Low-density lipoprotein receptor gene family

The low-density lipoprotein receptor gene family

• LDLR
• VLDLR
  )
• LRP8
• Low density lipoprotein receptor-related protein 4
  • also known as multiple epidermal growth factor (EGF) repeat-containing protein (MEGF7)
• LDLR-related protein 1
• LDLR-related protein 1b
• Megalin.

Human proteins containing this domain

Listed below are human proteins containing low-density lipoprotein receptor domains:

Class A

• Soluble low-density lipoprotein receptor-related protein (sLRP) - impaired function is related to Alzheimer's disease.

Structure

The members of the LDLR family are characterized by distinct functional domains present in characteristic numbers. These modules are:

• LDL receptor type A (LA) repeats of 40 residues each, displaying a triple-disulfide-bond-stabilized negatively charged surface; certain head-to-tail combinations of these repeats are believed to specify ligand interactions;
• LDL receptor type B repeats, also known as EGF precursor homology regions, containing EGF-like repeats and
  YWTD beta propeller domains
  ;
• a transmembrane domain, and
• the cytoplasmic region with (a) signal(s) for receptor internalization via coated pits, containing the consensus tetrapeptide Asn-Pro-Xaa-Tyr (NPxY). This cytoplasmic tail controls both endocytosis and signaling by interacting with the phosphotyrosine binding (PTB) domain-containing proteins.

In addition to these domains which can be found in all receptors of the gene family, LDL receptor and certain isoforms of ApoER2 and VLDLR contain a short region which can undergo O-linked glycosylation, known as O-linked sugar domain. ApoER2 moreover, can harbour a cleavage site for the protease furin between type A and type B repeats which enables production of a soluble receptor fragment by furin-mediated processing.

References