Sterol carrier protein X is peroxisomal 3-oxoacyl coenzyme A thiolase with intrinsic sterol carrier and lipid transfer activity.
Sterol carrier protein 2 (SCP2; also called nonspecific lipid transfer protein) is a small basic sterol carrier and lipid transfer protein assumed to participate in the intracellular transport of sterols and certain other lipids. Upon cloning and sequencing SCP2-encoding cDNAs, we and others found cDNAs containing unexpected in-frame 5'-extensions of up to 1,250 nucleotides upstream of the initiator ATG of the cDNA encoding pre-SCP2. The corresponding transcripts are primarily expressed in the liver and are predicted to encode a previously undescribed fusion protein containing a 143-amino acid C-terminal domain completely identical to pre-SCP2 and a 404-amino acid N-terminal domain with unknown biochemical activity or function (named sterol carrier protein x, SCPx). Here, we show that purified recombinant SCPx cleaves 3-oxoacyl(n)-CoA to yield acetyl-CoA and acyl(n-2)-CoA. Like SCP2, recombinant SCPx also stimulates the microsomal conversion of 7-dehydrocholesterol to cholesterol and transfers phosphatidylcholine and 7-dehydrocholesterol from small unilamellar vesicles to acceptor membranes in vitro. Furthermore, SCPx epitopes are primarily detected within peroxisomes. These findings suggest that SCPx is a previously undescribed peroxisomal 3-ketoacyl-CoA thiolase (EC 2.3.1.16) with intrinsic sterol carrier and lipid transfer activity (suggested name: SCP2/3-oxoacyl-CoA thiolase).
Seedorf
U
U
Institut für Arterioskleroseforschung, Westfälischen Wilhelms Universität, Münster, Federal Republic of Germany.
Brysch
P
P
Engel
T
T
Schrage
K
K
Assmann
G
G
D000101:Acetyl-CoA C-Acetyltransferase; D000102:Acetyl-CoA C-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary; D006801:Humans; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology; D008830:Microbodies / Q000201:enzymology*; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013261:Sterols / Q000378:metabolism*
D002352:Carrier Proteins; D018076:DNA, Complementary; D010713:Phosphatidylcholines; D013261:Sterols; C072087:sterol carrier proteins; D000102:Acetyl-CoA C-Acyltransferase; D000101:Acetyl-CoA C-Acetyltransferase