LDLRAP1

LDLRAP1 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 a

Full Name

low density lipoprotein receptor adaptor protein 1

Function

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 endocytosis 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. Required for trafficking of LRP2 to the endocytic recycling compartment which is necessary for LRP2 proteolysis, releasing a tail fragment which translocates to the nucleus and mediates transcriptional repression (By similarity).

Biological Process

Amyloid precursor protein metabolic processManual Assertion Based On ExperimentIMP:BHF-UCL
Cellular response to cytokine stimulusManual Assertion Based On ExperimentIMP:BHF-UCL
Cholesterol homeostasisManual Assertion Based On ExperimentIMP:BHF-UCL
Cholesterol metabolic process1 PublicationNAS:UniProtKB
Cholesterol transport1 PublicationNAS:UniProtKB
Low-density lipoprotein particle clearanceManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of cholesterol metabolic process1 PublicationIC:BHF-UCL
Positive regulation of low-density lipoprotein particle clearanceManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of receptor-mediated endocytosisManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of receptor-mediated endocytosis involved in cholesterol transportManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of vascular associated smooth muscle cell proliferationManual Assertion Based On ExperimentIMP:BHF-UCL
Receptor internalizationManual Assertion Based On ExperimentIMP:BHF-UCL
Receptor-mediated endocytosisManual Assertion Based On ExperimentIDA:BHF-UCL
Receptor-mediated endocytosis involved in cholesterol transportManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of protein bindingManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of protein localization to plasma membraneManual Assertion Based On ExperimentIMP:BHF-UCL

Cellular Location

Cytoplasm

Involvement in disease

Hypercholesterolemia, familial, 4 (FHCL4):
A form of hypercholesterolemia, a disorder of lipoprotein metabolism characterized by elevated serum low-density lipoprotein (LDL) cholesterol levels, which result in excess deposition of cholesterol in tissues and leads to xanthelasma, xanthomas, accelerated atherosclerosis and increased risk of premature coronary heart disease. FHCL4 inheritance is autosomal recessive.