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FLASH GENE
Symbol STIM1 contributors: mct/npt/pgu - updated : 16-03-2015
HGNC name stromal interaction molecule 1
HGNC id 11386
Corresponding disease
IMD10 immunodeficiency 10
TBAM tubular-aggregate myopathy
Location 11p15.4      Physical location : 3.876.932 - 4.114.440
Synonym name would be different from SCTZ104
Synonym symbol(s) D11S4896E, GOK, STIM1L
DNA
TYPE functioning gene
SPECIAL FEATURE antisens
text
  • head-to-tail configuration with the ribonucleotide reductase 1 gene RRM1
  • the 3' end of this gene is located 1,6kb from the 5'end of RRM1 gene
  • STRUCTURE 237.51 kb     12 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence
    MAPPING cloned Y linked N status provisional
    Map pter - NUP98 - STIM1 - RRM1 - cen
    Physical map
    PHLDA2 11p15.5 pleckstrin homology-like domain, family A, member 2 NAP1L4 11p15.5 nucleosome assembly protein 1-like 4 PRO0943 11p15.5 hypothetical protein PRO0943 CARS 11p15.5 cysteinyl-tRNA synthetase OSBPL5 11p15.4 oxysterol binding protein-like 5 FLJ36102 11p15.5 hypothetical protein FLJ36102 MRGE 11p15.5 mas-related G protein-coupled MRGE ZNF195 11p15.5 zinc finger protein 195 OR7E12P 11p15.5 olfactory receptor, family 7, subfamily E, member 12 pseudogene LOC387744 11 similar to asparagine-linked glycosylation 1 homolog (yeast, beta-1,4-mannosyltransferase); beta-1,4 mannosyltransferase LOC387745 11 similar to hypothetical protein SB153 LOC387746 11 LOC387746 LOC341141 11p15.5 similar to seven transmembrane helix receptor TRPC2 11p15.4-p15.3 transient receptor potential cation channel, subfamily C, member 2 ART5 11p15.5 ADP-ribosyltransferase 5 ART1 11p15.5 ADP-ribosyltransferase 1 CHRNA10 11p15.5 cholinergic receptor, nicotinic, alpha polypeptide 10 NUP98 11p15.5 nucleoporin 98kDa FRAG1 11p15.5 nucleoporin 98kDa ARHG 11p15.5-p15.4 ras homolog gene family, member G (rho G) STIM1 11p15.5 stromal interaction molecule 1 RRM1 11p15.5 ribonucleotide reductase M1 polypeptide LOC390030 11 similar to olfactory receptor GA_x6K02T2PBJ9-5199377-5198367 LOC340977 11p15.4 similar to Chain A, Crystal Structure Of The Radixin Ferm Domain Complexed With Inositol-(1,4,5)-Triphosphate LOC196120 11p15.4 similar to RIKEN cDNA 1500011L16 LOC390031 11 similar to RIKEN cDNA 1500011L16 LOC256875 11p15.4 similar to RIKEN cDNA 1500011L16 LOC390032 11 similar to RIKEN cDNA 1500011L16 LOC143506 11p15.4 similar to RIKEN cDNA 1500011L16 LOC390033 11 similar to RIKEN cDNA 1500011L16 LOC143496 11p15.4 similar to Olfactory receptor 52B4 LOC387747 11 similar to seven transmembrane helix receptor SSA1 11p15.5 Sjogren syndrome antigen A1 (52kDa, ribonucleoprotein autoantigen SS-A/Ro) LOC390034 11 similar to olfactory receptor MOR16-1 LOC119775 11p15.4 similar to seven transmembrane helix receptor LOC119774 11p15.4 similar to Olfactory receptor 52K2 LOC390035 11 similar to Olfactory receptor 52K2 LOC390036 11 similar to Olfactory receptor 52K1 LOC338637 11p15.4 similar to olfactory receptor GA_x6K02T2PBJ9-5333671-5332712 LOC119772 11p15.4 similar to seven transmembrane helix receptor NOV1 11p15.5 NOV1 LOC143502 11p15.4 similar to Olfactory receptor 52I2 LOC390037 11 similar to Olfactory receptor 52I1 RNF137 11p15.4 ring finger protein 137 LOC390038 11 similar to seven transmembrane helix receptor MGC24137 11p15.4 hypothetical protein MGC24137 LOC390039 11 similar to olfactory receptor MOR11-2 OR51E2 11p15 olfactory receptor, family 51, subfamily E, member 2 LOC390040 11 similar to olfactory receptor MOR14-2
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 4062 74 685 - 2009 19182790
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    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
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialabsorptive excretorydigestive epithelium (mucosa)   Rattus norvegicusAdult
    Muscularstriatumskeletal highly Homo sapiensAdult
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticplatelet Homo sapiens
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 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
    HOMOLOGY
    interspecies homolog to murine Stim1 (96.8pc)
    Homologene
    FAMILY
  • ezrin/radixin/moesin family
  • CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,granule
    intracellular,cytoplasm,cytoskeleton,microtubule
    text
  • 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
  • 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
  • CELLULAR PROCESS cell cycle, progression
    cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    text ion transport
    PATHWAY
    metabolism
    signaling
    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
  • INTERACTION
    DNA
    RNA
    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 CTID domain determines access of SARAF to SOAR to regulate ORAI1 channel function
  • cell & other
    REGULATION
    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
    ASSOCIATED DISORDERS
    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
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • plays an essential role in the development of cardiomyocyte hypertrophy
  • Marker
    Therapy target
    ANIMAL & CELL MODELS
  • 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