Defensin
Encyclopedia
Defensins are small cysteine
-rich cationic proteins found in both vertebrate
s and invertebrate
s. They have also been reported in plants. They are, and function as, host defense peptides. They are active against bacteria
, fungi
and many enveloped and nonenveloped viruses. They consist of 18-45 amino acid
s including six (in vertebrates) to eight conserved cysteine
residues. Cells of the immune system
contain these peptides to assist in killing phagocytized
bacteria, for example in neutrophil granulocyte
s and almost all epithelial cells. Most defensins function by binding to the microbial cell membrane
, and, once embedded, forming pore-like membrane defects that allow efflux of essential ions and nutrients.
. Some aspects are conserved, however; the hallmarks of a β-defensin are its small size, high density of cationic charge, and six-cysteine-residue motif. In general, they are encoded by two-exon
genes, wherein the first exon encodes for a hydrophobic leader sequence and the second for a peptide containing the cysteine motif.
! style="width:70px" | Type
! Gene Symbol
! style="width:120px" | Gene Name
! style="width:140px" | Protein Name
! Description
|-
| rowspan="6" | 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="8" | β-defensins
| DEFB1
| Defensin, beta 1
| Beta-defensin 1
| rowspan="8" | 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.
|-
| DEFB2
| Defensin, beta 2
| Beta-defensin 2
|-
| DEFB103A
| Defensin, beta 103B
| Beta-defensin 103
|-
| ...
| ...
| ...
|-
| DEFB107B
| Defensin, beta 107A
| Beta-defensin 107
|-
| DEFB110
| Defensin, beta 110
| Beta-defensin 110
|-
| ...
| ...
| ...
|-
| DEFB136
| Defensin, beta 136
| Beta-defensin 136
|-
| 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
and the olive baboon, Papio anubis, being vestigial in humans and other primates.>
is underdeveloped at the time of birth, defensins play a major role in defense against pathogens. They are produced in the milk of the mother as well as by the young marsupial in question.
Human genome contains theta-defensin genes, but they have a premature stop codon
, hampering their expression. An artificial human theta-defensin, retrocyclin, was created by `fixing' the pseudogene
, and it was shown to be effective against HIV 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.
Defensin-like proteins are also a component of platypus
venom.
s.
peptides are increased in chronic inflammatory conditions.
Alpha defensin
are increased in several cancers, including colorectal cancer.
An imbalance of defensins in the skin may contribute to acne.
A reduction of ileal
defensins may predispose to Crohn's disease
.
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.
Defensins are found in the human skin during inflammatory conditions like psoriasis
and also during wound healing
.
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
-rich cationic proteins found in both vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
s and invertebrate
Invertebrate
An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group...
s. They have also been reported in plants. They are, and function as, host defense peptides. They are active against bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, fungi
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...
and many enveloped and nonenveloped viruses. They consist of 18-45 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s including six (in vertebrates) to eight conserved cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
residues. Cells of the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
contain these peptides to assist in killing phagocytized
Phagocyte
Phagocytes are the white blood cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are...
bacteria, for example in neutrophil granulocyte
Neutrophil granulocyte
Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...
s and almost all epithelial cells. Most defensins function by binding to the microbial cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
, and, once embedded, forming pore-like membrane defects that allow efflux of essential ions and nutrients.
Varieties
The underlying genes responsible for defensin production are highly polymorphicPolymorphism (biology)
Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
. Some aspects are conserved, however; the hallmarks of a β-defensin are its small size, high density of cationic charge, and six-cysteine-residue motif. In general, they are encoded by two-exon
Exon
An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...
genes, wherein the first exon encodes for a hydrophobic leader sequence and the second for a peptide containing the cysteine motif.
! Gene Symbol
! style="width:120px" | Gene Name
! style="width:140px" | Protein Name
! Description
|-
| rowspan="6" | α-defensins
Alpha defensin
Alpha defensins are a family of mammalian defensin peptides.Defensins are 2-6 kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses, containing three pairs of intramolecular disulfide bonds...
| 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
DEFA5
Defensin, alpha 5 also known as human alpha defensin 5 is a human protein that is encoded by the DEFA5 gene. DEFA5 is expressed in the Paneth cells of the ileum.-Further reading:...
and DEFA6
DEFA6
Defensin, alpha 6 also known as human alpha defensin 6 is a human protein that is encoded by the DEFA6 gene. DEFA6 is expressed in the Paneth cells of the ileum.- Function :...
are expressed in Paneth cells
Paneth cells
Paneth cells, along with goblet cells, enterocytes, and enteroendocrine cells, represent the principal cell types of the epithelium of the small intestine...
of the small intestine, where they may regulate and maintain microbial balance in the intestinal lumen.
|-
| DEFA1B
DEFA1B
Defensin, alpha 1B a human protein that is encoded by the DEFA1B gene....
| Defensin, alpha 1B
| Defensin, alpha 1
|-
| DEFA3
DEFA3
Defensin, alpha 3 also known as human alpha defensin 3, human neutrophil peptide 3 or neutrophil defensin 3 is a human protein that is encoded by the DEFA3 gene...
| Defensin, alpha 3, neutrophil-specific
| Neutrophil defensin 3
|-
| DEFA4
DEFA4
Defensin, alpha 4 , also known as neutrophil defensin 4 or HNP4, is a human defensin peptide that is encoded by the DEFA4 gene. The human variant of the peptide is known as human alpha defensin 4 or human neutrophil peptide 4...
| Defensin, alpha 4, corticostatin
| Neutrophil defensin 4
|-
| DEFA5
DEFA5
Defensin, alpha 5 also known as human alpha defensin 5 is a human protein that is encoded by the DEFA5 gene. DEFA5 is expressed in the Paneth cells of the ileum.-Further reading:...
