Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPAD5S1)

DOT Name Adhesion G-protein coupled receptor G2 (ADGRG2)
Synonyms G-protein coupled receptor 64; Human epididymis-specific protein 6; He6
Gene Name ADGRG2
Related Disease
Carcinoma ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Infertility ( )
Malignant soft tissue neoplasm ( )
Primary hyperparathyroidism ( )
Sarcoma ( )
Male infertility ( )
Renal agenesis, unilateral ( )
Congenital bilateral absence of vas deferens ( )
Neoplasm ( )
Osteoarthritis ( )
UniProt ID
AGRG2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00002 ; PF01825
Sequence
MVFSVRQCGHVGRTEEVLLTFKIFLVIICLHVVLVTSLEEDTDNSSLSPPPAKLSVVSFA
PSSNGTPEVETTSLNDVTLSLLPSNETEKTKITIVKTFNASGVKPQRNICNLSSICNDSA
FFRGEIMFQYDKESTVPQNQHITNGTLTGVLSLSELKRSELNKTLQTLSETYFIMCATAE
AQSTLNCTFTIKLNNTMNACAVIAALERVKIRPMEHCCCSVRIPCPSSPEELEKLQCDLQ
DPIVCLADHPRGPPFSSSQSIPVVPRATVLSQVPKATSFAEPPDYSPVTHNVPSPIGEIQ
PLSPQPSAPIASSPAIDMPPQSETISSPMPQTHVSGTPPPVKASFSSPTVSAPANVNTTS
APPVQTDIVNTSSISDLENQVLQMEKALSLGSLEPNLAGEMINQVSRLLHSPPDMLAPLA
QRLLKVVDDIGLQLNFSNTTISLTSPSLALAVIRVNASSFNTTTFVAQDPANLQVSLETQ
APENSIGTITLPSSLMNNLPAHDMELASRVQFNFFETPALFQDPSLENLSLISYVISSSV
ANLTVRNLTRNVTVTLKHINPSQDELTVRCVFWDLGRNGGRGGWSDNGCSVKDRRLNETI
CTCSHLTSFGVLLDLSRTSVLPAQMMALTFITYIGCGLSSIFLSVTLVTYIAFEKIRRDY
PSKILIQLCAALLLLNLVFLLDSWIALYKMQGLCISVAVFLHYFLLVSFTWMGLEAFHMY
LALVKVFNTYIRKYILKFCIVGWGVPAVVVTIILTISPDNYGLGSYGKFPNGSPDDFCWI
NNNAVFYITVVGYFCVIFLLNVSMFIVVLVQLCRIKKKKQLGAQRKTSIQDLRSIAGLTF
LLGITWGFAFFAWGPVNVTFMYLFAIFNTLQGFFIFIFYCVAKENVRKQWRRYLCCGKLR
LAENSDWSKTATNGLKKQTVNQGVSSSSNSLQSSSNSTNSTTLLVNNDCSVHASGNGNAS
TERNGVSFSVQNGDVCLHDFTGKQHMFNEKEDSCNGKGRMALRRTSKRGSLHFIEQM
Function Orphan receptor. Could be involved in a signal transduction pathway controlling epididymal function and male fertility. May regulate fluid exchange within epididymis.
Tissue Specificity
Epididymis-specific expression (at protein level). Both subunits are associated with apical membranes of efferent ductule and proximal epididymal duct epithelia. Mainly expressed in the nonciliated principal cells of the proximal excurrent ducts. Specifically over-expressed in Ewing sarcomas but also up-regulated in a number of carcinomas derived from prostate, kidney or lung.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Carcinoma DISH9F1N Strong Altered Expression [1]
Endometrial cancer DISW0LMR Strong Biomarker [2]
Endometrial carcinoma DISXR5CY Strong Altered Expression [2]
Infertility DISAMOWP Strong CausalMutation [3]
Malignant soft tissue neoplasm DISTC6NO Strong Altered Expression [1]
Primary hyperparathyroidism DISB4U1Q Strong Biomarker [4]
Sarcoma DISZDG3U Strong Altered Expression [1]
Male infertility DISY3YZZ moderate Biomarker [5]
Renal agenesis, unilateral DIS53ZJ8 moderate Biomarker [6]
Congenital bilateral absence of vas deferens DISR15UU Supportive Autosomal recessive [3]
Neoplasm DISZKGEW Disputed Biomarker [2]
Osteoarthritis DIS05URM Limited Biomarker [7]
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⏷ Show the Full List of 12 Disease(s)
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 decreases the methylation of Adhesion G-protein coupled receptor G2 (ADGRG2). [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Adhesion G-protein coupled receptor G2 (ADGRG2). [20]
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14 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Adhesion G-protein coupled receptor G2 (ADGRG2). [9]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Adhesion G-protein coupled receptor G2 (ADGRG2). [10]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Adhesion G-protein coupled receptor G2 (ADGRG2). [11]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Adhesion G-protein coupled receptor G2 (ADGRG2). [12]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Adhesion G-protein coupled receptor G2 (ADGRG2). [13]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Adhesion G-protein coupled receptor G2 (ADGRG2). [14]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Adhesion G-protein coupled receptor G2 (ADGRG2). [15]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Adhesion G-protein coupled receptor G2 (ADGRG2). [16]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Adhesion G-protein coupled receptor G2 (ADGRG2). [17]
Sodium lauryl sulfate DMLJ634 Approved Sodium lauryl sulfate increases the expression of Adhesion G-protein coupled receptor G2 (ADGRG2). [18]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Adhesion G-protein coupled receptor G2 (ADGRG2). [19]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Adhesion G-protein coupled receptor G2 (ADGRG2). [21]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Adhesion G-protein coupled receptor G2 (ADGRG2). [22]
GALLICACID DM6Y3A0 Investigative GALLICACID decreases the expression of Adhesion G-protein coupled receptor G2 (ADGRG2). [23]
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⏷ Show the Full List of 14 Drug(s)

