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 Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

homeostasis In biology, homeostasis (British English, British also homoeostasis) Help:IPA/English, (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physics, physical, and chemistry, chemical conditions maintained by organism, living systems. Thi ...

(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 densit ...

(LDL) and removed by the liver via

endocytosis Endocytosis is a cellular process in which 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 containing the ingested material. E ...

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) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...

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

LDLR 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 th ...

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 T. Yamamoto, ...

( VLDLR) *

ApoER2 Low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), is a protein that in humans is encoded by the ''LRP8'' gene. ApoER2 is a cell surface receptor that is part of the low-density lipopro ...

, or

LRP8 Low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), is a protein that in humans is encoded by the ''LRP8'' gene. ApoER2 is a cell surface receptor that is part of the low-density lipopro ...

Low density lipoprotein receptor-related protein 4 Low-density lipoprotein receptor-related protein 4 (LRP-4), also known as multiple epidermal growth factor-like domains 7 (MEGF7), is a protein that in humans is encoded by the ''LRP4'' gene. LRP-4 is a member of the Lipoprotein receptor-related p ...

** 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 The ''DGCR2'' gene encodes the protein integral membrane protein DGCR2/IDD in humans. Deletions of the 22q11.2 have been associated with a wide range of developmental defects (notably DiGeorge syndrome, velocardiofacial syndrome, conotruncal anom ...

;

HSPG2 Perlecan (PLC) also known as basement membrane-specific heparan sulfate proteoglycan core protein (HSPG) or heparan sulfate proteoglycan 2 (HSPG2), is a protein that in humans is encoded by the ''HSPG2'' gene. The HSPG2 gene codes for a 4,391 amin ...

;

; LDLRAD2; LDLRAD3;

LRP1 Low density lipoprotein receptor-related protein 1 (LRP1), also known as alpha-2-macroglobulin receptor (A2MR), apolipoprotein E receptor (APOER) or cluster of differentiation 91 (CD91), is a protein forming a receptor found in the plasma membra ...

; LRP10;

LRP11 Low density lipoprotein receptor-related protein 11 is a protein in humans that is encoded by the LRP11 gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." m ...

;

LRP12 Low density lipoprotein receptor-related protein 1 (LRP1), also known as alpha-2-macroglobulin receptor (A2MR), apolipoprotein E receptor (APOER) or cluster of differentiation 91 (CD91), is a protein forming a receptor found in the plasma membran ...

;

LRP1B Low-density lipoprotein receptor-related protein 1B is a protein that in humans is encoded by the ''LRP1B'' gene. Function LRP1B belongs to the LDL receptor The low-density lipoprotein receptor (LDL-R) is a mosaic protein of 839 amino acid ...

;

LRP2 Low density lipoprotein receptor-related protein 2 also known as LRP-2 or megalin is a protein which in humans is encoded by the ''LRP2'' gene. Function LRP2 was identified as the antigen of rat experimental membranous nephropathy (Heyman neph ...

; LRP3; LRP4; LRP5; LRP6;

; MAMDC4;

MFRP Membrane frizzled-related protein is a protein that in humans is encoded by the ''MFRP'' gene. References Further reading

* * * * * * * * {{protein-stub ...

; PRSS7;

RXFP1 Relaxin/insulin-like family peptide receptor 1, also known as RXFP1, is a human G protein coupled receptor that is one of the relaxin receptors. It is a rhodopsin-like GPCR which is unusual in this class as it contains a large extracellular bindin ...

; RXFP2;

SORL1 Sortilin-related receptor, L(DLR class) A repeats containing is a protein that in humans is encoded by the SORL1 gene. SORL1 (also known as SORLA, SORLA1, or LR11) is a neuronal apolipoprotein E receptor, the gene for which is predominantly expres ...

;

SPINT1 Kunitz-type protease inhibitor 1 is an enzyme that in humans is encoded by the ''SPINT1'' gene. The protein encoded by this gene is a member of the Kunitz family of serine protease inhibitors. The protein is a potent inhibitor specific for HGF ac ...

;

SSPO SCO-spondin is a protein that in humans is encoded by the ''SSPO'' gene. SCO-spondin is secreted by the subcommissural organ, and contributes to commissure, commissural Axon#Development and growth, axon growth and the formation of Reissner's fiber ...

;

ST14 Suppressor of tumorigenicity 14 protein, also known as matriptase, is a protein that in humans is encoded by the ST14 gene. ST14 orthologs have been identified in most mammals for which complete genome data are available. Function Matriptase ...

; TMPRSS4; TMPRSS6; TMPRSS7; TMPRSS9 ( serase-1B); VLDLR;

Class B

EGF;

;

; LRP10;

;

; LRP4; LRP5; LRP5L; LRP6;

;

NID1 Nidogen-1 (NID-1), formerly known as entactin, is a protein that in humans is encoded by the ''NID1'' gene. Both nidogen-1 and nidogen-2 are essential components of the basement membrane alongside other components such as type IV collagen, proteog ...

;

NID2 Nidogen-2, also known as osteonidogen, is a basal lamina protein of the nidogen family. It was the second nidogen to be described after nidogen-1 (entactin). Both play key roles during late embryonic development. In humans it is encoded by the ' ...

;

; 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 synthesise ...

, 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