Editing Protease (section)

==Biodiversity of proteases==
Proteases occur in all organisms, from [[prokaryote]]s to [[eukaryote]]s to [[viruses]]. These enzymes are involved in a multitude of physiological reactions from simple digestion of food proteins to highly regulated cascades (e.g., the [[coagulation|blood-clotting
 cascade]], the [[complement system]], [[apoptosis]] pathways, and the invertebrate prophenoloxidase-activating cascade). Proteases can either break specific peptide bonds (''limited proteolysis''), depending on the [[amino acid]] sequence of a protein, or completely break down a peptide to amino acids (''unlimited proteolysis''). The activity can be a destructive change (abolishing a protein's function or digesting it to its principal components), it can be an activation of a function, or it can be a signal in a signalling pathway.

===Plants===

Plant genomes encode hundreds of proteases, largely of unknown function. Those with known function are largely involved in [[development (biology)|developmental]] regulation.<ref>{{cite journal | vauthors = van der Hoorn RA | title = Plant proteases: from phenotypes to molecular mechanisms | journal = Annual Review of Plant Biology | volume = 59 | pages = 191–223 | year = 2008 | issue = 1 | pmid = 18257708 | doi = 10.1146/annurev.arplant.59.032607.092835 | bibcode = 2008AnRPB..59..191V | hdl-access = free | hdl = 11858/00-001M-0000-0012-37C7-9 }}</ref> Plant proteases also play a role in regulation of [[photosynthesis]].<ref>{{cite journal | vauthors = Zelisko A, Jackowski G | title = Senescence-dependent degradation of Lhcb3 is mediated by a thylakoid membrane-bound protease | journal = Journal of Plant Physiology | volume = 161 | issue = 10 | pages = 1157–1170 | date = October 2004 | pmid = 15535125 | doi = 10.1016/j.jplph.2004.01.006 | bibcode = 2004JPPhy.161.1157Z }}</ref>

===Animals===
Proteases are used throughout an organism for various metabolic processes. Acid proteases secreted into the stomach (such as [[pepsin]]) and serine proteases present in the [[duodenum]] ([[trypsin]] and [[chymotrypsin]]) enable the digestion of protein in food. Proteases present in blood serum ([[thrombin]], [[plasmin]], [[Hageman factor]], etc.) play an important role in blood-clotting, as well as lysis of the clots, and the correct action of the immune system. Other proteases are present in leukocytes ([[elastase]], [[cathepsin G]]) and play several different roles in metabolic control. Some [[snake venoms]] are also proteases, such as [[pit viper]] [[haemotoxin]] and interfere with the victim's blood clotting cascade. Proteases determine the lifetime of other proteins playing important physiological roles like hormones, antibodies, or other enzymes. This is one of the fastest "switching on" and "switching off" regulatory mechanisms in the physiology of an organism.

By a complex cooperative action, proteases can catalyze [[biochemical cascade|cascade]] reactions, which result in rapid and efficient amplification of an organism's response to a physiological signal.

===Bacteria===
[[Bacteria]] secrete proteases to [[hydrolyse]] the peptide bonds in proteins and therefore break the proteins down into their constituent [[amino acid]]s.  Bacterial and fungal proteases are particularly important to the global [[carbon]] and [[nitrogen]] cycles in the recycling of proteins, and such activity tends to be regulated by nutritional signals in these organisms.<ref>{{cite journal | vauthors = Sims GK | year = 2006 | title = Nitrogen Starvation Promotes Biodegradation of N-Heterocyclic Compounds in Soil | url = https://naldc-legacy.nal.usda.gov/naldc/download.xhtml?id=6863&content=PDF | journal = Soil Biology & Biochemistry | volume = 38 | issue = 8 | pages = 2478–2480 | doi = 10.1016/j.soilbio.2006.01.006 | bibcode = 2006SBiBi..38.2478S | access-date = 2018-12-29 | archive-date = 2021-04-28 | archive-url = https://web.archive.org/web/20210428115940/https://naldc-legacy.nal.usda.gov/naldc/download.xhtml?id=6863&content=PDF | url-status = dead }}</ref>  The net impact of nutritional regulation of protease activity among the thousands of species present in soil can be observed at the overall microbial community level as proteins are broken down in response to carbon, nitrogen, or sulfur limitation.<ref>{{cite journal | vauthors = Sims GK, Wander MM | year = 2002 | title = Proteolytic activity under nitrogen or sulfur limitation | journal = Appl. Soil Ecol. | volume = 568 | issue = 3 | pages = 1–5 | doi = 10.1016/S0929-1393(01)00192-5 | bibcode = 2002AppSE..19..217S }}</ref>

Bacteria contain proteases responsible for general protein quality control (e.g. the AAA+ [[proteasome]]) by degrading [[protein denaturation|unfolded or misfolded proteins]].

