CD59

CD59
Estruturas dispoñibles
PDB	Buscar ortólogos: PDBe, RCSB Lista de códigos PDB 1CDQ, 1CDR, 1CDS, 1ERG, 1ERH, 2J8B, 2OFS, 2UWR, 2UX2, 4BIK ;
Identificadores
Nomenclatura	Outros nomes CD59, 16.3A5, 1F5, EJ16, EJ30, EL32, G344, HRF-20, HRF20, MAC-IP, MACIF, MEM43, MIC11, MIN1, MIN2, MIN3, MIRL, MSK21, p18-20, molécula CD59, molécula CD59 (grupo sanguíneo CD59) ;
Identificadores; externos	OMIM: 107271 ; MGI: 1888996 ; HomoloGene: 56386 ; EBI: CD59 ; GeneCards: Xene CD59 ; UniProt: CD59 ;
Locus	Cr. 11 p13
Ontoloxía Xénica	Referencias: AmiGO / QuickGO
	Referencias: AmiGO / QuickGO
Ortólogos
Especies
Humano	Rato
Entrez
966	333883
Ensembl
Véxase HS	Véxase MM
UniProt
P13987	P58019
RefSeq; (ARNm)
NM_203331	NM_181858
RefSeq; (proteína) NCBI
NP_000602	NP_862906
Localización (UCSC)
Cr. 11:; 33.7 – 33.74 Mb	Cr. 2:; 103.9 – 103.92 Mb
PubMed (Busca)
966 ;	333883

O CD59 ou glicoproteína CD59, tamén coñecida como proteína inhibidora do MAC (MAC-IP), inhibidor de membrana de lise reactiva (MIRL) ou protectina, é unha proteína da superficie celular que nos humanos está codificada no xene CD59 do cromosoma 11.^[1] Ten un dominio LU e pertence á familia de proteínas LY6/uPAR/alfa-neurotoxina.^[2]

CD59 únese ás células hóspede por unha áncora de glicofosfatidilinositol (GPI). Os microdominios que conteñen colesterol axudan á actividade de CD59 ao estimularen un "punto de evaxinación" na membrana lipídica durante a ensamblaxe do complexo de ataque á membrana (MAC) para impedir a formación de poros e inhibir a lise.^[3] Cando a activación do sistema do complemento orixina o depósito de C5b678 nas células hóspede, o CD59 pode impedir que C9 se polimerice e forme o complexo de ataque á membrana do complemento.^[4] Pode tamén enviar sinais á célula para realizar medidas activas como a endocitose do complexo CD59-C9.^[2] A endocitose deste complexo leva á destrución da formación da canle iónica que este complexo proporciona ao MAC. Estas canles iónicas utilízanse para a transferencia de diferentes ións para manter a correcta concentración de minerais a un lado e outro da membrana, e sen este debido mantemento, poden producirse síntomas graves e doenzas como a dexeneración neuronal e a enfermidade de Alzheimer.^[5]

As mutacións que afectan GPI que reducen a expresión de CD59 e do factor acelerador da descomposición en glóbulos vermellos orixinan hemoglobinuria nocturna paroxística.^[6] Unha mutación no GPI e a consecuente redución da expresión de CD59 orixínase por unha mutación con cambio de sentido de cisteína por tirosina, que impide a formación dunha ponte disulfuro, o que acaba por distorsionar a estrutura terciaria da proteína e impedir unha unión axeitada do complexo GPI-CD59.^[7]

Os virus como o VIH, o citomegalovirus humano e o da vaccinia incorporan o CD59 da célula hóspede na súa propia envoltura viral para impediren a súa destrución polo complemento.^[8] Ademais, o investigouse o CD59 como diana para a inmunoterapia cando se tratan certos cancros, como o cancro de mama. Atopouse que unha vez que se neutralizou o CD59, prodúcese unha regulación á alza de Fas e da caspase-3, creando un aumento da apoptose e a supresión do crecemento tumoral en células MCF-7 (unha liña celular de cancro de mama).^[9]

