Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGRV2LW)

• DOT Name: Scaffold attachment factor B1 (SAFB)
• Synonyms: SAF-B; SAF-B1; HSP27 estrogen response element-TATA box-binding protein; HSP27 ERE-TATA-binding protein
• Gene Name: SAFB
• Related Disease:
  Adenocarcinoma
  Melanoma
  Pneumonia
  Skin cancer
  Autism spectrum disorder
  Autoimmune disease
  Barrett esophagus
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma of liver and intrahepatic biliary tract
  Cholangiocarcinoma
  Eosinophilic esophagitis
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Familial multiple trichoepithelioma
  Gastroesophageal reflux disease
  Influenza
  Liver cancer
  Myocardial infarction
  Schizoaffective disorder
  Smith-Lemli-Opitz syndrome
  Squamous cell carcinoma
  Syphilis
  Triple negative breast cancer
  Vitiligo
  Advanced cancer
  Graft-versus-host disease
  Hepatocellular carcinoma
  Lupus nephritis
  Methicillin-resistant staphylococci infection
  Pancreatic cancer
  Neoplasm
  Bipolar I disorder
  Connective tissue disorder
  Malaria
  Prostate cancer
  Prostate carcinoma
  Psychotic disorder
  Pulmonary arterial hypertension
• UniProt ID: SAFB1_HUMAN
• Pfam ID: PF00076 ; PF02037
• Sequence:
  MAETLSGLGDSGAAGAAALSSASSETGTRRLSDLRVIDLRAELRKRNVDSSGNKSVLMER
  LKKAIEDEGGNPDEIEITSEGNKKTSKRSSKGRKPEEEGVEDNGLEENSGDGQEDVETSL
  ENLQDIDIMDISVLDEAEIDNGSVADCVEDDDADNLQESLSDSRELVEGEMKELPEQLQE
  HAIEDKETINNLDTSSSDFTILQEIEEPSLEPENEKILDILGETCKSEPVKEESSELEQP
  FAQDTSSVGPDRKLAEEEDLFDSAHPEEGDLDLASESTAHAQSSKADSLLAVVKREPAEQ
  PGDGERTDCEPVGLEPAVEQSSAASELAEASSEELAEAPTEAPSPEARDSKEDGRKFDFD
  ACNEVPPAPKESSTSEGADQKMSSPEDDSDTKRLSKEEKGRSSCGRNFWVSGLSSTTRAT
  DLKNLFSKYGKVVGAKVVTNARSPGARCYGFVTMSTAEEATKCINHLHKTELHGKMISVE
  KAKNEPVGKKTSDKRDSDGKKEKSSNSDRSTNLKRDDKCDRKDDAKKGDDGSGEKSKDQD
  DQKPGPSERSRATKSGSRGTERTVVMDKSKGVPVISVKTSGSKERASKSQDRKSASREKR
  SVVSFDKVKEPRKSRDSESHSRVRERSEREQRMQAQWEREERERLEIARERLAFQRQRLE
  RERMERERLERERMHVEHERRREQERIHREREELRRQQELRYEQERRPAVRRPYDLDRRD
  DAYWPEAKRAALDERYHSDFNRQDRFHDFDHRDRGRYPDHSVDRREGSRSMMGEREGQHY
  PERHGGPERHGRDSRDGWGGYGSDKRMSEGRGLPPPPRRDWGDHGRREDDRSWQGTADGG
  MMDRDHKRWQGGERSMSGHSGPGHMMNRGGMSGRGSFAPGGASRGHPIPHGGMQGGFGGQ
  SRGSRPSDARFTRRY
• Function: Binds to scaffold/matrix attachment region (S/MAR) DNA and forms a molecular assembly point to allow the formation of a 'transcriptosomal' complex (consisting of SR proteins and RNA polymerase II) coupling transcription and RNA processing. Functions as an estrogen receptor corepressor and can also bind to the HSP27 promoter and decrease its transcription. Thereby acts as a negative regulator of cell proliferation. When associated with RBMX, binds to and stimulates transcription from the SREBF1 promoter.
