Ensembl; ENST00000376062; ENSP00000365230; ENSG00000171552.
DR Ensembl; ENST00000420653; ENSP00000405563; ENSG00000171552.
DR GeneID; 598; -.
DR KEGG; hsa:598; -.
DR UCSC; uc002wwl.3; human.
DR CTD; 598; -.
DR GeneCards; GC20M030252; -.
DR HGNC; HGNC:992; BCL2L1.
DR HPA; CAB000105; -.
DR MIM; 600039; gene.
DR neXtProt; NX_Q07817; -.
DR PharmGKB; PA76; -.
DR eggNOG; NOG300479; -.
DR HOGENOM; HOG000056452; -.
DR InParanoid; Q07817; -.
DR KO; K04570; -.
DR OMA; NGSPSWH; -.
DR OrthoDB; EOG70GMGD; -.
DR PhylomeDB; Q07817; -.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; BCL2L1; human.
DR EvolutionaryTrace; Q07817; -.
DR GeneWiki; BCL2-like_1_(gene); -.
DR GenomeRNAi; 598; -.
DR NextBio; 2433; -.
DR PMAP-CutDB; Q07817; -.
DR PRO; PR:Q07817; -.
DR ArrayExpress; Q07817; -.
DR Bgee; Q07817; -.
DR CleanEx; HS_BCL2L1; -.
DR Genevestigator; Q07817; -.
DR GO; GO:0097136; C:Bcl-2 family protein complex; IDA:UniProtKB.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005741; C:mitochondrial outer membrane; NAS:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030672; C:synaptic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008283; P:cell proliferation; IEA:Ensembl.
DR GO; GO:0060154; P:cellular process regulating host cell cycle in response to virus; IEA:Ensembl.
DR GO; GO:0071312; P:cellular response to alkaloid; IEA:Ensembl.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl.
DR GO; GO:0071480; P:cellular response to gamma radiation; IEA:Ensembl.
DR GO; GO:0000910; P:cytokinesis; IMP:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0009566; P:fertilization; IEA:Ensembl.
DR GO; GO:0007281; P:germ cell development; IEA:Ensembl.
DR GO; GO:0040007; P:growth; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0007093; P:mitotic cell cycle checkpoint; IMP:UniProtKB.
DR GO; GO:2000811; P:negative regulation of anoikis; IMP:UniProtKB.
DR GO; GO:0010507; P:negative regulation of autophagy; TAS:UniProtKB.
DR GO; GO:0090005; P:negative regulation of establishment of protein localization to plasma membrane; IDA:BHF-UCL.
DR GO; GO:1900118; P:negative regulation of execution phase of apoptosis; IDA:UniProtKB.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; TAS:BHF-UCL.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IDA:UniProtKB.
DR GO; GO:1902230; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage; IDA:BHF-UCL.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IC:BHF-UCL.
DR GO; GO:0035872; P:nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway; TAS:Reactome.
DR GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; IDA:HGNC.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IDA:HGNC.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IDA:HGNC.
DR GO; GO:0046898; P:response to cycloheximide; IEA:Ensembl.
DR GO; GO:0034097; P:response to cytokine stimulus; IDA:MGI.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR GO; GO:0019050; P:suppression by virus of host apoptotic process; IDA:MGI.
DR InterPro; IPR013279; Apop_reg_BclX.
DR InterPro; IPR002475; Bcl2-like.
DR InterPro; IPR004725; Bcl2/BclX.
DR InterPro; IPR020717; Bcl2_BH1_motif_CS.
DR InterPro; IPR020726; Bcl2_BH2_motif_CS.
DR InterPro; IPR020728; Bcl2_BH3_motif_CS.
DR InterPro; IPR003093; Bcl2_BH4.
DR InterPro; IPR020731; Bcl2_BH4_motif_CS.
DR InterPro; IPR026298; Blc2_fam.
DR PANTHER; PTHR11256; PTHR11256; 1.
DR PANTHER; PTHR11256:SF12; PTHR11256:SF12; 1.
DR Pfam; PF00452; Bcl-2; 1.
DR Pfam; PF02180; BH4; 1.
DR PRINTS; PR01864; APOPREGBCLX.
DR PRINTS; PR01862; BCL2FAMILY.
DR SMART; SM00265; BH4; 1.
DR TIGRFAMs; TIGR00865; bcl-2; 1.
DR PROSITE; PS50062; BCL2_FAMILY; 1.
DR PROSITE; PS01080; BH1; 1.
DR PROSITE; PS01258; BH2; 1.
DR PROSITE; PS01259; BH3; 1.
DR PROSITE; PS01260; BH4_1; 1.
DR PROSITE; PS50063; BH4_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cell junction;
KW Complete proteome; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton;
KW Endocytosis; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Mitochondrion outer membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Synapse; Transmembrane; Transmembrane helix.
FT CHAIN 1 233 Bcl-2-like protein 1.
FT /FTId=PRO_0000143062.
FT TRANSMEM 210 226 Helical; (Potential).
FT MOTIF 4 24 BH4.
FT MOTIF 86 100 BH3.
FT MOTIF 129 148 BH1.
FT MOTIF 180 195 BH2.
FT SITE 61 62 Cleavage; by caspase-1.
FT MOD_RES 49 49 Phosphoserine; by PLK3.
FT MOD_RES 62 62 Phosphoserine; by CDK1.
FT VAR_SEQ 126 188 Missing (in isoform Bcl-X(S)).
FT /FTId=VSP_000515.
FT VAR_SEQ 189 233 DTFVELYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSL
FT FSRK -> VRTKPLVCPFSLASGQRSPTALLLYLFLLCWVI
FT VGDVDS (in isoform Bcl-X(beta)).
FT /FTId=VSP_000516.
FT MUTAGEN 49 49 S->A: Less stable at G2 checkpoint after
FT DNA damage.
FT MUTAGEN 61 61 D->A: No cleavage by caspase-1 nor by
FT caspase-3.
FT MUTAGEN 131 133 FRD->VRA: No heterodimerization with BAX.
FT MUTAGEN 135 137 VNW->AIL: Loss of anti-apoptotic
FT activity.
FT MUTAGEN 138 140 GRI->ELN: Loss of anti-apoptotic
FT activity.
FT MUTAGEN 138 138 G->A: No heterodimerization with BAX.
FT MUTAGEN 145 147 SFG->YCC: Decreases interaction with
FT DNM1L, no effect on endocytosis
FT enhancement.
FT MUTAGEN 148 148 G->E: No heterodimerization with BAX.
FT MUTAGEN 156 156 D->A: No effect on caspase-1 cleavage.
FT MUTAGEN 176 176 D->A: No effect on caspase-1 cleavage.
FT MUTAGEN 188 191 WDTF->SVTC: Abolishes interaction with
FT DNM1L and endocytosis enhancement.
FT MUTAGEN 188 189 WD->GA: Reduces anti-apoptotic activity
FT by about half.
FT MUTAGEN 189 189 D->A: No effect on caspase-1 cleavage.
FT CONFLICT 70 70 G -> A (in Ref. 1; CAA80661).
FT CONFLICT 168 168 A -> V (in Ref. 4; CAI56777).
FT HELIX 3 18
FT TURN 19 21
FT HELIX 24 26
FT STRAND 29 36
FT STRAND 38 41
FT TURN 42 44
FT TURN 65 68
FT TURN 70 73
FT HELIX 85 101
FT HELIX 102 104
FT HELIX 108 111
FT TURN 116 118
FT HELIX 120 130
FT TURN 131 133
FT HELIX 137 156
FT HELIX 162 177
FT HELIX 179 184
FT TURN 185 187
FT HELIX 188 198
FT HELIX 199 205
FT STRAND 206 208
SQ SEQUENCE 233 AA; 26049 MW; E09D3CDD851AE9BE CRC64;
MSQSNRELVV DFLSYKLSQK GYSWSQFSDV EENRTEAPEG TESEMETPSA INGNPSWHLA
DSPAVNGATG HSSSLDAREV IPMAAVKQAL REAGDEFELR YRRAFSDLTS QLHITPGTAY
QSFEQVVNEL FRDGVNWGRI VAFFSFGGAL CVESVDKEMQ VLVSRIAAWM ATYLNDHLEP
WIQENGGWDT FVELYGNNAA AESRKGQERF NRWFLTGMTV AGVVLLGSLF SRK
//
ID B2CL1_HUMAN Reviewed; 233 AA.
