Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTME98V7)

• DOT Name: Latent-transforming growth factor beta-binding protein 3 (LTBP3)
• Synonyms: LTBP-3
• Gene Name: LTBP3
• Related Disease:
  Brachyolmia-amelogenesis imperfecta syndrome
  Breast cancer
  Breast carcinoma
  Amelogenesis imperfecta
  Anxiety
  Anxiety disorder
  Autoimmune disease
  Bone disease
  Brachyolmia
  Cardiac disease
  Cardiac failure
  Cervical cancer
  Cervical carcinoma
  Colon cancer
  Colon carcinoma
  Congestive heart failure
  Depression
  Epilepsy
  Esophageal squamous cell carcinoma
  Geleophysic dysplasia 3
  Glaucoma/ocular hypertension
  Head and neck cancer
  Head and neck carcinoma
  Hepatocellular carcinoma
  Major depressive disorder
  Melanoma
  Mental disorder
  Mitral valve prolapse
  Mood disorder
  Neoplasm
  Obsessive compulsive disorder
  Obstructive sleep apnea
  Osteoarthritis
  Plasma cell myeloma
  Post-traumatic stress disorder
  Advanced cancer
  Carcinoma
  Nasopharyngeal carcinoma
  Nervous system disease
  Obesity
  Squamous cell carcinoma
  Tooth agenesis
  Tooth agenesis, selective, 1
  Acromicric dysplasia
  Geleophysic dysplasia
  Malignant mesothelioma
  Mesothelioma
• UniProt ID: LTBP3_HUMAN
• Pfam ID: PF12662 ; PF07645 ; PF12661 ; PF00683
• Sequence:
  MPGPRGAAGGLAPEMRGAGAAGLLALLLLLLLLLLGLGGRVEGGPAGERGAGGGGALARE
  RFKVVFAPVICKRTCLKGQCRDSCQQGSNMTLIGENGHSTDTLTGSGFRVVVCPLPCMNG
  GQCSSRNQCLCPPDFTGRFCQVPAGGAGGGTGGSGPGLSRTGALSTGALPPLAPEGDSVA
  SKHAIYAVQVIADPPGPGEGPPAQHAAFLVPLGPGQISAEVQAPPPVVNVRVHHPPEASV
  QVHRIESSNAESAAPSQHLLPHPKPSHPRPPTQKPLGRCFQDTLPKQPCGSNPLPGLTKQ
  EDCCGSIGTAWGQSKCHKCPQLQYTGVQKPGPVRGEVGADCPQGYKRLNSTHCQDINECA
  MPGVCRHGDCLNNPGSYRCVCPPGHSLGPSRTQCIADKPEEKSLCFRLVSPEHQCQHPLT
  TRLTRQLCCCSVGKAWGARCQRCPTDGTAAFKEICPAGKGYHILTSHQTLTIQGESDFSL
  FLHPDGPPKPQQLPESPSQAPPPEDTEEERGVTTDSPVSEERSVQQSHPTATTTPARPYP
  ELISRPSPPTMRWFLPDLPPSRSAVEIAPTQVTETDECRLNQNICGHGECVPGPPDYSCH
  CNPGYRSHPQHRYCVDVNECEAEPCGPGRGICMNTGGSYNCHCNRGYRLHVGAGGRSCVD
  LNECAKPHLCGDGGFCINFPGHYKCNCYPGYRLKASRPPVCEDIDECRDPSSCPDGKCEN
  KPGSFKCIACQPGYRSQGGGACRDVNECAEGSPCSPGWCENLPGSFRCTCAQGYAPAPDG
  RSCLDVDECEAGDVCDNGICSNTPGSFQCQCLSGYHLSRDRSHCEDIDECDFPAACIGGD
  CINTNGSYRCLCPQGHRLVGGRKCQDIDECSQDPSLCLPHGACKNLQGSYVCVCDEGFTP
  TQDQHGCEEVEQPHHKKECYLNFDDTVFCDSVLATNVTQQECCCSLGAGWGDHCEIYPCP
  VYSSAEFHSLCPDGKGYTQDNNIVNYGIPAHRDIDECMLFGSEICKEGKCVNTQPGYECY
  CKQGFYYDGNLLECVDVDECLDESNCRNGVCENTRGGYRCACTPPAEYSPAQRQCLSPEE
  MDVDECQDPAACRPGRCVNLPGSYRCECRPPWVPGPSGRDCQLPESPAERAPERRDVCWS
  QRGEDGMCAGPLAGPALTFDDCCCRQGRGWGAQCRPCPPRGAGSHCPTSQSESNSFWDTS
  PLLLGKPPRDEDSSEEDSDECRCVSGRCVPRPGGAVCECPGGFQLDASRARCVDIDECRE
  LNQRGLLCKSERCVNTSGSFRCVCKAGFARSRPHGACVPQRRR
• Function: Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space. Associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGF-beta, and regulates integrin-dependent activation of TGF-beta.
• Tissue Specificity: Isoform 2: Expressed prominently in heart, skeletal muscle, prostate, testis, small intestine and ovary . Isoform 1: Strongly expressed in pancreas and liver .
• Reactome Pathway:
  TGF-beta receptor signaling activates SMADs (R-HSA-2173789)
  Molecules associated with elastic fibres (R-HSA-2129379)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Brachyolmia-amelogenesis imperfecta syndrome	DISTPSZ0	Definitive	Autosomal recessive	[1]
Breast cancer	DIS7DPX1	Definitive	Biomarker	[2]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[2]
Amelogenesis imperfecta	DISGYR9E	Strong	Genetic Variation	[3]
Anxiety	DISIJDBA	Strong	Genetic Variation	[4]
Anxiety disorder	DISBI2BT	Strong	Genetic Variation	[4]
Autoimmune disease	DISORMTM	Strong	Biomarker	[5]
Bone disease	DISE1F82	Strong	Biomarker	[6]
Brachyolmia	DISK6FWF	Strong	Biomarker	[1]
Cardiac disease	DISVO1I5	Strong	Genetic Variation	[7]
Cardiac failure	DISDC067	Strong	Altered Expression	[8]
Cervical cancer	DISFSHPF	Strong	Biomarker	[9]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[9]
Colon cancer	DISVC52G	Strong	Biomarker	[9]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[9]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[8]
Depression	DIS3XJ69	Strong	Genetic Variation	[10]
Epilepsy	DISBB28L	Strong	Biomarker	[11]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[12]
Geleophysic dysplasia 3	DIS1WMWE	Strong	Autosomal dominant	[13]
Glaucoma/ocular hypertension	DISLBXBY	Strong	Biomarker	[14]
Head and neck cancer	DISBPSQZ	Strong	Genetic Variation	[15]
Head and neck carcinoma	DISOU1DS	Strong	Genetic Variation	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[17]
Melanoma	DIS1RRCY	Strong	Biomarker	[18]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[19]
Mitral valve prolapse	DISNCHQ3	Strong	Biomarker	[20]
Mood disorder	DISLVMWO	Strong	Biomarker	[21]
Neoplasm	DISZKGEW	Strong	Biomarker	[22]
Obsessive compulsive disorder	DIS1ZMM2	Strong	Biomarker	[23]
Obstructive sleep apnea	DIS0SVD1	Strong	Biomarker	[24]
Osteoarthritis	DIS05URM	Strong	Biomarker	[25]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[26]
Post-traumatic stress disorder	DISHL1EY	Strong	Biomarker	[27]
Advanced cancer	DISAT1Z9	moderate	Genetic Variation	[28]
Carcinoma	DISH9F1N	moderate	Biomarker	[22]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Biomarker	[29]
Nervous system disease	DISJ7GGT	moderate	Biomarker	[30]
Obesity	DIS47Y1K	moderate	Biomarker	[30]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[22]
Tooth agenesis	DIS1PWC7	moderate	Biomarker	[20]
Tooth agenesis, selective, 1	DIS84ERL	moderate	Biomarker	[20]
Acromicric dysplasia	DISMV8M7	Supportive	Autosomal dominant	[13]
Geleophysic dysplasia	DISZOO1G	Supportive	Autosomal dominant	[13]
Malignant mesothelioma	DISTHJGH	Limited	Altered Expression	[31]
Mesothelioma	DISKWK9M	Limited	Altered Expression	[31]

