TMEM97 Protein, Human (sf9)

TMEM97 is a Sigma-2 receptor that contributes to ameliorating dysfunctional cellular processes and slowing degenerative progression by regulating cell functions such as cholesterol biosynthesis/trafficking, membrane trafficking, autophagy, lipid membrane-bound protein trafficking, and receptor stabilization at the cell surface (Probable). It forms a ternary complex with the PGRMC1 receptor and low-density lipoprotein receptor (LDLR) at the plasma membrane, enhancing LDLR-mediated LDL cholesterol internalization. TMEM97 likely reduces the availability of the lysosomal sterol transporter NPC1 to the cell, probably through NPC1-binding, thereby controlling lipid transport, including cholesterol and LBPA, outside late endosomes/lysosomes. It binds the regio- and stereoselective ligand 20(S)-hydroxycholesterol (20(S)-OHC), which enhances TMEM97-NPC1 interaction while decreasing TMEM97-PGRMC1 and TMEM97-TSPO interactions, linking OHC binding to cholesterol homeostasis (By similarity: also binds cholesterol). At the ER membrane, it binds the salivary peptide histatin 1 (Hst 1)/HN1, which is critical for increasing mitochondria-ER contacts and stimulating Hst1's wound-healing properties. TMEM97 may alter the activity of some cytochrome P450 proteins. Although it shares homology with sterol isomerases (EXPERA domain), it cannot catalyze sterol isomerization (Probable) but may act as a sensor for these molecules. Additionally, it serves as a quality control factor in the ER, promoting the proteolytic degradation of nonproductive and extramitochondrial precursor proteins in the ER membrane, thereby removing them from the ER surface (By similarity).