Complement Component 2
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Complement C2 is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''C2''
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
. The protein encoded by this gene is part of the
classical pathway The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune system. The classical complement pathway is initiated by antigen-antibody complexes with the antibody isotypes IgG and I ...
of the
complement system The complement system, also known as complement cascade, is a part of the humoral, innate immune system and enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inf ...
, acting as a multi-domain serine protease. Deficiency of C2 has been associated with certain autoimmune diseases. The Complement system is generated to regulate self protection from infection. The overall Complement system is composed of protein groups that collaborate in destroying foreign invaders, which ultimately remove debris from cells and tissues. When the body detects a foreign invader, the body signals the Complement system and the Complement component 2 protein attaches to Complement system 4 resulting in a
immune response.
Complement component 2 protein is critical for regulating the body's immune response.


Function

In the classical and
lectin Lectins are carbohydrate-binding proteins that are highly specific for sugar Moiety (chemistry), groups that are part of other molecules, so cause agglutination (biology), agglutination of particular cells or precipitation of glycoconjugates an ...
pathways of
complement activation The complement system, also known as complement cascade, is a part of the humoral, innate immune system and enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote infla ...
, formation of the C3-convertase and
C5-convertase C5 convertase is an enzyme belonging to a family of serine proteases that play key role in the innate immunity. It participates in the complement system ending with cell death. There are four different C5 convertases able to specifically co ...
s requires binding of C2 to an activated surface-bound C4b in the presence of Mg2+; the resultant C4bC2 complex is cleaved by
C1s Complement component 1s (, ''C1 esterase'', ''activated complement C1s'', ''complement C overbar 1r'', ''C1s'') is a protein involved in the complement system. C1s is part of the C1 complex. In humans, it is encoded by the ''C1S'' gene. C1s clea ...
or MASP2 into C2a and C2b. It is thought that cleavage of C2 by C1s, while bound to C4b, results in a conformational rotation of C2b whereas the released C2a fragment may retain most of its original structure. C2b is the smallest, enzymatically active, fragment of C3 convertase in this pathway, C4b2b (NB: some sources now refer to the larger fragment of C2 as C2b, making the C3 convertase C4b2b, whereas older sources refer to the larger fragment of C2 as C2a, making the C3 convertase C4b2a). The smaller fragment, C2a (or C2b, depending on the source) is released into the fluid phase.


Complement Component 2 Deficiency

In the Molecular Biology, th
deficiency of Complement Component 2 i
s a disorder that causes a major effect in the immune system, resulting in a form of immunodeficiency. This effect results in an inability to protect the body against any foreign invader. Complement component 2 deficiency is also connected with an increased risk of developing autoimmune disorders, such as systemic vasculitis. Complement deficiencies is a challenge to understand due to insufficient clinical trails. Using a hemolytic-plaque assay, RNA extraction, and blot analysis, it is fair to note that complement component 2 deficiency is a result of pre-translational regulatory detect in C2 gene expression. This detects a lack of synthesis within the C2 protein. This deficiency can be further understood by incorporating plasma protein deficiencies, especially those in tissue macrophages. It is also important to note that Complement component 2 deficiency can be caused by genetic and environmental factors. In genetic inheritance, Autosomal recessive conditions are inherited with mutations in both copies of the gene where parents of autosomal recessive condition typically do not show symptoms.


Development of SLE

Complement component 2 deficiency is associated with an increased risk of developing autoimmune disorders, with females more likely to have SLE. Systemic lupus erythematosus (lupus) is a chronic autoimmune disease that causes inflammation and tissue damage, affecting many parts of the body. Lupus can range from mild to severe and can cause inflammation in organs, such as joints, skin, kidneys, and brain. The severity of the disorder varies. C2 is an important component of both the classical and lectin pathways of complement activation, and is essential for first line defense agains
microbial infection.
It binds to MBL or ficolins to form the C3 convertase C4b2a. In C2 deficiency, C3 is not efficiently cleaved, leading to limited deposition of C3 fragments on immune complexes and apoptotic cells, leading to chronic activation of the complement system.


