Complement component 2

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C2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2I6S, 3ERB,%%s2ODQ
Identifiers
Aliases	C2, ARMD14, CO2, complement component 2, complement C2
External IDs	OMIM: 613927; MGI: 88226; HomoloGene: 45; GeneCards: C2; OMA:C2 - orthologs
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p21.33 Start 31,897,785 bp[1] End 31,945,673 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17 B1|17 18.41 cM Start 35,081,580 bp[2] End 35,117,241 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in liver right lobe of liver placenta spleen upper lobe of left lung gallbladder appendix right lung lymph node duodenum Top expressed in iris decidua adrenal gland white adipose tissue left lobe of liver tunica adventitia of aorta lumbar spinal ganglion mesenteric lymph nodes sciatic nerve ileum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptidase activity serine-type peptidase activity hydrolase activity metal ion binding serine-type endopeptidase activity protein binding Cellular component extracellular region extracellular exosome extracellular space Biological process complement activation positive regulation of apoptotic cell clearance regulation of complement activation response to nutrient proteolysis complement activation, classical pathway immune system process innate immune response Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 717 12263 Ensembl ENSG00000206372 ENSG00000235017 ENSG00000235696 ENSG00000226560 ENSG00000204364 ENSG00000166278 ENSG00000231543 ENSMUSG00000024371 UniProt P06681 Q5JP69 P21180 RefSeq (mRNA) NM_000063 NM_001145903 NM_001178063 NM_001282457 NM_001282458 NM_001282459 NM_013484 RefSeq (protein) NP_000054 NP_001139375 NP_001171534 NP_001269386 NP_001269387 NP_001269388 NP_000054.2 NP_038512 Location (UCSC) Chr 6: 31.9 – 31.95 Mb Chr 17: 35.08 – 35.12 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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, which are a class of enzymes that cleave peptide bonds in other proteins. Deficiency of C2 has been associated with certain autoimmune diseases.^[5]

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 complement system becomes activated.

This activation process involves complement component 2 protein attaching to complement component 4 protein to form the complement system. Complement component 4 is a protein involved in autoimmunity, and when this protein attaches to complement component 2, it triggers an immune response. While component 4 protein is imperative for connection recognition pathways for the antibody-antigen response, complement component 2 protein is critical for regulation of these processes.

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]

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.

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.

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 the 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 complement deficiency.

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.

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.

Photosensitive patients with C2 type I deficiency have a poor prognosis. C2 type I deficiency is caused by a 28-base pair gene deletion, resulting in a premature termination codon and a 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 the risk of autoimmune disorders, which may be managed by receiving adequate care. Clinically, this is significant since Complement component 2 deficiency increases the risk of recurrent bacterial infections, which may be life-threatening.

This gene is also known as:

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

• Complement+2 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)