Bcl-2-like protein 1

Details

Name
Bcl-2-like protein 1
Synonyms
  • Apoptosis regulator Bcl-X
  • Bcl2-L-1
  • BCL2L
  • BCLX
Gene Name
BCL2L1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0006782|Bcl-2-like protein 1
MSQSNRELVVDFLSYKLSQKGYSWSQFSDVEENRTEAPEGTESEMETPSAINGNPSWHLA
DSPAVNGATGHSSSLDAREVIPMAAVKQALREAGDEFELRYRRAFSDLTSQLHITPGTAY
QSFEQVVNELFRDGVNWGRIVAFFSFGGALCVESVDKEMQVLVSRIAAWMATYLNDHLEP
WIQENGGWDTFVELYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK
Number of residues
233
Molecular Weight
26048.8
Theoretical pI
4.58
GO Classification
Functions
BH3 domain binding / identical protein binding / protein heterodimerization activity / protein homodimerization activity / protein kinase binding
Processes
apoptotic mitochondrial changes / apoptotic process / apoptotic process in bone marrow / cell proliferation / cellular process regulating host cell cycle in response to virus / cellular response to alkaloid / cellular response to amino acid stimulus / cellular response to gamma radiation / cytokinesis / endocytosis / extrinsic apoptotic signaling pathway in absence of ligand / fertilization / germ cell development / growth / hepatocyte apoptotic process / in utero embryonic development / innate immune response / intrinsic apoptotic signaling pathway / intrinsic apoptotic signaling pathway in response to DNA damage / male gonad development / mitochondrion morphogenesis / mitotic cell cycle checkpoint / negative regulation of anoikis / negative regulation of apoptotic process / negative regulation of autophagy / negative regulation of establishment of protein localization to plasma membrane / negative regulation of execution phase of apoptosis / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / negative regulation of intrinsic apoptotic signaling pathway / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage / negative regulation of neuron apoptotic process / negative regulation of release of cytochrome c from mitochondria / neuron apoptotic process / nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / ovarian follicle development / positive regulation of cell proliferation / positive regulation of intrinsic apoptotic signaling pathway / programmed cell death / regulation of mitochondrial membrane permeability / regulation of mitochondrial membrane potential / release of cytochrome c from mitochondria / response to cycloheximide / response to cytokine / spermatogenesis / suppression by virus of host apoptotic process
Components
Bcl-2 family protein complex / cell junction / centrosome / cytoplasm / cytosol / integral component of membrane / mitochondrial inner membrane / mitochondrial matrix / mitochondrial outer membrane / mitochondrion / nuclear membrane / synaptic vesicle membrane
General Function
Protein kinase binding
Specific Function
Potent inhibitor of cell death. Inhibits activation of caspases. Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.Isoform Bcl-X(L) also regulates presynaptic plasticity, including neurotransmitter release and recovery, number of axonal mitochondria as well as size and number of synaptic vesicle clusters. During synaptic stimulation, increases ATP availability from mitochondria through regulation of mitochondrial membrane ATP synthase F(1)F(0) activity and regulates endocytic vesicle retrieval in hippocampal neurons through association with DMN1L and stimulation of its GTPase activity in synaptic vesicles. May attenuate inflammation impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785).Isoform Bcl-X(S) promotes apoptosis.
