Low-density lipoprotein receptor gene family The low-density lipoprotein receptor gene family codes for a class of structurally related cell surface receptors that fulfill diverse biological functions in different organs, tissues, and cell types . The role that is most commonly associated with this evolutionarily ancient family is cholesterol homeostasis . In humans, excess cholesterol in the blood is captured by low-density lipoprotein and removed by the liver via endocytosis of the LDL receptor . Recent evidence indicates that the members of the LDL receptor gene family are active in the cell signalling pathways between specialized cells in many, if not all, multicellular organisms . There are seven members of the LDLR family in mammals, namely: Listed below are human proteins containing low-density lipoprotein receptor domains:Class A ; 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 ; VLDLR ;Class B ; LDLR; LRP1; LRP10; LRP1B; LRP2; LRP4; LRP5;LRP5L ; LRP6; LRP8; NID1 ; NID2 ; SORL1; VLDLR;Structure The members of the LDLR family are characterized by distinct functional domains present in characteristic numbers . These modules are: LDL receptor type A 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 signal for receptor internalization via coated pits , containing the consensus tetrapeptide Asn-Pro-Xaa-Tyr. This cytoplasmic tail controls both endocytosis and signaling by interacting with the phosphotyrosine binding 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.
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