Alternative titles; symbols
HGNC Approved Gene Symbol: SCP2
Cytogenetic location: 1p32.3 Genomic coordinates (GRCh38): 1:52,927,276-53,051,698 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1p32.3 | ?Leukoencephalopathy with dystonia and motor neuropathy | 613724 | Autosomal recessive | 3 |
SCP2 is a peroxisomal enzyme with thiolase activity that is required for the breakdown of branched-chain fatty acids (summary by Ferdinandusse et al., 2006).
SCP2 was the second peroxisomal thiolase to be identified; see ACAA1 (604054).
Yamamoto et al. (1991) used rat SCP2 cDNA to isolate a homologous human liver SCP2 cDNA. SCP2 encodes a deduced 143-amino acid protein that shares 89% sequence identity with the rat protein. SCP2 contains a 20-residue N-terminal leader sequence before the mature 13.2-kD polypeptide, which contains a C-terminal tripeptide related to the peroxisome targeting sequence. Northern blot analysis identified 2 mRNA transcripts of 1.8 and 3.2 kb in liver; in fibroblasts and placenta, the 1.8-kb transcript was most abundant.
Yamamoto et al. (1991) used sequences in the 3-prime untranslated region of the SCP2 cDNA to design PCR primers for use in mapping studies of human/rodent somatic cell hybrids. In this way, they demonstrated that the gene is located on the segment 1pter-p21 (He et al., 1991).
Vesa et al. (1994) refined the chromosomal assignment of SCP2 to 1p32 by analysis of a somatic cell hybrid panel by both PCR and hybridization methods applied to cell lines with various rearrangements of chromosome 1.
By interspecific backcross analysis, Welch et al. (1996) mapped the Scp2 gene to mouse chromosome 4.
Yamamoto et al. (1991) noted that in steroid hormone producing cells SCP2 is thought to facilitate the transport of cholesterol to mitochondria, where the first committed step in steroidogenesis takes place. Yamamoto et al. (1991) demonstrated that 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.
Sterol carrier protein-2 is present in low levels in Zellweger syndrome (see 214100), in which the cells are deficient in peroxisomes (van Amerongen et al., 1987).
Huang et al. (2016) showed that recombinant human SCP2 bound endocannabinoids (ECs) directly, as well as inhibitors of SCP2 and FABPs (e.g., FABP1; 134650), suggesting that SCP2 functions with FABP1 as an additional cytosolic EC chaperone.
Using purified recombinant proteins, Storey et al. (2017) showed that neither human SCP2 nor mouse Fabp1 bound phytol, but that both had high affinity for its metabolite, phytanic acid.
In a patient with leukoencephalopathy, dystonia, and motor neuropathy (LKDMN; 613724) who was found to have deficiency of SCP2, Ferdinandusse et al. (2006) identified a homozygous 1-nucleotide insertion (545_546insA; 184755.0001) in the SCP2 gene.
Storey et al. (2017) found that loss of both Fabp1 and Scp2 in mice exacerbated hepatic accumulation of phytol metabolites in females and less so in males. At the same time, dietary phytol increased hepatic levels of total long-chain fatty acids (LCFAs) in both male and female wildtype and mutant mice. Moreover, in both wildtype and mutant female mice, dietary phytol increased hepatic ratios of saturated/unsaturated and polyunsaturated/monounsaturated LCFAs while decreasing the peroxidizability index. However, in male mice, dietary phytol selectively increased the saturated/unsaturated ratio only in mutant mice, while decreasing the peroxidizability index in both wildtype and mutant mice. The results suggested a greater role for Fabp1 in transporting phytanic acid from the endoplasmic reticulum to peroxisomes, and for Scp2 in intraperoxisomal transport of phytanoyl-CoA and/or subsequent metabolites to oxidative enzymes within the peroxisomal matrix.
