BCL2L2

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]

BCL2L2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1MK3, 1O0L, 1ZY3, 2Y6W, 4CIM
Identifiers
Aliases	BCL2L2, BCL-W, BCL2-L-2, BCLW, PPP1R51, BCL2 like 2
External IDs	OMIM: 601931; MGI: 108052; HomoloGene: 2989; GeneCards: BCL2L2; OMA:BCL2L2 - orthologs
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q11.2 Start 23,298,790 bp[1] End 23,311,751 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14 C3|14 27.98 cM Start 55,120,834 bp[2] End 55,125,691 bp[2]
RNA expression pattern Bgee Human Mouse (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 Species Human Mouse 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 Mb Chr 14: 55.12 – 55.13 Mb PubMed search [3] [4]
Wikidata
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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:

• BCL2L11^[11][12]
• BAD,^{[13][14][15][16]} and
• PPP1CA.^[13]