The low-density lipoprotein receptor gene family

codes In communications and information processing, code is a system of rules to convert information—such as a letter, word, sound, image, or gesture—into another form, sometimes shortened or secret, for communication through a communication ch ...

for a class of structurally related

cell surface receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integra ...

s 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 Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

homeostasis In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...

(maintenance of appropriate concentration of cholesterol). In humans, excess cholesterol in the blood is captured by

low-density lipoprotein Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall density ...

(LDL) and removed by the liver via

endocytosis Endocytosis is a cellular process in which Chemical substance, substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a Vesicle (biology and chem ...

of the

LDL receptor The low-density lipoprotein receptor (LDL-R) is a mosaic protein of 839 amino acids (after removal of 21-amino acid signal peptide) that mediates the endocytosis of cholesterol-rich low-density lipoprotein (LDL). It is a cell-surface receptor ...

. Recent evidence indicates that the members of the LDL receptor gene family are active in the

cell signalling In biology, cell signaling (cell signalling in British English) is the process by which a cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all cellular life in both prokaryotes and eukary ...

pathways between specialized cells in many, if not all, multicellular organisms. There are seven members of the LDLR family in mammals, namely: * LDLR *

VLDL receptor The very-low-density-lipoprotein receptor (VLDLR) is a transmembrane lipoprotein receptor of the low-density-lipoprotein (LDL) receptor family. VLDLR shows considerable homology with the members of this lineage. Discovered in 1992 by Tokuo. Yama ...

( 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 SCO-spondin is a protein that in humans is encoded by the ''SSPO'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed t ...

; 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;

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 ''O''-linked glycosylation is the attachment of a sugar molecule to the oxygen atom of serine (Ser) or threonine (Thr) residues in a protein. ''O''-glycosylation is a post-translational modification that occurs after the protein has been synthesis ...

, 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

External links