A protein isoform is any of several different forms of the same protein. Different forms of a protein may be produced from very closely related gene duplicates—as 'same protein' or 'a protein' makes no sense for highly diverged paralogs that arose from a single ancestral gene that duplicated billions of years ago and subsequently diverged greatly in sequence, structure and functionality—or may arise from the same gene by alternative splicing. In older literature one can also encounter the use of the term isoform to describe alleles of the same gene, but currently the terms refers mostly to paralogous and alternatively spliced proteins, not alleles.
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. However for the vast majority of alternative splice form transcripts, there is no evidence whatsoever for their translation, proper folding, stability to proteolytic recycling, or functionality at the protein level—they may simply represent transcriptional noise or splicing errors instead.
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, has 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.
- Barre L, Fournel-Gigleux S, Finel M, Netter P, Magdalou J, Ouzzine M (March 2007). "Substrate specificity of the human UDP-glucuronosyltransferase UGT2B4 and UGT2B7. Identification of a critical aromatic amino acid residue at position 33". FEBS J. 274 (5): 1256–64. doi:10.1111/j.1742-4658.2007.05670.x. PMID 17263731.
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