CD59
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCD59, 16.3A5, 1F5, EJ16, EJ30, EL32, G344, HRF-20, HRF20, MAC-IP, MACIF, MEM43, MIC11, MIN1, MIN2, MIN3, MIRL, MSK21, p18-20, CD59 molecule, CD59 molecule (CD59 blood group)
External IDsOMIM: 107271 MGI: 1888996 HomoloGene: 56386 GeneCards: CD59
Orthologs
SpeciesHumanMouse
Entrez

966

333883

Ensembl

ENSG00000085063

ENSMUSG00000068686

UniProt

P13987
Q6FHM9

P58019

RefSeq (mRNA)

NM_181858
NM_001368215

RefSeq (protein)

NP_862906
NP_001355144

Location (UCSC)Chr 11: 33.7 – 33.74 MbChr 2: 103.9 – 103.92 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5] It is an LU domain and belongs to the LY6/uPAR/alpha-neurotoxin protein family.[6]

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.[7] When complement activation leads to deposition of C5b678 on host cells, CD59 can prevent C9 from polymerizing and forming the complement membrane attack complex.[8] It may also signal the cell to perform active measures such as endocytosis of the CD59-C9 complex.[6]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.[9]

Mutations affecting GPI that reduce expression of CD59 and decay-accelerating factor on red blood cells result in paroxysmal nocturnal hemoglobinuria.[10]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.[11]

Viruses such as HIV, human cytomegalovirus and vaccinia incorporate host cell CD59 into their own viral envelope to prevent lysis by complement.[12]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.[13]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000085063 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000068686 - Ensembl, May 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.
  5. ↑ "Entrez Gene: CD59 molecule, complement regulatory protein".
  6. 1 2 Maio M, Brasoveanu LI, Coral S, Sigalotti L, Lamaj E, Gasparollo A, Visintin A, Altomonte M, Fonsatti E (Aug 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): 305–18. doi:10.3892/ijo.13.2.305. PMID 9664126.
  7. ↑ Couves EC, Gardner S, Voisin TB, Bickel JK, Stansfeld PJ, Tate EW, Bubeck D (2023-02-16). "Structural basis for membrane attack complex inhibition by CD59". Nature Communications. 14 (1): 890. Bibcode:2023NatCo..14..890C. doi:10.1038/s41467-023-36441-z. ISSN 2041-1723. PMC 9935631. PMID 36797260.
  8. ↑ Huang Y, Qiao F, Abagyan R, Hazard S, Tomlinson S (September 2006). "Defining the CD59-C9 binding interaction". J. Biol. Chem. 281 (37): 27398–27404. doi:10.1074/jbc.M603690200. PMID 16844690.
  9. ↑ Farkas I, Baranyi L, Ishikawa Y, Okada N, Bohata C, Budai D, Fukuda A, Imai M, Okada H (2002–2003). "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 (2): 537–545. doi:10.1113/jphysiol.2001.013381. ISSN 0022-3751. PMC 2290142. PMID 11882685.
  10. ↑ Parker C, Omine M, Richards S, et al. (2005). "Diagnosis and management of paroxysmal nocturnal hemoglobinuria". Blood. 106 (12): 3699–709. doi:10.1182/blood-2005-04-1717. PMC 1895106. PMID 16051736.
  11. ↑ 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 (2013-01-03). "CD59 deficiency is associated with chronic hemolysis and childhood relapsing immune-mediated polyneuropathy". Blood. 121 (1): 129–135. doi:10.1182/blood-2012-07-441857. ISSN 0006-4971. PMID 23149847. S2CID 19110288.
  12. ↑ Bohana-Kashtan O, Ziporen L, Donin N, Kraus S, Fishelson Z (July 2004). "Cell signals transduced by complement". Mol. Immunol. 41 (6–7): 583–597. doi:10.1016/j.molimm.2004.04.007. PMID 15219997.
  13. ↑ 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. doi:10.1016/j.cellimm.2011.09.006. PMID 22000275.

Further reading

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