Apolipoprotein is the protein part of lipoprotein. The primary function of apolipoproteins is to serve as structural components of lipoproteins and to transport lipids through the blood and lymph. Synthesis of apolipoproteins occurs in the intestine and liver. Their synthesis is regulated by the fat content of the diet and other internal factors. In addition to their role as structural components of lipoproteins, apolipoproteins also serve as ligands for cell surface receptors and as cofactors for enzymes.
   

Shell: apolipoproteins, monolayer phospholipids and cholesterol

Apolipoproteins are mainly A, B, C, D, and E, including H, L, (a), etc. The various types of apolipoproteins can be subdivided into several subclasses, which are indicated by Roman numerals, and their basic functions are to transport lipid substances and stabilize the structure of lipoproteins, some of the apolipoproteins also have the functions of activating the enzyme for metabolism of lipoproteins and recognizing the receptors, which are mainly synthesized in the liver (and partly in the small intestine). For example, ApoA can be divided into AⅠ, AⅡ, AⅢ, and ApoB can be divided into B100 and B48. The main physiological functions of apolipoproteins are to maintain the structure and density of lipoproteins, transport lipids, participate in the regulation of various enzyme activities, and recognize receptor binding.
 
The primary role of monolayer phospholipids is to form a biofilm, with the hydrophilic end facing outward and the hydrophobic end facing inward, forming a hydrophobic inner core.
 
The cholesterol on the outer shell, also called free cholesterol, is not esterified with fatty acids.

 

Kernel: cholesterol esters and triglycerides

Esterification of cholesterol with fatty acids increases hydrophobicity, making cholesteryl esters the most suitable form of cholesterol transport and the major form of cholesterol in lipoproteins.
 
Triglycerides, because of their hydrophobicity, can only be located in the inner core for transportation.
 

Function of Apolipoprotein

Apolipoproteins have an important role in the metabolism of lipoproteins and in accomplishing their physiological functions. Their main functions are:
 

1. To constitute and stabilize the structure of lipoproteins;
2. Modifying and influencing the metabolism and activity of lipoprotein-related enzymes;
3. Cofactors for some enzymes;
4. As a ligand for lipoprotein receptors, it determines and participates in the binding of lipoproteins to cell surface lipoprotein receptors and in their metabolism.

Distribution of Apolipoprotein

Apolipoproteins are components of different lipoproteins and are categorized as non-exchangeable and exchangeable.ApoB is non-exchangeable on lipoproteins, whereas ApoA1, ApoE, ApoD, ApoJ, ApoH, and apoM are exchangeable and can be transferred between different lipoprotein particles. ApoA1 and ApoB are the major protein components of HDL and LDL, respectively. ApoB has two forms: apoB-100 and apoB-48. apoB-100 is produced in the liver and is incorporated into low-density lipoproteins (LDL), whereas apoB-48 is found in the intestine as a component of celiac particles. ApoB-100 mediates ligand-receptor uptake of LDL, and approximately 98% of all plasma is in the form of apoB-100. ApoE is found primarily in VLDL and HDL. HDL particles contain a large number of proteins such as ApoD, ApoM, ApoH, and ApoJ. However, these apolipoproteins are also interlinked with other lipoproteins, while ApoH circulates in its free form.  
 

Major Classes and Functions of Apolipoprotein

Gene Name: LPA
Alternative Name: AK38, APOA, LP, LPA
Gene Location: Chromosome6, NC_000006.12(160531482..160664275,complement)
Function: The protein encoded by this gene is a serine protease that inhibits tissue-type fibrinogen activator I activity. The encoded protein constitutes an important part of lipoprotein (a) and is cleaved by protein hydrolysis to produce fragments that attach to atherosclerotic lesions and thus promote thrombosis. Elevated protein levels of this plasma are associated with atherosclerosis.
 
Gene Name: LPAL2
Alternative Name：APOA2, APOAL, APOARGC, apo(a)rg-C
Gene Location: Chromosome6, NC_000006.12(160466555..160511124,complement)
Function: Apolipoprotein (a) is a particular component of lipoprotein (a). Elevated plasma levels are associated with an increased risk of atherosclerosis. This gene is similar to the lipoprotein Lp(a) gene, but all transcripts produced by this gene contain a truncated open reading frame and are candidates for nonsense-mediated decay. Therefore, it is considered a pseudogene. Selective splicing resulted in multiple transcript variants.
 
