View source for Defensin

{{short description|Group of antimicrobial peptides}}
{{cs1 config|name-list-style=vanc}}{{Infobox protein family
| Symbol = Defensin
| Name = Defensin
| image = Defensin examples.png
| width =
| caption = Example defensins with alpha helix in red, beta strands in blue, disulphide bonds in yellow ({{PDB|1MR4|2KOZ|1FJN|2LXZ|1IJV|2RNG}})
| Pfam =
| Pfam_clan =  CL0075
| InterPro =
| SMART =
| PROSITE =
| MEROPS =
| SCOP =
| TCDB =
| OPM family = 54
| OPM protein = 6cs9
| CAZy =
| CDD =
}}

'''Defensins''' are small [[cysteine]]-rich [[cationic]] [[proteins]] across cellular life, including [[vertebrate]]<ref>{{cite journal | vauthors = Hazlett L, Wu M | s2cid = 2234617 | title = Defensins in innate immunity | journal = Cell and Tissue Research | volume = 343 | issue = 1 | pages = 175–88 | date = January 2011 | pmid = 20730446 | doi = 10.1007/s00441-010-1022-4 }}</ref> and [[invertebrate]]<ref>{{cite journal | vauthors = Tassanakajon A, Somboonwiwat K, Amparyup P | title = Sequence diversity and evolution of antimicrobial peptides in invertebrates | journal = Developmental and Comparative Immunology | volume = 48 | issue = 2 | pages = 324–41 | date = February 2015 | pmid = 24950415 | doi = 10.1016/j.dci.2014.05.020 | series = Specific immunity in invertebrates }}</ref> animals, [[plants]],<ref>{{cite journal | vauthors = Thomma BP, Cammue BP, Thevissen K | s2cid = 19356421 | title = Plant defensins | journal = Planta | volume = 216 | issue = 2 | pages = 193–202 | date = December 2002 | pmid = 12447532 | doi = 10.1007/s00425-002-0902-6 | bibcode = 2002Plant.216..193T }}</ref><ref>{{cite journal | vauthors = Sathoff AE, Samac DA | title = Antibacterial Activity of Plant Defensins | journal = Molecular Plant-Microbe Interactions | volume = 32 | issue = 5 | pages = 507–514 | date = May 2019 | pmid = 30501455 | doi = 10.1094/mpmi-08-18-0229-cr | doi-access = free }}</ref> and [[fungi]].<ref>{{cite journal | vauthors = Wu J, Gao B, Zhu S | title = The fungal defensin family enlarged | journal = Pharmaceuticals | volume = 7 | issue = 8 | pages = 866–80 | date = August 2014 | pmid = 25230677 | pmc = 4165938 | doi = 10.3390/ph7080866 | doi-access = free }}</ref> They are [[host defense peptides]], with members displaying either direct [[Antimicrobial|antimicrobial activity]], [[Immune system|immune]] signaling activities, or both. They are variously active against [[bacteria]], [[fungus|fungi]] and many enveloped and nonenveloped [[viruses]]. They are typically 18-45 [[amino acid]]s in length, with three or four highly conserved [[disulphide bonds]].

In animals, they are produced by cells of the [[innate immune system]] and [[epithelial cells]], whereas in plants and fungi they are produced by a wide variety of tissues. An organism usually produces many different defensins, some of which are stored inside the cells (e.g. in [[neutrophil granulocyte]]s to kill [[Phagocyte|phagocytosed]] bacteria), and others are secreted into the extracellular medium. For those that directly kill microbes, their mechanism of action varies from disruption of the [[microbial]] [[cell membrane]] to metabolic disruption.

==Varieties==
{{Multiple image
| align =
| direction = vertical
| total_width = 300
| image1 = Trans-defensin disulphides.svg
| alt1 =
| caption1 = ''Trans''-defensin superfamily: In yellow, the two most conserved disulphides link a beta strand to two different secondary structure elements (motif = CC). On the right, an example structure ({{PDB|1IJV}}).
| image2 = Cis-defensin disulphides.svg
| caption2 = ''Cis''-defensin superfamily: In yellow, the two most conserved disulphides link a beta strand to the same alpha helix (motif = CxC...CxxxC). On the right, an example structure ({{PDB|1MRR4}}).
| header = Characteristic disulphide linkages
| footer =
}}
The name 'defensin' was coined in the mid-1980s, though the proteins have been called 'Cationic Antimicrobial Proteins,' 'Neutrophil peptides,' 'Gamma thionins' amongst others.<ref>{{cite journal | vauthors = Lehrer RI | s2cid = 8774156 | title = Primate defensins | journal = Nature Reviews. Microbiology | volume = 2 | issue = 9 | pages = 727–38 | date = September 2004 | pmid = 15372083 | doi = 10.1038/nrmicro976 }}</ref>

