Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBI1RZ6)

• DOT Name: Adipocyte enhancer-binding protein 1 (AEBP1)
• Synonyms: AE-binding protein 1; Aortic carboxypeptidase-like protein
• Gene Name: AEBP1
• Related Disease:
  Abdominal aortic aneurysm
  Adult glioblastoma
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Childhood acute lymphoblastic leukemia
  Colorectal carcinoma
  Ehlers-Danlos syndrome
  Ehlers-Danlos syndrome, classic-like, 2
  Glioblastoma multiforme
  Glioma
  Neoplasm
  Non-alcoholic fatty liver disease
  Osteoporosis
  Pulmonary fibrosis
  Melanoma
  Advanced cancer
  Carpal tunnel syndrome
  Chronic obstructive pulmonary disease
  Colon adenocarcinoma
  Connective tissue disorder
  Gastric cancer
  Metastatic malignant neoplasm
  Non-alcoholic steatohepatitis
  Stomach cancer
• UniProt ID: AEBP1_HUMAN
• Pfam ID: PF13620 ; PF00754 ; PF00246
• Sequence:
  MAAVRGAPLLSCLLALLALCPGGRPQTVLTDDEIEEFLEGFLSELEPEPREDDVEAPPPP
  EPTPRVRKAQAGGKPGKRPGTAAEVPPEKTKDKGKKGKKDKGPKVPKESLEGSPRPPKKG
  KEKPPKATKKPKEKPPKATKKPKEKPPKATKKPKEKPPKATKKPPSGKRPPILAPSETLE
  WPLPPPPSPGPEELPQEGGAPLSNNWQNPGEETHVEAREHQPEPEEETEQPTLDYNDQIE
  REDYEDFEYIRRQKQPRPPPSRRRRPERVWPEPPEEKAPAPAPEERIEPPVKPLLPPLPP
  DYGDGYVIPNYDDMDYYFGPPPPQKPDAERQTDEEKEELKKPKKEDSSPKEETDKWAVEK
  GKDHKEPRKGEELEEEWTPTEKVKCPPIGMESHRIEDNQIRASSMLRHGLGAQRGRLNMQ
  TGATEDDYYDGAWCAEDDARTQWIEVDTRRTTRFTGVITQGRDSSIHDDFVTTFFVGFSN
  DSQTWVMYTNGYEEMTFHGNVDKDTPVLSELPEPVVARFIRIYPLTWNGSLCMRLEVLGC
  SVAPVYSYYAQNEVVATDDLDFRHHSYKDMRQLMKVVNEECPTITRTYSLGKSSRGLKIY
  AMEISDNPGEHELGEPEFRYTAGIHGNEVLGRELLLLLMQYLCREYRDGNPRVRSLVQDT
  RIHLVPSLNPDGYEVAAQMGSEFGNWALGLWTEEGFDIFEDFPDLNSVLWGAEERKWVPY
  RVPNNNLPIPERYLSPDATVSTEVRAIIAWMEKNPFVLGANLNGGERLVSYPYDMARTPT
  QEQLLAAAMAAARGEDEDEVSEAQETPDHAIFRWLAISFASAHLTLTEPYRGGCQAQDYT
  GGMGIVNGAKWNPRTGTINDFSYLHTNCLELSFYLGCDKFPHESELPREWENNKEALLTF
  MEQVHRGIKGVVTDEQGIPIANATISVSGINHGVKTASGGDYWRILNPGEYRVTAHAEGY
  TPSAKTCNVDYDIGATQCNFILARSNWKRIREIMAMNGNRPIPHIDPSRPMTPQQRRLQQ
  RRLQHRLRLRAQMRLRRLNATTTLGPHTVPPTLPPAPATTLSTTIEPWGLIPPTTAGWEE
  SETETYTEVVTEFGTEVEPEFGTKVEPEFETQLEPEFETQLEPEFEEEEEEEKEEEIATG
  QAFPFTTVETYTVNFGDF
• Function: [Isoform 1]: As a positive regulator of collagen fibrillogenesis, it is probably involved in the organization and remodeling of the extracellular matrix; [Isoform 2]: May positively regulate MAP-kinase activity in adipocytes, leading to enhanced adipocyte proliferation and reduced adipocyte differentiation. May also positively regulate NF-kappa-B activity in macrophages by promoting the phosphorylation and subsequent degradation of I-kappa-B-alpha (NFKBIA), leading to enhanced macrophage inflammatory responsiveness. Can act as a transcriptional repressor.
• Tissue Specificity: Expressed in osteoblast and visceral fat.

