TMEM110, also designated as STIMATE, is an ER-resident multi-transmembrane protein identified through a proteomic study on the ER-PM junctions. The ER-PM junctions are defined as specialized junctional sites, also known as membrane contact sites that connect the endoplasmic reticulum (ER) and the plasma membrane (PM), and are closely implicated in controlling lipid and calcium homeostasis in mammalian cells.
Basic Information of STIMATE | |
Protein Name | Store-operated calcium entry regulator STIMATE |
Gene Name | STIMATE |
Aliases | TMEM110 |
Organism | Homo sapiens (Human) |
UniProt ID | Q86TL2 |
Transmembrane Times | 5 |
Length (aa) | 294 |
Sequence | MQGPAGNASRGLPGGPPSTVASGAGRCESGALMHSFGIFLQGLLGVVAFSTLMLKRFREPKHERRPWRIWFLDTSKQAIGMLFIHFANVYLADLTEEDPCSLYLINFLLDATVGMLLIYVGVRAVSVLVEWQQWESLRFGEYGDPLQCGAWVGQCALYIVIMIFEKSVVFIVLLILQWKKVALLNPIENPDLKLAIVMLIVPFFVNALMFWVVDNFLMRKGKTKAKLEERGANQDSRNGSKVRYRRAASHEESESEILISADDEMEESDVEEDLRRLTPLKPVKKKKHRFGLPV |
TMEM110 is a positive modulator of calcium flux mediated by the STIM-ORAI signaling in vertebrates. STIMATE can physically associate with STIM1 to promote conformational switch of STIM1 from inactive toward an activated state, thereby coupling to and gating the ORAI calcium channels on the plasma membrane. Depletion of TMEM110 with RNAi knockdown or Cas9-mediated gene disruption substantially reduces the puncta formation of STIM1 at ER-PM junctions and remarkably inhibits the calcium/calcineurin/ NFAT signaling axis. Genetic depletion of STIMATE substantially reduces STIM1 puncta formation at ER-PM junctions and suppresses the Ca2+-NFAT signaling.
Fig.1 Tentative model of channels and Na+ /H+ ion exchanger in cell proliferation. (Lang, 2013)
This study inferred STIMATE (TMEM110) gene family phylogenetic trees in 69 sequenced chordate genomes by an integrated pipeline.
Authors reported that an ER-resident membrane protein identified in a previous genome-wide RNAi screen, transmembrane protein 110 (TMEM110), regulated the long-term maintenance of ER-plasma membrane junctions and the short-term physiological remodeling of the junctions during store-dependent calcium signaling.
This study showed that STIMATE, as a regulator of Ca2+ influx in vertebrates, promoted STIM1 conformational switch by physically interacting with STIM1.
This study was to estimate the effect of SNP marker for semen volume (SV) and total number of sperm (TNS) and identified three genes (DCP1A, SFMBT1, TMEM110) located near some significant markers.
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