Proteins called 'defensins' are not all evolutionarily related to one another.<ref name=":1">{{cite journal | vauthors = Shafee TM, Lay FT, Hulett MD, Anderson MA | title = The Defensins Consist of Two Independent, Convergent Protein Superfamilies | journal = Molecular Biology and Evolution | volume = 33 | issue = 9 | pages = 2345–56 | date = September 2016 | pmid = 27297472 | doi = 10.1093/molbev/msw106 | doi-access = free }}</ref> Instead fall into two broad [[Protein superfamily|superfamilies]], each of which contains multiple [[Protein family|families]].<ref name=":1" /><ref name=":2">{{cite journal | vauthors = Shafee TM, Lay FT, Phan TK, Anderson MA, Hulett MD | s2cid = 24741736 | title = Convergent evolution of defensin sequence, structure and function | journal = Cellular and Molecular Life Sciences | volume = 74 | issue = 4 | pages = 663–682 | date = February 2017 | pmid = 27557668 | doi = 10.1007/s00018-016-2344-5 | url = https://figshare.com/articles/journal_contribution/13211600 | pmc = 11107677 }}</ref> One superfamily, the ''trans''-defensins, contains the defensins found in humans and other vertebrates,<ref name=":3" /><ref name="Evolution of cnidarian trans-defens">{{cite journal | vauthors = Mitchell ML, Shafee T, Papenfuss AT, Norton RS | title = Evolution of cnidarian trans-defensins: Sequence, structure and exploration of chemical space | journal = Proteins | volume = 87 | issue = 7 | pages = 551–560 | date = July 2019 | pmid = 30811678 | doi = 10.1002/prot.25679 | s2cid = 73469576 | doi-access = free | hdl = 11343/285595 | hdl-access = free }}</ref> as well as some invertebrates.<ref>{{cite journal | vauthors = Zhu S, Gao B | title = Evolutionary origin of β-defensins | journal = Developmental and Comparative Immunology | volume = 39 | issue = 1–2 | pages = 79–84 | date = 2013 | pmid = 22369779 | doi = 10.1016/j.dci.2012.02.011 }}</ref><ref>{{cite journal | vauthors = Montero-Alejo V, Corzo G, Porro-Suardíaz J, Pardo-Ruiz Z, Perera E, Rodríguez-Viera L, Sánchez-Díaz G, Hernández-Rodríguez EW, Álvarez C, Peigneur S, Tytgat J, Perdomo-Morales R | s2cid = 19734223 | title = Panusin represents a new family of β-defensin-like peptides in invertebrates | journal = Developmental and Comparative Immunology | volume = 67 | pages = 310–321 | date = February 2017 | pmid = 27616720 | doi = 10.1016/j.dci.2016.09.002 }}</ref> The other superfamily, ''cis''-defensins, contains the defensins found in invertebrates, plants, and fungi.<ref>{{cite journal | vauthors = Dias RD, Franco OL | title = Cysteine-stabilized αβ defensins: From a common fold to antibacterial activity | journal = Peptides | volume = 72 | pages = 64–72 | date = October 2015 | pmid = 25929172 | doi = 10.1016/j.peptides.2015.04.017 | series = Festschrift to highlight the career of Abba J. Kastin as a founding editor, researcher, and educator in the peptide field | s2cid = 17846143 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Shafee T, Anderson MA | s2cid = 51968286 | title = A quantitative map of protein sequence space for the cis-defensin superfamily | journal = Bioinformatics | volume = 35 | issue = 5 | pages = 743–752 | date = March 2019 | pmid = 30102339 | doi = 10.1093/bioinformatics/bty697 | url = https://figshare.com/articles/journal_contribution/A_quantitative_map_of_protein_sequence_space_for_the_cis-defensin_superfamily/13213259/1/files/25443932.pdf }}</ref><ref>{{cite journal | vauthors = Zhu S | title = Discovery of six families of fungal defensin-like peptides provides insights into origin and evolution of the CSalphabeta defensins | journal = Molecular Immunology | volume = 45 | issue = 3 | pages = 828–38 | date = February 2008 | pmid = 17675235 | doi = 10.1016/j.molimm.2007.06.354 }}</ref> The superfamilies and families are determined by the overall tertiary structure, and each family usually has a conserved pattern of disulphide bonds.<ref name=":3">{{cite book |last1=Hollox|first1=Edward J.|last2=Abujaber|first2=Razan |chapter =Evolution and Diversity of Defensins in Vertebrates|date=2017| title =Evolutionary Biology: Self/Nonself Evolution, Species and Complex Traits Evolution, Methods and Concepts|pages=27–50|editor-last=Pontarotti|editor-first=Pierre|publisher=Springer International Publishing|language=en|doi=10.1007/978-3-319-61569-1_2|isbn=978-3-319-61569-1}}</ref><ref>{{cite journal | vauthors = Wang YP, Lai R | title = [Insect antimicrobial peptides: structures, properties and gene regulation] | journal = Dong Wu Xue Yan Jiu = Zoological Research | volume = 31 | issue = 1 | pages = 27–34 | date = February 2010 | pmid = 20446450 | doi = 10.3724/sp.j.1141.2010.01027 | s2cid = 4692675 | url = http://www.bioline.org.br/abstract?id=zr10004 | doi-access = free | hdl = 1807/64439 | hdl-access = free }}</ref> 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 [[Polymorphism (biology)|polymorphic]].{{cn|date=March 2023}}