| Defensin, alpha 5, Paneth cell-specific
| Defensin-5
|-
| DEFA6
DEFA6
Defensin, alpha 6 also known as human alpha defensin 6 is a human protein that is encoded by the DEFA6 gene. DEFA6 is expressed in the Paneth cells of the ileum.- Function :...
| Defensin, alpha 6, Paneth cell-specific
| Defensin-6
|-
| rowspan="8" | β-defensins
Beta defensin
Beta defensins are a family of mammalian defensins. The beta defensins are antimicrobial peptides implicated in theresistance of epithelial surfaces to microbial colonization....
| DEFB1
Defensin, beta 1
Beta-defensin 1 is a protein that in humans is encoded by the DEFB1 gene.-Further reading:...
| Defensin, beta 1
| Beta-defensin 1
| rowspan="8" | 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
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
arises from the inhibition of β-defensin activity on the epithelial surfaces of the lungs and trachea due to higher salt content.
|-
| DEFB2
| Defensin, beta 2
| Beta-defensin 2
|-
| DEFB103A
DEFB103A
Beta-defensin 103 is a protein that in humans is encoded by the DEFB103A gene.-Further reading:...
| Defensin, beta 103B
| Beta-defensin 103
|-
| ...
| ...
| ...
|-
| DEFB107B
| Defensin, beta 107A
| Beta-defensin 107
|-
| DEFB110
| Defensin, beta 110
| Beta-defensin 110
|-
| ...
| ...
| ...
|-
| DEFB136
| Defensin, beta 136
| Beta-defensin 136
|-
| θ-defensins
Theta defensin
Theta defensins are a family of mammalian defensin peptides. They are found in some non-human primates, but not in human, gorilla, bonobo, and chimpanzee.- Description :...
| 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
Rhesus Macaque
The Rhesus macaque , also called the Rhesus monkey, is one of the best-known species of Old World monkeys. It is listed as Least Concern in the IUCN Red List of Threatened Species in view of its wide distribution, presumed large population, and its tolerance of a broad range of habitats...
and the olive baboon, Papio anubis, being vestigial in humans and other primates.>
Function
In immature marsupials, because their immune systemImmune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
is underdeveloped at the time of birth, defensins play a major role in defense against pathogens. They are produced in the milk of the mother as well as by the young marsupial in question.
Human genome contains theta-defensin genes, but they have a premature stop codon
Stop codon
In the genetic code, a stop codon is a nucleotide triplet within messenger RNA that signals a termination of translation. Proteins are based on polypeptides, which are unique sequences of amino acids. Most codons in messenger RNA correspond to the addition of an amino acid to a growing polypeptide...
, hampering their expression. An artificial human theta-defensin, retrocyclin, was created by `fixing' the pseudogene
Pseudogene
Pseudogenes are dysfunctional relatives of known genes that have lost their protein-coding ability or are otherwise no longer expressed in the cell...
, and it was shown to be effective against HIV and other viruses, including herpes simplex virus
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
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
Exotoxin
An exotoxin is a toxin excreted by a microorganism, like bacteria, fungi, algae, and protozoa. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host...
produced by anthrax (Bacillus anthracis
Bacillus anthracis
Bacillus anthracis is the pathogen of the Anthrax acute disease. It is a Gram-positive, spore-forming, rod-shaped bacterium, with a width of 1-1.2µm and a length of 3-5µm. It can be grown in an ordinary nutrient medium under aerobic or anaerobic conditions.It is one of few bacteria known to...
). 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.
Defensin-like proteins are also a component of platypus
Platypus
The platypus is a semi-aquatic mammal endemic to eastern Australia, including Tasmania. Together with the four species of echidna, it is one of the five extant species of monotremes, the only mammals that lay eggs instead of giving birth to live young...
venom.
Defensin-mimetics as antibiotics
Similar molecules (eg. PMX-30063) are being developed as antibioticAntibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s.
Pathology
The alpha defensinAlpha defensin
Alpha defensins are a family of mammalian defensin peptides.Defensins are 2-6 kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses, containing three pairs of intramolecular disulfide bonds...
peptides are increased in chronic inflammatory conditions.
Alpha defensin
Alpha defensin
Alpha defensins are a family of mammalian defensin peptides.Defensins are 2-6 kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses, containing three pairs of intramolecular disulfide bonds...
are increased in several cancers, including colorectal cancer.
An imbalance of defensins in the skin may contribute to acne.
A reduction of ileal
Ileum
The ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum...
defensins may predispose to Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
.
In one small study, a significant increase in alpha defensin
Alpha defensin
Alpha defensins are a family of mammalian defensin peptides.Defensins are 2-6 kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses, containing three pairs of intramolecular disulfide bonds...
levels was detected in T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
lysates of schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
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.
Defensins are found in the human skin during inflammatory conditions like psoriasis
Psoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...
and also during wound healing
Wound healing
Wound healing, or cicatrisation, is an intricate process in which the skin repairs itself after injury. In normal skin, the epidermis and dermis exists in a steady-state equilibrium, forming a protective barrier against the external environment...
.
External links
- Defensins Database, Singapore
- Innate ( Nonspecific ) Immunity at Western Kentucky UniversityWestern Kentucky UniversityWestern Kentucky University is a public university in Bowling Green, Kentucky, USA. It was formally founded by the Commonwealth of Kentucky in 1906, though its roots reach back a quarter-century earlier....
- Vertebrate defensins and related sea anemone sodium channel toxins - Defensins from insects and plants and scorpion toxins