Notas

↑ "Entrez Gene: CD59 molecule, complement regulatory protein".
1 2 Maio M, Brasoveanu LI, Coral S, Sigalotti L, Lamaj E, Gasparollo A, Visintin A, Altomonte M, Fonsatti E (agosto de 1998). "Structure, distribution, and functional role of protectin (CD59) in complement-susceptibility and in immunotherapy of human malignancies (Review)". International Journal of Oncology 13 (2): 305–318. PMID 9664126. doi:10.3892/ijo.13.2.305.
↑ Couves EC, Gardner S, Voisin TB, Bickel JK, Stansfeld PJ, Tate EW, Bubeck D (February 2023). "Structural basis for membrane attack complex inhibition by CD59". Nature Communications 14 (1): 890. Bibcode:2023NatCo..14..890C. PMC 9935631. PMID 36797260. doi:10.1038/s41467-023-36441-z.
↑ Huang Y, Qiao F, Abagyan R, Hazard S, Tomlinson S (setembro de 2006). "Defining the CD59-C9 binding interaction". The Journal of Biological Chemistry 281 (37): 27398–27404. PMID 16844690. doi:10.1074/jbc.M603690200.
↑ Farkas I, Baranyi L, Ishikawa Y, Okada N, Bohata C, Budai D, Fukuda A, Imai M, Okada H (marzo de 2002). "CD59 blocks not only the insertion of C9 into MAC but inhibits ion channel formation by homologous C5b-8 as well as C5b-9". The Journal of Physiology 539 (Pt 2): 537–545. PMC 2290142. PMID 11882685. doi:10.1113/jphysiol.2001.013381.
↑ Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R, Hillmen P, Luzzatto L, Young N, Kinoshita T, Rosse W, Socié G (decembro de 2005). "Diagnosis and management of paroxysmal nocturnal hemoglobinuria". Blood 106 (12): 3699–3709. PMC 1895106. PMID 16051736. doi:10.1182/blood-2005-04-1717.
↑ Nevo Y, Ben-Zeev B, Tabib A, Straussberg R, Anikster Y, Shorer Z, Fattal-Valevski A, Ta-Shma A, Aharoni S, Rabie M, Zenvirt S, Goldshmidt H, Fellig Y, Shaag A, Mevorach D, Elpeleg O (xaneiro de 2013). "CD59 deficiency is associated with chronic hemolysis and childhood relapsing immune-mediated polyneuropathy". Blood 121 (1): 129–135. PMID 23149847. doi:10.1182/blood-2012-07-441857.
↑ Bohana-Kashtan O, Ziporen L, Donin N, Kraus S, Fishelson Z (xullo de 2004). "Cell signals transduced by complement". Molecular Immunology 41 (6–7): 583–597. PMID 15219997. doi:10.1016/j.molimm.2004.04.007.
↑ Li B, Chu X, Gao M, Xu Y (2011). "The effects of CD59 gene as a target gene on breast cancer cells". Cellular Immunology 272 (1): 61–70. PMID 22000275. doi:10.1016/j.cellimm.2011.09.006.

