STIM1 notes

Deep research providers unavailable (no API keys). Notes from UniProt Q13586 and cached literature.

Identity / topology

• Single-pass type I membrane protein of the endoplasmic reticulum. UniProt topology: lumenal (labelled
  "Extracellular") N-terminal region 23-213 containing the EF-hand pair and SAM domain; TM 214-234;
  cytoplasmic region 235-685 containing the SOAR/CAD domain, coiled coils and the polybasic/EB1 tip.
• The lumenal EF-hand senses ER Ca2+; store depletion triggers oligomerization and a conformational switch
  exposing SOAR/CAD, which traps and gates ORAI channels across ER-PM junctions.

Function

• UniProt FUNCTION (ECO:0000269): "Acts as a Ca(2+) sensor that gates two major inward rectifying Ca(2+) channels at the plasma membrane: Ca(2+) release-activated Ca(2+) (CRAC) channels and arachidonate-regulated Ca(2+)-selective (ARC) channels... Plays a role in mediating store-operated Ca(2+) entry (SOCE)."
• PMID:16005298 STIM is the ER Ca2+ sensor essential for store-depletion-triggered Ca2+ influx; "translocation of STIM1 into puncta that accumulated near the plasma membrane".
• PMID:19249086.
• PMID:17517596.
• PMID:26322679 ER-PM junction proteomics: "The ER-resident Ca2+ sensor protein, STIM1".

Localization conclusion

Core location is the ER membrane (and cortical ER at ER-PM junctions; SR membrane in muscle). STIM1 gates
ORAI from the ER side across the ER-PM gap; it is NOT primarily a plasma-membrane protein. A minor
glycosylated surface pool has been reported (several IDA "plasma membrane" rows) and is kept as non-core.

Disease

Gain-of-function STIM1 → tubular aggregate myopathy / Stormorken syndrome [PMID:23332920, PMID:25326555];
loss-of-function → CRAC channelopathy with immunodeficiency; also enamel maturation PMID:24621671.