*4.5. Prediction of Protein Intrinsic Disorder*

Protein intrinsic disorder prediction was carried out using IUPred [28] for regions of disorder of at least 30 amino acids ("long" option). IUPred predicts tendency for polypeptide chains to be intrinsically disordered or ordered by analyzing the composition of amino acids within a window of 30 consecutive amino acids. It does so by utilizing an energy predictor matrix to estimate the tendency for pairs of amino acids to form strong stabilizing connections, the underlying assumption being that globular proteins form strong stabilizing contacts whereas structurally disordered proteins lack this capacity. IUPred reports a disorder score for each residue ranging from 0 to 1, conferring complete order to disorder, respectively. In this study, we used a threshold of >0.4 to calculate the proportion of amino acids within each protein that were likely to be in disordered regions.

#### *4.6. Statistical Analyses*

Statistical analyses were conducted using R [41]. Partial correlation analyses were conducted using the R function pcor.test [42]. Tests repeated on all 20 amino acids were corrected for multiple testing using the Benjamini-Hochberg approach [43].

#### **Supplementary Materials:** Supplementary materials can be found at http://www.mdpi.com/1422-0067/19/8/ 2276/s1.

**Author Contributions:** M.X.R.-G., F.V.-S., M.A.P.-A. and M.A.F. conceived, designed, and conducted the experiments and microarray analyses. D.A.-P. conceived and designed the bioinformatics analyses. D.A.-P. and F.F. conducted the bioinformatics analyses. D.A.-P. and M.X.R.-G. wrote the paper. All authors contributed to editing the manuscript, read, and approved the manuscript, except M.A.F., who is a posthumous author.

**Funding:** D.A.-P. and F.F. were supported by funds from the University of Nevada, Reno, and by pilot grants from Nevada INBRE (P20GM103440) and the Smooth Muscle Plasticity COBRE from the University of Nevada, Reno (5P30GM110767-04), both funded by the National Institute of General Medical Sciences (National Institutes of Health). M.X.R.-G. and M.A.F. were supported by grants from Science Foundation Ireland (12/IP/1637) and the Spanish Ministerio de Economía y Competitividad, Spain (MINECO-FEDER; BFU201236346 and BFU2015-66073-P) to MAF. MXRG was supported by a JAE DOC fellowship from the MINECO, Spain. F.V.-S. and M.A.P.-A. were supported by grant BIO2014-55946-P from MINECO-FEDER.

**Acknowledgments:** D.A.-P., M.X.R.-G., F.V.-S., F.F. and M.A.P.-A. dedicate this work to the memory of M.A.F. Current address of F.F.: Structural Genomics Consortium; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom.

**Conflicts of Interest:** The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.
