LRP1
Function
Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells (PubMed:11907044, PubMed:12713657). Required for early embryonic development (By similarity). Involved in cellular lipid homeostasis. Involved in the plasma clearance of chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin), as well as the local metabolism of complexes between plasminogen activators and their endogenous inhibitors. Acts as an LRPAP1 alpha-2-macroglobulin receptor (PubMed:1702392, PubMed:26142438). Acts as TAU/MAPT receptor and controls the endocytosis of TAU/MAPT as well as its subsequent spread (PubMed:32296178). May modulate cellular events, such as APP metabolism, kinase-dependent intracellular signaling, neuronal calcium signaling as well as neurotransmission (PubMed:12888553). Acts also as a receptor for IGFBP3 to mediate cell growth inhibition (PubMed:9252371).
(Microbial infection) Functions as a receptor for Pseudomonas aeruginosa exotoxin A.
Involvement in disease
Keratosis pilaris atrophicans
KPA
A group of rare genodermatoses characterized by keratotic follicular papules, variable degrees of inflammation, and secondary atrophic scarring. Most cases are associated with an atopic diathesis and keratosis pilaris on the extensor extremities. KPA is comprised of three distinct clinical subtypes: keratosis pilaris atrophicans faciei, atrophoderma vermiculatum, and keratosis follicularis spinulosa decalvans. Affected individuals may present with features overlapping the 3 subtypes.
None
The disease is caused by variants affecting the gene represented in this entry.
Developmental dysplasia of the hip 3
DDH3
An autosomal dominant form of congenital dysplasia of the hip, a common skeletal anomaly in which the normal seating of the femoral head in the acetabulum is disrupted. Its severity ranges from mild instability of the femoral head with slight capsular laxity, permitting minimal lateral displacement, through moderate lateral displacement of the femoral head, without loss of contact of the head with the acetabulum, up to complete dislocation of the femoral head from the acetabulum.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Cleaved into a 85 kDa membrane-spanning subunit (LRP-85) and a 515 kDa large extracellular domain (LRP-515) that remains non-covalently associated. Gamma-secretase-dependent cleavage of LRP-85 releases the intracellular domain from the membrane.
The N-terminus is blocked.
Phosphorylated on serine and threonine residues.
Phosphorylated on tyrosine residues upon stimulation with PDGF. Tyrosine phosphorylation promotes interaction with SHC1.
Sequence Similarities
Belongs to the LDLR family.
Tissue Specificity
Most abundant in liver, brain and lung.
Cellular localization
- Low-density lipoprotein receptor-related protein 1 85 kDa subunit
- Cell membrane
- Single-pass type I membrane protein
- Membrane
- Coated pit
- Low-density lipoprotein receptor-related protein 1 515 kDa subunit
- Cell membrane
- Peripheral membrane protein
- Extracellular side
- Membrane
- Coated pit
- Low-density lipoprotein receptor-related protein 1 intracellular domain
- Cytoplasm
- Nucleus
- After cleavage, the intracellular domain (LRPICD) is detected both in the cytoplasm and in the nucleus.
- Golgi outpost
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Localizes to the postsynaptic Golgi apparatus region, also named Golgi outpost, which shapes dendrite morphology by functioning as sites of acentrosomal microtubule nucleation.
Alternative names
CD91, A2MR, APR, LRP1, Prolow-density lipoprotein receptor-related protein 1, LRP-1, Alpha-2-macroglobulin receptor, Apolipoprotein E receptor, APOER