Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9EUZX3)

DOT Name Apolipoprotein B receptor (APOBR)
Synonyms Apolipoprotein B-100 receptor; Apolipoprotein B-48 receptor; Apolipoprotein B48 receptor; apoB-48R
Gene Name APOBR
Related Disease
Arteriosclerosis ( )
Atherosclerosis ( )
Hypothyroidism ( )
Asthma ( )
UniProt ID
APOBR_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MDFLRLYLPGLHQALRGALDSLGTFVSYLLGDAVPTVEREAQAAEELGVVAVGKTGKIVE
EEAQEDLEGLRGSQNEGAGRLRGPGDDRRHEVGSSAVEQTWGWGDGSSHGSQAERQDSGA
GETAKAARCQEPSAHLEARKKSKAGSGACQDRSGQAQERQESHEQEVNREERLRSWEQEE
EEEEVRAREPGMARGAESEWTWHGETEGKAGAVGPKAAGDNREMEQGVREADAGETEEPG
AEGAGKGEEVVVVEKACESTRAWGTWGPGAEPEDWGILGREEARTTPGREEARAILDGEE
ARTISGGEEAETASGGEEAETASGGEEAGTASGGEEAGIASGGEAGTASGGEEAGTASGG
EEAGTASGGDEAWTTSGKEEADLLGVRQTEYGAVPGERLLEATGKVWVLEEEGDEEREAE
VSPFPKQPQVLGTERTEEAAESQTAGREAVGGQEAGESFEGQVDLRGKEAEMRQDLGIRA
DRARMEELVQAEEAQEERGSSRDPVAELPSDGEAEGTADLEATPEARPEEELTGEESEAA
QTSCGLLGVEWGGLTHSVTKGQGPELMGGAQTPTKQPEEREAGEVELMGVLALSKEEQER
SLEAGPRHAGSVKPEASEAFPGAWENRTRKDMERGNTQEDAADGEQREEEETAGGQTLAA
EAEGDRESELSEVPEAGGEGLTTQDAGCGTEEGEASVSENQELDGSTGADAGPCPSLGEA
YARETEDEEAEADRTSRRGWRLQAVAVGLPDREDAQTGSVAAGIMGGDVVPHISAAGAGE
ALEGVLGQGWDSKEKEEAAAGEHAGGQEFGLEGSAEEEVTGRGSQVEAFESREGGPWGGR
VEAEESAGAEDSCGLDPAGSQTARAEGMGAMVEAGGLLEKWTLLEEEAVGWQEREQREDS
EGRCGDYHPEGEAPRLLDAEGLMVTGGRRAEAKETEPESLEHVRGQEEQPTHQAPAEAAP
ESVGEAETAEAMGSARGGAANSWSEAPLPGSLLDVSVPRSRVHLSRSSSQRRSRPSFRRT
PAWEQQEEPPAPNPPEEELSAPEQRPLQLEEPLEPSPLRHDGTPVPARRRPLGHGFGLAH
PGMMQELQARLGRPKPQ
Function
Macrophage receptor that binds to the apolipoprotein B48 (APOB) of dietary triglyceride (TG)-rich lipoproteins (TRL) or to a like domain of APOB in hypertriglyceridemic very low density lipoprotein (HTG-VLDL). Binds and internalizes TRL when out of the context of the macrophage. May provide essential lipids to reticuloendothelial cells. Could also be involved in foam cell formation with elevated TRL and remnant lipoprotein (RLP). Mediates the rapid high-affinity uptake of chylomicrons (CM), HTG-VLDL, and trypsinized (tryp) VLDL devoid of APOE in vitro in macrophages.
Tissue Specificity
Expressed in peripheral blood leukocytes > bone marrow = spleen > lymph node, and only faintly visible in appendix and thymus. Expressed in the brain, heart, kidney, liver, lung, pancreas, and placenta. Expressed primarily by reticuloendothelial cells: monocytes, macrophages, and endothelial cells. Expressed in atherosclerotic lesion foam cells.
Reactome Pathway
VLDL clearance (R-HSA-8964046 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Arteriosclerosis DISK5QGC Strong Biomarker [1]
Atherosclerosis DISMN9J3 Strong Biomarker [1]
Hypothyroidism DISR0H6D Strong Biomarker [2]
Asthma DISW9QNS Limited Biomarker [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Apolipoprotein B receptor (APOBR). [4]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Apolipoprotein B receptor (APOBR). [5]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Apolipoprotein B receptor (APOBR). [6]
Bortezomib DMNO38U Approved Bortezomib decreases the expression of Apolipoprotein B receptor (APOBR). [7]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Apolipoprotein B receptor (APOBR). [8]
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References

1 Pitavastatin inhibits remnant lipoprotein-induced macrophage foam cell formation through ApoB48 receptor-dependent mechanism.Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):424-9. doi: 10.1161/01.ATV.0000152632.48937.2d. Epub 2004 Dec 9.
2 A family with hypothyroidism caused by fatty acid synthase and apolipoprotein B receptor mutations.Mol Med Rep. 2018 Dec;18(6):4904-4912. doi: 10.3892/mmr.2018.9499. Epub 2018 Sep 20.
3 A common 16p11.2 inversion underlies the joint susceptibility to asthma and obesity.Am J Hum Genet. 2014 Mar 6;94(3):361-72. doi: 10.1016/j.ajhg.2014.01.015. Epub 2014 Feb 20.
4 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
5 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
6 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
7 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
8 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.