Low density lipoprotein receptor gene family
Encyclopedia
The low density lipoprotein receptor gene family code
for a class of structurally closely 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
(maintenance of appropriate concentration of cholesterol). In humans, excess cholesterol in the blood is captured by low-density lipoprotein (LDL) and removed in the liver by the 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:
; Complement component 7
; Complement component 8A; Complement component 8B; Complement component 9
; 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; serase-1B;
; 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;
; LDLR; LRP1
; LRP10
; LRP1B
; LRP2
; LRP4
; LRP5
;
LRP5L; LRP6
; LRP8; NID1; NID2
; SORL1
; VLDLR;
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.
Genetic code
The genetic code is the set of rules by which information encoded in genetic material is translated into proteins by living cells....
for a class of structurally closely 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
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
homeostasis
Homeostasis
Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...
(maintenance of appropriate concentration of cholesterol). In humans, excess cholesterol in the blood is captured by low-density lipoprotein (LDL) and removed in the liver by the endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
of the LDL receptor
LDL receptor
The Low-Density Lipoprotein Receptor is a mosaic protein of ~840 amino acids that mediates the endocytosis of cholesterol-rich LDL. It is a cell-surface receptor that recognizes the apoprotein B100 which is embedded in the phospholipid outer layer of LDL particles...
. 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:
- LDLRLDL receptorThe Low-Density Lipoprotein Receptor is a mosaic protein of ~840 amino acids that mediates the endocytosis of cholesterol-rich LDL. It is a cell-surface receptor that recognizes the apoprotein B100 which is embedded in the phospholipid outer layer of LDL particles...
- VLDL receptorVLDL receptorThe very-low-density-lipoprotein receptor is a lipoprotein receptor that shows considerable similarity to the low-density-lipoprotein receptor...
(VLDLR) - ApoER2, or LRP8
- Multiple epidermal growth factor (EGF) repeat-containing protein (MEGF7LRP4LRP4 can refer to:* CORIN* low density lipoprotein receptor-related protein 4...
) - LDLR-related protein 1LRP1Low density lipoprotein receptor-related protein 1 , also known as alpha-2-macroglobulin receptor , apolipoprotein E receptor or cluster of differentiation 91 , is a protein forming a receptor found in the plasma membrane of cells involved in receptor-mediated endocytosis...
- LDLR-related protein 1bLRP1BLow-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 gene family. These receptors play a wide variety of roles in normal cell function and development due to their interactions with multiple ligands....
- MegalinLRP2Low density lipoprotein-related protein 2 also known as LRP2 or megalin is a protein which in humans is encoded by the LRP2 gene.-Function:...
.
Human proteins containing this domain
Complement component 6Complement component 6
Complement component 6 is a protein that in humans is encoded by the C6 gene.Complement component 6 is a protein involved in the complement system. It is part of the membrane attack complex which can insert into the cell membrane and cause cell to lyse....
; Complement component 7
Complement component 7
Complement component 7 is a protein involved in the complement system....
; Complement component 8A; Complement component 8B; Complement component 9
Complement component 9
Complement component 9 is a protein involved in the complement system....
; CD320
CD320
CD320 is a human gene....
; CFI
CFI
CFI may refer to:* CAD Framework Initiative, a standardization organization for CAD systems in the EDA area* Canada Foundation for Innovation* Canal France International* Canonical Format Indicator, a field in the IEEE 802.1Q protocol...
; CORIN
CORIN
Atrial natriuretic peptide-converting enzyme is a protein that in humans is encoded by the CORIN gene.-Further reading:...
; DGCR2
DGCR2
Integral membrane protein DGCR2/IDD is a protein that in humans is encoded by the DGCR2 gene.Deletions of the 22q11.2 have been associated with a wide range of developmental defects classified under the acronym CATCH 22...
; HSPG2; LDLR; LDLRAD2; LDLRAD3; LRP1
LRP1
Low density lipoprotein receptor-related protein 1 , also known as alpha-2-macroglobulin receptor , apolipoprotein E receptor or cluster of differentiation 91 , is a protein forming a receptor found in the plasma membrane of cells involved in receptor-mediated endocytosis...
