CD46

CD46, also known as membrane cofactor protein (MCP), is a human cell-surface glycoprotein that functions in the regulation of the complement system. It is encoded by the CD46 gene on chromosome 1q32. The protein is a type I transmembrane glycoprotein with an extracellular region containing several short consensus repeats, a membrane-proximal spacer, a single-pass transmembrane segment, and a cytoplasmic tail that exists in at least two alternative forms (CYT-1 and CYT-2) due to alternative splicing.

Expression and distribution: CD46 is broadly expressed on all nucleated human cells, with higher levels on epithelial and endothelial cells and many immune cells, and is present in tissues such as placenta and testes.

Function: The main role of CD46 is as a regulatory protein of the complement system. It acts as a cofactor for factor I–mediated proteolytic inactivation of C3b and C4b, thereby limiting complement activation on host cells and protecting them from lysis. The cytoplasmic tails mediate intracellular signaling that can influence T cell activation and regulatory responses.

Pathogen interactions: CD46 serves as a receptor for a variety of pathogens. Notably, several species B adenoviruses use CD46 to gain entry, and measles virus can use CD46 as an attachment receptor in certain cell types. Some other microbes interact with CD46 in a host-pathogen context.

Clinical significance: Mutations or deficiencies in CD46 are associated with atypical hemolytic uremic syndrome (aHUS), a thrombotic microangiopathy, due to failure of complement regulation. Altered CD46 expression has also been explored in transplantation and immunotherapy contexts.