Pfam Domain Function
Transmembrane Regions
210-226
Cellular Location
Mitochondrion inner membrane
Gene sequence
>lcl|BSEQ0017127|Bcl-2-like protein 1 (BCL2L1)
ATGTCTCAGAGCAACCGGGAGCTGGTGGTTGACTTTCTCTCCTACAAGCTTTCCCAGAAA
GGATACAGCTGGAGTCAGTTTAGTGATGTGGAAGAGAACAGGACTGAGGCCCCAGAAGGG
ACTGAATCGGAGATGGAGACCCCCAGTGCCATCAATGGCAACCCATCCTGGCACCTGGCA
GACAGCCCCGCGGTGAATGGAGCCACTGGCCACAGCAGCAGTTTGGATGCCCGGGAGGTG
ATCCCCATGGCAGCAGTAAAGCAAGCGCTGAGGGAGGCAGGCGACGAGTTTGAACTGCGG
TACCGGCGGGCATTCAGTGACCTGACATCCCAGCTCCACATCACCCCAGGGACAGCATAT
CAGAGCTTTGAACAGGATACTTTTGTGGAACTCTATGGGAACAATGCAGCAGCCGAGAGC
CGAAAGGGCCAGGAACGCTTCAACCGCTGGTTCCTGACGGGCATGACTGTGGCCGGCGTG
GTTCTGCTGGGCTCACTCTTCAGTCGGAAATGA
Chromosome Location
20
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ07817
UniProtKB Entry NameB2CL1_HUMAN
GenBank Gene IDBC019307
GenAtlas IDBCL2L1
HGNC IDHGNC:992
General References
  1. Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G, Thompson CB: bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell. 1993 Aug 27;74(4):597-608. [Article]
  2. Ban J, Eckhart L, Weninger W, Mildner M, Tschachler E: Identification of a human cDNA encoding a novel Bcl-x isoform. Biochem Biophys Res Commun. 1998 Jul 9;248(1):147-52. [Article]
  3. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [Article]
  4. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. [Article]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  6. Sedlak TW, Oltvai ZN, Yang E, Wang K, Boise LH, Thompson CB, Korsmeyer SJ: Multiple Bcl-2 family members demonstrate selective dimerizations with Bax. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7834-8. [Article]
  7. Cheng EH, Levine B, Boise LH, Thompson CB, Hardwick JM: Bax-independent inhibition of apoptosis by Bcl-XL. Nature. 1996 Feb 8;379(6565):554-6. [Article]
  8. Clem RJ, Cheng EH, Karp CL, Kirsch DG, Ueno K, Takahashi A, Kastan MB, Griffin DE, Earnshaw WC, Veliuona MA, Hardwick JM: Modulation of cell death by Bcl-XL through caspase interaction. Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):554-9. [Article]
  9. Schmitt E, Paquet C, Beauchemin M, Dever-Bertrand J, Bertrand R: Characterization of Bax-sigma, a cell death-inducing isoform of Bax. Biochem Biophys Res Commun. 2000 Apr 21;270(3):868-79. [Article]
  10. Rebollo A, Ayllon V, Fleischer A, Martinez CA, Zaballos A: The association of Aiolos transcription factor and Bcl-xL is involved in the control of apoptosis. J Immunol. 2001 Dec 1;167(11):6366-73. [Article]
  11. Yu J, Zhang L, Hwang PM, Kinzler KW, Vogelstein B: PUMA induces the rapid apoptosis of colorectal cancer cells. Mol Cell. 2001 Mar;7(3):673-82. [Article]
  12. Xue L, Chu F, Cheng Y, Sun X, Borthakur A, Ramarao M, Pandey P, Wu M, Schlossman SF, Prasad KV: Siva-1 binds to and inhibits BCL-X(L)-mediated protection against UV radiation-induced apoptosis. Proc Natl Acad Sci U S A. 2002 May 14;99(10):6925-30. [Article]
  13. Lo SC, Hannink M: PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the redox-regulated Keap1-dependent ubiquitin ligase complex. J Biol Chem. 2006 Dec 8;281(49):37893-903. Epub 2006 Oct 17. [Article]
  14. Bruey JM, Bruey-Sedano N, Luciano F, Zhai D, Balpai R, Xu C, Kress CL, Bailly-Maitre B, Li X, Osterman A, Matsuzawa S, Terskikh AV, Faustin B, Reed JC: Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by interaction with NALP1. Cell. 2007 Apr 6;129(1):45-56. [Article]
  15. Terrano DT, Upreti M, Chambers TC: Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol. 2010 Feb;30(3):640-56. doi: 10.1128/MCB.00882-09. Epub 2009 Nov 16. [Article]
  16. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  17. Wang J, Beauchemin M, Bertrand R: Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal. 2011 Dec;23(12):2030-8. doi: 10.1016/j.cellsig.2011.07.017. Epub 2011 Aug 5. [Article]
