Protein isoform

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Protein A, B and C are isoforms encoded from the same gene through alternative splicing.

A protein isoform is a version of a protein with only small differences to another isoform of the same protein. Different forms of a protein may be produced from different but related genes, or may arise from the same gene by alternative splicing. A large number of isoforms are caused by single nucleotide polymorphisms, small genetic differences between alleles of the same gene.

The discovery of isoforms explains the apparently small number of coding genes revealed in the human genome project: the ability to create catalytically different proteins from the same gene increases the diversity of the proteome. Isoforms are readily described and discovered by microarray studies and cDNA libraries.

Theoretical isoforms

A protein isoform, or "protein variant",[1] is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences.[2]

Many human genes possess confirmed alternative splicing isoforms. It has been estimated that ~100,000 expressed sequence tags (ESTs) can be identified in humans.[1] Isoforms at the protein level can manifest in the deletion of whole domains or shorter loops, usually located on the surface of the protein.[3]

Def. any "of several different forms of the same protein, arising from either single nucleotide polymorphisms,[4] differential splicing of mRNA, or post-translational modifications (e.g. sulfation, glycosylation, etc.)"[5] is called an isoform, or protein isoform.

Def. a "different sequence of a gene (locus)"[6] is called a variant.


A glycoform is an isoform where different ways of a glycoprotein have different polysaccharides attached to them, by either posttranslational or cotranslational modifications.


  • 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.


  1. 1.0 1.1 Brett D, Pospisil H, Valcárcel J, Reich J, Bork P (January 2002). "Alternative splicing and genome complexity". Nature Genetics. 30 (1): 29–30. doi:10.1038/ng803. PMID 11743582.
  2. Schlüter H, Apweiler R, Holzhütter HG, Jungblut PR (September 2009). "Finding one's way in proteomics: a protein species nomenclature". Chemistry Central Journal. 3: 11. doi:10.1186/1752-153X-3-11. PMC 2758878. PMID 19740416.
  3. Kozlowski, L.; Orlowski, J.; Bujnicki, J. M. (2012). "Structure Prediction for Alternatively Spliced Proteins". Alternative pre-mRNA Splicing. p. 582. doi:10.1002/9783527636778.ch54. ISBN 9783527636778.
  4. SemperBlotto (6 January 2007). "isoform". San Francisco, California: Wikimedia Foundation, Inc. Retrieved 2 December 2018.
  5. (30 November 2008). "isoform". San Francisco, California: Wikimedia Foundation, Inc. Retrieved 2 December 2018.
  6. Pdeitiker (26 July 2008). "variant". San Francisco, California: Wikimedia Foundation, Inc. Retrieved 25 March 2020.


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