Affinage

APOB

Apolipoprotein B-100 · UniProt P04114

Length
4563 aa
Mass
515.5 kDa
Annotated
2026-06-09
100 papers in source corpus 31 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ApoB-100 is the principal structural protein of atherogenic lipoproteins, serving as a single non-exchangeable scaffold (4536 residues encoded by one gene on chromosome 2) onto which triglyceride- and cholesterol-rich particles are assembled and around which a mature particle is wrapped (PMID:3030729, PMID:8187250, PMID:3840371). Lipoprotein assembly is co-translational: nascent ApoB is progressively lipidated during translocation into the ER lumen, producing particles whose density falls as polypeptide length increases (PMID:1315773). This lipidation requires direct, ionic binding of ApoB's N-terminal betaalpha1 domain to MTP, an interaction modulated by lipid and separable from MTP's lipid-transfer activity; loss of MTP function or local charge mutations such as R463W traps ApoB in the ER and drives its degradation rather than secretion, the latter causing familial hypobetalipoproteinemia (PMID:12518019, PMID:10769147, PMID:12588952, PMID:12551903). ApoB that fails to acquire lipid is eliminated through tightly regulated quality-control routes: a cytosolic proteasomal pathway acting on incompletely translocated chains and a DTT-sensitive ER-luminal pathway acting on fully translocated chains (PMID:9111073), with gp78-mediated ubiquitination committing ApoB to p97-driven retrotranslocation/ERAD, and Derlin-1/UBXD8 routing lipidated ApoB to the lipid-droplet surface for proteasomal degradation (PMID:22238364, PMID:21421992). ApoB stability and output are further set by an ER TM6SF2-ERLIN1/2 complex that binds and stabilizes ApoB, by MDM2-mediated (p53-independent) degradation, and by vigilin-dependent translational control, linking these regulators to VLDL secretion, hepatic steatosis, and atherosclerosis (PMID:32776921, PMID:35524581, PMID:27665711). Once secreted, ApoB-100 is the sole protein ligand for the LDL receptor, engaging LDLR repeat LR5 at defined sites in a Ca2+/pH-sensitive manner that underlies endosomal ligand release (PMID:24447298). ApoB transcription is controlled by NF-BA1 and by p53, and intestinal generation of ApoB-48 arises from C-to-U mRNA editing by an apobec-1/ACF complex antagonized by CUGBP2, GRY-RBP, and hnRNP-C1 and modulated hormonally (PMID:2254327, PMID:20890106, PMID:16920700, PMID:1597147). Beyond its structural and receptor roles, ApoB couples apo(a) secretion through noncovalent intracellular complexes (PMID:35045727) and serves as a carrier protein for circulating ligands.

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1986 High

    Establishing that ApoB-100 is a single large protein from one gene with amphipathic lipid-binding helices and an apoE-like LDL-receptor-binding region defined the molecule as the structural scaffold and receptor ligand of LDL.

    Evidence Full-length cDNA sequencing and secondary structure prediction, with chromosomal mapping to 2p23-pter by somatic cell hybrids

    PMID:3030729 PMID:3840371

    Open questions at the time
    • Receptor-binding domain inferred from sequence homology, not direct binding
    • No experimental tertiary structure
  2. 1992 High

    Showing that ApoB is lipidated co-translationally during ER translocation answered whether particle assembly is post-translational, establishing the co-translational assembly model.

    Evidence Puromycin/cycloheximide pulse-chase, gradient fractionation, EM, and truncated minigene transfection

    PMID:1315773

    Open questions at the time
    • Did not identify the lipid-transfer machinery responsible
    • Mechanism coupling length to density not resolved
  3. 1994 Medium

    Disulfide and domain mapping defined ApoB-100 as an elongated, five-domain protein wrapping the LDL particle and nominated Cys3734 as the apo(a) linkage site, framing its architecture and Lp(a) connection.

    Evidence HPLC sulfhydryl/disulfide mapping, fluorescent probe, and trypsin domain mapping

    PMID:8187250

    Open questions at the time
    • No high-resolution structure
    • apo(a) linkage to Cys3734 proposed but not directly demonstrated here
  4. 1997 High

    Resolving ApoB into two degradation routes — cytosolic/proteasomal versus ER-luminal — explained how cells dispose of secretion-incompetent ApoB and linked lipid supply (oleate) to its fate.

    Evidence Pharmacological dissection (BFA, ALLN, DTT) with pulse-chase in HepG2 cells

    PMID:9111073

    Open questions at the time
    • E3 ligases and luminal proteases not identified
    • Single cell line
  5. 2003 High

    Mapping high-affinity ApoB-MTP binding to the betaalpha1 domain via ionic interactions, and showing MTP loss causes rapid ApoB degradation without ER stress, defined MTP as the obligate assembly partner separable from lipid transfer.

    Evidence Co-IP, mutagenesis, AGI-S17 antagonist, plus Cre MTP knockout and chemical inhibition in mice; R463W FHBL mutant analysis

    PMID:10769147 PMID:12518019 PMID:12551903 PMID:12588952

    Open questions at the time
    • Stoichiometry and dynamics of the ApoB-MTP interaction during assembly not defined
    • Structural basis of the ionic contacts unresolved
  6. 2011 High

    Identifying gp78 as the E3 ligase ubiquitinating ApoB upstream of p97 retrotranslocation placed ApoB ERAD within a defined ubiquitin-proteasome circuit and showed its inhibition raises secretion.

