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Defensin
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<h2 id="varieties">Varieties</h2> <p>The name 'defensin' was coined in the mid-1980s, though the proteins have been called 'Cationic Antimicrobial Proteins,' 'Neutrophil peptides,' 'Gamma thionins' amongst others.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> </p><p>Proteins called 'defensins' are not all evolutionarily related to one another.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> Instead fall into two broad <a href="/facts/Protein_superfamily/FJTXCha0">superfamilies</a>, each of which contains multiple <a href="/facts/Protein_family/EHt5xwCA">families</a>.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a><a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> One superfamily, the <i>trans</i>-defensins, contains the defensins found in humans and other vertebrates,<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a><a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> as well as some invertebrates.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a><a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> The other superfamily, <i>cis</i>-defensins, contains the defensins found in invertebrates, plants, and fungi.<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a><a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a><a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a> The superfamilies and families are determined by the overall tertiary structure, and each family usually has a conserved pattern of disulphide bonds.<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a><a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a> All defensins form small and compact folded structures, typically with a high positive charge, that are highly stable due to the multiple disulphide bonds. In all families, the underlying genes responsible for defensin production are highly <a href="/facts/Polymorphism_(biology)/lf32kgfV">polymorphic</a>. </p> <h3>Trans-defensins</h3> <p>Vertebrate defensins are primarily <a href="/facts/Alpha_defensin/ADmhByVs">α-defensins</a> and <a href="/facts/Beta_defensin/2gpeXAmp">β-defensins</a>. Some primates additionally have the much smaller <a href="/facts/Theta_defensin/QIfs904f">θ-defensins</a>. In general, both α- and β-defensins are encoded by two-<a href="/facts/Exon/8KWJtLuN">exon</a> genes, where the first exon encodes for a hydrophobic leader sequence (removed after <a href="/facts/Translation_(biology)/JcPC1rth">translation</a>) and the cysteine-rich sequence (the mature peptide). The disulfide linkages formed by the cysteines have been suggested to be essential for activities related to innate immunity in mammals, but are not necessarily required for antimicrobial activity.<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a><a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a> <a href="/facts/Theta_defensin/QIfs904f">Theta defensins</a> form a single <a href="/facts/Beta_hairpin/wHmw5Yfx">beta-hairpin</a> structure and represent a distinct group. Only alpha and beta-defensins are expressed in humans.<a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a> </p> Table of human defensins<table><tbody><tr><th>Type</th><th>Gene Symbol</th><th>Gene Name</th><th>Protein Name</th><th>Description</th></tr><tr><td rowspan="6"><a href="/facts/Alpha_defensin/ADmhByVs">α-defensins</a></td><td><a href="/facts/DEFA1/LcS62dd4">DEFA1</a></td><td>Defensin, alpha 1</td><td>Neutrophil defensin 1</td><td rowspan="6">Are expressed primarily in <a href="/facts/Neutrophils/KL6oTt8b">neutrophils</a> as well as in <a href="/facts/NK_cells/A3THWxrJ">NK cells</a> and certain T-lymphocyte subsets. <a href="/facts/DEFA5/pKmw8YJw">DEFA5</a> and <a href="/facts/DEFA6/BeKPSCoC">DEFA6</a> are expressed in <a href="/facts/Paneth_cells/GsT8zpXf">Paneth cells</a> of the small intestine, where they may regulate and maintain microbial balance in the intestinal lumen.