  18. Li H, Alavian KN, Lazrove E, Mehta N, Jones A, Zhang P, Licznerski P, Graham M, Uo T, Guo J, Rahner C, Duman RS, Morrison RS, Jonas EA: A Bcl-xL-Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis. Nat Cell Biol. 2013 Jul;15(7):773-85. doi: 10.1038/ncb2791. Epub 2013 Jun 23. [Article]
  19. Li L, Yao YC, Gu XQ, Che D, Ma CQ, Dai ZY, Li C, Zhou T, Cai WB, Yang ZH, Yang X, Gao GQ: Plasminogen kringle 5 induces endothelial cell apoptosis by triggering a voltage-dependent anion channel 1 (VDAC1) positive feedback loop. J Biol Chem. 2014 Nov 21;289(47):32628-38. doi: 10.1074/jbc.M114.567792. Epub 2014 Oct 8. [Article]
  20. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  21. Muchmore SW, Sattler M, Liang H, Meadows RP, Harlan JE, Yoon HS, Nettesheim D, Chang BS, Thompson CB, Wong SL, Ng SL, Fesik SW: X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature. 1996 May 23;381(6580):335-41. [Article]
  22. Sattler M, Liang H, Nettesheim D, Meadows RP, Harlan JE, Eberstadt M, Yoon HS, Shuker SB, Chang BS, Minn AJ, Thompson CB, Fesik SW: Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science. 1997 Feb 14;275(5302):983-6. [Article]
  23. Petros AM, Nettesheim DG, Wang Y, Olejniczak ET, Meadows RP, Mack J, Swift K, Matayoshi ED, Zhang H, Thompson CB, Fesik SW: Rationale for Bcl-xL/Bad peptide complex formation from structure, mutagenesis, and biophysical studies. Protein Sci. 2000 Dec;9(12):2528-34. [Article]
  24. Manion MK, O'Neill JW, Giedt CD, Kim KM, Zhang KY, Hockenbery DM: Bcl-XL mutations suppress cellular sensitivity to antimycin A. J Biol Chem. 2004 Jan 16;279(3):2159-65. Epub 2003 Oct 8. [Article]
  25. Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, Bruncko M, Deckwerth TL, Dinges J, Hajduk PJ, Joseph MK, Kitada S, Korsmeyer SJ, Kunzer AR, Letai A, Li C, Mitten MJ, Nettesheim DG, Ng S, Nimmer PM, O'Connor JM, Oleksijew A, Petros AM, Reed JC, Shen W, Tahir SK, Thompson CB, Tomaselli KJ, Wang B, Wendt MD, Zhang H, Fesik SW, Rosenberg SH: An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005 Jun 2;435(7042):677-81. Epub 2005 May 15. [Article]
  26. O'Neill JW, Manion MK, Maguire B, Hockenbery DM: BCL-XL dimerization by three-dimensional domain swapping. J Mol Biol. 2006 Feb 17;356(2):367-81. Epub 2005 Dec 1. [Article]
  27. Oberstein A, Jeffrey PD, Shi Y: Crystal structure of the Bcl-XL-Beclin 1 peptide complex: Beclin 1 is a novel BH3-only protein. J Biol Chem. 2007 Apr 27;282(17):13123-32. Epub 2007 Mar 2. [Article]
  28. Bruncko M, Oost TK, Belli BA, Ding H, Joseph MK, Kunzer A, Martineau D, McClellan WJ, Mitten M, Ng SC, Nimmer PM, Oltersdorf T, Park CM, Petros AM, Shoemaker AR, Song X, Wang X, Wendt MD, Zhang H, Fesik SW, Rosenberg SH, Elmore SW: Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL. J Med Chem. 2007 Feb 22;50(4):641-62. Epub 2007 Jan 26. [Article]
  29. Ambrosi E, Capaldi S, Bovi M, Saccomani G, Perduca M, Monaco HL: Structural changes in the BH3 domain of SOUL protein upon interaction with the anti-apoptotic protein Bcl-xL. Biochem J. 2011 Sep 1;438(2):291-301. doi: 10.1042/BJ20110257. [Article]
  30. Follis AV, Chipuk JE, Fisher JC, Yun MK, Grace CR, Nourse A, Baran K, Ou L, Min L, White SW, Green DR, Kriwacki RW: PUMA binding induces partial unfolding within BCL-xL to disrupt p53 binding and promote apoptosis. Nat Chem Biol. 2013 Mar;9(3):163-8. doi: 10.1038/nchembio.1166. Epub 2013 Jan 20. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB071084'-FLUORO-1,1'-BIPHENYL-4-CARBOXYLIC ACIDexperimentalunknownDetails
DB13044GossypolinvestigationalunknownDetails