Non-enzymatic component of C3 and C5 convertases and thus essential for the propagation of the classical complement pathway. Covalently binds to immunoglobulins and immune complexes and enhances the solubilization of immune aggregates and the clearance of IC through CR1 on erythrocytes ().

Also known as Complement C4-A (Acidic complement C4) (C3 and PZP-like alpha-2-macroglobulin domain-containing protein 2).
C4A: C4 plays a central role in the activation of the classical pathway of the complement system. It is processed by activated C1 which removes from the alpha chain the C4a anaphylatoxin. The remaining alpha chain fragment C4b is the major activation product and is an essential subunit of the C3 convertase (C4b2a) and the C5 convertase (C3bC4b2a) enzymes of the classical complement pathway. Defects in C4A are the cause of complement component 4A deficiency (C4AD). A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus with or without associated glomerulonephritis. Defects in C4A are a cause of susceptibility to systemic lupus erythematosus (SLE). A chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system. Interindividual copy- number variation (CNV) of complement component C4 and associated polymorphisms result in different susceptibilities to SLE. The risk of SLE susceptibility has been shown to be significantly increased among subjects with only two copies of total C4. A high copy number is a protective factor against SLE.

Protein type: Inhibitor; Secreted; Secreted, signal peptide

Chromosomal Location of Human Ortholog: 6p21.3

Cellular Component: axon; cell soma; dendrite; extracellular region; extracellular space; plasma membrane; synapse

Molecular Function: complement component C1q binding; serine-type endopeptidase activity

Biological Process: complement activation; regulation of complement activation

Disease: Blood Group, Chido/rodgers System; Complement Component 4a Deficiency

C4B: C4 plays a central role in the activation of the classical pathway of the complement system. It is processed by activated C1 which removes from the alpha chain the C4a anaphylatoxin. The remaining alpha chain fragment C4b is the major activation product and is an essential subunit of the C3 convertase (C4b2a) and the C5 convertase (C3bC4b2a) enzymes of the classical complement pathway. Defects in C4B are a cause of susceptibility to systemic lupus erythematosus (SLE). A chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system. Interindividual copy- number variation (CNV) of complement component C4 and associated polymorphisms result in different susceptibilities to SLE. The risk of SLE susceptibility has been shown to be significantly increased among subjects with only two copies of total C4. A high copy number is a protective factor against SLE. Defects in C4B are the cause of complement component 4B deficiency (C4BD). A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus with or without associated glomerulonephritis.

Protein type: Secreted; Secreted, signal peptide

Cellular Component: axon; cell soma; dendrite; extracellular region; extracellular space; synapse

Molecular Function: carbohydrate binding; complement binding; complement component C1q binding

Biological Process: complement activation; immunoglobulin mediated immune response