Prosaposin

Details

Name
Prosaposin
Synonyms
  • GLBA
  • Proactivator polypeptide
  • SAP1
Gene Name
PSAP
Organism
Humans
Amino acid sequence
>lcl|BSEQ0002337|Prosaposin
MYALFLLASLLGAALAGPVLGLKECTRGSAVWCQNVKTASDCGAVKHCLQTVWNKPTVKS
LPCDICKDVVTAAGDMLKDNATEEEILVYLEKTCDWLPKPNMSASCKEIVDSYLPVILDI
IKGEMSRPGEVCSALNLCESLQKHLAELNHQKQLESNKIPELDMTEVVAPFMANIPLLLY
PQDGPRSKPQPKDNGDVCQDCIQMVTDIQTAVRTNSTFVQALVEHVKEECDRLGPGMADI
CKNYISQYSEIAIQMMMHMQPKEICALVGFCDEVKEMPMQTLVPAKVASKNVIPALELVE
PIKKHEVPAKSDVYCEVCEFLVKEVTKLIDNNKTEKEILDAFDKMCSKLPKSLSEECQEV
VDTYGSSILSILLEEVSPELVCSMLHLCSGTRLPALTVHVTQPKDGGFCEVCKKLVGYLD
RNLEKNSTKQEILAALEKGCSFLPDPYQKQCDQFVAEYEPVLIEILVEVMDPSFVCLKIG
ACPSAHKPLLGTEKCIWGPSYWCQNTETAAQCNAVEHCKRHVWN
Number of residues
524
Molecular Weight
58112.135
Theoretical pI
4.82
GO Classification
Functions
enzyme activator activity / G-protein coupled receptor binding / lipid binding
Processes
adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway / blood coagulation / cellular response to organic substance / epithelial cell differentiation involved in prostate gland development / glycosphingolipid metabolic process / lipid transport / negative regulation of hydrogen peroxide-induced cell death / platelet activation / platelet degranulation / positive regulation of catalytic activity / positive regulation of MAPK cascade / prostate gland growth / regulation of lipid metabolic process / small molecule metabolic process / sphingolipid metabolic process
Components
extracellular exosome / extracellular region / extracellular space / integral component of membrane / lysosomal lumen / lysosomal membrane / mitochondrion
General Function
Lipid binding
Specific Function
Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate.Saposin-B stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases.Saposin-D is a specific sphingomyelin phosphodiesterase activator (EC 3.1.4.12).Prosaposin: Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosphorylation signaling.Saposins are specific low-molecular mass non-enzymic proteins, they participate in the lysosomal degradation of sphingolipids, which takes place by the sequential action of specific hydrolases.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Lysosome
Gene sequence
>lcl|BSEQ0016338|Prosaposin (PSAP)
ATGTACGCCCTCTTCCTCCTGGCCAGCCTCCTGGGCGCGGCTCTAGCCGGCCCGGTCCTT
GGACTGAAAGAATGCACCAGGGGCTCGGCAGTGTGGTGCCAGAATGTGAAGACGGCGTCC
GACTGCGGGGCAGTGAAGCACTGCCTGCAGACCGTTTGGAACAAGCCAACAGTGAAATCC
CTTCCCTGCGACATATGCAAAGACGTTGTCACCGCAGCTGGTGATATGCTGAAGGACAAT
GCCACTGAGGAGGAGATCCTTGTTTACTTGGAGAAGACCTGTGACTGGCTTCCGAAACCG
AACATGTCTGCTTCATGCAAGGAGATAGTGGACTCCTACCTCCCTGTCATCCTGGACATC
ATTAAAGGAGAAATGAGCCGTCCTGGGGAGGTGTGCTCTGCTCTCAACCTCTGCGAGTCT
CTCCAGAAGCACCTAGCAGAGCTGAATCACCAGAAGCAGCTGGAGTCCAATAAGATCCCA
GAGCTGGACATGACTGAGGTGGTGGCCCCCTTCATGGCCAACATCCCTCTCCTCCTCTAC
CCTCAGGACGGCCCCCGCAGCAAGCCCCAGCCAAAGGATAATGGGGACGTTTGCCAGGAC
TGCATTCAGATGGTGACTGACATCCAGACTGCTGTACGGACCAACTCCACCTTTGTCCAG
GCCTTGGTGGAACATGTCAAGGAGGAGTGTGACCGCCTGGGCCCTGGCATGGCCGACATA
TGCAAGAACTATATCAGCCAGTATTCTGAAATTGCTATCCAGATGATGATGCACATGCAG
GATCAGCAACCCAAGGAGATCTGTGCGCTGGTTGGGTTCTGTGATGAGGTGAAAGAGATG
CCCATGCAGACTCTGGTCCCCGCCAAAGTGGCCTCCAAGAATGTCATCCCTGCCCTGGAA
CTGGTGGAGCCCATTAAGAAGCACGAGGTCCCAGCAAAGTCTGATGTTTACTGTGAGGTG
TGTGAATTCCTGGTGAAGGAGGTGACCAAGCTGATTGACAACAACAAGACTGAGAAAGAA
ATACTCGACGCTTTTGACAAAATGTGCTCGAAGCTGCCGAAGTCCCTGTCGGAAGAGTGC
CAGGAGGTGGTGGACACGTACGGCAGCTCCATCCTGTCCATCCTGCTGGAGGAGGTCAGC
CCTGAGCTGGTGTGCAGCATGCTGCACCTCTGCTCTGGCACGCGGCTGCCTGCACTGACC
GTTCACGTGACTCAGCCAAAGGACGGTGGCTTCTGCGAAGTGTGCAAGAAGCTGGTGGGT
TATTTGGATCGCAACCTGGAGAAAAACAGCACCAAGCAGGAGATCCTGGCTGCTCTTGAG
AAAGGCTGCAGCTTCCTGCCAGACCCTTACCAGAAGCAGTGTGATCAGTTTGTGGCAGAG
TACGAGCCCGTGCTGATCGAGATCCTGGTGGAGGTGATGGATCCTTCCTTCGTGTGCTTG
AAAATTGGAGCCTGCCCCTCGGCCCATAAGCCCTTGTTGGGAACTGAGAAGTGTATATGG
