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{{other uses|Parkin (disambiguation)}}
{{Infobox_gene}}
'''Parkin''' is a 465-[[amino acid]] [[residue (chemistry)|residue]] [[E3 ubiquitin ligase]], a [[protein]] that in humans is encoded by the ''PARK2'' [[gene]].<ref name="pmid9560156">{{cite journal | vauthors = Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N | title = Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism | journal = Nature | volume = 392 | issue = 6676 | pages = 605–8 | date = April 1998 | pmid = 9560156 | doi = 10.1038/33416 | bibcode = 1998Natur.392..605K | s2cid = 4432261 }}</ref><ref name="pmid9570960">{{cite journal | vauthors = Matsumine H, Yamamura Y, Hattori N, Kobayashi T, Kitada T, Yoritaka A, Mizuno Y | title = A microdeletion of D6S305 in a family of autosomal recessive juvenile parkinsonism (PARK2) | journal = Genomics | volume = 49 | issue = 1 | pages = 143–6 | date = April 1998 | pmid = 9570960 | doi = 10.1006/geno.1997.5196 }}</ref> Parkin plays a critical role in [[ubiquitination]] – the process whereby molecules are covalently labelled with [[ubiquitin]] (Ub) and directed towards degradation in [[proteasomes]] or [[lysosomes]]. Ubiquitination involves the sequential action of three enzymes. First, an [[E1 ubiquitin-activating enzyme]] binds to inactive Ub in [[eukaryotic cells]] via a [[thioester]] bond and mobilises it in an ATP-dependent process. Ub is then transferred to an [[E2 ubiquitin-conjugating enzyme]] before being conjugated to the target protein via an E3 ubiquitin ligase.<ref name="Pickart and Eddins 2004">{{cite journal | vauthors = Pickart CM, Eddins MJ | title = Ubiquitin: structures, functions, mechanisms | journal = Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | volume = 1695 | issue = 1–3 | pages = 55–72 | date = November 2004 | pmid = 15571809 | doi = 10.1016/j.bbamcr.2004.09.019 | doi-access = free }}</ref> There exists a multitude of E3 ligases, which differ in structure and substrate specificity to allow selective targeting of proteins to intracellular degradation.
In particular, parkin recognises proteins on the outer membrane of [[mitochondria]] upon cellular insult and mediates the clearance of damaged mitochondria via [[autophagy]] and proteasomal mechanisms.<ref name="Seirafi_2015">{{cite journal | vauthors = Seirafi M, Kozlov G, Gehring K | title = Parkin structure and function | journal = The FEBS Journal | volume = 282 | issue = 11 | pages = 2076–88 | date = June 2015 | pmid = 25712550 | pmc = 4672691 | doi = 10.1111/febs.13249 }}</ref> Parkin also enhances cell survival by suppressing both mitochondria-dependent and -independent [[apoptosis]]. [[Mutations]] are associated with mitochondrial dysfunction, leading to neuronal death in [[Parkinson’s disease]]<ref name="Dawson 2014">{{cite journal | vauthors = Dawson TM, Dawson VL | author1-link=Ted M. Dawson | title = The role of parkin in familial and sporadic Parkinson's disease | journal = Movement Disorders | volume = 25 | issue = Suppl 1 | pages = S32-9 | date = 2014 | pmid = 20187240 | doi = 10.1002/mds.22798 | pmc=4115293}}</ref> and aberrant [[metabolism]] in [[tumourigenesis]].<ref name="Zhang 2011">{{cite journal | vauthors = Zhang C, Lin M, Wu R, Wang X, Yang B, Levine AJ, Hu W, Feng Z | title = Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the Warburg effect | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 39 | pages = 16259–64 | year = 2011 | pmid = 21930938 | pmc = 3182683 | doi = 10.1073/pnas.1113884108 | bibcode = 2011PNAS..10816259Z | doi-access = free }}</ref>
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