Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL61503)

• DOT Name: Transmembrane protein adipocyte-associated 1 (TPRA1)
• Synonyms: Integral membrane protein GPR175; Transmembrane protein 227
• Gene Name: TPRA1
• UniProt ID: TPRA1_HUMAN
• Pfam ID: PF10160
• Sequence:
  MDTLEEVTWANGSTALPPPLAPNISVPHRCLLLLYEDIGTSRVRYWDLLLLIPNVLFLIF
  LLWKLPSARAKIRITSSPIFITFYILVFVVALVGIARAVVSMTVSTSNAATVADKILWEI
  TRFFLLAIELSVIILGLAFGHLESKSSIKRVLAITTVLSLAYSVTQGTLEILYPDAHLSA
  EDFNIYGHGGRQFWLVSSCFFFLVYSLVVILPKTPLKERISLPSRRSFYVYAGILALLNL
  LQGLGSVLLCFDIIEGLCCVDATTFLYFSFFAPLIYVAFLRGFFGSEPKILFSYKCQVDE
  TEEPDVHLPQPYAVARREGLEAAGAAGASAASYSSTQFDSAGGVAYLDDIASMPCHTGSI
  NSTDSERWKAINA
• Tissue Specificity: Ubiquitous, with higher levels in heart, placenta and kidney.

Molecular Interaction Atlas (MIA) of This DOT

12 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 Transmembrane protein adipocyte-associated 1 (TPRA1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transmembrane protein adipocyte-associated 1 (TPRA1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane protein adipocyte-associated 1 (TPRA1).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Transmembrane protein adipocyte-associated 1 (TPRA1).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Transmembrane protein adipocyte-associated 1 (TPRA1).	[5]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Transmembrane protein adipocyte-associated 1 (TPRA1).	[6]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Transmembrane protein adipocyte-associated 1 (TPRA1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transmembrane protein adipocyte-associated 1 (TPRA1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transmembrane protein adipocyte-associated 1 (TPRA1).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Transmembrane protein adipocyte-associated 1 (TPRA1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transmembrane protein adipocyte-associated 1 (TPRA1).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transmembrane protein adipocyte-associated 1 (TPRA1).	[12]

References

• [1] 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.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] 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.
• [4] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [5] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [6] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [7] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [10] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [11] 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.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.