Véxase tamén

Bibliografía

Tandon N, Morgan BP, Weetman AP (febreiro de 1992). "Expression and function of membrane attack complex inhibitory proteins on thyroid follicular cells". Immunology 75 (2): 372–377. PMC 1384722. PMID 1372592.
Holmes CH, Simpson KL, Okada H, Okada N, Wainwright SD, Purcell DF, Houlihan JM (xuño de 1992). "Complement regulatory proteins at the feto-maternal interface during human placental development: distribution of CD59 by comparison with membrane cofactor protein (CD46) and decay accelerating factor (CD55)". European Journal of Immunology 22 (6): 1579–1585. PMID 1376264. doi:10.1002/eji.1830220635.
Hahn WC, Menu E, Bothwell AL, Sims PJ, Bierer BE (xuño de 1992). "Overlapping but nonidentical binding sites on CD2 for CD58 and a second ligand CD59". Science 256 (5065): 1805–1807. Bibcode:1992Sci...256.1805H. PMID 1377404. doi:10.1126/science.1377404.
Ninomiya H, Sims PJ (xullo de 1992). "The human complement regulatory protein CD59 binds to the alpha-chain of C8 and to the "b"domain of C9". The Journal of Biological Chemistry 267 (19): 13675–13680. PMID 1377690. doi:10.1016/S0021-9258(18)42266-1.
Petranka JG, Fleenor DE, Sykes K, Kaufman RE, Rosse WF (setembro de 1992). "Structure of the CD59-encoding gene: further evidence of a relationship to murine lymphocyte antigen Ly-6 protein". Proceedings of the National Academy of Sciences of the United States of America 89 (17): 7876–7879. Bibcode:1992PNAS...89.7876P. PMC 49817. PMID 1381503. doi:10.1073/pnas.89.17.7876.
Motoyama N, Okada N, Yamashina M, Okada H (outubro de 1992). "Paroxysmal nocturnal hemoglobinuria due to hereditary nucleotide deletion in the HRF20 (CD59) gene". European Journal of Immunology 22 (10): 2669–2673. PMID 1382994. doi:10.1002/eji.1830221029.
Rooney IA, Morgan BP (agosto de 1992). "Characterization of the membrane attack complex inhibitory protein CD59 antigen on human amniotic cells and in amniotic fluid". Immunology 76 (4): 541–547. PMC 1421564. PMID 1383132.
Tone M, Walsh LA, Waldmann H (outubro de 1992). "Gene structure of human CD59 and demonstration that discrete mRNAs are generated by alternative polyadenylation". Journal of Molecular Biology 227 (3): 971–976. PMID 1383553. doi:10.1016/0022-2836(92)90239-G.
Philbrick WM, Palfree RG, Maher SE, Bridgett MM, Sirlin S, Bothwell AL (January 1990). "The CD59 antigen is a structural homologue of murine Ly-6 antigens but lacks interferon inducibility". European Journal of Immunology 20 (1): 87–92. PMID 1689664. doi:10.1002/eji.1830200113.
Sawada R, Ohashi K, Anaguchi H, Okazaki H, Hattori M, Minato N, Naruto M (abril de 1990). "Isolation and expression of the full-length cDNA encoding CD59 antigen of human lymphocytes". DNA and Cell Biology 9 (3): 213–220. PMID 1692709. doi:10.1089/dna.1990.9.213.
Yamashina M, Ueda E, Kinoshita T, Takami T, Ojima A, Ono H, Tanaka H, Kondo N, Orii T, Okada N (outubro de 1990). "Inherited complete deficiency of 20-kilodalton homologous restriction factor (CD59) as a cause of paroxysmal nocturnal hemoglobinuria". The New England Journal of Medicine 323 (17): 1184–1189. PMID 1699124. doi:10.1056/NEJM199010253231707.
Rooney IA, Morgan BP (novembro de 1990). "Protection of human amniotic epithelial cells (HAEC) from complement-mediated lysis: expression on the cells of three complement inhibitory membrane proteins". Immunology 71 (3): 308–311. PMC 1384423. PMID 1702747.
Watts MJ, Dankert JR, Morgan EP (xaneiro de 1990). "Isolation and characterization of a membrane-attack-complex-inhibiting protein present in human serum and other biological fluids". The Biochemical Journal 265 (2): 471–477. PMC 1136908. PMID 2302178. doi:10.1042/bj2650471.
Okada H, Nagami Y, Takahashi K, Okada N, Hideshima T, Takizawa H, Kondo J (agosto de 1989). "20 KDa homologous restriction factor of complement resembles T cell activating protein". Biochemical and Biophysical Research Communications 162 (3): 1553–1559. PMID 2475111. doi:10.1016/0006-291X(89)90852-8.
Davies A, Simmons DL, Hale G, Harrison RA, Tighe H, Lachmann PJ, Waldmann H (setembro de 1989). "CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cells". The Journal of Experimental Medicine 170 (3): 637–654. PMC 2189447. PMID 2475570. doi:10.1084/jem.170.3.637.
Sawada R, Ohashi K, Okano K, Hattori M, Minato N, Naruto M (agosto de 1989). "Complementary DNA sequence and deduced peptide sequence for CD59/MEM-43 antigen, the human homologue of murine lymphocyte antigen Ly-6C". Nucleic Acids Research 17 (16): 6728. PMC 318369. PMID 2476718. doi:10.1093/nar/17.16.6728.
Sugita Y, Tobe T, Oda E, Tomita M, Yasukawa K, Yamaji N, Takemoto T, Furuichi K, Takayama M, Yano S (October 1989). "Molecular cloning and characterization of MACIF, an inhibitor of membrane channel formation of complement". Journal of Biochemistry 106 (4): 555–557. PMID 2606909. doi:10.1093/oxfordjournals.jbchem.a122893.
Bora NS, Gobleman CL, Atkinson JP, Pepose JS, Kaplan HJ (decembro de 1993). "Differential expression of the complement regulatory proteins in the human eye". Investigative Ophthalmology & Visual Science 34 (13): 3579–3584. PMID 7505007.
Kieffer B, Driscoll PC, Campbell ID, Willis AC, van der Merwe PA, Davis SJ (abril de 1994). "Three-dimensional solution structure of the extracellular region of the complement regulatory protein CD59, a new cell-surface protein domain related to snake venom neurotoxins". Biochemistry 33 (15): 4471–4482. PMID 7512825. doi:10.1021/bi00181a006.
Kennedy SP, Rollins SA, Burton WV, Sims PJ, Bothwell AL, Squinto SP, Zavoico GB (maio de 1994). "Protection of porcine aortic endothelial cells from complement-mediated cell lysis and activation by recombinant human CD59". Transplantation 57 (10): 1494–1501. PMID 7515200. doi:10.1097/00007890-199405000-00017.

