Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAKW7R9)

• DOT Name: Arrestin domain-containing protein 3 (ARRDC3)
• Synonyms: TBP-2-like inducible membrane protein; TLIMP
• Gene Name: ARRDC3
• Related Disease:
  Advanced cancer
  Breast neoplasm
  Cervical cancer
  Cervical carcinoma
  Human papillomavirus infection
  Non-alcoholic fatty liver disease
  Prostate cancer
  Prostate carcinoma
  Clear cell renal carcinoma
  Renal cell carcinoma
  Triple negative breast cancer
  Breast cancer
  Breast carcinoma
  Neoplasm
  Obesity
• UniProt ID: ARRD3_HUMAN
• PDB ID: 4N7H; 4R7V; 4R7X
• Pfam ID: PF02752 ; PF00339
• Sequence:
  MVLGKVKSLTISFDCLNDSNVPVYSSGDTVSGRVNLEVTGEIRVKSLKIHARGHAKVRWT
  ESRNAGSNTAYTQNYTEEVEYFNHKDILIGHERDDDNSEEGFHTIHSGRHEYAFSFELPQ
  TPLATSFEGRHGSVRYWVKAELHRPWLLPVKLKKEFTVFEHIDINTPSLLSPQAGTKEKT
  LCCWFCTSGPISLSAKIERKGYTPGESIQIFAEIENCSSRMVVPKAAIYQTQAFYAKGKM
  KEVKQLVANLRGESLSSGKTETWNGKLLKIPPVSPSILDCSIIRVEYSLMVYVDIPGAMD
  LFLNLPLVIGTIPLHPFGSRTSSVSSQCSMNMNWLSLSLPERPEAPPSYAEVVTEEQRRN
  NLAPVSACDDFERALQGPLFAYIQEFRFLPPPLYSEIDPNPDQSADDRPSCPSR
• Function: Adapter protein that plays a role in regulating cell-surface expression of adrenergic receptors and probably also other G protein-coupled receptors. Plays a role in NEDD4-mediated ubiquitination and endocytosis af activated ADRB2 and subsequent ADRB2 degradation. May recruit NEDD4 to ADRB2. Alternatively, may function as adapter protein that does not play a major role in recruiting NEDD4 to ADRB2, but rather plays a role in a targeting ADRB2 to endosomes.
• Tissue Specificity: Highly expressed in skeletal muscle, placenta, kidney, lung, liver, blood, adrenal gland, lymph node, mammary gland, thyroid, and trachea . Very low levels in colon, thymus, spleen, small intestine, bladder and bone marrow . Strong expression in differentiated adipocytes compared to preadipocytes . Detected in omental fat and subcutaneous fat tissue .

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Cervical cancer	DISFSHPF	Strong	Biomarker	[3]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[3]
Human papillomavirus infection	DISX61LX	Strong	Biomarker	[3]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[4]
Prostate cancer	DISF190Y	Strong	Altered Expression	[5]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[5]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[6]
Renal cell carcinoma	DISQZ2X8	moderate	Biomarker	[6]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[7]
Breast cancer	DIS7DPX1	Limited	Biomarker	[8]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[8]
Neoplasm	DISZKGEW	Limited	Biomarker	[6]
Obesity	DIS47Y1K	Limited	Biomarker	[9]

1 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 Arrestin domain-containing protein 3 (ARRDC3).	[10]

30 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 Arrestin domain-containing protein 3 (ARRDC3).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[15]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[16]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[17]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[18]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[18]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Arrestin domain-containing protein 3 (ARRDC3).	[19]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[20]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[21]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[22]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[23]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[24]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[25]
Prednisolone	DMQ8FR2	Approved	Prednisolone increases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[26]
Ampicillin	DMHWE7P	Approved	Ampicillin decreases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[11]
Racecadotril	DMFOTZ7	Approved	Racecadotril increases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[27]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[30]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[32]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[33]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[16]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[26]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[11]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Arrestin domain-containing protein 3 (ARRDC3).	[34]

References

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• [2] Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1.Nat Genet. 2014 Aug;46(8):886-90. doi: 10.1038/ng.3041. Epub 2014 Jul 20.
• [3] Genome-wide association study of cervical cancer suggests a role for ARRDC3 gene in human papillomavirus infection.Hum Mol Genet. 2019 Jan 15;28(2):341-348. doi: 10.1093/hmg/ddy390.
• [4] Possible association of arrestin domain-containing protein 3 and progression of non-alcoholic fatty liver disease.Int J Med Sci. 2019 Jun 2;16(7):909-921. doi: 10.7150/ijms.34245. eCollection 2019.
• [5] ARRDC3 Inhibits the Progression of Human Prostate Cancer Through ARRDC3-ITG4 Pathway.Curr Mol Med. 2017;17(3):221-229. doi: 10.2174/1566524017666170807144711.
• [6] ARRDC1 and ARRDC3 act as tumor suppressors in renal cell carcinoma by facilitating YAP1 degradation.Am J Cancer Res. 2018 Jan 1;8(1):132-143. eCollection 2018.
• [7] Arrestin Domain Containing 3 Reverses Epithelial to Mesenchymal Transition and Chemo-Resistance of TNBC Cells by Up-Regulating Expression of miR-200b.Cells. 2019 Jul 10;8(7):692. doi: 10.3390/cells8070692.
• [8] The Role of Arrestin Domain-Containing 3 in Regulating Endocytic Recycling and Extracellular Vesicle Sorting of Integrin 4 in Breast Cancer.Cancers (Basel). 2018 Dec 11;10(12):507. doi: 10.3390/cancers10120507.
• [9] Healthy diet is associated with gene expression in blood: the Framingham Heart Study.Am J Clin Nutr. 2019 Sep 1;110(3):742-749. doi: 10.1093/ajcn/nqz060.
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• [19] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [20] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [22] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [23] Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
• [24] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [25] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [26] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [27] Successful validation of genomic biomarkers for human immunotoxicity in Jurkat T cells in vitro. J Appl Toxicol. 2015 Jul;35(7):831-41.
• [28] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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• [31] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [32] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
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