Isoform

Protein isoforms, or "protein variants" is an ambiguous term describing either several different forms of protein coded from the same gene, or proteins with amino acid sequence and functional similarities, even when they are products of different genes. Through RNA splicing mechanisms, mRNA has the ability to select different protein-coding segments (exons), or even different parts of exons from RNA to form different mRNA sequences. Each unique sequence produces a specific form of a protein. Among all RNA splicing mechanisms, alternative splicing is the most predominant one which is responsible for most of protein isoforms.

The discovery of isoforms could explain the small number of protein coding regions genes revealed by the human genome project: different proteins encoded by the same gene could increase the diversity of the proteome. Isoforms at the DNA level are readily characterized by cDNA transcript studies. Many human genes possess confirmed alternative splicing isoforms. It has been estimated that ~100,000 ESTs can be identified in humans. Isoforms at the protein level can manifest in deletion of whole domains or shorter loops, usually located on the surface of the protein.

One single gene has the ability to produce multiple proteins. All these proteins are different both in structure and composition and this process is regulated by alternative splicing of mRNA and have a large impact in proteome diversity. The specificity of produced proteins is derived by protein structure/function, development stage and even the cell type. It becomes more complicated when a protein has multiple subunits and each subunit has multiple isoforms.

For example, the 5' AMP-activated protein kinase (AMPK), an enzyme, which performs different roles in human cells, has 3 subunits:

In human skeletal muscle, the preferred form is α2β2γ1. But in the human liver, the most abundant form is α1β2γ1.

Alternative splicing is a post-transcriptional modification process which is the major molecular mechanism that contributes to the protein diversity.

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