• Tissue Specificity: Ubiquitous. Expressed at high levels in the CNS and at low levels in the liver. Expressed in a wide number of breast cancer cell lines.
• Reactome Pathway: SUMOylation of transcription cofactors (R-HSA-3899300)

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Biomarker	[1]
Melanoma	DIS1RRCY	Definitive	Biomarker	[2]
Pneumonia	DIS8EF3M	Definitive	Biomarker	[3]
Skin cancer	DISTM18U	Definitive	Biomarker	[2]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[4]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[5]
Barrett esophagus	DIS416Y7	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[9]
Cholangiocarcinoma	DIS71F6X	Strong	Altered Expression	[10]
Eosinophilic esophagitis	DISR8WSB	Strong	Biomarker	[11]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[12]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[13]
Familial multiple trichoepithelioma	DISKZAUY	Strong	Altered Expression	[14]
Gastroesophageal reflux disease	DISQ8G5S	Strong	Biomarker	[15]
Influenza	DIS3PNU3	Strong	Genetic Variation	[16]
Liver cancer	DISDE4BI	Strong	Biomarker	[9]
Myocardial infarction	DIS655KI	Strong	Biomarker	[17]
Schizoaffective disorder	DISLBW6B	Strong	Genetic Variation	[18]
Smith-Lemli-Opitz syndrome	DISX9ZUA	Strong	Genetic Variation	[19]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[20]
Syphilis	DISJ73BS	Strong	Biomarker	[21]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[22]
Vitiligo	DISR05SL	Strong	Genetic Variation	[5]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[23]
Graft-versus-host disease	DIS0QADF	moderate	Biomarker	[24]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[9]
Lupus nephritis	DISCVGPZ	moderate	Biomarker	[25]
Methicillin-resistant staphylococci infection	DIS6DRDZ	moderate	Biomarker	[26]
Pancreatic cancer	DISJC981	moderate	Biomarker	[27]
Neoplasm	DISZKGEW	Disputed	Biomarker	[2]
Bipolar I disorder	DISD09EH	Limited	Genetic Variation	[28]
Connective tissue disorder	DISKXBS3	Limited	Biomarker	[29]
Malaria	DISQ9Y50	Limited	Biomarker	[30]
Prostate cancer	DISF190Y	Limited	Altered Expression	[31]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[31]
Psychotic disorder	DIS4UQOT	Limited	Genetic Variation	[28]
Pulmonary arterial hypertension	DISP8ZX5	Limited	Biomarker	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Scaffold attachment factor B1 (SAFB).	[32]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Scaffold attachment factor B1 (SAFB).	[33]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Scaffold attachment factor B1 (SAFB).	[34]
Selenium	DM25CGV	Approved	Selenium increases the expression of Scaffold attachment factor B1 (SAFB).	[35]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Scaffold attachment factor B1 (SAFB).	[37]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Scaffold attachment factor B1 (SAFB).	[38]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Scaffold attachment factor B1 (SAFB).	[41]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Scaffold attachment factor B1 (SAFB).	[43]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Scaffold attachment factor B1 (SAFB).	[44]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Scaffold attachment factor B1 (SAFB).	[45]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Scaffold attachment factor B1 (SAFB).	[36]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Scaffold attachment factor B1 (SAFB).	[40]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Scaffold attachment factor B1 (SAFB).	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Scaffold attachment factor B1 (SAFB).	[39]

References

• [1] Cytoplasmic overexpression of CD95L in esophageal adenocarcinoma cells overcomes resistance to CD95-mediated apoptosis.Neoplasia. 2011 Mar;13(3):198-205. doi: 10.1593/neo.101304.
• [2] A commensal strain of Staphylococcus epidermidis protects against skin neoplasia.Sci Adv. 2018 Feb 28;4(2):eaao4502. doi: 10.1126/sciadv.aao4502. eCollection 2018 Feb.
