The Evolutionary History of Prosaposin: Two Successive Tandem-Duplication Events Gave Rise to the Four Saposin Domains in Vertebrates

  title={The Evolutionary History of Prosaposin: Two Successive Tandem-Duplication Events Gave Rise to the Four Saposin Domains in Vertebrates},
  author={Einat Hazkani-Covo and Neta Altman and Mia Horowitz and Dan Graur},
  journal={Journal of Molecular Evolution},
Abstract. Prosaposin is a multifunctional protein encoded by a single-copy gene. It contains four saposin domains (A, B, C, and D) occurring as tandem repeats connected by linker sequences. Because the saposin domains are similar to one another, it is deduced that they were created by sequential duplications of an ancestral domain. There are two types of evolutionary scenarios that may explain the creation of the four-domain gene: (1) two rounds of tandem internal gene duplication and (2) three… 
Trichinella spiralis secretes a homologue of prosaposin.
Crystal structures of saposins A and C
The crystal structures of human saposins A and C are determined, and both reveal the compact, monomeric saposin fold, which is likely to be relevant to how these small proteins interact with lipids, membranes, and hydrolase enzymes.
Purified recombinant human prosaposin forms oligomers that bind procathepsin D and affect its autoactivation.
It is demonstrated that proSAP forms oligomers that are capable ofbinding proCD spontaneously and independent of the mammalian type N-glycosylation but not capable of binding mature cathepsin D.
Distribution of Prosaposin mRNA in the Central Nervous System of the Pigeon (Columba livia)
The results suggest that the cDNA sequence of pigeon prosaposin is comparable to other vertebrates, and the general distribution pattern of prosapOSin mRNA resembles those found in mammals.
A Saposin deficiency model in Drosophila: lysosomal storage, progressive neurodegeneration, sensory physiological decline and defective calcium homeostasis
Drosophila saposin-related (dSap-r) mutants show a reduced longevity, progressive neurodegeneration, lysosomal storage, dramatic swelling of neuronal soma, perturbations in sphingolipid catabolism, and sensory physiological deterioration, and a genetic interaction with a calcium exchanger (CalX), suggesting that calcium homeostasis may be altered in saPOSin deficiency.
A Tetrameric Assembly of Saposin A: Increasing Structural Diversity in Lipid Transfer Proteins
The crystal structure of a unique tetrameric assembly of murine saposin A produced serendipitously, following modifications of published protocols for making lipoprotein nanodiscs is presented.
Identification of testis-relevant genes using in silico analysis from testis ESTs and cDNA microarray in the black tiger shrimp (Penaeus monodon)
Identification and expression analysis of saposin and Dmc1 homologs demonstrate the power of expressed sequence tag (EST) and cDNA microarray analyses for characterizing functionally important genes in P. monodon.
Associations of polymorphisms in four immune-related genes with antibody kinetics and body weight in chickens.
It is demonstrated that the novel IFNG promoter SNP was associated with antibody kinetics for BA and SRBC in laying hens, and also with BW, suggesting that this cytokine may play a pivotal role in the relationship between immune function and growth.
Prosaposin mediates inflammation in atherosclerosis
Using myeloid cell–specific nanobiologics in apolipoprotein E–deficient mice, it was found that targeting the mTOR and ribosomal protein S6 kinase-1 (S6K1) signaling pathways rapidly diminished plaque macrophages’ inflammatory activity.


Structure and evolution of the human prosaposin chromosomal gene.
Saposin-like proteins (SAPLIP) carry out diverse functions on a common backbone structure.
It is proposed that three intradomain disulfide linkages create a common structural framework upon which amino acids in four amphipathic alpha helices can carry out diverse functions.
Conformational and amino acid residue requirements for the saposin C neuritogenic effect.
It is shown that the neuritogenic activity of saPOSin C requires specific placement of amino acids, and that Y30 of saposin A significantly alters local conformation in this critical region and suppresses neuritogens activity.
Lysosomal proteolysis of prosaposin, the precursor of saposins (sphingolipid activator proteins): its mechanism and inhibition by ganglioside.
The finding indicates that prosaposin may be protected from lysosomal proteolysis by forming a complex with gangliosides in vivo, and that, in addition to cathepsin D, other proteases appear to be involved in the maturation of saposin B, C, and D in lysOSomes.
SEAVIEW and PHYLO_WIN: two graphic tools for sequence alignment and molecular phylogeny
SEAVIEW and PHYLO_WIN are two graphic tools for X Windows-Unix computers dedicated to sequence alignment and molecular phylogenetics. SEAVIEW is a sequence alignment editor allowing manual or
The rapid generation of mutation data matrices from protein sequences
An efficient means for generating mutation data matrices from large numbers of protein sequences is presented, by means of an approximate peptide-based sequence comparison algorithm, which is fast enough to process the entire SWISS-PROT databank in 20 h on a Sun SPARCstation 1, and is fastenough to generate a matrix from a specific family or class of proteins in minutes.
Saposin proteins: structure, function, and role in human lysosomal storage disorders
  • J. O'brienY. Kishimoto
  • Chemistry, Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1991
Characterization of these four activator proteins, two of which were recently discovered, and their importance in human health and disease are reviewed, including their role in human lysosomal storage disorders.
Saposins (sap) A and C activate the degradation of galactosylceramide in living cells
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original.
Gaucher's disease: deficiency of 'acid' -glucosidase and reconstitution of enzyme activity in vitro.
  • M. HoJ. O'brien
  • Medicine, Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1971
The spleen from a patient with adult Gaucher's disease was shown to be deficient in a beta-glucosidase (EC isoenzyme that has optimal activity at pH 4.0-4.3, and is stimulated by 0.02%