AC Q07817; E1P5L6; Q5CZ89; Q5TE65; Q92976;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1995, sequence version 1.
DT 22-JAN-2014, entry version 170.
DE RecName: Full=Bcl-2-like protein 1;
DE Short=Bcl2-L-1;
DE AltName: Full=Apoptosis regulator Bcl-X;
GN Name=BCL2L1; Synonyms=BCL2L, BCLX;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BCL-X(L) AND BCL-X(S)).
RX PubMed=8358789; DOI=10.1016/0092-8674(93)90508-N;
RA Boise L.H., Gonzalez-Garcia M., Postema C.E., Ding L., Lindsten T.,
RA Turka L.A., Mao X., Nunez G., Thompson C.B.;
RT "bcl-x, a bcl-2-related gene that functions as a dominant regulator of
RT apoptotic cell death.";
RL Cell 74:597-608(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BCL-X(BETA)), AND INTERACTION WITH
RP BAX.
RX PubMed=9675101; DOI=10.1006/bbrc.1998.8907;
RA Ban J., Eckhart L., Weninger W., Mildner M., Tschachler E.;
RT "Identification of a human cDNA encoding a novel Bcl-x isoform.";
RL Biochem. Biophys. Res. Commun. 248:147-152(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM BCL-X(BETA)).
RA Inohara N., Ohta S.;
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BCL-X(L)).
RC TISSUE=Colon carcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BCL-X(L)).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BCL-X(L)).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP MUTAGENESIS OF GLY-138, AND HETERODIMERIZATION.
RX PubMed=7644501; DOI=10.1073/pnas.92.17.7834;
RA Sedlak T.W., Oltvai Z.N., Yang E., Wang K., Boise L.H., Thompson C.B.,
RA Korsmeyer S.J.;
RT "Multiple Bcl-2 family members demonstrate selective dimerizations
RT with Bax.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:7834-7838(1995).
RN [10]
RP MUTAGENESIS OF BH1 AND BH2 MOTIFS.
RX PubMed=8596636; DOI=10.1038/379554a0;
RA Cheng E.H.-Y., Levine B., Boise L.H., Thompson C.B., Hardwick J.M.,
RA Korsmeyer S.J.;
RT "Bax-independent inhibition of apoptosis by Bcl-XL.";
RL Nature 379:554-556(1996).
RN [11]
RP CLEAVAGE BY CASPASES, AND MUTAGENESIS OF ASP-61.
RX PubMed=9435230; DOI=10.1073/pnas.95.2.554;
RA Clem R.J., Cheng E.H.-Y., Karp C.L., Kirsch D.G., Ueno K.,
RA Takahashi A., Kastan M.B., Griffin D.E., Earnshaw W.C., Veliuona M.A.,
RA Hardwick J.M.;
RT "Modulation of cell death by Bcl-xL through caspase interaction.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:554-559(1998).
RN [12]
RP INTERACTION WITH BAX.
RX PubMed=10772918; DOI=10.1006/bbrc.2000.2537;
RA Schmitt E., Paquet C., Beauchemin M., Dever-Bertrand J., Bertrand R.;
RT "Characterization of Bax-sigma, a cell death-inducing isoform of
RT Bax.";
RL Biochem. Biophys. Res. Commun. 270:868-879(2000).
RN [13]
RP INTERACTION WITH IKZF3.
RX PubMed=11714801;
RA Rebollo A., Ayllon V., Fleischer A., Martinez C.A., Zaballos A.;
RT "The association of Aiolos transcription factor and Bcl-xL is involved
RT in the control of apoptosis.";
RL J. Immunol. 167:6366-6373(2001).
RN [14]
RP INTERACTION WITH BCL2 AND BBC3.
RX PubMed=11463391; DOI=10.1016/S1097-2765(01)00213-1;
RA Yu J., Zhang L., Hwang P.M., Kinzler K.W., Vogelstein B.;
RT "PUMA induces the rapid apoptosis of colorectal cancer cells.";
RL Mol. Cell 7:673-682(2001).
RN [15]
RP INTERACTION WITH SIVA1.
RX PubMed=12011449; DOI=10.1073/pnas.102182299;
RA Xue L., Chu F., Cheng Y., Sun X., Borthakur A., Ramarao M., Pandey P.,
RA Wu M., Schlossman S.F., Prasad K.V.S.;
RT "Siva-1 binds to and inhibits BCL-X(L)-mediated protection against UV
RT radiation-induced apoptosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:6925-6930(2002).
RN [16]
RP INTERACTION WITH PGAM5.
RX PubMed=17046835; DOI=10.1074/jbc.M606539200;
RA Lo S.-C., Hannink M.;
RT "PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the
RT redox-regulated Keap1-dependent ubiquitin ligase complex.";
RL J. Biol. Chem. 281:37893-37903(2006).
RN [17]
RP FUNCTION IN APOPTOSIS, PHOSPHORYLATION AT SER-62 BY CDK1, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19917720; DOI=10.1128/MCB.00882-09;
RA Terrano D.T., Upreti M., Chambers T.C.;
RT "Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts
RT as a functional link coupling mitotic arrest and apoptosis.";
RL Mol. Cell. Biol. 30:640-656(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-49, AND
RP MUTAGENESIS OF SER-49.
RX PubMed=21840391; DOI=10.1016/j.cellsig.2011.07.017;
RA Wang J., Beauchemin M., Bertrand R.;
RT "Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle
RT progression and checkpoints.";
RL Cell. Signal. 23:2030-2038(2011).
RN [20]
RP INTERACTION WITH DNM1L, FUNCTION, AND MUTAGENESIS OF 145-SER--GLY-147
RP AND 188-TRP--PHE-191.
RX PubMed=23792689; DOI=10.1038/ncb2791;
RA Li H., Alavian K.N., Lazrove E., Mehta N., Jones A., Zhang P.,
RA Licznerski P., Graham M., Uo T., Guo J., Rahner C., Duman R.S.,
RA Morrison R.S., Jonas E.A.;
RT "A Bcl-xL-Drp1 complex regulates synaptic vesicle membrane dynamics
RT during endocytosis.";
RL Nat. Cell Biol. 15:773-785(2013).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), AND STRUCTURE BY NMR OF 1-209.
RX PubMed=8692274; DOI=10.1038/381335a0;
RA Muchmore S.W., Sattler M., Liang H., Meadows R.P., Harlan J.E.,
RA Yoon H.S., Nettesheim D., Chang B.S., Thompson C.B., Wong S.L.,
RA Ng S.L., Fesik S.W.;
RT "X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed
RT cell death.";
RL Nature 381:335-341(1996).
RN [22]
RP STRUCTURE BY NMR OF 1-209.
RX PubMed=9020082; DOI=10.1126/science.275.5302.983;
RA Sattler M., Liang H., Nettesheim D., Meadows R.P., Harlan J.E.,
RA Eberstadt M., Yoon H.S., Shuker S.B., Chang B.S., Minn A.J.,
RA Thompson C.B., Fesik S.W.;
RT "Structure of Bcl-xL-Bak peptide complex: recognition between
RT regulators of apoptosis.";
RL Science 275:983-986(1997).
RN [23]
RP STRUCTURE BY NMR OF 1-209 IN COMPLEX WITH BAD.
RX PubMed=11206074; DOI=10.1017/S096183680000331X;
RA Petros A.M., Nettesheim D.G., Wang Y., Olejniczak E.T., Meadows R.P.,
RA Mack J., Swift K., Matayoshi E.D., Zhang H., Thompson C.B.,
RA Fesik S.W.;
RT "Rationale for Bcl-xL/Bad peptide complex formation from structure,
RT mutagenesis, and biophysical studies.";
RL Protein Sci. 9:2528-2534(2000).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 1-211.
RX PubMed=14534311; DOI=10.1074/jbc.M306021200;
RA Manion M.K., O'Neill J.W., Giedt C.D., Kim K.M., Zhang K.Y.Z.,
RA Hockenbery D.M.;
RT "Bcl-XL mutations suppress cellular sensitivity to antimycin A.";
RL J. Biol. Chem. 279:2159-2165(2004).
RN [25]
RP STRUCTURE BY NMR OF 1-209.
