Nucleotide sequence data and analysis commands the bulk of my attention on most days. But certainly post-translational modification of proteins has a lot of influence on the ultimate function (or dysfunction, in some cases) of the genes in play in a given situation. A recent paper reminded me of a resource that I’ve known about for a long time, but I was pleased to have a fresh look at, PhosphoSitePlus. Although it has phosphorylation in the name, it’s broader than that–hence the “Plus”, I imagine.
PhosphoSitePlus® (PSP) is a publicly-accessible web-based portal offering detailed information on post-translational modifications (PTM) of proteins. The PTMs include various types of modifications, not only phosphorylation, but also methylation, acetylation, glycosylation, caspase cleavage, and ubiquitination, among others. There’s a helpful summary on the landing page of the numbers and types of PTMs.
The information comes from high quality curation of literature (low-throughput, LTP) as well as from many high-throughput (HTP) studies. They have been building this resource over many years, and have been refining the collection over that time. In fact, they re-examined some of the older data they had and re-evaluated the quality to improve their collection. So it is actively being built and maintained.
They have a nice video tutorial, which is this week’s Video Tip of the Week. But it’s hosted on their site and I can’t locate an embed feature, so you will have to go over there to have a look. Here’s an image of it below. It has my favorite structure: overview, intro, advanced, and examples. I thought it was a helpful walk through the types of information you can get from their site. You can navigate to different sections with their menu, or you can close that menu out of the way as the material proceeds. In under 20 minutes you’ll have a great grasp of the features of the site.
In the new paper they reference some features that weren’t in their prior tutorial. Special emphasis on mutations and variations that affect modification sites are now included in their PTMVar collection. This is one of the newer features described in the paper, and this component of their collection offers a look at missense mutations that can impact post-translational modification aspects. This is particularly helpful as we get more sequence information from individuals, and we may come across some that affect PTM sites. The new paper provides details on the sources of this information, which includes cancer resources and OMIM, as well as UniProt.
I also found their Motif Analysis Tool quite handy. On the homepage in the Downloads and Applications area–check out the options. It will let you enter your sequences to analyze and deliver a Sequence Logo if you would like one. Again, there’s more details and nice examples in the paper of the logos. There’s also the option of downloading a Cytoscape plug-in.
So check out PhosphoSitePlus for knowledge about post-translational modifications on proteins you are interested in, and further details on motifs and pathways that are involved.
PhosphoSitePlus® tutorial: http://www.phosphosite.org/staticTrainingTutorial.do
Hornbeck P.V., B. Zhang, B. Murray, J. M. Kornhauser, V. Latham & E. Skrzypek (2014). PhosphoSitePlus, 2014: mutations, PTMs and recalibrations, Nucleic Acids Research, DOI: http://dx.doi.org/10.1093/nar/gku1267
Hornbeck P.V., J. M. Kornhauser, S. Tkachev, B. Zhang, E. Skrzypek, B. Murray, V. Latham & M. Sullivan (2011). PhosphoSitePlus: a comprehensive resource for investigating the structure and function of experimentally determined post-translational modifications in man and mouse, Nucleic Acids Research, 40 (D1) D261-D270. DOI: http://dx.doi.org/10.1093/nar/gkr1122