Coding of two sphingolipid activator proteins (SAP-1 and SAP-2) by same genetic locus.
Several complementary DNAs (cDNAs) coding for sphingolipid activator protein-2 (SAP-2) were isolated from a lambda gt-11 human hepatoma library by means of polyclonal antibodies. The nucleotide sequence of the largest cDNA was colinear with the derived amino acid sequence of SAP-2 and with the nucleotide sequence of the cDNA coding for the 70-kilodalton precursor of SAP-1 (SAP precursor cDNA). The coding sequence for mature SAP-2 was located 3' to that coding for SAP-1 in the SAP precursor cDNA. Both SAP-1 and SAP-2 appeared to be derived by proteolytic processing from a common precursor that is coded by a genetic locus on human chromosome 10. Two other domains similar to SAP-1 and SAP-2 were also identified in SAP precursor protein. Each of the four domains was approximately 80 amino acid residues long, had nearly identical placement of cysteine residues, potential glycosylation sites, and proline residues. Each domain also contained internal amino acid sequences capable of forming amphipathic helices separated by helix breakers to give a cylindrical hydrophobic domain that is probably stabilized by disulfide bridges. Protein immunoblotting experiments indicated that SAP precursor protein (70 kilodaltons) as well as immunoreactive SAP-like proteins of intermediate sizes (65, 50, and 31 kilodaltons) are present in most human tissues.
O'Brien
J S
JS
Department of Neurosciences, University of California, San Diego, La Jolla 92093.
Kretz
K A
KA
Dewji
N
N
Wenger
D A
DA
Esch
F
F
Fluharty
A L
AL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000032:analysis; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000032:analysis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D011487:Protein Conformation; D011498:Protein Precursors / Q000032:analysis / Q000235:genetics; D011499:Protein Processing, Post-Translational; D051381:Rats; D049231:Saposins; D049128:Sphingolipid Activator Proteins; D014018:Tissue Distribution
D006023:Glycoproteins; C483345:PSAP protein, human; D011498:Protein Precursors; C483344:Psap protein, mouse; C483347:Psap protein, rat; D049231:Saposins; D049128:Sphingolipid Activator Proteins; D004247:DNA