=== Trans-defensins ===
Vertebrate defensins are primarily [[Alpha defensin|α-defensins]] and [[Beta defensin|β-defensins]]. Some primates additionally have the much smaller [[Theta defensin|θ-defensins]]. In general, both α- and β-defensins are encoded by two-[[exon]] genes, where the first exon encodes for a hydrophobic leader sequence (removed after [[Translation (biology)|translation]]) 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.<ref>{{cite journal | vauthors = Varkey J, Singh S, Nagaraj R | s2cid = 21104756 | title = Antibacterial activity of linear peptides spanning the carboxy-terminal beta-sheet domain of arthropod defensins | journal = Peptides | volume = 27 | issue = 11 | pages = 2614–23 | date = November 2006 | pmid = 16914230 | doi = 10.1016/j.peptides.2006.06.010 }}</ref><ref>{{cite journal | vauthors = Varkey J, Nagaraj R | title = Antibacterial activity of human neutrophil defensin HNP-1 analogs without cysteines | journal = Antimicrobial Agents and Chemotherapy | volume = 49 | issue = 11 | pages = 4561–6 | date = November 2005 | pmid = 16251296 | pmc = 1280114 | doi = 10.1128/AAC.49.11.4561-4566.2005 }}</ref> [[Theta defensin]]s form a single [[beta hairpin|beta-hairpin]] structure and represent a distinct group. Only alpha and beta-defensins are expressed in humans.<ref>{{cite journal | vauthors = Dhople V, Krukemeyer A, Ramamoorthy A | title = The human beta-defensin-3, an antibacterial peptide with multiple biological functions | journal = Biochimica et Biophysica Acta (BBA) - Biomembranes | volume = 1758 | issue = 9 | pages = 1499–512 | date = September 2006 | pmid = 16978580 | doi = 10.1016/j.bbamem.2006.07.007 | doi-access =  | s2cid = 36461159 }}</ref>

{| class="wikitable sortable mw-collapsible mw-collapsed" style="text-align:center;width:100%;"
|+ style="border:1px #aaa solid; background:#eaeaea; padding:0.2em;" | Table of human defensins
 ! style="width:70px" | Type
 ! Gene Symbol
 ! style="width:120px" | Gene Name
 ! style="width:140px" | Protein Name
 ! Description
 |-
 |  rowspan="6" | [[Alpha defensin|α-defensins]]
 | [[DEFA1]]
 | Defensin, alpha 1
 | Neutrophil defensin 1
 | rowspan="6" | Are expressed primarily in [[neutrophils]] as well as in [[NK cells]] and certain T-lymphocyte subsets. [[DEFA5]] and [[DEFA6]] are expressed in [[Paneth cells]] of the small intestine, where they may regulate and maintain microbial balance in the intestinal lumen.
 |-
 | [[DEFA1B]]
 | Defensin, alpha 1B
 | Defensin, alpha 1
 |-
 | [[DEFA3]]
 | Defensin, alpha 3, neutrophil-specific
 | Neutrophil defensin 3
 |-
 | [[DEFA4]]
 | Defensin, alpha 4, corticostatin
 | Neutrophil defensin 4
 |-
 | [[DEFA5]]
 | Defensin, alpha 5, Paneth cell-specific
 | Defensin-5
 |-
 | [[DEFA6]]
 | Defensin, alpha 6, Paneth cell-specific
 | Defensin-6
 |-
 | rowspan="11" | [[Beta defensin|β-defensins]]
 | [[Defensin, beta 1|DEFB1]]
 | Defensin, beta 1
 | Beta-defensin 1
 | rowspan="11" | Are the most widely distributed, being secreted by [[leukocytes]] and [[epithelial]] 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 [[cystic fibrosis]] arises from the inhibition of β-defensin activity on the epithelial surfaces of the lungs and trachea due to higher salt content.
 |-
 | [[Beta-defensin 2|DEFB2]]
 | Defensin, beta 2
 | Beta-defensin 2
|-
| [[Beta-defensin 3|DEFB3]]
| Defensin, beta 3
| Beta-defensin 3
 |-
 | [[DEFB103A]]
 | Defensin, beta 103B
 | Beta-defensin 103
 |-
 | <sup>'''...'''</sup>
 | <sup>'''...'''</sup>
 | <sup>'''...'''</sup>
 |-
 | [[DEFB106A]]
 | Defensin, beta 106A
 | Beta-defensin 106A
 |-
 | [[DEFB106]]B
 | Defensin, beta 106B
 | Beta-defensin 106B
 |-

