The domain within your query sequence starts at position 27 and ends at position 60; the E-value for the SAPA domain shown below is 1.27e-16.
SSLECAQGPQFWCQSLEHAVQCRALGHCLQEVWG
SAPA
Saposin/surfactant protein-B A-type DOMAIN
SMART accession number:
SM00162
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.
The saposin A-type domain is a ~40 amino acid domain present in the saposin precursor, prosaposin, in the propeptides that are cleaved off in the activation reaction. 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 four saposin B-type domains yielding the active saposins A, B, C and D after proteolytic cleavage, and two saposin A-type domains in the extremities that are removed in the activation reaction. 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:11856752) (PUBMED:8702672) ].
Some proteins known to contain a saposin A-type domain:
Mammalian proactivator polypeptide, the saposin precursor (prosaposin) that is processed into saposins A, B, C and D.
Mammalian pulmonary surfactant-associated protein B (SP-B), a surface tension reducing surfactant secreted by type II epithelial cells.
Family alignment:
There are 1737 SAPA domains in 1080 proteins in SMART's nrdb database.
Click on the following links for more information.
Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing SAPA domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with SAPA domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing SAPA domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
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.
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.
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.
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)