    Evidence gp78/p97 single and double siRNA epistasis with ubiquitination assays and lipoprotein fractionation in HepG2

    PMID:21421992

    Open questions at the time
    • Substrate determinants recognized by gp78 unknown
    • Relationship to luminal pathway unclear
  7. 2012 High

    Distinguishing Derlin-1 (pre-dislocation) from UBXD8 (post-dislocation, p97 recruitment to lipid droplets) explained how lipidated ApoB reaches the LD surface for proteasomal degradation.

    Evidence Reciprocal siRNA knockdowns, colocalization, ubiquitination and p97 recruitment assays in Huh7

    PMID:22238364

    Open questions at the time
    • Trigger selecting lipidated ApoB for dislocation unknown
    • Relationship to gp78 pathway not integrated
  8. 2012 Medium

    Demonstrating that the ApoB protein particle (not its lipids) downregulates VEGFR1 revealed a non-lipid signaling role for ApoB in negatively regulating angiogenesis.

    Evidence Zebrafish mtp forward genetic screen with ApoB-level rescue and particle-vs-lipid dissection, validated in hyperlipidemic mice

    PMID:22581286

    Open questions at the time
    • Molecular receptor/mechanism by which ApoB lowers VEGFR1 unknown
    • Human relevance not established
  9. 2014 High

    Solving how LDLR repeat LR5 binds ApoB-100 at two sites with Ca2+/pH-sensitivity provided a structural mechanism for endosomal ligand release independent of beta-propeller displacement.

    Evidence NMR and SPR with synthetic ApoB peptides and LR5 under pH/Ca2+ titration

    PMID:24447298

    Open questions at the time
    • Uses peptides, not intact ApoB on a particle
    • Full receptor-particle complex geometry not resolved
  10. 2020 High

    Identifying a TM6SF2-ERLIN1/2-APOB ER complex showed how the NAFLD-associated E167K variant lowers hepatic ApoB and lipid handling by destabilizing TM6SF2.

    Evidence TAP-MS, Co-IP, TM6SF2 luminal-loop domain mapping, and Tm6sf2 knockout/Erlin knockdown mice

    PMID:32776921

    Open questions at the time
    • Degradation pathway engaged when TM6SF2 is lost not defined
    • How ERLINs stabilize TM6SF2 mechanistically unclear
  11. 2022 High

    Showing MDM2 directly binds and degrades ApoB independent of p53, and that apo(a) forms noncovalent intracellular complexes with ApoB required for apo(a) secretion, expanded ApoB regulation and connected it to Lp(a) biogenesis.

    Evidence Hepatocyte-specific MDM2 knockout, Co-IP, MDM2-ApoB inhibitor; Co-IP/PLA/colocalization with apo(a) LBS7,8 mutants and APOB siRNA

    PMID:35045727 PMID:35524581

    Open questions at the time
    • MDM2 recognition determinants on ApoB unknown
    • Covalent disulfide maturation of Lp(a) downstream of the noncovalent complex not addressed here

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple ApoB degradation pathways (cytosolic proteasomal, luminal, LD-associated, gp78-, MDM2-, TM6SF2-dependent) are coordinated and selected for a given particle lipidation state remains unresolved.
  • No unifying model linking lipidation status to degradation route choice
  • Substrate recognition codes for the distinct E3 ligases undefined
  • In vivo hierarchy of these pathways in human liver unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0008289 lipid binding 3 GO:0140104 molecular carrier activity 2 GO:0048018 receptor ligand activity 1
Localization
GO:0005783 endoplasmic reticulum 5 GO:0005576 extracellular region 2 GO:0005768 endosome 1 GO:0005794 Golgi apparatus 1 GO:0005811 lipid droplet 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-1430728 Metabolism 3 R-HSA-382551 Transport of small molecules 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953854 Metabolism of RNA 3
Partners
AMFRERLIN1LDLRLIPCLPAMDM2MTTPTM6SF2
Complex memberships
ApoB-MTP complexLp(a) (apoB-apo(a) complex)TM6SF2-ERLIN1/2-APOB ER complexapoB mRNA editing complex (apobec-1/ACF)