| [[DEFB107B]]
 | Defensin, beta 107A
 | Beta-defensin 107
 |-
| [[DEFB110]]
 | Defensin, beta 110
|Beta-defensin 110
 |-
| <sup>'''...'''</sup>
 | <sup>'''...'''</sup>
|<sup>'''...'''</sup>
 |-
| [[DEFB136]]
 | Defensin, beta 136
|Beta-defensin 136
 |-
 | [[Theta defensin|θ-defensins]]
 | [[DEFT1P]]
 | Defensin, theta 1 pseudogene
 | not expressed in humans
 | Are rare, and thus far have been found only in the leukocytes of the [[rhesus macaque]]<ref name="pmid18160518">{{cite journal | vauthors = Tran D, Tran P, Roberts K, Osapay G, Schaal J, Ouellette A, Selsted ME | title = Microbicidal properties and cytocidal selectivity of rhesus macaque theta defensins | journal = Antimicrobial Agents and Chemotherapy | volume = 52 | issue = 3 | pages = 944–53 | date = March 2008 | pmid = 18160518 | pmc = 2258523 | doi = 10.1128/AAC.01090-07 }}</ref> and the olive baboon, [[Papio anubis]], the gene coding for it is corrupted in humans and other primates.<ref name="olivebaboon1">{{cite journal |first1=Angie Eva |last1=Garcia |first2=Michael |last2=Selsted |date=March 2008 |title=Olive baboon θ-defensins |doi=10.1096/fasebj.22.1_supplement.673.11 |journal=The FASEB Journal |volume=22 |issue=1 Suppl |pages=673.11 |doi-access= free|s2cid=89807163 }}</ref><ref name="pmid18852242">{{cite journal | vauthors = Garcia AE, Osapay G, Tran PA, Yuan J, Selsted ME | title = Isolation, synthesis, and antimicrobial activities of naturally occurring theta-defensin isoforms from baboon leukocytes | journal = Infection and Immunity | volume = 76 | issue = 12 | pages = 5883–91 | date = December 2008 | pmid = 18852242 | pmc = 2583559 | doi = 10.1128/IAI.01100-08 }}</ref>
|}
Although the most well-studied defensins are from vertebrates, a family of trans-defensins called '{{visible anchor|big defensin}}s' are found in [[molluscs]], [[arthropods]] and [[lancelet]]s.<ref name=":1" /><ref name=":2" />

=== Cis-defensins ===
[[Arthropod defensin]]s are the best-characterised defensins from invertebrates (especially those from insects).<ref>{{cite journal | vauthors = Koehbach J | title = Structure-Activity Relationships of Insect Defensins | language = English | journal = Frontiers in Chemistry | volume = 5 | pages = 45 | date = 2017 | pmid = 28748179 | pmc = 5506212 | doi = 10.3389/fchem.2017.00045 | bibcode = 2017FrCh....5...45K | doi-access = free }}</ref> Other invertebrates known to produce defensins from this protein superfamily include [[molluscs]], [[annelid]]s and [[cnidaria]].<ref>{{cite journal | vauthors = Greco S, Gerdol M, Edomi P, Pallavicini A | title = Molecular Diversity of Mytilin-Like Defense Peptides in Mytilidae (Mollusca, Bivalvia) | journal = Antibiotics | volume = 9 | issue = 1 | pages = 37 | date = January 2020 | pmid = 31963793 | doi = 10.3390/antibiotics9010037 | pmc = 7168163 | doi-access = free }}</ref>

