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FLASH GENE

Symbol

ORAI1

contributors: mct/npt/pgu - updated : 25-09-2015

HGNC name	ORAI calcium release-activated calcium modulator 1
HGNC id	25896

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive salivary gland         Lymphoid/Immune lymph node       highly Reproductive female system ovary     highly   female system uterus cervix     Respiratory respiratory tract larynx

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose       Muscular striatum     highly Homo sapiens Adult

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

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional         a single missense mutation in ORAI1 in some SCID patients

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive breast Both ATP2C22 and ORAI1 emerge as druggable targets of therapeutic potential in the treatment of some breast cancer subtypes neuromuscular myopathy   targeting Orai1 activity may be a promising therapeutic approach for the prevention and treatment of muscular dystrophy allergy asthm   strategies that target ORAI1 or the BPIFA1 deficiency in asthma may lead to novel therapies to treat this disease

ANIMAL & CELL MODELS