CD46

CD46 complement regulatory protein also known as CD46 (is_associated_with::cluster of differentiation 46) and Membrane Cofactor Protein is a is_associated_with::protein which in humans is encoded by the CD46 is_associated_with::gene. CD46 is an inhibitory is_associated_with::complement receptor.

Gene
This gene is found in a cluster on is_associated_with::chromosome 1q32 with other genes encoding structural components of the complement system. At least fourteen different transcript variants encoding fourteen different isoforms have been found for this gene.

Function
The protein encoded by this gene is a type I membrane protein and is a regulatory part of the is_associated_with::complement system.

The encoded protein has cofactor activity for inactivation (through cleavage) of complement components is_associated_with::C3b and is_associated_with::C4b by serum factor I, which protects the host cell from damage by complement.

The protein encoded by this gene may be involved in the fusion of the is_associated_with::spermatozoa with the is_associated_with::oocyte during fertilization.

Clinical Significance
The encoded protein can act as a receptor for the Edmonston strain of is_associated_with::measles virus, is_associated_with::human herpesvirus-6 (HHV-6), and type IV pili of pathogenic is_associated_with::Neisseria.

The extracellular region of CD46 contains four short consensus repeats (SCR) of about 60 amino acids that fold into a compact is_associated_with::beta-barrel domain surrounded by flexible loops. As has been demonstrated for CD46 with other ligands, the CD46 protein structure is believed to linearize upon binding HHV-6. While their precise interaction has not yet been determined, the second and third SCR domains have been demonstrated to be required for HHV-6 receptor binding and cellular entry. The heterotetramer gH/gL/gQ1/gQ2 complex of HHV-6 has been identified as a CD46 ligand.

Established is_associated_with::medulloblastoma (a malignant brain tumor common in childhood) specimens express CD46, and that medulloblastoma specimens removed from patients had a high level of CD46 expression. Therefore a vaccine made of the Edmonston strain of measles virus could treat the medulloblastoma. Such a vaccine has already been tested in a number of trials involving other tumor types which have a high expression of CD46, including one type of adult brain tumor.

Interactions
CD46 has been shown to interact with is_associated_with::CD9, is_associated_with::CD151 and is_associated_with::CD29.