Treatment and Management

Complement deficiency is managed on a case-by-case basis with antibiotics and regular visits with an immunologist. A form to treat complement component 2 deficiency includes replacing the missing component of the cascade, either through direct infusion of the protein or through gene therapy. Patients should be aware of symptoms of meningococcal infection and receive routine vaccinations. Patients should seek for accessible resources offered by the medical provider and take the necessary actions needed to treat for complement deficiency.


Patient Education

Patients and parents should be educated on the symptoms of serious illness and seek care immediately. Vaccination is an important preventive measure for the deficiency of complement component 2. Early diagnosis, antibiotic prophylaxis, and vaccinations can help prevent life-threatening infections in hereditary C2 deficiency.


Promoting Health Care Outcomes

The interprofessional team must be aware of the clinical features of patients with complement deficiency or immunodeficiency, and refer them to allergist/immunologists when necessary. Infection prevention and treatment of infections are key for complement deficiencies. Patient organizations build public awareness and support research to improve patients' lives. Patient organizations provide access to information, resources, and support.


Clinical Significance

Photosensitive patients with C2 type I deficiency have poor prognosis. C2 type I deficiency is caused by a 28-base pair gene deletion, resulting in premature termination codon and lack of C2 protein. Patients with LE associated with complement C4 or C2 deficiencies have a better prognosis than those without inherited deficiencies. Complement component 2 deficiency increases risk of autoimmune disorders which may be managed by receiving the adequate care. Clinically, this is significant since Complement component 2 deficiency increases the risk of recurrent bacterial infections, which may be life-threatening.


Other Names

There are numerous forms of naming this gene. For example: * ARMD14 * C3/C5 convertase * CO2 * complement component 2 * complement component C2


References


Citations


Bibliography

* Jonsson G, Truedsson L, Sturfelt G, Oxelius VA, Braconier JH, Sjoholm AG. Hereditary C2 deficiency in Sweden: frequent occurrence of invasive infection, atherosclerosis, and rheumatic disease. Medicine (Baltimore). 2005Jan;84(1):23-34. doi: 10.1097/01.md.0000152371.22747.1e. Citation on PubMed (https://pubmed.ncb i.nlm.nih.gov/15643297) * Complement+2 at the U.S. National Library of Medicine Medical Subject Headings (MeSH) Sjöholm AG, Jönsson G, Braconier JH, Sturfelt G, Truedsson L. Complement deficiency and disease: an update. Mol Immunol. 2006 Jan;43(1-2):78-85. doi: 10.1016/j.molimm.2005.06.025. PMID 16026838. * Wen L, Atkinson JP, Giclas PC. Clinical and laboratory evaluation of complement deficiency. J Allergy Clin Immunol. 2004 Apr;113(4):585-93; quiz 594. doi: 10.1016/j.jaci.2004.02.003. PMID 15100659. * Chen HH, Tsai LJ, Lee KR, Chen YM, Hung WT, Chen DY. Genetic association of complement component 2 polymorphism with systemic lupus erythematosus. Tissue Antigens. 2015 Aug;86(2):122-33. doi: 10.1111/tan.12602. Epub 2015 Jul 14. PMID 26176736.


Further reading

* * * * * * * * * * * * * * * * * * * Liu C-C, Ahearn JM. Complement and systemic lupus erythematosus. 7th ed. In: Wallace DJ, Hahn BH, editors. Dubois’ Lupus Erythematosus. (Chap. 13), Philadelphia: Lippincott Williams & Wilkins (2007). p. 214–35. * Grammatikos AP, Tsokos GC. Immunodeficiency and autoimmunity: lessons from systemic lupus erythematosus. Trends Mol Med (2012) 18:101–8. doi:10.1016/j.molmed.2011.10.005 * Ippolito A, Wallace DJ, Gladman D, Fortin PR, Urowitz M, Werth V, et al. Auto-antibodies in systemic lupus erythematosus: comparison of historical and current assessment of seropositivity. Lupus (2011) 20:250–5. doi:10.1177/0961203310385738 * Outer surface lipoproteins from the Lyme disease spirochete exploit the molecular switch mechanism of the complement protease C1s. arrigues et al.Journal of Biological ChemistrySeptember 29, 2022 * Paip2A inhibits translation by competitively binding to the RNA recognition motifs of PABPC1 and promoting its dissociation from the poly(A) tail * Sagae et al.Journal of Biological ChemistryMarch 17, 2022


External links

* {{Complement system Complement system