Multifunctional Proteins : Involvement in Human Diseases and Targets of Current Drugs

Multifunctionality or multitasking is the capability of some proteins to execute two or more biochemical functions. The objective of this work is to explore the relationship between multifunctional proteins, human diseases and drug targeting. The analysis of the proportion of multitasking proteins from the MultitaskProtDB-II database shows that 78% of the proteins analyzed are involved in human diseases. This percentage is much higher than the 17.9% found in human proteins in general. A similar analysis using drug target databases shows that 48% of these analyzed human multitasking proteins are targets of current drugs, while only 9.8% of the human proteins present in UniProt are specified as drug targets. In almost 50% of these proteins, both the canonical and moonlighting functions are related to the molecular basis of the disease. A procedure to identify multifunctional proteins from disease databases and a method to structurally map the canonical and moonlighting functions of the protein have also been proposed here. Both of the previous percentages suggest that multitasking is not a rare phenomenon in proteins causing human diseases, and that their detailed study might explain some collateral drug effects. This research was supported by Ministerio de Economía y Competitividad of Spain [BFU2013-50176-EXP, BIO2013-48704-R and BIO2017-84166R], by the Centre de Referència de R+D de Biotecnologia de la Generalitat de Catalunya, and from the Comisión Coordinadora del Interior de Uruguay.