apolipoprotein b apolipoprotein b apolipoprotein b (apob) is a protein that in humans is encoded by the apob gene. apobidentifiersaliasesapob, fldb, ldlcq4, apob-100, apob-48, apolipoprotein b, fchl2external idsomim: 107730 mgi: 88052 homologene: 328 genecards: apob gene location (human)chr.chromosome 2 (human)band2p24.1start21,001,429 bpend21,044,073 bpgene location (mouse)chr.chromosome 12 (mouse)band12 a1.1|12 3.53 cmstart8,027,648 bpend8,066,835 bprna expression patternbgeehumanmouse (ortholog)top expressed injejunal mucosaliverright lobe of liverduodenumright ventriclemyocardiumleft ventricleascending aortapopliteal arterysynovial jointtop expressed inleft lobe of liverjejunumyolk sacduodenumileumgallbladderprimitive streakintestinal epitheliumintestinal villuspaneth cellmore reference expression databiogpsmore reference expression datagene ontologymolecular function protein binding lipid binding lipid transporter activity cholesterol transfer activity lipase binding low-density lipoprotein particle receptor binding phospholipid binding heparin binding signaling receptor binding cellular component early endosome chylomicron remnant vesicle lumen endoplasmic reticulum endosome membrane mature chylomicron endoplasmic reticulum lumen vesicle membrane endosome lumen intermediate-density lipoprotein particle clathrin-coated endocytic vesicle membrane endoplasmic reticulum membrane extracellular exosome endocytic vesicle lumen neuronal cell body cytoplasm chylomicron very-low-density lipoprotein particle low-density lipoprotein particle endoplasmic reticulum exit site extracellular space smooth endoplasmic reticulum cytosol plasma membrane lysosomal lumen intracellular membrane-bounded organelle extracellular region high-density lipoprotein particle biological process artery morphogenesis in utero embryonic development fertilization receptor-mediated endocytosis positive regulation of cholesterol storage lipid metabolism cholesterol metabolic process cholesterol transport regulation of cholesterol biosynthetic process lipid transport nervous system development leukocyte migration response to carbohydrate retinoid metabolic process steroid metabolic process triglyceride mobilization lipid catabolic process response to lipopolysaccharide positive regulation of macrophage derived foam cell differentiation cellular response to prostaglandin stimulus response to virus positive regulation of lipid storage cellular response to tumor necrosis factor response to selenium ion flagellated sperm motility positive regulation of gene expression response to organic substance cholesterol homeostasis spermatogenesis triglyceride catabolic process cholesterol efflux post-embryonic development lipoprotein transport toll-like receptor signaling pathway response to estradiol membrane organization chylomicron remodeling low-density lipoprotein particle remodeling chylomicron assembly very-low-density lipoprotein particle assembly chylomicron remnant clearance low-density lipoprotein particle clearance very-low-density lipoprotein particle clearance lipoprotein metabolic process lipoprotein biosynthetic process lipoprotein catabolic process post-translational protein modification transport sources:amigo / quickgoorthologsspecieshumanmouseentrez338238055ensemblensg00000084674ensmusg00000020609uniprotp04114e9q414refseq (mrna)nm_000384nm_009693refseq (protein)np_000375np_033823location (ucsc)chr 2: 21 – 21.04 mbchr 12: 8.03 – 8.07 mbpubmed searchwikidataview/edit humanview/edit mouse function apolipoprotein b is the primary apolipoprotein of chylomicrons, vldl, lp(a), idl, and ldl particles (ldl—commonly known as "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 to all cells within all tissues. while all the functional roles of apob within the ldl (and all larger) particles remain 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 and 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. genetic disorders 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. mouse studies mice have been used as model organisms in apob study as they express an equivalent protein known as mouse apob (mapob). mice overexpressing mapob have increased levels of ldl and decreased levels of hdl. 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. molecular biology 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. apob 48 is a unique protein to chylomicrons from the small intestine. after most of the lipids in the chylomicron have been absorbed, apob48 returns to the liver as part of the chylomicron remnant, where it is endocytosed and degraded. clinical significance role in innate immune system very low-density lipoproteins and low-density lipoproteins interfere with the quorum sensing system that upregulates genes required for invasive staphylococcus aureus infection. the mechanism of antagonism entails binding apob, to a s. aureus autoinducer pheromone, preventing signaling through its receptor. mice deficient in apob are more susceptible to invasive bacterial infection. role in insulin resistance overproduction of apolipoprotein b can result in lipid-induced endoplasmic reticulum stress and insulin resistance in the liver. role in lipoproteins and atherosclerosis apob100 is found in lipoproteins originating from the liver (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, they are a far better predictor of it than are ldl-c concentrations. reason: ldl-c does not reflect actual particle concentrations & cholesterol cannot dissolve or move (in water) without particles to carry it. a simple way to understand this