Overview
| Uniprot ID | Q5BJF2 |
|---|
| Protein Name | Sigma intracellular receptor 2 |
|---|
| Gene Name | TMEM97 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 130 |
FSKASGFKGQRPETL |
| 48 |
VEFRNLLKWYAKEFK |
Function
Sigma-2 receptor implicated in the regulation of multiple cellular processes, including cholesterol biosynthesis and trafficking, membrane trafficking, autophagy, lipid membrane-associated protein trafficking, and stabilization of receptors at the cell surface, thereby contributing to the maintenance of cellular homeostasis(PubMed:19583955, PubMed:23922215, PubMed:25620095, PubMed:27378690, PubMed:28559337, PubMed:30443021, PubMed:34233061, PubMed:34799735, PubMed:35970844, PubMed:25566323). Forms a ternary complex with PGRMC1 and LDLR at the plasma membrane, promoting LDLR-mediated internalization of LDL cholesterol (PubMed:30443021). Reduces the availability of the lysosomal sterol transporter NPC1, likely through direct interaction, thereby regulating lipid transport, including cholesterol and LBPA, outside of late endosome/lysosome (PubMed:19583955, PubMed:27378690). Binds the regio- and stereoselective oxysterol 20(S)-hydroxycholesterol (20(S)-OHC). Ligand binding enhances association with NPC1 and modulates TMEM97-containing protein complexes involving PGRMC1 and TSPO, consistent with a role in cholesterol homeostasis (PubMed:34799735, PubMed:37047353). Also able to bind cholesterol (By similarity). Interacts with the salivary peptide histatin 1 (Hst 1/HTN1) at the ER membrane, which is critical for increasing mitochondria-ER contacts and stimulating Hst 1 wound healing properties (PubMed:34233061, PubMed:35970844). May alter the activity of some cytochrome P450 proteins (PubMed:22292588). Although sharing homology with sterol isomerases through the EXPERA domain, lacks sterol isomerase activity; instead, may function as a sterol or oxysterol sensor (PubMed:34880501, PubMed:25566323). Acts as an ER quality control factor by promoting proteolytic degradation of nonproductive and extramitochondrial precursor proteins in the ER membrane, thereby removing them from the ER surface (By similarity)
Protein Sequence
10
MGAPATRRCV
20
EWLLGLYFLS
30
HIPITLFMDL
40
QAVLPRELYP
50
VEFRNLLKWY
60
AKEFKDPLLQ
70
EPPAWFKSFL
80
FCELVFQLPF
90
FPIATYAFLK
100
GSCKWIRTPA
110
IIYSVHTMTT
120
LIPILSTFLF
130
EDFSKASGFK
140
GQRPETLHER
150
LTLVSVYAPY
160
LLIPFILLIF
170
MLRSPYYKYE
EKRKKK
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005783 |
endoplasmic reticulum |
| Cellular Component |
GO:0005764 |
lysosome |
| Cellular Component |
GO:0031965 |
nuclear membrane |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Cellular Component |
GO:0005791 |
rough endoplasmic reticulum |
| Cellular Component |
GO:0030867 |
rough endoplasmic reticulum membrane |
| Molecular Function |
GO:0015485 |
cholesterol binding |
| Molecular Function |
GO:0008142 |
oxysterol binding |
| Biological Process |
GO:0042632 |
cholesterol homeostasis |
| Biological Process |
GO:0140077 |
positive regulation of lipoprotein transport |
| Biological Process |
GO:0090303 |
positive regulation of wound healing |
| Biological Process |
GO:0001558 |
regulation of cell growth |
| Biological Process |
GO:0032383 |
regulation of intracellular cholesterol transport |
| Biological Process |
GO:0032377 |
regulation of intracellular lipid transport |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.