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Stromal interaction molecule 1

Domain

The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends.

The EF-hand domain is responsible for Ca(2+) sensitivity. It consists of a canonical helix-loop-helix EF motif (alpha1beta1alpha2; EF-hand 1) paired to a second helix-loop-helix EF motif (alpha3beta2alpha4; EF-hand 2). EF-hand 1 binds Ca(2+) whereas EF-hand 2 mediates the interactions with SAM domain.

The sterile alpha motif (SAM) domain folds into a characteristic 5-helix bundle (alpha6-alpha10) which interacts with the EF-hand pairs enabling concerted folding and stability of EF-hand and SAM domains.

The STIM1 Orai-activating region/CRAC-activating domain (SOAR/CAD) directly interacts with ORAI1 subunits and mediates CRAC channel gating.

The polybasic Lys-rich region (residues 672-685) functionally interacts with the Pro-rich region of ORAI1 (residues 3-47) and regulates CRAC channel gating at negative membrane potentials.

Function

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).

Involvement in disease

Immunodeficiency 10

IMD10

An immune disorder characterized by recurrent infections, impaired activation and proliferative response of T-cells, decreased T-cell production of cytokines, lymphadenopathy, and normal lymphocytes counts and serum immunoglobulin levels. Additional features include thrombocytopenia, autoimmune hemolytic anemia, myopathy, partial iris hypoplasia, hepatosplenomegaly and defective enamel dentition.

None

The disease is caused by variants affecting the gene represented in this entry.

Myopathy, tubular aggregate, 1

TAM1

A rare congenital myopathy characterized by regular arrays of membrane tubules on muscle biopsies without additional histopathological hallmarks. Tubular aggregates in muscle are structures of variable appearance consisting of an outer tubule containing either one or more microtubule-like structures or amorphous material. They may occur in a variety of circumstances, including inherited myopathies, alcohol- and drug-induced myopathies, exercise-induced cramps or muscle weakness.

None

The disease is caused by variants affecting the gene represented in this entry.

Stormorken syndrome

STRMK

A rare autosomal dominant disease characterized by mild bleeding tendency, thrombocytopathy, thrombocytopenia, mild anemia, asplenia, tubular aggregate myopathy, miosis, headache, and ichthyosis.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Glycosylation is required for cell surface expression.

Phosphorylated predominantly on Ser residues.

Tissue specificity

Ubiquitously expressed in various human primary cells and tumor cell lines.

Cellular localization

  • Cell membrane
  • Single-pass type I membrane protein
  • Endoplasmic reticulum membrane
  • Single-pass type I membrane protein
  • Cytoplasm
  • Cytoskeleton
  • Sarcoplasmic reticulum
  • Translocates from the endoplasmic reticulum to the cell membrane in response to a depletion of intracellular calcium and is detected at punctae corresponding to junctions between the endoplasmic reticulum and the cell membrane (PubMed:16005298, PubMed:16208375, PubMed:18854159, PubMed:19182790, PubMed:19249086). Associated with the microtubule network at the growing distal tip of microtubules (PubMed:19632184). Colocalizes with ORAI1 at the cell membrane (PubMed:27185316). Colocalizes preferentially with CASQ1 at endoplasmic reticulum in response to a depletion of intracellular calcium (PubMed:27185316).

Alternative names

GOK, STIM1, Stromal interaction molecule 1

Target type

Proteins

Primary research area

Neuroscience

Molecular weight

77423Da

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