Details of Drug Off-Target (DOT)

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

• DOT Name: Scm-like with four MBT domains protein 1 (SFMBT1)
• Synonyms: hSFMBT; Renal ubiquitous protein 1
• Gene Name: SFMBT1
• Related Disease:
  Chronic renal failure
  Advanced cancer
  Brain cancer
  Cervical cancer
  Cervical carcinoma
  Clear cell renal carcinoma
  Renal cell carcinoma
  Ulcerative colitis
  Gout
  Schizophrenia
• UniProt ID: SMBT1_HUMAN
• Pfam ID: PF02820 ; PF00536 ; PF12140
• Sequence:
  MNGEQQLDADAGSGMEEVELSWEDYLEETGSTAVPYGSFKHVDTRLQNGFAPGMKLEVAV
  RTDPETYWVATVITTCEQLLLLRYDGYGEDRRADFWCDIRKADLYPIGWCEQNKKTLEAP
  EGIRDKVSDWDEFLRQTLIGACSPPVPLLEGLRNGRNPLDLIAPGSRLECQAFQDSLSTW
  IVTVVENIGGRLKLRYEGLESSDNYEHWLYYLDPFLHHVGWAAQQGYELQPPSAIRHLKN
  EAEWQEILAKVKEEEEEPLPSYLFKDKQVIGIHTFSVNMKLEAVDPWSPFGISPATVVKV
  FDEKYFLVEMDDLRPENHARRSFVCHADSPGIFPVQWSLKNGLHISPPPGYPSQDFDWAD
  YLKQCGAEAAPQRCFPPLISEHEFKENMKLEAVNPILPEEVCVATITAVRGSYLWLQLEG
  SKKPIPECIVSVESMDIFPLGWCETNGHPLSTPRRARVYKQRKIAVVQPEKQVPSSRTVH
  EGLRNQELNSTESVMINGKYCCPKIYFNHRCFSGPYLNKGRIAELPQCVGPGNCVLVLRE
  VLTLLINAAYKPSRVLRELQLDKDSVWHGCGEVLKAKYKGKSYRATVEIVKTADRVTEFC
  RQTCIKLECCPNLFGPRMVLDKCSENCSVLTKTKYTHYYGKKKNKRIGRPPGGHSNLACA
  LKKASKRRKRRKNVFVHKKKRSSASVDNTPAGSPQGSGGEDEDDPDEGDDDSLSEGSTSE
  QQDELQEESEMSEKKSCSSSPTQSEISTSLPPDRQRRKRELRTFSFSDDENKPPSPKEIR
  IEVAERLHLDSNPLKWSVADVVRFIRSTDCAPLARIFLDQEIDGQALLLLTLPTVQECMD
  LKLGPAIKLCHHIERIKFAFYEQFAN
• Function: Histone-binding protein, which is part of various corepressor complexes. Mediates the recruitment of corepressor complexes to target genes, followed by chromatin compaction and repression of transcription. Plays a role during myogenesis: required for the maintenance of undifferentiated states of myogenic progenitor cells via interaction with MYOD1. Interaction with MYOD1 leads to the recruitment of associated corepressors and silencing of MYOD1 target genes. Part of the SLC complex in germ cells, where it may play a role during spermatogenesis.
• Tissue Specificity: Expressed in all cell lines and normal tissues tested, including the thymus.
• KEGG Pathway: Polycomb repressive complex (hsa03083)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Posttranslational Modification	[2]
Brain cancer	DISBKFB7	Strong	Biomarker	[2]
Cervical cancer	DISFSHPF	Strong	Biomarker	[3]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[3]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[4]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[4]
Ulcerative colitis	DIS8K27O	moderate	Genetic Variation	[5]
Gout	DISHC0U7	Limited	Genetic Variation	[6]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[7]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Uric acid	DMA1MKT	Investigative	Scm-like with four MBT domains protein 1 (SFMBT1) affects the abundance of Uric acid.	[15]

4 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 Scm-like with four MBT domains protein 1 (SFMBT1).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Scm-like with four MBT domains protein 1 (SFMBT1).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Scm-like with four MBT domains protein 1 (SFMBT1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Scm-like with four MBT domains protein 1 (SFMBT1).	[12]

4 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 Scm-like with four MBT domains protein 1 (SFMBT1).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Scm-like with four MBT domains protein 1 (SFMBT1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Scm-like with four MBT domains protein 1 (SFMBT1).	[14]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Scm-like with four MBT domains protein 1 (SFMBT1).	[13]

References

• [1] Identification of CDC42BPG as a novel susceptibility locus for hyperuricemia in a Japanese population.Mol Genet Genomics. 2018 Apr;293(2):371-379. doi: 10.1007/s00438-017-1394-1. Epub 2017 Nov 9.
• [2] The malignant brain tumor (MBT) domain protein SFMBT1 is an integral histone reader subunit of the LSD1 demethylase complex for chromatin association and epithelial-to-mesenchymal transition.J Biol Chem. 2013 Sep 20;288(38):27680-27691. doi: 10.1074/jbc.M113.482349. Epub 2013 Aug 8.
• [3] MicroRNA-218 inhibits EMT, migration and invasion by targeting SFMBT1 and DCUN1D1 in cervical cancer.Oncotarget. 2016 Jul 19;7(29):45622-45636. doi: 10.18632/oncotarget.9850.
• [4] Renal cell neoplasms contain shared tumor type-specific copy number variations.Am J Pathol. 2012 Jun;180(6):2427-39. doi: 10.1016/j.ajpath.2012.01.044. Epub 2012 Apr 3.
• [5] Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.Nat Genet. 2015 Sep;47(9):979-986. doi: 10.1038/ng.3359. Epub 2015 Jul 20.
• [6] Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.Nat Genet. 2019 Oct;51(10):1459-1474. doi: 10.1038/s41588-019-0504-x. Epub 2019 Oct 2.
• [7] Genome-wide association study of schizophrenia in Ashkenazi Jews.Am J Med Genet B Neuropsychiatr Genet. 2015 Dec;168(8):649-59. doi: 10.1002/ajmg.b.32349. Epub 2015 Jul 21.
• [8] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [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] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [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] 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.
• [15] Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013 Feb;45(2):145-54. doi: 10.1038/ng.2500. Epub 2012 Dec 23.