Editing Protein splicing (section)

==Intein==
An '''intein''' is a segment of a [[protein]] that is able to excise itself and join the remaining portions (the '''exteins''') with a [[peptide bond]]  during protein splicing.<ref>{{cite journal |author1=Anraku, Y |author2=Mizutani, R |author3=Satow, Y  | title=Protein splicing: its discovery and structural insight into novel chemical mechanisms | journal=IUBMB Life | volume=57 | issue=8 | pages=563–74 | year=2005 | pmid=16118114 | doi=10.1080/15216540500215499| doi-access=free }}</ref> Inteins have also been called '''protein introns''', by analogy with (RNA) [[intron]]s. 
[[File:Intein_splicing_dogma.png|thumb|248x248px|Intein splicing occurs post-translationally in a self-catalytic process. Here, the extein is shown in red and the intein in blue. Image created with Biorender.com.]]

===Naming conventions===
The first part of an intein name is based on the [[Binomial nomenclature|scientific name]] of the [[organism]] in which it is found, and the second part is based on the name of the corresponding gene or extein. For example, the intein found in ''[[Thermoplasma acidophilum]]'' and associated with Vacuolar ATPase subunit A (VMA) is called "Tac VMA".

Normally, as in this example, just three letters suffice to specify the organism, but there are variations. For example, additional letters may be added to indicate a strain. If more than one intein is encoded in the corresponding gene, the inteins are given a numerical suffix starting from [[Directionality (molecular biology)|5{{prime}} to 3{{prime}}]] or in order of their identification (for example, "Msm dnaB-1").

The segment of the gene that encodes the intein is usually given the same name as the intein, but to avoid confusion the name of the intein proper is usually capitalized (''e.g.'', Pfu RIR1-1), whereas the name of the corresponding gene segment is italicized (''e.g.'', Pfu ''rir1-1'').  A different disambiguating convention is to place a lowercase "i" after the source protein name, ''e.g.'' "Msm DnaBi1".<ref>{{cite journal |last1=Kelley |first1=Danielle S. |last2=Lennon |first2=Christopher W. |last3=Li |first3=Zhong |last4=Miller |first4=Michael R. |last5=Banavali |first5=Nilesh K. |last6=Li |first6=Hongmin |last7=Belfort |first7=Marlene |title=Mycobacterial DnaB helicase intein as oxidative stress sensor |journal=Nature Communications |date=19 October 2018 |volume=9 |issue=1 |page=4363 |doi=10.1038/s41467-018-06554-x|pmid=30341292 |pmc=6195587 |bibcode=2018NatCo...9.4363K |doi-access=free }}</ref>

===Types of inteins===
Inteins can be classified on many criteria.
* Based on how they splice themselves out, they can be classified into ''cis-splicing'' (which means that they splice themselves out) or ''trans-splicing'' (which means they need outside help). Most studied inteins are cis-splicing. Split inteins (see below) usually involves two halves helping each other out, so they are ''trans-splicing''.<ref name="pmid33339089">{{cite journal |last1=Nanda |first1=A |last2=Nasker |first2=SS |last3=Mehra |first3=A |last4=Panda |first4=S |last5=Nayak |first5=S |title=Inteins in Science: Evolution to Application. |journal=Microorganisms |date=16 December 2020 |volume=8 |issue=12 |page=2004 |doi=10.3390/microorganisms8122004 |pmid=33339089 |pmc=7765530 |doi-access=free }}</ref>
* Based on whether they contain the endonuclease domain. Ones that have an endonuclease domain is called a "maxi-intein", otherwise a "mini-intein".<ref name="pmid33339089"/>
* Based on their splicing mechanism, which can be partially<ref name=pmid21317331/> inferred based on the sequence. Class 1 intein is the most-studied type and are marked by a cysteine or serine as the first residue. Class 2 intein, or "alanine intein" has alanine as the first residue and no WCT motif. Class 3 intein has alanine as the first residue and a noncontiguous "WCT" motif.<ref name="pmid33339089"/> It has also been proposed that inteins that start with a serine and contain a "WCT" motif should be also classed as class 3.<ref name=pmid21317331>{{cite journal |last1=Tori |first1=K |last2=Perler |first2=FB |title=Expanding the definition of class 3 inteins and their proposed phage origin. |journal=Journal of Bacteriology |date=April 2011 |volume=193 |issue=8 |pages=2035–41 |doi=10.1128/JB.01407-10 |pmid=21317331|pmc=3133030 |doi-access=free }}</ref>

==== Full and mini inteins ====
Inteins can contain a [[Homing endonuclease| homing endonuclease gene]] (HEG) domain in addition to the splicing domains. This domain is responsible for the spread of the intein by cleaving DNA at an intein-free [[allele]] on the [[homologous chromosome]], triggering the [[DNA repair#Double-strand breaks|DNA double-stranded break repair]] (DSBR) system, which then repairs the break, thus copying the intein-coding DNA into a previously intein-free site.<ref name="pmid33339089"/> The HEG domain is not necessary for intein splicing, and so it can be lost, forming a ''minimal'', or ''mini'', ''intein''. Several studies have demonstrated the modular nature of inteins by adding or removing HEG domains and determining the activity of the new construct.{{Citation needed| date=November 2011}}

==== Split inteins ====
Sometimes, the intein of the precursor protein comes from two genes. In this case, the intein is said to be a ''split intein''. For example, in [[cyanobacteria]], [[DnaE]], the catalytic subunit α of [[DNA polymerase III holoenzyme|DNA polymerase III]], is encoded by two separate genes, ''dnaE-n'' and ''dnaE-c''. The ''dnaE-n'' [[gene product|product]] consists of an N-extein sequence followed by a 123-AA intein sequence, whereas the ''dnaE-c'' product consists of a 36-AA intein sequence followed by a C-extein sequence.<ref name="DnaE">{{Cite journal | doi=10.1073/pnas.95.16.9226 | last1=Wu | first1=H. | last2=Hu | first2=Z. | last3=Liu | first3=X. Q. 
| title=Protein trans-splicing by a split intein encoded in a split DnaE gene of Synechocystis sp. PCC6803 
| journal=Proceedings of the National Academy of Sciences of the United States of America | volume=95 | issue=16 | pages=9226–9231 | year=1998 | pmid=9689062 | pmc=21320| bibcode=1998PNAS...95.9226W | doi-access=free }}</ref>