| 1.C.67 The SphH Hemolysin (SphH) Family The Leptospira interrogans hemolysin, SphH, also called sphingomyelinase C precursor, does not hydrolyze phospholipids or sphingomyelin although homologues do (Lee et al., 2002). Instead, it exhibits hemolysis activity on erythrocytes and forms pores in several mammalian cell types, accounting in part for its toxic activity (Lee et al., 2002). Morphological pore-like structures in the membranes of sheep erythrocytes could be seen by transmission electron microscopy (Lee et al., 2002). SphH is 554 aas in length and exhibits a single hydrophobic TMS at its N-terminus, probably a cleavable leader sequence. Otherwise it is a hydrophilic protein. It is homologous to a variety of sphingomyelinases, phospholipases and β-hemolysins (β-toxins) from a wide range of Gram-negative and Gram-positive bacteria. Distant homologues are also present in eukaryotes. The transport reaction catalyzed by pore-forming SphH is: large and small molecules (in)  molecules (out)
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| References: |
Lee, S.H., S. Kim, S.C. Park, and M.J. Kim. (2002). Cytotoxic activities of Leptospira interrogans hemolysin SphH as a pore-forming protein on mammalian cells. Infect. Immun. 70: 315-322.
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Li, Q., N. Chen, C. Liu, Z. Zhao, M. Huang, J. Li, and G. Yang. (2025). β-hemolysin impairs oxygen transport without causing hemolysis. Virulence 16: 2490208.
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| Examples: |
| TC# | Name | Organismal Type | Example |
| 1.C.67.1.1 | The pore-forming hemolysin, SphH | Bacteria | SphH of Leptospira interrogans (AAB68647) |
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| 1.C.67.1.2 | Uncharacterized protein of 380 aas homologous to pyrophosphatases such as sphingomyelinases. | Amoebozoa | UP of Entamoeba histolytica |
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| 1.C.67.1.3 | Phospholipase C, Hlb, of 330 aas. Bacterial hemolysins are exotoxins that attack blood cell membranes and
cause cell rupture. Beta-hemolysin is a phospholipase C with specific
activity toward sphingomyelins. It has a high specificity for
sphingomyelin, hydrolyzes lysophosphatidylcholine at a much lower rate,
but has no activity towards phosphatidylcholine,
phosphatidylethanolamine, or phosphatidylserine. S. aureus β-hemolysin impairs oxygen transport without causing hemolysis. A novel role for Hlb as a sphingomyelinase in impairing RBC function under
non-lytic conditions, sheds light on the mechanism behind hypoxia
associated with S. aureus infection (Li et al. 2025). | | Hlb of Staphylococcus aureus |
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