TMEM38A

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.

TMEM38A
Identifiers
Aliases	TMEM38A, TRIC-A, TRICA, transmembrane protein 38A
External IDs	OMIM: 611235; MGI: 1921416; HomoloGene: 11449; GeneCards: TMEM38A; OMA:TMEM38A - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.11 Start 16,661,139 bp[1] End 16,690,023 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 B3.3 Start 72,572,055 bp[2] End 72,587,282 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in muscle of thigh gastrocnemius muscle quadriceps femoris muscle vastus lateralis muscle skeletal muscle tissue tibialis anterior muscle Skeletal muscle tissue of rectus abdominis deltoid muscle biceps brachii Skeletal muscle tissue of biceps brachii Top expressed in interventricular septum muscle of thigh skeletal muscle tissue medial head of gastrocnemius muscle triceps brachii muscle quadriceps femoris muscle tibialis anterior muscle temporal muscle sternocleidomastoid muscle vastus lateralis muscle More reference expression data BioGPS n/a
Gene ontology Molecular function potassium channel activity cation channel activity calcium-activated potassium channel activity Cellular component sarcoplasmic reticulum integral component of membrane nuclear membrane extracellular exosome membrane sarcoplasmic reticulum membrane nucleus Biological process potassium ion transport ion transport potassium ion transmembrane transport transport endoplasmic reticulum organization regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion release of sequestered calcium ion into cytosol by sarcoplasmic reticulum protein homotrimerization cellular response to caffeine Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 79041 74166 Ensembl ENSG00000072954 ENSMUSG00000031791 UniProt Q9H6F2 Q3TMP8 RefSeq (mRNA) NM_024074 NM_144534 RefSeq (protein) NP_076979 NP_653117 NP_001344207 NP_001344208 NP_001344209 NP_001344213 Location (UCSC) Chr 19: 16.66 – 16.69 Mb Chr 8: 72.57 – 72.59 Mb PubMed search [3] [4]
Wikidata
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Structure

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).

Function

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.

Clinical significance

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).

See also

• TMEM38B
• Trimeric intracellular cation-selective channel