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 ApoB-100 is a single protein of 4560 amino acids (513 kDa) encoded by a single gene; structural analysis predicted amphipathic alpha-helices and beta-sheets as lipid-binding domains, and identified a region (residues 3352-3369) with sequence homology to the LDL receptor-binding site of apoE, flanked by positively charged regions (3174-3681) proposed as the LDL receptor-binding domain. Full-length cDNA sequencing, S1 nuclease mapping of transcription start site, computer secondary structure analysis The EMBO journal High 3030729
1992 ApoB-100 is cotranslationally integrated into lipoproteins during translocation into the ER lumen; nascent apoB polypeptides are released from ribosomes (via puromycin) and found on lipoprotein particles whose density is inversely related to polypeptide length, establishing that lipoprotein assembly begins co-translationally. Pulse-chase with puromycin/cycloheximide treatment, sucrose gradient ultracentrifugation, electron microscopy, transfection of truncated apoB minigenes, sodium carbonate extraction The Journal of biological chemistry High 1315773
2003 MTP binds apoB with high affinity at multiple sites within the N-terminal betaalpha1 structural domain of apoB; this binding is mediated by ionic interactions, is modulated by lipids (lipids on MTP increase binding while lipids on apoB decrease it), and is functionally important for apoB secretion as demonstrated by site-directed mutagenesis, deletion analyses, and a specific antagonist (AGI-S17) that inhibits apoB-MTP binding without affecting MTP lipid transfer activity. Co-immunoprecipitation, site-directed mutagenesis, deletion analysis, antagonist (AGI-S17) inhibition, lipid modulation experiments Journal of lipid research High 10769147 12518019
1997 ApoB-100 undergoes post-translational degradation via two distinct pathways: (1) a cytosolic/proteasome-dependent pathway (ALLN-sensitive) that degrades partially translocated apoB at the cytosolic face of the ER membrane, and (2) an ER luminal pathway (ALLN-resistant, DTT-sensitive) that degrades fully translocated apoB; oleate facilitates translocation of apoB into the lumen, exposing it to the second pathway. Brefeldin A block of ER-to-Golgi transport, ALLN inhibition, DTT reduction, pulse-chase metabolic labeling, inhibitor combination studies in HepG2 cells The Journal of biological chemistry High 9111073
2003 Blocking MTP function (by Cre-mediated gene disruption or chemical inhibition) prevents apoB-100 secretion and causes rapid degradation of apoB without its accumulation in ER microsomes; MTP inhibition does not induce ER stress markers (GRP78, GRP94, HSPs), indicating the liver degrades secretion-incompetent apoB rapidly. Cre-mediated MTP gene knockout, chemical MTP inhibitor, plasma lipid measurements, Western blot of apoB in microsomes and chaperones, mouse studies Journal of lipid research High 12588952
2003 A naturally occurring nontruncating APOB mutation R463W causes familial hypobetalipoproteinemia by retaining apoB in the ER and reducing secretion efficiency by ~45%; the positive charge at position 463 is critical (Ala substitution reduces secretion; Lys substitution has no effect); the R463W mutant shows increased binding to MTP compared to wild-type, implicating this local domain in apoB-MTP interaction and lipoprotein assembly. Transfection of McA-RH7777 cells with recombinant apoB constructs, pulse-chase analysis, site-directed mutagenesis (Ala, Lys, Glu, Asp substitutions), co-transfection/binding assays with MTP, molecular modeling The Journal of biological chemistry High 12551903
2012 After lipidation in the ER lumen, apoB-100 can be dislocated to the cytoplasmic surface of lipid droplets (LDs) where it accumulates as ubiquitinated ApoB for proteasomal degradation; Derlin-1 mediates the pre-dislocation step (its abrogation causes lipidated apoB to accumulate in ER lumen without increasing ubiquitinated apoB on LDs), while UBXD8 (localized to LDs) mediates the post-dislocation step by recruiting p97 to LDs. siRNA knockdown of UBXD8 and Derlin-1 in Huh7 cells, immunoprecipitation, colocalization studies, ubiquitination assays, p97 recruitment assays Molecular biology of the cell High 22238364
2011 The E3 ubiquitin ligase gp78 ubiquitinates apoB-100, committing it to p97-mediated retrotranslocation and ERAD; siRNA knockdown of gp78 reduces apoB-100 ubiquitination and cytosolic apoB-ubiquitin conjugates, increases apoB-100 secretion, and unexpectedly enhances VLDL assembly. If p97 is knocked down simultaneously with gp78, cellular apoB returns toward baseline, confirming that ubiquitination precedes p97-mediated retrotranslocation. siRNA knockdown of gp78 and p97 in HepG2 cells, radiolabeling pulse-chase, ubiquitination assays, density gradient fractionation of secreted lipoproteins Journal of lipid research High 21421992
2020 TM6SF2 forms a complex with ERLIN1/2 and APOB in the ER; TM6SF2 binds and stabilizes APOB via two luminal loops; ERLINs stabilize TM6SF2 (and thereby indirectly stabilize APOB, without directly binding APOB); the NAFLD-associated E167K mutation destabilizes TM6SF2, reducing APOB protein levels; knockout of Tm6sf2 or knockdown of Erlins in mice decreases hepatic APOB protein and causes hepatic lipid accumulation. Tandem affinity purification coupled to mass spectrometry, co-immunoprecipitation, domain mapping (TM6SF2 luminal loop mutants), mouse Tm6sf2 knockout and Erlins knockdown, Western blot for APOB PLoS genetics High 32776921