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Abdominal aortic aneurysm	DISD06OF	Strong	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[6]
Ehlers-Danlos syndrome	DISSVBRR	Strong	Biomarker	[7]
Ehlers-Danlos syndrome, classic-like, 2	DISAVQ0W	Strong	Autosomal recessive	[8]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[6]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[9]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[7]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[10]
Melanoma	DIS1RRCY	moderate	Altered Expression	[11]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[12]
Carpal tunnel syndrome	DISHQ3BE	Limited	Genetic Variation	[13]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Biomarker	[14]
Colon adenocarcinoma	DISDRE0J	Limited	Biomarker	[14]
Connective tissue disorder	DISKXBS3	Limited	Biomarker	[15]
Gastric cancer	DISXGOUK	Limited	Biomarker	[12]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[12]
Non-alcoholic steatohepatitis	DIST4788	Limited	Biomarker	[16]
Stomach cancer	DISKIJSX	Limited	Biomarker	[12]

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Adipocyte enhancer-binding protein 1 (AEBP1).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Adipocyte enhancer-binding protein 1 (AEBP1).	[18]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Adipocyte enhancer-binding protein 1 (AEBP1).	[19]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Adipocyte enhancer-binding protein 1 (AEBP1).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Adipocyte enhancer-binding protein 1 (AEBP1).	[22]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Adipocyte enhancer-binding protein 1 (AEBP1).	[21]

References

• [1] AEBP1 Promotes the Occurrence and Development of Abdominal Aortic Aneurysm by Modulating Inflammation via the NF-B Pathway.J Atheroscler Thromb. 2020 Mar 1;27(3):255-270. doi: 10.5551/jat.49106. Epub 2019 Aug 28.
• [2] AEBP1 down regulation induced cell death pathway depends on PTEN status of glioma cells.Sci Rep. 2019 Oct 10;9(1):14577. doi: 10.1038/s41598-019-51068-1.
• [3] Association of AEBP1 and NRN1 RNA expression with Alzheimer's disease and neurofibrillary tangle density in middle temporal gyrus.Brain Res. 2019 Sep 15;1719:217-224. doi: 10.1016/j.brainres.2019.06.004. Epub 2019 Jun 6.
• [4] Proteome Profiling Outperforms Transcriptome Profiling for Coexpression Based Gene Function Prediction.Mol Cell Proteomics. 2017 Jan;16(1):121-134. doi: 10.1074/mcp.M116.060301. Epub 2016 Nov 11.
• [5] Attenuating the abnormally high expression of AEBP1 suppresses the pathogenesis of childhood acute lymphoblastic leukemia via p53-dependent signaling pathway.Eur Rev Med Pharmacol Sci. 2019 Feb;23(3):1184-1195. doi: 10.26355/eurrev_201902_17011.
• [6] MicroRNA 214 inhibits adipocyte enhancer-binding protein 1 activity and increases the sensitivity of chemotherapy in colorectal cancer.Oncol Lett. 2019 Jan;17(1):55-62. doi: 10.3892/ol.2018.9623. Epub 2018 Oct 26.
• [7] Bi-allelic AEBP1 mutations in two patients with Ehlers-Danlos syndrome.Hum Mol Genet. 2019 Jun 1;28(11):1853-1864. doi: 10.1093/hmg/ddz024.
• [8] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [9] Potential Regulators Driving the Transition in Nonalcoholic Fatty Liver Disease: a Stage-Based View.Cell Physiol Biochem. 2017;41(1):239-251. doi: 10.1159/000456061. Epub 2017 Jan 30.
• [10] Aortic carboxypeptidase-like protein is expressed in fibrotic human lung and its absence protects against bleomycin-induced lung fibrosis.Am J Pathol. 2009 Mar;174(3):818-28. doi: 10.2353/ajpath.2009.080856. Epub 2009 Jan 29.
• [11] AEBP1 upregulation confers acquired resistance to BRAF (V600E) inhibition in melanoma.Cell Death Dis. 2013 Nov 7;4(11):e914. doi: 10.1038/cddis.2013.441.
• [12] AEBP1 promotes epithelial-mesenchymal transition of gastric cancer cells by activating the NF-B pathway and predicts poor outcome of the patients.Sci Rep. 2018 Aug 10;8(1):11955. doi: 10.1038/s41598-018-29878-6.
• [13] A genome-wide association analysis identifies 16 novel susceptibility loci for carpal tunnel syndrome.Nat Commun. 2019 Mar 4;10(1):1030. doi: 10.1038/s41467-019-08993-6.
• [14] AEBP1, a prognostic indicator, promotes colon adenocarcinoma cell growth and metastasis through the NF-B pathway.Mol Carcinog. 2019 Oct;58(10):1795-1808. doi: 10.1002/mc.23066. Epub 2019 Jun 10.
• [15] A biallelic truncating AEBP1 variant causes connective tissue disorder in two siblings.Am J Med Genet A. 2019 Jan;179(1):50-56. doi: 10.1002/ajmg.a.60679. Epub 2018 Dec 11.
• [16] Aortic carboxypeptidase-like protein, a WNT ligand, exacerbates nonalcoholic steatohepatitis.J Clin Invest. 2018 Apr 2;128(4):1581-1596. doi: 10.1172/JCI92863. Epub 2018 Mar 19.
• [17] 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.
• [18] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [19] Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 2006 Dec 1;66(23):11187-93. doi: 10.1158/0008-5472.CAN-06-1274.
• [20] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [21] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [22] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.