Low-density lipoprotein receptor gene family
Protein domain
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Through Genetic code
There are seven members of the LDLR family in mammals, namely:
- LDLR
- VLDL receptor (VLDLR)
- ApoER2, or 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
C6; C7; 8A; 8B; C9; CD320; CFI; CORIN; DGCR2; HSPG2; LDLR; LDLRAD2; LDLRAD3; LRP1; LRP10; LRP11; LRP12; LRP1B; LRP2; LRP3; LRP4; LRP5; LRP6; LRP8; MAMDC4; MFRP; PRSS7; RXFP1; RXFP2; SORL1; SPINT1; SSPO; ST14; TMPRSS4; TMPRSS6; TMPRSS7; TMPRSS9 (serase-1B); VLDLR;
Class B
EGF; LDLR; LRP1; LRP10; LRP1B; LRP2; LRP4; LRP5; LRP5L; LRP6; LRP8; NID1; NID2; SORL1; VLDLR;
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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.