RX PubMed=15902208; DOI=10.1038/nature03579;
RA Oltersdorf T., Elmore S.W., Shoemaker A.R., Armstrong R.C.,
RA Augeri D.J., Belli B.A., Bruncko M., Deckwerth T.L., Dinges J.,
RA Hajduk P.J., Joseph M.K., Kitada S., Korsmeyer S.J., Kunzer A.R.,
RA Letai A., Li C., Mitten M.J., Nettesheim D.G., Ng S.-C., Nimmer P.M.,
RA O'Connor J.M., Oleksijew A., Petros A.M., Reed J.C., Shen W.,
RA Tahir S.K., Thompson C.B., Tomaselli K.J., Wang B., Wendt M.D.,
RA Zhang H., Fesik S.W., Rosenberg S.H.;
RT "An inhibitor of Bcl-2 family proteins induces regression of solid
RT tumours.";
RL Nature 435:677-681(2005).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (3.45 ANGSTROMS) OF 1-211, AND HOMODIMERIZATION.
RX PubMed=16368107; DOI=10.1016/j.jmb.2005.11.032;
RA O'Neill J.W., Manion M.K., Maguire B., Hockenbery D.M.;
RT "BCL-XL dimerization by three-dimensional domain swapping.";
RL J. Mol. Biol. 356:367-381(2006).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 83-209 IN COMPLEX WITH BECN1.
RX PubMed=17337444; DOI=10.1074/jbc.M700492200;
RA Oberstein A., Jeffrey P.D., Shi Y.;
RT "Crystal structure of the Bcl-XL-Beclin 1 peptide complex: Beclin 1 is
RT a novel BH3-only protein.";
RL J. Biol. Chem. 282:13123-13132(2007).
RN [28]
RP STRUCTURE BY NMR OF 1-209.
RX PubMed=17256834; DOI=10.1021/jm061152t;
RA Bruncko M., Oost T.K., Belli B.A., Ding H., Joseph M.K., Kunzer A.,
RA Martineau D., McClellan W.J., Mitten M., Ng S.-C., Nimmer P.M.,
RA Oltersdorf T., Park C.-M., Petros A.M., Shoemaker A.R., Song X.,
RA Wang X., Wendt M.D., Zhang H., Fesik S.W., Rosenberg S.H.,
RA Elmore S.W.;
RT "Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL.";
RL J. Med. Chem. 50:641-662(2007).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 1-209 IN COMPLEX WITH HEBP2,
RP AND INTERACTION WITH HEBP2.
RX PubMed=21639858; DOI=10.1042/BJ20110257;
RA Ambrosi E., Capaldi S., Bovi M., Saccomani G., Perduca M.,
RA Monaco H.L.;
RT "Structural changes in the BH3 domain of SOUL protein upon interaction
RT with the anti-apoptotic protein Bcl-xL.";
RL Biochem. J. 438:291-301(2011).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 1-209 IN COMPLEX WITH BBC3,
RP STRUCTURE BY NMR OF 1-209 IN COMPLEX WITH BBC3, AND INTERACTION WITH
RP BBC3 AND TP53.
RX PubMed=23340338; DOI=10.1038/nchembio.1166;
RA Follis A.V., Chipuk J.E., Fisher J.C., Yun M.K., Grace C.R.,
RA Nourse A., Baran K., Ou L., Min L., White S.W., Green D.R.,
RA Kriwacki R.W.;
RT "PUMA binding induces partial unfolding within BCL-xL to disrupt p53
RT binding and promote apoptosis.";
RL Nat. Chem. Biol. 9:163-168(2013).
CC -!- FUNCTION: Potent inhibitor of cell death. Inhibits activation of
CC caspases. Appears to regulate cell death by blocking the voltage-
CC dependent anion channel (VDAC) by binding to it and preventing the
CC release of the caspase activator, CYC1, from the mitochondrial
CC membrane. Also acts as a regulator of G2 checkpoint and
CC progression to cytokinesis during mitosis.
CC -!- FUNCTION: Isoform Bcl-X(L) also regulates presynaptic plasticity,
CC including neurotransmitter release and recovery, number of axonal
CC mitochondria as well as size and number of synaptic vesicle
CC clusters. During synaptic stimulation, increases ATP availability
CC from mitochondria through regulation of mitochondrial membrane ATP
CC synthase F(1)F(0) activity and regulates endocytic vesicle
CC retrieval in hippocampal neurons through association with DMN1L
CC and stimulation of its GTPase activity in synaptic vesicles.
CC -!- FUNCTION: Isoform Bcl-X(S) promotes apoptosis.
CC -!- SUBUNIT: Homodimer. Isoform Bcl-X(L) forms heterodimers with BAX,
CC BAK or BCL2. Heterodimerization with BAX does not seem to be
CC required for anti-apoptotic activity. Interacts with BCL2L11.
CC Interacts with BAD. Interacts (isoform Bcl-X(L)) with SIVA1
CC (isoform 1); the interaction inhibits the anti-apoptotic activity.
CC Interacts with BECN1 and PGAM5. Isoform Bcl-X(L) interacts with
CC IKZF3. Interacts with HEBP2. Isoform Bcl-X(L) interacts with
CC BOP/C22orf29. Interacts with p53/TP53 and BBC3; interaction with
CC BBC3 disrupts the interaction with p53/TP53. Isoform Bcl-X(L)
CC interacts with DNM1L and CLTA; DNM1L and BCL2L1 isoform BCL-X(L)
CC may form a complex in synaptic vesicles that also contains
CC clathrin and MFF. Interacts with ATP5A and ATP5B; the interactions
CC mediate the association of isoform Bcl-X(L) with the mitochondrial
CC membrane ATP synthase F(1)F(0) ATP synthase.
CC -!- INTERACTION:
CC Self; NbExp=2; IntAct=EBI-78035, EBI-78035;
CC Q92934:BAD; NbExp=6; IntAct=EBI-287195, EBI-700771;
CC Q61337:Bad (xeno); NbExp=2; IntAct=EBI-287195, EBI-400328;
CC Q16611:BAK1; NbExp=8; IntAct=EBI-287195, EBI-519866;
CC Q07812:BAX; NbExp=13; IntAct=EBI-287195, EBI-516580;
CC Q9BXH1:BBC3; NbExp=7; IntAct=EBI-287195, EBI-519884;
CC Q99ML1:Bbc3 (xeno); NbExp=3; IntAct=EBI-287195, EBI-727801;
CC O43521:BCL2L11; NbExp=10; IntAct=EBI-287195, EBI-526406;
CC O43521-1:BCL2L11; NbExp=2; IntAct=EBI-287195, EBI-526416;
CC Q14457:BECN1; NbExp=4; IntAct=EBI-287195, EBI-949378;
CC P55957:BID; NbExp=6; IntAct=EBI-287195, EBI-519672;
CC Q13323:BIK; NbExp=3; IntAct=EBI-287195, EBI-700794;
CC P30429:ced-4 (xeno); NbExp=3; IntAct=EBI-78035, EBI-494118;
CC P10909-4:CLU; NbExp=6; IntAct=EBI-287195, EBI-4322678;
CC O00198:HRK; NbExp=3; IntAct=EBI-287195, EBI-701322;
CC Q9C000:NLRP1; NbExp=9; IntAct=EBI-78035, EBI-1220518;
CC O15304:SIVA1; NbExp=2; IntAct=EBI-78035, EBI-520756;
CC O15304-1:SIVA1; NbExp=5; IntAct=EBI-287195, EBI-520766;
CC Q9H2V7:SPNS1; NbExp=3; IntAct=EBI-78035, EBI-1386527;
CC P04637:TP53; NbExp=18; IntAct=EBI-287195, EBI-366083;
CC P02340:Tp53 (xeno); NbExp=3; IntAct=EBI-287195, EBI-474016;
CC Q13625:TP53BP2; NbExp=4; IntAct=EBI-287195, EBI-77642;
CC Q86Y07-1:VRK2; NbExp=2; IntAct=EBI-287195, EBI-1207633;
CC -!- SUBCELLULAR LOCATION: Isoform Bcl-X(L): Mitochondrion inner
CC membrane (By similarity). Mitochondrion outer membrane (By
CC similarity). Mitochondrion matrix (By similarity). Cytoplasmic
CC vesicle, secretory vesicle, synaptic vesicle membrane (By
CC similarity). Cytoplasm, cytosol (By similarity). Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome. Nucleus
CC membrane; Single-pass membrane protein; Cytoplasmic side (By
CC similarity). Note=After neuronal stimulation, translocates from
CC cytosol to synaptic vesicle and mitochondrion membrane in a
CC calmodulin-dependent manner (By similarity). Localizes to the
CC centrosome when phosphorylated at Ser-49.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Bcl-X(L); Synonyms=Bcl-xL;
CC IsoId=Q07817-1; Sequence=Displayed;
CC Name=Bcl-X(S); Synonyms=Bcl-xS;
CC IsoId=Q07817-2; Sequence=VSP_000515;
CC Name=Bcl-X(beta);
CC IsoId=Q07817-3; Sequence=VSP_000516;
CC -!- TISSUE SPECIFICITY: Bcl-X(S) is expressed at high levels in cells
CC that undergo a high rate of turnover, such as developing
CC lymphocytes. In contrast, Bcl-X(L) is found in tissues containing
CC long-lived postmitotic cells, such as adult brain.