[[Plant defensin]]s were discovered in 1990 and have subsequently been found in most plant tissues with antimicrobial activities, with both antifungal and antibacterial examples.<ref name=":5">{{cite journal | vauthors = Parisi K, Shafee TM, Quimbar P, van der Weerden NL, Bleackley MR, Anderson MA | title = The evolution, function and mechanisms of action for plant defensins | journal = Seminars in Cell & Developmental Biology | volume = 88 | pages = 107–118 | date = April 2019 | pmid = 29432955 | doi = 10.1016/j.semcdb.2018.02.004 | s2cid = 3543741 | url = https://figshare.com/articles/journal_contribution/13213427 }}</ref> They have been identified in all major groups of [[vascular plant]]s, but not in ferns, mosses or algae.<ref name=":5" />

[[Fungal defensin]]s were first identified in 2005.<ref>{{cite journal | vauthors = Mygind PH, Fischer RL, Schnorr KM, Hansen MT, Sönksen CP, Ludvigsen S, Raventós D, Buskov S, Christensen B, De Maria L, Taboureau O, Yaver D, Elvig-Jørgensen SG, Sørensen MV, Christensen BE, Kjaerulff S, Frimodt-Moller N, Lehrer RI, Zasloff M, Kristensen HH | title = Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus | journal = Nature | volume = 437 | issue = 7061 | pages = 975–80 | date = October 2005 | pmid = 16222292 | doi = 10.1038/nature04051 | bibcode = 2005Natur.437..975M | s2cid = 4423851 }}</ref> Studied examples mainly have anti-bacterial activities and have been found in both main [[Division (mycology)|divisions]] of fungi ([[Ascomycota]] and [[Basidiomycota]]), as well as in the more basal groups of [[Zygomycota]] and [[Glomeromycota]].<ref>{{cite journal | vauthors = Wu J, Gao B, Zhu S | title = The fungal defensin family enlarged | journal = Pharmaceuticals | volume = 7 | issue = 8 | pages = 866–80 | date = August 2014 | pmid = 25230677 | pmc = 4165938 | doi = 10.3390/ph7080866 | doi-access = free }}</ref>

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.<ref>{{cite journal | vauthors = Dash TS, Shafee T, Harvey PJ, Zhang C, Peigneur S, Deuis JR, Vetter I, Tytgat J, Anderson MA, Craik DJ, Durek T, Undheim EA | title = A Centipede Toxin Family Defines an Ancient Class of CSαβ Defensins | journal = Structure | volume = 27 | issue = 2 | pages = 315–326.e7 | date = February 2019 | pmid = 30554841 | doi = 10.1016/j.str.2018.10.022 | doi-access = free }}</ref>

=== Related defensin-like proteins ===
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.

==== Toxins ====
There appear to have been multiple evolutionary recruitments of defensins to be toxin proteins used in the venoms of animals;<ref name="Defensins and the convergent evolut">{{cite journal | vauthors = Whittington CM, Papenfuss AT, Bansal P, Torres AM, Wong ES, Deakin JE, Graves T, Alsop A, Schatzkamer K, Kremitzki C, Ponting CP, Temple-Smith P, Warren WC, Kuchel PW, Belov K | title = Defensins and the convergent evolution of platypus and reptile venom genes | journal = Genome Research | volume = 18 | issue = 6 | pages = 986–94 | date = June 2008 | pmid = 18463304 | pmc = 2413166 | doi = 10.1101/gr.7149808 }}</ref> they act via a completely different mechanism to their antimicrobial relatives, from binding directly to [[ion channel]]s to disrupting [[nerve signal]]s. Examples include the [[crotamine]] toxin in [[snake venom]],<ref>{{cite journal | vauthors = Batista da Cunha D, Pupo Silvestrini AV, Gomes da Silva AC, Maria de Paula Estevam D, Pollettini FL, de Oliveira Navarro J, Alves AA, Remédio Zeni Beretta AL, Annichino Bizzacchi JM, Pereira LC, Mazzi MV | s2cid = 205440053 | title = Mechanistic insights into functional characteristics of native crotamine | journal = Toxicon | volume = 146 | pages = 1–12 | date = May 2018 | pmid = 29574214 | doi = 10.1016/j.toxicon.2018.03.007 | hdl = 11449/170828 | hdl-access = free }}</ref> many [[scorpion toxin]]s,<ref>{{cite journal | vauthors = Possani LD, Becerril B, Delepierre M, Tytgat J | title = Scorpion toxins specific for Na+-channels | journal = European Journal of Biochemistry | volume = 264 | issue = 2 | pages = 287–300 | date = September 1999 | pmid = 10491073 | doi = 10.1046/j.1432-1327.1999.00625.x | doi-access = free }}</ref> some [[Sea anemone neurotoxin|sea anemone toxins]],<ref name="Evolution of cnidarian trans-defens"/> and one of the toxins in [[platypus venom]].<ref name="Defensins and the convergent evolut"/> Indeed, an insect defensin has been experimentally converted into a toxin by deletion of a small loop that otherwise [[Steric effects#steric hindrance|sterically hindered]] interactions with the ion channels.<ref name=":0">{{cite journal | vauthors = Zhu S, Peigneur S, Gao B, Umetsu Y, Ohki S, Tytgat J | title = Experimental conversion of a defensin into a neurotoxin: implications for origin of toxic function | journal = Molecular Biology and Evolution | volume = 31 | issue = 3 | pages = 546–59 | date = March 2014 | pmid = 24425781 | doi = 10.1093/molbev/msu038 | doi-access = free }}</ref>