Gene Name: Apo A I
Alternative Name：HPALP2, apo(a)
Gene Location:Chromosome11,NC_000011.10(116835751..116837950,complement)
Function: This gene encodes apolipoprotein A-1, the major protein component of high-density lipoprotein (HDL) in plasma. The encoded preprotein undergoes protein hydrolysis to produce mature proteins that facilitate the efflux of cholesterol from tissues to the liver for excretion and is a cofactor for lecithin cholestanol transferase (LCAT). Defects in this gene have been associated with high-density lipoprotein deficiency (including Tangier disease) and systemic non-neurologic amyloidosis. Selective splicing results in multiple transcript variants, at least one of which encodes a preprotein.
 
Gene Name: Apo A ll
Alternative Name：Apo-All, ApoA-ll, apoAll
Gene Location: Chromosome1,NC_000001.11(161222292..161223628,complement)
Function: This gene encodes apolipoprotein (apo-) A-II, the second most abundant protein in HDL particles. The protein exists in plasma as a monomer, homodimer, or heterodimer and binds to apolipoprotein D. The gene encodes apolipoprotein (apo-) A-II, the second most abundant protein in HDL particles. Defects in this gene may result in apolipoprotein A-II deficiency or hypercholesterolemia.
 
Gene Name: Apo A IV
Gene Location:Chromosome11,NC_000011.10(116820700..116823304,complement)
Function: The ApoA-IV gene consists of three exons and two introns. A sequence polymorphism was found in the 3'UTR of the third exon. The major translation product is a 396-residue preprotein that is synthesized in the intestine and secreted after proteolytic processing to bind to celiac particles. Although its exact function is unknown, ApoA-IV is a potent activator of lecithin-cholesterol acyltransferase in vitro.
 
Gene Name: Apo AV
Alternative Name: APOAV, RAP3
Gene Location:Chromosome11,NC_000011.10(116789367..116792420,complement)
Function: The protein encoded by this gene is an apolipoprotein that plays an important role in the regulation of plasma triglyceride levels, a major risk factor for coronary heart disease. It is a component of HDL and is very similar to the rat protein that is upregulated in response to liver injury. Mutations in this gene have been associated with hypertriglyceridemia and hyperlipoproteinemia type 5.
 
Gene Name: Apo B
Alternative Name：FCHL2, FLDB,LDLCQ4, apoB-100, apoB-48
Gene Location: Chromosome 2, NC_000002.12(21001429..21044073,complement)
Function: The gene product is the major apolipoprotein of celiac disease and low-density lipoprotein (LDL) and is a ligand for the LDL receptor. It occurs in plasma as two major isoforms apoB-48 and apoB-100: the former is synthesized exclusively in the intestine and the latter in the liver. The intestinal and hepatic apoB types are encoded by a single gene with a long mRNA. Mutations in this gene or its regulatory region can lead to hypobeta-lipoproteinemia, normotriglyceridemic hypobeta-lipoproteinemia, and hypercholesterolemia.
 
Gene Name: Apo C I
Alternative Name：Apo-Cl, ApoC-l, apo- CIB, apoC-IB
Gene Location: Chromosome 19, NC_000019.10(44914325..44919346)
Function: This gene encodes a member of the apolipoprotein C1 family. The gene is expressed primarily in the liver and is activated when monocytes differentiate into macrophages. The encoded protein plays an important role in both high-density lipoprotein (HDL) and Very Low-Density Lipoprotein (VLDL) metabolism. This protein has also been shown to inhibit cholesteryl ester transfer protein in plasma. A pseudogene of this gene is located 4kb downstream of it. Selective splicing and the use of selective promoters result in multiple transcript variants.
 
Gene Name: Apo C ll
Alternative Name：APO-CII, APOC-II
Gene Location: Chromosome 19, NC_000019.10(44946051..44949565)
Function: This gene encodes a component of very low-density lipoprotein. This protein activates the enzyme lipoprotein lipase, which hydrolyzes triglycerides to provide cells with free fatty acids. Mutations in this gene cause hyperlipoproteinemia type IB, which is characterized by an increased risk of hypertriglyceridemia, xanthomas, pancreatitis, and early atherosclerosis. There is a natural read-through transcription between this gene and the neighboring upstream apolipoprotein C-IV (APOC4) gene.
 