2022 The E3 ubiquitin ligase MDM2 promotes proteasomal degradation of ApoB through direct protein-protein interaction; hepatocyte-specific deletion of MDM2 increases TG-VLDL secretion and protects against diet-induced hepatic steatosis; pharmacological blockage of the MDM2-ApoB interaction alleviates hepatic steatohepatitis and fibrosis; the effect of MDM2 on VLDL metabolism is p53-independent. Hepatocyte-specific MDM2 knockout mice, co-immunoprecipitation, pharmacological MDM2-ApoB interaction inhibitor, pulse-chase/ubiquitination assays, high-fat diet model Advanced science High 35524581
2016 The RNA-binding protein vigilin binds CU-rich regions in the Apob mRNA coding sequence and controls VLDL secretion by modulating ApoB translation; hepatic vigilin knockdown decreases VLDL/LDL levels and atherosclerotic plaque formation in Ldlr-/- mice. Crosslinking-based RNA-binding studies, in vivo vigilin knockdown (siRNA), VLDL/LDL quantification, atherosclerosis scoring in Ldlr-/- mice, genomic approaches Nature communications High 27665711
2001 LPS-binding protein (LBP) circulates in association with LDL and VLDL, and apoB accounts at least in part for LBP's interaction with these lipoproteins; LBP association with LDL/VLDL strongly enhances their capacity to bind LPS, providing a mechanism for lipoprotein-mediated LPS scavenging. Immunoprecipitation/affinity studies with purified LBP and apoB, in vitro LPS binding assays, serum fractionation from healthy persons and septic patients The Journal of clinical investigation Medium 11160139
1990 A 60-kDa transcriptional activator protein NF-BA1 binds the apoB promoter region (-79 to -63) and is essential for transcriptional activation of the apoB gene in hepatic and intestinal cells; purified NF-BA1 stimulates apoB transcription in in vitro complementation experiments and also binds regulatory regions of apoCIII, apoAII, and apoAI genes. Protein purification (Q-Sepharose, Bio-Rex 70, DNA affinity chromatography), in vitro transcription complementation, footprinting analysis, photoaffinity cross-linking The Journal of biological chemistry High 2254327
1992 Growth hormone (GH) regulates apoB mRNA editing in rat liver: hypophysectomy reduces the proportion of edited apoB mRNA (and thus apoB-48) from ~62% to ~29%, while GH replacement restores it to normal levels; GH regulates both editing of apoB mRNA and the proportion of apoB-48 synthesized and secreted. Hypophysectomy with hormone replacement (GH, T4, cortisol) in vivo, S1 nuclease/sequencing for mRNA editing measurement, metabolic labeling of hepatocytes, in vivo labeling experiments Endocrinology Medium 1597147
2010 p53 transcriptionally regulates apoB expression: p53 response elements were identified in the apoB and apobec1 genes; ChIP confirmed p53 binding; in vivo adriamycin (p53 inducer) treatment increased intestinal/liver apoB mRNA; irradiated wild-type but not p53-knockout mice showed elevated hepatic and intestinal apoB mRNA, establishing p53 as a direct transcriptional regulator of apoB. Luciferase reporter assays, chromatin immunoprecipitation (ChIP), RT-PCR in cancer cell lines, adriamycin and irradiation of C57bl/6 and p53-/- mice Cell cycle Medium 20890106
2006 ApoB mRNA editing is regulated by a coordinated modulation of multiple editing complex components: inhibitory components CUGBP2, GRY-RBP, and hnRNP-C1 suppress editing, while apobec-1 and ACF promote it; siRNA knockdown of CUGBP2, GRY-RBP, or hnRNP-C1 in Caco-2 cells increased editing, confirming their inhibitory function. siRNA knockdown of editing components in Caco-2 cells, quantitative RT-PCR for editing levels and component expression, developmental time-course in mouse fetal intestine American journal of physiology. Gastrointestinal and liver physiology Medium 16920700
1998 Hepatic lipase (HL) binds directly to apoB (including apoB-26, apoB-48, and apoB-100) but not to apoE or apoA-I, as shown by ligand blot and plate-binding assays; this HL-apoB interaction facilitates cellular uptake of LDL, as HL-enhanced LDL binding and uptake are significantly inhibited by anti-apoB monoclonal antibodies; the interaction differs from LPL in that both amino- and carboxyl-terminal apoB antibodies block HL binding equally. Ligand blot (HL binding to apoB), LDL-coated plate binding assay, 125I-LDL uptake in cell culture, anti-apoB monoclonal antibody inhibition, heparin-agarose binding assay with Kd determination The Journal of biological chemistry Medium 9685400
2011 Human resistin stimulates hepatic ApoB secretion up to 10-fold by increasing MTP activity and by reducing expression/phosphorylation of insulin signaling pathway proteins (IRS-2, Akt, ERK), thereby stabilizing ApoB; resistin also increases hepatocyte lipid content via SREBP1/SREBP2-dependent de novo lipogenesis; antibody immunoprecipitation removal of serum resistin from obese human serum reduces ApoB secretion. Human hepatocyte treatment with resistin, MTP activity assays, Western blot of insulin signaling proteins, SREBP pathway analysis, antibody immunoprecipitation of serum resistin, apoB secretion assays Circulation research Medium 21293001
2001 Naringenin and hesperetin decrease apoB secretion from HepG2 cells by (1) reducing ACAT1 and ACAT2 activities, (2) selectively decreasing ACAT2 mRNA expression, and (3) reducing MTP activity and expression; these effects reduce lipid availability for apoB-containing lipoprotein assembly. HepG2 cell apoB secretion assay, cholesterol esterification assay, ACAT1/ACAT2-transfected CHO cells (isoform selectivity), RT-PCR for ACAT2 mRNA, MTP activity assay, 125I-LDL uptake Journal of lipid research Medium 11352979
2012 ApoB negatively regulates angiogenesis by downregulating VEGFR1 (which acts as a decoy receptor for VEGF); genetic screen identified MTP mutation in zebrafish causing vascular defects, which was rescued by manipulating apoB levels; it is the ApoB protein particle (not lipid moieties) that mediates this effect on VEGFR1 and angiogenesis, and VEGFR1 downregulation was also observed in hyperlipidemic mice. Zebrafish forward genetic screen (mtp mutant), zebrafish lipoprotein concentration manipulation, zebrafish and mouse VEGFR1 expression analysis, particle vs. lipid dissection experiments Nature medicine Medium 22581286