Ligazóns externas

CD59 Antigen Medical Subject Headings (MeSH) na Biblioteca Nacional de Medicina dos EUA.
Localización no xenoma humano de CD59 e páxina con detalles sobre o xene CD59 no UCSC Genome Browser.

[1] "Entrez Gene: CD59 molecule, complement regulatory protein".

[pmid9664126-2] 1 2 Maio M, Brasoveanu LI, Coral S, Sigalotti L, Lamaj E, Gasparollo A, Visintin A, Altomonte M, Fonsatti E (agosto de 1998). "Structure, distribution, and functional role of protectin (CD59) in complement-susceptibility and in immunotherapy of human malignancies (Review)". International Journal of Oncology 13 (2): 305–318. PMID 9664126. doi:10.3892/ijo.13.2.305.

[3] Couves EC, Gardner S, Voisin TB, Bickel JK, Stansfeld PJ, Tate EW, Bubeck D (February 2023). "Structural basis for membrane attack complex inhibition by CD59". Nature Communications 14 (1): 890. Bibcode:2023NatCo..14..890C. PMC 9935631. PMID 36797260. doi:10.1038/s41467-023-36441-z.

[pmid16844690-4] Huang Y, Qiao F, Abagyan R, Hazard S, Tomlinson S (setembro de 2006). "Defining the CD59-C9 binding interaction". The Journal of Biological Chemistry 281 (37): 27398–27404. PMID 16844690. doi:10.1074/jbc.M603690200.

[5] Farkas I, Baranyi L, Ishikawa Y, Okada N, Bohata C, Budai D, Fukuda A, Imai M, Okada H (marzo de 2002). "CD59 blocks not only the insertion of C9 into MAC but inhibits ion channel formation by homologous C5b-8 as well as C5b-9". The Journal of Physiology 539 (Pt 2): 537–545. PMC 2290142. PMID 11882685. doi:10.1113/jphysiol.2001.013381.

[parker2005-6] Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R, Hillmen P, Luzzatto L, Young N, Kinoshita T, Rosse W, Socié G (decembro de 2005). "Diagnosis and management of paroxysmal nocturnal hemoglobinuria". Blood 106 (12): 3699–3709. PMC 1895106. PMID 16051736. doi:10.1182/blood-2005-04-1717.

[7] Nevo Y, Ben-Zeev B, Tabib A, Straussberg R, Anikster Y, Shorer Z, Fattal-Valevski A, Ta-Shma A, Aharoni S, Rabie M, Zenvirt S, Goldshmidt H, Fellig Y, Shaag A, Mevorach D, Elpeleg O (xaneiro de 2013). "CD59 deficiency is associated with chronic hemolysis and childhood relapsing immune-mediated polyneuropathy". Blood 121 (1): 129–135. PMID 23149847. doi:10.1182/blood-2012-07-441857.

[pmid15219997-8] Bohana-Kashtan O, Ziporen L, Donin N, Kraus S, Fishelson Z (xullo de 2004). "Cell signals transduced by complement". Molecular Immunology 41 (6–7): 583–597. PMID 15219997. doi:10.1016/j.molimm.2004.04.007.

[9] Li B, Chu X, Gao M, Xu Y (2011). "The effects of CD59 gene as a target gene on breast cancer cells". Cellular Immunology 272 (1): 61–70. PMID 22000275. doi:10.1016/j.cellimm.2011.09.006.

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