Editing Anaphylatoxin

{{Infobox protein family
| Symbol = ANATO
| Name = Anaphylotoxin-like domain
| image = PDB 1c5a EBI.jpg
| width =
| caption = Structure of porcine C5adesArg.<ref name="pmid2337573">{{cite journal | vauthors = Williamson MP, Madison VS | title = Three-dimensional structure of porcine C5adesArg from 1H nuclear magnetic resonance data | journal = Biochemistry | volume = 29 | issue = 12 | pages = 2895–905 | date = March 1990 | pmid = 2337573 | doi = 10.1021/bi00464a002 }}</ref>
| Pfam= PF01821
| InterPro= IPR000020
| SMART=  ANATO
| Prosite = PDOC00906
| SCOP = 1c5a
| TCDB =
| OPM family=
| OPM protein=
| PDB=
{{PDB3|2a73}}B:693-728   {{PDB3|1c5a}} :21-55     {{PDB3|1cfa}}A:698-732
{{PDB3|1kjs}} :698-732
}}

'''Anaphylatoxins''', or '''complement peptides''', are fragments ([[C3 (complement)|C3a]], [[C4a]] and [[Complement component 5a|C5a]]) that are produced as part of the activation of the [[complement system]].<ref name = "pmid3542363">{{cite journal | vauthors = Hugli TE | title = Biochemistry and biology of anaphylatoxins | journal = Complement | volume = 3 | issue = 3 | pages = 111–27 | year = 1986 | pmid = 3542363 | doi = 10.1159/000467889 }}</ref> Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defense.<ref name = "PUB00003181">{{cite journal | vauthors = Fritzinger DC, Petrella EC, Connelly MB, Bredehorst R, Vogel CW | title = Primary structure of cobra complement component C3 | journal = Journal of Immunology | volume = 149 | issue = 11 | pages = 3554–62 | date = December 1992 | doi = 10.4049/jimmunol.149.11.3554 | pmid = 1431125 | s2cid = 10452671 | doi-access = free }}</ref> They have a wide variety of biological activities and are proteolytically activated by cleavage at a specific site, forming a- and b-fragments.<ref name = "PUB00002512">{{cite journal | vauthors = Ogata RT, Rosa PA, Zepf NE | title = Sequence of the gene for murine complement component C4 | journal = The Journal of Biological Chemistry | volume = 264 | issue = 28 | pages = 16565–72 | date = October 1989 | doi = 10.1016/S0021-9258(19)84744-0 | pmid = 2777798 | doi-access = free }}</ref> A-fragments form distinct structural domains of approximately 76 amino acids, coded for by a single exon within the complement protein gene. The C3a, C4a and C5a components are referred to as anaphylatoxins:<ref name = "PUB00002512" /><ref name = "PUB00001343">{{cite journal | vauthors = Gennaro R, Simonic T, Negri A, Mottola C, Secchi C, Ronchi S, Romeo D | title = C5a fragment of bovine complement. Purification, bioassays, amino-acid sequence and other structural studies | journal = European Journal of Biochemistry | volume = 155 | issue = 1 | pages = 77–86 | date = February 1986 | pmid = 3081348 | doi = 10.1111/j.1432-1033.1986.tb09460.x | doi-access = free }}</ref> they cause smooth muscle contraction, vasodilation, histamine release from mast cells, and enhanced vascular permeability.<ref name="PUB00001343" /> They also mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals.<ref name="PUB00001343" /> The proteins are highly hydrophilic, with a mainly alpha-helical structure held together by 3 disulfide bridges.<ref name="PUB00001343" />

== Function ==

Anaphylatoxins are able to trigger [[degranulation]] (release of substances) of [[endothelial cells]], [[mast cells]] or [[phagocytes]], which produce a local inflammatory response. If the degranulation is widespread, it can cause a shock-like syndrome similar to that of an [[allergic reaction]].

Anaphylatoxins indirectly mediate:
* [[smooth muscle|smooth muscle cells]] contraction, for example [[bronchospasm]]s
* increase in the permeability of [[capillary|blood capillaries]]
* C5a indirectly mediates [[chemotaxis]]&mdash;[[receptor (biochemistry)|receptor]]-mediated movement of [[leukocyte]]s in the direction of the increasing concentration of anaphylatoxins

== Examples ==
Important anaphylatoxins:

* C5a has the highest specific biological activity and is able to act directly on neutrophils and monocytes to speed up the phagocytosis of pathogens.
* C3a works with C5a to activate mast cells, recruit antibody, complement and phagocytic cells and increase fluid in the tissue, all of which contribute to the initiation of the [[adaptive immune response]].
* C4a is the least active anaphylatoxin.

== Terminology ==
Although some drugs ([[morphine]], [[codeine]], synthetic [[ACTH]]) and some [[neurotransmitter]]s ([[norepinephrine]], [[substance P]]) are important mediators of degranulation of mast cells or basophils, they are generally not called anaphylatoxins. This term is reserved only for fragments of the complement system.

== Human proteins containing this domain ==
[[complement component 3|C3]], [[C4A]], [[Complement component 4|C4B]], [[C4B-1]], [[complement component 5|C5]], [[FBLN1]], [[FBLN2]]

== See also ==
{{col div|colwidth=30em}}
*[[Allergy]]
*[[Anaphylatoxin receptors]]
*[[Anaphylaxis]]
*[[Complement system]]
*[[Inflammation]]
*[[Immune system]]
*[[Nervous system]]
{{colend}}

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Gerard C, Gerard NP | title = C5A anaphylatoxin and its seven transmembrane-segment receptor | journal = Annual Review of Immunology | volume = 12 | pages = 775–808 | year = 1994 | pmid = 8011297 | doi = 10.1146/annurev.iy.12.040194.004015 }}
* {{cite journal | vauthors = Pan ZK | title = Anaphylatoxins C5a and C3a induce nuclear factor kappaB activation in human peripheral blood monocytes | journal = Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression | volume = 1443 | issue = 1–2 | pages = 90–8 | date = November 1998 | pmid = 9838061 | doi = 10.1016/S0167-4781(98)00198-5 }}
{{refend}}

== External links ==
* {{MeshName|Anaphylatoxin}}

{{Immune system}}

{{InterPro content|IPR000020}}

[[Category:Complement system]]
[[Category:Protein families]]