Complement Component C2

What is C2 C2 Function C2 Deficiency C2 Test Drug Discovery

Complement component C2 (C2) is a pivotal serine protease within the classical and lectin pathways of the complement system. Acting as a vital proteolytic component of the C3 convertase in both the classical and lectin pathways, C2 plays a pivotal role in microbial defense, immune complex clearance, and inflammatory signaling. As research into complement-driven disorders grows, understanding C2's structure and function has become a priority across immunology, infection biology, and drug development sectors.

Creative Biolabs provides comprehensive research services to explore complement proteins, including functional activity assays and C2-specific pathway analysis.

What is C2 Complement?

The content of C2 in human plasma is generally small, and it is mainly involved in the innate immune response to infection or injury through activation of the classical complement pathway. The activation of C2 involves the binding of C1 to the Fc portion of the antibody in the antigen-antibody complex. This binding forms C1 esterase, which cleaves C2 and C4.

C2 shares homology with complement factor B and belongs to the trypsin-like serine protease family. Upon cleavage by C1s or MASP-2, C2 yields two fragments:

Fig. 1 Molecular structure of C2. (By Emw - Own work, https://commons.wikimedia.org/wiki/File:Protein_C2_PDB_2i6q.png)Fig. 1 Molecular structure of C2.1

C2 is a single-chain glycoprotein with a molecular weight of approximately 100–110 kDa. Its structure is characterized by:

C2 Protein Function

C2 serves as the catalytic core of the classical and lectin complement pathways, driving immune defense through its enzymatic activity in convertase complexes. Its functional role spans activation, amplification, and regulation of complement-mediated responses, making it indispensable for host protection and immune homeostasis.

Table 1 Functional role of C2 in complement activation.

Mechanistic Role Description
Activation and Cleavage C2 is activated through proteolytic cleavage by C1s (classical pathway) or MASP-2 (lectin pathway) when bound to surface-associated C4b in the presence of Mg2+.
This cleavage generates two fragments:
  • C2a: The larger fragment (509 residues) contains the serine protease domain and forms the catalytic subunit of C3/C5 convertases.
  • C2b: The smaller fragment (223 residues) is released into the fluid phase and may regulate inflammatory responses.
Convertase Formation C2a binds to C4b to form two critical enzymatic complexes:
  • C3 Convertase (C4b2a): Cleaves C3 into C3a (anaphylatoxin) and C3b (opsonin), amplifying opsonization and inflammation.
  • C5 Convertase (C4b2a3b): Processes C5 into C5a (chemotactic factor) and C5b, initiating the membrane attack complex (MAC) for pathogen lysis.
These convertases are short-lived, ensuring localized activity to prevent systemic damage.

Enzymatic Activity and Substrate Specificity

C2 Protein Deficiency

C2 is the most commonly deficient component among classical pathway proteins. C2 deficiency is inherited in an autosomal recessive pattern and results in impaired formation of C3 convertase. Clinical manifestations include:

Chronic complement activation via the C2-driven pathway is associated with the following processes.

Given its central role, C2 is an attractive target for therapeutic intervention. Selective modulation of the classical pathway by inhibition of C2 activity provides a means of inhibiting pathologic complement activation without compromising the function of the alternative pathway.

Complement C2 Test

Complement C2 testing is a specialized laboratory assessment used to evaluate the activity or concentration of the C2 in serum. Creative Biolabs has a robust standardized complement test platform and a variety of test technologies, such as nephelometry, ELISA, RID, and TRIFMA assays, to deliver fast, reliable & objective, easy to interpret results within 3 hours. We provide our customers with routine quantitative tests and functional activity test for individual components as well as a full range of complement components testing services.

Experimental Tools and Assays Involving C2

Table 2 Experimental tools and assays.

Tool Application
ELISA kits Quantification of C2 concentration in serum/plasma
Western blotting Detection of full-length or cleaved C2 fragments
Hemolytic assays (CH50) Assess classical pathway functionality
Recombinant C2 proteins Functional studies, structural biology, and screening assays
Gene editing Create C2 knockout cell or animal models

Interpretation of Results

Table 3 Interpretation of results

Result Type Clinical Implication
Normal Functional C2 present; classical pathway is intact
Low/Absent Suggests C2 deficiency, increasing risk for recurrent infections and autoimmune disease (e.g., SLE)
Elevated May be seen in acute phase response, but is less clinically significant
Equivocal Partial deficiency or decreased activity, may require repeat or additional testing

C2 Research in Drug Discovery

Inhibiting C2 offers pathway-selective control, avoiding the systemic suppression seen with terminal complement inhibitors. This strategy is particularly beneficial for treating disorders where the classical pathway is overactivated while preserving the alternative pathway's microbial defense role.

Small-molecule inhibitors, monoclonal antibodies, and RNAi-based therapeutics targeting C2 are currently being investigated in preclinical models. These approaches offer promising pharmacological profiles with high specificity.

As the field of complementology evolves, C2 emerges not only as a classical cascade component but also as a promising therapeutic target. Targeted inhibition, biomarker discovery, and structural-functional studies of C2 may unlock novel treatment strategies for complement-driven disorders.

Creative Biolabs continues to support global researchers with advanced solutions in complement component analysis. With a robust portfolio of reagents, assay systems, and expert consulting, we are committed to accelerating discoveries in innate immunity.

If you want more information, please feel free to contact us.

Reference

  1. From Wikipedia: By Emw - Own work, CC BY-SA 3.0 https://commons.wikimedia.org/wiki/File:Protein_C2_PDB_2i6q.png
For Research Use Only.
Related Sections:
Support

Online Inquiry