NCBI Reference Sequence: NG_008057.1.

- Total range: NG_008057.1
- exon 1: (1..98); total length: 98; strand: plus
- exon 2: (2870..2985); total length: 116; strand: plus
- exon 3: (5012..5056); total length: 45; strand: plus
- exon 4: (13528..13563); total length: 36; strand: plus
- exon 5a: (13753..13844); total length: 92; strand: plus
- exon 5b :(13753..13909); total length: 157; strand: plus
- exon 5c: (13753..14101); total length: 349; strand: plus
- exon 5d: (14017..14101); total length: 85; strand: plus
- exon 6: (19009..19110); total length: 102; strand: plus
- exon 7: (26137..33470); total length: 7,334; strand: plus.
Transcription results in 22 different mRNAs (20 alternatively spliced variants and 2 unspliced forms). Despite the very high number of different CD59 transcripts, most of them vary at their 5 and/or 3 ends and encode a unique CD59 protein. However, different splicing variants have alternative promoters and stabilising sequences which is likely to affect the expression level of the protein.

CD59 is a 128aa-long protein. No polymorphisms have been described in the protein coding sequence of the CD59 gene. All transcription variants of CD59 result in the synthesis of a single CD59 protein with molecular mass between 18 and 22 kDa, depending on the level of glycosylation. CD59 has sites for both N- and O-glycosylation.

CD59 is expressed in all organs and in almost all cell types. It is essential to protect cells from self-destruction by complement-mediated lysis. The highest expression in humans has been detected in cardiomyocytes and smooth muscles (Su et al., 2004). Some nucleated blood cells (CD14 monocytes, T cells) either lack CD59 expression or express it very low which makes them highly susceptible to complement lysis.

CD59 is expressed on the surface of cells. It is attached to the cellular membrane via a glycosylphosphatidylinositol tail (GPI-anchored molecule). In urine, CD59 can be found as soluble protein.

The major and well-studied role of CD59 protein is to protect cells from self-destruction by our complement system. CD59 is the only membrane-bound inhibitor of the terminal pathway of complement cascade. However, in more recent years, some other functions of CD59 were described. CD59 was found to attenuate angiogenesis by preventing the complement-mediated lysis of newly grown blood vessels (Ekdahl et al., 2006). In addition, it was found that via CD59, the LPS signal is transduced into the nucleus via NF-kappaB activation inducing cytokine generation (Yamamoto et al., 2003).

CD59 protein does not show significant homology with other proteins. However, there is a high cross-primates homology for CD59. Human CD59 has 84% homology with CD59 in Macaca fascicularis and 91% homology in Pongo abelii (BLAST search). Homology between human CD59 protein and CD59 in rodents, however, is less than 50% (BLAST analysis).

No polymorphisms have been described for CD59 gene which affect the protein sequence. However, analysis of the sequence of the human CD59 gene revealed the presence of a (GT)19 dinucleotide repeat ~800bp upstream from exon 1 (Nöthen and Dewald, 1995). This polymorphism might affect expression and/or stability of CD59 transcripts, however, there is no experimental information on this matter.
A mutation in another gene, PIGA gene, however, indirectly results in lack of CD59 on red blood cells (RBCs). This condition is called paroxysmal nocturnal haemoglobinuria (PNH) and is a clonal disorder of RBCs. As a result of defective PIGA function, affected RBCs lack all GPI-linked membrane proteins, including CD59. The lack of CD59 renders PNH-RBCs susceptible to autologous complement lysis (Botto et al., 2009).

Chromosomal in situ hybridization and pulsed field gel electrophoresis mapped the CD59 gene to 11p13, distal to the breakpoint of acute TCL2 (T-Cell Leukemia) and proximal to the Wilms tumor gene (WT1) (Heckl-Ostreicher et al., 1993).