An assessment of the human Sortilin1 protein network, its expression and targetability using small molecules
Abstract
Abstract Background Sortilin1 (SORT1) is a ubiquitously expressed transporter involved in sorting or clearing proteins and is pathologically linked to tissue fibrosis and calcification. Targeting SORT1 may have potential clinical efficacy in controlling or reversing cardiovascular fibrosis and/or calcification. Hence this study assessed the protein-protein network of human SORT1 and its targetability using small molecule nutra/pharmaceuticals. Material and methods Network proteins of SORT1 in homo sapiens was identified using the String database, and the affinity of the protein-protein interaction of this network was analysed using Chimera software. The tissue specific expression profile of SORT1 was evaluated and assessed for enrichment in different cell types including the immune cells. A library of in-house small molecules and currently used therapeutics for cardiovascular diseases were screened using AutoDock vina to assess targetability of human SORT1. Concentration affinity (CA) ratio of the small molecules was estimated to assess the clinical feasibility of targeting SORT1. Results IGF2R, NTRK2, GRN and GGA1 were identified as high affinity interaction networks of SORT1. Of these high affinity interactions, IGF2R and GRN can be considered as relevant networks in regulating tissue fibrosis or microcalcification process due to their influence on T-cell activation, inflammation, wound repair, and tissue remodelling process. The tissue cell type enrichment indicated major…
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