1999 Myeloperoxidase (MPO) selectively oxidizes apoB-100 in LDL via HOCl generation; oxidation with MPO-H2O2-chloride system produces DNPH-reactive carbonyl modifications in specific apoB-100 tryptic peptides (including residues 53-66), with cysteinyl azo and methionine sulfoxide modifications identified; the modifications differ from those produced by reagent HOCl, suggesting direct LDL-MPO interaction at the enzyme active site. In vitro LDL oxidation with MPO, DNPH derivatization, tryptic peptide isolation by HPLC, mass spectrometric peptide characterization Journal of lipid research Medium 10191293
1994 ApoB-100 primary structure analysis identified 16 of 25 cysteine residues in disulfide form (all 14 N-terminal cysteines are disulfide-linked); two free sulfhydryl groups are at positions Cys3734 and Cys4190; trypsin susceptibility defines five structural domains; apoB-100 appears elongated and wraps around the LDL particle, with Cys3734 proposed as the cysteine linked to apo(a) in Lp(a). HPLC-based sulfhydryl/disulfide mapping, fluorescent sulfhydryl probe (iodoacetoamidofluorescein), trypsin domain mapping, protein sequencing combined with recombinant DNA Chemistry and physics of lipids Medium 8187250
2022 Apo(a) and apoB form noncovalent intracellular complexes within hepatocytes in the ER, trans-Golgi, and early endosomes (not lysosomes); this noncovalent interaction (mediated by apo(a) LBS7,8 sites) is required for apo(a) secretion; PCSK9 enhances apo(a) secretion in an interaction-dependent manner; lomitapide reduces apo(a) secretion dependently on the noncovalent interaction; apoB siRNA knockdown reduces apo(a) secretion. Co-immunoprecipitation, coimmunofluorescence, proximity ligation assay, pulse-chase metabolic labeling, apo(a) LBS7,8 deletion mutant, PCSK9 and lomitapide treatment, siRNA knockdown of APOB Arteriosclerosis, thrombosis, and vascular biology High 35045727
2015 Mutations in RAD21 that disrupt its transcriptional repressor function cause overexpression of APOB48 in patients with chronic intestinal pseudo-obstruction; wild-type RAD21 protein binds the APOB promoter and represses APOB expression in HEK293 cells, but the p.622 Ala>Thr mutant RAD21 fails to bind the APOB promoter. Mobility shift assay (APOB promoter binding), HEK293 cell transfection with wild-type vs. mutant RAD21, RT-PCR for APOB expression, serum APOB48 measurements in patients Gastroenterology Medium 25575569
2014 The LDLR repeat LR5 binds apoB-100 at two sites (site A and site B) and apoE at its receptor-binding region, at the hydrophilic convex face of LR5; these complexes are weakened at low Ca2+ and low pH, supporting a mechanism where endosomal conditions (low pH, low Ca2+) promote ligand dissociation from LDLR independent of beta-propeller displacement. NMR spectroscopy, surface plasmon resonance (SPR) with synthetic apoB peptides and LR5, pH and Ca2+ titration The FEBS journal High 24447298
2011 ApoB-100-containing lipoproteins are the major carriers of 3-iodothyronamine (T1AM) in human serum; apoB-100 was identified as the T1AM-binding protein by T1AM-affinity chromatography and sequence analysis; T1AM binds apoB-100-containing LDL particles with Kd ~17 nM and 1:1 stoichiometry; the binding site is highly selective for T1AM; apoB-100-containing particles enhance intracellular T1AM uptake. T1AM-affinity chromatography, protein sequence analysis, competitive binding assays with Kd determination, intracellular uptake assays, in vivo multidose T1AM treatment The Journal of biological chemistry Medium 22128163
2001 ApoB-100 secondary structure (alpha-helical content) is markedly decreased and its conformation is severely altered in electronegative LDL(-), as measured by circular dichroism; tryptophan fluorescence lifetime data indicate that oxidative modification causes apoB-100 to sink into the hydrophobic lipid core of LDL(-), possibly accounting for its reduced LDL receptor binding properties. Circular dichroism spectropolarimetry, tryptophan fluorescence lifetime measurements, Laurdan generalized polarization for lipid packing Free radical biology & medicine Medium 11425493
2011 HBV infection inhibits apoB production by suppressing MTP expression; HepG2.2.15 cells (HBV-expressing) show reduced apoB mRNA and protein vs. HepG2; HBV genomic clone transfection dose-dependently reduces MTP mRNA and protein, which in turn reduces apoB expression. RT-PCR and Western blot in HepG2 vs. HepG2.2.15 cells, transfection of HBV infectious clone pHBV1.3, dose-response analysis of MTP suppression Lipids in health and disease Low 22074108
1985 The human APOB-100 gene was localized to the p23-pter region of chromosome 2 by filter hybridization with apoB-100 cDNA probes and human-mouse somatic cell hybrids containing chromosome 2 translocations. Southern blot hybridization of human-mouse somatic cell hybrids containing chromosome 2 translocations with radiolabeled apoB-100 cDNA probes Biochemical and biophysical research communications Medium 3840371
1990 The delipidated apoB-apo(a) complex from Lp(a) is freely water-soluble at pH>6.4 (unlike delipidated apoB alone); apoB-apo(a) has amphipathic properties with apo(a) providing hydrophilic capacity and apoB providing hydrophobic lipid-binding interactions; the complex has avidity for triglyceride-rich lipoprotein particles, demonstrating that apoB's lipid-binding hydrophobic domains are accessible when freed from lipids. Delipidation of Lp(a), solubility assays, sandwich ELISA with apo(a)- and apoB-specific antibodies, interaction with Intralipid emulsion, lipoprotein binding experiments Journal of lipid research Medium 2143212

