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

. Upon activation of the

IP3 receptor Inositol trisphosphate receptor (InsP3R) is a membrane glycoprotein complex acting as a Ca2+ channel activated by inositol trisphosphate (InsP3). InsP3R is very diverse among organisms, and is necessary for the control of cellular and physiol ...

, 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 release-activated calcium channel protein 1 is a calcium selective ion channel that in humans is encoded by the ''ORAI1'' gene. Orai channels play an important role in the activation of T-lymphocytes. The loss of function mutation of Orai ...

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 In cell biology, adherens junctions (or zonula adherens, intermediate junction, or "belt desmosome") are protein complexes that occur at cell–cell junctions and cell–matrix junctions in epithelial and endothelial tissues, usually more basal ...

. 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 Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with

TMEM110 Definition and cellular localization TMEM110, also designated as ''STIMATE'' (for STIM-activating enhancer), is an ER-resident multi-transmembrane protein identified through a proteomic study on the ER-PM junctions. The ER-PM junctions are define ...

(STIMATE),

SERCA SERCA, or sarcoplasmic/endoplasmic reticulum Ca2+-ATPase, or SR Ca2+-ATPase, is a calcium ATPase-type P-ATPase. Its major function is to transport calcium from the cytosol into the sarcoplasmic reticulum. Function SERCA is a P-type ATPase. It ...

, TMEM66 ( SARAF), and STIM2.

Clinical relevance

STIM1 mutations are associated with Immunodeficiency 10, Tubular aggregate myopathy type 1 (TAM1), and Stormorken syndrome.

References

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