</td></tr><tr><td><a href="/facts/DEFA1B/TgDAP8TY">DEFA1B</a></td><td>Defensin, alpha 1B</td><td>Defensin, alpha 1</td></tr><tr><td><a href="/facts/DEFA3/tfHUrh34">DEFA3</a></td><td>Defensin, alpha 3, neutrophil-specific</td><td>Neutrophil defensin 3</td></tr><tr><td><a href="/facts/DEFA4/Lmx8cDLC">DEFA4</a></td><td>Defensin, alpha 4, corticostatin</td><td>Neutrophil defensin 4</td></tr><tr><td><a href="/facts/DEFA5/pKmw8YJw">DEFA5</a></td><td>Defensin, alpha 5, Paneth cell-specific</td><td>Defensin-5</td></tr><tr><td><a href="/facts/DEFA6/BeKPSCoC">DEFA6</a></td><td>Defensin, alpha 6, Paneth cell-specific</td><td>Defensin-6</td></tr><tr><td rowspan="11"><a href="/facts/Beta_defensin/2gpeXAmp">β-defensins</a></td><td><a href="/facts/Defensin%2c_beta_1/K2HEb5VF">DEFB1</a></td><td>Defensin, beta 1</td><td>Beta-defensin 1</td><td rowspan="11">Are the most widely distributed, being secreted by <a href="/facts/Leukocytes/vsDunUK0">leukocytes</a> and <a href="/facts/Epithelial/ecKHcHC3">epithelial</a> cells of many kinds. For example, they can be found on the tongue, skin, cornea, salivary glands, kidneys, esophagus, and respiratory tract. It has been suggested (but also challenged) that some of the pathology of <a href="/facts/Cystic_fibrosis/tlNK5BAH">cystic fibrosis</a> arises from the inhibition of β-defensin activity on the epithelial surfaces of the lungs and trachea due to higher salt content.</td></tr><tr><td><a href="/facts/Beta-defensin_2/D1h2lluM">DEFB2</a></td><td>Defensin, beta 2</td><td>Beta-defensin 2</td></tr><tr><td><a href="/facts/Beta-defensin_3/qFlMthXN">DEFB3</a></td><td>Defensin, beta 3</td><td>Beta-defensin 3</td></tr><tr><td><a href="/facts/DEFB103A/xH5I1ID9">DEFB103A</a></td><td>Defensin, beta 103B</td><td>Beta-defensin 103</td></tr><tr><td>...</td><td>...</td><td>...</td></tr><tr><td><a href="/facts/DEFB106A/Gh0HNYY4">DEFB106A</a></td><td>Defensin, beta 106A</td><td>Beta-defensin 106A</td></tr><tr><td><a href="/facts/DEFB106/Gh0HNYY4">DEFB106</a>B</td><td>Defensin, beta 106B</td><td>Beta-defensin 106B</td></tr><tr><td>DEFB107B</td><td>Defensin, beta 107A</td><td>Beta-defensin 107</td></tr><tr><td>DEFB110</td><td>Defensin, beta 110</td><td>Beta-defensin 110</td></tr><tr><td>...</td><td>...</td><td>...</td></tr><tr><td>DEFB136</td><td>Defensin, beta 136</td><td>Beta-defensin 136</td></tr><tr><td><a href="/facts/Theta_defensin/QIfs904f">θ-defensins</a></td><td>DEFT1P</td><td>Defensin, theta 1 pseudogene</td><td>not expressed in humans</td><td>Are rare, and thus far have been found only in the leukocytes of the <a href="/facts/Rhesus_macaque/TkffMX9v">rhesus macaque</a><a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> and the olive baboon, <a href="/facts/Papio_anubis/4p7DxP3j">Papio anubis</a>, the gene coding for it is corrupted in humans and other primates.<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a><a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a></td></tr></tbody></table> <p>Although the most well-studied defensins are from vertebrates, a family of trans-defensins called 'big defensins' are found in <a href="/facts/Molluscs/1elgknsQ">molluscs</a>, <a href="/facts/Arthropods/JKJLTFzp">arthropods</a> and <a href="/facts/Lancelet/r1s2Ef9J">lancelets</a>.<a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a><a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a> </p> <h3>Cis-defensins</h3> <p><a href="/facts/Arthropod_defensin/TKCG0yzl">Arthropod defensins</a> are the best-characterised defensins from invertebrates (especially those from insects).<a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a> Other invertebrates known to produce defensins from this protein superfamily include <a href="/facts/Molluscs/1elgknsQ">molluscs</a>, <a href="/facts/Annelid/PQvb7NAM">annelids</a> and <a href="/facts/Cnidaria/d0HRc6w0">cnidaria</a>.<a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a> </p><p><a href="/facts/Plant_defensin/IkgaBX6L">Plant defensins</a> were discovered in 1990 and have subsequently been found in most plant tissues with antimicrobial activities, with both antifungal and antibacterial examples.