View source for CD59

{{Short description|Mammalian protein found in humans}}
{{for|the inflammation pro-resolving mediators|Protectin D1}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox_gene}}
'''CD59 glycoprotein''', also known as '''MAC-inhibitory protein''' (MAC-IP), '''membrane inhibitor of reactive lysis''' (MIRL), or '''protectin''',  is a [[protein]] that in humans is encoded by the ''CD59'' [[gene]].<ref>{{cite web |url=https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=retrieve&dopt=default&list_uids=966&rn=1 |title=Entrez Gene: CD59 molecule, complement regulatory protein}}</ref> It is an [[LU domain]] and belongs to the [[LY6]]/[[Urokinase receptor|uPAR]]/[[alpha-neurotoxin]] [[protein family]].<ref name="pmid9664126">{{cite journal | vauthors = Maio M, Brasoveanu LI, Coral S, Sigalotti L, Lamaj E, Gasparollo A, Visintin A, Altomonte M, Fonsatti E | title = Structure, distribution, and functional role of protectin (CD59) in complement-susceptibility and in immunotherapy of human malignancies (Review) | journal = International Journal of Oncology | volume = 13 | issue = 2 | pages = 305–318 | date = August 1998 | pmid = 9664126 | doi = 10.3892/ijo.13.2.305 }}</ref>

CD59 attaches to host cells via a [[glycophosphatidylinositol]] (GPI) anchor.  Cholesterol-containing microdomains aid in CD59 activity by stimulating a "pinch point" in the lipid membrane during MAC assembly to prevent pore-formation and inhibit lysing.<ref>{{cite journal | vauthors = Couves EC, Gardner S, Voisin TB, Bickel JK, Stansfeld PJ, Tate EW, Bubeck D | title = Structural basis for membrane attack complex inhibition by CD59 | journal = Nature Communications | volume = 14 | issue = 1 | pages = 890 | date = February 2023 | pmid = 36797260 | pmc = 9935631 | doi = 10.1038/s41467-023-36441-z | bibcode = 2023NatCo..14..890C }}</ref> When [[Complement system|complement]] activation leads to deposition of C5b678 on host cells, CD59 can prevent [[complement component 9|C9]] from polymerizing and forming the [[complement membrane attack complex]].<ref name="pmid16844690">{{cite journal | vauthors = Huang Y, Qiao F, Abagyan R, Hazard S, Tomlinson S | title = Defining the CD59-C9 binding interaction | journal = The Journal of Biological Chemistry | volume = 281 | issue = 37 | pages = 27398–27404 | date = September 2006 | pmid = 16844690 | doi = 10.1074/jbc.M603690200 | doi-access = free }}</ref> It may also [[signal transduction|signal]] the cell to perform active measures such as [[endocytosis]] of the CD59-C9 complex.<ref name = "pmid9664126"/> Endocytosis of this complex leads to the destruction of the ion channel formation that this complex provides to the MAC. These ion channels are used for transfer of different ions to maintain the correct concentration of minerals inside and outside of the membrane, and without this correct maintenance, severe symptoms and diseases can occur such as neuron degeneration and [[Alzheimer's disease]].<ref>{{cite journal | vauthors = Farkas I, Baranyi L, Ishikawa Y, Okada N, Bohata C, Budai D, Fukuda A, Imai M, Okada H | title = CD59 blocks not only the insertion of C9 into MAC but inhibits ion channel formation by homologous C5b-8 as well as C5b-9 | journal = The Journal of Physiology | volume = 539 | issue = Pt 2 | pages = 537–545 | date = March 2002 | pmid = 11882685 | pmc = 2290142 | doi = 10.1113/jphysiol.2001.013381 }}</ref>

Mutations affecting GPI that reduce expression of CD59 and [[decay-accelerating factor]] on [[red blood cell]]s result in [[paroxysmal nocturnal hemoglobinuria]].<ref name=parker2005>{{cite journal | vauthors = Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R, Hillmen P, Luzzatto L, Young N, Kinoshita T, Rosse W, Socié G | title = Diagnosis and management of paroxysmal nocturnal hemoglobinuria | journal = Blood | volume = 106 | issue = 12 | pages = 3699–3709 | date = December 2005 | pmid = 16051736 | pmc = 1895106 | doi = 10.1182/blood-2005-04-1717 }}</ref> GPI mutation and consequent reduction in CD59 expression results from a cysteine to tyrosine missense mutation, which prevents disulfide bridge formation, ultimately disrupting tertiary protein structure and preventing proper GPI-CD59 complex binding.<ref>{{cite journal | vauthors = 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 | title = CD59 deficiency is associated with chronic hemolysis and childhood relapsing immune-mediated polyneuropathy | journal = Blood | volume = 121 | issue = 1 | pages = 129–135 | date = January 2013 | pmid = 23149847 | doi = 10.1182/blood-2012-07-441857 | s2cid = 19110288 | doi-access = free }}</ref>

