Details of Drug Off-Target (DOT)

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

• DOT Name: Tectonin beta-propeller repeat-containing protein 1 (TECPR1)
• Gene Name: TECPR1
• UniProt ID: TCPR1_HUMAN
• PDB ID: 4TQ1; 8P5P
• Pfam ID: PF06462 ; PF06398 ; PF19193
• Sequence:
  MPNSVLWAVDLFGRVYTLSTAGQYWEMCKDSQLEFKRVSATTQCCWGIACDNQVYVYVCA
  SDVPIRRREEAYENQRWNPMGGFCEKLLLSDRWGWSDVSGLQHRPLDRVALPSPHWEWES
  DWYVDENFGGEPTEKGGWTYAIDFPATYTKDKKWNSCVRRRKWIRYRRYKSRDIWAKIPS
  KDDPKELPDPFNDLSVGGWEITEEPVGRLSVWAVSLQGKVWYREDVSHSNPEGSSWSLLD
  TPGEVVQISCGPHDLLWATLWEGQALVREGINRSNPKGSSWSIVEPPGSENGVMHISVGV
  SVVWAVTKDWKVWFRRGVNSHNPCGTSWIEMVGEMTMVNVGMNDQVWGIGCEDRAVYFRQ
  GVTPSELSGKTWKAIIAARECDRSHSGSSSSLLSAGCFFGDEVRGSGESAPSDTDASSEV
  ERPGPGQILPAEPLDDSKNATGNSASGLGAGRTAEDTVEDACPAEGSREARPNTHPGPAP
  TPAELPWTNIDLKEAKKVPSHSAAGFPETTSLSSLGLLPLGLEEPYGVDDHPLWAWVSGG
  GCVVEACAMPRWFTVQAGLSSSVHMLSLSITPAQTAAWRKQIFQQLTERTKRELENFRHY
  EQAVEQSVWVKTGALQWWCDWKPHKWVDVRLALEQFTGHDGVRDSILFIYYVVHEEKKYI
  HIFLNEVVALVPVLNETKHSFALYTPERTRQRWPVRLAAATEQDMNDWLALLSLSCCESR
  KVQGRPSPQAIWSITCKGDIFVSEPSPDLEAHEHPLPCDQMFWRQMGGHLRMVEANSRGV
  VWGIGYDHTAWVYTGGYGGGCFQGLASSTSNIYTQSDVKCVHIYENQRWNPVTGYTSRGL
  PTDRYMWSDASGLQECTKAGTKPPSLQWAWVSDWFVDFSVPGGTDQEGWQYASDFPASYH
  GSKTMKDFVRRRCWARKCKLVTSGPWLEVPPIALRDVSIIPESPGAEGSGHSIALWAVSD
  KGDVLCRLGVSELNPAGSSWLHVGTDQPFASISIGACYQVWAVARDGSAFYRGSVYPSQP
  AGDCWYHIPSPPRQRLKQVSAGQTSVYALDENGNLWYRQGITPSYPQGSSWEHVSNNVCR
  VSVGPLDQVWVIANKVQGSHSLSRGTVCHRTGVQPHEPKGHGWDYGIGGGWDHISVRANA
  TRAPRSSSQEQEPSAPPEAHGPVCC
• Function: Tethering factor involved in autophagy. Involved in autophagosome maturation by promoting the autophagosome fusion with lysosomes: acts by associating with both the ATG5-ATG12 conjugate and phosphatidylinositol-3-phosphate (PtdIns(3)P) present at the surface of autophagosomes. Also involved in selective autophagy against bacterial pathogens, by being required for phagophore/preautophagosomal structure biogenesis and maturation.
• KEGG Pathway: Shigellosis (hsa05131)

Molecular Interaction Atlas (MIA) of This DOT

3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tectonin beta-propeller repeat-containing protein 1 (TECPR1).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tectonin beta-propeller repeat-containing protein 1 (TECPR1).	[2]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tectonin beta-propeller repeat-containing protein 1 (TECPR1).	[4]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Tectonin beta-propeller repeat-containing protein 1 (TECPR1).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Tectonin beta-propeller repeat-containing protein 1 (TECPR1).	[5]

References

• [1] 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.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] 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.
• [4] 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.
• [5] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.