| SMART accession number: | SM00162
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| Description: |
Present as four and three degenerate copies, respectively, in prosaposin and surfactant protein B. Single copies in acid sphingomyelinase, NK-lysin amoebapores and granulysin. Putative phospholipid membrane binding domains. |
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| Interpro abstract (IPR003119): |
Saposins are small lysosomal proteins that serve as activators of various lysosomal lipid-degrading enzymes [(PUBMED:7595087)]. They probably act by isolating the lipid substrate from the membrane surroundings, thus making it more accessible to the soluble degradative enzymes. All mammalian saposins are synthesized as a single precursor molecule (prosaposin) which contains four Saposin-B domains, yielding the active saposins after proteolytic cleavage, and two Saposin-A domains that are removed in the activation reaction. The Saposin-B domains also occur in other proteins, many of them active in the lysis of membranes [(PUBMED:8003971), (PUBMED:8868085)]. The saposin A-type domain may play a role in targeting, as propeptides containing the saposin A-type domain of the C terminus of prosaposin and of the N-terminal part of pulmonary surfactant-associated protein B are involved in the transport to the lysosome and to secretory granules (lamellar bodies, which are lysosomal-like organelles), respectively [(PUBMED:8702672)].
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| Family alignment: |
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Click on the following links for more information.
- Evolution (species in which this domain is found)
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- Literature (relevant references for this domain)
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Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Liepinsh E, Andersson M, Ruysschaert JM, Otting G
- Saposin fold revealed by the NMR structure of NK-lysin.
- Nat Struct Biol. 1997; 4: 793-5
- Display abstract
NK-lysin is the first representative of a family of sequence related proteins--saposins, surfactant-associated protein B, pore forming amoeba proteins, and domains of acid sphingomyelinase, acyloxyacylhydrolase and plant aspartic proteinases--for which a structure has been determined.
- Ponting CP
- Acid sphingomyelinase possesses a domain homologous to its activator proteins: saposins B and D.
- Protein Sci. 1994; 3: 359-61
- Display abstract
An N-terminal region of the acid sphingomyelinase sequence (residues 89-165) is shown to be homologous to saposin-type sequences. By analogy with the known functions of saposins, this sphingomyelinase saposin-type domain may possess lipid-binding and/or sphingomyelinase-activator properties. This finding may prove to be important in the understanding of Niemann-Pick disease, which results from sphingomyelinase deficiency.
- Staab JF, Ginkel DL, Rosenberg GB, Munford RS
- A saposin-like domain influences the intracellular localization, stability, and catalytic activity of human acyloxyacyl hydrolase.
- J Biol Chem. 1994; 269: 23736-42
- Display abstract
Acyloxyacyl hydrolase, a leukocyte enzyme that acts on bacterial lipopolysaccharides (LPSs) and many glycerolipids, is synthesized as a precursor polypeptide that undergoes internal disulfide linkage before being proteolytically processed into two subunits. The larger subunit contains an amino acid sequence (Gly-X-Ser-X-Gly) that is found at the active sites of many lipases, while the smaller subunit has amino acid sequence similarity to saposins (sphingolipid activator proteins), cofactors for sphingolipid glycohydrolases. We show here that both acyloxyacyl hydrolase subunits are required for catalytic activity toward LPS and glycerophosphatidylcholine. In addition, mutations that truncate or delete the small subunit have profound effects on the intracellular localization, proteolytic processing, and stability of the enzyme in baby hamster kidney cells. Remarkably, proteolytic cleavage of the precursor protein increases the activity of the enzyme toward LPS by 10-20-fold without altering its activity toward glycerophosphatidylcholine. Proper orientation of the two subunits thus seems very important for the substrate specificity of this unusual enzyme.
- Patthy L
- Homology of the precursor of pulmonary surfactant-associated protein SP-B with prosaposin and sulfated glycoprotein 1.
- J Biol Chem. 1991; 266: 6035-7
- Display abstract
The precursor of pulmonary surfactant-associated protein, SP-B, is composed of an NH2-terminal domain of 30 residues (a-type domain) and three tandem repeats of about 90 residues (b-type domain); biophysically active mature SP-B corresponds to the second b-type repeat. Consensus sequences constructed for the b-type repeats were used to search the data base for homologous sequences, and the search has revealed that prosaposin and sulfated glycoprotein 1 show a remarkable homology with these repeats. The domain organizations of the latter proteins, however, differ from that of SP-B precursor inasmuch as they contain four tandem copies of the b-type domain and a-type domains are present both in the NH2-terminal and COOH-terminal parts of the proteins. The implications of the homology of saposins and SP-B for their structure and function are discussed.
- Links (links to other resources describing this domain)
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