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly. Journal of lipid research 466 12518019
1978 Metabolsim of apoB and apoC lipoproteins in man: kinetic studies in normal and hyperlipoproteininemic subjects. Journal of lipid research 218 202659
1986 The complete sequence and structural analysis of human apolipoprotein B-100: relationship between apoB-100 and apoB-48 forms. The EMBO journal 213 3030729
2004 Lipid disorders and mutations in the APOB gene. Clinical chemistry 168 15308601
2013 New therapies targeting apoB metabolism for high-risk patients with inherited dyslipidaemias: what can the clinician expect? Cardiovascular drugs and therapy 161 23913122
2001 Secretion of hepatocyte apoB is inhibited by the flavonoids, naringenin and hesperetin, via reduced activity and expression of ACAT2 and MTP. Journal of lipid research 149 11352979
2013 The regulation of ApoB metabolism by insulin. Trends in endocrinology and metabolism: TEM 134 23721961
1992 The assembly and secretion of ApoB 100-containing lipoproteins in Hep G2 cells. ApoB 100 is cotranslationally integrated into lipoproteins. The Journal of biological chemistry 130 1315773
2001 LPS-binding protein circulates in association with apoB-containing lipoproteins and enhances endotoxin-LDL/VLDL interaction. The Journal of clinical investigation 124 11160139
2018 Lipid transfer proteins in the assembly of apoB-containing lipoproteins. Journal of lipid research 118 29650752
2011 MMP-2 and MMP-9 are prominent matrix metalloproteinases during atherosclerosis development in the Ldlr(-/-)Apob(100/100) mouse. International journal of molecular medicine 109 21567073
2012 ApoB-containing lipoproteins regulate angiogenesis by modulating expression of VEGF receptor 1. Nature medicine 100 22581286
2012 Derlin-1 and UBXD8 are engaged in dislocation and degradation of lipidated ApoB-100 at lipid droplets. Molecular biology of the cell 95 22238364
2007 Hypercholesterolemia increases myocardial oxidative and nitrosative stress thereby leading to cardiac dysfunction in apoB-100 transgenic mice. Cardiovascular research 90 17658498
2003 Blocking microsomal triglyceride transfer protein interferes with apoB secretion without causing retention or stress in the ER. Journal of lipid research 89 12588952
1997 A two-site model for ApoB degradation in HepG2 cells. The Journal of biological chemistry 82 9111073
2013 Atheroprotective Vaccination with MHC-II Restricted Peptides from ApoB-100. Frontiers in immunology 75 24416033
2003 A novel nontruncating APOB gene mutation, R463W, causes familial hypobetalipoproteinemia. The Journal of biological chemistry 72 12551903
2003 Effects of atorvastatin versus fenofibrate on apoB-100 and apoA-I kinetics in mixed hyperlipidemia. Journal of lipid research 72 14523053
2012 Prevalence of ANGPTL3 and APOB gene mutations in subjects with combined hypolipidemia. Arteriosclerosis, thrombosis, and vascular biology 68 22247256
2015 Mutations in RAD21 disrupt regulation of APOB in patients with chronic intestinal pseudo-obstruction. Gastroenterology 67 25575569
2015 Anacetrapib lowers LDL by increasing ApoB clearance in mildly hypercholesterolemic subjects. The Journal of clinical investigation 66 25961461
1995 Exencephaly and hydrocephaly in mice with targeted modification of the apolipoprotein B (Apob) gene. Teratology 65 7597652
2013 Novel functional APOB mutations outside LDL-binding region causing familial hypercholesterolaemia. Human molecular genetics 63 24234650
2001 Loss of apoB-100 secondary structure and conformation in hydroperoxide rich, electronegative LDL(-). Free radical biology & medicine 61 11425493
1999 Selective modification of apoB-100 in the oxidation of low density lipoproteins by myeloperoxidase in vitro. Journal of lipid research 61 10191293
2014 Impact of myeloperoxidase-LDL interactions on enzyme activity and subsequent posttranslational oxidative modifications of apoB-100. Journal of lipid research 60 24534704
1992 Effects of growth hormone on apolipoprotein-B (apoB) messenger ribonucleic acid editing, and apoB 48 and apoB 100 synthesis and secretion in the rat liver. Endocrinology 57 1597147
2017 The impact of APOA5, APOB, APOC3 and ABCA1 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis. Atherosclerosis 55 28865324
1994 ApoB-100 gene EcoRI polymorphism. Relations to plasma lipoprotein changes associated with abdominal visceral obesity. Arteriosclerosis and thrombosis : a journal of vascular biology 55 7908536
2000 Decreased secretion of ApoB follows inhibition of ApoB-MTP binding by a novel antagonist. Biochemistry 53 10769147
2003 PPAR(alpha) and PPAR(gamma) activators suppress the monocyte-macrophage apoB-48 receptor. Journal of lipid research 52 12700342
