CD59

CD59
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1CDQ, 1CDR, 1CDS, 1ERG, 1ERH, 2J8B, 2OFS, 2UWR, 2UX2, 4BIK
Identifiers
Aliases	CD59, 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 IDs	OMIM: 107271 MGI: 1888996 HomoloGene: 56386 GeneCards: CD59
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11p13 Start 33,703,010 bp[1] End 33,736,479 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 E2 Start 103,900,194 bp[2] End 103,921,532 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium bronchial epithelial cell right lung gallbladder upper lobe of left lung minor salivary glands tibial nerve smooth muscle tissue spinal ganglia right lobe of thyroid gland Top expressed in brown adipose tissue spermatid choroid plexus bone marrow quadriceps femoris muscle morula liver white adipose tissue blastocyst muscle tissue More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding complement binding Cellular component vesicle endoplasmic reticulum membrane membrane focal adhesion Golgi membrane plasma membrane extracellular region cell surface compact myelin anchored component of external side of plasma membrane ER to Golgi transport vesicle membrane anchored component of membrane sarcolemma extracellular exosome endoplasmic reticulum-Golgi intermediate compartment membrane extracellular space specific granule membrane tertiary granule membrane transport vesicle Biological process blood coagulation negative regulation of apoptotic process negative regulation of activation of membrane attack complex endoplasmic reticulum to Golgi vesicle-mediated transport cell surface receptor signaling pathway COPII vesicle coating positive regulation of T cell proliferation regulation of complement activation cell activation neutrophil degranulation regulation of complement-dependent cytotoxicity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 966 333883 Ensembl ENSG00000085063 ENSMUSG00000068686 UniProt P13987 Q6FHM9 P58019 RefSeq (mRNA) NM_203331 NM_000611 NM_001127223 NM_001127225 NM_001127226 NM_001127227 NM_203329 NM_203330 NM_181858 NM_001368215 RefSeq (protein) NP_000602 NP_001120695 NP_001120697 NP_001120698 NP_001120699 NP_976074 NP_976075 NP_976076 NP_000602.1 NP_001120695.1 NP_001120697.1 NP_001120698.1 NP_001120699.1 NP_976074.1 NP_976075.1 NP_976076.1 NP_862906 NP_001355144 Location (UCSC) Chr 11: 33.7 – 33.74 Mb Chr 2: 103.9 – 103.92 Mb PubMed search [3] [4]
Wikidata
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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

Further reading

External links

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