A secreted bacterial protease may also act as an exotoxin, and be an example of a [[virulence factor]] in bacterial [[pathogenesis]] (for example, [[Staphylococcus aureus#Toxins|exfoliative toxin]]).  Bacterial exotoxic proteases destroy extracellular structures.

===Viruses===
The genomes of some [[viruses]] encode one massive [[polyprotein]], which needs a protease to cleave this into functional units (e.g. the [[hepatitis C virus]] and the [[picornavirus]]es).<ref>{{cite journal | vauthors = Tong L | title = Viral proteases | journal = Chemical Reviews | volume = 102 | issue = 12 | pages = 4609–4626 | date = December 2002 | pmid = 12475203 | doi = 10.1021/cr010184f | name-list-style = vanc }}</ref> These proteases (e.g. [[TEV protease]]) have high specificity and only cleave a very restricted set of substrate sequences. They are therefore a common target for [[Protease inhibitor (pharmacology)|protease inhibitor]]s.<ref>{{cite journal | vauthors = Skoreński M, Sieńczyk M | title = Viral proteases as targets for drug design | journal = Current Pharmaceutical Design | volume = 19 | issue = 6 | pages = 1126–1153 | date = 2013 | pmid = 23016690 | doi = 10.2174/13816128130613 }}</ref><ref>{{cite journal | vauthors = Kurt Yilmaz N, Swanstrom R, Schiffer CA | title = Improving Viral Protease Inhibitors to Counter Drug Resistance | journal = Trends in Microbiology | volume = 24 | issue = 7 | pages = 547–557 | date = July 2016 | pmid = 27090931 | pmc = 4912444 | doi = 10.1016/j.tim.2016.03.010 }}</ref>

=== Archaea ===
[[Archaea]] use proteases to regulate various cellular processes from [[Cell signaling|cell-signaling]], [[metabolism]], [[secretion]] and protein quality control.<ref name=":1">{{cite journal | vauthors = Giménez MI, Cerletti M, De Castro RE | title = Archaeal membrane-associated proteases: insights on Haloferax volcanii and other haloarchaea | journal = Frontiers in Microbiology | volume = 6 | pages = 39 | date = 2015 | pmid = 25774151 | pmc = 4343526 | doi = 10.3389/fmicb.2015.00039 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Maupin-Furlow JA | title = Proteolytic systems of archaea: slicing, dicing, and mincing in the extreme | journal = Emerging Topics in Life Sciences | volume = 2 | issue = 4 | pages = 561–580 | date = December 2018 | pmid = 32953999 | pmc = 7497159 | doi = 10.1042/ETLS20180025 | editor-first = Nicholas P. | editor-last = Robinson }}</ref>  Only two ATP-dependent proteases are found in archaea: the membrane associated LonB protease and a soluble [[Proteasome|20S proteosome]] complex .<ref name=":1" />

===Tumours===

Proteases are associated with [[cancer progression]] due to their ability to degrade [[extracellular matrices]], which facilitates [[Cancer invasion|invasion]] and [[metastasis]]; these enzymes target a diversity of substrates and favour all steps of tumour production; some proteases have [[Tumour suppression|tumour-suppressive]] effects, associated with more than 30 different enzymes that belong to three distinct protease classes.<ref>{{Cite journal |date=2022-10-12 |title=Emerging roles of proteases in tumour suppression {{!}} Nature Reviews Cancer |journal=Nature Reviews Cancer |volume=7 |issue=10 |pages=800–808 |doi=10.1038/nrc2228 |url=https://www.nature.com/articles/nrc2228 |access-date=2025-02-14 |archive-url=https://web.archive.org/web/20221012002015/https://www.nature.com/articles/nrc2228 |archive-date=12 October 2022 |last1=López-Otín |first1=Carlos |last2=Matrisian |first2=Lynn M. |pmid=17851543 }}</ref>