CC -!- DOMAIN: The BH4 motif is required for anti-apoptotic activity. The
CC BH1 and BH2 motifs are required for both heterodimerization with
CC other Bcl-2 family members and for repression of cell death.
CC -!- PTM: Proteolytically cleaved by caspases during apoptosis. The
CC cleaved protein, lacking the BH4 motif, has pro-apoptotic
CC activity.
CC -!- PTM: Phosphorylated on Ser-62 by CDK1. This phosphorylation is
CC partial in normal mitotic cells, but complete in G2-arrested cells
CC upon DNA-damage, thus promoting subsequent apoptosis probably by
CC triggering caspases-mediated proteolysis. Phosphorylated by PLK3,
CC leading to regulate the G2 checkpoint and progression to
CC cytokinesis during mitosis. Phosphorylation at Ser-49 appears
CC during the S phase and G2, disappears rapidly in early mitosis
CC during prometaphase, metaphase and early anaphase, and re-appears
CC during telophase and cytokinesis.
CC -!- SIMILARITY: Belongs to the Bcl-2 family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/BCL2L1ID129ch20q11.html";
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DR EMBL; Z23115; CAA80661.1; -; mRNA.
DR EMBL; Z23116; CAA80662.1; -; mRNA.
DR EMBL; U72398; AAB17354.1; -; Genomic_DNA.
DR EMBL; CR936637; CAI56777.1; -; mRNA.
DR EMBL; BT007208; AAP35872.1; -; mRNA.
DR EMBL; AL160175; CAI12811.1; -; Genomic_DNA.
DR EMBL; AL117381; CAI12811.1; JOINED; Genomic_DNA.
DR EMBL; AL117381; CAI23025.1; -; Genomic_DNA.
DR EMBL; AL160175; CAI23025.1; JOINED; Genomic_DNA.
DR EMBL; CH471077; EAW76424.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76425.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76429.1; -; Genomic_DNA.
DR EMBL; BC019307; AAH19307.1; -; mRNA.
DR PIR; B47537; B47537.
DR PIR; JE0203; JE0203.
DR RefSeq; NP_001182.1; NM_001191.2.
DR RefSeq; NP_612815.1; NM_138578.1.
DR RefSeq; XP_005260543.1; XM_005260486.1.
DR RefSeq; XP_005260544.1; XM_005260487.1.
DR UniGene; Hs.516966; -.
DR PDB; 1BXL; NMR; -; A=1-209.
DR PDB; 1G5J; NMR; -; A=1-209.
DR PDB; 1LXL; NMR; -; A=1-209.
DR PDB; 1MAZ; X-ray; 2.20 A; A=1-209.
DR PDB; 1R2D; X-ray; 1.95 A; A=1-211.
DR PDB; 1R2E; X-ray; 2.10 A; A=1-211.
DR PDB; 1R2G; X-ray; 2.70 A; A=1-211.
DR PDB; 1R2H; X-ray; 2.20 A; A=1-211.
DR PDB; 1R2I; X-ray; 2.00 A; A=1-211.
DR PDB; 1YSG; NMR; -; A=1-209.
DR PDB; 1YSI; NMR; -; A=1-209.
DR PDB; 1YSN; NMR; -; A=1-209.
DR PDB; 2B48; X-ray; 3.45 A; A=1-211.
DR PDB; 2LP8; NMR; -; A=1-209.
DR PDB; 2LPC; NMR; -; A=1-209.
DR PDB; 2M03; NMR; -; A=1-209.
DR PDB; 2M04; NMR; -; A=1-209.
DR PDB; 2O1Y; NMR; -; A=1-209.
DR PDB; 2O2M; NMR; -; A=2-196.
DR PDB; 2O2N; NMR; -; A=2-196.
DR PDB; 2P1L; X-ray; 2.50 A; A/C/E/G=1-209.
DR PDB; 2PON; NMR; -; B=1-196.
DR PDB; 2YJ1; X-ray; 2.24 A; A/C=1-209.
DR PDB; 2YQ6; X-ray; 1.80 A; A=1-209.
DR PDB; 2YQ7; X-ray; 1.90 A; A=1-209.
DR PDB; 2YXJ; X-ray; 2.20 A; A/B=1-209.
DR PDB; 3CVA; X-ray; 2.70 A; X=1-211.
DR PDB; 3FDL; X-ray; 1.78 A; A=1-209.
DR PDB; 3FDM; X-ray; 2.26 A; A/B/C=1-209.
DR PDB; 3INQ; X-ray; 2.00 A; A/B=1-209.
DR PDB; 3IO8; X-ray; 2.30 A; A/C=1-209.
DR PDB; 3PL7; X-ray; 2.61 A; A/B=1-209.
DR PDB; 3QKD; X-ray; 2.02 A; A/B=1-209.
DR PDB; 3R85; X-ray; 1.95 A; A/B/C/D=1-209.
DR PDB; 3SP7; X-ray; 1.40 A; A=1-209.
DR PDB; 3SPF; X-ray; 1.70 A; A=1-200.
DR PDB; 3ZK6; X-ray; 2.48 A; A/B=1-209.
DR PDB; 3ZLN; X-ray; 2.29 A; A=1-209.
DR PDB; 3ZLO; X-ray; 2.60 A; A=1-209.
DR PDB; 3ZLR; X-ray; 2.03 A; A/B=1-209.
DR PDB; 4A1U; X-ray; 1.54 A; A=1-209.
DR PDB; 4A1W; X-ray; 2.50 A; A/B/C/D=1-209.
DR PDB; 4AQ3; X-ray; 2.40 A; A/B/C/D/E/F=15-44.
DR PDB; 4EHR; X-ray; 2.09 A; A=1-209.
DR PDB; 4HNJ; X-ray; 2.90 A; A/B=1-209.
DR PDB; 4IEH; X-ray; 2.10 A; A=15-44.
DR PDBsum; 1BXL; -.
DR PDBsum; 1G5J; -.
DR PDBsum; 1LXL; -.
DR PDBsum; 1MAZ; -.
DR PDBsum; 1R2D; -.
DR PDBsum; 1R2E; -.
DR PDBsum; 1R2G; -.
DR PDBsum; 1R2H; -.
DR PDBsum; 1R2I; -.
DR PDBsum; 1YSG; -.
DR PDBsum; 1YSI; -.
DR PDBsum; 1YSN; -.
DR PDBsum; 2B48; -.
DR PDBsum; 2LP8; -.
DR PDBsum; 2LPC; -.
DR PDBsum; 2M03; -.
DR PDBsum; 2M04; -.
DR PDBsum; 2O1Y; -.
DR PDBsum; 2O2M; -.
DR PDBsum; 2O2N; -.
DR PDBsum; 2P1L; -.
DR PDBsum; 2PON; -.
DR PDBsum; 2YJ1; -.
DR PDBsum; 2YQ6; -.
DR PDBsum; 2YQ7; -.
DR PDBsum; 2YXJ; -.
DR PDBsum; 3CVA; -.
DR PDBsum; 3FDL; -.
DR PDBsum; 3FDM; -.
DR PDBsum; 3INQ; -.
DR PDBsum; 3IO8; -.
DR PDBsum; 3PL7; -.
