The insulin superfamily of growth-promoting proteins

TL;DR

This paper explores the structural similarities among insulin, IGFs, growth hormone, and transferrin, suggesting they form an insulin superfamily with dual extracellular and nuclear localization, and a common affinity for the tumor suppressor RB.

Contribution

It provides in silico evidence supporting the existence of an insulin superfamily of growth-promoting proteins with shared motifs and nuclear localization.

Findings

Structural similarities support the insulin superfamily concept.

Proteins show dual localization in extracellular space and nucleus.

Shared motifs indicate common functional interactions with RB.

Abstract

Recently, structural analysis of the human transferrin and growth hormone (GH) amino acid sequences has unravelled that they harbor a motif identical to a pattern found in viral oncoproteins known to bind the primarily nuclear tumor suppressor retinoblastoma protein (RB). Since related signatures had previously been identified also in insulin and the two insulin-like growth factors (IGFs), the aim of the current study has been to investigate whether further hints substantiating these reported homologies can be found in silico. Here, additional similarities are presented supporting the notion of an insulin superfamily of growth-promoting proteins with dual localization in the extracellular environment and the intracellular space, particularly in the nucleus, as well as characterized by a tropism for RB.