Tuesday, April 11, 2017

Curating the C. elegans kinome in UniProt

One of the key strengths of the UniProt Knowledgebase is the expert curation that goes into the entries in the reviewed Swiss-Prot section. Here we give you an insight into a recent curation project to review and annotate the kinome of the nematode worm Caenorhabditis elegans. The image below shows an overview of the project, including the proportion of Swiss-Prot entries for C. elegans kinases at the start and end of the project, the breakdown of the kinome into kinase families and a word cloud of the most prevalent GO terms found in the C. elegans kinome. 

This project builds on previous work in the group to curate the human and mouse kinomes which was completed and published in 2008. In addition to the ongoing update of the human and mouse kinomes as new information becomes available, we decided to extend curation efforts to the C. elegans kinome. C. elegans contains 438 kinases and almost half have been functionally characterized, highlighting that C. elegans is a valuable model organism to understand the role of kinases in biological processes. In addition, studies in C. elegans can shed light on human biology and disease. For example, genetic studies of C. elegans lrk-1, a homolog of human kinase LRRK2 which is involved in Parkinson’s disease, have helped to shed light on its role in the development of the nervous system and provided some clues to help understand the progressive neurodegeneration caused by LRRK2 mutations.

Some key characteristics of the C.elegans kinome are:

  • It contains the same proportion of kinases as the human proteome (approximately 2% of both proteomes)
  • It contains members from all 10 kinase groups
  • Kinase domains are not only found in cytoplasmic proteins but also in transmembrane proteins while one C. elegans kinase, H03A11.1, is thought to be secreted based on similarity to human FAM20C which has been shown experimentally to be secreted
  • Pseudokinases represent 9% of the C. elegans kinome
  • C. elegans has many unique kinases including members of the CK1 group which have not been studied experimentally but understanding the function of these kinases could provide valuable information for developing strategies to eliminate parasitic worms

We recently published an article describing this effort in the Biochemical Journal so you can read the results of the project here http://www.biochemj.org/content/474/4/493!