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An anaphylatoxin is a small signaling peptide released from a complement system component during activation. C3a and C5a are important examples: fragments derived from larger circulating proteins act as ligands for cell-surface receptors, connecting complement system activation with cellular responses involved in inflammation.^[ref]

The historical name is best understood through measurements of activity. Viktor A. Bokisch and colleagues isolated C3a and measured its ability to contract smooth muscle. Its activity could be inhibited or lost without simply equating every Complement C3 fragment with the same effect. This supplies a concrete example of a protein cleavage product acquiring a signaling role distinguishable from the remainder of its precursor.^[ref]

An anaphylatoxin is therefore a host-derived signal, rather than necessarily an externally introduced poison. A response to a fragment must be specified by the receptor, responding cell and experimental readout.

C3a is a small protein fragment released when Complement C3 is cleaved during activation of the complement system. It is an anaphylatoxin, associated with inflammatory responses, and is distinct from the larger C3b product involved in surface-associated complement reactions. Proteolysis can thus produce different activities from different parts of one precursor.^[ref]

In 1969, Viktor A. Bokisch and collaborators isolated C3a by several methods and tested its smooth muscle-contracting activity. Antiserum directed against C3a inhibited the biological response, connecting the isolated fragment to the activity rather than identifying it solely by a separation band. Further enzyme treatment changed its measured activities, showing why the amount of a fragment and its retained function are separate questions.^[ref]

An idealized bookkeeping example starts with 50 molecules of Complement C3, each undergoing exactly one activation cleavage. It produces 50 C3a fragments and 50 C3b fragments: 100 product molecules, but no doubling of total protein material. In an actual sample, production, further processing and removal all affect the measured concentration of C3a.

C3c is a major proteolysis product of Complement C3. It is a processed fragment, distinct from the small inflammatory fragment C3a and the activated C3b from which later breakdown products can be generated. A fragment name identifies a particular piece of the original protein, rather than a separate gene product.

The 1969 fragment-isolation study separated C3c and a smaller fragment from enzyme-treated C3b and distinguished them antigenically. This is a biochemical way to establish that further processing yields different molecular pieces.^[ref]

In 2005, X-ray crystallography provided crystal structures of native Complement C3 and C3c. Comparing their protein domain arrangements connected cleavage with changes in molecular architecture. The deposited structures are 2A73 for native Complement C3 and 2A74 for C3c.^[ref]

Consider an original interpretation exercise: an antibody signal from a region retained in C3c could persist after the intact precursor has disappeared. Such a signal would not by itself measure intact Complement C3, newly generated C3a or surface-attached C3b. Knowing the recognized region and the sample's processing state is essential when choosing what an assay measures.

A C3 convertase is an enzymatic complex of the complement system that cleaves Complement C3 into C3a and C3b. Different activation routes assemble different C3-cleaving complexes. The important shared activity is selective substrate cleavage, rather than a universal single protein carrying the name.^[ref]

Assembly and lifetime matter because a catalytic complex can process many substrate molecules. In an idealized constant-rate example, $1\mathrm{nM}$ active complex turning over at $2{\mathrm{s}}^{-1}$ produces $20\mathrm{nM}$ cleavage products in ten seconds, provided substrate remains abundant. Each consumed C3 molecule supplies one C3a fragment and one C3b fragment; the enzyme is not consumed on every turnover.

A 2009 study of complement factor H combined structural and functional measurements. The tested factor-H fragment accelerated decay of preassembled C3 convertase and supported complement factor I-dependent C3b cleavage in a separate assay.^[ref]

These observations separate dismantling an active assembly from cutting its protein components. Both can regulate complement activity, but they are not the same measured reaction. Comparing complex lifetime, substrate cleavage and component abundance therefore gives more mechanistic information than measuring total complement protein alone.

Viktor A. Bokisch is the first-listed author of a 1969 study isolating C3a, a small fragment of the complement system protein Complement C3. The researchers connected the separated fragment with smooth muscle contraction and showed that antibodies recognizing C3a could inhibit its biological activity. This joined chemical separation with a functional test.^[ref]

The experiment illustrates why identifying a protein fragment requires more than detecting a smaller molecule. Separating it, distinguishing it from C3b with antibodies, and testing its effect gave complementary evidence. The study also found that a serum preparation could inactivate the anaphylatoxin activity, showing that generation and removal of an active signal are separate parts of complement system regulation.^[ref]