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Symbol STIM1 contributors: mct/npt/pgu - updated : 16-03-2016
HGNC name stromal interaction molecule 1
HGNC id 11386
Type ubiquitous
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Digestiveintestinelarge intestinecolon highly Rattus norvegicusAdult
Lymphoid/Immunethymus   highly
Reproductivefemale systemplacenta  moderately
Skin/Tegumentskin   highly
Urinarykidney   highly
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialabsorptive excretorydigestive epithelium (mucosa)   Rattus norvegicusAdult
Muscularstriatumskeletal highly Homo sapiensAdult
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticplatelet Homo sapiens
cell lineage
cell lines
fluid/secretion blood
physiological period pregnancy
Text placenta
  • N-terminus containing only the two EF-hands and sterile alpha motif (SAM) domains, designated the EF-SAM domain , sits inside the ER, where it senses luminal Ca2+ concentration
  • predicted signal peptide and transmembrane helix
  • 107-AA CRAC activation domain (CAD) binding directly to the N and C termini of ORAI1 to open the CRAC channel
  • a STIM1 ORAI activating region (SOAR) region (AA fragment 344-442), acting in combination with STIM1 (AA 450-485) to regulate the strength of interaction with ORAI1 , and formation of a SOAR dimer is necessary to activate the ORAI1 channel
  • coiled-coil domain (CCB9)in the C terminus crucial for its aggregation, sufficient for binding to and activation of ORAI1 CRAC channels independent of store depletion
  • C terminus multimerizes two ORAI1 dimers to form the active channel ; cytosolic C terminus is sufficient to activate ORAI1 currents independent of store depletion , and C-terminal 200 AAs are important to maintain STIM1 in an inactive state when Ca2+ stores are full, through predicted intramolecular shielding of the active STIM1 domains (SOAR/CAD and STIM1 homomerization domain) , it is cytoplasmic
  • coiled-coil domains are essential for its ER-retention and its stability
  • conjugated GlycoP
    mono polymer homomer , heteromer , oligo
    interspecies homolog to murine Stim1 (96.8pc)
  • ezrin/radixin/moesin family
  • CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • type 1 membrane protein
  • translocated across the membrane of the endoplasmic reticulum such that the SAM domain resides within the endoplasmic reticulum (ER) lumen
  • SURF4 associated with STIM1 in the endoplasmic reticulum
  • ASPH is a structural component of the ER-PM junctions where ORAI1 and STIM1 cluster and interact in T cells
  • translocating upon Ca2+ store depletion to the plasma membrane to activate calcium release-activated calcium channels
  • colocalized with T cell receptor molecules at the interface between T cells and dendritic cells
  • expressed in the lysosome-related organelles and dense granules in human platelets )
  • primarily residing in the ER
  • STIM1 and ORAI1 are both localized at the skeletal-muscle triad, a specialized junction between the ER and the plasma membrane
  • basic FUNCTION
  • implicated in tumor growth control and stromal-haematopoietic cell interactions
  • possible adhesion molecule with a role in early hematopoiesis by mediating attachment to stromal cells
  • playing a role in the negative regulation of progression through cell cycle
  • playing a role in the positive regulation of cell proliferation
  • being an essential component of CRAC (calcium-release-activated calcium) channel activation
  • activates the plasma membrane CRAC channels by binding to the N and C termini of ORAI1
  • involved in vascular smooth muscle cells proliferation
  • being a key signal for SOC channel activation
  • recruited to the immunological synapse between primary T cells and autologous dendritic cells
  • 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
  • playing a role as a trigger for calcium influx factor production
  • 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
  • may be communicating the intracellular Ca(2+) stores with the plasma membrane to mediate store-operated Ca(2+) entry
  • playing a role in the activation of store-operated Ca(2+) entry probably acting as a Ca(2+) sensor
  • essential function in mast cell activation and anaphylactic responses
  • transmembrane endoplasmic reticulum Ca2+ sensors, coupling directly to activate plasma membrane ORAI1 Ca2+ entry channels
  • 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
  • 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
  • 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
  • new actin-binding splice variant involved in fast repetitive Ca2+ release
  • endoplasmic reticulum (ER) membrane Ca(2+) sensor responsible for activation of store-operated Ca(2+) influx
  • calcium sensor in the endoplasmic reticulum, STIM1, activates ORAI1, a CRAC channel in the plasma membrane (PMId: 22451904)
  • essential for normal fertilization as it is involved in the maintenance of the long-lasting repetitive Ca(2+) signal (
  • STIM1 acts as an endoplasmic reticulum (ER) Ca2+ sensor that detects store depletion
  • modulatory function of SURF4 for STIM1-mediated SOCE
  • essential for correct growth cone navigation, playing multiple roles in growth cone motility, including the activation of SOCE
