Disease relevance of SYCP2

• We tested this using a clone (SC2A) of rat hepatoma cells that overexpress mature immunodetectable SCP-2 [1].
• Yellow fever mosquito sterol carrier protein (SCP-2) is known to bind to cholesterol [2].
• To assess the possibility that sterol carrier protein-2 (SCP-2) is involved in this transport, we studied the time course of newly synthesized cholesterol incorporation in the plasma membrane of normal and SCP-2-deficient (Zellweger syndrome) human fibroblasts [3].
• A sterol-carrier protein-2 (SCP-2) knockout mouse model shares a similar clinical phenotype to Refsum's disease, but no mutations in SCP-2 have been described to-date in man [4].
• In this study, recombinant liver fatty acid binding protein (L-FABP) and sterol carrier protein-2 (SCP-2) were used in conjunction with a series of fluorescent fatty acid probe molecules to compare the relative dielectric properties of the ligand binding sites and to examine the effects of ethanol in vitro on ligand interaction with these proteins [5].

High impact information on SYCP2

• The patients with gallstones also had significantly increased cytosolic total and free cholesterol levels (P < 0.001), which correlated strongly with increased cytosolic levels of SCP2/nsLTP (r = 0.80, P < 0.001 and r = 0.81, P < 0.001, respectively) [6].
• The expressed cDNA in COS-7 cells yields a 15.3-kDa polypeptide and increased amounts of a 13.2-kDa polypeptide, both reacting with a specific rabbit antiserum to rat liver SCP2 [7].
• The 1.3-kilobase (kb) cDNA contains an open reading frame which encompasses a 143-amino acid sequence which is 89% identical to the rat SCP2 amino acid sequence [7].
• Southern blot analysis suggests either that there are multiple copies of the SCP2 gene in the human genome or that the SCP2 gene is very large [7].
• Coexpression of the SCP2 cDNA with expression vectors for cholesterol side-chain cleavage enzyme and adrenodoxin resulted in a 2.5-fold enhancement of progestin synthesis over that obtained with expression of the steroidogenic enzyme system alone [7].

Biological context of SYCP2

• Such upregulated genes included those involved in nuclear structure and meiosis (SYCP2), DNA repair (RFC5), and transcription regulation (ZNF238) [8].
• We find that the synaptonemal complex protein 3 (SCP3) is a main determinant of axial-element assembly and is required for attachment of this structure to meiotic chromosomes, whereas SCP2 helps shape the in vivo structure of the axial element [9].
• Although NBD-stearic acid bound with high affinity to both proteins, emission spectra showed that the relative dielectric constant of the ligand binding site in SCP-2 was significantly lower than in L-FABP, 2 vs 24 [5].
• Both proteins share identical cDNA and amino acid sequences for 13-kDa SCP-2 at their C-termini [10].
• Sterol carrier protein-2 (SCP-2) is an intracellular, small, basic protein domain that in vitro enhances the transfer of lipids between membranes [11].

Anatomical context of SYCP2

• These results suggest that in normal fibroblasts the major fraction of newly synthesized cholesterol is transported to the plasma membrane by a SCP-2-dependent mechanism [3].
• In contrast, sterol carrier protein-2 (SCP-2) was only 2.2-fold more effective in mediating sterol transfer from steroidogenic cell mitochondria [12].
• After SCP-2 antisense oligonucleotides treatment of normal fibroblasts, the rapid transport was reduced by 81% with a simultaneous increase of the slower one [3].
• The effect of sterol carrier protein-2 (SCP-2) on dolichol biosynthesis by rat liver microsomes was investigated. cis-Prenyltransferase activity was stimulated 7-fold in the presence of 5 micrograms of purified SCP-2/mg of microsomal protein, which was similar to the increase obtained by adding detergent [13].
• Incubation with cytosol pretreated with anti-SCP-2 showed no stimulatory effect and led to the accumulation of shorter polyisoprenoids [13].

Associations of SYCP2 with chemical compounds

• Cholesterol transfer was rapid, cytoskeleton-independent, and Golgi-independent in normal cells, but it was slower, cytoskeleton-dependent, and Golgi-dependent in SCP-2-deficient cells [3].
• Interestingly, the orientation of the fatty acid is opposite to the observed orientation for Triton X-100 in the SCP-2-like domain from the peroxisomal multifunctional enzyme (Haapalainen, A. M., van Aalten, D. M., Merilainen, G., Jalonen, J. E., Pirila, P., Wierenga, R. K., Hiltunen, J. K., and Glumoff, T. (2001) J. Mol. Biol. 313, 1127-1138) [2].
• The clones were equally sensitive to tert-butyl hydroperoxide, suggesting that the 7alpha-OOH effect was SCP-2-specific [1].
• We report here the three-dimensional structure of the complex of SCP-2 from Aedes aegypti with a C16 fatty acid to 1.35-A resolution [2].
• SCP-2 had no appreciable effect on polyprenol alpha-saturase, dolichol kinase, dolichyl phosphate phosphatase, or acyl-CoA:dolichol acyltransferase [13].

Analytical, diagnostic and therapeutic context of SYCP2

• Circular dichroism also showed that these chemical-shift changes, upon oleic acid binding, did not alter the secondary structure of SCP-2 [10].
• Differential polarized phase fluorometry revealed decreased SCP-2 tryptophan rotational correlation time upon cholesterol binding [14].
• We used protein modelling and site-directed mutagenesis to investigate why the BODIPY-PC transfer mediated by E. lagascae SCP-2 is not sensitive to sterols, whereas the transfer mediated by A. thaliana SCP-2 shows sterol sensitivity [15].
• In contrast, the level of sterol carrier protein 2 (SCP2), a Leydig cell-specific protein, was affected by hypophysectomy much less than the other parameters measured [16].
• By immunoblotting, peroxisome-deficient cells were confirmed to contain either no detectable SCP2 or far less SCP2 than corresponding normal cells [17].

References