Saposin

From Proteopedia

Function Saposin (Sap) is a small protein which functions as activator of lipid-degrading enzymes. They act by isolating the lipid substrate from the membrane. Sap is synthesized as a precursor – prosaposin – which contain 4 SapB active domains (cleaved to saposin A,B,C and D) and 2 SapA domains which are cleaved off[1]. See also Lipid metabolism. Saposin A and C stimulate hydrolysis of methylumbelliferyl β-galactoside by β-glucosylceramidase and of galactocerebrocide by β-galactosylceramidase[2]. For more details see Molecular Playground/Saposin C. Saposin B facilitates lipid binding to CD1d[3]. Saposin D stimulates acid ceramidase activity[4]. Disease Mutations in saposin B are autosomal recessive trait resulting in clinical metachromatic leukodystrophy[5]. Mutations in saposin D cause urinary system defects[6].

spinqualitylabelsall models Human saposin A complex with Ca+2 2dob Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

3D Structures of Saposin

Updated on 14-November-2023

Saposin A residues 60-143

2dob, 4uex – hSapA – human

4ddj – hSapA + LDAO

7p4d – mSapA – mouse

5nxb – mSapA + galactocerebrosidase

Saposin A residues 1-81

6d80 – hSapA + mitochondrial calcium uniporter

Saposin B

1n69 – hSapB + lipid

4v2o – hSapB + chloroquine

Saposin C

1m12, 1sn6 – hSapC – NMR

2gtg, 2qyp, 2z9a – hSapC residues 311-391

Saposin D

3bqp, 3bqq, 2r1q, 2rb3 - hSapD residues 405-484

5u85 - mSapD residues 438-519

References

1. ↑ O'Brien JS, Kishimoto Y. Saposin proteins: structure, function, and role in human lysosomal storage disorders. FASEB J. 1991 Mar 1;5(3):301-8. PMID:2001789
2. ↑ Morimoto S, Martin BM, Yamamoto Y, Kretz KA, O'Brien JS, Kishimoto Y. Saposin A: second cerebrosidase activator protein. Proc Natl Acad Sci U S A. 1989 May;86(9):3389-93. PMID:2717620
3. ↑ Yuan W, Qi X, Tsang P, Kang SJ, Illarionov PA, Besra GS, Gumperz J, Cresswell P. Saposin B is the dominant saposin that facilitates lipid binding to human CD1d molecules. Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5551-6. Epub 2007 Mar 19. PMID:17372201 doi:http://dx.doi.org/10.1073/pnas.0700617104
4. ↑ Azuma N, O'Brien JS, Moser HW, Kishimoto Y. Stimulation of acid ceramidase activity by saposin D. Arch Biochem Biophys. 1994 Jun;311(2):354-7. PMID:8203897
5. ↑ Deconinck N, Messaaoui A, Ziereisen F, Kadhim H, Sznajer Y, Pelc K, Nassogne MC, Vanier MT, Dan B. Metachromatic leukodystrophy without arylsulfatase A deficiency: a new case of saposin-B deficiency. Eur J Paediatr Neurol. 2008 Jan;12(1):46-50. Epub 2007 Jul 5. PMID:17616409 doi:http://dx.doi.org/10.1016/j.ejpn.2007.05.004
6. ↑ Matsuda J, Kido M, Tadano-Aritomi K, Ishizuka I, Tominaga K, Toida K, Takeda E, Suzuki K, Kuroda Y. Mutation in saposin D domain of sphingolipid activator protein gene causes urinary system defects and cerebellar Purkinje cell degeneration with accumulation of hydroxy fatty acid-containing ceramide in mouse. Hum Mol Genet. 2004 Nov 1;13(21):2709-23. Epub 2004 Sep 2. PMID:15345707 doi:http://dx.doi.org/10.1093/hmg/ddh281