DR PDBsum; 3QKD; -.
DR PDBsum; 3R85; -.
DR PDBsum; 3SP7; -.
DR PDBsum; 3SPF; -.
DR PDBsum; 3ZK6; -.
DR PDBsum; 3ZLN; -.
DR PDBsum; 3ZLO; -.
DR PDBsum; 3ZLR; -.
DR PDBsum; 4A1U; -.
DR PDBsum; 4A1W; -.
DR PDBsum; 4AQ3; -.
DR PDBsum; 4EHR; -.
DR PDBsum; 4HNJ; -.
DR PDBsum; 4IEH; -.
DR DisProt; DP00298; -.
DR ProteinModelPortal; Q07817; -.
DR SMR; Q07817; 1-210.
DR DIP; DIP-30916N; -.
DR IntAct; Q07817; 54.
DR MINT; MINT-89538; -.
DR STRING; 9606.ENSP00000302564; -.
DR BindingDB; Q07817; -.
DR ChEMBL; CHEMBL4625; -.
DR TCDB; 1.A.21.1.1; the bcl-2 (bcl-2) family.
DR PhosphoSite; Q07817; -.
DR DMDM; 728955; -.
DR PaxDb; Q07817; -.
DR PRIDE; Q07817; -.
DR DNASU; 598; -.
DR Ensembl; ENST00000307677; ENSP00000302564; ENSG00000171552.
DR Ensembl; ENST00000376055; ENSP00000365223; ENSG00000171552.
DR Ensembl; ENST00000376062; ENSP00000365230; ENSG00000171552.
DR Ensembl; ENST00000420653; ENSP00000405563; ENSG00000171552.
DR GeneID; 598; -.
DR KEGG; hsa:598; -.
DR UCSC; uc002wwl.3; human.
DR CTD; 598; -.
DR GeneCards; GC20M030252; -.
DR HGNC; HGNC:992; BCL2L1.
DR HPA; CAB000105; -.
DR MIM; 600039; gene.
DR neXtProt; NX_Q07817; -.
DR PharmGKB; PA76; -.
DR eggNOG; NOG300479; -.
DR HOGENOM; HOG000056452; -.
DR InParanoid; Q07817; -.
DR KO; K04570; -.
DR OMA; NGSPSWH; -.
DR OrthoDB; EOG70GMGD; -.
DR PhylomeDB; Q07817; -.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; BCL2L1; human.
DR EvolutionaryTrace; Q07817; -.
DR GeneWiki; BCL2-like_1_(gene); -.
DR GenomeRNAi; 598; -.
DR NextBio; 2433; -.
DR PMAP-CutDB; Q07817; -.
DR PRO; PR:Q07817; -.
DR ArrayExpress; Q07817; -.
DR Bgee; Q07817; -.
DR CleanEx; HS_BCL2L1; -.
DR Genevestigator; Q07817; -.
DR GO; GO:0097136; C:Bcl-2 family protein complex; IDA:UniProtKB.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005741; C:mitochondrial outer membrane; NAS:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030672; C:synaptic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008283; P:cell proliferation; IEA:Ensembl.
DR GO; GO:0060154; P:cellular process regulating host cell cycle in response to virus; IEA:Ensembl.
DR GO; GO:0071312; P:cellular response to alkaloid; IEA:Ensembl.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl.
DR GO; GO:0071480; P:cellular response to gamma radiation; IEA:Ensembl.
DR GO; GO:0000910; P:cytokinesis; IMP:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0009566; P:fertilization; IEA:Ensembl.
DR GO; GO:0007281; P:germ cell development; IEA:Ensembl.
DR GO; GO:0040007; P:growth; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0007093; P:mitotic cell cycle checkpoint; IMP:UniProtKB.
DR GO; GO:2000811; P:negative regulation of anoikis; IMP:UniProtKB.
DR GO; GO:0010507; P:negative regulation of autophagy; TAS:UniProtKB.
DR GO; GO:0090005; P:negative regulation of establishment of protein localization to plasma membrane; IDA:BHF-UCL.
DR GO; GO:1900118; P:negative regulation of execution phase of apoptosis; IDA:UniProtKB.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; TAS:BHF-UCL.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IDA:UniProtKB.
DR GO; GO:1902230; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage; IDA:BHF-UCL.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IC:BHF-UCL.
DR GO; GO:0035872; P:nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway; TAS:Reactome.
DR GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; IDA:HGNC.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IDA:HGNC.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IDA:HGNC.
DR GO; GO:0046898; P:response to cycloheximide; IEA:Ensembl.
DR GO; GO:0034097; P:response to cytokine stimulus; IDA:MGI.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR GO; GO:0019050; P:suppression by virus of host apoptotic process; IDA:MGI.
DR InterPro; IPR013279; Apop_reg_BclX.
DR InterPro; IPR002475; Bcl2-like.
DR InterPro; IPR004725; Bcl2/BclX.
DR InterPro; IPR020717; Bcl2_BH1_motif_CS.
DR InterPro; IPR020726; Bcl2_BH2_motif_CS.
DR InterPro; IPR020728; Bcl2_BH3_motif_CS.
DR InterPro; IPR003093; Bcl2_BH4.
DR InterPro; IPR020731; Bcl2_BH4_motif_CS.
DR InterPro; IPR026298; Blc2_fam.
DR PANTHER; PTHR11256; PTHR11256; 1.
DR PANTHER; PTHR11256:SF12; PTHR11256:SF12; 1.
DR Pfam; PF00452; Bcl-2; 1.
DR Pfam; PF02180; BH4; 1.
DR PRINTS; PR01864; APOPREGBCLX.
DR PRINTS; PR01862; BCL2FAMILY.
DR SMART; SM00265; BH4; 1.
DR TIGRFAMs; TIGR00865; bcl-2; 1.
DR PROSITE; PS50062; BCL2_FAMILY; 1.
DR PROSITE; PS01080; BH1; 1.
DR PROSITE; PS01258; BH2; 1.
DR PROSITE; PS01259; BH3; 1.
DR PROSITE; PS01260; BH4_1; 1.
DR PROSITE; PS50063; BH4_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cell junction;
KW Complete proteome; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton;
KW Endocytosis; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Mitochondrion outer membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Synapse; Transmembrane; Transmembrane helix.
FT CHAIN 1 233 Bcl-2-like protein 1.
FT /FTId=PRO_0000143062.
FT TRANSMEM 210 226 Helical; (Potential).
FT MOTIF 4 24 BH4.
FT MOTIF 86 100 BH3.
FT MOTIF 129 148 BH1.
FT MOTIF 180 195 BH2.
FT SITE 61 62 Cleavage; by caspase-1.
FT MOD_RES 49 49 Phosphoserine; by PLK3.
FT MOD_RES 62 62 Phosphoserine; by CDK1.
FT VAR_SEQ 126 188 Missing (in isoform Bcl-X(S)).
FT /FTId=VSP_000515.
FT VAR_SEQ 189 233 DTFVELYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSL
FT FSRK -> VRTKPLVCPFSLASGQRSPTALLLYLFLLCWVI
FT VGDVDS (in isoform Bcl-X(beta)).
FT /FTId=VSP_000516.
FT MUTAGEN 49 49 S->A: Less stable at G2 checkpoint after
FT DNA damage.
FT MUTAGEN 61 61 D->A: No cleavage by caspase-1 nor by
FT caspase-3.
FT MUTAGEN 131 133 FRD->VRA: No heterodimerization with BAX.
FT MUTAGEN 135 137 VNW->AIL: Loss of anti-apoptotic
FT activity.
FT MUTAGEN 138 140 GRI->ELN: Loss of anti-apoptotic
FT activity.
FT MUTAGEN 138 138 G->A: No heterodimerization with BAX.
FT MUTAGEN 145 147 SFG->YCC: Decreases interaction with
FT DNM1L, no effect on endocytosis
FT enhancement.
FT MUTAGEN 148 148 G->E: No heterodimerization with BAX.
FT MUTAGEN 156 156 D->A: No effect on caspase-1 cleavage.
FT MUTAGEN 176 176 D->A: No effect on caspase-1 cleavage.
FT MUTAGEN 188 191 WDTF->SVTC: Abolishes interaction with
FT DNM1L and endocytosis enhancement.
