Editing Protein isoform (section)

== Definition ==
One single gene has the ability to produce multiple proteins that differ both in structure and composition;<ref name=":0">{{cite journal | vauthors = Andreadis A, Gallego ME, Nadal-Ginard B | title = Generation of protein isoform diversity by alternative splicing: mechanistic and biological implications | journal = Annual Review of Cell Biology | volume = 3 | issue = 1 | pages = 207–42 | date = 1987-01-01 | pmid = 2891362 | doi = 10.1146/annurev.cb.03.110187.001231 }}</ref><ref name=":1">{{cite journal | vauthors = Breitbart RE, Andreadis A, Nadal-Ginard B | title = Alternative splicing: a ubiquitous mechanism for the generation of multiple protein isoforms from single genes | journal = Annual Review of Biochemistry | volume = 56 | issue = 1 | pages = 467–95 | date = 1987-01-01 | pmid = 3304142 | doi = 10.1146/annurev.bi.56.070187.002343 }}</ref> this process is regulated by the [[alternative splicing]] of mRNA, though it is not clear to what extent such a process affects the diversity of the human proteome, as the abundance of mRNA transcript isoforms does not necessarily correlate with the abundance of protein isoforms.<ref>{{cite journal | vauthors = Liu Y, Beyer A, Aebersold R | title = On the Dependency of Cellular Protein Levels on mRNA Abundance | journal = Cell | volume = 165 | issue = 3 | pages = 535–50 | date = April 2016 | pmid = 27104977 | doi = 10.1016/j.cell.2016.03.014 | doi-access = free | hdl = 20.500.11850/116226 | hdl-access = free }}</ref> Three-dimensional protein structure comparisons can be used to help determine which, if any, isoforms represent functional protein products, and the structure of most isoforms in the human proteome has been predicted by [[AlphaFold]] and publicly released at [https://www.isoform.io isoform.io]. <ref>{{Cite journal |last1=Sommer |first1=Markus J. |last2=Cha |first2=Sooyoung |last3=Varabyou |first3=Ales |last4=Rincon |first4=Natalia |last5=Park |first5=Sukhwan |last6=Minkin |first6=Ilia |last7=Pertea |first7=Mihaela |last8=Steinegger |first8=Martin |last9=Salzberg |first9=Steven L. |date=2022-12-15 |title=Structure-guided isoform identification for the human transcriptome |journal=eLife |volume=11 |pages=e82556 |language=en |doi=10.7554/eLife.82556|pmid=36519529 |pmc=9812405 |doi-access=free }}</ref> The specificity of translated isoforms is derived by the protein's structure/function, as well as the cell type and developmental stage during which they are produced.<ref name=":0" /><ref name=":1" /> Determining specificity becomes more complicated when a protein has multiple subunits and each subunit has multiple isoforms.

For example, the '''[[AMP-activated protein kinase|5' AMP-activated protein kinase]]''' (AMPK), an enzyme, which performs different roles in human cells, has 3 subunits:<ref name=":2">{{cite journal | vauthors = Dasgupta B, Chhipa RR | title = Evolving Lessons on the Complex Role of AMPK in Normal Physiology and Cancer | language = English | journal = Trends in Pharmacological Sciences | volume = 37 | issue = 3 | pages = 192–206 | date = March 2016 | pmid = 26711141 | pmc = 4764394 | doi = 10.1016/j.tips.2015.11.007 }}</ref>
* α, catalytic domain, has two isoforms: α1 and α2 which are encoded from [[PRKAA1]] and [[PRKAA2]]
* β, regulatory domain, has two isoforms: β1 and β2 which are encoded from [[PRKAB1]] and [[PRKAB2]]
* γ, regulatory domain, has three isoforms: γ1, γ2, and γ3 which are encoded from [[PRKAG1]], [[PRKAG2]], and [[PRKAG3]]
In human skeletal muscle, the preferred form is α2β2γ1.<ref name=":2" /> But in the human liver, the most abundant form is α1β2γ1.<ref name=":2" />