ARH Antibody – Mouse Monoclonal

The protein encoded by this gene is a cytosolic protein which contains a phosphotyrosine binding (PTD) domain. The PTD domain has been found to interact with the cytoplasmic tail of the LDL receptor. Mutations in this gene lead to LDL receptor malfunction and cause the disorder autosomal recessive hypercholesterolaemia. [provided by RefSeq, Jul 2008]

LDLRAP1: Adapter protein (clathrin-associated sorting protein (CLASP)) required for efficient endocytosis of the LDL receptor (LDLR) in polarized cells such as hepatocytes and lymphocytes, but not in non-polarized cells (fibroblasts). May be required for LDL binding and internalization but not for receptor clustering in coated pits. May facilitate the endocytocis of LDLR and LDLR-LDL complexes from coated pits by stabilizing the interaction between the receptor and the structural components of the pits. May also be involved in the internalization of other LDLR family members. Binds to phosphoinositides, which regulate clathrin bud assembly at the cell surface. Defects in LDLRAP1 are the cause of autosomal recessive hypercholesterolemia (ARH). ARH is a disorder caused by defective internalization of LDL receptors (LDLR) in the liver. ARH has the clinical features of familial hypercholesterolemia (FH) homozygotes, including severely elevated plasma LDL cholesterol, tuberous and tendon xanthomata, and premature atherosclerosis. LDL receptor (LDLR) activity measured in skin fibroblasts is normal, as the LDL binding ability.

Chromosomal Location of Human Ortholog: 1p36.11

Cellular Component: recycling endosome; internal side of plasma membrane; AP-1 adaptor complex; axon; early endosome; basal plasma membrane; neurofilament; AP-2 adaptor complex; cytosol

Molecular Function: protein binding; phosphatidylinositol-4,5-bisphosphate binding; clathrin binding; receptor signaling complex scaffold activity; phosphotyrosine binding; low-density lipoprotein receptor binding; beta-amyloid binding

Biological Process: receptor-mediated endocytosis; cholesterol metabolic process; cholesterol homeostasis; positive regulation of signal transduction; transport; amyloid precursor protein metabolic process; regulation of protein binding; receptor internalization; positive regulation of receptor-mediated endocytosis

Disease: Hypercholesterolemia, Autosomal Recessive