==== Signalling ====
In vertebrates, some α- and β-defensins are involved in signalling between the [[Innate immune system|innate immune]] and [[Adaptive immune system|adaptive immune]] systems.<ref>{{cite journal | vauthors = Petrov V, Funderburg N, Weinberg A, Sieg S | title = Human β defensin-3 induces chemokines from monocytes and macrophages: diminished activity in cells from HIV-infected persons | journal = Immunology | volume = 140 | issue = 4 | pages = 413–20 | date = December 2013 | pmid = 23829433 | pmc = 3839645 | doi = 10.1111/imm.12148 }}</ref><ref>{{cite journal | vauthors = Semple F, Dorin JR | title = β-Defensins: multifunctional modulators of infection, inflammation and more? | journal = Journal of Innate Immunity | volume = 4 | issue = 4 | pages = 337–48 | date = 2012 | pmid = 22441423 | pmc = 6784047 | doi = 10.1159/000336619 }}</ref> In plants, a specialised family of DLPs is involved in signalling to detect if [[self-pollination]] has occurred and induce [[Sporophytic self-incompatibility|self-incompatibility]] to prevent inbreeding.<ref>{{cite book | vauthors = Fobis-Loisy I, Ivanov R, Gaude T |chapter=The S-LOCUS CYSTEINE-RICH PROTEIN (SCR): A Small Peptide with a High Impact on the Evolution of Flowering Plants |date=2012|pages=77–92|publisher=Springer Berlin Heidelberg|isbn=978-3-642-27602-6 |doi=10.1007/978-3-642-27603-3_5|title=Plant Signaling Peptides|volume=16|series=Signaling and Communication in Plants}}</ref>

==== Enzyme inhibitors ====
Some antimicrobial defensins also have [[enzyme inhibitor]]y activity, and some DLPs function primarily as enzyme inhibitors, acting as [[antifeedant]]s (discouraging animals from eating them).<ref>{{cite news|title=Porcine pancreatic alpha-amylase in complex with helianthamide, a novel proteinaceous inhibitor| vauthors = Williams LK, Brayer GD |date=2015-11-25|doi=10.2210/pdb4x0n/pdb}}</ref><ref>{{cite news|title=Minimized NMR structure of ATT, an Arabidopsis trypsin/chymotrypsin inhibitor| vauthors = Zhao Q, Chae YK, Markley JL |date=2003-01-07 |doi=10.2210/pdb1jxc/pdb}}</ref><ref>{{cite journal | vauthors = Pelegrini PB, Lay FT, Murad AM, Anderson MA, Franco OL | title = Novel insights on the mechanism of action of alpha-amylase inhibitors from the plant defensin family | journal = Proteins | volume = 73 | issue = 3 | pages = 719–29 | date = November 2008 | pmid = 18498107 | doi = 10.1002/prot.22086 | s2cid = 28378146 }}</ref>

== Function ==
In immature [[marsupials]], because their [[immune system]] is underdeveloped at the time of birth, defensins play a major role in defense against [[pathogens]]. {{Citation needed|date=November 2015}} They are produced in the milk of the mother as well as by the young marsupial in question.

In human breast milk, defensins play a central role in neonate immunity.<ref name="pmid23198942">{{cite journal | vauthors = Barrera GJ, Sanchez G, Gonzalez JE | title = Trefoil factor 3 isolated from human breast milk downregulates cytokines (IL8 and IL6) and promotes human beta defensin (hBD2 and hBD4) expression in intestinal epithelial cells HT-29 | journal = Bosnian Journal of Basic Medical Sciences | volume = 12 | issue = 4 | pages = 256–64 | date = November 2012 | pmid = 23198942 | pmc = 4362502 | doi = 10.17305/bjbms.2012.2448 }}</ref>

The human genome contains theta-defensin genes, but they have a premature [[stop codon]], hampering their expression. An artificial human theta-defensin,<ref>{{MeshName|retrocyclin}}</ref> '''retrocyclin''', was created by 'fixing' the [[pseudogene]], and it was shown to be effective against [[Human immunodeficiency virus|HIV]]<ref name="pmid14585219">{{cite journal | vauthors = Münk C, Wei G, Yang OO, Waring AJ, Wang W, Hong T, Lehrer RI, Landau NR, Cole AM | title = The theta-defensin, retrocyclin, inhibits HIV-1 entry | journal = AIDS Research and Human Retroviruses | volume = 19 | issue = 10 | pages = 875–81 | date = October 2003 | pmid = 14585219 | doi = 10.1089/088922203322493049 }}</ref> and other viruses, including [[herpes simplex virus]] and [[influenza A]]. They act primarily by preventing these viruses from entering their target cells.

