UniProt release 14.9

Hush, Little Fly...

Most organisms slumber and so do flies. As in humans, caffeine or amphetamines keep them awake, while antihistamines make them fall asleep. Not surprisingly, prolonged sleep deprivation can lead to lethality. These and other similarities prompted researchers to use Drosophila melanogaster as a model organism to study the genetic basis of sleep.

Sleep is regulated by two main processes: circadian and homeostatic. The first says it is time to sleep, the second signals the need to rest, independently of the hour of the day. In July 2008, Koh et al. showed that in Drosophila, mutations in a single protein, Quiver, well-renamed Sleepless by the authors, deeply perturb the homeostatic control. Loss of this protein causes an extreme reduction in sleep (>80%). About 9% of the flies don't sleep at all. Although the mutants had a shortened lifespan, they were still capable of flying and mating!

Quiver is thought to act through the regulation of the Shaker K+ channel, lowering membrane excitability by modulating its expression and activity. It could thus be a signaling molecule that links homeostatic sleep drive to neuronal excitability.

Although Quiver is well-conserved in other insect species and a potential ortholog has been identified in C.elegans, there are no obvious homologs in vertebrates. However, many members of the Shaker potassium channel family are known from yeast to humans.

If there is indeed a common mechanism for sleep control between humans and flies, one might envision relieving some form of insomnia by acting on K+ channels. In the meantime, we advise you to keep counting sheep, or flies, when you can't get sleep...

Quiver is now available in UniProtKB/Swiss-Prot and the first Protein Spotlight issue of this year has been devoted to this protein.

UniProtKB News

Cross-references to TCDB

Cross-references have been added to the Transport Classification Database TCDB. TCDB details a comprehensive IUBMB approved classification system for membrane transport proteins known as the Transporter Classification (TC) system. The TC system is analogous to the Enzyme Commission (EC) system for classification of enzymes, but incorporates phylogenetic information additionally.

TCDB is available at http://www.tcdb.org/.

The format of the explicit links in the flat file is:

P0A903:
DR   TCDB; 1.B.33.1.3; outer membrane protein insertion porin (OmpIP) family.

P0AC02:
DR   TCDB; 1.B.33.1.3; outer membrane protein insertion porin (OmpIP) family.

O60840:
DR   TCDB; 1.A.1.11.11; voltage-gated ion channel (VIC) superfamily.
DR   TCDB; 1.A.1.11.15; voltage-gated ion channel (VIC) superfamily.

Cross-references to Pathway_Interaction_DB

Cross-references have been added to the Pathway Interaction Database Pathway_Interaction_DB. The Pathway Interaction Database is a highly-structured, curated collection of information about known biomolecular interactions and key cellular processes assembled into signaling pathways.

Pathway_Interaction_DB is available at http://pid.nci.nih.gov/.

The format of the explicit links in the flat file is:

O00422:
DR   Pathway_Interaction_DB; hdac_classi_pathway; Signaling events mediated by HDAC Class I.
DR   Pathway_Interaction_DB; hedgehog_glipathway; Hedgehog signaling events mediated by Gli proteins.
DR   Pathway_Interaction_DB; smad2_3nuclearpathway; Regulation of nuclear SMAD2/3 signaling.
DR   Pathway_Interaction_DB; telomerasepathway; Regulation of Telomerase.

O14640:
DR   Pathway_Interaction_DB; ps1pathway; Presenilin action in Notch and Wnt signaling.
DR   Pathway_Interaction_DB; wnt_canonical_pathway; Canonical Wnt signaling pathway.

Changes concerning keywords

New keywords:

• Disulfide bond
• Hypogonadotropic hypogonadism
• Isopeptide bond

Modified keyword:

• Polyneuropathy -> Neuropathy