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Domain

The four transmembrane helices are all kinked owing to the presence of proline residues in each, creating a ligand-binding cavity near the center of the protein.

The EXPERA domain doesn't possess any sterol isomerase catalytic activity.

Function

Sigma-2 receptor which contributes to ameliorate dysfunctional cellular processes and slow degenerative progression by regulating cell functions including cholesterol biosynthesis/trafficking, membrane trafficking, autophagy, lipid membrane-bound protein trafficking, and receptor stabilization at the cell surface (Probable) (PubMed:19583955, PubMed:23922215, PubMed:25620095, PubMed:27378690, PubMed:28559337, PubMed:30443021, PubMed:34233061, PubMed:34799735, PubMed:35970844). Forms a ternary complex with PGRMC1 receptor and low density lipoprotein receptor/LDLR at the plasma membrane, which increases LDLR-mediated LDL cholesterol internalization (PubMed:30443021). Decreases lysosomal sterol transporter NPC1 availability to the cell, probably through NPC1-binding, hence controlling lipid transport, including cholesterol and LBPA, outside of late endosome/lysosome (PubMed:19583955, PubMed:27378690). Binds regio- and stereoselective ligand 20(S)-hydroxycholesterol (20(S)-OHC) which enhances TMEM97-NPC1 interaction and decreases TMEM97-PGRMC1 and TMEM97-TSPO interactions, thereby linking OHC binding to cholesterol homeostasis (PubMed:34799735, PubMed:37047353). Also able to bind cholesterol (By similarity). Binds histatin 1 (Hst 1)/HN1 salivary peptide at the ER membrane, which is critical for increasing mitochondria-ER contacts and stimulating Hst1 wound healing properties (PubMed:34233061, PubMed:35970844). May alter the activity of some cytochrome P450 proteins (PubMed:22292588). Although shows homologies with sterol isomerases (EXPERA domain), not able to catalyze sterol isomerization (Probable) (PubMed:34880501). However, may act as sensors of these molecules (Probable) (PubMed:34880501). Acts as a quality control factor in the ER, promoting the proteolytic degradation of nonproductive and extramitochondrial precursor proteins in the ER membrane thus removing them from the ER surface (By similarity).

Sequence similarities

Belongs to the TMEM97/sigma-2 receptor family.

Tissue specificity

Widely expressed in normal tissues. Expressed in pancreatic, renal, breast, colon, ovarian surface epithelial (OSE) cells. Highly expressed in various proliferating cancer cells (PubMed:23922215).

Cellular localization

  • Rough endoplasmic reticulum membrane
  • Multi-pass membrane protein
  • Nucleus membrane
  • Multi-pass membrane protein
  • Localized at cell membrane and in lysosomes in sterol-depleted cells when expression of endogenous TMEM97 is stimulated (PubMed:19583955). Localized at cell membrane, probably in lipid rafts, in serum-starved conditions (PubMed:30443021).

Alternative names

MAC30, S2R, TMEM97, Sigma intracellular receptor 2, Sigma-2 receptor, Sigma2 receptor, Meningioma-associated protein 30, Transmembrane protein 97

Target type

Proteins

Primary research area

Neuroscience

Molecular weight

20848Da

We found 4 products in 3 categories

Primary Antibodies

Target

Application

Reactive species

Proteins & Peptides

Target

Species of origin

Cell Lines & Lysates

Target

Cell type

Species or organism