1.C.35 The Amoebapore (Amoebapore) Family

Amoebapores are protein capable of forming ion channels (pores) in lipid membranes. They are synthesized by the human protozoan parasite, Entamoeba histolytica, the causative agent of amoebiasis. The major pathogenic effect of E. histolytica is its cytolytic capability which is due to amoebapore which kills target cells. Three isoforms of amoebapore have been isolated and characterized biochemically. The mature proteins are 77-88 amino acids in length, although the precursor proteins are larger. Active peptides are present inside cytoplasmic granules of the amoeba trophozoite. Release allows amoebapore to be inserted into the membrane of a target cell without dependency on a specific receptor. The inserted amoebapore protein oligomerizes to form ion channels which lyse the cell. Distant homologues are found in mammals and slime molds. For example, NK-lysin is an effector peptide of cytolytic T-cells and natural killer (NK) cells. Its synthesis is induced by interleukin 2, and it exhibits antibacterial, antifungal, and antitumor activities.

The amoebapore superfamily includes in addition to the amoebapores (1) the saposins, (2) the NK-lysins and granulysins, (3) the pulmonary surfactant proteins B, (4) the acid sphingomyelinases, (5) acyloxyacyl hydrolases and (6) the aspartic proteases. These amoebapore homologues have many properties in common including membrane binding and stability. A new protein, countin, from the cellular slime mold, Dictyostelium discoideum, comprises the eighth family within this superfamily. Most of these other families includes proteins that have not been shown to function in pore-formation.

The generalized transport reaction catalyzed by amoebapores and their homologues is:

Small molecules (in) Small molecules (out)



Andersson, M., H. Gunne, B. Agerberth, A. Boman, T. Bergman, B. Olsson, A. Dagerlind, H. Wigzell, H.G. Boman, and G.H. Gudmundsson. (1996). NK-lysin, structure and function of a novel effector molecule of porcine T and NK cells. Vet Immunol Immunopathol 54: 123-126.

Andersson, M., H. Gunne, B. Agerberth, A. Boman, T. Bergman, R. Sillard, H. Jörnvall, V. Mutt, B. Olsson, and H. Wigzell (1995). NK-lysin, a novel effector peptide of cytotoxic T and NK cells. Structure and cDNA cloning of the porcine form, induction by interleukin 2, antibacterial and antitumour activity. EMBO J. 14: 1615-1625.

Bracha, R., Y. Nuchamowitz, M. Leippe and D. Mirelman (1999). Antisense inhibition of amoebapore expression in Entamoeba histolytica causes a decrease in amoebic virulence. Mol. Microbiol. 34: 463-472.

Dotiwala, F., S. Mulik, R.B. Polidoro, J.A. Ansara, B.A. Burleigh, M. Walch, R.T. Gazzinelli, and J. Lieberman. (2016). Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites. Nat. Med. 22: 210-216.

Hao, Y.J., R. Montiel, S. Abubucker, M. Mitreva, and N. Simões. (2010). Transcripts analysis of the entomopathogenic nematode Steinernema carpocapsae induced in vitro with insect haemolymph. Mol Biochem Parasitol 169: 79-86.

Hiraiwa, M., W.M. Campana, A.P. Mizisin, L. Mohiuddin, and J.S. O''Brien. (1999). Prosaposin: a myelinotrophic protein that promotes expression of myelin constituents and is secreted after nerve injury. Glia 26: 353-360.

Vaccaro, A.M., R. Salvioli, M. Tatti, and F. Ciaffoni. (1999). Saposins and their interaction with lipids. Neurochem Res 24: 307-314.

Zhai, Y. and M.H. Saier Jr. (2000). The amoebapore superfamily. Biochim. Biophys. Acta 1469: 87-99.


TC#NameOrganismal TypeExample
1.C.35.1.1Amoebapore A Protozoans Amoebapore A of Entamoeba histolytica
1.C.35.1.2Amoebapore B Protozoans Amoebapore B of Entamoeba histolytica
1.C.35.1.3Amoebapore C Protozoans Amoebapore C of Entamoeba histolytica
1.C.35.1.4Nonpathogenic pore-forming peptide precursor, APNP Protozoans APNP of Entamoeba histolytica

Pore-forming protein-like protein of 79 aas, saposin B type, SapB

SapB of Steinernema carpocapsae (Entomopathogenic nematode)


TC#NameOrganismal TypeExample

Cerebroside sulfate activator protein, CSAP or prosaposin (PSAP, GLBA, SAP1) of 524 aas. Saposin A, B, C and D are derived from prosaposin by proteolysis. Saposin-A and C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase and galactosylceramide by beta-galactosylceramidase. Saposin-C apparently acts by combining with the enzyme and acidic lipids to form an activated complex, rather than by solubilizing the substrate. Saposin-B stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A, GM1 gangliosides by β-galactosidase and globotriaosylceramide by α-galactosidase A. Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases. Saposin-D is a specific sphingomyelin phosphodiesterase activator. Prosaposin behaves as a myelinotrophic and neurotrophic factor; these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosphorylation signaling (Hiraiwa et al. 1999).


CSAP of Homo sapiens


Saposin-like protein (Saplip C; SalA) of 157 aas.  Important for lipid interactions and lysosomal degradation of several sphingolipids (Vaccaro et al. 1999).

Saplip C of Dictyostelium discoideum (Slime mold)


Saposin of 254 aas and 1 N-terminal TMS (Hao et al. 2010).

Saposin of Steinernema carpocapsae (Entomopathogenic nematode)


TC#NameOrganismal TypeExample

 Antimicrobial natural killer cell lysin, NK-lysin of 129 aas.  NK-lysin is involved in the inducible cytotoxicity of T and NK cells (Andersson et al. 1996).


NK lysin of Sus scrofa


Granulosin of 145 aas and 1 TMS.  Functions probably by pore-formation by natural killer (NK) and T lympocyces to combat intracellular parasites, both bacterial and eukaryotic (Dotiwala et al. 2016).


Granulosin of Homo sapiens


TC#NameOrganismal TypeExample
1.C.35.4.1Countin Slime molds Countin of Dictyostelium discoideum