[[Viruses]] such as [[HIV]], human [[cytomegalovirus]] and [[vaccinia virus|vaccinia]] incorporate host cell CD59 into their own [[viral envelope]] to prevent lysis by complement.<ref name="pmid15219997">{{cite journal | vauthors = Bohana-Kashtan O, Ziporen L, Donin N, Kraus S, Fishelson Z | title = Cell signals transduced by complement | journal = Molecular Immunology | volume = 41 | issue = 6–7 | pages = 583–597 | date = July 2004 | pmid = 15219997 | doi = 10.1016/j.molimm.2004.04.007 }}</ref> Additionally, CD59 has been investigated as a target for immunotherapy when treating certain cancers such as breast cancer. Researchers have found that once CD59 had been targeted, there is an upregulation in fas and caspase-3, creating an increase in apoptosis and tumor growth suppression in [[MCF-7]] cells.<ref>{{cite journal | vauthors = Li B, Chu X, Gao M, Xu Y | title = The effects of CD59 gene as a target gene on breast cancer cells | journal = Cellular Immunology | volume = 272 | issue = 1 | pages = 61–70 | date = 2011 | pmid = 22000275 | doi = 10.1016/j.cellimm.2011.09.006 }}</ref>

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Tandon N, Morgan BP, Weetman AP | title = Expression and function of membrane attack complex inhibitory proteins on thyroid follicular cells | journal = Immunology | volume = 75 | issue = 2 | pages = 372–377 | date = February 1992 | pmid = 1372592 | pmc = 1384722 }}
* {{cite journal | vauthors = Holmes CH, Simpson KL, Okada H, Okada N, Wainwright SD, Purcell DF, Houlihan JM | title = 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) | journal = European Journal of Immunology | volume = 22 | issue = 6 | pages = 1579–1585 | date = June 1992 | pmid = 1376264 | doi = 10.1002/eji.1830220635 | s2cid = 25836496 }}
* {{cite journal | vauthors = Hahn WC, Menu E, Bothwell AL, Sims PJ, Bierer BE | title = Overlapping but nonidentical binding sites on CD2 for CD58 and a second ligand CD59 | journal = Science | volume = 256 | issue = 5065 | pages = 1805–1807 | date = June 1992 | pmid = 1377404 | doi = 10.1126/science.1377404 | bibcode = 1992Sci...256.1805H }}
* {{cite journal | vauthors = Ninomiya H, Sims PJ | title = The human complement regulatory protein CD59 binds to the alpha-chain of C8 and to the "b"domain of C9 | journal = The Journal of Biological Chemistry | volume = 267 | issue = 19 | pages = 13675–13680 | date = July 1992 | pmid = 1377690 | doi = 10.1016/S0021-9258(18)42266-1 | doi-access = free }}
* {{cite journal | vauthors = Petranka JG, Fleenor DE, Sykes K, Kaufman RE, Rosse WF | title = Structure of the CD59-encoding gene: further evidence of a relationship to murine lymphocyte antigen Ly-6 protein | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 17 | pages = 7876–7879 | date = September 1992 | pmid = 1381503 | pmc = 49817 | doi = 10.1073/pnas.89.17.7876 | doi-access = free | bibcode = 1992PNAS...89.7876P }}
* {{cite journal | vauthors = Motoyama N, Okada N, Yamashina M, Okada H | title = Paroxysmal nocturnal hemoglobinuria due to hereditary nucleotide deletion in the HRF20 (CD59) gene | journal = European Journal of Immunology | volume = 22 | issue = 10 | pages = 2669–2673 | date = October 1992 | pmid = 1382994 | doi = 10.1002/eji.1830221029 | s2cid = 23829471 }}
* {{cite journal | vauthors = Rooney IA, Morgan BP | title = Characterization of the membrane attack complex inhibitory protein CD59 antigen on human amniotic cells and in amniotic fluid | journal = Immunology | volume = 76 | issue = 4 | pages = 541–547 | date = August 1992 | pmid = 1383132 | pmc = 1421564 }}
* {{cite journal | vauthors = Tone M, Walsh LA, Waldmann H | title = Gene structure of human CD59 and demonstration that discrete mRNAs are generated by alternative polyadenylation | journal = Journal of Molecular Biology | volume = 227 | issue = 3 | pages = 971–976 | date = October 1992 | pmid = 1383553 | doi = 10.1016/0022-2836(92)90239-G }}
* {{cite journal | vauthors = Philbrick WM, Palfree RG, Maher SE, Bridgett MM, Sirlin S, Bothwell AL | title = The CD59 antigen is a structural homologue of murine Ly-6 antigens but lacks interferon inducibility | journal = European Journal of Immunology | volume = 20 | issue = 1 | pages = 87–92 | date = January 1990 | pmid = 1689664 | doi = 10.1002/eji.1830200113 | s2cid = 23636682 }}
