Low-density lipoprotein (LDL) receptor class A, conserved site
IPR023415
Definition
Low-density lipoprotein (LDL) receptors are the major cholesterol-carrying lipoproteins of plasma. Seven successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein PMID:6091915. Similar domains have been found (see references in PMID:7603991) in other extracellular and membrane proteins which are listed below: Vertebrate very low density lipoprotein (VLDL) receptor, which binds and transports VLDL. Its extracellular domain is composed of 8 LDLRA domains, 3 EGF-like domains and 6 LDL-receptor class B domains (LDLRB). Vertebrate low-density lipoprotein receptor-related protein 1 (LRP1) (reviewed in PMID:7979249), which may act as a receptor for the endocytosis of extracellular ligands. LRP1 contains 31 LDLRA domains and 22 EGF-like domains. Vertebrate low-density lipoprotein receptor-related protein 2 (LRP2) (also known as gp330 or megalin). LRP2 contains 36 LDLRA domains and 17 EGF-like domains. A LRP-homologue from Caenorhabditis elegans, which contains 35 LDLRA domains and 17 EGF-like domains. Drosophila putative vitellogenin receptor, with 13 copies of LDLRA domains and 17 EGF-like repeats. Complement factor I, which is responsible for cleaving the alpha-chains of C4b and C3b. It consists of a FIMAC domain (Factor I/MAC proteins C6/C7), a scavenger receptor-like domain, 2 copies of LDLRA and a C-terminal serine protease domain. Complement components C6, C7, C8 and C9. They contain each one LDLRA domain. Perlecan, a large multidomain basement membrane heparan sulphate proteoglycan composed of 4 LDLRA domains, 3 LamB domains, 12 laminin EGF- like domains, 14-21 IG-like domains, 3 LamG domains, and 4 EGF-like domains. A similar but shorter proteoglycan (UNC52) is found in Caenorhabditis elegans which has 3 repeats of LDLRA. Invertebrate giant extracellular hemoglobin linker chains, which allow heme-containing chains to construct giant hemoglobin (1 LDLRA domain). G-protein coupled receptor Grl101 of the snail Lymnaea stagnalis, which might directly transduce signals carried by large extracellular proteins. Vertebrate enterokinase (EC 3.4.21.9), a type II membrane protein of the intestinal brush border, which activates trypsinogen. It consists at least of a catalytic light chain and a multidomain heavy chain which has 2 LDLRA, a MAM domain (see [prositedoc:PDOC00604]), a SRCR domain (see [prositedoc:PDOC00348]) and a CUB domain (see [prositedoc:PDOC00908]). Human autosomal dominant polycystic kidney disease protein 1 (PKD1), which is involved in adhesive protein-protein and protein-carbohydrate interactions. The potential calcium-binding site of its single LDLRA domain is missing. Vertebrate integral membrane protein DGCR2/IDD, a potential adhesion receptor with 1 LDLRA domain, a C-type lectin and a VWFC domain (see [prositedoc:PDOC00928]). Drosophila serine protease nudel (EC 3.4.21.-), which is involved in the induction of dorsoventral polarity of the embryo. It has 11 LDLRA domains, 3 of which miss the first disulphide bond (C1-C3). Avian subgroup A rous sarcoma virus receptor (1 copy of LDLRA). Bovine Sco-spondin, which is secreted by the subcommissural organ in embryos and is involved in the modulation of neuronal aggregation. It contains at least 2 EGF-like domains and 3 LDLRA domains. The LDL-receptor class A domain contains 6 disulphide-bound cysteines PMID:7548065 and a highly conserved cluster of negatively charged amino acids, of which many are clustered on one face of the module PMID:7603991. A schematic representation of this domain is shown here: +---------------------+ +--------------------------------+ | | | | -CxxxxxxxxxxxxCxxxxxxxxCxxxxxxxxCxxxxxxxxxxCxxxxxxxxxxxxxxxxxxxxxC- | ******************************************* | | +----------------------------+ 'C': conserved cysteine involved in a disulphide bond. 'x': any residue. '*': position of the pattern. In LDL-receptors the class A domains form the binding site for LDL PMID:6091915 and calcium. The acidic residues between the fourth and sixth cysteines are important for high-affinity binding of positively charged sequences in LDLR's ligands PMID:3283935. The repeat has been shown PMID:7603991 to consist of a β-hairpin structure followed by a series of β-turns. The binding of calcium seems to induce no significant conformational change.
40 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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