| TMEM38A | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | TMEM38A , TRIC-A, TRICA, transmembrane protein 38A | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 611235 MGI: 1921416 HomoloGene: 11449 GeneCards: TMEM38A | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Trimeric intracellular cation-selective channel A (TRIC-A) is a monovalent cation channel in the SR and nuclear membranes of skeletal muscle cells, [5] [6] encoded by the transmembrane protein 38A (TMEM38A) gene. It is one of two known TRIC proteins, the other being TRIC-B.
TRIC-A is a 33kDa [7] transmembrane protein, expressed predominantly in excitable tissues including skeletal muscle and brain. [5] Its N-terminal region is located in the SR lumen [7] or within the nucleus while its C-terminal region projects into the cytoplasm. [5] In situ, TRIC-A forms homo-trimers, producing its "bullet-shaped" three-dimensional structure (see Venturi et al. (2012), Figure 1 for a three-dimensional rendering of TRIC-A).
TRIC-A is permeable to both Na+ and K+ but not divalent cations like Ca2+. [5] The channel exhibits marked voltage-dependence, becoming more open when the cytosol is more positively charged than the ER lumen. TMEM38A-knockout mice exhibit reduced Ryanodine receptor 1-mediated Ca2+ release; [5] as such, K+ flux into the SR through TRIC-A is thought to support RyR1-mediated efflux of Ca2+ ions from the sarcoplasmic reticulum into the cytosol. These knockouts also develop hypertension during early adulthood, whereas transgenic mice overexpressing TRIC-A develop hypotension. These results are thought to reflect a role for TRIC-A in the excitability of vascular smooth muscle cells.
TRIC-A has been implicated in the regulation of arterial blood pressure through regulating the excitability of vascular smooth muscle cells. [5] Several single-nucleotide polymorphisms (SNPs) in close proximity to the TRIC-A locus increase the risk of hypertension and reduce the efficiency of antihypertensive drugs in its treatment. [8] Such SNPs are in positive linkage disequilibrium with TRIC-A, meaning they are unlikely to be separated by genetic recombination and so are more frequently inherited together from the same parent chromosome. As such, TRIC-A SNPs can provide biomarkers for the diagnosis of essential hypertension and, in future, may help to determine which treatments may be most well-suited to a given individual [5] (see personalized medicine).
Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction of all muscle cell types, and in fertilization. Many enzymes require calcium ions as a cofactor, including several of the coagulation factors. Extracellular calcium is also important for maintaining the potential difference across excitable cell membranes, as well as proper bone formation.
Calcium release-activated channels (CRAC) are specialized plasma membrane Ca2+ ion channels. When calcium ions (Ca2+) are depleted from the endoplasmic reticulum (a major store of Ca2+) of mammalian cells, the CRAC channel is activated to slowly replenish the level of calcium in the endoplasmic reticulum. The Ca2+ Release-activated Ca2+ (CRAC) Channel (CRAC-C) Family (TC# 1.A.52) is a member of the Cation Diffusion Facilitator (CDF) Superfamily. These proteins typically have between 4 and 6 transmembrane α-helical spanners (TMSs). The 4 TMS CRAC channels arose by loss of 2TMSs from 6TMS CDF carriers, an example of 'reverse' evolution'.
Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. Second messengers trigger physiological changes at cellular level such as proliferation, differentiation, migration, survival, apoptosis and depolarization.
Ryanodine receptors form a class of intracellular calcium channels in various forms of excitable animal tissue like muscles and neurons. There are three major isoforms of the ryanodine receptor, which are found in different tissues and participate in different signaling pathways involving calcium release from intracellular organelles. The RYR2 ryanodine receptor isoform is the major cellular mediator of calcium-induced calcium release (CICR) in animal cells.
Calcium signaling is the use of calcium ions (Ca2+) to communicate and drive intracellular processes often as a step in signal transduction. Ca2+ is important for cellular signalling, for once it enters the cytosol of the cytoplasm it exerts allosteric regulatory effects on many enzymes and proteins. Ca2+ can act in signal transduction resulting from activation of ion channels or as a second messenger caused by indirect signal transduction pathways such as G protein-coupled receptors.
Transient receptor potential cation channel, subfamily M, member 2, also known as TRPM2, is a protein that in humans is encoded by the TRPM2 gene.