; LRP10
LRP10
Low-density lipoprotein receptor-related protein 10 is a protein that in humans is encoded by the LRP10 gene....
;
LRP11; LRP12; LRP1B
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 gene family. These receptors play a wide variety of roles in normal cell function and development due to their interactions with multiple ligands....
; LRP2
LRP2
Low density lipoprotein-related protein 2 also known as LRP2 or megalin is a protein which in humans is encoded by the LRP2 gene.-Function:...
; LRP3
LRP3
Low density lipoprotein receptor-related protein 3 is a protein that in humans is encoded by the LRP3 gene....
; LRP4
LRP4
LRP4 can refer to:* CORIN* low density lipoprotein receptor-related protein 4...
; LRP5
LRP5
Low-density lipoprotein receptor-related protein 5 is a protein that in humans is encoded by the LRP5 gene.- Function :LRP5 is a transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis...
; LRP6
LRP6
Low-density lipoprotein receptor-related protein 6 is a protein that in humans is encoded by the LRP6 gene....
;
LRP8; MAMDC4; MFRP
MFRP
Membrane frizzled-related protein is a protein that in humans is encoded by the MFRP gene.-Further reading:...
; PRSS7; RXFP1; RXFP2; SORL1
SORL1
SORL1 is a neuronal apolipoprotein E receptor, the gene for which is predominantly expressed in the central nervous system.-Connection with Alzheimer's disease:...
; SPINT1
SPINT1
Kunitz-type protease inhibitor 1 is an enzyme that in humans is encoded by the SPINT1 gene.-Further reading:...
;
SSPO
SSPO
SCO-spondin is a protein that in humans is encoded by the SSPO gene.-Further reading:...
; ST14
ST14
Suppression of tumorigenicity 14 , also known as ST14, is a human gene. ST14 orthologs have been identified in most mammals for which complete genome data are available.-Further reading:...
; TMPRSS4; TMPRSS6
TMPRSS6
Transmembrane protease, serine 6 is an enzyme that in humans is encoded by the TMPRSS6 gene.-Further reading:...
; TMPRSS7; TMPRSS9; VLDLR; serase-1B;
Class A
C6Complement component 6
Complement component 6 is a protein that in humans is encoded by the C6 gene.Complement component 6 is a protein involved in the complement system. It is part of the membrane attack complex which can insert into the cell membrane and cause cell to lyse....
; C7
Complement component 7
Complement component 7 is a protein involved in the complement system....
; 8A; 8B; C9
Complement component 9
Complement component 9 is a protein involved in the complement system....
; CD320
CD320
CD320 is a human gene....
; CFI
CFI
CFI may refer to:* CAD Framework Initiative, a standardization organization for CAD systems in the EDA area* Canada Foundation for Innovation* Canal France International* Canonical Format Indicator, a field in the IEEE 802.1Q protocol...
;
CORIN
CORIN
Atrial natriuretic peptide-converting enzyme is a protein that in humans is encoded by the CORIN gene.-Further reading:...
; DGCR2
DGCR2
Integral membrane protein DGCR2/IDD is a protein that in humans is encoded by the DGCR2 gene.Deletions of the 22q11.2 have been associated with a wide range of developmental defects classified under the acronym CATCH 22...
; HSPG2; LDLR; LDLRAD2; LDLRAD3; LRP1
LRP1
Low density lipoprotein receptor-related protein 1 , also known as alpha-2-macroglobulin receptor , apolipoprotein E receptor or cluster of differentiation 91 , is a protein forming a receptor found in the plasma membrane of cells involved in receptor-mediated endocytosis...
; LRP10
LRP10
Low-density lipoprotein receptor-related protein 10 is a protein that in humans is encoded by the LRP10 gene....
;
LRP11; LRP12; LRP1B
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 gene family. These receptors play a wide variety of roles in normal cell function and development due to their interactions with multiple ligands....
