The saposin B-type domain is a ~80 amino acid domain present in saposins and related proteins that interact with lipids. The domain is named after the small lysosomal proteins, saposins, which serve as sphingolipid hydrolase activator proteins in vertebrates. The mammalian saposins are synthesized as a single precursor molecule (prosaposin) which contains two saposin A-type domains in the extremities that are removed in the activation reaction (see <PDOC51110>), and four saposin B-type domains yielding the active saposins A, B, C and D after proteolytic cleavage. Saposin-like proteins (SAPLIPs) can have different functions, such as enzymatic activities, as cofactors of enzymes involved in lipid metabolism, as components of lung surfactant reducing the surface tension, as part of a complex involved in stage regulation of Dictyostelium, as antimicrobial effector molecules, or as a stimulator of dendritic outgrowth [1,2,3,4].

The 3D structures of different SAPLIPs have been resolved, and show that the saposin B-type domain is formed by a four/five helical bundle (see <PDB:1SN6>). The saposin B-type domain is characterized by six conserved cysteine residues involved in three disulfide bridges: one between helices 2 and 3, one between the first and the last helix and one from the N-terminal part of the first helix to the C-terminus. In plant aspartic proteinases the two subdomains that are connected by the disulfide bridges occur in inversed order, these are called "swaposin" domains [5,6,7]. In these phytepsin proteins the two half saposin B-type domains occur in combination with the aspartyl protease signature (see <PDOC00128>) [3,8].

Some proteins known to contain a saposin B-type domain:

• Mammalian proactivator polypeptide, the saposin precursor (prosapin) that is processed into saposins A, B, C and D. Saposins A and C bind as activating cofactors to β-glucosylceramidase and galactosylceramidase. Saposin B facilitates the hydrolysis of cerebroside sulfate by arylsulfatase A. Saposin D is a specific sphingomyelin phosphodiesterase activator.
• Mammalian acid sphingomyelinase, an enzyme activated by saposins B and D, which converts sphingomyelin to ceramide.
• Mammalian acyloxyacyl-hydrolase, an enzyme which removes the secondary fatty acyl chains from the lipid A region of bacterial lipopolysaccharides.
• Mammalian pulmonary surfactant-associated protein B (SP-B), a surface tension reducing surfactant secreted by type II epithelial cells.
• Mammalian lymfocyte proteins NK-lysin and granulysin, antimicrobial effector molecules from natural killer cells and T-cells.
• Entamoeba histolytica amoebapores, membrane-interacting pore-forming proteins with a key role in the pathogenicity of amoeba.
• Plant aspartic proteases related to cyprosin and phytepsin. These proteins have a peculiar saposin B-type domain where the two halves are "swapped".
• Dictyostelium discoideum countin, an inhibitor of glucose-6-phosphatase and a component of the secreted counting factor complex (CF) involved in cell group size regulation.
• Mammalian MIR-interacting saposin-like protein (MSAP), a positive regulator of neurite outgrowth.

The profile we developed covers the entire saposin B-type domain and has been manually adapted to detect the two halves of the "swaposin" domain and to accept inserts like in MSAP.