The Prostacyclin receptor, also termed the prostaglandin I2 receptor or just IP, is a receptor belonging to the prostaglandin (PG) group of receptors. IP binds to and mediates the biological actions of prostacyclin (also termed Prostaglandin I2, PGI2, or when used as a drug, epoprostenol). IP is encoded in humans by the PTGIR gene. While possessing many functions as defined in animal model studies, the major clinical relevancy of IP is as a powerful vasodilator: stimulators of IP are used to treat severe and even life-threatening diseases involving pathological vasoconstriction.
Calcium-activated potassium channel subunit alpha-1 also known as large conductance calcium-activated potassium channel, subfamily M, alpha member 1 (KCa1.1), or BK channel alpha subunit, is a voltage gated potassium channel encoded by the KCNMA1 gene and characterized by their large conductance of potassium ions (K+) through cell membranes.
Calcium-activated potassium channel subunit beta-1 is a protein that in humans is encoded by the KCNMB1 gene.
Potassium voltage-gated channel, Shab-related subfamily, member 1, also known as KCNB1 or Kv2.1, is a protein that, in humans, is encoded by the KCNB1 gene.
Chloride intracellular channel protein 5 is a protein that in humans is encoded by the CLIC5 gene.
Junctophilin-3 is a protein that in humans, is encoded by the JPH3 gene. The gene is approximately 97 kilobases long and is located at position 16q24.2. Junctophilin proteins are associated with the formation of junctional membrane complexes linking the plasma membrane with the endoplasmic reticulum in excitable cells. Junctophilin-3 is specific to the brain and has an active role in neurons involved in motor coordination and memory.
Junctophilin 2, also known as JPH2, is a protein which in humans is encoded by the JPH2 gene. Alternative splicing has been observed at this locus and two variants encoding distinct isoforms are described.
Junctophilin-1 is a protein that in humans is encoded by the JPH1 gene.
Anoctamin-1 (ANO1) also known as Transmembrane member 16A (TMEM16A) is a protein that, in humans, is encoded by the ANO1 gene. Anoctamin-1 is a voltage-gated calcium-activated anion channel, which acts as a chloride channel and a bicarbonate channel. additionally Anoctamin-1 is apical iodide channel. It is expressed in smooth muscle, epithelial cells, vomeronasal neurons, olfactory sustentacular cells, and is highly expressed in interstitial cells of Cajal (ICC) throughout the gastrointestinal tract.
Calcium buffering describes the processes which help stabilise the concentration of free calcium ions within cells, in a similar manner to how pH buffers maintain a stable concentration of hydrogen ions. The majority of calcium ions within the cell are bound to intracellular proteins, leaving a minority freely dissociated. When calcium is added to or removed from the cytoplasm by transport across the cell membrane or sarcoplasmic reticulum, calcium buffers minimise the effect on changes in cytoplasmic free calcium concentration by binding calcium to or releasing calcium from intracellular proteins. As a result, 99% of the calcium added to the cytosol of a cardiomyocyte during each cardiac cycle becomes bound to calcium buffers, creating a relatively small change in free calcium.
Stimulator of interferon genes (STING), also known as transmembrane protein 173 (TMEM173) and MPYS/MITA/ERIS is a protein that in humans is encoded by the STING1 gene.
The Calcium-Dependent Chloride Channel (Ca-ClC) proteins (or calcium-activated chloride channels, are heterogeneous groups of ligand-gated ion channels for chloride that have been identified in many epithelial and endothelial cell types as well as in smooth muscle cells. They include proteins from several structurally different families: chloride channel accessory, bestrophin, and calcium-dependent chloride channel anoctamin channels ANO1 is highly expressed in human gastrointestinal interstitial cells of Cajal, which are proteins which serve as intestinal pacemakers for peristalsis. In addition to their role as chloride channels some CLCA proteins function as adhesion molecules and may also have roles as tumour suppressors. These eukaryotic proteins are "required for normal electrolyte and fluid secretion, olfactory perception, and neuronal and smooth muscle excitability" in animals. Members of the Ca-CIC family are generally 600 to 1000 amino acyl residues in length and exhibit 7 to 10 transmembrane segments.
Trimeric intracellular cation-selective channel B (TRIC-B) is a monovalent cation channel in the ER membrane encoded by the transmembrane protein 38B (TMEM38B) gene. It is one of two known TRIC proteins, the other being TRIC-A.
The trimeric intracellular cation-selective channels or TRIC proteins are a group of homo-trimeric cation channel proteins of ~300 residues in the ER membrane. There are two known TRIC proteins, TRIC-A and TRIC-B.