FT MUTAGEN 188 189 WD->GA: Reduces anti-apoptotic activity
FT by about half.
FT MUTAGEN 189 189 D->A: No effect on caspase-1 cleavage.
FT CONFLICT 70 70 G -> A (in Ref. 1; CAA80661).
FT CONFLICT 168 168 A -> V (in Ref. 4; CAI56777).
FT HELIX 3 18
FT TURN 19 21
FT HELIX 24 26
FT STRAND 29 36
FT STRAND 38 41
FT TURN 42 44
FT TURN 65 68
FT TURN 70 73
FT HELIX 85 101
FT HELIX 102 104
FT HELIX 108 111
FT TURN 116 118
FT HELIX 120 130
FT TURN 131 133
FT HELIX 137 156
FT HELIX 162 177
FT HELIX 179 184
FT TURN 185 187
FT HELIX 188 198
FT HELIX 199 205
FT STRAND 206 208
SQ SEQUENCE 233 AA; 26049 MW; E09D3CDD851AE9BE CRC64;
MSQSNRELVV DFLSYKLSQK GYSWSQFSDV EENRTEAPEG TESEMETPSA INGNPSWHLA
DSPAVNGATG HSSSLDAREV IPMAAVKQAL REAGDEFELR YRRAFSDLTS QLHITPGTAY
QSFEQVVNEL FRDGVNWGRI VAFFSFGGAL CVESVDKEMQ VLVSRIAAWM ATYLNDHLEP
WIQENGGWDT FVELYGNNAA AESRKGQERF NRWFLTGMTV AGVVLLGSLF SRK
//
MIM
600039
*RECORD*
*FIELD* NO
600039
*FIELD* TI
*600039 BCL2-LIKE 1; BCL2L1
;;BCL2-RELATED GENE; BCLX
BCL2-RELATED PROTEIN, LONG ISOFORM, INCLUDED; BCLXL, INCLUDED;;
read moreBCL2-RELATED PROTEIN, SHORT ISOFORM, INCLUDED; BCLXS, INCLUDED
*FIELD* TX
CLONING
Boise et al. (1993) isolated a BCL2 (151430)-related gene, which they
designated BCLX, and showed that it can function as a BCL2-independent
regulator of programmed cell death (apoptosis). Alternative splicing
resulted in 2 distinct BCLX mRNAs. The protein product of the larger
mRNA (BCLXL) was similar in size and predicted structure to BCL2. When
stably transfected into an IL3-dependent cell line, it inhibited cell
death upon growth factor withdrawal at least as well as BCL2.
Unexpectedly, the smaller mRNA species (BCLXS) encodes a protein that
inhibits the ability of BCL2 to enhance the survival of growth
factor-deprived cells. In vivo, the smaller BCLX mRNA was expressed at
high levels in cells that undergo a high rate of turnover, such as
developing lymphocytes. In contrast, the large form of BCLX was found in
tissues containing long-lived postmitotic cells, such as adult brain.
Together these data suggested that BCLX plays an important role in both
positive and negative regulation of programmed cell death. Boise et al.
(1993) found that BCLX is highly conserved in vertebrate evolution.
By microarray analysis, Jun et al. (2001) demonstrated expression of the
BCL2L1 gene in human donor corneas.
GENE FUNCTION
Vander Heiden et al. (1997) observed in Jurkat cells that a wide variety
of apoptotic and necrotic stimuli induce progressive mitochondrial
swelling and outer mitochondrial membrane rupture. Discontinuity of the
outer mitochondrial membrane results in cytochrome c redistribution from
the intermembrane space to the cytosol, followed by subsequent inner
mitochondrial membrane depolarization. The mitochondrial membrane
protein BCLX could inhibit these changes in cells treated with apoptotic
stimuli. In addition, BCLX-expressing cells adapt to growth factor
withdrawal or staurosporine treatment by maintaining a decreased
mitochondrial membrane potential. BCLX expression also prevents
mitochondrial swelling in response to agents that inhibit oxidative
phosphorylation. These data suggested to Vander Heiden et al. (1997)
that BCLX promotes cell survival by regulating the electrical and
osmotic homeostasis of mitochondria.
Silva et al. (1998) found that erythroid cells from patients with
polycythemia vera (263300) survived in vitro without erythropoietin.
This finding correlated with the expression of BCLX protein, even in
mature erythroblasts that normally do not express BCLX. The large BCLX
mRNA was the predominant form detected in the erythropoietin-independent
erythroid cells. They concluded that deregulated expression of BCLX may
contribute to the erythropoietin-independent survival of
erythroid-lineage cells in polycythemia vera and thereby contribute to
the pathogenesis of this disorder. Moliterno et al. (1998)
simultaneously reported impaired expression of the thrombopoietin
receptor (MPL; 159530) by platelets from patients with polycythemia
vera.
During transduction of an apoptotic signal into the cell, there is an
alteration in the permeability of the membranes of the cell's
mitochondria, which causes the translocation of the apoptogenic protein
cytochrome c into the cytoplasm, which in turn activates death-driving
proteolytic proteins known as caspases (see 147678). The BCL2 family of
proteins, whose members may be antiapoptotic or proapoptotic, regulates
cell death by controlling this mitochondrial membrane permeability
during apoptosis. Shimizu et al. (1999) created liposomes that carried
the mitochondrial porin channel VDAC (604492) to show that the
recombinant proapoptotic proteins Bax (600040) and Bak (600516)
accelerate the opening of VDAC, whereas the antiapoptotic protein BCLXL
closes VDAC by binding to it directly. Bax and Bak allow cytochrome c to
pass through VDAC out of liposomes, but passage is prevented by BCLXL.
In agreement with this, VDAC1-deficient mitochondria from a mutant yeast
did not exhibit a Bax/Bak-induced loss in membrane potential and
cytochrome c release, both of which were inhibited by BCLXL. Shimizu et
al. (1999) concluded that the BCL2 family of proteins bind to the VDAC
in order to regulate the mitochondrial membrane potential and the
release of cytochrome c during apoptosis.
The therapeutic value of DNA-damaging antineoplastic agents is dependent
upon their ability to induce tumor cell apoptosis while sparing most
normal tissues. Deverman et al. (2002) showed that a component of the
apoptotic response to these agents in several different types of tumor
cells is the deamidation of 2 asparagines in the unstructured loop of
BCLXL. Deamidation of these asparagines imparted susceptibility to
apoptosis by disrupting the ability of BCLXL to block the proapoptotic
activity of BH3 domain-only proteins. Conversely, BCLXL deamidation was
actively suppressed in fibroblasts, and suppression of deamidation was
an essential component of their resistance to DNA damage-induced
apoptosis. The authors concluded that regulation of BCLXL deamidation
has a critical role in the tumor-specific activity of DNA-damaging
antineoplastic agents.
Kanauchi et al. (2003) examined whether apoptosis-regulating genes,
BCLXL and FAS (134637), and the telomere-related gene TERF1 (600951)
differ in expression between adrenal cortical cancers and benign adrenal
tumors. Tissues from 4 adrenal cortical cancers were compared with 7
normal adrenal tissues, 17 cortical adenomas, 4 cortical hyperplasias,
and 20 pheochromocytomas for expressions of BCLXL and FAS by RT-PCR, and
for expressions of TERF1 by real-time quantitative RT-PCR. All benign
adrenal tissues expressed both the antiapoptosis gene BCLXL and the
proapoptosis gene FAS, but the adrenal cortical cancers expressed only
BCLXL and not FAS.
The p53 (191170) gene product functions in the nucleus to regulate
proapoptotic genes, whereas cytoplasmic p53 directly activates
proapoptotic BCL2 (151430) proteins to permeabilize mitochondria and
initiate apoptosis. Chipuk et al. (2005) demonstrated that a tripartite
nexus between BCLXL, cytoplasmic p53, and PUMA (605854) coordinates
these distinct p53 functions. After genotoxic stress, BCLXL sequestered
cytoplasmic p53. Nuclear p53 caused expression of PUMA, which then
displaced p53 from BCLXL, allowing p53 to induce mitochondrial
permeabilization. Mutant BCLXL that bound p53, but not PUMA, rendered
cells resistant to p53-induced apoptosis irrespective of PUMA
expression. Thus, Chipuk et al. (2005) concluded that PUMA couples the
nuclear and cytoplasmic proapoptotic functions of p53.
