Protein isoform
Encyclopedia
A protein isoform is any of several different forms of the same protein
. Different forms of a protein may be produced from related genes
, or may arise from the same gene by alternative splicing
. A large number of isoforms are caused by single-nucleotide polymorphisms or SNPs, small genetic differences between alleles of the same gene. These occur at specific individual nucleotide positions within a gene.
The discovery of isoforms partly explains the apparently small number of coding regions (genes
) revealed by the human genome project
: the ability to create categorically different proteins from the same gene increases the diversity of the proteome
. Isoforms are readily described and discovered by microarray
studies and cDNA libraries.
. 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
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
. Different forms of a protein may be produced from related genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
, or may arise from the same gene by alternative splicing
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...
. A large number of isoforms are caused by single-nucleotide polymorphisms or SNPs, small genetic differences between alleles of the same gene. These occur at specific individual nucleotide positions within a gene.
The discovery of isoforms partly explains the apparently small number of coding regions (genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
) revealed by the human genome project
Human Genome Project
The Human Genome Project is an international scientific research project with a primary goal of determining the sequence of chemical base pairs which make up DNA, and of identifying and mapping the approximately 20,000–25,000 genes of the human genome from both a physical and functional...
: the ability to create categorically different proteins from the same gene increases the diversity of the proteome
Proteome
The proteome is the entire set of proteins expressed by a genome, cell, tissue or organism. More specifically, it is the set of expressed proteins in a given type of cells or an organism at a given time under defined conditions. The term is a portmanteau of proteins and genome.The term has been...
. Isoforms are readily described and discovered by microarray
Microarray
A microarray is a multiplex lab-on-a-chip. It is a 2D array on a solid substrate that assays large amounts of biological material using high-throughput screening methods.Types of microarrays include:...
studies and cDNA libraries.
Glycoforms
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 oligosaccharideOligosaccharide
An oligosaccharide is a saccharide polymer containing a small number of component sugars, also known as simple sugars...
. These modifications may result from differences in biosynthesis
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
during the process of glycosylation
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
, 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
Lectin
Lectins are sugar-binding proteins that are highly specific for their sugar moieties. They play a role in biological recognition phenomena involving cells and proteins. For example, some viruses use lectins to attach themselves to the cells of the host organism during infection...
affinity electrophoresis
Affinity electrophoresis
Affinity electrophoresis is a general name for many analytical methods used in biochemistry and biotechnology. Both qualitative and quantitative information may be obtained through affinity electrophoresis. The methods include the so-called mobility shift electrophoresis, charge shift...
. Typical examples of glycoproteins consisting of glycoforms are the blood proteins
Blood proteins
Blood proteins, also termed serum proteins or plasma proteins, are proteins found in blood plasma. Serum total protein in blood is 7g/dl...
as orosomucoid
Orosomucoid
Orosomucoid or alpha-1-acid glycoprotein is an acute phase plasma alpha-globulin glycoprotein and is modulated by two polymorphic genes. It is synthesized primarily in hepatocytes and has a normal plasma concentration between 0.6-1.2 mg/mL...
, antitrypsin, and haptoglobin
Haptoglobin
Haptoglobin is a protein that in humans is encoded by the HP gene. In blood plasma, haptoglobin binds free hemoglobin released from erythrocytes with high affinity and thereby inhibits its oxidative activity. The haptoglobin-hemoglobin complex will then be removed by the reticuloendothelial system...
. An unusual glycoform variation is seen in neuronal cell adhesion molecule, NCAM
Neural Cell Adhesion Molecule
Neural Cell Adhesion Molecule is a homophilic binding glycoprotein expressed on the surface of neurons, glia, skeletal muscle and natural killer cells...
involving polysialic acids, PSA
Polysialic acid
Polysialic acid is an unusual posttranslational modification that occurs on neural cell adhesion molecules . Polysialic acid is considerably anionic. This strong negative charge gives this modification the ability to change the protein's surface charge and binding ability. In the synapse,...
.
Examples
- G-actin, despite its conserved nature, has varying number of isoforms, with a single isoform in yeasts and multiple (at least six in mammals) in eukaryotes.
- Creatine kinaseCreatine kinaseCreatine kinase , also known as creatine phosphokinase or phospho-creatine kinase , is an enzyme expressed by various tissues and cell types. CK catalyses the conversion of creatine and consumes adenosine triphosphate to create phosphocreatine and adenosine diphosphate...
, the presence of which in the blood can be used as an aid in the diagnosis of myocardial infarctionMyocardial infarctionMyocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
, exists in 3 isoforms. - Hyaluronan synthaseHyaluronan synthaseHyaluronan synthases are membrane-bound enzymes which use UDP-α-N-acetyl-D-glucosamine and UDP-α-D-glucuronate as substrates to produce the glycosaminoglycan hyaluronan at the cell surface and extrude it through the membrane into the extracellular space....
, 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.