observation is the fact that apob100, one per particle, reflects actual lipoprotein particle concentration (independent of their cholesterol, or other lipid content). in this way, one can understand that the number of apob100-containing lipoprotein particles which can carry lipids into the artery walls is a key determinant, driver 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 competition at the apob100 receptor (i.e. ldl receptor) of peripheral cells. since such competition will prolong the residence time of ldl particles in the circulation, it may lead to greater opportunity for them to undergo oxidation and/or other chemical modifications. such modifications may lessen the particles' ability to be cleared by the classic ldl receptor and/or increase their ability to interact with so-called "scavenger" receptors. the net result is the shunting of ldl particles to these scavenger receptors. scavenger receptors typically are found on macrophages, with cholesterol-laden macrophages being better known as "foam cells". foam cells characterize atherosclerotic lesions. in addition to this possible mechanism of foam cell generation, an increase in the levels of chemically modified ldl particles may also lead to an increase in endothelial damage. this occurs as a result of modified-ldl's toxic effect on vascular endothelium as well as its ability both to recruit immune effector cells and to promote platelet activation. the interheart study found that the apob100 / apoa1 ratio is more effective at predicting heart attack risk, in patients who had had an acute myocardial infarction, than either the apob100 or apoa1 measure alone. (apoa1 is the major hdl protein.) in the general population this remains unclear although in a recent study apob was the strongest risk marker for cardiovascular events. interactions apob has been shown to interact with apo(a), ppib, calcitonin receptor and hsp90b1. interaction of apob with proteoglycans, collagen, and fibronectin is believed to cause atherosclerosis. interactive pathway map click on genes, proteins and metabolites below to link to respective articles. [[file: |alt=statin pathway edit]] statin pathway edit the interactive pathway map can be edited at wikipathways: "statin_pathway_wp430". regulation the expression of apob is regulated by cis-regulatory elements in the apob 5′ utr and 3′ utr. rna editing the mrna of this protein is subject to cytidine to uridine (c to u) site-specific rna editing. apob100 and apob48 are encoded by the same gene, however, the differences in the translated proteins are not due to alternative splicing but are due to the tissue-specific rna editing event. apob mrna editing was the first example of editing observed in vertebrates. editing of apob mrna occurs in all placental mammals. editing occurs post transcriptionally as the nascent polynucleotides do not contain edited nucleosides. type c to u editing of apob mrna requires an editing complex or holoenzyme (editosome) consisting of the c to u-editing enzyme apolipoprotein b mrna editing enzyme, catalytic polypeptide 1 (apobec-1) as well as other auxiliary factors. apobec-1 is a protein that in humans is encoded by the apobec1 gene.it is a member of the cytidine deaminase family. apobec-1 alone is not sufficient for the editing of apob mrna and requires at least one of these auxiliary factors, apobec1 complementation factor (a1cf) for editing to occur. a1cf contains 3 non identical repeats. it acts as the rna binding subunit and directs apobec-1 to the apob mrna downstream of the edited cytidine. other auxiliary factors are known to be part of the holoenzyme. some of these proteins have been identified. these are cug binding protein 2 (cugbp2), syncrip (glycine-arginine-tyrosine-rich rna binding protein, gry-rbp), heterogeneous nuclear ribonucleoprotein (hnrnp)-c1 (hnrnpc), apobec-1 binding protein abbp1 (hnrnpab), abbp2, kh-type splicing regulatory binding protein (khsrp), bcl-2-associated athanogene 4 (bag4), and auxiliary factor (aux)240. all these proteins have been identified using detection assays and have all been demonstrated to interact with either apobec-1, a1cf, or apob rna. the function of these auxiliary proteins in the editing complex are unknown. as well as editing apob mrna, the apobec-1 editsome also edits the mrna of nf1. mrna editing of apob mrna is the best defined example of this type of c to u rna editing in humans. location despite being a 14,000 residue long transcript, a single cytidine is targeted for editing. within the apob mrna a sequence consisting of 26 nucleotides necessary for editing is found. this is known as the editing motif. these nucleotides (6662–6687) were determined to be essential by site specific mutagenesis experiments. an 11 nucleotide portion of this sequence 4–5 nucleotides downstream from the editing site is an important region known as the mooring sequence. a region called the spacer element is found 2–8 nucleotides between the edited nucleoside and this mooring sequence. there is also a regulatory sequence 3′ to the editing site. the active site of apobec-1, the catalytic component of the editing holoenzyme is thought to bind to an au rich region of the mooring sequence with the aid of acf in binding the complex to the mrna. the edited cytidine residue is located at nucleotide 6666 located in exon 26 of the gene. editing at this site results in a codon change from a glutamine codon (caa) to an inframe stop codon (uaa). computer modelling has detected for editing to occur, the edited cytidine is located in a loop. the