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
- 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.
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see