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FLASH GENE
Symbol STIM2 contributors: npt/mct/pgu - updated : 15-11-2016
HGNC name stromal interaction molecule 2
HGNC id 19205
Location 4p15.2      Physical location : 26.862.312 - 27.027.003
Synonym symbol(s) KIAA1482, FLJ39527
DNA
TYPE functioning gene
STRUCTURE 164.70 kb     12 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
12 splicing 3924 - 746 ER resident 2015 26033257
  • STIM2.2 or STIM2alpha
  • produced after cleavage of the 101-AA STIM2 signal peptide following translocation across the ER membrane
  • - - - - - cytosolic preSTIM2 2015 26033257
  • escapes ER targeting to remain signal peptide intact within the cytosol
  • stably associates with the plasma membrane, where it regulates basal Ca2+ concentration in a store-independent manner
  • displays impressive targeting to the inner leaflet of the plasma membrane
  • preSTIM2 N terminus may also play a regulatory role in ORAI1 activation as co-expression of ORAI1
  • - - - - 91 cytosolic SPF 2015 26033257
  • synthesized after cleavage of the STIM2 signal peptide into a 91 AAS SPF
  • released into the cytosol, the SPF regulates NF-KB transcription
  • 13 splicing 5178 - 754 - 2015 26033257
  • STIM2.1 or STIM2beta
  • is a potent inhibitor of SOCE, through a sequence-specific allosteric interaction with ORAI1
  • is an additional player tuning ORAI1 activation
  • 13 splicing 5222 - 599 - 2015 26033257
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   highly
    Cardiovascularheart   highly
    Endocrinethyroid   highly
    Lymphoid/Immunelymph node   predominantly
    Reproductivefemale systemovary  highly
    Respiratorylung   highly
    Visualeye   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticplatelet Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal ER-luminal Ca2+-sensing domains, confering decreased Ca2+ entry and controling the activation kinetics of ORAI1 channels
  • a 14 aa signal peptide
  • an unpaired EF-hand domain
  • a SAM (sterile alpha motif) domain
  • two coiled-coil regions (CC1 and CC2)
  • a proline-rich domains (P)
  • lysine-rich domains
  • secondary structure the K-rich domain of STIM2, but not of STIM1, forms an amphipathic alpha-helix
    conjugated GlycoP , PhosphoP
    mono polymer oligo
    isoforms Precursor preSTIM2 (cleavage of the 101-aa STIM2 signal peptide following translocation across the ER membrane)
    HOMOLOGY
    interspecies homolog to rattus Stim2 (91.4 pc)
    homolog to murine Stim2 (90.4 pc)
    Homologene
    FAMILY
  • stromal interaction molecule (STIM) gene family
  • CATEGORY regulatory , transport
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,granule
    text
  • single-pass type 1 membrane protein
  • sensors of endoplasmic reticulum (ER) luminal Ca2+ changes and rapidly translocate into near plasma membrane (PM) junctions to activate Ca2+ entry
  • expressed in the lysosome-related organelles and dense granules in human platelets
  • exists in at least three distinct functional forms that reside in the ER and in the cytosol
  • basic FUNCTION
  • inhibiting STIM1-mediated Ca(2+) influx
  • involved in negative regulation of calcium ion transport via store-operated calcium channel
  • having two distinct modes of activating Ca2+ release-activated Ca2+ channels
  • transmembrane endoplasmic reticulum Ca2+ sensors, coupling directly to activate plasma membrane ORAI1 Ca2+ entry channels
  • play a relevant role in intracellular Ca2+ homeostasis as a feedback regulator that stabilizes resting cytosolic and ER Ca2+ concentrations
  • both STIM1 and STIM2 have a capacity to bind to a chaperone, calnexin as well as two protein-transporters, exportin1 and transportin1
  • 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
  • unlike STIM1, STIM2 can regulate ORAI1 in a store-dependent and store-independent manner
  • STIM2 signal peptide functions to augment NF-KB-mediated gene transcription after its release as a &
  • 8764;91-aa SPF into the cytosol
  • potential role for STIM1, STIM2 proteins and T-cell function in the pathogenesis of Sjögren syndrome
  • 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
  • STIM1, STIM2, and ORAI1 regulate store-operated calcium entry and purinergic activation of microglia
  • is a central organizer of excitatory synapses, and influences the formation of dendritic spines and shapes basal synaptic transmission in excitatory neurons
  • unique mechanism of synaptic plasticity driven by dynamic assembly of a STIM2 signaling complex at ER-plasma membrane (PM) contact sites
  • protects hippocampal mushroom spines from amyloid synaptotoxicity
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text Ca2+ transport
    PATHWAY
    metabolism
    signaling
    a component
  • oligomer with STIM1
  • part of STIM2/ORAI1 complex, may be under the control of both luminal and cytoplasmic Ca2+ levels
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to STIM1
  • 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
  • associates with ORAI1 and ATP2A3 upon discharge of the acidic Ca2+ stores in human platelets (
  • preSTIM2 and ORAI1 synergize to regulate constitutive Ca2+ entry
  • SARAF, with STIM2, may act on a similar Ca2+ permeation pathway
  • STIM2 enhances agonist-mediated activation of SOCE by promoting STIM1 clustering in ER-PM junctions at low stimulus intensities
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    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
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mice deficient for both endoplasmic reticulum calcium sensor Stim1 and Stim2 was immunized with T-cell dependent and independent antigens