From the research laboratory to the database: the Caenorhabditis elegans kinome in UniProtKB

Abstract

Protein kinases form one of the largest protein families and are found in all species, from viruses to humans. They catalyze the reversible phosphorylation of proteins, often modifying their activity and localization. They are implicated in virtually all cellular processes and are one of the most intensively studied protein families. In recent years, they have become key therapeutic targets in drug development as natural mutations affecting kinase genes are the cause of many diseases. The vast amount of data contained in the primary literature and across a variety of biological data collections highlights the need for a repository where this information is stored in a concise and easily accessible manner. The UniProt Knowledgebase meets this need by providing the scientific community with a comprehensive, high-quality and freely accessible resource of protein sequence and functional information. Here, we describe the expert curation process for kinases, focusing on the Caenorhabditis elegans kinome. The C. elegans kinome is composed of 438 kinases and almost half of them have been functionally characterized, highlighting that C. elegans is a valuable and versatile model organism to understand the role of kinases in biological processes.

The Differential Phosphorylation-Dependent Signaling and Glucose Immunometabolic Responses Induced during Infection by Salmonella Enteritidis and Salmonella Heidelberg in Chicken Macrophage-like cells

“…Microsoft Excel 2016 (Redmond, WA) files containing kinomic data were generated and further analyzed using the online normalization and analysis tool known as Platform for Intelligent, Integrated Kinome Analysis (PIIKA2) [ 40 ]. The kinome peptide array data generated from PIIKA2 were analyzed by using other online databases like STRING [ 41 ], KEGG color and search pathway [ 42 ], UniProt [ 43 , 44 , 45 ], and PhosphosSitePlus [ 46 ].…”

Emerging concepts in pseudoenzyme classification, evolution, and signaling

“…As an experimental test bed for the curation and annotation of procedures to create pseudoenzyme databases, UniProtKB has recently reviewed and updated the annotation of the complete kinome (30) and phosphatome of the model worm Caenorhabditis elegans, which contain 438 kinases and 237 phosphatases, respectively. Among 208 kinase genes whose function has been experimentally characterized, 41 are annotated as pseudokinases, although supporting evidence is often lacking beyond predicted sequence information.…”

“…Pseudoenzymes have now been identified in many major enzyme families across the tree of life; predictably, this has been predominantly through computational sequence-based analyses (Table 1) (24,30). Most studies have traditionally compared the sequence of a relative of unknown structure and functional residues against sequences of relatives, which have been structurally characterized and annotated with known catalytic residues that have been confirmed experimentally (14).…”

Challenges in the annotation of pseudoenzymes in databases: the UniProtKB approach

“…A). While the annotation of enzymes is well‐established , the current annotation of pseudoenzymes needed to be revised to integrate new advances in the field. The revision process involved addressing various challenges to make sure that the new annotation workflow was appropriate.…”

“…These ECO codes are shown directly in the text version of the entries, while on the UniProtKB website, they are transformed into user‐friendly, easy‐to‐understand labels (Fig. ) . For instance, for information inferred from experimental data, we provide a link to the original paper.…”