Bivona et al. (2006) found that the subcellular localization and
function of Kras (see KRAS2; 190070) in mammalian cells was modulated by
Pkc (see 176960). Phosphorylation of Kras by Pkc agonists induced rapid
translocation of Kras from the plasma membrane to several intracellular
membranes, including the outer mitochondrial membrane, where Kras
associated with Bclxl. Phosphorylated Kras required Bclxl for induction
of apoptosis.
*FIELD* RF
1. Bivona, T. G.; Quatela, S. E.; Bodemann, B. O.; Ahearn, I. M.;
Soskis, M. J.; Mor, A.; Miura, J.; Wiener, H. H.; Wright, L.; Saba,
S. G.; Yim, D.; Fein, A.; Perez de Castro, I.; Li, C.; Thompson, C.
B.; Cox, A. D.; Philips, M. R.: PKC regulates a farnesyl-electrostatic
switch on K-Ras that promotes its association with Bcl-X(L) on mitochondria
and induces apoptosis. Molec. Cell 21: 481-493, 2006.
2. Boise, L. H.; Gonzalez-Garcia, M.; Postema, C. E.; Ding, L.; Lindsten,
T.; Turka, L. A.; Mao, X.; Nunez, G.; Thompson, C. B.: Bcl-x, a bcl-2-related
gene that functions as a dominant regulator of apoptotic cell death. Cell 74:
597-608, 1993.
3. Chipuk, J. E.; Bouchier-Hayes, L.; Kuwana, T.; Newmeyer, D. D.;
Green, D. R.: PUMA couples the nuclear and cytoplasmic proapoptotic
function of p53. Science 309: 1732-1735, 2005.
4. Deverman, B. E.; Cook, B. L.; Manson, S. R.; Niederhoff, R. A.;
Langer, E. M.; Rosova, I.; Kulans, L. A.; Fu, X.; Weinberg, J. S.;
Heinecke, J. W.; Roth, K. A.; Weintraub, S. J.: Bcl-x(L) deamidation
is a critical switch in the regulation of the response to DNA damage. Cell 111:
51-62, 2002. Note: Erratum: Cell: 115: 503 only, 2003.
5. Jun, A. S.; Liu, S. H.; Koo, E. H.; Do, D. V.; Stark, W. J.; Gottsch,
J. D.: Microarray analysis of gene expression in human donor corneas. Arch.
Ophthal. 119: 1629-1634, 2001.
6. Kanauchi, H.; Wada, N.; Ginzinger, D. G.; Yu, M.; Wong, M. G.;
Clark, O. H.; Duh, Q.-Y.: Diagnostic and prognostic value of Fas
and telomeric-repeat binding factor-1 genes in adrenal tumors. J.
Clin. Endocr. Metab. 88: 3690-3693, 2003.
7. Moliterno, A. R.; Hankins, W. D.; Spivak, J. L.: Impaired expression
of the thrombopoietin receptor by platelets from patients with polycythemia
vera. New Eng. J. Med. 338: 572-580, 1998.
8. Shimizu, S.; Narita, M.; Tsujimoto, Y.: Bcl-2 family proteins
regulate the release of apoptogenic cytochrome c by the mitochondrial
channel VDAC. Nature 399: 483-487, 1999. Note: Erratum: Nature 407:
767 only, 2000.
9. Silva, M.; Richard, C.; Benito, A.; Sanz, C.; Olalla, I.; Fernandez-Luna,
J. L.: Expression of Bcl-x in erythroid precursors from patients
with polycythemia vera. New Eng. J. Med. 338: 564-571, 1998.
10. Vander Heiden, M. G.; Chandel, N. S.; Williamson, E. K.; Schumacker,
P. T.; Thompson, C. B.: Bcl-X(L) regulates the membrane potential
and volume homeostasis of mitochondria. Cell 91: 627-637, 1997.
*FIELD* CN
Patricia A. Hartz - updated: 3/30/2006
Ada Hamosh - updated: 9/27/2005
John A. Phillips, III - updated: 11/4/2004
Stylianos E. Antonarakis - updated: 1/29/2003
Jane Kelly - updated: 11/21/2002
Ada Hamosh - updated: 6/23/1999
Victor A. McKusick - updated: 3/10/1998
Stylianos E. Antonarakis - updated: 12/19/1997
*FIELD* CD
Victor A. McKusick: 7/18/1994
*FIELD* ED
terry: 10/03/2012
alopez: 9/12/2012
wwang: 3/30/2006
alopez: 9/29/2005
terry: 9/27/2005
alopez: 11/4/2004
mgross: 1/29/2003
carol: 11/21/2002
joanna: 10/17/2001
alopez: 2/2/2000
alopez: 6/23/1999
alopez: 1/19/1999
alopez: 1/4/1999
alopez: 12/15/1998
psherman: 3/11/1998
terry: 3/10/1998
carol: 12/19/1997
mimadm: 7/30/1994
jason: 7/18/1994
*RECORD*
*FIELD* NO
600039
*FIELD* TI
*600039 BCL2-LIKE 1; BCL2L1
;;BCL2-RELATED GENE; BCLX
BCL2-RELATED PROTEIN, LONG ISOFORM, INCLUDED; BCLXL, INCLUDED;;
read moreBCL2-RELATED PROTEIN, SHORT ISOFORM, INCLUDED; BCLXS, INCLUDED
*FIELD* TX
CLONING
Boise et al. (1993) isolated a BCL2 (151430)-related gene, which they
designated BCLX, and showed that it can function as a BCL2-independent
regulator of programmed cell death (apoptosis). Alternative splicing
resulted in 2 distinct BCLX mRNAs. The protein product of the larger
mRNA (BCLXL) was similar in size and predicted structure to BCL2. When
stably transfected into an IL3-dependent cell line, it inhibited cell
death upon growth factor withdrawal at least as well as BCL2.
Unexpectedly, the smaller mRNA species (BCLXS) encodes a protein that
inhibits the ability of BCL2 to enhance the survival of growth
factor-deprived cells. In vivo, the smaller BCLX mRNA was expressed at
high levels in cells that undergo a high rate of turnover, such as
developing lymphocytes. In contrast, the large form of BCLX was found in
tissues containing long-lived postmitotic cells, such as adult brain.
Together these data suggested that BCLX plays an important role in both
positive and negative regulation of programmed cell death. Boise et al.
(1993) found that BCLX is highly conserved in vertebrate evolution.
By microarray analysis, Jun et al. (2001) demonstrated expression of the
BCL2L1 gene in human donor corneas.
GENE FUNCTION
Vander Heiden et al. (1997) observed in Jurkat cells that a wide variety
of apoptotic and necrotic stimuli induce progressive mitochondrial
swelling and outer mitochondrial membrane rupture. Discontinuity of the
outer mitochondrial membrane results in cytochrome c redistribution from
the intermembrane space to the cytosol, followed by subsequent inner
mitochondrial membrane depolarization. The mitochondrial membrane
protein BCLX could inhibit these changes in cells treated with apoptotic
stimuli. In addition, BCLX-expressing cells adapt to growth factor
withdrawal or staurosporine treatment by maintaining a decreased
mitochondrial membrane potential. BCLX expression also prevents
mitochondrial swelling in response to agents that inhibit oxidative
phosphorylation. These data suggested to Vander Heiden et al. (1997)
that BCLX promotes cell survival by regulating the electrical and
osmotic homeostasis of mitochondria.
Silva et al. (1998) found that erythroid cells from patients with
polycythemia vera (263300) survived in vitro without erythropoietin.
This finding correlated with the expression of BCLX protein, even in
mature erythroblasts that normally do not express BCLX. The large BCLX
mRNA was the predominant form detected in the erythropoietin-independent
erythroid cells. They concluded that deregulated expression of BCLX may
contribute to the erythropoietin-independent survival of
erythroid-lineage cells in polycythemia vera and thereby contribute to
the pathogenesis of this disorder. Moliterno et al. (1998)
simultaneously reported impaired expression of the thrombopoietin
receptor (MPL; 159530) by platelets from patients with polycythemia
vera.