4 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 Latent-transforming growth factor beta-binding protein 3 (LTBP3).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Latent-transforming growth factor beta-binding protein 3 (LTBP3).	[40]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Latent-transforming growth factor beta-binding protein 3 (LTBP3).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Latent-transforming growth factor beta-binding protein 3 (LTBP3).	[44]

9 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 Latent-transforming growth factor beta-binding protein 3 (LTBP3).	[33]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Latent-transforming growth factor beta-binding protein 3 (LTBP3).	[34]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Latent-transforming growth factor beta-binding protein 3 (LTBP3).	[35]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Latent-transforming growth factor beta-binding protein 3 (LTBP3).	[36]
Marinol	DM70IK5	Approved	Marinol increases the expression of Latent-transforming growth factor beta-binding protein 3 (LTBP3).	[37]
Selenium	DM25CGV	Approved	Selenium increases the expression of Latent-transforming growth factor beta-binding protein 3 (LTBP3).	[38]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Latent-transforming growth factor beta-binding protein 3 (LTBP3).	[39]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Latent-transforming growth factor beta-binding protein 3 (LTBP3).	[41]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Latent-transforming growth factor beta-binding protein 3 (LTBP3).	[43]

References

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• [16] HBx-related long non-coding RNA MALAT1 promotes cell metastasis via up-regulating LTBP3 in hepatocellular carcinoma.Am J Cancer Res. 2017 Apr 1;7(4):845-856. eCollection 2017.
• [17] Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.Nat Neurosci. 2019 Mar;22(3):343-352. doi: 10.1038/s41593-018-0326-7. Epub 2019 Feb 4.
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• [21] Artificial Intelligence based facial recognition for Mood Charting among men on life style modification and it's correlation with cortisol.Asian J Psychiatr. 2019 Jun;43:101-104. doi: 10.1016/j.ajp.2019.05.017. Epub 2019 May 11.
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• [31] Latent TGF- binding proteins (LTBPs) 1 and 3 differentially regulate transforming growth factor- activity in malignant mesothelioma.Hum Pathol. 2011 Feb;42(2):269-78. doi: 10.1016/j.humpath.2010.07.005. Epub 2010 Nov 24.
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• [33] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [34] 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.
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• [38] 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.
• [39] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [40] 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.
• [41] 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.
• [42] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [43] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
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