<a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a> They have been identified in all major groups of <a href="/facts/Vascular_plant/5nWI2huT">vascular plants</a>, but not in ferns, mosses or algae.<a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a> </p><p>Fungal defensins were first identified in 2005.<a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a> Studied examples mainly have anti-bacterial activities and have been found in both main <a href="/facts/Division_(mycology)/ELT3Jyax">divisions</a> of fungi (<a href="/facts/Ascomycota/4GJdsf2e">Ascomycota</a> and <a href="/facts/Basidiomycota/LuFeC7D2">Basidiomycota</a>), as well as in the more basal groups of <a href="/facts/Zygomycota/goveV5cH">Zygomycota</a> and <a href="/facts/Glomeromycota/kfbrKPT3">Glomeromycota</a>.<a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a> </p><p>Bacterial defensins have also been identified, but are by far the least studied. They include variants with only four cysteines, whereas defensins from eukaryote defensins almost all have six or eight.<a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a> </p> <h3>Related defensin-like proteins</h3> <p>In addition to the defensins involved in host defence, there are a number of related Defensin-Like Peptides (DLPs) that have evolved to have other activities. </p> <h4>Toxins</h4> <p>There appear to have been multiple evolutionary recruitments of defensins to be toxin proteins used in the venoms of animals;<a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a> they act via a completely different mechanism to their antimicrobial relatives, from binding directly to <a href="/facts/Ion_channel/A46LARFH">ion channels</a> to disrupting <a href="/facts/Nerve_signal/Sz8yCRqx">nerve signals</a>. Examples include the <a href="/facts/Crotamine/CBqY7uJ8">crotamine</a> toxin in <a href="/facts/Snake_venom/BBYrAvSh">snake venom</a>,<a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a> many <a href="/facts/Scorpion_toxin/pnWg0gpr">scorpion toxins</a>,<a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a> some <a href="/facts/Sea_anemone_neurotoxin/DpjyHfcT">sea anemone toxins</a>,<a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a> and one of the toxins in <a href="/facts/Platypus_venom/Bmj8nRwY">platypus venom</a>.<a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a> Indeed, an insect defensin has been experimentally converted into a toxin by deletion of a small loop that otherwise <a href="/facts/Steric_effects/TnX5c8HG">sterically hindered</a> interactions with the ion channels.<a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a> </p> <h4>Signalling</h4> <p>In vertebrates, some α- and β-defensins are involved in signalling between the <a href="/facts/Innate_immune_system/lz4BpSQI">innate immune</a> and <a href="/facts/Adaptive_immune_system/bc7zT1Jo">adaptive immune</a> systems.<a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a><a class="footnote-ref" id="fnref:41" href="#fn:41"><sup>41</sup></a> In plants, a specialised family of DLPs is involved in signalling to detect if <a href="/facts/Self-pollination/zvnJrYSx">self-pollination</a> has occurred and induce <a href="/facts/Sporophytic_self-incompatibility/dn0bjr1T">self-incompatibility</a> to prevent inbreeding.<a class="footnote-ref" id="fnref:42" href="#fn:42"><sup>42</sup></a> </p> <h4>Enzyme inhibitors</h4> <p>Some antimicrobial defensins also have <a href="/facts/Enzyme_inhibitor/MkFwGXHJ">enzyme inhibitory</a> activity, and some DLPs function primarily as enzyme inhibitors, acting as <a href="/facts/Antifeedant/q2ofHuQF">antifeedants</a> (discouraging animals from eating them).<a class="footnote-ref" id="fnref:43" href="#fn:43"><sup>43</sup></a><a class="footnote-ref" id="fnref:44" href="#fn:44"><sup>44</sup></a><a class="footnote-ref" id="fnref:45" href="#fn:45"><sup>45</sup></a> </p> <h2 id="function">Function</h2> <p>In immature <a href="/facts/Marsupials/zN5s4bMq">marsupials</a>, because their <a href="/facts/Immune_system/HRCTf1pb">immune system</a> is underdeveloped at the time of birth, defensins play a major role in defense against <a href="/facts/Pathogens/axMXtV1M">pathogens</a>. They are produced in the milk of the mother as well as by the young marsupial in question. </p><p>In human breast milk, defensins play a central role in neonate immunity.