Also interesting is the effect of alpha-defensins on the [[exotoxin]] produced by anthrax (''[[Bacillus anthracis]]''). Chun Kim et al. showed how anthrax, which produces a [[metalloprotease]] lethal factor (LF) protein to target [[MAPKK]], is vulnerable to human neutrophil protein-1 (HNP-1). This group showed HNP-1 to behave as a reversible noncompetitive inhibitor of LF.<ref>{{cite journal | vauthors = Kim C, Gajendran N, Mittrücker HW, Weiwad M, Song YH, Hurwitz R, Wilmanns M, Fischer G, Kaufmann SH | title = Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 13 | pages = 4830–5 | date = March 2005 | pmid = 15772169 | pmc = 555714 | doi = 10.1073/pnas.0500508102 | bibcode = 2005PNAS..102.4830K | doi-access = free }}</ref>

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.<ref name="pmid23198942" /><ref>{{cite journal | vauthors = Barrera GJ, Tortolero GS | title = Trefoil factor 3 (TFF3) from human breast milk activates PAR-2 receptors, of the intestinal epithelial cells HT-29, regulating cytokines and defensins | journal = Bratislavske Lekarske Listy | volume = 117 | issue = 6 | pages = 332–9 | year = 2016 | pmid = 27546365 | doi = 10.4149/bll_2016_066 | doi-access = free }}</ref>

== Pathology ==
The [[alpha defensin]] peptides are increased in chronic inflammatory conditions.

[[Alpha defensin]] are increased in several cancers, including colorectal cancer.<ref>{{cite journal | vauthors = Albrethsen J, Bøgebo R, Gammeltoft S, Olsen J, Winther B, Raskov H | title = Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours: a biomarker study | journal = BMC Cancer | volume = 5 | pages = 8 | date = January 2005 | pmid = 15656915 | pmc = 548152 | doi = 10.1186/1471-2407-5-8 | doi-access = free }}</ref>

An imbalance of defensins in the skin may contribute to acne.<ref>{{cite journal | vauthors = Philpott MP | title = Defensins and acne | journal = Molecular Immunology | volume = 40 | issue = 7 | pages = 457–62 | date = November 2003 | pmid = 14568392 | doi = 10.1016/S0161-5890(03)00154-8 }}</ref>

A reduction of [[ileum|ileal]] defensins may predispose to [[Crohn's disease]].<ref>{{cite journal |journal=Genomics & Genetics Weekly |title=Researchers discover a possible cause of chronic inflammations of Crohn Disease |date=August 11, 2006 |pages=72 }}</ref><ref>{{cite journal | vauthors = Wehkamp J, Salzman NH, Porter E, Nuding S, Weichenthal M, Petras RE, Shen B, Schaeffeler E, Schwab M, Linzmeier R, Feathers RW, Chu H, Lima H, Fellermann K, Ganz T, Stange EF, Bevins CL | title = Reduced Paneth cell alpha-defensins in ileal Crohn's disease | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 50 | pages = 18129–34 | date = December 2005 | pmid = 16330776 | pmc = 1306791 | doi = 10.1073/pnas.0505256102 | bibcode = 2005PNAS..10218129W | doi-access = free }}</ref>

In one small study, a significant increase in [[alpha defensin]] levels was detected in [[T cell]] lysates of [[schizophrenia]] 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.<ref name="pmid18349140">{{cite journal | vauthors = Craddock RM, Huang JT, Jackson E, Harris N, Torrey EF, Herberth M, Bahn S | title = Increased alpha-defensins as a blood marker for schizophrenia susceptibility | journal = Molecular & Cellular Proteomics | volume = 7 | issue = 7 | pages = 1204–13 | date = July 2008 | pmid = 18349140 | doi = 10.1074/mcp.M700459-MCP200 | s2cid = 35381828 | doi-access = free }}</ref>

Defensins are found in the human skin during inflammatory conditions like [[psoriasis]]<ref>{{cite journal | vauthors = Harder J, Bartels J, Christophers E, Schroder JM | title = Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic | journal = The Journal of Biological Chemistry | volume = 276 | issue = 8 | pages = 5707–13 | date = February 2001 | pmid = 11085990 | doi = 10.1074/jbc.M008557200 | s2cid = 9516726 | doi-access = free }}</ref> and also during [[wound healing]].

