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[uredi | uredi izvor]

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[uredi | uredi izvor]

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[uredi | uredi izvor]

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[uredi | uredi izvor]

Pokazano je da BCL2L2 ima interakcije sa:

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

Reference[uredi | uredi izvor]

^ ^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[uredi | uredi izvor]

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[uredi | uredi izvor]

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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