Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZDB0JX)

• DOT Name: Nonsense-mediated mRNA decay factor SMG7 (SMG7)
• Synonyms: SMG-7 homolog; hSMG-7
• Gene Name: SMG7
• Related Disease:
  Coeliac disease
  Myositis disease
  Rheumatoid arthritis
  Systemic lupus erythematosus
  Systemic sclerosis
  Tuberculosis
  Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2
  Autoimmune disease
• UniProt ID: SMG7_HUMAN
• PDB ID: 1YA0
• Pfam ID: PF10374 ; PF10373
• Sequence:
  MSLQSAQYLRQAEVLKADMTDSKLGPAEVWTSRQALQDLYQKMLVTDLEYALDKKVEQDL
  WNHAFKNQITTLQGQAKNRANPNRSEVQANLSLFLEAASGFYTQLLQELCTVFNVDLPCR
  VKSSQLGIISNKQTHTSAIVKPQSSSCSYICQHCLVHLGDIARYRNQTSQAESYYRHAAQ
  LVPSNGQPYNQLAILASSKGDHLTTIFYYCRSIAVKFPFPAASTNLQKALSKALESRDEV
  KTKWGVSDFIKAFIKFHGHVYLSKSLEKLSPLREKLEEQFKRLLFQKAFNSQQLVHVTVI
  NLFQLHHLRDFSNETEQHTYSQDEQLCWTQLLALFMSFLGILCKCPLQNESQEESYNAYP
  LPAVKVSMDWLRLRPRVFQEAVVDERQYIWPWLISLLNSFHPHEEDLSSISATPLPEEFE
  LQGFLALRPSFRNLDFSKGHQGITGDKEGQQRRIRQQRLISIGKWIADNQPRLIQCENEV
  GKLLFITEIPELILEDPSEAKENLILQETSVIESLAADGSPGLKSVLSTSRNLSNNCDTG
  EKPVVTFKENIKTREVNRDQGRSFPPKEVRRDYSKGITVTKNDGKKDNNKRKTETKKCTL
  EKLQETGKQNVAVQVKSQTELRKTPVSEARKTPVTQTPTQASNSQFIPIHHPGAFPPLPS
  RPGFPPPTYVIPPPVAFSMGSGYTFPAGVSVPGTFLQPTAHSPAGNQVQAGKQSHIPYSQ
  QRPSGPGPMNQGPQQSQPPSQQPLTSLPAQPTAQSTSQLQVQALTQQQQSPTKAVPALGK
  SPPHHSGFQQYQQADASKQLWNPPQVQGPLGKIMPVKQPYYLQTQDPIKLFEPSLQPPVM
  QQQPLEKKMKPFPMEPYNHNPSEVKVPEFYWDSSYSMADNRSVMAQQANIDRRGKRSPGV
  FRPEQDPVPRMPFEKSLLEKPSELMSHSSSFLSLTGFSLNQERYPNNSMFNEVYGKNLTS
  SSKAELSPSMAPQETSLYSLFEGTPWSPSLPASSDHSTPASQSPHSSNPSSLPSSPPTHN
  HNSVPFSNFGPIGTPDNRDRRTADRWKTDKPAMGGFGIDYLSATSSSESSWHQASTPSGT
  WTGHGPSMEDSSAVLMESLKSIWSSSMMHPGPSALEQLLMQQKQKQQRGQGTMNPPH
• Function: Plays a role in nonsense-mediated mRNA decay. Recruits UPF1 to cytoplasmic mRNA decay bodies. Together with SMG5 is thought to provide a link to the mRNA degradation machinery involving exonucleolytic pathways, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation.
• KEGG Pathway: mR. surveillance pathway (hsa03015)
• Reactome Pathway: Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) (R-HSA-975957)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coeliac disease	DISIY60C	Strong	Genetic Variation	[1]
Myositis disease	DISCIXF0	Strong	Genetic Variation	[2]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[2]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[2]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[2]
Tuberculosis	DIS2YIMD	Strong	Genetic Variation	[3]
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2	DISMS4O6	Limited	Genetic Variation	[4]
Autoimmune disease	DISORMTM	No Known	Autosomal dominant	[5]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Josamycin	DMKJ8LB	Approved	Nonsense-mediated mRNA decay factor SMG7 (SMG7) affects the response to substance of Josamycin.	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nonsense-mediated mRNA decay factor SMG7 (SMG7).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nonsense-mediated mRNA decay factor SMG7 (SMG7).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Nonsense-mediated mRNA decay factor SMG7 (SMG7).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Nonsense-mediated mRNA decay factor SMG7 (SMG7).	[9]
Marinol	DM70IK5	Approved	Marinol increases the expression of Nonsense-mediated mRNA decay factor SMG7 (SMG7).	[10]
Selenium	DM25CGV	Approved	Selenium increases the expression of Nonsense-mediated mRNA decay factor SMG7 (SMG7).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Nonsense-mediated mRNA decay factor SMG7 (SMG7).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Nonsense-mediated mRNA decay factor SMG7 (SMG7).	[15]

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 decreases the methylation of Nonsense-mediated mRNA decay factor SMG7 (SMG7).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Nonsense-mediated mRNA decay factor SMG7 (SMG7).	[13]

References

• [1] Functional implications of disease-specific variants in loci jointly associated with coeliac disease and rheumatoid arthritis.Hum Mol Genet. 2016 Jan 1;25(1):180-90. doi: 10.1093/hmg/ddv455. Epub 2015 Nov 5.
• [2] Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases.Ann Rheum Dis. 2019 Mar;78(3):311-319. doi: 10.1136/annrheumdis-2018-214127. Epub 2018 Dec 20.
• [3] A Novel Genetic Variation in NCF2, the Core Component of NADPH Oxidase, Contributes to the Susceptibility of Tuberculosis in Western Chinese Han Population.DNA Cell Biol. 2020 Jan;39(1):57-62. doi: 10.1089/dna.2019.5082. Epub 2019 Dec 2.
• [4] Two CGD Families with a Hypomorphic Mutation in the Activation Domain of p67(phox).J Clin Cell Immunol. 2014 Jun 30;5(3):1000231.
• [5] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [11] 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.
• [12] 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.
• [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] Genome-wide distribution of histone trimethylation reveals a global impact of bisphenol A on telomeric binding proteins and histone acetyltransferase factors: a pilot study with human and in vitro data. Clin Epigenetics. 2022 Dec 26;14(1):186. doi: 10.1186/s13148-022-01408-2.
• [15] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [16] A genome-wide analysis of targets of macrolide antibiotics in mammalian cells. J Biol Chem. 2020 Feb 14;295(7):2057-2067. doi: 10.1074/jbc.RA119.010770. Epub 2020 Jan 8.