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
. Similar domains have been found (see references in ) 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 ), which may act as a receptor for the endocytosis of
extracellular ligands. LRP1 contains 31 LDLRA domains and 22 EGF-like
Vertebrate low-density lipoprotein receptor-related protein 2 (LRP2) (also
known as gp330 or megalin). LRP2 contains 36 LDLRA domains and 17 EGF-like
A LRP-homolog 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 α-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
Complement components C6, C7, C8 and C9. They contain each one LDLRA
Perlecan, a large multidomain basement membrane heparan sulfate
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 188.8.131.52), 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 <PDOC00604>), a SRCR domain (see <PDOC00348>) and a CUB
domain (see <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
Vertebrate integral membrane protein DGCR2/IDD, a potential adhesion
receptor with 1 LDLRA domain, a C-type lectin and a VWFC domain (see
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 disulfide 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 disulfide-bound cysteines  and a
highly conserved cluster of negatively charged amino acids, of which many are
clustered on one face of the module . A schematic representation of this
domain is shown here:
'C': conserved cysteine involved in a disulfide bond.
'x': any residue.
'*': position of the pattern.
In LDL-receptors the class A domains form the binding site for LDL  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 . The repeat has been shown  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.
April 2006 / Pattern revised.
PROSITE methods (with tools and information) covered by this documentation:
Yamamoto T., Davis C.G., Brown M.S., Schneider W.J., Casey M.L., Goldstein J.L., Russell D.W.
The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA.
PROSITE is copyright. It is produced by the SIB Swiss Institute
Bioinformatics. There are no restrictions on its use by non-profit
institutions as long as its content is in no way modified. Usage by and
for commercial entities requires a license agreement. For information
about the licensing scheme send an email to
or see: prosite_license.html.