Sterol-sensing domains are present in various proteins involved in key aspects of cholesterol homeostasis and signalling. Multiple sequence alignments using
Clustal W have shown that these proteins can be grouped in seven different families according to their SSDs. The following SSD-containing proteins represent each family: •
HMG-CoA reductase (HMGCR), involved in the biosynthesis of cholesterol. This was the first protein with an SSD to be discovered. Upon binding to cholesterol, this protein undergoes
endoplasmic-reticulum-associated protein degradation. The SSD is not required for the catalytic activity of HMGCR. •
SREBP cleavage-activating protein (SCAP), which regulates transcription of genes with sterol response elements by proteolytically activating
sterol regulatory element-binding proteins (SREBPs). This was the second SSD-containing protein to be discovered. •
7-dehydrocholesterol reductase (7DHCR), involved in the last step of cholesterol biosynthesis. •
Niemann-Pick type C1 (NPC1), involved in intracellular cholesterol transport. •
Niemann-Pick type C1-like 1 (NPC1L1), a regulator of cholesterol absorption in
enterocytes. •
Patched (
PTCH1,
PTCH2), involved in the
hedgehog signaling pathway and also cytokinesis. Its SSD binds the cholesterol moiety of hedgehog, and it is essential for its activity. •
Dispatched (DISP1, DISP2, DISP3), also involved in hedgehog signaling. DISP is required for the secretion of hedgehog. •
Patched-related protein (PTR), structurally similar to patched. Its functions are not fully understood. == Disease ==