BCL2L2

Protein-coding gene in the species Homo sapiens
BCL2L2
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1MK3, 1O0L, 1ZY3, 2Y6W, 4CIM

Identifiers
AliasesBCL2L2, BCL-W, BCL2-L-2, BCLW, PPP1R51, BCL2 like 2
External IDsOMIM: 601931; MGI: 108052; HomoloGene: 2989; GeneCards: BCL2L2; OMA:BCL2L2 - orthologs
Gene location (Human)
Chromosome 14 (human)
Chr.Chromosome 14 (human)[1]
Chromosome 14 (human)
Genomic location for BCL2L2
Genomic location for BCL2L2
Band14q11.2Start23,298,790 bp[1]
End23,311,751 bp[1]
Gene location (Mouse)
Chromosome 14 (mouse)
Chr.Chromosome 14 (mouse)[2]
Chromosome 14 (mouse)
Genomic location for BCL2L2
Genomic location for BCL2L2
Band14 C3|14 27.98 cMStart55,120,834 bp[2]
End55,125,691 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • C1 segment

  • prefrontal cortex

  • amygdala

  • right frontal lobe

  • postcentral gyrus

  • lateral nuclear group of thalamus

  • Brodmann area 9

  • orbitofrontal cortex

  • cingulate gyrus

  • muscle layer of sigmoid colon
Top expressed in
  • medial dorsal nucleus

  • lobe of cerebellum

  • habenula

  • subiculum

  • cerebellar vermis

  • medial geniculate nucleus

  • pontine nuclei

  • ventral tegmental area

  • medial vestibular nucleus

  • lateral geniculate nucleus
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
  • protein binding
  • protein homodimerization activity
  • disordered domain specific binding
  • identical protein binding
  • protein heterodimerization activity
  • BH domain binding
Cellular component
  • cytoplasm
  • cytosol
  • mitochondrial membranes
  • mitochondrion
  • membrane
  • mitochondrial outer membrane
  • Bcl-2 family protein complex
  • nucleus
  • nuclear inclusion body
Biological process
  • spermatogenesis
  • regulation of apoptotic process
  • negative regulation of apoptotic process
  • Sertoli cell proliferation
  • apoptotic process
  • intrinsic apoptotic signaling pathway in response to DNA damage
  • extrinsic apoptotic signaling pathway in absence of ligand
  • negative regulation of intrinsic apoptotic signaling pathway
  • cellular response to estradiol stimulus
  • cellular response to amyloid-beta
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

599

12050

Ensembl

ENSG00000129473

ENSMUSG00000089682

UniProt

Q92843

P70345

RefSeq (mRNA)

NM_004050
NM_001199839

NM_007537

RefSeq (protein)

NP_001186768
NP_004041

NP_031563

Location (UCSC)Chr 14: 23.3 – 23.31 MbChr 14: 55.12 – 55.13 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Bcl-2-like protein 2 is a 193-amino acid protein that in humans is encoded by the BCL2L2 gene on chromosome 14 (band q11.2-q12).[5][6][7] It was originally discovered by Leonie Gibson, Suzanne Cory and colleagues at the Walter and Eliza Hall Institute of Medical Research, who called it Bcl-w.[8]

Function

This gene encodes a pro-survival (anti-apoptotic) member of the bcl-2 protein family, and is most similar to Bcl-xL.[7] The proteins of this family form hetero- or homodimers and act as anti- and pro-apoptotic regulators. Expression of this gene in cells has been shown to contribute to reduced cell apoptosis under cytotoxic conditions. Studies of the related gene in mice indicated a role in the survival of NGF- and BDNF-dependent neurons. Mutation and knockout studies of the mouse gene demonstrated an essential role in adult spermatogenesis.[6][9][7]

Clinical significance

High levels of Bcl-w are seen in many cancers, including glioblastoma, colorectal cancer, non-small-cell lung carcinoma, and breast cancer.[7] Breast cancer patients with metastasis have higher Bcl-w than breast cancer patients only having primary tumor.[7] Elevated levels of Bcl-w has been shown to protect neurons from cell death induced by amyloid beta.[7] Parkinson's disease patients with a mutant PARK2 gene have elevated Bcl-w.[7] Bcl-w has been shown to contribute to cellular senescence.[7]