  • potential role for STIM1, STIM2 proteins and T-cell function in the pathogenesis of Sjögren syndrome
  • could be an important molecule responsible for airway remodeling
  • is the endoplasmic reticulum (ER) Ca(2+) sensor to control ER Ca(2+) levels
  • store-operated Ca(2+) entry and STIM1 are involved in the regulation of mitochondrial shape and bioenergetics and play a role in oxidative stress
  • positive feedback control between STIM1/SOCE and NFATC3 is required for efficient induction and progression of myoblast differentiation
  • main Ca2+ sensor in the endoplasmic reticulum
  • oligomerizes and thereby triggers extracellular Ca2+ entry
  • importance of STIM1 in blood platelets, T cell activation, and normal skeletal-muscle structure and function
  • acts as an endoplasmic reticulum Ca(2+) sensor that communicates the filling state of the intracellular stores to the store-operated channels (
  • functional role of plasma membrane-resident STIM1 in the regulation of store-operated divalent cation entry, which at least involves the EF-hand motif and the C-terminal polybasic lysine-rich domain (
  • key component of intracellular Ca(2+) signaling, involved in the regulation not only of basolateral but also of apical Ca(2+) influx
  • central role of STIM1 and ORAI1 in SCDI (Slow Ca(2+)-dependent inactivation)
  • STIM1 and STIM2 Ca2+ sensors oligomerize upon Ca2+ depletion in the ER lumen, contact phosphoinositides at the PM via their cytosolic lysine (K)-rich domains, and activate Ca2+ channels
  • STIM1 and STIM2 are endoplasmic reticulum (ER) Ca(2+) sensor proteins able to translocate within the ER membrane to physically couple with and gate plasma membrane ORAI1 Ca(2+) channels
  • in the mammalian nervous system STIM1 is a key regulator of intracellular Ca(2+) signaling, metabotropic glutamate receptor-dependent synaptic transmission, and motor coordination
  • STIM1, STIM2, and ORAI1 regulate store-operated calcium entry and purinergic activation of microglia
  • STIM2 enhances agonist-mediated activation of SOCE by promoting STIM1 clustering in ER-PM junctions at low stimulus intensities
  • ability of STIM proteins to induce cortical ER formation is dispensable for SOCE and requires the lysine-rich tail of STIM1 involved in binding to phosphoinositides
  • CELLULAR PROCESS cell cycle, progression
    cell life, proliferation/growth
    text ion transport
    a component
  • forming oligomer with STIM2
  • component of Ca2+ release-activated Ca2+ channels (CRACs), with ORAI1
  • essential component of SOCE
  • formation of the STIM1–SLC35G1 complex with ATP2B1 attenuates Ca2+ pump activity and may sustain cytosolic Ca2+ elevation
    small molecule metal binding,
  • Mn2+
  • Ca2+
  • protein
  • interacting with ORAI1
  • dynamic interplay between 2 membrane proteins, STIM1 and 2 and ORAI1 to 3, underlies an intricate coupling between Ca2+ release from endoplasmic reticulum (ER) stores and Ca2+ entry across the plasma membrane
  • colocalizes with ORAI1 Ca(2+) channels and interacts with actin to form permanent clusters
  • PDIA3 interacts with the ER luminal domain of STIM1, with this interaction involving two conserved cysteine residues, C(49) and C(56)
  • SLC35G1 is an interacting partner of STIM1 that enables STIM1 binding to multiple transporters
  • ORAI1 channel activation and changes in ion selectivity probably result from the same underlying energetic changes that are driven by STIM1 binding
  • SLN and STIM1 act in opposing fashions to govern store operated Ca(2+) entry (SOCE) during myogenesis
  • alternate mechanism to recruit STIM1 into the ER-plasma membrane junctions via binding to ASPH
  • ASPH is an interacting partner of ORAI1-STIM1 complex
  • SURF4 associated with STIM1 in the endoplasmic reticulum, and modulates STIM1-mediated SOCE
  • sarcoplasmic reticulum (SR) Ca(2+) sensor that activates ORAI1, the Ca(2+) channel responsible for store-operated Ca(2+) entry (SOCE)
  • STIM1 and STIM1L bind to ORAI1, TRPC3, and TRPC6
  • STIM1 CTID domain determines access of SARAF to SOAR to regulate ORAI1 channel function
  • NEUROD2, neurogenic transcription factor, binding to an intronic element within the STIM1 gene
  • cell & other
    Other phosphorylated during mitosis leading to suppression of store-operated calcium entry
    mitochondrial depolarization selectively regulates trafficking of STIM1 multimers to the plasma membrane and in a manner dependent on the mitochondrial protein MFN2
    STIM1 is transcriptionally regulated by NFATC3
    corresponding disease(s) TBAM , IMD10
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in rhabdomyosarcoma and rhabdoid tumor
    constitutional       loss of function
    of STIM1 and STIM2 in T cells, and the consequent aberrations in T cell function, underlies the onset and progression of salivary gland autoimmunopathy in Sjögren syndrome
    Variant & Polymorphism
    Candidate gene
  • plays an essential role in the development of cardiomyocyte hypertrophy
  • Marker
    Therapy target
  • mice lacking functional STIM1 die perinatally from a skeletal myopathy
  • mice deficient for both endoplasmic reticulum calcium sensor Stim1 and Stim2 was immunized with T-cell dependent and independent antigens