Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
GoGreen Membership

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 26 August 1988:
Vol. 241. no. 4869, pp. 1098 - 1101
DOI: 10.1126/science.2842863
Prev | Table of Contents | Next

Articles

Science, Vol 241, Issue 4869, 1098-1101
Copyright © 1988 by American Association for the Advancement of Science

articles

Coding of two sphingolipid activator proteins (SAP-1 and SAP-2) by same genetic locus

JS O'Brien, KA Kretz, N Dewji, DA Wenger, F Esch, and AL Fluharty

Department of Neurosciences, University of California, San Diego, La Jolla 92093.

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.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Neurological deficits and glycosphingolipid accumulation in saposin B deficient mice.
Y. Sun, D. P. Witte, H. Ran, M. Zamzow, S. Barnes, H. Cheng, X. Han, M. T. Williams, M. R. Skelton, C. V. Vorhees, et al. (2008)
Hum. Mol. Genet. 17, 2345-2356
   Abstract »    Full Text »    PDF »
Combined saposin C and D deficiencies in mice lead to a neuronopathic phenotype, glucosylceramide and {alpha}-hydroxy ceramide accumulation, and altered prosaposin trafficking.
Y. Sun, D. P. Witte, M. Zamzow, H. Ran, B. Quinn, J. Matsuda, and G. A. Grabowski (2007)
Hum. Mol. Genet. 16, 957-971
   Abstract »    Full Text »    PDF »
Progressive Deafness and Altered Cochlear Innervation in Knock-Out Mice Lacking Prosaposin.
O. Akil, J. Chang, H. Hiel, J.-H. Kong, E. Yi, E. Glowatzki, and L. R. Lustig (2006)
J. Neurosci. 26, 13076-13088
   Abstract »    Full Text »    PDF »
Conditional expression of human acid {beta}-glucosidase improves the visceral phenotype in a Gaucher disease mouse model.
Y. Sun, B. Quinn, Y.-H. Xu, T. Leonova, D. P. Witte, and G. A. Grabowski (2006)
J. Lipid Res. 47, 2161-2170
   Abstract »    Full Text »    PDF »
Gaucher disease mouse models: point mutations at the acid {beta}-glucosidase locus combined with low-level prosaposin expression lead to disease variants.
Y. Sun, B. Quinn, D. P. Witte, and G. A. Grabowski (2005)
J. Lipid Res. 46, 2102-2113
   Abstract »    Full Text »    PDF »
Saposin C Is Required for Normal Resistance of Acid {beta}-Glucosidase to Proteolytic Degradation.
Y. Sun, X. Qi, and G. A. Grabowski (2003)
J. Biol. Chem. 278, 31918-31923
   Abstract »    Full Text »    PDF »
The Lysosomal Transport of Prosaposin Requires the Conditional Interaction of Its Highly Conserved D Domain with Sphingomyelin.
S. Lefrancois, T. May, C. Knight, D. Bourbeau, and C. R. Morales (2002)
J. Biol. Chem. 277, 17188-17199
   Abstract »    Full Text »    PDF »
J3-crystallin of the jellyfish lens: Similarity to saposins.
J. Piatigorsky, B. Norman, L. J. Dishaw, L. Kos, J. Horwitz, P. J. Steinbach, and Z. Kozmik (2001)
PNAS 98, 12362-12367
   Abstract »    Full Text »    PDF »
Sphingolipid activator proteins: proteins with complex functions in lipid degradation and skin biogenesis.
C. G. Schuette, B. Pierstorff, S. Huettler, and K. Sandhoff (2001)
Glycobiology 11, 81R-90R
   Abstract »    Full Text »    PDF »
A novel mutation in the coding region of the prosaposin gene leads to a complete deficiency of prosaposin and saposins, and is associated with a complex sphingolipidosis dominated by lactosylceramide accumulation.
H. Hulkova, M. Cervenkova, J. Ledvinova, M. Tochackova, M. Hrebicek, H. Poupetova, A. Befekadu, L. Berna, B.C. Paton, K. Harzer, et al. (2001)
Hum. Mol. Genet. 10, 927-940
   Abstract »    Full Text »    PDF »
