Kelch Like Protein 12 (KLHL12)

KLHL12, a BTB-Kelch protein, specifically binds to this polymorphic region of the D4 receptor through its Kelch domain. KLHL12 also interacts with Cullin3 and thereby functions as an adaptor to target the D4 receptor to an E3 ubiquitin ligase complex. Overexpression of KLHL12 strongly promotes ubiquitination of the D4 receptor. KLHL12 promotes poly-ubiquitination of the receptor by performing ubiquitination assays in eukaryotic cells. KLHL12 not only interacts with both immature, ER-associated and mature, plasma membrane-associated D4 receptors, but also promotes ubiquitination of both receptor subpools. KLHL12-mediated receptor ubiquitination does not promote proteasomal degradation of newly synthesized receptors through the ER-associated degradation pathway or lysosomal degradation of mature receptors.