• 1F-5Ag
• H19
• HRF20
• MACIF
• MIRL
• P-18
• Protectin

MAJOR LINKS FOR CD59  

• NCBI LocusLink Record: 966
• Mendelian Inheritance in Man (OMIM): 107271
• SwissProt annotated protein record: P13987

• Associates with C9, inhibiting incorporation into C5b-8 preventing terminal steps in polymerization of the (MAC) in plasma membranes

CELLULAR FUNCTION OF CD59  

• CD59 inhibits formation of membrane attack complex (MAC), thus protecting cells from complement mediated lysis
• Has a signaling role, as a GPI-anchored molecule, in T cell activation
• Appears to have some role in cell adhesion through CD2 (controversial)

DISEASE RELEVANCE OF CD59 AND FUNCTION OF CD59 IN INTACT ANIMAL  

• Genetic defects in GPI-anchor attachment that cause a reduction or loss of both CD59 and CD55 on erythrocytes produce the symptoms of the disease paroxysmal nocturnal hemoglobinuria (PNH)*
• Transgenic mice, rats and pigs have been made to study xenotransplantation
• CD59 is incorporated in HIV envelope and protects virus and HIV infected cells against complement deposition

• Families in which CD59 is a member
  • CD59-->Glycosyl phosphatidyl inositol anchored
• MEMBERS of CD59
  • Ly6 superfamily

MOLECULAR STRUCTURE OF CD59  

• Single chain, glycosylphosphatidylinositol (GPI)-anchored cell surface protein
• Structurally related to snake venom neurotoxins
• Five disulfide bonds, shown by NMR to be: 1-5; 2-3; 4-6; 7-8; 9-10
• Described from NMR studies as a relatively flat, disk-shaped molecule, with a 2-stranded beta-sheet finger loosely packed against a core formed by a 3-stranded beta-sheet and a short helix

MOLECULAR MASS OF CD59  

POST-TRANSCRIPTIONAL MODIFICATION OF CD59   - No information

POST-TRANSLATIONAL MODIFICATION OF CD59  

• Residue 18 used as site for N-glycanation (Yu et al, J Exp Med 185:745, 1997; and Suzuki et al, FEBS Lett 399:272, 1996)*
• N-glycanation not essential for function by mutagenesis studies

SUBSTRATES FOR CD59   - No information

ENZYMES WHICH MODIFY CD59   - No information

LIGANDS FOR CD59 AND MOLECULES ASSOCIATED WITH CD59  

• Possible interaction with CD2. Some studies demonstrate this by adhesion, by blocking antibodies and recombinant protein*

• Widely expressed on cells in all tissues
• Expression on erythrocytes is important for their survival

• CD59 has been widely studied because of its roles in paroxysmal nocturnal hemoglobinuria and kinase signaling as a GPI-anchored protein. Homologous proteins have been found in many mammalian species, and most function less efficiently with complement components obtained from non-homologous species. It is highly efficient at protecting cells through inhibition of MAC formation, and can be viewed as "catching" inappropriately activated complement that has escaped the multiple inhibitors at the C3/C5 amplification steps. The role of the GPI-anchor in CD59 function appears to have not been fully studied yet

SELECTION OF OTHER CD59-SPECIFIC REFERENCE MAB  

REVIEWS

1. Davies A,Lachmann PJ Membrane defence against complement lysis: the structure and biological properties of CD59. Immunol Res 1993 12:258 PubMed

2. Lachmann PJ The control of homologous lysis. Immunol Today 1991 12:312 PubMed

3. Liszewski MK,Farries TC,Lublin DM,Rooney IA,Atkinson JP Control of the complement system. Adv Immunol 1996 61:201 PubMed

4. Venneker GT,Asghar SS CD59: a molecule involved in antigen presentation as well as downregulation of membrane attack complex. Exp Clin Immunogenet 1992 9:33 PubMed

5. Walsh LA,Tone M,Thiru S,Waldmann H The CD59 antigen--a multifunctional molecule. Tissue Antigens 1992 40:213 PubMed

PRIMARY CITATIONS

6. Bickmore WA,Longbottom D,Oghene K,Fletcher JM,van Heyningen V Colocalization of the human CD59 gene to 11p13 with the MIC11 cell surface antigen. Genomics 1993 17:129 PubMed

7. Byrne GW,McCurry KR,Martin MJ,McClellan SM,Platt JL,Logan JS Transgenic pigs expressing human CD59 and decay-accelerating factor produce an intrinsic barrier to complement-mediated damage. Transplantation 1997 63:149 PubMed

8. Cerny J,Stockinger H,Horejsi V Noncovalent associations of T lymphocyte surface proteins. Eur J Immunol 1996 26:2335 PubMed

9. Holguin MH,Martin CB,Eggett T,Parker CJ Analysis of the gene that encodes the complement regulatory protein, membrane inhibitor of reactive lysis (CD59). Identification of an alternatively spliced exon and characterization of the transcriptional regulatory regions of the promoter. J Immunol 1996 157:1659 PubMed

10. Husler T,Lockert DH,Sims PJ Role of a disulfide-bonded peptide loop within human complement C9 in the species-selectivity of complement inhibitor CD59. Biochemistry 1996 35:3263 PubMed

11. Kieffer B,Driscoll PC,Campbell ID,Willis AC,van der Merwe PA,Davis SJ 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 1994 33:4471 PubMed

12. Kroshus TJ,Bolman RM III,Dalmasso AP,Rollins SA,Guilmette ER,Williams BL,Squinto SP,Fodor WL Expression of human CD59 in transgenic pig organs enhances organ survival in an ex vivo xenogeneic perfusion model. Transplantation 1996 61:1513 PubMed

13. Meri S,Waldmann H,Lachmann PJ Distribution of protectin (CD59), a complement membrane attack inhibitor, in normal human tissues. Lab Invest 1991 65:532 PubMed

14. Solomon KR,Rudd CE,Finberg RW The association between glycosylphosphatidylinositol-anchored proteins and heterotrimeric G protein alpha subunits in lymphocytes. Proc Natl Acad Sci U S A 1996 93:6053 PubMed

15. Spear GT,Lurain NS,Parker CJ,Ghassemi M,Payne GH,Saifuddin M Host cell-derived complement control proteins CD55 and CD59 are incorporated into the virions of two unrelated enveloped viruses. Human T cell leukemia/lymphoma virus type I (HTLV-I) and human cytomegalovirus (HCMV). J Immunol 1995 155:4376 PubMed

16. Venneker GT,Das PK,Meinardi MM,van Marle J,van Veen HA,Bos JD,Asghar SS Glycosylphosphatidylinositol (GPI)-anchored membrane proteins are constitutively down-regulated in psoriatic skin. J Pathol 1994 172:189 PubMed

17. Yu J,Abagyan R,Dong S,Gilbert A,Nussenzweig V,Tomlinson S Mapping the active site of CD59. J Exp Med 1997 185:745 PubMed

18. van den Berg CW,Cinek T,Hallett MB,Horejsi V,Morgan BP Exogenous glycosyl phosphatidylinositol-anchored CD59 associates with kinases in membrane clusters on U937 cells and becomes Ca(2+)-signaling competent. J Cell Biol 1995 131:669 PubMed

19. van den Berg CW,Morgan BP Complement-inhibiting activities of human CD59 and analogues from rat, sheep, and pig are not homologously restricted. J Immunol 1994 152:4095 PubMed

WWW RESOURCES

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99   mpr@mail.nih.gov