<a class="footnote-ref" id="fnref:46" href="#fn:46"><sup>46</sup></a> </p><p>The human genome contains theta-defensin genes, but they have a premature <a href="/facts/Stop_codon/1yuAkq9X">stop codon</a>, hampering their expression. An artificial human theta-defensin,<a class="footnote-ref" id="fnref:47" href="#fn:47"><sup>47</sup></a> retrocyclin, was created by 'fixing' the <a href="/facts/Pseudogene/VfbL4L07">pseudogene</a>, and it was shown to be effective against <a href="/facts/Human_immunodeficiency_virus/ulY2rgzu">HIV</a><a class="footnote-ref" id="fnref:48" href="#fn:48"><sup>48</sup></a> and other viruses, including <a href="/facts/Herpes_simplex_virus/pStCydgY">herpes simplex virus</a> and <a href="/facts/Influenza_A/bKMeST8Q">influenza A</a>. They act primarily by preventing these viruses from entering their target cells. </p><p>Also interesting is the effect of alpha-defensins on the <a href="/facts/Exotoxin/j18H60P0">exotoxin</a> produced by anthrax (<i><a href="/facts/Bacillus_anthracis/suoM7vhx">Bacillus anthracis</a></i>). Chun Kim et al. showed how anthrax, which produces a <a href="/facts/Metalloprotease/ShDT6dbf">metalloprotease</a> lethal factor (LF) protein to target <a href="/facts/MAPKK/EAels6HG">MAPKK</a>, is vulnerable to human neutrophil protein-1 (HNP-1). This group showed HNP-1 to behave as a reversible noncompetitive inhibitor of LF.<a class="footnote-ref" id="fnref:49" href="#fn:49"><sup>49</sup></a> </p><p>They have generally been considered to contribute to mucosal health; however, it is possible that these peptides can be considered biological factors that can be upregulated by bioactive compounds present in human breast milk. In this sense, the intestinal production of antimicrobial peptides as hBD2 and hBD4 by trefoil from milk might play an important role on neonate colonization, thereby enhancing the immune response of newborns against pathogens with which they may come in contact.<a class="footnote-ref" id="fnref:50" href="#fn:50"><sup>50</sup></a><a class="footnote-ref" id="fnref:51" href="#fn:51"><sup>51</sup></a> </p> <h2 id="pathology">Pathology</h2> <p>The <a href="/facts/Alpha_defensin/ADmhByVs">alpha defensin</a> peptides are increased in chronic inflammatory conditions. </p><p><a href="/facts/Alpha_defensin/ADmhByVs">Alpha defensin</a> are increased in several cancers, including colorectal cancer.<a class="footnote-ref" id="fnref:52" href="#fn:52"><sup>52</sup></a> </p><p>An imbalance of defensins in the skin may contribute to acne.<a class="footnote-ref" id="fnref:53" href="#fn:53"><sup>53</sup></a> </p><p>A reduction of <a href="/facts/Ileum/rCWGkFuf">ileal</a> defensins may predispose to <a href="/facts/Crohn%2527s_disease/zm55cBtd">Crohn's disease</a>.<a class="footnote-ref" id="fnref:54" href="#fn:54"><sup>54</sup></a><a class="footnote-ref" id="fnref:55" href="#fn:55"><sup>55</sup></a> </p><p>In one small study, a significant increase in <a href="/facts/Alpha_defensin/ADmhByVs">alpha defensin</a> levels was detected in <a href="/facts/T_cell/5z6PQ9UN">T cell</a> lysates of <a href="/facts/Schizophrenia/FMP4lQ57">schizophrenia</a> patients; in discordant twin pairs, unaffected twins also had an increase, although not as high as that of their ill siblings. The authors suggested that alpha-defensin levels might prove a useful marker for schizophrenia risk.<a class="footnote-ref" id="fnref:56" href="#fn:56"><sup>56</sup></a> </p><p>Defensins are found in the human skin during inflammatory conditions like <a href="/facts/Psoriasis/WW1k1LsH">psoriasis</a><a class="footnote-ref" id="fnref:57" href="#fn:57"><sup>57</sup></a> and also during <a href="/facts/Wound_healing/3NlzV5Qn">wound healing</a>. </p> <h2 id="applications">Applications</h2> <h3>Defensins</h3> <p>At present, the widespread spread of antibiotic resistance requires the search and development of new antimicrobial drugs. From this point of view, defensins (as well as antimicrobial peptides in general) are of great interest. It was shown that defensins have pronounced antibacterial activity against a wide range of pathogens.