Gene Name: Apo C III
Alternative Name：APOCIII
Gene Location: Chromosome 11, NC_000011.10(116829907..116833072)
Function: This gene encodes the protein component of triglyceride (TG)-rich lipoproteins (TRLs), including very low-density lipoprotein (VLDL), high-density lipoprotein (HDL), and celiac disease. The encoded protein is involved in the metabolism of TRLs in several ways. This protein promotes the secretion of VLDL1, inhibits lipoprotein lipase activity, and delays the catabolism of TRL remnants. Mutations in this gene have been associated with low plasma triglyceride levels and a reduced risk of ischemic cardiovascular disease, as well as hyperlipoproteinemia, which is characterized by elevated levels of high-density lipoprotein (HDL) and HDL cholesterol in human patients.
 
Gene Name: Apo C IV
Alternative Name：APO-CIV, APOC-IV
Gene Location: Chromosome 19, NC_000019.10(44942237..44945496)
Function: This gene encodes a lipid-binding protein that belongs to the apolipoprotein gene family. This protein is thought to play a role in lipid metabolism. Polymorphisms in this gene may affect circulating lipid levels and may be associated with the risk of coronary artery disease. There is a natural read-through transcription with the neighboring downstream apolipoprotein C-ll (APOC2) gene.
 
Gene Name: Apo D
Gene Location: Chromosome3,NC_000003.12(195568705..195583940,complement)
Function: This gene encodes an HDL component that has no significant similarity to other ApoE sequences. It is highly homologous to plasma retinol-binding proteins and other members of the carrier protein alpha2 microglobulin superfamily (also known as lipocalins). Closely related to lecithin: cholesterol acyltransferase-an enzyme involved in lipoprotein metabolism.
 
Gene Name: Apo E
Alternative Name: AD2, APO- E, ApoE4, LDLCQ5, LPG
Gene Location: Chromosome 19, NC_000019.10(44905796..44909393)
Function: The protein encoded by this gene is the major apolipoprotein of celiac disease. It binds to specific liver and peripheral cell receptors and is essential for the normal catabolism of triglyceride-rich lipoprotein components. Mutations in this gene result in familial beta-lipoproteinemia, or hyperlipoproteinemia type III (HLP-III), in which elevated plasma cholesterol and triglycerides are the result of impaired clearance of celiac and VLDL remnants.
 
Gene Name: Apo F
Alternative Name: Apo-F, LTIP
Gene Location: Chromosome 12, NC_000012.12(56360568..56362857, complement)
Function: The product of this gene is one of the minor apolipoproteins found in plasma. This protein is complexed with lipoproteins and may be involved in cholesterol transport/esterification.
 
Gene Name: Apo H
Alternative Name：B2G1, B2GP1,BG
Gene Location: Chromosome 17, NC_000017.11(66212033..66229415,complement)
Function: Apolipoprotein H, or beta-2-glycoprotein I, is a component of circulating plasma lipoproteins. It is involved in various physiological pathways, including lipoprotein metabolism, coagulation, hemostasis, and the production of antiphospholipid autoantibodies. APOH may be a cofactor required for binding antiphospholipid autoantibodies to anionic phospholipids in the sera of patients with lupus and primary antiphospholipid syndrome (APS). Anti-β(2)glycoprotein I antibodies from APS patients mediate the inhibition of activated protein C, which has anticoagulant properties. Since β-2-GPI is the major autoantigen in APS patients, disruption of this pathway by autoantibodies may be an important mechanism of thrombosis in APS patients.
 
Gene Name: Apo J
Alternative Name: CLI; AAG4; APOJ; CLU1; CLU2; KUB1; SGP2; APO-J; SGP-2; SP-40, TRPM2; TRPM-2; NA1/NA2; clusterin
Gene Location: Chromosome 8, NC_000008.11(27596917..27614700, complement)
Function: The protein encoded by this gene is a secreted chaperonin that can also be found in the cell cytoplasm under certain stress conditions. It has been implicated in fundamental biological events such as cell death, tumor progression, and neurodegenerative diseases. Alternate splicing results in coding and non-coding variants.
 
Gene Name: Apo L1
Alternative Name：APO-L, APOL, APOL-1, FSGS4
Gene Location: Chromosome 22, NC_000022.11(36253071..36267531)
Function: This gene encodes a secreted HDL that binds to apolipoprotein a-l. Apolipoprotein a-l is a relatively abundant plasma protein and is the major apolipoprotein of HDL. This gene is involved in the formation of most of the cholesterol esters in plasma and also promotes cholesterol efflux from cells. This member of the apolipoprotein L family may play a role in systemic lipid exchange and transport, as well as in the retrograde transport of cholesterol from peripheral cells to the liver. Transcript variants exist.
 
