Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2W80XC)

• DOT Name: DNA-binding protein SATB2 (SATB2)
• Synonyms: Special AT-rich sequence-binding protein 2
• Gene Name: SATB2
• Related Disease:
  Chromosome 2q32-q33 deletion syndrome
  SATB2 associated disorder
  Advanced cancer
  Anxiety
  Appendiceal neoplasm
  Breast cancer
  Carcinoma
  Clear cell renal carcinoma
  Cleft palate
  Cleft soft palate
  Colorectal adenocarcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Endometrial carcinoma
  Esophageal squamous cell carcinoma
  Gastric cancer
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Inflammatory bowel disease
  Isolated cleft palate
  Laryngeal squamous cell carcinoma
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Mucinous adenocarcinoma
  Neurodevelopmental disorder
  Neuroendocrine neoplasm
  Osteoarthritis
  Pancreatic cancer
  Parkinson disease
  Rheumatoid arthritis
  Schizophrenia
  Sleep disorder
  Squamous cell carcinoma
  Stomach cancer
  Tooth agenesis
  Triple negative breast cancer
  Bone osteosarcoma
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Movement disorder
  Small-cell lung cancer
  Autism
  Intellectual disability
  Osteoporosis
• UniProt ID: SATB2_HUMAN
• PDB ID: 1WI3; 1WIZ; 2CSF
• Pfam ID: PF02376 ; PF16557 ; PF00046 ; PF16534
• Sequence:
  MERRSESPCLRDSPDRRSGSPDVKGPPPVKVARLEQNGSPMGARGRPNGAVAKAVGGLMI
  PVFCVVEQLDGSLEYDNREEHAEFVLVRKDVLFSQLVETALLALGYSHSSAAQAQGIIKL
  GRWNPLPLSYVTDAPDATVADMLQDVYHVVTLKIQLQSCSKLEDLPAEQWNHATVRNALK
  ELLKEMNQSTLAKECPLSQSMISSIVNSTYYANVSATKCQEFGRWYKKYKKIKVERVERE
  NLSDYCVLGQRPMHLPNMNQLASLGKTNEQSPHSQIHHSTPIRNQVPALQPIMSPGLLSP
  QLSPQLVRQQIAMAHLINQQIAVSRLLAHQHPQAINQQFLNHPPIPRAVKPEPTNSSVEV
  SPDIYQQVRDELKRASVSQAVFARVAFNRTQGLLSEILRKEEDPRTASQSLLVNLRAMQN
  FLNLPEVERDRIYQDERERSMNPNVSMVSSASSSPSSSRTPQAKTSTPTTDLPIKVDGAN
  INITAAIYDEIQQEMKRAKVSQALFAKVAANKSQGWLCELLRWKENPSPENRTLWENLCT
  IRRFLNLPQHERDVIYEEESRHHHSERMQHVVQLPPEPVQVLHRQQSQPAKESSPPREEA
  PPPPPPTEDSCAKKPRSRTKISLEALGILQSFIHDVGLYPDQEAIHTLSAQLDLPKHTII
  KFFQNQRYHVKHHGKLKEHLGSAVDVAEYKDEELLTESEENDSEEGSEEMYKVEAEEENA
  DKSKAAPAEIDQR
• Function: Binds to DNA, at nuclear matrix- or scaffold-associated regions. Thought to recognize the sugar-phosphate structure of double-stranded DNA. Transcription factor controlling nuclear gene expression, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin-loop remodeling. Acts as a docking site for several chromatin remodeling enzymes and also by recruiting corepressors (HDACs) or coactivators (HATs) directly to promoters and enhancers. Required for the initiation of the upper-layer neurons (UL1) specific genetic program and for the inactivation of deep-layer neurons (DL) and UL2 specific genes, probably by modulating BCL11B expression. Repressor of Ctip2 and regulatory determinant of corticocortical connections in the developing cerebral cortex. May play an important role in palate formation. Acts as a molecular node in a transcriptional network regulating skeletal development and osteoblast differentiation.
• Tissue Specificity: High expression in adult brain, moderate expression in fetal brain, and weak expression in adult liver, kidney, and spinal cord and in select brain regions, including amygdala, corpus callosum, caudate nucleus, and hippocampus.
