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FLASH GENE
Symbol ORAI1 contributors: mct/npt/pgu - updated : 25-09-2017
HGNC name ORAI calcium release-activated calcium modulator 1
HGNC id 25896
Corresponding disease
IMD9 Immunodeficiency 9
Location 12q24.31      Physical location : 122.064.454 - 122.079.946
Synonym name
  • hypothetical protein LOC84876
  • CRAC (Ca2+-release-activated Ca2+) modulator 1
  • transmembrane protein 142A
    • Synonym symbol(s) FLJ14466, CRACM1, TMEM142A, CRAC, ORAT1
    DNA
    TYPE functioning gene
    STRUCTURE 15.49 kb     2 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 1497 33 301 - 2012 2264169
  • ORAI1 alpha
    • - splicing - - 23 - 2012 2264169
  • arises from alternative translation initiation from a methionine at position 64, and possibly also 71, in the longer ORAI1 alpha form
  • significantly faster than ORAI1alpha for mobility in the plasma membrane
    • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland    
    Lymphoid/Immunelymph node   highly
    Reproductivefemale systemovary  highly
     female systemuteruscervix  
    Respiratoryrespiratory tractlarynx   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    Muscularstriatum  highly Homo sapiensAdult
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four putative transmembrane segments participating
    • in ORAI1-ORAI1 interactions
  • cytoplasmic C terminus required for its interaction with STIM1
    • HOMOLOGY
    Homologene
    FAMILY
  • Orai family
    • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • colocalized with T cell receptor molecules at the interface between T cells and dendritic cells
  • STIM1 and ORAI1 are both localized at the skeletal-muscle triad, a specialized junction between the ER and the plasma membrane
  • ASPH is a structural component of the ER-PM junctions where ORAI1 and STIM1 cluster and interact in T cells
    • basic FUNCTION
  • is essential for store-operated Ca2+ entry
  • may be an essential component or regulator of the CRAC channel complex
  • essential properties of ORAI1 function can be rationalized by interactions with discrete regions of STIM1
  • plasma membrane Ca(2+) channel that migrate and become tethered by STIM within the ER-PM junctions, where they mediate exceedingly selective Ca(2+) entry
  • likely candidate for mediating ATP2C2-regulated, store-independent Ca2+ influx in breast cancer cells
  • pivotal role of the ORAI1 channel in mediation of SOCE that gives rise to the sustained Ca2+ response in cells exposed to FASL
  • activation of platelets by thrombin leads to up-regulation of SGK1 and ORAI1 protein expression, an effect expected to further enhance activation-dependent Ca2+ entry into platelets with subsequent Ca2+-dependent degranulation, adhesion, aggregation and thrombus formation
  • involved in the function but not in the differentiation of osteoblasts, and potentially plays a critical role in bone homeostasis by regulating both osteoblasts and osteoclastsv
  • mediates exacerbated Ca(2+) entry in dystrophic skeletal muscle
  • mediates detrimental calcium influx caused by endogenous oxidative stress
  • its function is essential for T cell homing to lymph nodes
  • central role of STIM1 and ORAI1 in SCDI (Slow Ca(2+)-dependent inactivation)
  • STIM1, STIM2, and ORAI1 regulate store-operated calcium entry and purinergic activation of microglia
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • components of Ca2+ release-activated Ca2+ channels (CRACs) 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
  • interacting with 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
  • ATP2C2 interacts with ORAI1 to mediate Ca2+ entry
  • STIM2 associates with ORAI1 and ATP2A3 upon discharge of the acidic Ca2+ stores in human platelets
  • biological role of Ca2+ and the ORAI1 channel that drives a transient negative feedback loop, introducing a lag phase in the early steps of the FAS signal
  • ASPH is an interacting partner of ORAI1-STIM1 complex
  • ORAI1 channel activation and changes in ion selectivity probably result from the same underlying energetic changes that are driven by STIM1 binding
  • STIM1 activates ORAI1, the Ca(2+) channel responsible for store-operated Ca(2+) entry (SOCE)
  • ubiquilin 1 downregulates intracellular Ca(2+) mobilization and its downstream signaling by promoting the ubiquitination and lysosomal degradation of ORAI1
  • 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
  • expression of ANO4 caused a delayed activation of membrane-localized ANO6 channels, solely through store-operated Ca2+ entry via ORAI1
    • cell & other
    REGULATION
    activated by by the STIM1 C terminus, but the Ser/Pro and polybasic Lys domains are not required for activation of ORAI1
    Other activation of platelets stimulates the translational expression of ORAI1, thus augmenting platelet Ca(2+) signaling
    ASSOCIATED DISORDERS
    corresponding disease(s) IMD9
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional        
    a single missense mutation in ORAI1 in some SCID patients
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    Both ATP2C22 and ORAI1 emerge as druggable targets of therapeutic potential in the treatment of some breast cancer subtypes
    neuromuscularmyopathy 
    targeting Orai1 activity may be a promising therapeutic approach for the prevention and treatment of muscular dystrophy
    allergyasthm 
    strategies that target ORAI1 or the BPIFA1 deficiency in asthma may lead to novel therapies to treat this disease
    ANIMAL & CELL MODELS