BCL2L2

BCL2L2
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1MK3, 1O0L, 1ZY3, 2Y6W, 4CIM
Identifikatori
Aliasi	BCL2L2
Vanjski ID-jevi	OMIM: 601931 MGI: 108052 HomoloGene: 2989 GeneCards: BCL2L2
Lokacija gena (čovjek)
Hrom.	Hromosom 14 (čovjek)
Kraj	23,311,751 bp
Lokacija gena (miš)
Hrom.	Hromosom 14 (miš)
Kraj	55,125,691 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• GO:0001948, GO:0016582 vezivanje za proteine; • protein homodimerization activity; • disordered domain specific binding; • vezivanje identičnih proteina; • protein heterodimerization activity; • BH domain binding;
Ćelijska komponenta	• citoplazma; • citosol; • mitochondrial membranes; • mitohondrija; • membrana; • mitochondrial outer membrane; • Bcl-2 family protein complex; • jedro; • nuclear inclusion body;
Biološki proces	• Spermatogeneza; • regulation of apoptotic process; • negative regulation of apoptotic process; • Sertoli cell proliferation; • GO:0097285 apoptoza; • 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;
	Izvori:Amigo / QuickGO
Ortolozi
	599
	12050
	ENSG00000129473
	ENSMUSG00000089682
	Q92843
	P70345
	NM_004050; NM_001199839
	NM_007537
	NP_001186768; NP_004041
	NP_031563
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Bcl-2-liki protein 2 je 193-aminokiselinski protein koji je kod ljudi kodiran genom BCL2L2 sa hromosoma 14, sekvenca q11.2-q12.^[5]^[6]^[7] Izvorno su ga otkrili Leonie Gibson, Suzanne Cory i kolege sa Walter i Eliza Hall Institute of Medical Research, koji su ga nazvali Bcl-w.^[8]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 193 aminokiseline, a molekulska težina 20.746 Da^[9].

10	20	30	40	50
MATPASAPDT	RALVADFVGY	KLRQKGYVCG	AGPGEGPAAD	PLHQAMRAAG
DEFETRFRRT	FSDLAAQLHV	TPGSAQQRFT	QVSDELFQGG	PNWGRLVAFF
VFGAALCAES	VNKEMEPLVG	QVQEWMVAYL	ETQLADWIHS	SGGWAEFTAL
YGDGALEEAR	RLREGNWASV	RTVLTGAVAL	GALVTVGAFF	ASK

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

Funkcija

Ovaj gen kodira člana za preživljavanje (antiapoptotoznog) iz porodice protrina bcl-2, a najsličniji je Bcl-xL.^[7] Proteini ove porodice tvore hetero– ili homodimere i djeluju kao anti– i proapoptozni regulatori . Pokazalo se da ekspresija ovog gena u ćelijama doprinosi smanjenoj učestalosti apoptoza ćelija u uslovima citotoksičnosti. Studije srodnog gena na miševima ukazale su na ulogu u preživljavanju NGF i BDNF-zavisnih neurona. Studije mutacije i gena nokaut-miševa pokazale su ključnu ulogu u spermatogenezi kod odraslih.^[6]^[7]^[10]

Klinički značaj

Visok nivo Bcl-w uočen je kod mnogih karcinoma, uključujući glioblastom, kolorektumski karcinom, karcinom pluća nemalih ćelija i rak dojke.^[7] Pacijenti sa rakom dojke sa metastazama imaju veći Bcl-w od onih sa rakom dojke koji imaju samo primarni tumor.^[7] Pokazano je da povišeni nivoi Bcl-w štite neurone od ćelijske smrti izazvane amieloidom-beta.^[7] Pacijenti sa Parkinsonovim bolesti, sa mutiranim genom PARK2 imaju povišeni Bcl-w. Pokazano je da ^[7] Bcl-w doprinosi ćelijskom starenju.^[7]

Pokazano je da kvercetin inhibira PI3K/AKT put, što dovodi do podregulacije Bcl-w.^[7]^[11]

Interakcije

Pokazano je da BCL2L2 ima interakcije sa:

BCL2L11^[12]^[13]
BAD,^[14]^[15]^[16]^[17] i
PPP1CA.^[14]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000129473 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000089682 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Gibson L, Holmgreen SP, Huang DC, Bernard O, Copeland NG, Jenkins NA, Sutherland GR, Baker E, Adams JM, Cory S (oktobar 1996). "bcl-w, a novel member of the bcl-2 family, promotes cell survival". Oncogene. 13 (4): 665–75. PMID 8761287.
^ ^a ^b "Entrez Gene: BCL2L2 BCL2-like 2".
^ ^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.
^ 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.
^ "UniProt, Q92843". Pristupljeno 21. 7. 2021.
^ Kelly, Gemma L.; Strasser, Andreas (2020). "Toward Targeting Antiapoptotic MCL-1 for Cancer Therapy". Annual Review of Cancer Biology. 4: 299–313. doi:10.1146/annurev-cancerbio-030419-033510.
^ 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.
^ Hsu SY, Lin P, Hsueh AJ (septembar 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.
^ O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC (januar 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.
^ ^a ^b Ayllón V, Cayla X, García A, Fleischer A, Rebollo A (juli 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.
^ Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC (februar 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.
^ Bae J, Hsu SY, Leo CP, Zell K, Hsueh AJ (oktobar 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.
^ Holmgreen SP, Huang DC, Adams JM, Cory S (juni 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.

Dopunska literatura

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. 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. 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.

Vanjski linkovi

Lokacija ljudskog genoma BCL2L2 i stranica sa detaljima o genu BCL2L2 u UCSC Genome Browseru.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000129473 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000089682 - Ensembl, maj 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.

[pmid8761287-5] Gibson L, Holmgreen SP, Huang DC, Bernard O, Copeland NG, Jenkins NA, Sutherland GR, Baker E, Adams JM, Cory S (oktobar 1996). "bcl-w, a novel member of the bcl-2 family, promotes cell survival". Oncogene. 13 (4): 665–75. PMID 8761287.

[entrez-6] "Entrez Gene: BCL2L2 BCL2-like 2".

[pmid32317622-7] ^ ^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.

[Gibson1996-8] 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.

[UniProt-9] "UniProt, Q92843". Pristupljeno 21. 7. 2021.

[10] Kelly, Gemma L.; Strasser, Andreas (2020). "Toward Targeting Antiapoptotic MCL-1 for Cancer Therapy". Annual Review of Cancer Biology. 4: 299–313. doi:10.1146/annurev-cancerbio-030419-033510.

[pmid31746100-11] 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.

[pmid9731710-12] Hsu SY, Lin P, Hsueh AJ (septembar 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.

[pmid9430630-13] O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC (januar 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.

[pmid12115603-14] Ayllón V, Cayla X, García A, Fleischer A, Rebollo A (juli 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.

[pmid15694340-15] Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC (februar 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.

[pmid11483855-16] Bae J, Hsu SY, Leo CP, Zell K, Hsueh AJ (oktobar 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.

[pmid10381646-17] Holmgreen SP, Huang DC, Adams JM, Cory S (juni 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.

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