| 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)
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| References: |
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.
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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.
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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.
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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.
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Fan, Y., Z. Feng, K. Fan, W. Yin, N. Sun, P. Sun, Y. Sun, and H. Li. (2023). [Procine recombinant NK-lysin inhibits hepatocellular carcinoma metastasis by downregulating FKBP3 and inhibiting oxidative phosphorylation and glycolysis: a proteomic analysis]. Nan Fang Yi Ke Da Xue Xue Bao 43: 1116-1126.
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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.
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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.
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Vaccaro, A.M., R. Salvioli, M. Tatti, and F. Ciaffoni. (1999). Saposins and their interaction with lipids. Neurochem Res 24: 307-314.
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Zhai, Y. and M.H. Saier Jr. (2000). The amoebapore superfamily. Biochim. Biophys. Acta 1469: 87-99.
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| Examples: |
| TC# | Name | Organismal Type | Example |
| 1.C.35.1.1 | Amoebapore A | Protozoans | Amoebapore A of Entamoeba histolytica |
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| 1.C.35.1.2 | Amoebapore B | Protozoans | Amoebapore B of Entamoeba histolytica |
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| 1.C.35.1.3 | Amoebapore C | Protozoans | Amoebapore C of Entamoeba histolytica |
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| 1.C.35.1.4 | Nonpathogenic pore-forming peptide precursor, APNP | Protozoans | APNP of Entamoeba histolytica |
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| 1.C.35.1.5 | Pore-forming protein-like protein of 79 aas, saposin B type, SapB
| | SapB of Steinernema carpocapsae (Entomopathogenic nematode) |
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| Examples: |
| TC# | Name | Organismal Type | Example |
| 1.C.35.2.1 | 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). | Mammals | CSAP of Homo sapiens |
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| 1.C.35.2.2 | 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) |
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| 1.C.35.2.3 | Saposin of 254 aas and 1 N-terminal TMS (Hao et al. 2010). | | Saposin of Steinernema carpocapsae (Entomopathogenic nematode) |
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| Examples: |
| TC# | Name | Organismal Type | Example |
| 1.C.35.3.1 | 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). Recombinant NK-lysin inhibits hepatocellular carcinoma metastasis by downregulating FKBP3 and inhibiting oxidative phosphorylation and glycolysis (Fan et al. 2023). | Mammals | NK lysin of Sus scrofa |
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| 1.C.35.3.2 | 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). | Mammals | Granulosin of Homo sapiens |
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| 1.C.35.3.3 | Antimicrobial peptide NK-lysin-like protein of 147 aas and 1 N-terminal TMS. It has two sequential domains, Saposin A (SapA) and SapB. | | NK-lysin-like protein of Grus japonensis (Red-crowned crane) |
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| 1.C.35.3.4 | Antimicrobial peptide NK-lysin isoform X1 of 240 aas and 1 N-terminal TMS. | | NK-lysin of Taeniopygia guttata (zebra finch) |
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| 1.C.35.3.5 | Uncharacterized protein of 268 aas and 2 TMSs, one N-terminal and one at about residue 140. | | UP of Albula glossodonta |
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| Examples: |
| TC# | Name | Organismal Type | Example |
| 1.C.35.4.1 | Countin of 258 aas with 1 N-terminal TMS. | Slime molds | Countin of Dictyostelium discoideum |
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| 1.C.35.4.2 | Countin3 of 237 aas and 1 or 2 TMSs, one at the N-terminus and the second at about residue 80. | | Countin3 of Cavenderia fasciculata |
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| 1.C.35.4.3 | Uncharacterized protein of 413 aas and 4 clear peaks of hydrophobicity between residues 50 and 200. | | UP of Rotaria sp. Silwood1 |
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| 1.C.35.4.4 | Uncharacterized protein of 120 aas and possibly one TMS near the N-terminus. | | UP of Bugula neritina |
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| 1.C.35.4.5 | Uncharacterized protein of 176 aas and possibly 2 TMSs at about residies 80 and 120. | | UP of Naegleria fowleri |
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| 1.C.35.4.6 | Uncharacterized protein of 237 aas and one N-terminal TMS. | | UP of Lottia gigantea (owl limpet) |
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