| Literature References | 1. DEWJI, N., WENGER, D., FUJINAYASHI, S., DONOVIEL, M., ESCH, F., HILL, F.
AND O'BRIEN, J.S.
Molecular cloning of the sphingolipid activator protein-1 (SAP-1), the
sulfatide sulfatase activator.
BIOCHEM.BIOPHYS.RES.COMMUN. 134 989-994 (1986).
2. RORMAN, E.G. AND GRABOWSKI, G.A.
Molecular cloning of a human co-beta-glucosidase cDNA: evidence that four
sphingolipid hydrolase activator proteins are encoded by single genes in
humans and rats.
GENOMICS 5 486-492 (1989).
3. HOLTSCHMIDT, H., SANDHOFF, K., KWON, H.Y., HARZER, K., NAKANO, T. AND
SUZUKI, K.
Sulfatide activator protein. Alternative splicing that generates three mRNAs
and a newly found mutation responsible for a clinical disease.
J.BIOL.CHEM. 266 7556-7560 (1991).
4. HERBST, R., OTT, C., JACOBS, T., MARTI, T., MARCIANO-CABRAL, F. AND
LIEPPE, M.
Pore-forming peptides of the pathogenic protozoan Naegleria fowleri.
J.BIOL.CHEM. 277 22353-22360 (2002).
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| Documentation | Sphingolipids are bioactive compounds found in lower and higher eukaryotes.
They are involved in the regulation of various cellular functions, such as
growth, differentiation and apoptosis, and are believed to be essential in
a healthy diet [1]. Sphigolipids are degraded in the lysosome, and the
products from their hydrolysis are used in other biosynthetic and regulatory
pathways in the host [1].
There are a number of lysosomal enzymes involved in the breakdown of
sphinogolipids, and these act in sequence to degrade the moieties [2].
These enzymes require co-proteins called sphingolipid activator proteins,
(SAPs or saposins), to stabilise and activate them as necessary [2]. SAPs
are non-enzymic and usually have a low molecular weight. They are conserved
across a wide range of eukaryotes and contain specific saposin domains that
aid in the activation of hydrolase enzymes [3]. There have been four human
saposins described so far, sharing significant similarity with each other
and with other euakaryotic SAP proteins [3].
Mutations in SAP genes have been linked to a number of conditions. A defect
in the saposin B region leads to metachromatic leucodystrophy (MLD), while
a single nucleotide polymorphism in the SAP-C region may give rise to
Gaucher disease [3]. More recently, an opportunistic protozoan parasite
protein has shown similarity both to the higher and lower eukaryotic
saposins [4]. The pore-forming protein isolated from virulent Naegleria
fowleri trophoziotes has been dubbed Naegleriapore A. It also shares
structural similarity with cytolytic bacterial peptides, although this
similarity does not extend to the sequence level [4].
SAPOSINA is a 13-element fingerprint that provides a signature for the
saposin family. The fingerprint was derived from an initial alignment of
6 sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length - motifs 1-2 encode the first propeptide; motifs
3-4 span the saposin A domain; motif 5 encodes the second propeptide; motifs
6-7 span the saposin B domain; motifs 8-9 span the saposin C domain; motifs
10-12 span the saposin D domain; and motif 13 encodes the third propeptide.
Two iterations on SPTR40_20f were required to reach convergence, at which
point a true set comprising 7 sequences was identified. Several partial
matches were also found, all of which are related saposins, surfactant
proteins and Naegleriapore A pore-forming proteins that fail to match 7 or
more motifs.
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