UNIPROT #

Q14114

PROTEIN NAME

ApoER2

SYNONYMS

APOER2 antibody; Apolipoprotein E receptor 2 antibody; low density lipoprotein receptor-related protein 8 antibody; Low-density lipoprotein receptor-related protein 8 antibody; LRP-8 antibody; LRP8 antibody; LRP8_HUMAN antibody

SEQUENCE SIMILARITIES

Belongs to the LDLR family.

TISSUE SPECIFICITY

Expressed mainly in brain and placenta. Also expressed in platelets and megakaryocytic cells. Not expressed in the liver.

POST-TRANSLATIONAL MODIFICATION

O-glycosylated. Some alternatively spliced isoforms lack the O-linked sugar domain (By similarity).; Undergoes sequential, furin and gamma-secretase dependent, proteolytic processing, resulting in the extracellular release of the entire ligand-binding domain as a soluble polypeptide and in the intracellular domain (ICD) release into the cytoplasm. The gamma-secretase-dependent proteolytical processing occurs after the bulk of the extracellular domain has been shed, in a furin-dependent manner, in alternatively spliced isoforms carrying the furin cleavage site. Hypoglycosylation (mainly hypo-O-glycosylation) leads to increased extracellular cleavage, which in turn results in accelerating release of the intracellular domain (ICD) by the gamma-secretase. The resulting receptor fragment is able to inhibit Reelin signaling and in particular the Reelin-induced DAB1 phosphorylation (By similarity).; Tyrosine phosphorylated upon apoE binding.; Ubiquitinated by MYLIP leading to degradation.

SUBCELLULAR LOCATION

Cell membrane. Secreted.

FUNCTION

ApoER2 (apolipoprotein E receptor 2), also designated LRP8, is a member of the LDL receptor gene family, which includes LDL receptor, LRP, megalin, VLDLR and ApoER2. The LDL receptor family is characterized by a cluster of cysteine-rich class A repeats, epidermal growth factor (EGF)-like repeats, YWTD repeats and an O-linked sugar domain. ApoER2 is expressed in brain and placenta and has several splice variants. ApoER2 is thought to mediate the interaction of extracellular Reelin and cytosolic mDab1 (mammalian disabled protein), which activates a tyrosine kinase. This pathway regulates the migration of neurons along the radial glial fiber network during brain development.