Apolipoprotein B

338238055ENSG00000084674ENSMUSG00000020609P04114E9Q414NM_000384NM_009693NP_000375NP_033823Apolipoprotein B (ApoB) is a protein that in humans is encoded by the APOB gene. Apolipoprotein B (ApoB) is a protein that in humans is encoded by the APOB gene. Apolipoprotein B is the primary apolipoprotein of chylomicrons, VLDL, IDL, and LDL particles (LDL - known commonly by the misnomer 'bad cholesterol' when in reference to both heart disease and vascular disease in general), which is responsible for carrying fat molecules (lipids), including cholesterol, around the body (within the water outside cells) to all cells within all tissues. While all the functional roles of ApoB within the LDL (and all larger) particles remains somewhat unclear, it is the primary organizing protein (of the entire complex shell enclosing/carrying fat molecules within) component of the particles and is absolutely required for the formation of these particles. What is also clear is that the ApoB on the LDL particle acts as a ligand for LDL receptors in various cells throughout the body (i.e., less formally, ApoB indicates fat carrying particles are ready to enter any cells with ApoB receptors and deliver fats carried within into the cells). Through mechanisms only partially understood, high levels of ApoB, especially associated with the higher LDL particle concentrations, are the primary driver of plaques that cause vascular disease (atherosclerosis), commonly first becoming obviously symptomatic as heart disease, stroke & many other body wide complications after decades of progression. There is considerable evidence that concentrations of ApoB and especially the NMR assay (specific for LDL-particle concentrations) are superior indicators of vascular/heart disease driving physiology than either total cholesterol or LDL-cholesterol (as long promoted by the NIH starting in the early 1970s). However, primarily for historic cost/complexity reasons, cholesterol, and estimated LDL-cholesterol by calculation, remains the most commonly promoted lipid test for the risk factor of atherosclerosis. ApoB is routinely measured using immunoassays such as ELISA or nephelometry. Refined and automated NMR methods allow measurement distinctions between the many different ApoB particles. High levels of ApoB are related to heart disease.Hypobetalipoproteinemia is a genetic disorder that can be caused by a mutation in the ApoB gene, APOB. Abetalipoproteinaemia is usually caused by a mutation in the MTP gene, MTP.Mutations in gene APOB100 can also cause familial hypercholesterolemia, a hereditary (autosomal dominant) form of metabolic disorder Hypercholesterolemia. 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'. 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. The protein occurs in the plasma in 2 main isoforms, ApoB48 and ApoB100. The first is synthesized exclusively by the small intestine, the second by the liver. ApoB-100 is the largest of the apoB group of proteins, consisting of 4563 amino acids. Both isoforms are coded by APOB and by a single mRNA transcript larger than 16 kb. ApoB48 is generated when a stop codon (UAA) at residue 2153 is created by RNA editing. There appears to be a trans-acting tissue-specific splicing gene that determines which isoform is ultimately produced. Alternatively, there is some evidence that a cis-acting element several thousand 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. In fact, ApoB48 is so called because it constitutes 48% of the sequence for ApoB100.