Details of Drug Off-Target (DOT)

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

• DOT Name: Selenocysteine insertion sequence-binding protein 2-like (SECISBP2L)
• Synonyms: SECIS-binding protein 2-like
• Gene Name: SECISBP2L
• Related Disease:
  Lung cancer
  Lung neoplasm
  Neoplasm
  Lung carcinoma
• UniProt ID: SBP2L_HUMAN
• Pfam ID: PF01248
• Sequence:
  MDRAPTEQNVKLSAEVEPFIPQKKSPDTFMIPMALPNDNGSVSGVEPTPIPSYLITCYPF
  VQENQSNRQFPLYNNDIRWQQPNPNPTGPYFAYPIISAQPPVSTEYTYYQLMPAPCAQVM
  GFYHPFPTPYSNTFQAANTVNAITTECTERPSQLGQVFPLSSHRSRNSNRGSVVPKQQLL
  QQHIKSKRPLVKNVATQKETNAAGPDSRSKIVLLVDASQQTDFPSDIANKSLSETTATML
  WKSKGRRRRASHPTAESSSEQGASEADIDSDSGYCSPKHSNNQPAAGALRNPDSGTMNHV
  ESSMCAGGVNWSNVTCQATQKKPWMEKNQTFSRGGRQTEQRNNSQVGFRCRGHSTSSERR
  QNLQKRPDNKHLSSSQSHRSDPNSESLYFEDEDGFQELNENGNAKDENIQQKLSSKVLDD
  LPENSPINIVQTPIPITTSVPKRAKSQKKKALAAALATAQEYSEISMEQKKLQEALSKAA
  GKKNKTPVQLDLGDMLAALEKQQQAMKARQITNTRPLSYTVVTAASFHTKDSTNRKPLTK
  SQPCLTSFNSVDIASSKAKKGKEKEIAKLKRPTALKKVILKEREEKKGRLTVDHNLLGSE
  EPTEMHLDFIDDLPQEIVSQEDTGLSMPSDTSLSPASQNSPYCMTPVSQGSPASSGIGSP
  MASSTITKIHSKRFREYCNQVLCKEIDECVTLLLQELVSFQERIYQKDPVRAKARRRLVM
  GLREVTKHMKLNKIKCVIISPNCEKIQSKGGLDEALYNVIAMAREQEIPFVFALGRKALG
  RCVNKLVPVSVVGIFNYFGAESLFNKLVELTEEARKAYKDMVAAMEQEQAEEALKNVKKV
  PHHMGHSRNPSAASAISFCSVISEPISEVNEKEYETNWRNMVETSDGLEASENEKEVSCK
  HSTSEKPSKLPFDTPPIGKQPSLVATGSTTSATSAGKSTASDKEEVKPDDLEWASQQSTE
  TGSLDGSCRDLLNSSITSTTSTLVPGMLEEEEDEDEEEEEDYTHEPISVEVQLNSRIESW
  VSETQRTMETLQLGKTLNGSEEDNVEQSGEEEAEAPEVLEPGMDSEAWTADQQASPGQQK
  SSNCSSLNKEHSDSNYTTQTT
• Function: Binds SECIS (Sec insertion sequence) elements present on selenocysteine (Sec) protein mRNAs, but does not promote Sec incorporation into selenoproteins in vitro.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung neoplasm	DISVARNB	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[1]

14 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 Selenocysteine insertion sequence-binding protein 2-like (SECISBP2L).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Selenocysteine insertion sequence-binding protein 2-like (SECISBP2L).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Selenocysteine insertion sequence-binding protein 2-like (SECISBP2L).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Selenocysteine insertion sequence-binding protein 2-like (SECISBP2L).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Selenocysteine insertion sequence-binding protein 2-like (SECISBP2L).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Selenocysteine insertion sequence-binding protein 2-like (SECISBP2L).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Selenocysteine insertion sequence-binding protein 2-like (SECISBP2L).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Selenocysteine insertion sequence-binding protein 2-like (SECISBP2L).	[9]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Selenocysteine insertion sequence-binding protein 2-like (SECISBP2L).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Selenocysteine insertion sequence-binding protein 2-like (SECISBP2L).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Selenocysteine insertion sequence-binding protein 2-like (SECISBP2L).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Selenocysteine insertion sequence-binding protein 2-like (SECISBP2L).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Selenocysteine insertion sequence-binding protein 2-like (SECISBP2L).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Selenocysteine insertion sequence-binding protein 2-like (SECISBP2L).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Selenocysteine insertion sequence-binding protein 2-like (SECISBP2L).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Selenocysteine insertion sequence-binding protein 2-like (SECISBP2L).	[13]

References

• [1] Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.Nat Genet. 2017 Jul;49(7):1126-1132. doi: 10.1038/ng.3892. Epub 2017 Jun 12.
• [2] Overexpression of Aurora-A bypasses cytokinesis through phosphorylation of suppressed in lung cancer.Am J Physiol Cell Physiol. 2019 Sep 1;317(3):C600-C612. doi: 10.1152/ajpcell.00032.2019. Epub 2019 Jul 17.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] 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.
• [9] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [10] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.