; LRP2
LRP2
Low density lipoprotein-related protein 2 also known as LRP2 or megalin is a protein which in humans is encoded by the LRP2 gene.-Function:...
; LRP3
LRP3
Low density lipoprotein receptor-related protein 3 is a protein that in humans is encoded by the LRP3 gene....
; LRP4
LRP4
LRP4 can refer to:* CORIN* low density lipoprotein receptor-related protein 4...
; LRP5
LRP5
Low-density lipoprotein receptor-related protein 5 is a protein that in humans is encoded by the LRP5 gene.- Function :LRP5 is a transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis...
; LRP6
LRP6
Low-density lipoprotein receptor-related protein 6 is a protein that in humans is encoded by the LRP6 gene....
;
LRP8; MAMDC4; MFRP
MFRP
Membrane frizzled-related protein is a protein that in humans is encoded by the MFRP gene.-Further reading:...
; PRSS7; RXFP1; RXFP2; SORL1
SORL1
SORL1 is a neuronal apolipoprotein E receptor, the gene for which is predominantly expressed in the central nervous system.-Connection with Alzheimer's disease:...
; SPINT1
SPINT1
Kunitz-type protease inhibitor 1 is an enzyme that in humans is encoded by the SPINT1 gene.-Further reading:...
;
SSPO
SSPO
SCO-spondin is a protein that in humans is encoded by the SSPO gene.-Further reading:...
; ST14
ST14
Suppression of tumorigenicity 14 , also known as ST14, is a human gene. ST14 orthologs have been identified in most mammals for which complete genome data are available.-Further reading:...
; TMPRSS4; TMPRSS6
TMPRSS6
Transmembrane protease, serine 6 is an enzyme that in humans is encoded by the TMPRSS6 gene.-Further reading:...
; TMPRSS7; TMPRSS9; VLDLR;
Class B
EGFEGF
EGF can refer to several things:*Epidermal growth factor, a growth factor in biology*Exponential generating function, a function in mathematics*European Gendarmerie Force, a European intervention force...
; LDLR; LRP1
LRP1
Low density lipoprotein receptor-related protein 1 , also known as alpha-2-macroglobulin receptor , apolipoprotein E receptor or cluster of differentiation 91 , is a protein forming a receptor found in the plasma membrane of cells involved in receptor-mediated endocytosis...
; LRP10
LRP10
Low-density lipoprotein receptor-related protein 10 is a protein that in humans is encoded by the LRP10 gene....
; LRP1B
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 gene family. These receptors play a wide variety of roles in normal cell function and development due to their interactions with multiple ligands....
; LRP2
LRP2
Low density lipoprotein-related protein 2 also known as LRP2 or megalin is a protein which in humans is encoded by the LRP2 gene.-Function:...
; LRP4
LRP4
LRP4 can refer to:* CORIN* low density lipoprotein receptor-related protein 4...
; LRP5
LRP5
Low-density lipoprotein receptor-related protein 5 is a protein that in humans is encoded by the LRP5 gene.- Function :LRP5 is a transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis...
;
LRP5L; LRP6
LRP6
Low-density lipoprotein receptor-related protein 6 is a protein that in humans is encoded by the LRP6 gene....
; LRP8; NID1; NID2
NID2
Nidogen-2 is a protein that in humans is encoded by the NID2 gene.-Further reading:...
; SORL1
SORL1
SORL1 is a neuronal apolipoprotein E receptor, the gene for which is predominantly expressed in the central nervous system.-Connection with Alzheimer's disease:...
; VLDLR;
See also
- Soluble low density lipoprotein receptor-related proteinSoluble low density lipoprotein receptor-related proteinSoluble low density lipoprotein receptor-related protein is a biological substance naturally produced by the human body. This protein has been found to bind to and neutralize anywhere from 70 to 90 percent of the amyloid-beta peptide that also naturally circulates in healthy human or mouse plasma...
(sLRP) - impaired function is related to Alzheimer's DiseaseAlzheimer's diseaseAlzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
.
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, 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.