Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1HQR88)

DOT Name Serine/threonine-protein kinase receptor R3 (ACVRL1)
Synonyms SKR3; EC 2.7.11.30; Activin receptor-like kinase 1; ALK-1; TGF-B superfamily receptor type I; TSR-I
Gene Name ACVRL1
Related Disease
Telangiectasia, hereditary hemorrhagic, type 2 ( )
Hereditary hemorrhagic telangiectasia ( )
UniProt ID
ACVL1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2LCR; 3MY0; 4FAO; 6SF1; 6SF2; 6SF3; 7PPC
EC Number
2.7.11.30
Pfam ID
PF07714 ; PF08515
Sequence
MTLGSPRKGLLMLLMALVTQGDPVKPSRGPLVTCTCESPHCKGPTCRGAWCTVVLVREEG
RHPQEHRGCGNLHRELCRGRPTEFVNHYCCDSHLCNHNVSLVLEATQPPSEQPGTDGQLA
LILGPVLALLALVALGVLGLWHVRRRQEKQRGLHSELGESSLILKASEQGDSMLGDLLDS
DCTTGSGSGLPFLVQRTVARQVALVECVGKGRYGEVWRGLWHGESVAVKIFSSRDEQSWF
RETEIYNTVLLRHDNILGFIASDMTSRNSSTQLWLITHYHEHGSLYDFLQRQTLEPHLAL
RLAVSAACGLAHLHVEIFGTQGKPAIAHRDFKSRNVLVKSNLQCCIADLGLAVMHSQGSD
YLDIGNNPRVGTKRYMAPEVLDEQIRTDCFESYKWTDIWAFGLVLWEIARRTIVNGIVED
YRPPFYDVVPNDPSFEDMKKVVCVDQQTPTIPNRLAADPVLSGLAQMMRECWYPNPSARL
TALRIKKTLQKISNSPEKPKVIQ
Function
Type I receptor for TGF-beta family ligands BMP9/GDF2 and BMP10 and important regulator of normal blood vessel development. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. May bind activin as well.
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )
Reactome Pathway
Signaling by BMP (R-HSA-201451 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Telangiectasia, hereditary hemorrhagic, type 2 DISOYV2U Definitive Autosomal dominant [1]
Hereditary hemorrhagic telangiectasia DISXTDNT Supportive Autosomal dominant [2]
------------------------------------------------------------------------------------
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Serine/threonine-protein kinase receptor R3 (ACVRL1). [3]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Serine/threonine-protein kinase receptor R3 (ACVRL1). [8]
------------------------------------------------------------------------------------
7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Serine/threonine-protein kinase receptor R3 (ACVRL1). [4]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Serine/threonine-protein kinase receptor R3 (ACVRL1). [5]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of Serine/threonine-protein kinase receptor R3 (ACVRL1). [6]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Serine/threonine-protein kinase receptor R3 (ACVRL1). [7]
Tamibarotene DM3G74J Phase 3 Tamibarotene decreases the expression of Serine/threonine-protein kinase receptor R3 (ACVRL1). [4]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Serine/threonine-protein kinase receptor R3 (ACVRL1). [9]
KOJIC ACID DMP84CS Investigative KOJIC ACID decreases the expression of Serine/threonine-protein kinase receptor R3 (ACVRL1). [10]
------------------------------------------------------------------------------------
⏷ Show the Full List of 7 Drug(s)

References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Hereditary Hemorrhagic Telangiectasia. 2000 Jun 26 [updated 2021 Nov 24]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
3 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.
4 Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
5 Gene expression profile of multiple myeloma cell line treated by arsenic trioxide. J Huazhong Univ Sci Technolog Med Sci. 2007 Dec;27(6):646-9. doi: 10.1007/s11596-007-0606-z.
6 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
7 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
8 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.
9 Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
10 Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.