STIM1

STIM1 plays a role in mediating store-operated Ca²⁺ entry (SOCE), a Ca²⁺ influx following depletion of intracellular Ca²⁺ stores. STIM1 acts as Ca²⁺ sensor in the endoplasmic reticulum via its EF-hand domain. Upon Ca2+ depletion, STIM1 translocates from the endoplasmic reticulum to the plasma membrane where it activates the Ca²⁺ release-activated Ca²⁺ (CRAC) channel subunit, TMEM142A/ORAI1.

STIM1 Related Areas

Signal Transduction>>Calcium Signaling>>Calcium Binding Protein>>STIM1

STIM1 Alternative Names

STIM1, D11S4896E, GOK [Homo sapiens]

Stim1, SIM [Mus musculus]

Summaries for STIM1

Entrez Gene summary for STIM1:

STIM1 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. STIM1 gene may play a role in malignancies and disease that involve this region, as well as early hematopoiesis, by mediating attachment to stromal cells. STIM1 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.[provided by RefSeq, Jan 2009]

OMIM - description for STIM1:

STIM1 is a calcium sensor that conveys the calcium load of the endoplasmic reticulum (ER) to store-operated channels (SOCs) at the plasma membrane (Yuan et al., 2007).

Wikipedia summary for STIM1:

Stromal interaction molecule 1 is a protein that in humans is encoded by the STIM1 gene. STIM1 has a single transmembrane domain, and is localized to the endoplasmic reticulum, and to a lesser extent to the plasma membrane.
Even though the protein has been identified earlier, its function was unknown until recently. In 2005, it was discovered that STIM1 functions as a calcium sensor in the endoplasmic reticulum . Upon activation of the IP3 receptor, the calcium concentration in the endoplasmic reticulum decreases, which is sensed by STIM1, via its EF hand domain. STIM1 activates the "store-operated" ORAI1 calcium ion channels in the plasma membrane, via protein protein interaction

Human STIM1 Protein General Information

 

• Protein names: Stromal interaction molecule 1
  Short name=STIM1
• Sequence length: 685 AA.
• Domain: The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends.
• Sequence similarities: Contains 1 EF-hand domain.
  Contains 1 SAM (sterile alpha motif) domain.
• Post-translational modification: Glycosylation is required for cell surface expression. Phosphorylated predominantly on Ser residues.
• Subunit structure: Forms homooligomers and heterooligomers with STIM2. Interacts with ORAI1. Interacts with MAPRE1; probably required for targeting to the growing microtubule plus ends. Interacts with EFCAB4B/CRACR2A; the interaction is direct and takes place in absence of Ca²⁺. Forms a complex with EFCAB4B/CRACR2A and ORAI1 at low concentration of Ca²⁺, the complex dissociates at elevated Ca²⁺ concentrations. Interacts with TMEM66/SARAF, promoting a slow inactivation of STIM1-dependent SOCE activity, possibly by facilitating the deoligomerization of STIM1.
• Subcellular location: Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Cytoplasm › cytoskeleton. Note: Translocates from the endoplasmic reticulum to the cell membrane in response to a depletion of intracellular calcium. Associated with the microtubule network at the growing distal tip of microtubules.
• Tissue specificity: Ubiquitously expressed in various human primary cells and tumor cell lines.
• Involvement in disease: Defects in STIM1 are the cause of immune dysfunction with T-cell inactivation due to calcium entry defect type 2 (IDTICED2) . IDTICED2 is an immune disorder characterized by recurrent infections, impaired T-cell activation and proliferative response, decreased T-cell production of cytokines, lymphadenopathy, and normal lymphocytes counts and serum immunoglobulin levels. Additional features include thrombocytopenia, autoimmune hemolytic anemia, non-progressive myopathy, partial iris hypoplasia, hepatosplenomegaly and defective enamel dentition.
• Miscellaneous: Transfection of STIM1 into cells derived from a rhabdoid tumor and from a rhabdomyosarcoma that do not express detectable levels of STIM1 can induce cell death, suggesting a possible role in the control of rhabdomyosarcomas and rhabdoid tumors.

General information above from UniProt

Function for STIM1 Protein

UniProtKB:

STIM1 plays a role in mediating store-operated Ca²⁺ entry (SOCE), a Ca²⁺ influx following depletion of intracellular Ca²⁺ stores. STIM1 acts as Ca²⁺ sensor in the endoplasmic reticulum via its EF-hand domain. Upon Ca2+ depletion, STIM1 translocates from the endoplasmic reticulum to the plasma membrane where it activates the Ca²⁺ release-activated Ca²⁺ (CRAC) channel subunit, TMEM142A/ORAI1.

Genatlas:

• STIM1 is implicated in tumor growth control and stromal-haematopoietic cell interactions
• STIM1 is possible adhesion molecule with a role in early hematopoiesis by mediating attachment to stromal cells
• STIM1 plays a role in the negative regulation of progression through cell cycle
• STIM1 plays a role in the positive regulation of cell proliferation
• STIM1 is an essential component of CRAC (calcium-release-activated calcium) channel activation
• STIM1 activates the plasma membrane CRAC channels by binding to the N and C termini of ORAI1
• STIM1 is involved in vascular smooth muscle cells proliferation
• STIM1 is a key signal for SOC channel activation
• STIM1 is recruited to the immunological synapse between primary T cells and autologous dendritic cells
• STIM1 is critically involved in initiating of production of calcium influx factor (CIF), a diffusible messenger that can deliver the signal from the stores to plasma membrane
• STIM1 plays a role as a trigger for calcium influx factor production
• STIM1 responds to depletion of ER Ca2+ stores by rearranging from tubular structures throughout the ER into punctate structures near the plasma membrane, where it activates ORAI store-operated Ca2+ entry (SOCE) channels
• STIM1 may be communicating the intracellular Ca(2+) stores with the plasma membrane to mediate store-operated Ca(2+) entry
• STIM1 plays a role in the activation of store-operated Ca(2+) entry probably acting as a Ca(2+) sensor
• STIM1 has essential function in mast cell activation and anaphylactic responses
• STIM1 is transmembrane endoplasmic reticulum Ca2+ sensors, coupling directly to activate plasma membrane ORAI1 Ca2+ entry channels
• STIM1 gates the store-operated calcium channel ORAI1
• Both STIM1 and STIM2 have a capacity to bind to a chaperone, calnexin as well as two protein-transporters, exportin1 and transportin1
• STIM1 is maintained in an inactive state in interphase with full Ca2+ stores through intramolecular shielding of the active domains (SOAR/CAD and SHD) by the C-terminal end of the molecule (positions 486–669)
• STIM1 clustering inhibition during meiosis is independent of the C-terminal 200 AAs
• STIM1 plays potential functional role for STIM1 and STIM2 located in the acidic Ca2+ stores
• Expression of STIM1 and STIM2 in acidic organelles that function as agonist-sensitive Ca2+ stores

Homology for human STIM1

• homolog to murine Stim1 (96.8pc)

Phenotype Information for STIM1

• Gene/Locus: STIM1
• Phenotype: Immune dysfunction, with T-cell inactivation due to calcium entry defect 2

Phenotype Information for STIM1 from OMIM (Online Mendelian Inheritance in Man)