Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIALEI1)

• DOT Name: BOS complex subunit NOMO1 (NOMO1)
• Synonyms: Nodal modulator 1; pM5 protein
• Gene Name: NOMO1
• Related Disease:
  T-cell leukaemia
  Adult lymphoma
  Colorectal carcinoma
  Glioma
  Lymphoma
  Neoplasm
  Pediatric lymphoma
  Acute myelogenous leukaemia
  Tricho-dento-osseous syndrome
• UniProt ID: NOMO1_HUMAN
• Pfam ID: PF13620 ; PF17802
• Sequence:
  MLVGQGAGPLGPAVVTAAVVLLLSGVGPAHGSEDIVVGCGGFVKSDVEINYSLIEIKLYT
  KHGTLKYQTDCAPNNGYFMIPLYDKGDFILKIEPPLGWSFEPTTVELHVDGVSDICTKGG
  DINFVFTGFSVNGKVLSKGQPLGPAGVQVSLRNTGTEAKIQSTVTQPGGKFAFFKVLPGD
  YEILATHPTWALKEASTTVRVTNSNANAASPLIVAGYNVSGSVRSDGEPMKGVKFLLFSS
  LVTKEDVLGCNVSPVPGFQPQDESLVYLCYTVSREDGSFSFYSLPSGGYTVIPFYRGERI
  TFDVAPSRLDFTVEHDSLKIEPVFHVMGFSVTGRVLNGPEGDGVPEAVVTLNNQIKVKTK
  ADGSFRLENITTGTYTIHAQKEHLYFETVTIKIAPNTPQLADIIATGFSVCGQISIIRFP
  DTVKQMNKYKVVLSSQDKDKSLVTVETDAHGSFCFKAKPGTYKVQVMVPEAETRAGLTLK
  PQTFPLTVTNRPMMDVAFVQFLASVSGKVSCLDTCGDLLVTLQSLSRQGEKRSLQLSGKV
  NAMTFTFDNVLPGKYKISIMHEDWCWKNKSLEVEVLEDDMSAVEFRQTGYMLRCSLSHAI
  TLEFYQDGNGRENVGIYNLSKGVNRFCLSKPGVYKVTPRSCHRFEQAFYTYDTSSPSILT
  LTAIRHHVLGTITTDKMMDVTVTIKSSIDSEPALVLGPLKSVQELRREQQLAEIEARRQE
  REKNGNEEGEERMTKPPVQEMVDELQGPFSYDFSYWARSGEKITVTPSSKELLFYPPSME
  AVVSGESCPGKLIEIHGKAGLFLEGQIHPELEGVEIVISEKGASSPLITVFTDDKGAYSV
  GPLHSDLEYTVTSQKEGYVLTAVEGTIGDFKAYALAGVSFEIKAEDDQPLPGVLLSLSGG
  LFRSNLLTQDNGILTFSNLSPGQYYFKPMMKEFRFEPSSQMIEVQEGQNLKITITGYRTA
  YSCYGTVSSLNGEPEQGVAMEAVGQNDCSIYGEDTVTDEEGKFRLRGLLPGCVYHVQLKA
  EGNDHIERALPHHRVIEVGNNDIDDVNIIVFRQINQFDLSGNVITSSEYLPTLWVKLYKS
  ENLDNPIQTVSLGQSLFFHFPPLLRDGENYVVLLDSTLPRSQYDYILPQVSFTAVGYHKH
  ITLIFNPTRKLPEQDIAQGSYIALPLTLLVLLAGYNHDKLIPLLLQLTSRLQGVRALGQA
  ASDNSGPEDAKRQAKKQKTRRT
• Function: Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes. The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions.
• Tissue Specificity: Expressed in colon tumor tissue and in adjacent normal colonic mucosa.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
T-cell leukaemia	DISJ6YIF	Definitive	Biomarker	[1]
Adult lymphoma	DISK8IZR	Strong	Genetic Variation	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Genetic Variation	[4]
Lymphoma	DISN6V4S	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[3]
Pediatric lymphoma	DIS51BK2	Strong	Genetic Variation	[2]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[5]
Tricho-dento-osseous syndrome	DISXZOGV	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of BOS complex subunit NOMO1 (NOMO1).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of BOS complex subunit NOMO1 (NOMO1).	[9]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 affects the binding of BOS complex subunit NOMO1 (NOMO1).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of BOS complex subunit NOMO1 (NOMO1).	[10]

References

• [1] Rac1 signaling protects monocytic AML cells expressing the MLL-AF9 oncogene from caspase-mediated apoptotic death.Apoptosis. 2013 Aug;18(8):963-79. doi: 10.1007/s10495-013-0842-6.
• [2] Cyclic Cystine-Bridged Peptides from the Marine Sponge Clathria basilana Induce Apoptosis in Tumor Cells and Depolarize the Bacterial Cytoplasmic Membrane.J Nat Prod. 2017 Nov 22;80(11):2941-2952. doi: 10.1021/acs.jnatprod.7b00477. Epub 2017 Nov 2.
• [3] NOMO-1 gene is deleted in early-onset colorectal cancer.Oncotarget. 2017 Apr 11;8(15):24429-24436. doi: 10.18632/oncotarget.15478.
• [4] Genotype-based gene signature of glioma risk.Neuro Oncol. 2017 Jul 1;19(7):940-950. doi: 10.1093/neuonc/now288.
• [5] Aberrant Mer receptor tyrosine kinase expression contributes to leukemogenesis in acute myeloid leukemia.Oncogene. 2013 Nov 14;32(46):5359-68. doi: 10.1038/onc.2013.40. Epub 2013 Mar 11.
• [6] DLX3 promotes bone marrow mesenchymal stem cell proliferation through H19/miR-675 axis.Clin Sci (Lond). 2017 Nov 13;131(22):2721-2735. doi: 10.1042/CS20171231. Print 2017 Nov 15.
• [7] 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.
• [8] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [9] 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.
• [10] 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.