• Reactome Pathway:
  RUNX2 regulates osteoblast differentiation (R-HSA-8940973)
  SUMOylation of chromatin organization proteins (R-HSA-4551638)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chromosome 2q32-q33 deletion syndrome	DIS3SJ9R	Definitive	Autosomal dominant	[1]
SATB2 associated disorder	DISAVFKY	Definitive	Autosomal dominant	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Anxiety	DISIJDBA	Strong	Genetic Variation	[4]
Appendiceal neoplasm	DIS2XZ0U	Strong	Altered Expression	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Carcinoma	DISH9F1N	Strong	Altered Expression	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[8]
Cleft palate	DIS6G5TF	Strong	Biomarker	[9]
Cleft soft palate	DISCN11I	Strong	Biomarker	[10]
Colorectal adenocarcinoma	DISPQOUB	Strong	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[11]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[12]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[13]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[14]
Gastric cancer	DISXGOUK	Strong	Biomarker	[15]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[17]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[11]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[9]
Laryngeal squamous cell carcinoma	DIS9UUVF	Strong	Biomarker	[18]
Lung cancer	DISCM4YA	Strong	Biomarker	[19]
Lung carcinoma	DISTR26C	Strong	Biomarker	[19]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[20]
Mucinous adenocarcinoma	DISKNFE8	Strong	Biomarker	[21]
Neurodevelopmental disorder	DIS372XH	Strong	Genetic Variation	[22]
Neuroendocrine neoplasm	DISNPLOO	Strong	Altered Expression	[23]
Osteoarthritis	DIS05URM	Strong	Biomarker	[24]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[25]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[26]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[24]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[27]
Sleep disorder	DIS3JP1U	Strong	Genetic Variation	[28]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[6]
Stomach cancer	DISKIJSX	Strong	Biomarker	[15]
Tooth agenesis	DIS1PWC7	Strong	Biomarker	[29]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[30]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[31]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[6]
Colon cancer	DISVC52G	moderate	Biomarker	[32]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[32]
Movement disorder	DISOJJ2D	moderate	Genetic Variation	[33]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[34]
Autism	DISV4V1Z	Limited	Genetic Variation	[35]
Intellectual disability	DISMBNXP	Limited	Biomarker	[9]
Osteoporosis	DISF2JE0	Limited	Biomarker	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	DNA-binding protein SATB2 (SATB2) affects the response to substance of Mitoxantrone.	[55]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of DNA-binding protein SATB2 (SATB2).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of DNA-binding protein SATB2 (SATB2).	[48]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of DNA-binding protein SATB2 (SATB2).	[49]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of DNA-binding protein SATB2 (SATB2).	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA-binding protein SATB2 (SATB2).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of DNA-binding protein SATB2 (SATB2).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of DNA-binding protein SATB2 (SATB2).	[40]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of DNA-binding protein SATB2 (SATB2).	[41]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of DNA-binding protein SATB2 (SATB2).	[42]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of DNA-binding protein SATB2 (SATB2).	[43]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of DNA-binding protein SATB2 (SATB2).	[44]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of DNA-binding protein SATB2 (SATB2).	[45]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of DNA-binding protein SATB2 (SATB2).	[46]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of DNA-binding protein SATB2 (SATB2).	[47]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of DNA-binding protein SATB2 (SATB2).	[47]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of DNA-binding protein SATB2 (SATB2).	[50]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of DNA-binding protein SATB2 (SATB2).	[52]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of DNA-binding protein SATB2 (SATB2).	[53]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of DNA-binding protein SATB2 (SATB2).	[54]

References

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• [2] 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.
• [3] Deregulation of SATB2 in carcinogenesis with emphasis on miRNA-mediated control.Carcinogenesis. 2019 May 14;40(3):393-402. doi: 10.1093/carcin/bgz020.
• [4] Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
• [5] SATB2 protein expression by immunohistochemistry is a sensitive and specific marker of appendiceal and rectosigmoid well differentiated neuroendocrine tumours.Histopathology. 2020 Mar;76(4):550-559. doi: 10.1111/his.14012. Epub 2020 Jan 24.
• [6] SATB2 suppresses non-small cell lung cancer invasiveness by G9a.Clin Exp Med. 2018 Feb;18(1):37-44. doi: 10.1007/s10238-017-0464-3. Epub 2017 Jun 30.
• [7] MiR-34a inhibits the proliferation, migration, and invasion of oral squamous cell carcinoma by directly targeting SATB2.J Cell Physiol. 2020 May;235(5):4856-4864. doi: 10.1002/jcp.29363. Epub 2019 Oct 29.
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• [10] Satb2 haploinsufficiency phenocopies 2q32-q33 deletions, whereas loss suggests a fundamental role in the coordination of jaw development.Am J Hum Genet. 2006 Oct;79(4):668-78. doi: 10.1086/508214. Epub 2006 Aug 30.
