ORAI1
Encyclopedia
Calcium release-activated calcium channel protein 1 is a calcium selective ion channel
that in humans is encoded by the ORAI1 gene
. Orai1 channels play important role in the activation of T-lymphocytes. The loss of function mutation of Orai1 causes severe combined immunodeficiency
(SCID) in humans The mammalian orai family has two additional homologs, orai2 and orai3. Orai proteins share no homology with any other ion channel family of any other known proteins. They have 4 transmembrane domains and form tetramers.
Orai channels are activated upon the depletion of internal calcium stores, which is called the "store-operated" or the "capacitative" mechanism. They are molecular constituents of the "calcium release activated calcium currents" (ICRAC
). Upon activation of phospholipase C
by various cell surface receptors, inositol trisphosphate is formed that releases calcium from the endoplasmic reticulum
. The decreased calcium concentration in the endoplasmic reticulum is sensed by the STIM1
protein. STIM1 clusters upon the depletion of the calcium stores and forms "puncta", and relocates near the plasma membrane, where it activates orai1 via protein protein interaction.
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
that in humans is encoded by the ORAI1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. Orai1 channels play important role in the activation of T-lymphocytes. The loss of function mutation of Orai1 causes severe combined immunodeficiency
Severe combined immunodeficiency
Severe combined immunodeficiency , is a genetic disorder in which both "arms" of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency...
(SCID) in humans The mammalian orai family has two additional homologs, orai2 and orai3. Orai proteins share no homology with any other ion channel family of any other known proteins. They have 4 transmembrane domains and form tetramers.
Orai channels are activated upon the depletion of internal calcium stores, which is called the "store-operated" or the "capacitative" mechanism. They are molecular constituents of the "calcium release activated calcium currents" (ICRAC
ICRAC
ICRAC stands for Calcium-Release Activated Calcium Current. When calcium ions are depleted from the endoplasmic reticulum of mammalian cells, a special plasma membrane Ca2+ channel, the CRAC channel, is activated to slowly replenish the level of calcium in the endoplasmic reticulum.-Structure:The...
). Upon activation of phospholipase C
Phospholipase C
Phosphoinositide phospholipase C is a family of eukaryotic intracellular enzymes that play an important role in signal transduction processes. In general, this enzyme is denoted as Phospholipase C, although three other families of phospholipase C enzymes have been identified in bacteria and in...
by various cell surface receptors, inositol trisphosphate is formed that releases calcium from the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
. The decreased calcium concentration in the endoplasmic reticulum is sensed by the STIM1
STIM1
Stromal interaction molecule 1 is a protein that in humans is encoded by the STIM1 gene. STIM1 has a single transmembrane domain, and is localized to the endoplasmic reticulum, and to a lesser extent to the plasma membrane....
protein. STIM1 clusters upon the depletion of the calcium stores and forms "puncta", and relocates near the plasma membrane, where it activates orai1 via protein protein interaction.