1999 Decreased production rates of VLDL triglycerides and ApoB-100 in subjects heterozygous for familial hypobetalipoproteinemia. Arteriosclerosis, thrombosis, and vascular biology 52 10559016
2020 Disruption of the ERLIN-TM6SF2-APOB complex destabilizes APOB and contributes to non-alcoholic fatty liver disease. PLoS genetics 51 32776921
1997 Oxidative modifications of apoB-100 by exposure of low density lipoproteins to HOCL in vitro. Free radical biology & medicine 50 9165300
2018 Clinical significance of APOB inactivation in hepatocellular carcinoma. Experimental & molecular medicine 49 30429453
2011 Human resistin stimulates hepatic overproduction of atherogenic ApoB-containing lipoprotein particles by enhancing ApoB stability and impairing intracellular insulin signaling. Circulation research 45 21293001
2016 The RNA-binding protein vigilin regulates VLDL secretion through modulation of Apob mRNA translation. Nature communications 44 27665711
1990 Solubility, immunochemical, and lipoprotein binding properties of apoB-100-apo[a], the protein moiety of lipoprotein[a]. Journal of lipid research 44 2143212
1997 Estimation of the age of the ancestral arginine3500-->glutamine mutation in human apoB-100. Genomics 43 9339363
2022 Hepatic MDM2 Causes Metabolic Associated Fatty Liver Disease by Blocking Triglyceride-VLDL Secretion via ApoB Degradation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 41 35524581
2011 Antisense oligonucleotide reduction of apoB-ameliorated atherosclerosis in LDL receptor-deficient mice. Journal of lipid research 39 21343632
1987 The chromogenicity and quantitation of apoB-100 and apoB-48 of human plasma lipoproteins on analytical SDS gel electrophoresis. Atherosclerosis 39 3606734
2013 Impact of ApoB-100 expression on cognition and brain pathology in wild-type and hAPPsl mice. Neurobiology of aging 36 23643485
2022 Immunization using ApoB-100 peptide-linked nanoparticles reduces atherosclerosis. JCI insight 35 35536648
2004 A new but frequent mutation of apoB-100-apoB His3543Tyr. Atherosclerosis 35 15135245
2004 LDL phospholipid hydrolysis produces modified electronegative particles with an unfolded apoB-100 protein. Journal of lipid research 35 15489541
1994 ApoB metabolism in familial hypercholesterolemia. Inconsistencies with the LDL receptor paradigm. Arteriosclerosis and thrombosis : a journal of vascular biology 35 8148348
2011 Ubiquitination regulates the assembly of VLDL in HepG2 cells and is the committing step of the apoB-100 ERAD pathway. Journal of lipid research 34 21421992
2011 ApoB-100-containing lipoproteins are major carriers of 3-iodothyronamine in circulation. The Journal of biological chemistry 33 22128163
2021 The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia. Genes 32 33418990
1998 Genetic heterogeneity in familial hypobetalipoproteinemia: linkage and non-linkage to the apoB gene in Caucasian families. American journal of medical genetics 32 9508071
1991 The molecular mechanism for the assembly and secretion of ApoB-100-containing lipoproteins. Progress in lipid research 31 1823939
1990 Purification and characterization of the nuclear factor BA1. A transcriptional activator of the human apoB gene. The Journal of biological chemistry 31 2254327
1985 Human ApoB-100 gene resides in the p23----pter region of chromosome 2. Biochemical and biophysical research communications 31 3840371
2021 ApoB-Specific CD4+ T Cells in Mouse and Human Atherosclerosis. Cells 30 33669769
2014 LDL receptor/lipoprotein recognition: endosomal weakening of ApoB and ApoE binding to the convex face of the LR5 repeat. The FEBS journal 30 24447298
2019 ApoB, small-dense LDL-C, Lp(a), LpPLA2 activity, and cognitive change. Neurology 29 31043469
2017 Identification of apoB-100 Peptide-Specific CD8+ T Cells in Atherosclerosis. Journal of the American Heart Association 29 28711866
2010 apoB and apobec1, two genes key to lipid metabolism, are transcriptionally regulated by p53. Cell cycle (Georgetown, Tex.) 29 20890106
2009 Splicing therapeutics in SMN2 and APOB. Current opinion in molecular therapeutics 29 19330716
1989 Metabolic behavior of hepatic VLDL and plasma LDL apoB-100 in African green monkeys. Journal of lipid research 29 2723543
2015 ApoB-100-related peptide vaccine protects against angiotensin II-induced aortic aneurysm formation and rupture. Journal of the American College of Cardiology 28 25677313
2008 Kupffer cell products and interleukin 1beta directly promote VLDL secretion and apoB mRNA up-regulation in rodent hepatocytes. Innate immunity 28 18669611
1988 Intracellular apoA-I and apoB distribution in rat intestine is altered by lipid feeding. Journal of lipid research 28 3141543
2017 Associations of the APOB rs693 and rs17240441 polymorphisms with plasma APOB and lipid levels: a meta-analysis. Lipids in health and disease 27 28874158
