Apolipoprotein B

Apolipoprotein B (including Ag(x) antigen)

Identifiers

Symbol(s)

APOB; FLDB

External IDs

OMIM: 107730 MGI: 88052 Homologene: 328

Gene Ontology
Molecular Function:	• receptor binding • lipid transporter activity • heparin binding
Cellular Component:	• extracellular region • soluble fraction • endoplasmic reticulum • microsome • chylomicron
Biological Process:	• lipid metabolic process • triacylglycerol mobilization • lipid transport • signal transduction • circulation • steroid metabolic process • cholesterol metabolic process • cholesterol transport

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Entrez

338

238055

Ensembl

ENSG00000084674

ENSMUSG00000020609

Uniprot

P04114

Refseq

NM_000384 (mRNA)
NP_000375 (protein)

XM_001000646 (mRNA)
XP_001000646 (protein)

Location

Chr 2: 21.08 - 21.12 Mb

Chr 12: 8 - 8.04 Mb

Pubmed search

[1]

[2]

Apolipoprotein B (APOB) is the primary apolipoprotein of low density lipoproteins (LDL or "bad cholesterol, and more specifically, LDL-cholesterol, remains the primary lipid target and risk factor for atherosclerosis.

Genetic disorders

High levels of APOB are related to heart disease. While there does appear to be a genetic component, the environmental component (what you eat) is a significant factor that should not be ignored.

Hypobetalipoproteinemia is a genetic disorder that can be caused by a mutation in the APOB gene, APOB, although it is usually caused by a mutation in the MTP gene, MTP.

Mouse studies

Most relevant information regarding mouse APOB homologue, mApoB, has come from mouse studies. Mice overexpressing mApoB have increased levels of LDL "bad cholesterol" and decreased levels of HDL "good cholesterol" ^[1]. Mice containing only one functional copy of the mApoB gene show the opposite effect, being resistant to hypercholesterolemia. Mice containing no functional copies of the gene are not viable ^[2].

Molecular biology

The bp upstream determines which isoform is produced.

As a result of the RNA editing, APOB48 and APOB100 share a common N-terminal sequence, but APOB48 lacks APOB100's C-terminal LDL-receptor binding region.

Role in Lipoproteins and Atherosclerosis

APOB100 is found in VLDL, IDL, LDL). Importantly, there is one APOB100 molecule per hepatic-derived lipoprotein. Hence, using that fact, one can quantify the number of lipoprotein particles by noting the total APOB100 concentration in the circulation. Since there is one and only one APOB100 per particle, the number of particles is reflected by the APOB100 concentration. The same technique can be applied to individual lipoprotein classes (e.g. LDL) and thereby enable one to count them as well.

It is well established that APOB100 levels are associated with coronary heart disease, and are even a better predictor of it than is LDL level. A naive way of explaining this observation is to use the idea that APOB100 reflects lipoprotein particle number (independent of their cholesterol content). In this way, one can infer that the number of APOB100-containing lipoprotein particles is a determinant of atherosclerosis and heart disease.

One way to explain the above is to consider that large numbers of lipoprotein particles, and, in particular large numbers of LDL particles, lead to competetion at the APOB100 receptor (i.e. LDL receptor) of peripheral cells. Since such a competition will prolong the residence time of LDL particles in the circulation, it may lead to greater opportunity for them to undergo platelet activation.

References

^a Transgenic mice that overexpress mouse apolipoprotein B. Evidence that the DNA sequences controlling intestinal expression of the apolipoprotein B gene are distant from the structural gene. J Biol Chem. 1996 May 17; 271(20): 11963-70; PubMed Free text
^a Knockout of the Mouse Apolipoprotein B Gene Results in Embryonic Lethality in Homozygotes and Protection Against Diet-Induced Hypercholesterolemia in Heterozygotes. Proc Natl Acad Sci USA. 1995 Feb 28; 92(5): 1774-8; PubMed Free text