<a class="footnote-ref" id="fnref:58" href="#fn:58"><sup>58</sup></a> In addition, defensins can enhance the effectiveness of conventional antibiotics.<a class="footnote-ref" id="fnref:59" href="#fn:59"><sup>59</sup></a> </p> <h3>Defensin-mimetics</h3> <p>Defensin <a href="/facts/Mimesis/9hT9c6Hg">mimetics</a>, also called host defense peptide (HDP) mimetics, are completely synthetic, non-peptide, small molecule structures that mimic defensins in structure and activity.<a class="footnote-ref" id="fnref:60" href="#fn:60"><sup>60</sup></a> Similar molecules, such as <a href="/facts/Brilacidin/qcM27hBf">brilacidin</a>, are being developed as <a href="/facts/Antibiotic/sF1kIfxg">antibiotics</a>,<a class="footnote-ref" id="fnref:61" href="#fn:61"><sup>61</sup></a> <a href="/facts/Anti-inflammatories/W27poSUd">anti-inflammatories</a> for oral <a href="/facts/Mucositis/CunXJnVJ">mucositis</a>,<a class="footnote-ref" id="fnref:62" href="#fn:62"><sup>62</sup></a><a class="footnote-ref" id="fnref:63" href="#fn:63"><sup>63</sup></a> and <a href="/facts/Antifungals/WEk5nS2B">antifungals</a>, especially for <a href="/facts/Candidiasis/gklGEfuq">candidiasis</a>.<a class="footnote-ref" id="fnref:64" href="#fn:64"><sup>64</sup></a><a class="footnote-ref" id="fnref:65" href="#fn:65"><sup>65</sup></a><a class="footnote-ref" id="fnref:66" href="#fn:66"><sup>66</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Host_defense_peptides/sNRRb6sC">Host defense peptides</a>, to which defensins belong</li></ul> <h2 id="external-links">External links</h2> Wikimedia Commons has media related to Defensin. <ul><li><a href="http://defensins.bii.a-star.edu.sg/">Defensins Database, Singapore</a> <a href="https://web.archive.org/web/20080424094014/http://defensins.bii.a-star.edu.sg/">Archived</a> 2008-04-24 at the <a href="/facts/Wayback_Machine/nmQ3a6JC">Wayback Machine</a></li> <li><a href="https://web.archive.org/web/20061005132116/http://bioweb.wku.edu/courses/biol328/Innate.htm">Innate ( Nonspecific ) Immunity</a> at <a href="/facts/Western_Kentucky_University/JvBCpTpk">Western Kentucky University</a></li> <li><a href="/facts/Orientations_of_Proteins_in_Membranes_database/R1bTDgkq">UMich Orientation of Proteins in Membranes</a> <i><a href="http://opm.phar.umich.edu/families.php?superfamily=56">families/superfamily-56</a></i> - Vertebrate defensins and related sea anemone sodium channel toxins</li> <li><a href="/facts/Orientations_of_Proteins_in_Membranes_database/R1bTDgkq">UMich Orientation of Proteins in Membranes</a> <i><a href="http://opm.phar.umich.edu/families.php?superfamily=61">families/superfamily-61</a></i> - Defensins from insects and plants and scorpion toxins</li> <li><a href="https://meshb.nlm.nih.gov/record/ui?name=Defensins">Defensins</a> at the U.S. National Library of Medicine <a href="/facts/Medical_Subject_Headings/C57g2JuF">Medical Subject Headings</a> (MeSH)</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Hazlett L, Wu M (January 2011). "Defensins in innate immunity". Cell and Tissue Research. 343 (1): 175–88. doi:10.1007/s00441-010-1022-4. PMID 20730446. S2CID 2234617. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Tassanakajon A, Somboonwiwat K, Amparyup P (February 2015). "Sequence diversity and evolution of antimicrobial peptides in invertebrates". Developmental and Comparative Immunology. Specific immunity in invertebrates. 48 (2): 324–41. doi:10.1016/j.dci.2014.05.020. PMID 24950415. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Thomma BP, Cammue BP, Thevissen K (December 2002). "Plant defensins". Planta. 216 (2): 193–202. Bibcode:2002Plant.216..193T. doi:10.1007/s00425-002-0902-6. PMID 12447532. 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