References

1 G-Protein coupled receptor 64 promotes invasiveness and metastasis in Ewing sarcomas through PGF and MMP1.J Pathol. 2013 May;230(1):70-81. doi: 10.1002/path.4170. Epub 2013 Mar 14.
2 G-protein coupled receptor 64 (GPR64) acts as a tumor suppressor in endometrial cancer.BMC Cancer. 2019 Aug 14;19(1):810. doi: 10.1186/s12885-019-5998-1.
3 Truncating Mutations in the Adhesion G Protein-Coupled Receptor G2 Gene ADGRG2 Cause an X-Linked Congenital Bilateral Absence of Vas Deferens. Am J Hum Genet. 2016 Aug 4;99(2):437-42. doi: 10.1016/j.ajhg.2016.06.012. Epub 2016 Jul 28.
4 Orphan Adhesion GPCR GPR64/ADGRG2 Is Overexpressed in Parathyroid Tumors and Attenuates Calcium-Sensing Receptor-Mediated Signaling.J Bone Miner Res. 2017 Mar;32(3):654-666. doi: 10.1002/jbmr.3023. Epub 2016 Nov 25.
5 Gq activity- and -arrestin-1 scaffolding-mediated ADGRG2/CFTR coupling are required for male fertility.Elife. 2018 Feb 2;7:e33432. doi: 10.7554/eLife.33432.
6 Novel ADGRG2 truncating variants in patients with X-linked congenital absence of vas deferens.Andrology. 2020 May;8(3):618-624. doi: 10.1111/andr.12744. Epub 2019 Dec 26.
7 Distinctive gene expression signatures in rheumatoid arthritis synovial tissue fibroblast cells: correlates with disease activity.Genes Immun. 2007 Sep;8(6):480-91. doi: 10.1038/sj.gene.6364400. Epub 2007 Jun 14.
8 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.
9 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
10 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
11 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.
12 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
13 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
14 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
15 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
16 Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
17 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
18 CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
19 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
20 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.
21 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.
22 Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
23 Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.