• [3] A Nurse-Driven Oral Care Protocol to Reduce Hospital-Acquired Pneumonia.Am J Nurs. 2019 Feb;119(2):44-51. doi: 10.1097/01.NAJ.0000553204.21342.01.
• [4] Screening of Autism Spectrum Disorders in Geriatric Psychiatry.J Autism Dev Disord. 2017 Sep;47(9):2679-2689. doi: 10.1007/s10803-017-3185-2.
• [5] Evaluation of NLRP1 gene polymorphisms in Vogt-Koyanagi-Harada disease.Jpn J Ophthalmol. 2011 Jan;55(1):57-61. doi: 10.1007/s10384-010-0887-9. Epub 2011 Feb 18.
• [6] Deoxycholic acid promotes development of gastroesophageal reflux disease and Barrett's oesophagus by modulating integrin-v trafficking.J Cell Mol Med. 2017 Dec;21(12):3612-3625. doi: 10.1111/jcmm.13271. Epub 2017 Sep 22.
• [7] Unravelling the RNA-Binding Properties of SAFB Proteins in Breast Cancer Cells.Biomed Res Int. 2015;2015:395816. doi: 10.1155/2015/395816. Epub 2015 Jul 26.
• [8] Scaffold attachment factors SAFB1 and SAFB2: Innocent bystanders or critical players in breast tumorigenesis?.J Cell Biochem. 2003 Nov 1;90(4):653-61. doi: 10.1002/jcb.10685.
• [9] The Munich-Transarterial Chemoembolisation Score Holds Superior Prognostic Capacities Compared to TACE-Tailored Modifications of 9 Established Staging Systems for Hepatocellular Carcinoma.Digestion. 2019;100(1):15-26. doi: 10.1159/000493136. Epub 2018 Oct 3.
• [10] The expression of HSP27 is associated with poor clinical outcome in intrahepatic cholangiocarcinoma.BMC Cancer. 2007 Dec 21;7:232. doi: 10.1186/1471-2407-7-232.
• [11] FGF9-induced proliferative response to eosinophilic inflammation in oesophagitis.Gut. 2009 Feb;58(2):166-73. doi: 10.1136/gut.2008.157628. Epub 2008 Oct 31.
• [12] Pathogenic BRCA1 mutations may be necessary but not sufficient for tissue genomic heterogeneity: Deep sequencing data from ovarian cancer patients.Gynecol Oncol. 2019 Feb;152(2):375-386. doi: 10.1016/j.ygyno.2018.11.016. Epub 2018 Nov 14.
• [13] Downregulation of long non-coding RNA GAS5 promotes cell proliferation, migration and invasion in esophageal squamous cell carcinoma.Oncol Lett. 2018 Aug;16(2):1801-1808. doi: 10.3892/ol.2018.8797. Epub 2018 May 24.
• [14] The decreased expression of Beclin-1 correlates with progression to esophageal adenocarcinoma: the role of deoxycholic acid.Am J Physiol Gastrointest Liver Physiol. 2012 Apr 15;302(8):G864-72. doi: 10.1152/ajpgi.00340.2011. Epub 2012 Feb 2.
• [15] HCl-induced and ATP-dependent upregulation of TRPV1 receptor expression and cytokine production by human esophageal epithelial cells.Am J Physiol Gastrointest Liver Physiol. 2012 Sep 1;303(5):G635-45. doi: 10.1152/ajpgi.00097.2012. Epub 2012 Jul 12.
• [16] Identification and characterization of App: an immunogenic autotransporter protein of Neisseria meningitidis.Mol Microbiol. 2001 Aug;41(3):611-23. doi: 10.1046/j.1365-2958.2001.02516.x.
• [17] Cellular FLICE-inhibitory protein protects against cardiac remodelling after myocardial infarction.Basic Res Cardiol. 2012 Jan;107(1):239. doi: 10.1007/s00395-011-0239-z. Epub 2011 Dec 28.
