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Protein / target

Stromal interaction molecule 1

Encoded bySTIM1Q13586Homo sapiensSwiss-Prot
UniProt: Q13586Ensembl: ENSG00000167323HGNC: HGNC:11386NCBI Gene: 6786
Small-molecule tractable
Druggability
High-Quality Ligand
1
Research papers

Protein at a glance

Biological role

Calcium channel regulator

Strongest disease association

Severe Combined Immunodeficiency

Via encoding gene STIM1 · Genetic literature evidence · score 0.76

Research activity

Emerging research

1 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

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.

View complete UniProt function annotation

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 (PubMed:15866891, PubMed:16005298, PubMed:16208375, PubMed:16537481, PubMed:16733527, PubMed:16766533, PubMed:16807233, PubMed:18854159, PubMed:19182790, PubMed:19249086, PubMed:19622606, PubMed:19706554, PubMed:22464749, PubMed:24069340, PubMed:24351972, PubMed:24591628, PubMed:25326555, PubMed:26322679, PubMed:28219928, PubMed:32415068). Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Upon Ca(2+) depletion, translocates from the endoplasmic reticulum to the plasma membrane where it activates CRAC channel pore-forming subunits ORA1, ORA2 and ORAI3 to generate sustained and oscillatory Ca(2+) entry (PubMed:16208375, PubMed:16537481, PubMed:32415068). Involved in enamel formation (PubMed:24621671). Plays a role in regulating the type I interferon response by retaining the signaling adapter STING at the endoplasmic reticulum (PubMed:30643259)

Subcellular location

Cell membraneEndoplasmic reticulum membraneCytoplasm, cytoskeletonSarcoplasmic reticulum
Domains and Gene Ontology detail (24)

Domains & features

EF-hand 1EF-hand 2SAM

Gene Ontology

  • Ccortical endoplasmic reticulum
  • Cendoplasmic reticulum
  • Cendoplasmic reticulum membrane
  • Cmicrotubule
  • Cplasma membrane
  • Cplasma membrane raft
  • Csarcoplasmic reticulum membrane
  • Fcalcium channel regulator activity
  • Fcalcium ion binding
  • Fidentical protein binding
  • Fmicrotubule plus-end binding
  • Fprotease binding

685 aa · 77 kDa · 2 isoforms

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene STIM1

Gene-level evidence surfaced through the gene STIM1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Severe Combined Immunodeficiency
0.61Moderately supported

Genetic literature evidence dominant · Open Targets 0.47

T-B- severe combined immunodeficiency
0.61Moderately supported

Genetic literature evidence dominant · Open Targets 0.46

View evidence synthesis (2)
Severe Combined ImmunodeficiencyModerately supported
0.61
agreement 0.46–0.77
Genetic literature97%Literature3%

Open Targets aggregate 0.47 · 2 independent evidence families

T-B- severe combined immunodeficiencyModerately supported
0.61
agreement 0.45–0.76
Genetic literature100%

Open Targets aggregate 0.46 · 1 independent evidence family

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Severe Combined Immunodeficiency0.47
T-B- severe combined immunodeficiency0.46

Tractability

Small molecules — Emerging

Feasibility evidence (high-quality ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (go cc high conf and uniprot loc med conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (7)
SM · High-Quality LigandAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

L-type Ca<sup>2+</sup> channel activation of STIM1-Orai1 signaling remodels the dendritic spine ER to maintain long-term structural plasticity.7 cites

Dittmer PJ · Proceedings of the National Academy of Sciences of the United States of America · 2024

Recent

L-type Ca<sup>2+</sup> channel activation of STIM1-Orai1 signaling remodels the dendritic spine ER to maintain long-term structural plasticity.

Dittmer PJ · Proceedings of the National Academy of Sciences of the United States of America · 2024

Europe PMC papers linked directly to this protein.