UniProt functional annotation for P01130

UniProt code: P01130.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
 
Function: Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. In case of HIV-1 infection, functions as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells.
 
Subunit: Interacts with LDLRAP1, ARRB1, SNX17. Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Interacts with the full length immature form of PCSK9 (via C-terminus). Interacts with HCV E1/E2 heterodimer. Interacts with HIV-1 Tat.
Subcellular location: Cell membrane; Single-pass type I membrane protein. Endomembrane system; Single-pass type I membrane protein. Membrane, clathrin-coated pit; Single-pass type I membrane protein. Golgi apparatus. Early endosome. Late endosome. Cell surface. Lysosome. Note=Found distributed from the plasma membrane to intracellular compartments. Localizes to the Golgi apparatus, early and late endosomes/lysosomes and cell surface in the presence of PCSK9.
Domain: The NPXY motif mediates the interaction with the clathrin adaptor DAB2 involved in receptor internalization (By similarity).
Ptm: N- and O-glycosylated.
Ptm: Ubiquitinated by MYLIP leading to degradation.
Disease: Familial hypercholesterolemia (FH) [MIM:143890]: Common autosomal semi-dominant disease that affects about 1 in 500 individuals. The receptor defect impairs the catabolism of LDL, and the resultant elevation in plasma LDL-cholesterol promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and coronary arteries (atherosclerosis). Note=The disease is caused by mutations affecting the gene represented in this entry.
Similarity: Belongs to the LDLR family.
Similarity: Contains 3 EGF-like domains.
Similarity: Contains 7 LDL-receptor class A domains.
Similarity: Contains 6 LDL-receptor class B repeats.
Sequence caution: Sequence=BAD92646.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;

Annotations taken from UniProtKB at the EBI.