 
Gene Name: Apo L2
Alternative Name：APOL-II, APOL2
Gene Location: Chromosome 22, NC_000022.11(36226209..36239954, complement)
Function: This gene is a member of the apolipoprotein L gene family. The encoded protein is found in the cytoplasm, where it may influence the movement of lipids or allow lipids to bind to organelles.
 
Gene Name: Apo L3
Alternative Name：APOLIII, CG121, CG12_ 1, apoL-III
Gene Location: Chromosome 22, NC_000022.11(36140323..36166177,complement)
Function: This gene is a member of the apolipoprotein L gene family. The encoded protein is present in the cytoplasm, where it may influence the movement of lipids (including cholesterol)/allow lipid binding to organelles. In addition, it is regulated by TNF-α in normal and atherosclerotic iliac artery and aortic endothelial cells resulting in upregulated expression. Selective splicing resulted in multiple transcript variants.
 
Gene Name: Apo L4
Alternative Name：APOL-IV, APOLIV
Gene Location: Chromosome 22, NC_000022.11(36189128..36204833,complement)
Function: This gene encodes a member of the apolipoprotein L family. The encoded protein may play a role in systemic lipid exchange and transport, as well as in the reverse transport of cholesterol from peripheral cells to the liver. Selective splicing results in multiple transcript variants.
 
Gene Name: Apo L5
Alternative Name：APOL-V, APOLV
Gene Location: Chromosome 22, NC_000022.11(35708424..35730325)
Function: This gene is a member of the apolipoprotein L gene family. The encoded protein is found in the cytoplasm, where it may influence the movement of lipids or allow lipids to bind to organelles.
 
Gene Name: Apo L6
Alternative Name: APOL-VI, APOLVI
Gene Location: Chromosome 22, NC_000022.11(35648316..35668406)
Function: This gene is a member of the apolipoprotein L gene family. The encoded protein is found in the cytoplasm, where it may influence the movement of lipids or allow lipids to bind to organelles.
 
Gene Name: Apo LD1
Alternative Name: VERGE
Gene Location: Chromosome 12, NC_000012.12(12725917..12791466)
Function：APOLD1 is an endothelial cell early response protein that may play a role in regulating endothelial cell signaling and vascular function.
 
Gene Name: Apo M
Alternative Name: G3a, HSPC336, NG 20, apo-M 
Gene Location: Chromosome 6, NC_000006.12(31652404..31658210)
Function: The protein encoded by this gene is apolipoprotein, which belongs to the family of lipid transporter proteins. It was found to be associated with high-density lipoproteins and to a lesser extent with low-density lipoproteins and triglyceride-rich lipoproteins. The encoded protein is secreted through the plasma membrane but remains membrane-bound and is involved in lipid transport. Selective splicing results in coding and non-coding variants of the gene.
 
Gene Name: Apo O
Alternative Name: FAM121B, MIC26, MICOS26, Mic23, Myo25
Gene Location: Chromosome X, NC_000023.11(23833348..23907938, complement)
Function: This gene is a member of the apolipoprotein family. Members of this family of proteins are involved in the transportation and metabolism of lipids. The encoded protein binds to high-density lipoproteins, low-density lipoproteins, and very-low-density lipoproteins and is characterized by glycosylation with chondroitin sulfate. This protein may be involved in preventing myocardial lipid accumulation in obese and diabetic patients. Selective splicing results in multiple transcript variants. Pseudogenes for this gene are present on chromosomes 3, 4, 5, 12, and 16.
 
Gene Name: Apo OL
Alternative Name: CXorf33, FAM121A, MICOS27, Mic27, UNQ8193
Gene Location: Chromosome X, NC_000023.11(85003852..85093315)
Function: This gene encodes a protein that contains a structural domain of the apolipoprotein O superfamily. This structural domain is present in proteins of the circulating lipoprotein complex.
 

Disease Involvement of Apolipoprotein

It is well known that there is a relationship between apolipoproteins and different diseases. For example, ApoA1 and ApoB are associated with cardiovascular disease, and ApoE and ApoJ with Alzheimer's disease. ApoD has been reported to have a role in several different neurological disorders including schizophrenia and Alzheimer's disease, such as metabolic syndrome, and lipid disorders such as diabetes mellitus. ApoH, also known as beta 2 glycoprotein I, is involved in autoimmune diseases such as antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Recently, ApoM is associated with the pathogenesis of atherosclerosis, diabetes mellitus, and renal diseases, and polymorphisms in the ApoM gene have been associated with coronary heart disease and diabetes mellitus. Therefore, ApoM has become a key risk marker for the prediction and diagnosis of different diseases.
 
 

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