Изоформы белков: разнообразие и функциональные особенности.

Forms of a protein produced from different genes

A protein isoform, or "protein variant", While many perform the same or similar biological roles, some isoforms have unique functions. A set of protein isoforms may be formed from alternative splicings, variable promoter usage, or other post transcriptional modifications of a single gene; post translational modifications are generally not considered. (For that, see Proteoforms.) Through RNA splicing mechanisms, mRNA has the ability to select different protein coding segments (exons) of a gene, or even different parts of exons from RNA to form different mRNA sequences. Each unique sequence produces a specific form of a protein. The discovery of isoforms could explain the discrepancy between the small number of protein coding regions of genes revealed by the human genome project and the large diversity of proteins seen in an organism: different proteins encoded by the same gene could increase the diversity of the proteome. Isoforms at the RNA level are readily characterized by cDNA transcript studies. Many human genes possess confirmed alternative splicing isoforms. It has been estimated that ~100,000 expressed sequence tags (ESTs) can be identified in humans. Isoforms at the protein level can manifest in the deletion of whole domains or shorter loops, usually located on the surface of the protein.

Generally, one protein isoform is labeled as the canonical sequence based on criteria such as its prevalence and similarity to orthologous—or functionally analogous—sequences in other species. Isoforms are assumed to have similar functional properties, as most have similar sequences, and share some to most exons with the canonical sequence. However, some isoforms show much greater divergence (for example, through trans splicing), and can share few to no exons with the canonical sequence. In addition, they can have different biological effects—for example, in an extreme case, the function of one isoform can promote cell survival, while another promotes cell death—or can have similar basic functions but differ in their sub cellular localization. A 2016 study, however, functionally characterized all the isoforms of 1,492 genes and determined that most isoforms behave as "functional alloforms." The authors came to the conclusion that isoforms behave like distinct proteins after observing that the functional of most isoforms did not overlap. Because the study was conducted on cells in vitro, it is not known if the isoforms in the expressed human proteome share these characteristics. Additionally, because the function of each isoform must generally be determined separately, most identified and predicted isoforms still have unknown functions.

A glycoform is an isoform of a protein that differs only with respect to the number or type of attached glycan. Glycoproteins often consist of a number of different glycoforms, with alterations in the attached saccharide or oligosaccharide. These modifications may result from differences in biosynthesis during the process of glycosylation, or due to the action of glycosidases or glycosyltransferases. Glycoforms may be detected through detailed chemical analysis of separated glycoforms, but more conveniently detected through differential reaction with lectins, as in lectin affinity chromatography and lectin affinity electrophoresis. Typical examples of glycoproteins consisting of glycoforms are the blood proteins as orosomucoid, antitrypsin, and haptoglobin. An unusual glycoform variation is seen in neuronal cell adhesion molecule, NCAM involving polysialic acids, PSA.

G actin: despite its conserved nature, it has a varying number of isoforms (at least six in mammals). Creatine kinase, the presence of which in the blood can be used as an aid in the diagnosis of myocardial infarction, exists in 3 isoforms. Hyaluronan synthase, the enzyme responsible for the production of hyaluronan, has three isoforms in mammalian cells. UDP glucuronosyltransferase, an enzyme superfamily responsible for the detoxification pathway of many drugs, environmental pollutants, and toxic endogenous compounds has 16 known isoforms encoded in the human genome. G6PDA: normal ratio of active isoforms in cells of any tissue is 1:1 shared with G6PDG. This is precisely the normal isoform ratio in hyperplasia. Only one of these isoforms is found during neoplasia. Monoamine oxidase, a family of enzymes that catalyze the oxidation of monoamines, exists in two isoforms, MAO A and MAO B.