Quercetin has been shown to inhibit the PI3K/AKT pathway leading to downregulation of Bcl-w.[10][7]

Interactions

BCL2L2 has been shown to interact with:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000129473 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000089682 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Gibson L, Holmgreen SP, Huang DC, Bernard O, Copeland NG, Jenkins NA, Sutherland GR, Baker E, Adams JM, Cory S (October 1996). "bcl-w, a novel member of the bcl-2 family, promotes cell survival". Oncogene. 13 (4): 665–75. PMID 8761287.
  6. ^ a b "Entrez Gene: BCL2L2 BCL2-like 2".
  7. ^ a b c d e f g h i Hartman ML, Czyz M (2020). "BCL-w: apoptotic and non-apoptotic role in health and disease". Cell Death & Disease. 11 (4): 2260. doi:10.1038/s41419-020-2417-0. PMC 7174325. PMID 32317622.
  8. ^ Gibson L, Holmgreen SP, Huang DC, et al. (1996). "bcl-w, a novel member of the bcl-2 family, promotes cell survival". Oncogene. 13 (4): 665–75. PMID 8761287.
  9. ^ Kelly GL, Strasser A (2020). "Toward Targeting Antiapoptotic MCL-1 for Cancer Therapy". Annual Review of Cancer Biology. 4: 299–313. doi:10.1146/annurev-cancerbio-030419-033510. hdl:11343/252362.
  10. ^ Paez-Ribes M, González-Gualda E, Doherty GJ, Muñoz-Espín D (2019). "Targeting senescent cells in translational medicine". EMBO Molecular Medicine. 11 (12): e10234. doi:10.15252/emmm.201810234. PMC 6895604. PMID 31746100.
  11. ^ Hsu SY, Lin P, Hsueh AJ (September 1998). "BOD (Bcl-2-related ovarian death gene) is an ovarian BH3 domain-containing proapoptotic Bcl-2 protein capable of dimerization with diverse antiapoptotic Bcl-2 members". Mol. Endocrinol. 12 (9): 1432–40. doi:10.1210/mend.12.9.0166. PMID 9731710.
  12. ^ O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC (January 1998). "Bim: a novel member of the Bcl-2 family that promotes apoptosis". EMBO J. 17 (2): 384–95. doi:10.1093/emboj/17.2.384. PMC 1170389. PMID 9430630.
  13. ^ a b Ayllón V, Cayla X, García A, Fleischer A, Rebollo A (July 2002). "The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad". Eur. J. Immunol. 32 (7): 1847–55. doi:10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7. PMID 12115603.
  14. ^ Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC (February 2005). "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function". Mol. Cell. 17 (3): 393–403. doi:10.1016/j.molcel.2004.12.030. PMID 15694340.
  15. ^ Bae J, Hsu SY, Leo CP, Zell K, Hsueh AJ (October 2001). "Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis". Apoptosis. 6 (5): 319–30. doi:10.1023/A:1011319901057. PMID 11483855. S2CID 23119757.
  16. ^ Holmgreen SP, Huang DC, Adams JM, Cory S (June 1999). "Survival activity of Bcl-2 homologs Bcl-w and A1 only partially correlates with their ability to bind pro-apoptotic family members". Cell Death Differ. 6 (6): 525–32. doi:10.1038/sj.cdd.4400519. PMID 10381646.