Retro-Inverso Prosaptide Peptides Retain Bioactivity, Are Stable In Vivo, and Are Blood-Brain Barrier Permeable.
E. M. Taylor, D. A. Otero, W. A. Banks, and J. S. O'Brien (2000)
J. Pharmacol. Exp. Ther. 295, 190-194
   Abstract »    Full Text »
Processing, Activity, and Inhibition of Recombinant Cyprosin, an Aspartic Proteinase from Cardoon (Cynara cardunculus).
P. C. White, M. C. Cordeiro, D. Arnold, P. E. Brodelius, and J. Kay (1999)
J. Biol. Chem. 274, 16685-16693
   Abstract »    Full Text »    PDF »
Role of Sp Proteins and RORalpha in Transcription Regulation of Murine Prosaposin.
P. Jin, Y. Sun, and G. A. Grabowski (1998)
J. Biol. Chem. 273, 13208-13216
   Abstract »    Full Text »    PDF »
Effect of Saposins A and C on the Enzymatic Hydrolysis of Liposomal Glucosylceramide.
A. M. Vaccaro, M. Tatti, F. Ciaffoni, R. Salvioli, A. Barca, and C. Scerch (1997)
J. Biol. Chem. 272, 16862-16867
   Abstract »    Full Text »    PDF »
Biosynthesis, Processing, and Intracellular Transport of GM2 Activator Protein in Human Epidermal Keratinocytes. THE LYSOSOMAL TARGETING OF THE GM2 ACTIVATOR IS INDEPENDENT OF A MANNOSE-6-PHOSPHATE SIGNAL.
G. J. Glombitza, E. Becker, H. W. Kaiser, and K. Sandhoff (1997)
J. Biol. Chem. 272, 5199-5207
   Abstract »    Full Text »    PDF »
Biosynthesis, Processing, and Targeting of Sphingolipid Activator Protein (SAP )Precursor in Cultured Human Fibroblasts. MANNOSE 6-PHOSPHATE RECEPTOR-INDEPENDENT ENDOCYTOSIS OF SAP PRECURSOR.
G. Vielhaber, R. Hurwitz, and K. Sandhoff (1996)
J. Biol. Chem. 271, 32438-32446
   Abstract »    Full Text »    PDF »
Proteolytic Processing Patterns of Prosaposin in Insect and Mammalian Cells.
T. Leonova, X. Qi, A. Bencosme, E. Ponce, Y. Sun, and G. A. Grabowski (1996)
J. Biol. Chem. 271, 17312-17320
   Abstract »    Full Text »    PDF »
Characterization of an Alternatively Spliced G[IMAGE] Activator Protein, G[IMAGE] Protein.
Y. Y. Wu, S. Sonnino, Y.-T. Li, and S.-C. Li (1996)
J. Biol. Chem. 271, 10611-10615
   Abstract »    Full Text »    PDF »
Expression of the Three Alternative Forms of the Sphingolipid Activator Protein Precursor in Baby Hamster Kidney Cells and Functional Assays in a Cell Culture System.
M. Henseler, A. Klein, G. J. Glombitza, K. Suziki, and K. Sandhoff (1996)
J. Biol. Chem. 271, 8416-8423
   Abstract »    Full Text »    PDF »
Functional Organization of Saposin C.
X. Qi, W. Qin, Y. Sun, K. Kondoh, and G. A. Grabowski (1996)
J. Biol. Chem. 271, 6874-6880
   Abstract »    Full Text »    PDF »
Specific Recognition of N-Acetylneuraminic Acid in the G[IMAGE] Epitope by Human G[IMAGE] Activator Protein.
S.-C. Li, Y.-Y. Wu, E. Sugiyama, T. Taki, T. Kasama, R. Casellato, S. Sonnino, and Y.-T. Li (1995)
J. Biol. Chem. 270, 24246-24251
   Abstract »    Full Text »    PDF »
Structural Analysis of Saposin C and B.
A. M. Vaccaro, R. Salvioli, A. Barca, M. Tatti, F. Ciaffoni, B. Maras, R. Siciliano, F. Zappacosta, A. Amoresano, and P. Pucci (1995)
J. Biol. Chem. 270, 9953-9960
   Abstract »    Full Text »    PDF »
Identification of a Novel Sequence Involved in Lysosomal Sorting of the Sphingolipid Activator Protein Prosaposin.
Q. Zhao and C. R. Morales (2000)
J. Biol. Chem. 275, 24829-24839
   Abstract »    Full Text »    PDF »
Differential Membrane Interactions of Saposins A and C. IMPLICATIONS FOR THE FUNCTIONAL SPECIFICITY.
X. Qi and G. A. Grabowski (2001)
J. Biol. Chem. 276, 27010-27017
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)