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| {{STRUCTURE_1n69| PDB=1n69 | SIZE=400| SCENE= |right|CAPTIONHuman saposin C, [[1n69]] }}
| | <StructureSection load='2dob' size='350' side='right' scene='' caption='Human saposin A complex with Ca+2 [[2dob]]'> |
| | == 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<ref>PMID:2001789</ref>. See also [[Lipid metabolism]]. |
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| '''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 and 2 SapA domains which are cleaved off. For more details see [[Molecular Playground/Saposin C]]. | | *'''Saposin A and C''' stimulate hydrolysis of methylumbelliferyl β-galactoside by β-glucosylceramidase and of galactocerebrocide by β-galactosylceramidase<ref>PMID:2717620</ref>. For more details see [[Molecular Playground/Saposin C]].<br /> |
| | *'''Saposin B''' facilitates lipid binding to CD1d<ref>PMID:17372201</ref>.<br /> |
| | *'''Saposin D''' stimulates acid ceramidase activity<ref>PMID:8203897</ref>.<br /> |
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| | == Disease == |
| | Mutations in saposin B are autosomal recessive trait resulting in clinical metachromatic leukodystrophy<ref>PMID:17616409</ref>. Mutations in saposin D cause urinary system defects<ref>PMID:15345707</ref>. |
| | </StructureSection> |
| | == 3D Structures of Saposin == |
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| == 3D Structures of Saposin == | | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} |
| | {{#tree:id=OrganizedByTopic|openlevels=0| |
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| | *Saposin A residues 60-143 |
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| ===Saposin A===
| | **[[2dob]], [[4uex]] – hSapA – human<br /> |
| | **[[4ddj]] – hSapA + LDAO<br /> |
| | **[[7p4d]] – mSapA – mouse<br /> |
| | **[[5nxb]] – mSapA + galactocerebrosidase <br /> |
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| [[2dob]] – hSapA residues 60-140 – human
| | *Saposin A residues 1-81 |
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| ===Saposin B===
| | **[[6d80]] – hSapA + mitochondrial calcium uniporter<br /> |
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| [[1n69]] – hSapB
| | *Saposin B |
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| ===Saposin C===
| | **[[1n69]] – hSapB + lipid<br /> |
| | **[[4v2o]] – hSapB + chloroquine<br /> |
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| [[1m12]], [[1sn6]] – hSapC – NMR<br />
| | *Saposin C |
| [[2gtg]], [[2qyp]], [[2z9a]] – hSapC residues 311-391
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| ===Saposin D===
| | **[[1m12]], [[1sn6]] – hSapC – NMR<br /> |
| | **[[2gtg]], [[2qyp]], [[2z9a]] – hSapC residues 311-391 |
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| [[3bqp]], [[3bqq]], [[2r1q]], [[2rb3]] - hSapD residues 405-484<br />
| | *Saposin D |
| [[2r0r]] - hSapD residues 407-484 (mutant)
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| | **[[3bqp]], [[3bqq]], [[2r1q]], [[2rb3]] - hSapD residues 405-484<br /> |
| | **[[5u85]] - mSapD residues 438-519<br /> |
| | }} |
| | == References == |
| | <references/> |
| [[Category:Topic Page]] | | [[Category:Topic Page]] |
| 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].
- ↑ 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
- ↑ 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
- ↑ 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:https://dx.doi.org/10.1073/pnas.0700617104
- ↑ 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
- ↑ 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:https://dx.doi.org/10.1016/j.ejpn.2007.05.004
- ↑ 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:https://dx.doi.org/10.1093/hmg/ddh281
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3D Structures of Saposin
Updated on 14-November-2023
{"openlevels":0}
- Saposin A residues 60-143
- Saposin A residues 1-81
- 6d80 – hSapA + mitochondrial calcium uniporter
- Saposin B
- 1n69 – hSapB + lipid
- 4v2o – hSapB + chloroquine
- Saposin C
- Saposin D
References
