| STIM1 (Stromal Interaction Molecule 1) | |
|---|---|
| Gene | [STIM1](/genes/stim1) |
| UniProt ID | [Q13586](https://www.uniprot.org/uniprot/Q13586) |
| PDB | 2K60, 4IIT, 5F24 |
| Molecular Weight | 77.3 kDa |
| Localization | ER membrane |
| Family | STIM family, single-pass ER membrane proteins |
| Disease | Immunodeficiency, Stormorken syndrome, AD |
STIM1 (stromal interaction molecule 1) is an ER membrane protein that functions as the primary sensor of ER luminal calcium concentration. When ER calcium stores are depleted, STIM1 oligomerizes and translocates to ER-plasma membrane junctions to activate Orai1 calcium channels, initiating Store-Operated Calcium Entry (SOCE). STIM1 is critical for calcium homeostasis in neurons and immune cells.
STIM1 has several functional domains:
Activation mechanism[1]:
STIM1 regulates Store-Operated Calcium Entry (SOCE):
SOCE in neurons:
STIM1 dysfunction in AD[2]:
Mechanisms:
STIM1 in PD:
STIM1 loss-of-function mutations cause:
STIM1 gain-of-function mutations cause:
| Strategy | Mechanism | Status |
|---|---|---|
| SOCE enhancers | Boost STIM1-Orai1 signaling | Preclinical |
| SOCE inhibitors | Reduce Ca²⁺ entry (immunomodulation) | Clinical (transplant) |
| Calcineurin inhibitors | Block downstream effects | Clinical |
| STIM1 stabilizers | Enhance expression | Research |
Liou et al. STIM1 translocation to ER-PM junctions. 2005. ↩︎
Popugaeva et al. STIM1 in AD pathophysiology. Cell Calcium. 2013. ↩︎
Picard et al. STIM1 mutations in immunodeficiency. J Exp Med. 2009. ↩︎