Further reading

  • Nagase T, Seki N, Ishikawa K, et al. (1997). "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain". DNA Res. 3 (5): 321–9, 341–54. doi:10.1093/dnares/3.5.321. PMID 9039502.
  • O'Connor L, Strasser A, O'Reilly LA, et al. (1998). "Bim: a novel member of the Bcl-2 family that promotes apoptosis". EMBO J. 17 (2): 384–95. doi:10.1093/emboj/17.2.384. PMC 1170389. PMID 9430630.
  • Ross AJ, Waymire KG, Moss JE, et al. (1998). "Testicular degeneration in Bclw-deficient mice". Nat. Genet. 18 (3): 251–6. doi:10.1038/ng0398-251. PMID 9500547. S2CID 32843609.
  • Hsu SY, Lin P, Hsueh AJ (1998). "BOD (Bcl-2-related ovarian death gene) is an ovarian BH3 domain-containing proapoptotic Bcl-2 protein capable of dimerization with diverse antiapoptotic Bcl-2 members". Mol. Endocrinol. 12 (9): 1432–40. doi:10.1210/mend.12.9.0166. PMID 9731710.
  • Middleton G, Wyatt S, Ninkina N, Davies AM (2001). "Reciprocal developmental changes in the roles of Bcl-w and Bcl-x(L) in regulating sensory neuron survival". Development. 128 (3): 447–57. doi:10.1242/dev.128.3.447. PMID 11152643.
  • O'Reilly LA, Print C, Hausmann G, et al. (2001). "Tissue expression and subcellular localization of the pro-survival molecule Bcl-w". Cell Death Differ. 8 (5): 486–94. doi:10.1038/sj.cdd.4400835. PMID 11423909.
  • Bae J, Hsu SY, Leo CP, et al. (2001). "Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis". Apoptosis. 6 (5): 319–30. doi:10.1023/A:1011319901057. PMID 11483855. S2CID 23119757.
  • Puthalakath H, Villunger A, O'Reilly LA, et al. (2001). "Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis". Science. 293 (5536): 1829–32. Bibcode:2001Sci...293.1829P. doi:10.1126/science.1062257. PMID 11546872. S2CID 5638023.
  • Ayllón V, Cayla X, García A, et al. (2002). "The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad". Eur. J. Immunol. 32 (7): 1847–55. doi:10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7. PMID 12115603.
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
  • Denisov AY, Madiraju MS, Chen G, et al. (2003). "Solution structure of human BCL-w: modulation of ligand binding by the C-terminal helix". J. Biol. Chem. 278 (23): 21124–8. doi:10.1074/jbc.M301798200. PMID 12651847.
  • Hinds MG, Lackmann M, Skea GL, et al. (2003). "The structure of Bcl-w reveals a role for the C-terminal residues in modulating biological activity". EMBO J. 22 (7): 1497–507. doi:10.1093/emboj/cdg144. PMC 152889. PMID 12660157.
  • Wilson-Annan J, O'Reilly LA, Crawford SA, et al. (2003). "Proapoptotic BH3-only proteins trigger membrane integration of prosurvival Bcl-w and neutralize its activity". J. Cell Biol. 162 (5): 877–87. doi:10.1083/jcb.200302144. PMC 2172834. PMID 12952938.
  • Zhu X, Wang Y, Ogawa O, et al. (2004). "Neuroprotective properties of Bcl-w in Alzheimer disease". J. Neurochem. 89 (5): 1233–40. doi:10.1111/j.1471-4159.2004.02416.x. PMID 15147516.
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
  • Chen L, Willis SN, Wei A, et al. (2005). "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function". Mol. Cell. 17 (3): 393–403. doi:10.1016/j.molcel.2004.12.030. PMID 15694340.
  • Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
  • Denisov AY, Chen G, Sprules T, et al. (2006). "Structural model of the BCL-w-BID peptide complex and its interactions with phospholipid micelles". Biochemistry. 45 (7): 2250–6. doi:10.1021/bi052332s. PMID 16475813.
  • Certo M, Del Gaizo Moore V, Nishino M, et al. (2006). "Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members". Cancer Cell. 9 (5): 351–65. doi:10.1016/j.ccr.2006.03.027. PMID 16697956.

External links

  • v
  • t
  • e
  • 1mk3: SOLUTION STRUCTURE OF HUMAN BCL-W PROTEIN
    1mk3: SOLUTION STRUCTURE OF HUMAN BCL-W PROTEIN
  • 1o0l: THE STRUCTURE OF BCL-W REVEALS A ROLE FOR THE C-TERMINAL RESIDUES IN MODULATING BIOLOGICAL ACTIVITY
    1o0l: THE STRUCTURE OF BCL-W REVEALS A ROLE FOR THE C-TERMINAL RESIDUES IN MODULATING BIOLOGICAL ACTIVITY
  • 1zy3: Structural model of complex of Bcl-w protein with Bid BH3-peptide
    1zy3: Structural model of complex of Bcl-w protein with Bid BH3-peptide


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