• [18] Evidence for rare and common genetic risk variants for schizophrenia at protein kinase C, alpha.Mol Psychiatry. 2010 Nov;15(11):1101-11. doi: 10.1038/mp.2009.96. Epub 2009 Sep 29.
• [19] A highly sensitive method for analysis of 7-dehydrocholesterol for the study of Smith-Lemli-Opitz syndrome.J Lipid Res. 2014 Feb;55(2):329-37. doi: 10.1194/jlr.D043877. Epub 2013 Nov 20.
• [20] HSP 27 as possible prognostic factor in patients with oral squamous cell carcinoma.Histol Histopathol. 2004 Jan;19(1):119-28. doi: 10.14670/HH-19.119.
• [21] Analysis of the N-terminal region of the 47-kilodalton integral membrane lipoprotein of Treponema pallidum.Infect Immun. 1992 Apr;60(4):1568-76. doi: 10.1128/iai.60.4.1568-1576.1992.
• [22] CLImAT-HET: detecting subclonal copy number alterations and loss of heterozygosity in heterogeneous tumor samples from whole-genome sequencing data.BMC Med Genomics. 2017 Mar 15;10(1):15. doi: 10.1186/s12920-017-0255-4.
• [23] Downregulation of SAFB Sustains the NF-B Pathway by Targeting TAK1 during the Progression of Colorectal Cancer.Clin Cancer Res. 2017 Nov 15;23(22):7108-7118. doi: 10.1158/1078-0432.CCR-17-0747. Epub 2017 Sep 14.
• [24] Physical and psychosocial aspects of adolescent and young adults after allogeneic hematopoietic stem-cell transplantation: results from a prospective multicenter trial.J Cancer Res Clin Oncol. 2017 Aug;143(8):1613-1619. doi: 10.1007/s00432-017-2424-4. Epub 2017 Apr 19.
• [25] Urinary haptoglobin, alpha-1 anti-chymotrypsin and retinol binding protein identified by proteomics as potential biomarkers for lupus nephritis.Clin Exp Immunol. 2017 May;188(2):254-262. doi: 10.1111/cei.12930. Epub 2017 Feb 23.
• [26] Severity of disease and clinical outcomes in patients with hospital-acquired pneumonia due to methicillin-resistant Staphylococcus aureus strains not influenced by the presence of the Panton-Valentine leukocidin gene.Clin Infect Dis. 2011 Oct;53(8):766-71. doi: 10.1093/cid/cir541. Epub 2011 Aug 31.
• [27] Targeting Mechanoresponsive Proteins in Pancreatic Cancer: 4-Hydroxyacetophenone Blocks Dissemination and Invasion by Activating MYH14.Cancer Res. 2019 Sep 15;79(18):4665-4678. doi: 10.1158/0008-5472.CAN-18-3131. Epub 2019 Jul 29.
• [28] The association of white matter volume in psychotic disorders with genotypic variation in NRG1, MOG and CNP: a voxel-based analysis in affected individuals and their unaffected relatives.Transl Psychiatry. 2012 Oct 9;2(10):e167. doi: 10.1038/tp.2012.82.
• [29] Autoantibody to scaffold attachment factor B (SAFB): A novel connective tissue disease-related autoantibody associated with interstitial lung disease.J Autoimmun. 2017 Jan;76:101-107. doi: 10.1016/j.jaut.2016.09.006. Epub 2016 Sep 25.
• [30] Characterization of domains of the phosphoriboprotein P0 of Plasmodium falciparum.Mol Biochem Parasitol. 2000 Apr 15;107(2):143-54. doi: 10.1016/s0166-6851(99)00226-1.
• [31] Scaffold attachment factor B1 regulates the androgen receptor in concert with the growth inhibitory kinase MST1 and the methyltransferase EZH2.Oncogene. 2014 Jun 19;33(25):3235-45. doi: 10.1038/onc.2013.294. Epub 2013 Jul 29.
• [32] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [33] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [34] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [35] 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.
• [36] 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.
• [37] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [38] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [39] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [40] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [41] 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.
• [42] 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.
• [43] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [44] 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.
• [45] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.