Stromal interaction molecule 1 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''STIM1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
STIM1 has a single
transmembrane
A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently u ...
domain, and is localized to the
endoplasmic reticulum
The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...
, and to a lesser extent to the
plasma membrane
The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
.
Even though the protein has been identified earlier, its function was unknown until recently. In 2005, it was discovered that STIM1 functions as a calcium sensor in the
endoplasmic reticulum
The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...
.
Upon activation of the
IP3 receptor, the calcium concentration in the endoplasmic reticulum decreases, which is sensed by STIM1, via its
EF hand
The EF hand is a helix–loop–helix structural domain or ''motif'' found in a large family of calcium-binding proteins.
The EF-hand motif contains a helix–loop–helix topology, much like the spread thumb and forefinger of the human hand, in ...
domain. STIM1 activates the "store-operated"
ORAI1 calcium
ion channels
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ...
in the plasma membrane, via intracellular STIM1 movement, clustering under plasma membrane and protein interaction with ORAI isoforms.
STIM1-mediated calcium entry is required for
thrombin
Prothrombin (coagulation factor II) is encoded in the human by the F2-gene. It is proteolytically cleaved during the clotting process by the prothrombinase enzyme complex to form thrombin.
Thrombin (Factor IIa) (, fibrose, thrombase, throm ...
-induced disassembly of
VE-cadherin
Cadherin-5, or VE-cadherin (vascular endothelial cadherin), also known as CD144 ( Cluster of Differentiation 144), is a type of cadherin. It is encoded by the human gene ''CDH5''.
Function
VE-cadherin is a classical cadherin from the cadherin ...
adherens junctions.
2-Aminoethoxydiphenyl borate (2-APB) and 4-chloro-3-ethylphenol (4-CEP) cause STIM1 clustering in a cell and prevent STIM1 moving toward plasma membrane.
Interactions
STIM1 has been shown to
interact with
ORAI1,
TMEM110 (STIMATE),
SERCA, TMEM66 (
SARAF), and
STIM2.
Clinical relevance
STIM1 mutations are associated with Immunodeficiency 10, Tubular aggregate myopathy type 1 (TAM1), and Stormorken syndrome.
References
{{gene-11-stub