GGCCCAAGCTACTGGTGCCAGAACACAGAGACAGCAGCCCAGTGCAATGCTGTCGAGCAT
TGCAAACGCCATGTGTGGAACTAG
Chromosome Location
10
Locus
10q21-q22
External Identifiers
ResourceLink
UniProtKB IDP07602
UniProtKB Entry NameSAP_HUMAN
GenBank Protein ID220064
GenBank Gene IDD00422
GenAtlas IDPSAP
HGNC IDHGNC:9498
General References
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  9. Holtschmidt H, Sandhoff K, Furst W, Kwon HY, Schnabel D, Suzuki K: The organization of the gene for the human cerebroside sulfate activator protein. FEBS Lett. 1991 Mar 25;280(2):267-70. [Article]
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  11. Tyynela J, Palmer DN, Baumann M, Haltia M: Storage of saposins A and D in infantile neuronal ceroid-lipofuscinosis. FEBS Lett. 1993 Sep 6;330(1):8-12. [Article]
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  14. Kleinschmidt T, Christomanou H, Braunitzer G: Complete amino-acid sequence of the naturally occurring A2 activator protein for enzymic sphingomyelin degradation: identity to the sulfatide activator protein (SAP-1). Biol Chem Hoppe Seyler. 1988 Dec;369(12):1361-5. [Article]
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  20. Vaccaro AM, Salvioli R, Barca A, Tatti M, Ciaffoni F, Maras B, Siciliano R, Zappacosta F, Amoresano A, Pucci P: Structural analysis of saposin C and B. Complete localization of disulfide bridges. J Biol Chem. 1995 Apr 28;270(17):9953-60. [Article]
  21. Hiraiwa M, Campana WM, Mizisin AP, Mohiuddin L, O'Brien JS: Prosaposin: a myelinotrophic protein that promotes expression of myelin constituents and is secreted after nerve injury. Glia. 1999 Jun;26(4):353-60. [Article]
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  35. Rafi MA, Zhang XL, DeGala G, Wenger DA: Detection of a point mutation in sphingolipid activator protein-1 mRNA in patients with a variant form of metachromatic leukodystrophy. Biochem Biophys Res Commun. 1990 Jan 30;166(2):1017-23. [Article]
  36. Kretz KA, Carson GS, Morimoto S, Kishimoto Y, Fluharty AL, O'Brien JS: Characterization of a mutation in a family with saposin B deficiency: a glycosylation site defect. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2541-4. [Article]
  37. Holtschmidt H, Sandhoff K, Kwon HY, Harzer K, Nakano T, Suzuki K: Sulfatide activator protein. Alternative splicing that generates three mRNAs and a newly found mutation responsible for a clinical disease. J Biol Chem. 1991 Apr 25;266(12):7556-60. [Article]
  38. Schnabel D, Schroder M, Furst W, Klein A, Hurwitz R, Zenk T, Weber J, Harzer K, Paton BC, Poulos A, et al.: Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is caused by a mutation in the initiation codon of their common gene. J Biol Chem. 1992 Feb 15;267(5):3312-5. [Article]
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  40. Regis S, Filocamo M, Corsolini F, Caroli F, Keulemans JL, van Diggelen OP, Gatti R: An Asn > Lys substitution in saposin B involving a conserved amino acidic residue and leading to the loss of the single N-glycosylation site in a patient with metachromatic leukodystrophy and normal arylsulphatase A activity. Eur J Hum Genet. 1999 Feb-Mar;7(2):125-30. [Article]
  41. Wrobe D, Henseler M, Huettler S, Pascual Pascual SI, Chabas A, Sandhoff K: A non-glycosylated and functionally deficient mutant (N215H) of the sphingolipid activator protein B (SAP-B) in a novel case of metachromatic leukodystrophy (MLD). J Inherit Metab Dis. 2000 Feb;23(1):63-76. [Article]
  42. Hulkova H, Cervenkova M, Ledvinova J, Tochackova M, Hrebicek M, Poupetova H, Befekadu A, Berna L, Paton BC, Harzer K, Boor A, Smid F, Elleder M: 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. Hum Mol Genet. 2001 Apr 15;10(9):927-40. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01966Di-Stearoyl-3-Sn-PhosphatidylethanolamineexperimentalunknownDetails