Complement component 2

(Redirected from C2 (gene))

Complement C2 is a protein that in humans is encoded by the C2 gene.[5] The protein encoded by this gene is part of the classical pathway of the complement system, acting as a multi-domain serine protease. Deficiency of C2 has been associated with certain autoimmune diseases.[5]

C2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesC2, ARMD14, CO2, complement component 2, complement C2
External IDsOMIM: 613927; MGI: 88226; HomoloGene: 45; GeneCards: C2; OMA:C2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_013484

RefSeq (protein)

NP_038512

Location (UCSC)Chr 6: 31.9 – 31.95 MbChr 17: 35.08 – 35.12 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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 an immune response. Complement component 2 protein is critical for regulating the body's immune response.

Function

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In the classical and lectin pathways of complement activation, formation of the C3-convertase and C5-convertases requires binding of C2 to an activated surface-bound C4b in the presence of Mg2+; the resultant C4bC2 complex is cleaved by C1s 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.[6]

Complement Component 2 Deficiency

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Complement C2 is a protein that in humans is encoded by the C2 gene.

In the Molecular Biology, the 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.[7] 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

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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 against 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

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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

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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

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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.[8] Patient organizations build public awareness and support research to improve patients' lives. Patient organizations provide access to information, resources, and support.

Clinical Significance

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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

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There are numerous forms of naming this gene. For example:

  • ARMD14
  • C3/C5 convertase
  • CO2
  • complement component 2
  • complement component C2

References

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Citations

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  1. ^ a b c ENSG00000235017, ENSG00000235696, ENSG00000226560, ENSG00000204364, ENSG00000166278, ENSG00000231543 GRCh38: Ensembl release 89: ENSG00000206372, ENSG00000235017, ENSG00000235696, ENSG00000226560, ENSG00000204364, ENSG00000166278, ENSG00000231543Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024371Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: C2 complement component 2".
  6. ^ Krishnan V, Xu Y, Macon K, Volanakis JE, Narayana SV (2009). "The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation". Acta Crystallographica D. 65 (Pt 3): 266–274. doi:10.1107/S0907444909000389. PMC 2651757. PMID 19237749.
  7. ^ 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
  8. ^ "Complement Deficiencies | Immune Deficiency Foundation".

Bibliography

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  • 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[permanent dead link] 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

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