==Applications==

=== Defensins ===
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.<ref name=":4">{{cite journal| vauthors = Bolatchiev A |date=2020-11-25|title=Antibacterial activity of human defensins against Staphylococcus aureus and Escherichia coli |journal=PeerJ |volume=8 |pages=e10455 |doi=10.7717/peerj.10455 |pmid=33304659|pmc=7698690 |doi-access=free }}</ref> In addition, defensins can enhance the effectiveness of conventional antibiotics.<ref name=":4" />

===Defensin-mimetics===
Defensin [[Mimesis|mimetics]], also called host defense peptide (HDP) mimetics, are completely synthetic, non-peptide, small molecule structures that mimic defensins in structure and activity.<ref>{{cite press release|url=http://www.businesswire.com/news/home/20080509005466/en/PolyMedix-Receives-Regulatory-Clearance-Initiate-Phase-Clinical#.VPO70_nF9Qg|title=Press release: PolyMedix|date=2008-05-09}} Business Wire</ref> Similar molecules, such as [[brilacidin]], are being developed as [[antibiotic]]s,<ref>{{cite news |url=http://www.medicalnewstoday.com/releases/118978.php |title=PMX-30063 The First And Only Defensin Mimetic Systemic Antibiotic Drug In Human Clinical Trials |year=2008 }}</ref> [[anti-inflammatories]] for oral [[mucositis]],<ref>{{ClinicalTrialsGov|NCT02324335|Phase 2 Study to Evaluate the Safety & Efficacy of Brilacidin Oral Rinse in Patients With Head and Neck Cancer (Brilacidin)}}</ref><ref>{{cite web|url=http://cellceutix.com/brilacidin-om/#sthash.SDIn67NC.dpbs|title=Brilacidin-OM page|publisher=Cellceutix|access-date=2015-03-02|archive-url=https://web.archive.org/web/20150207051957/http://cellceutix.com/brilacidin-om/#sthash.SDIn67NC.dpbs|archive-date=2015-02-07|url-status=dead}}</ref> and [[antifungals]], especially for [[candidiasis]].<ref>{{cite web|url=http://cellceutix.com/candidiasis/#sthash.f36Zt7H7.dpbs|title=Candidiasis|publisher=Cellceutix|access-date=2015-03-02|archive-url=https://web.archive.org/web/20150207073612/http://cellceutix.com/candidiasis/#sthash.f36Zt7H7.dpbs|archive-date=2015-02-07|url-status=dead}}</ref><ref>{{cite journal|url=http://grantome.com/grant/NIH/R44-AI106270-05|title=A Novel Therapeutic For Invasive Candiasis | publisher = Fox Chase Chemical Diversity Center | journal = Grantome|last1=Diamond |first1=Gill |last2=Scott |first2=Richard }}</ref><ref>{{cite journal | vauthors = Ryan LK, Freeman KB, Masso-Silva JA, Falkovsky K, Aloyouny A, Markowitz K, Hise AG, Fatahzadeh M, Scott RW, Diamond G | title = Activity of potent and selective host defense peptide mimetics in mouse models of oral candidiasis | journal = Antimicrobial Agents and Chemotherapy | volume = 58 | issue = 7 | pages = 3820–7 | date = July 2014 | pmid = 24752272 | pmc = 4068575 | doi = 10.1128/AAC.02649-13 }}</ref>

== See also ==
* [[Host defense peptides]], to which defensins belong

== References ==
{{reflist|30em}}

== External links ==
{{commons category|Defensin}}
*  [http://defensins.bii.a-star.edu.sg/ Defensins Database, Singapore] {{Webarchive|url=https://web.archive.org/web/20080424094014/http://defensins.bii.a-star.edu.sg/ |date=2008-04-24 }}
* [https://web.archive.org/web/20061005132116/http://bioweb.wku.edu/courses/biol328/Innate.htm Innate ( Nonspecific ) Immunity] at [[Western Kentucky University]]
* {{UMichOPM|families|superfamily|56}} - Vertebrate defensins and related sea anemone sodium channel toxins
* {{UMichOPM|families|superfamily|61}} - Defensins from insects and plants and scorpion toxins
* {{MeshName|Defensins}}

{{Granule contents}}
{{Pore-forming toxins}}

[[Category:Defensins| ]]
[[Category:Antimicrobial peptides]]
[[Category:Cysteine-rich proteins]]