1qnd

Structural highlights

Disease

SCP2_HUMAN Leukoencephalopathy-dystonia-motor neuropathy syndrome. The disease is caused by variants affecting the gene represented in this entry. Expression at protein level is almost abolished in Zellweger syndrome. Cholesterol transfer from the endoplasmic reticulum to the plasma membrane was reduced in patient fibroblasts compared to controls.^[1]

Function

SCP2_HUMAN Plays a crucial role in the peroxisomal oxidation of branched-chain fatty acids (PubMed:10706581). Catalyzes the last step of the peroxisomal beta-oxidation of branched chain fatty acids and the side chain of the bile acid intermediates di- and trihydroxycoprostanic acids (DHCA and THCA) (PubMed:10706581). Also active with medium and long straight chain 3-oxoacyl-CoAs. Stimulates the microsomal conversion of 7-dehydrocholesterol to cholesterol and transfers phosphatidylcholine and 7-dehydrocholesterol between membrances, in vitro (By similarity). Isoforms SCP2 and SCPx cooperate in peroxisomal oxidation of certain naturally occurring tetramethyl-branched fatty acyl-CoAs (By similarity).[UniProtKB:P11915][UniProtKB:P32020]^[2] Mediates the transfer of all common phospholipids, cholesterol and gangliosides from the endoplasmic reticulum to the plasma membrane. May play a role in regulating steroidogenesis (PubMed:17157249, PubMed:8300590, PubMed:7642518). Stimulates the microsomal conversion of 7-dehydrocholesterol to cholesterol (By similarity). Also binds fatty acids and fatty acyl Coenzyme A (CoA) such as phytanoyl-CoA. Involved in the regulation phospholipid synthesis in endoplasmic reticulum enhancing the incorporation of exogenous fatty acid into glycerides. Seems to stimulate the rate-limiting step in phosphatidic acid formation mediated by GPAT3. Isoforms SCP2 and SCPx cooperate in peroxisomal oxidation of certain naturally occurring tetramethyl-branched fatty acyl-CoAs (By similarity).[UniProtKB:P11915][UniProtKB:P32020]^{[3] [4] [5]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Puglielli L, Rigotti A, Greco AV, Santos MJ, Nervi F. Sterol carrier protein-2 is involved in cholesterol transfer from the endoplasmic reticulum to the plasma membrane in human fibroblasts. J Biol Chem. 1995 Aug 11;270(32):18723-6. PMID:7642518 doi:10.1074/jbc.270.32.18723
2. ↑ Ferdinandusse S, Denis S, van Berkel E, Dacremont G, Wanders RJ. Peroxisomal fatty acid oxidation disorders and 58 kDa sterol carrier protein X (SCPx). Activity measurements in liver and fibroblasts using a newly developed method. J Lipid Res. 2000 Mar;41(3):336-42 PMID:10706581
3. ↑ Stanley WA, Filipp FV, Kursula P, Schuller N, Erdmann R, Schliebs W, Sattler M, Wilmanns M. Recognition of a functional peroxisome type 1 target by the dynamic import receptor pex5p. Mol Cell. 2006 Dec 8;24(5):653-63. PMID:17157249 doi:10.1016/j.molcel.2006.10.024
4. ↑ Puglielli L, Rigotti A, Greco AV, Santos MJ, Nervi F. Sterol carrier protein-2 is involved in cholesterol transfer from the endoplasmic reticulum to the plasma membrane in human fibroblasts. J Biol Chem. 1995 Aug 11;270(32):18723-6. PMID:7642518 doi:10.1074/jbc.270.32.18723
5. ↑ Seedorf U, Scheek S, Engel T, Steif C, Hinz HJ, Assmann G. Structure-activity studies of human sterol carrier protein 2. J Biol Chem. 1994 Jan 28;269(4):2613-8. PMID:8300590
6. ↑ Garcia FL, Szyperski T, Dyer JH, Choinowski T, Seedorf U, Hauser H, Wuthrich K. NMR structure of the sterol carrier protein-2: implications for the biological role. J Mol Biol. 2000 Jan 21;295(3):595-603. PMID:10623549 doi:10.1006/jmbi.1999.3355