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    STIM1

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    For Research Use Only. Not For Clinical Use.


    Background

    This gene encodes a type 1 transmembrane protein that mediates Ca2+ influx after depletion of intracellular Ca2+ stores by gating of store-operated Ca2+ influx channels (SOCs). It is one of several genes located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocrotical carcinoma, and lung, ovarian, and breast cancer. This gene may play a role in malignancies and disease that involve this region, as well as early hematopoiesis, by mediating attachment to stromal cells. Mutations in this gene are associated with fatal classic Kaposi sarcoma, immunodeficiency due to defects in store-operated calcium entry (SOCE) in fibroblasts, ectodermal dysplasia and tubular aggregate myopathy. This gene is oriented in a head-to-tail configuration with the ribonucleotide reductase 1 gene (RRM1), with the 3' end of this gene situated 1.6 kb from the 5' end of the RRM1 gene.
    Protein class

    Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Transporters

    Predicted location

    Intracellular, Membrane (different isoforms)

    Single cell type specificity

    Cell type enhanced (Oligodendrocyte precursor cells)

    Immune cell specificity

    Low immune cell specificity

    Cell line specificity

    Low cell line specificity

    Interaction

    Monomer in the presence of Ca(2+); it oligomerizes in absence of Ca(2+) (PubMed:18854159). Forms homooligomers and heterooligomers with STIM2 (PubMed:11463338, 11983428, 18854159, 22451904, 24351972, 24069340). Interacts (via the transmembrane region and the SOAR/CAD domain) with SPPL3; the interaction promotes the binding of STIM1 to ORAI1 (PubMed:25384971). Interacts with ORAI1 (PubMed:17905723, 19249086, 27185316, 24351972, 28219928, 30481768). Interacts with MAPRE1; probably required for targeting to the growing microtubule plus ends (PubMed:19632184). Interacts with CRACR2A/EFCAB4B; the interaction is direct and takes place in absence of Ca(2+) (PubMed:20418871). Forms a complex with CRACR2A/EFCAB4B and ORAI1 at low concentration of Ca(2+), the complex dissociates at elevated Ca(2+) concentrations (PubMed:20418871). Interacts with SARAF, promoting a slow inactivation of STIM1-dependent SOCE activity, possibly by facilitating the deoligomerization of STIM1 (PubMed:22464749, 30481768). Interacts with EFHB; the interaction takes place upon Ca(2+)-store depletion and inhibits the association with SARAF (PubMed:30481768). Interacts with ASPH (isoform 8) (PubMed:22586105). Interacts with SLC35G1; intracellular Ca(2+)-dependent. May interact with ATP1A1, ATP2A2, ATP2B1, ATP2B4, KPNB1 and XPO1; through SLC35G1 (PubMed:22084111). Interacts with TMEM203 (PubMed:25996873). Interacts with STIMATE, promoting STIM1 conformational switch (PubMed:26322679). Interacts with TMEM178A (By similarity). Interacts with CASQ1 (via C-terminal end and preferentially with the monomeric form); this interaction increases in response to a depletion of intracellular Ca(2+), decreases both STIM1 aggregation and clustering, interaction of STIM1 with ORAI1 and store-operated Ca(2+) entry (SOCE) activity (PubMed:27185316). Interacts with ADCY8 (PubMed:22494970).

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