* {{cite journal | vauthors = Sawada R, Ohashi K, Anaguchi H, Okazaki H, Hattori M, Minato N, Naruto M | title = Isolation and expression of the full-length cDNA encoding CD59 antigen of human lymphocytes | journal = DNA and Cell Biology | volume = 9 | issue = 3 | pages = 213–220 | date = April 1990 | pmid = 1692709 | doi = 10.1089/dna.1990.9.213 }}
* {{cite journal | vauthors = Yamashina M, Ueda E, Kinoshita T, Takami T, Ojima A, Ono H, Tanaka H, Kondo N, Orii T, Okada N | title = Inherited complete deficiency of 20-kilodalton homologous restriction factor (CD59) as a cause of paroxysmal nocturnal hemoglobinuria | journal = The New England Journal of Medicine | volume = 323 | issue = 17 | pages = 1184–1189 | date = October 1990 | pmid = 1699124 | doi = 10.1056/NEJM199010253231707 | doi-access = free }}
* {{cite journal | vauthors = Rooney IA, Morgan BP | title = Protection of human amniotic epithelial cells (HAEC) from complement-mediated lysis: expression on the cells of three complement inhibitory membrane proteins | journal = Immunology | volume = 71 | issue = 3 | pages = 308–311 | date = November 1990 | pmid = 1702747 | pmc = 1384423 }}
* {{cite journal | vauthors = Watts MJ, Dankert JR, Morgan EP | title = Isolation and characterization of a membrane-attack-complex-inhibiting protein present in human serum and other biological fluids | journal = The Biochemical Journal | volume = 265 | issue = 2 | pages = 471–477 | date = January 1990 | pmid = 2302178 | pmc = 1136908 | doi = 10.1042/bj2650471 }}
* {{cite journal | vauthors = Okada H, Nagami Y, Takahashi K, Okada N, Hideshima T, Takizawa H, Kondo J | title = 20 KDa homologous restriction factor of complement resembles T cell activating protein | journal = Biochemical and Biophysical Research Communications | volume = 162 | issue = 3 | pages = 1553–1559 | date = August 1989 | pmid = 2475111 | doi = 10.1016/0006-291X(89)90852-8 }}
* {{cite journal | vauthors = Davies A, Simmons DL, Hale G, Harrison RA, Tighe H, Lachmann PJ, Waldmann H | title = CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cells | journal = The Journal of Experimental Medicine | volume = 170 | issue = 3 | pages = 637–654 | date = September 1989 | pmid = 2475570 | pmc = 2189447 | doi = 10.1084/jem.170.3.637 }}
* {{cite journal | vauthors = Sawada R, Ohashi K, Okano K, Hattori M, Minato N, Naruto M | title = Complementary DNA sequence and deduced peptide sequence for CD59/MEM-43 antigen, the human homologue of murine lymphocyte antigen Ly-6C | journal = Nucleic Acids Research | volume = 17 | issue = 16 | pages = 6728 | date = August 1989 | pmid = 2476718 | pmc = 318369 | doi = 10.1093/nar/17.16.6728 }}
* {{cite journal | vauthors = Sugita Y, Tobe T, Oda E, Tomita M, Yasukawa K, Yamaji N, Takemoto T, Furuichi K, Takayama M, Yano S | title = Molecular cloning and characterization of MACIF, an inhibitor of membrane channel formation of complement | journal = Journal of Biochemistry | volume = 106 | issue = 4 | pages = 555–557 | date = October 1989 | pmid = 2606909 | doi = 10.1093/oxfordjournals.jbchem.a122893 }}
* {{cite journal | vauthors = Bora NS, Gobleman CL, Atkinson JP, Pepose JS, Kaplan HJ | title = Differential expression of the complement regulatory proteins in the human eye | journal = Investigative Ophthalmology & Visual Science | volume = 34 | issue = 13 | pages = 3579–3584 | date = December 1993 | pmid = 7505007 }}
* {{cite journal | vauthors = Kieffer B, Driscoll PC, Campbell ID, Willis AC, van der Merwe PA, Davis SJ | title = 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 | journal = Biochemistry | volume = 33 | issue = 15 | pages = 4471–4482 | date = April 1994 | pmid = 7512825 | doi = 10.1021/bi00181a006 }}
* {{cite journal | vauthors = Kennedy SP, Rollins SA, Burton WV, Sims PJ, Bothwell AL, Squinto SP, Zavoico GB | title = Protection of porcine aortic endothelial cells from complement-mediated cell lysis and activation by recombinant human CD59 | journal = Transplantation | volume = 57 | issue = 10 | pages = 1494–1501 | date = May 1994 | pmid = 7515200 | doi = 10.1097/00007890-199405000-00017 | doi-access = free }}
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== External links ==
{{Commons category}}
* {{MeshName|CD59+Antigen}}
* {{UCSC gene info|CD59}}

{{PDB Gallery|geneid=966}}
{{Clusters of differentiation}}
{{Complement system}}
{{transfusion medicine}}

[[Category:Clusters of differentiation]]
[[Category:Blood antigen systems]]
[[Category:Transfusion medicine]]