• [11] Colitis-associated colorectal adenocarcinomas are frequently associated with non-intestinal mucin profiles and loss of SATB2 expression.Mod Pathol. 2019 Jun;32(6):884-892. doi: 10.1038/s41379-018-0198-0. Epub 2019 Feb 1.
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• [17] Higher expression of SATB2 in hepatocellular carcinoma of African Americans determines more aggressive phenotypes than those of Caucasian Americans.J Cell Mol Med. 2019 Dec;23(12):7999-8009. doi: 10.1111/jcmm.14652. Epub 2019 Oct 11.
• [18] SATB1 and SATB2 play opposing roles in c-Myc expression and progression of colorectal cancer.Oncotarget. 2016 Jan 26;7(4):4993-5006. doi: 10.18632/oncotarget.6651.
• [19] Role of miR-31 and SATB2 in arsenic-induced malignant BEAS-2B cell transformation.Mol Carcinog. 2018 Aug;57(8):968-977. doi: 10.1002/mc.22817. Epub 2018 Apr 17.
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• [21] SATB2 is a supportive marker for the differentiation of a primary mucinous tumor of the ovary and an ovarian metastasis of a low-grade appendiceal mucinous neoplasm (LAMN): A series of seven cases.Pathol Res Pract. 2018 Mar;214(3):426-430. doi: 10.1016/j.prp.2017.12.008. Epub 2017 Dec 14.
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• [23] SATB2 in neuroendocrine neoplasms: strong expression is restricted to well-differentiated tumours of lower gastrointestinal tract origin and is most frequent in Merkel cell carcinoma among poorly differentiated carcinomas.Histopathology. 2020 Jan;76(2):251-264. doi: 10.1111/his.13943. Epub 2019 Nov 15.
• [24] Analysis of critical molecules and signaling pathways in osteoarthritis and rheumatoid arthritis.Mol Med Rep. 2013 Feb;7(2):603-7. doi: 10.3892/mmr.2012.1224. Epub 2012 Dec 4.
• [25] Role of SATB2 in human pancreatic cancer: Implications in transformation and a promising biomarker.Oncotarget. 2016 Sep 6;7(36):57783-57797. doi: 10.18632/oncotarget.10860.
• [26] Investigation of the roles of dysbindin-1 and SATB2 in the progression of Parkinson's disease.Eur Rev Med Pharmacol Sci. 2019 Sep;23(17):7510-7516. doi: 10.26355/eurrev_201909_18865.
• [27] Genes encoding SATB2-interacting proteins in adult cerebral cortex contribute to human cognitive ability.PLoS Genet. 2019 Feb 6;15(2):e1007890. doi: 10.1371/journal.pgen.1007890. eCollection 2019 Feb.
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• [29] Characterization of the first intragenic SATB2 duplication in a girl with intellectual disability, nearly absent speech and suspected hypodontia.Eur J Hum Genet. 2015 May;23(5):704-7. doi: 10.1038/ejhg.2014.163. Epub 2014 Aug 13.
• [30] MiR-31 inhibits migration and invasion by targeting SATB2 in triple negative breast cancer.Gene. 2016 Dec 5;594(1):47-58. doi: 10.1016/j.gene.2016.08.057. Epub 2016 Sep 1.
• [31] Dehydroandrographolide Inhibits Osteosarcoma Cell Growth and Metastasis by Targeting SATB2-mediated EMT.Anticancer Agents Med Chem. 2019;19(14):1728-1736. doi: 10.2174/1871520619666190705121614.
• [32] SATB2 and CDX2 are prognostic biomarkers in DNA mismatch repair protein deficient colon cancer.Mod Pathol. 2019 Jul;32(8):1217-1231. doi: 10.1038/s41379-019-0265-1. Epub 2019 Apr 8.
• [33] DEPDC5 mutations in familial and sporadic focal epilepsy.Clin Genet. 2017 Oct;92(4):397-404. doi: 10.1111/cge.12992. Epub 2017 Mar 30.
• [34] Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer.Nat Genet. 2012 Oct;44(10):1111-6. doi: 10.1038/ng.2405. Epub 2012 Sep 2.
• [35] Genes regulated by SATB2 during neurodevelopment contribute to schizophrenia and educational attainment.PLoS Genet. 2018 Jul 24;14(7):e1007515. doi: 10.1371/journal.pgen.1007515. eCollection 2018 Jul.
• [36] Estrogen regulates stemness and senescence of bone marrow stromal cells to prevent osteoporosis via ER-SATB2 pathway.J Cell Physiol. 2018 May;233(5):4194-4204. doi: 10.1002/jcp.26233. Epub 2017 Nov 16.
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