Reactome | PSAP is cleaved

PSAP is cleaved

Stable Identifier

R-HSA-9840334

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

lysosomal lumen, lysosomal membrane

ReviewStatus

5/5

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After its transport to lysosomes, prosaposin (PSAP) gets cleaved by unknown proteases into the fragments PSAP(60-142) (Saposin A), PSAP(195-273) (Saposin B), PSAP(311-391) (Saposin C) and PSAP(405-486) (Saposin D). Intermediate polyproteins during cleavage appear to be B-C-D, B-C, and C-D (Furst et al., 1988; Leonova et al., 1996; saposins were reviewed by O'Brien & Kishimoto, 1991; Morales et al., 1995; Kolter et al., 2005: Kolter & Sandhoff, 2010; Garrido-Arandia et al., 2018). Bioinformatics suggests that different peptidases, including trypsin, may be responsible for cleavage at different PSAP cleavage sites. In its dimerized form PSAP(195-273) (Saposin B) is centrally involved in mobilizing glycosphingolipids for catabolism, while PSAP(60-142) (Saposin A) and PSAP(405-486) (Saposin D) activate GALC and ASAH1, respectively.

Literature References

PubMed ID	Title	Journal	Year
16230343	Lipid-binding proteins in membrane digestion, antigen presentation, and antimicrobial defense Kolter, T, Winau, F, Schaible, UE, Leippe, M, Sandhoff, K	J Biol Chem	2005
3048308	The precursor of sulfatide activator protein is processed to three different proteins Fürst, W, Machleidt, W, Sandhoff, K	Biol Chem Hoppe Seyler	1988
8573994	Molecular role of sulfated glycoprotein-1 (SGP-1/prosaposin) in Sertoli cells Morales, CR, el-Alfy, M, Zhao, Q, Igdoura, S	Histol Histopathol	1995
2001789	Saposin proteins: structure, function, and role in human lysosomal storage disorders O'Brien, JS, Kishimoto, Y	FASEB J	1991
8663398	Proteolytic processing patterns of prosaposin in insect and mammalian cells Leonova, T, Qi, X, Bencosme, A, Ponce, E, Sun, Y, Grabowski, GA	J Biol Chem	1996
29443946	A Comparative Study of Human Saposins Garrido-Arandia, M, Cuevas-Zuviría, B, Díaz-Perales, A, Pacios, LF	Molecules	2018
19836391	Lysosomal degradation of membrane lipids Kolter, T, Sandhoff, K	FEBS Lett	2010