In a man with leukoencephalopathy with dystonia and motor neuropathy (LKDMN; 613724), Ferdinandusse et al. (2006) found homozygosity for a 1-bp insertion of an adenine after nucleotide position 545 (545_546insA) of the SCP2 gene, leading to a frameshift and premature stop codon (Ile184fsTer7). The patient reportedly had a similarly affected brother.
Ferdinandusse, S., Kostopoulos, P., Denis, S., Rusch, H., Overmars, H., Dillmann, U., Reith, W., Haas, D., Wanders, R. J. A., Duran, M., Marziniak, M. Mutations in the gene encoding peroxisomal sterol carrier protein X (SCPx) cause leukencephalopathy with dystonia and motor neuropathy. Am. J. Hum. Genet. 78: 1046-1052, 2006. [PubMed: 16685654] [Full Text: https://doi.org/10.1086/503921]
He, Z., Yamamoto, R., Furth, E. E., Schantz, L. J., Naylor, S. L., George, H., Billheimer, J. T., Strauss, J. F., III. cDNAs encoding members of a family of proteins related to human sterol carrier protein 2 and assignment of the gene to human chromosome 1p21-pter. DNA Cell Biol. 10: 559-569, 1991. [PubMed: 1718316] [Full Text: https://doi.org/10.1089/dna.1991.10.559]
Huang, H., McIntosh, A. L., Martin, G. G., Landrock, D., Chung, S., Landrock, K. K., Dangott, L. J., Li, S., Kier, A. B., Schroeder, F. FABP1: a novel hepatic endocannabinoid and cannabinoid binding protein. Biochemistry 55: 5243-5255, 2016. [PubMed: 27552286] [Full Text: https://doi.org/10.1021/acs.biochem.6b00446]
Storey, S. M., Huang, H., McIntosh, A. L., Martin, G. G., Kier, A. B., Schroeder, F. Impact of Fabp1/Scp-2/Scp-x gene ablation (TKO) on hepatic phytol metabolism in mice. J. Lipid Res. 58: 1153-1165, 2017. [PubMed: 28411199] [Full Text: https://doi.org/10.1194/jlr.M075457]
van Amerongen, A., Helms, J. B., van der Krift, T. P., Schutgens, R. B. H., Wirtz, K. W. A. Purification of nonspecific lipid transfer protein (sterol carrier protein 2) from human liver and its deficiency in livers from patients with cerebro-hepato-renal (Zellweger) syndrome. Biochim. Biophys. Acta 919: 149-155, 1987. [PubMed: 3555624] [Full Text: https://doi.org/10.1016/0005-2760(87)90201-3]
Vesa, J., Hellsten, E., Barnoski, B. L., Emanuel, B. S., Billheimer, J. T., Mead, S., Cowell, J. K., Strauss, J. F., III, Peltonen, L. Assignment of sterol carrier protein X/sterol carrier protein 2 to 1p32 and its exclusion as the causative gene for infantile neuronal ceroid lipofuscinosis. Hum. Molec. Genet. 3: 341-346, 1994. [PubMed: 8004106] [Full Text: https://doi.org/10.1093/hmg/3.2.341]
Welch, C. L., Xia, Y.-R., Billheimer, J. T., Strauss, J. F., III, Lusis, A. J. Assignment of the mouse sterol carrier protein gene (Scp2) to chromosome 4. Mammalian Genome 7: 624-625, 1996. [PubMed: 8678992] [Full Text: https://doi.org/10.1007/s003359900188]
Yamamoto, R., Kallen, C. B., Babalola, G. O., Rennert, H., Billheimer, J. T., Strauss, J. F., III. Cloning and expression of a cDNA encoding human sterol carrier protein 2. Proc. Nat. Acad. Sci. 88: 463-467, 1991. [PubMed: 1703300] [Full Text: https://doi.org/10.1073/pnas.88.2.463]
Yamamoto, R., Naylor, S. L., George, H., Billheimer, J. T., Strauss, J. F., III. Assignment of the gene encoding sterol carrier protein 2 to human chromosome 1pter-p21. (Abstract) Cytogenet. Cell Genet. 58: 1866-1867, 1991.