Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8U1P8E)

• DOT Name: NHS-like protein 2 (NHSL2)
• Gene Name: NHSL2
• UniProt ID: NHSL2_HUMAN
• Pfam ID: PF15273
• Sequence:
  MPFYRRTVVPQRLCPRNPPQQLAELRDVSHLAALSLLRQLADLCGHSLALLEDLEGHLLA
  LGRRTDSLYRRTVRLRRRLPCRLLGPEEDEEELAAANSGRENATATAHSRSSWRQPVNVF
  LSSGRPPSVEELLREAQLNLQSLLQEEYEEQYSEARLVGQTFRSSDEATKPTPNPRPQSA
  RRLEFILMPTKRQLSEDETTTQGVRAPEASLSLSTTADKQTAWNSLFPLPILEEKRWPQL
  CSTQSDIVPINISGQQFDKHASLRHSLFNTETAVNPKSTLRRRRTIIGFSNFSQRDQGHS
  NSPAGSVAHSTTSDIRPSHSVPEGVHGRVAVGQDARFPSLTSPVLRTPSSEPDEPHQARS
  GPNPPGMESMGMVYSVPSSCNGPTESTFSTSWKGDAFTYMTPSATSQSNQVNENGKNPSC
  GNSWVSLNKVPPLVPKEAATLLVARDNPAGCSGSAGYPERLIQQRHMPERPSKIGLLTSG
  TSRLETGPGGASRFRERSLSVPTDSGTTDVDYDEEQKANEACALPFASTSSEGSNSADNI
  ASLSAQQEAQHRRQRSKSISLRKAKKKPSPPTRSVSLVKDEPGLLPEGGSALPKDQRPKS
  LCLSLEHQGHHSSHPDAQGHPAIPNHKDPESTQFSHHWYLTDWKSGDTYQSLSSSSTATG
  TTVIECTQVQGSSESLASPSTSRATTPSQLSIEVEAREISSPGRPPGLMSPSSGYSSQSE
  TPTPTVSMSLTLGHLPPPSSSVRVRPVVPERKSSLPPTSPMEKFPKSRLSFDLPLTSSPN
  LDLSGMSISIRSKTKVSRHHSETNFGVKLAQKTNPNQPIMPMVTQSDLRSVRLRSVSKSE
  PEDDIESPEYAEEPRAEEVFTLPERKTKPPVAEKPPVARRPPSLVHKPPSVPEEYALTSP
  TLAMPPRSSIQHARPLPQDSYTVVRKPKPSSFPDGRSPGESTAPSSLVFTPFASSSDAFF
  SGTQQPPQGSVEDEGPKVRVLPERISLQSQEEAEKKKGKIPPPVPKKPSVLYLPLTSPTA
  QMEAYVAEPRLPLSPIITLEEDTKCPATGDDLQSLGQRVTSTPQADSEREASPLGSSVEP
  GTEEKSLISDKTAEWIAEDDDDVFVASRTTEDLFTVIHRSKRKLLGWKEPGEAFVGGRTS
  SHSPIKNTAESPISESTATAGSGSSANLDAGRNDDFKALLQKKGSKATPRSRPSAAELLK
  TTNPLARRIIAQFSKDYETTDNPST

Molecular Interaction Atlas (MIA) of This DOT

4 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 NHS-like protein 2 (NHSL2).	[1]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of NHS-like protein 2 (NHSL2).	[2]
Panobinostat	DM58WKG	Approved	Panobinostat affects the expression of NHS-like protein 2 (NHSL2).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 affects the expression of NHS-like protein 2 (NHSL2).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of NHS-like protein 2 (NHSL2).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of NHS-like protein 2 (NHSL2).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of NHS-like protein 2 (NHSL2).	[6]

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] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] The Bromodomain Inhibitor JQ1 and the Histone Deacetylase Inhibitor Panobinostat Synergistically Reduce N-Myc Expression and Induce Anticancer Effects. Clin Cancer Res. 2016 May 15;22(10):2534-44. doi: 10.1158/1078-0432.CCR-15-1666. Epub 2016 Jan 5.
• [5] 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.
• [6] 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.