2006 ApoB mRNA editing is mediated by a coordinated modulation of multiple apoB mRNA editing enzyme components. American journal of physiology. Gastrointestinal and liver physiology 27 16920700
1999 Known mutations of apoB account for only a small minority of hypobetalipoproteinemia. Journal of lipid research 27 10224165
1993 Metabolism of apoB-100-containing lipoproteins in familial hyperchylomicronemia. Journal of lipid research 27 8445339
2018 Directional ABCA1-mediated cholesterol efflux and apoB-lipoprotein secretion in the retinal pigment epithelium. Journal of lipid research 26 30076206
2012 Increased tau phosphorylation and impaired presynaptic function in hypertriglyceridemic ApoB-100 transgenic mice. PloS one 26 23029362
2013 Immune responses elicited by apoB-100-derived peptides in mice. Immunologic research 25 23345063
2002 Platelet activation by the apoB/E receptor-binding domain of LDL. Thrombosis and haemostasis 25 12038793
2018 Increased Calcific Aortic Valve Disease in response to a diabetogenic, procalcific diet in the LDLr-/-ApoB100/100 mouse model. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 24 29539583
2018 Further evidence of novel APOB mutations as a cause of familial hypercholesterolaemia. Atherosclerosis 22 30270084
2022 Apo(a) and ApoB Interact Noncovalently Within Hepatocytes: Implications for Regulation of Lp(a) Levels by Modulation of ApoB Secretion. Arteriosclerosis, thrombosis, and vascular biology 21 35045727
2016 LDLR, ApoB and ApoE genes polymorphisms and classical risk factors in premature coronary artery disease. Gene 21 27236033
2014 The apoB/apoA1 ratio predicts future cardiovascular events in patients with rheumatoid arthritis. Scandinavian journal of rheumatology 20 24689997
2011 Mutational analysis of the LDL receptor and APOB genes in Mexican individuals with autosomal dominant hypercholesterolemia. Atherosclerosis 20 21722902
1998 Secretion of apoB- and apoA-I-containing lipoproteins by chick kidney. Journal of lipid research 20 9555939
2020 Dietary sucrose induces metabolic inflammation and atherosclerotic cardiovascular diseases more than dietary fat in LDLr-/-ApoB100/100 mice. Atherosclerosis 19 32563005
2018 Cerebrovascular Pathology in Hypertriglyceridemic APOB-100 Transgenic Mice. Frontiers in cellular neuroscience 19 30410436
2018 A serum protein factor mediates maturation and apoB-association of HCV particles in the extracellular milieu. Journal of hepatology 19 30553840
2012 The relationship between high-sensitivity C-reactive protein and ApoB, ApoB/ApoA1 ratio in general population of China. Endocrine 19 22246850
2011 HBV inhibits apoB production via the suppression of MTP expression. Lipids in health and disease 19 22074108
1994 Primary structure of apoB-100. Chemistry and physics of lipids 19 8187250
2017 Association between polymorphisms in the APOB gene and hyperlipidemia in the Chinese Yugur population. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 18 28902930
2010 ApoB-100, ApoE and CYP7A1 gene polymorphisms in Mexican patients with cholesterol gallstone disease. World journal of gastroenterology 18 20872969
2008 Variable phenotypic expression of homozygous familial hypobetalipoproteinaemia due to novel APOB gene mutations. Clinical genetics 18 18492086
1987 The human apoB-100 gene: apoB-100 is encoded by a single copy gene in the human genome. Biochemical and biophysical research communications 18 3034278
2017 Effects of atorvastatin and diet interventions on atherosclerotic plaque inflammation and [18F]FDG uptake in Ldlr-/-Apob100/100 mice. Atherosclerosis 17 28457625
2017 MicroRNA-101-2-5p targets the ApoB gene in the liver of chicken (Gallus Gallus). Genome 17 28636837
2015 Relationship of the APOA5/A4/C3/A1 gene cluster and APOB gene polymorphisms with dyslipidemia. Genetics and molecular research : GMR 17 26345861
2003 Four novel mutations in APOB causing heterozygous and homozygous familial hypobetalipoproteinemia. Human mutation 17 12872264
1998 Interaction between ApoB and hepatic lipase mediates the uptake of ApoB-containing lipoproteins. The Journal of biological chemistry 17 9685400
2024 Rare Genetic Variants in LDLR, APOB, and PCSK9 Are Associated With Aortic Stenosis. Circulation 16 39222019
1994 Cotranslational inhibition of apoB-100 synthesis by cyclosporin A in the human hepatoma cell line HepG2. Arteriosclerosis and thrombosis : a journal of vascular biology 16 8172854
2013 Roles of ApoB-100 gene polymorphisms and the risks of gallstones and gallbladder cancer: a meta-analysis. PloS one 15 23637837
2002 Novel mutations of APOB cause ApoB truncations undetectable in plasma and familial hypobetalipoproteinemia. Human mutation 15 12124991
2022 Meta-GWAS of PCSK9 levels detects two novel loci at APOB and TM6SF2. Human molecular genetics 14 34590679

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