Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTE5GOJ)

• DOT Name: SAGA-associated factor 29 (SGF29)
• Synonyms: Coiled-coil domain-containing protein 101; SAGA complex-associated factor 29
• Gene Name: SGF29
• Related Disease:
  Nephropathy
  Chronic obstructive pulmonary disease
  Type-1 diabetes
  Neoplasm of esophagus
• UniProt ID: SGF29_HUMAN
• PDB ID: 3LX7; 3ME9; 3MEA; 3MET; 3MEU; 3MEV; 3MEW; 5C0M
• Pfam ID: PF07039
• Sequence:
  MALVSADSRIAELLTELHQLIKQTQEERSRSEHNLVNIQKTHERMQTENKISPYYRTKLR
  GLYTTAKADAEAECNILRKALDKIAEIKSLLEERRIAAKIAGLYNDSEPPRKTMRRGVLM
  TLLQQSAMTLPLWIGKPGDKPPPLCGAIPASGDYVARPGDKVAARVKAVDGDEQWILAEV
  VSYSHATNKYEVDDIDEEGKERHTLSRRRVIPLPQWKANPETDPEALFQKEQLVLALYPQ
  TTCFYRALIHAPPQRPQDDYSVLFEDTSYADGYSPPLNVAQRYVVACKEPKKK
• Function: Chromatin reader component of some histone acetyltransferase (HAT) SAGA-type complexes like the TFTC-HAT, ATAC or STAGA complexes. SGF29 specifically recognizes and binds methylated 'Lys-4' of histone H3 (H3K4me), with a preference for trimethylated form (H3K4me3). In the SAGA-type complexes, SGF29 is required to recruit complexes to H3K4me. Involved in the response to endoplasmic reticulum (ER) stress by recruiting the SAGA complex to H3K4me, thereby promoting histone H3 acetylation and cell survival. Also binds non-histone proteins that are methylated on Lys residues: specifically recognizes and binds CGAS monomethylated on 'Lys-506'.
• Reactome Pathway:
  Formation of WDR5-containing histone-modifying complexes (R-HSA-9772755)
  HATs acetylate histones (R-HSA-3214847)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nephropathy	DISXWP4P	Definitive	Genetic Variation	[1]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[2]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[3]
Neoplasm of esophagus	DISOLKAQ	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of SAGA-associated factor 29 (SGF29).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of SAGA-associated factor 29 (SGF29).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of SAGA-associated factor 29 (SGF29).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of SAGA-associated factor 29 (SGF29).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of SAGA-associated factor 29 (SGF29).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of SAGA-associated factor 29 (SGF29).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of SAGA-associated factor 29 (SGF29).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of SAGA-associated factor 29 (SGF29).	[14]

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 increases the methylation of SAGA-associated factor 29 (SGF29).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of SAGA-associated factor 29 (SGF29).	[11]

References

• [1] Genome-wide meta-analysis for severe diabetic retinopathy.Hum Mol Genet. 2011 Jun 15;20(12):2472-81. doi: 10.1093/hmg/ddr121. Epub 2011 Mar 26.
• [2] Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.Nat Genet. 2017 Mar;49(3):426-432. doi: 10.1038/ng.3752. Epub 2017 Feb 6.
• [3] A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci.PLoS Genet. 2011 Sep;7(9):e1002293. doi: 10.1371/journal.pgen.1002293. Epub 2011 Sep 29.
• [4] Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.Nat Genet. 2012 Oct;44(10):1090-7. doi: 10.1038/ng.2411. Epub 2012 Sep 9.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.