Protein isoform

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A protein isoform, or "protein variant" is a member of a very similar set of proteins derived from a single gene or gene family and is the result of genetic differences. While many perform the same or similar biological roles, some isoforms have unique functions. A set of protein isoforms may be formed from alternative splicing, use of variable promoters, or other post-transcription modifications of a single gene; post-translational modifications are generally not considered. Through the RNA coupling mechanism, mRNAs have the ability to select different protein (exon) segment segments from genes, or even different parts of the exons of RNA to form different mRNA sequences. Each unique sequence produces a specific form of protein.

The discovery of isoforms may explain the difference between the small number of protein-encoding genes disclosed by the human genome project and the large diversity of proteins seen in organisms: different proteins encoded by the same genes can increase the diversity of proteom. Isoform at the RNA level is easily characterized by cDNA transcription studies. Many human genes have confirmed alternative isoform splicing. It is estimated that ~ 100,000 EST can be identified in humans. Isoforms at the protein level can manifest in the elimination of entire domains or shorter loops, usually located on the surface of proteins.

Video Protein isoform

Definisi

A single gene has the ability to produce many different proteins in both structure and composition; this process is governed by alternative mRNA splicing, although it is unclear to what extent such a process affects the diversity of human proteom, since the amount of ischemic transcription of mRNA is not always correlated with the abundance of protein isoforms. The specificity of the translated isoform derives from the structure/function of the protein, as well as the cell type and stage of development during its manufacture. Determining the specificity becomes more complicated when a protein has several subunits and each subunit has several isoforms.

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

• ?, catalytic domain, has two isoforms :? 1 and? 2 encoded from PRKAA1 and PRKAA2
• ?, the regulatory domain, has two isoforms :? 1 and? 2 which is encoded from PRKAB1 and PRKAB2
• ?, the regulatory domain, has three isoforms :? 1,? 2, and? 3 which is encoded from PRKAG1, PRKAG2, and PRKAG3

In skeletal muscle, the preferred form is? 2? 2? 1. But in the human heart, the most abundant form is 1? 2? 1.

Maps Protein isoform

Mechanism

The main mechanisms that produce protein isoforms are alternative splicing and use of variable promoters, although modifications due to genetic alterations, such as mutations and polymorphisms are sometimes also considered different isoforms.

Alternative grafting is a major post-transcriptional modification process that produces mRNA transcription isoforms, and is a major molecular mechanism that can contribute to protein diversity. Spliceosome, a large ribonucleoprotein, is a molecular machine inside the nucleus responsible for cleavage and RNA ligation, eliminating the non-protein (intron) encoding segment.

Since splicing is a process that occurs between transcription and translation, the main effects are primarily studied through genomic techniques - for example, microarray analysis and RNA sequencing have been used to identify alternately connected transcripts and measure their abundance. Abundance of transcripts is often used as a proxy for the abundance of protein isoforms, although proteomic experiments using gel electrophoresis and mass spectrometry have shown that the correlations between transcripts and protein quantities are often low, and that one isoform protein is usually dominant. One study of 2015 suggests that the causes of this difference may occur after translation, although the mechanism is essentially unknown. Consequently, although alternative splicing has been implicated as an important link between variation and disease, there is no conclusive evidence that it acts primarily by generating new protein isoforms.

Alternative switching generally illustrates a strictly regulated process in which alternative transcripts are intentionally generated by splicing machines. However, such transcripts are also generated by splicing errors in a process called "noisy splicing," and are also potentially translatable into protein isoforms. Although ~ 95% of multi-exonic genes are suspected to be connected alternatively, a study of noisy splicing observes that most low abundance transcripts are noise, and predicts that the majority of all alternative transcription and protein isoforms are present in functionally functional cells.

Other transcriptional and post-transcriptional regulatory measures may also produce different protein isoforms. The use of variable promoters occurs when cell transcription machinery (RNA polymerase, transcription factors, and other enzymes) initiates transcription at different promoters - the area of ​​DNA near the gene that serves as the initial binding site - produces a slightly modified transcript and protein isoform.

src: essays.biochemistry.org

Characteristics

Generally, one protein isoform is labeled as a canonical sequence based on criteria such as its prevalence and similarity to the ortholog - or functionally analogue - sequences in other species. The Isoform is assumed to have the same functional properties, since most have the same sequence, and share some of the most exons with canonical sequences. However, some isoforms show much larger differences (eg, via trans-splicing), and may share less without exon in a canonical order. In addition, they can have different biological effects - for example, in extreme cases, the function of one isoform can increase cell survival, while others increase cell death - or can have the same basic functions but differ in their sub-cellular localization. A 2016 study, however, functionally characterized all isoforms of 1,492 genes and determined that most of the isoforms behave as "functional alloforms." The authors came to the conclusion that the isoform behaves like a different protein after observing that the function of the majority of isoforms does not overlap. Since the study was conducted on in vitro cells, it is not known whether the isoform in the expressed human proteome has this characteristic. In addition, since the function of each isoform must generally be determined separately, the majority of identified and predicted isoforms still have unknown functions.

src: www.frontiersin.org

Related Concepts

Glycoform

A glycoform is a protein isoform that is only distinct with respect to the amount or type of glycans attached. Glycoproteins often consist of a number of different glycosforms, with changes in saccharides or attached oligosaccharides. This modification may result from differences in biosynthesis during the glycosylation process, or by the action of glycosidase or glycosyltransferase. Glycoform can be detected through detailed chemical analysis of separate glycos, but more easily detected by differential reactions with lectins, such as affectative lectin chromatography and lectin affinity electrophoresis. Typical examples of glycoproteins consisting of glycopoforms are blood proteins as orosomucoid, antitrypsin, and haptoglobin. Unusual glycopic variations are seen in nerve cell adhesion molecules, NCAMs involving polyialic acid, PSA. ***

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Example

• G-actin: despite its sustainability, it has a variety of isoforms (at least six in mammals).
• Creatine kinase, a presence that in the blood can be used as an aid in the diagnosis of myocardial infarction, is present in 3 isoforms.
• Hyaluronan synthase, the enzyme responsible for hyaluronan production, has three isoforms in mammalian cells.
• UDP-glucuronosyltransferase, the superfamily enzyme responsible for the detoxification path of many drugs, environmental pollutants, and toxic endogenous compounds has 16 isoforms encoded in human genes.
• G6PDA: the normal ratio of active isoforms in any network cell is 1: 1 divided by G6PDG. This is exactly the normal isoform ratio in hyperplasia. Only one of these isoforms is found during neoplasia.

src: dev.biologists.org

See also

• Gen isoform

src: www.wormbook.org

References

src: www.pnas.org

External links

• isoform protein entry MESH
• Definitions of Isoform

Source of the article : Wikipedia