Worming into the Uncharacterized Human Proteome

Using neXtProt release 2019–01–11, we manually curated
a list of 1837 functionally uncharacterized human proteins. Using
OrthoList 2, we found that 270 of them have homologues in Caenorhabditis elegans, including 60 with a one-to-one orthology
relationship. According to annotations extracted from WormBase, the
vast majority of these 60 worm genes have RNAi experimental data or
mutant alleles, but manual inspection shows that only 15% have phenotypes
that could be interpreted in terms of a specific function. One third
of the worm orthologs have protein–protein interaction data,
and two of these interactions are conserved in humans. The combination
of phenotypic, protein–protein interaction, and gene expression
data provides functional hypotheses for 8 uncharacterized human proteins.
Experimental validation in human or orthologs is necessary before
they can be considered for annotation.