8.A.231.  The Quiver/Sleepless//Dreammist (QSD) Family  

QUIVER/SLEEPLESS/DREAMMIST orthologues in vaious animals are responsible for interactions with shaker-type potassium channels and nicotinic acetylcholine receptors (Wu et al. 2016).  It suppress excitability and synaptic transmission by upregulating potassium (K⁺) channels and downregulating nicotinic acetylcholine receptors (nAChRs) in wake-promoting neurons to facilitate sleep in Drosophila (Wu et al. 2016). Furthermore, the zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation (Barlow et al. 2023).  Dreammist (dmist), the loss of which results in behavioural hyperactivity and reduced sleep at night, is encoded by a gene that is neuronally expressed (the dmist gene) and is conserved across vertebrates. It encodes a small single- or double-pass transmembrane protein that is structurally similar to the Na⁺,K⁺-ATPase regulator, FXYD1/Phospholemman. Disruption of either fxyd1 or atp1a3a, a Na⁺,K⁺-ATPase alpha-3 subunit associated with several heritable movement disorders in humans, led to decreased night-time sleep. Since atpa1a3a and dmist mutants have elevated intracellular Na⁺ levels and non-additive effects on sleep amount at night,  Barlow et al. 2023 proposed that Dmist-dependent enhancement of Na⁺ pump function modulates neuronal excitability to maintain normal sleep behaviour.

There are two subfamilies, 1 and 2; they are of different lengths but the same topologies with two TMSs and the N-and C-termini.  However, membes of the two families do not bring each other up using TC BLAST.  Their common origin is not established.