During transduction of an apoptotic signal into the cell, there is an
alteration in the permeability of the membranes of the cell's
mitochondria, which causes the translocation of the apoptogenic protein
cytochrome c into the cytoplasm, which in turn activates death-driving
proteolytic proteins known as caspases (see 147678). The BCL2 family of
proteins, whose members may be antiapoptotic or proapoptotic, regulates
cell death by controlling this mitochondrial membrane permeability
during apoptosis. Shimizu et al. (1999) created liposomes that carried
the mitochondrial porin channel VDAC (604492) to show that the
recombinant proapoptotic proteins Bax (600040) and Bak (600516)
accelerate the opening of VDAC, whereas the antiapoptotic protein BCLXL
closes VDAC by binding to it directly. Bax and Bak allow cytochrome c to
pass through VDAC out of liposomes, but passage is prevented by BCLXL.
In agreement with this, VDAC1-deficient mitochondria from a mutant yeast
did not exhibit a Bax/Bak-induced loss in membrane potential and
cytochrome c release, both of which were inhibited by BCLXL. Shimizu et
al. (1999) concluded that the BCL2 family of proteins bind to the VDAC
in order to regulate the mitochondrial membrane potential and the
release of cytochrome c during apoptosis.
The therapeutic value of DNA-damaging antineoplastic agents is dependent
upon their ability to induce tumor cell apoptosis while sparing most
normal tissues. Deverman et al. (2002) showed that a component of the
apoptotic response to these agents in several different types of tumor
cells is the deamidation of 2 asparagines in the unstructured loop of
BCLXL. Deamidation of these asparagines imparted susceptibility to
apoptosis by disrupting the ability of BCLXL to block the proapoptotic
activity of BH3 domain-only proteins. Conversely, BCLXL deamidation was
actively suppressed in fibroblasts, and suppression of deamidation was
an essential component of their resistance to DNA damage-induced
apoptosis. The authors concluded that regulation of BCLXL deamidation
has a critical role in the tumor-specific activity of DNA-damaging
antineoplastic agents.
Kanauchi et al. (2003) examined whether apoptosis-regulating genes,
BCLXL and FAS (134637), and the telomere-related gene TERF1 (600951)
differ in expression between adrenal cortical cancers and benign adrenal
tumors. Tissues from 4 adrenal cortical cancers were compared with 7
normal adrenal tissues, 17 cortical adenomas, 4 cortical hyperplasias,
and 20 pheochromocytomas for expressions of BCLXL and FAS by RT-PCR, and
for expressions of TERF1 by real-time quantitative RT-PCR. All benign
adrenal tissues expressed both the antiapoptosis gene BCLXL and the
proapoptosis gene FAS, but the adrenal cortical cancers expressed only
BCLXL and not FAS.
The p53 (191170) gene product functions in the nucleus to regulate
proapoptotic genes, whereas cytoplasmic p53 directly activates
proapoptotic BCL2 (151430) proteins to permeabilize mitochondria and
initiate apoptosis. Chipuk et al. (2005) demonstrated that a tripartite
nexus between BCLXL, cytoplasmic p53, and PUMA (605854) coordinates
these distinct p53 functions. After genotoxic stress, BCLXL sequestered
cytoplasmic p53. Nuclear p53 caused expression of PUMA, which then
displaced p53 from BCLXL, allowing p53 to induce mitochondrial
permeabilization. Mutant BCLXL that bound p53, but not PUMA, rendered
cells resistant to p53-induced apoptosis irrespective of PUMA
expression. Thus, Chipuk et al. (2005) concluded that PUMA couples the
nuclear and cytoplasmic proapoptotic functions of p53.
Bivona et al. (2006) found that the subcellular localization and
function of Kras (see KRAS2; 190070) in mammalian cells was modulated by
Pkc (see 176960). Phosphorylation of Kras by Pkc agonists induced rapid
translocation of Kras from the plasma membrane to several intracellular
membranes, including the outer mitochondrial membrane, where Kras
associated with Bclxl. Phosphorylated Kras required Bclxl for induction
of apoptosis.
*FIELD* RF
1. Bivona, T. G.; Quatela, S. E.; Bodemann, B. O.; Ahearn, I. M.;
Soskis, M. J.; Mor, A.; Miura, J.; Wiener, H. H.; Wright, L.; Saba,
S. G.; Yim, D.; Fein, A.; Perez de Castro, I.; Li, C.; Thompson, C.
B.; Cox, A. D.; Philips, M. R.: PKC regulates a farnesyl-electrostatic
switch on K-Ras that promotes its association with Bcl-X(L) on mitochondria
and induces apoptosis. Molec. Cell 21: 481-493, 2006.
2. Boise, L. H.; Gonzalez-Garcia, M.; Postema, C. E.; Ding, L.; Lindsten,
T.; Turka, L. A.; Mao, X.; Nunez, G.; Thompson, C. B.: Bcl-x, a bcl-2-related
gene that functions as a dominant regulator of apoptotic cell death. Cell 74:
597-608, 1993.
3. Chipuk, J. E.; Bouchier-Hayes, L.; Kuwana, T.; Newmeyer, D. D.;
Green, D. R.: PUMA couples the nuclear and cytoplasmic proapoptotic
function of p53. Science 309: 1732-1735, 2005.
4. Deverman, B. E.; Cook, B. L.; Manson, S. R.; Niederhoff, R. A.;
Langer, E. M.; Rosova, I.; Kulans, L. A.; Fu, X.; Weinberg, J. S.;
Heinecke, J. W.; Roth, K. A.; Weintraub, S. J.: Bcl-x(L) deamidation
is a critical switch in the regulation of the response to DNA damage. Cell 111:
51-62, 2002. Note: Erratum: Cell: 115: 503 only, 2003.
5. Jun, A. S.; Liu, S. H.; Koo, E. H.; Do, D. V.; Stark, W. J.; Gottsch,
J. D.: Microarray analysis of gene expression in human donor corneas. Arch.
Ophthal. 119: 1629-1634, 2001.
6. Kanauchi, H.; Wada, N.; Ginzinger, D. G.; Yu, M.; Wong, M. G.;
Clark, O. H.; Duh, Q.-Y.: Diagnostic and prognostic value of Fas
and telomeric-repeat binding factor-1 genes in adrenal tumors. J.
Clin. Endocr. Metab. 88: 3690-3693, 2003.
7. Moliterno, A. R.; Hankins, W. D.; Spivak, J. L.: Impaired expression
of the thrombopoietin receptor by platelets from patients with polycythemia
vera. New Eng. J. Med. 338: 572-580, 1998.
8. Shimizu, S.; Narita, M.; Tsujimoto, Y.: Bcl-2 family proteins
regulate the release of apoptogenic cytochrome c by the mitochondrial
channel VDAC. Nature 399: 483-487, 1999. Note: Erratum: Nature 407:
767 only, 2000.
9. Silva, M.; Richard, C.; Benito, A.; Sanz, C.; Olalla, I.; Fernandez-Luna,
J. L.: Expression of Bcl-x in erythroid precursors from patients
with polycythemia vera. New Eng. J. Med. 338: 564-571, 1998.
10. Vander Heiden, M. G.; Chandel, N. S.; Williamson, E. K.; Schumacker,
P. T.; Thompson, C. B.: Bcl-X(L) regulates the membrane potential
and volume homeostasis of mitochondria. Cell 91: 627-637, 1997.
*FIELD* CN
Patricia A. Hartz - updated: 3/30/2006
Ada Hamosh - updated: 9/27/2005
John A. Phillips, III - updated: 11/4/2004
Stylianos E. Antonarakis - updated: 1/29/2003
Jane Kelly - updated: 11/21/2002
Ada Hamosh - updated: 6/23/1999
Victor A. McKusick - updated: 3/10/1998
Stylianos E. Antonarakis - updated: 12/19/1997
*FIELD* CD
Victor A. McKusick: 7/18/1994
*FIELD* ED
terry: 10/03/2012
alopez: 9/12/2012
wwang: 3/30/2006
alopez: 9/29/2005
terry: 9/27/2005
alopez: 11/4/2004
mgross: 1/29/2003
carol: 11/21/2002
joanna: 10/17/2001
alopez: 2/2/2000
alopez: 6/23/1999
alopez: 1/19/1999
alopez: 1/4/1999
alopez: 12/15/1998
psherman: 3/11/1998
terry: 3/10/1998
carol: 12/19/1997
mimadm: 7/30/1994
jason: 7/18/1994