Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT07ETZT)

• DOT Name: Transcription factor Sp7 (SP7)
• Synonyms: Zinc finger protein osterix
• Gene Name: SP7
• Related Disease:
  Bone disease
  Bone giant cell tumor
  Bone osteosarcoma
  Metastatic malignant neoplasm
  Myelodysplastic syndrome
  Osteogenesis imperfecta
  Osteogenesis imperfecta type 12
  Osteosarcoma
  Osteogenesis imperfecta type 4
  Neoplasm
• UniProt ID: SP7_HUMAN
• Pfam ID: PF00096
• Sequence:
  MASSLLEEEVHYGSSPLAMLTAACSKFGGSSPLRDSTTLGKAGTKKPYSVGSDLSASKTM
  GDAYPAPFTSTNGLLSPAGSPPAPTSGYANDYPPFSHSFPGPTGTQDPGLLVPKGHSSSD
  CLPSVYTSLDMTHPYGSWYKAGIHAGISPGPGNTPTPWWDMHPGGNWLGGGQGQGDGLQG
  TLPTGPAQPPLNPQLPTYPSDFAPLNPAPYPAPHLLQPGPQHVLPQDVYKPKAVGNSGQL
  EGSGGAKPPRGASTGGSGGYGGSGAGRSSCDCPNCQELERLGAAAAGLRKKPIHSCHIPG
  CGKVYGKASHLKAHLRWHTGERPFVCNWLFCGKRFTRSDELERHVRTHTREKKFTCLLCS
  KRFTRSDHLSKHQRTHGEPGPGPPPSGPKELGEGRSTGEEEASQTPRPSASPATPEKAPG
  GSPEQSNLLEI
• Function: Transcriptional activator essential for osteoblast differentiation. Binds to SP1 and EKLF consensus sequences and to other G/C-rich sequences.
• Tissue Specificity: Restricted to bone-derived cell.
• Reactome Pathway: RUNX2 regulates osteoblast differentiation (R-HSA-8940973)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone disease	DISE1F82	Strong	Altered Expression	[1]
Bone giant cell tumor	DIS0RGK9	Strong	Biomarker	[2]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[3]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[3]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[4]
Osteogenesis imperfecta	DIS7XQSD	Strong	Genetic Variation	[5]
Osteogenesis imperfecta type 12	DISUMXTO	Strong	Autosomal recessive	[6]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[3]
Osteogenesis imperfecta type 4	DIS8S46L	Supportive	Autosomal dominant	[7]
Neoplasm	DISZKGEW	Limited	Biomarker	[8]

2 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 Transcription factor Sp7 (SP7).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Transcription factor Sp7 (SP7).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transcription factor Sp7 (SP7).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcription factor Sp7 (SP7).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Transcription factor Sp7 (SP7).	[12]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Transcription factor Sp7 (SP7).	[13]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of Transcription factor Sp7 (SP7).	[14]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Transcription factor Sp7 (SP7).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcription factor Sp7 (SP7).	[16]
PD98059	DMZC90M	Investigative	PD98059 decreases the expression of Transcription factor Sp7 (SP7).	[11]
Alpha-ketoglutaric acid	DM5LFYN	Investigative	Alpha-ketoglutaric acid increases the expression of Transcription factor Sp7 (SP7).	[17]

References

• [1] Negative regulation of the osteoblast function in multiple myeloma through the repressor gene E4BP4 activated by malignant plasma cells.Clin Cancer Res. 2008 Oct 1;14(19):6081-91. doi: 10.1158/1078-0432.CCR-08-0219.
• [2] Expression of preosteoblast markers and Cbfa-1 and Osterix gene transcripts in stromal tumour cells of giant cell tumour of bone.Bone. 2004 Mar;34(3):393-401. doi: 10.1016/j.bone.2003.10.013.
• [3] The metastatic behavior of osteosarcoma by gene expression and cytogenetic analyses.Hum Pathol. 2013 Oct;44(10):2188-98. doi: 10.1016/j.humpath.2013.04.013. Epub 2013 Jul 8.
• [4] Phenotype of mesenchymal stem cells from patients with myelodyplastic syndrome maybe partly modulated by decitabine.Oncol Lett. 2019 Nov;18(5):4457-4466. doi: 10.3892/ol.2019.10788. Epub 2019 Sep 3.
• [5] Specificity Protein 7 Is Required for Proliferation and Differentiation of Ameloblasts and Odontoblasts.J Bone Miner Res. 2018 Jun;33(6):1126-1140. doi: 10.1002/jbmr.3401. Epub 2018 Mar 24.
• [6] The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002 Jan 11;108(1):17-29. doi: 10.1016/s0092-8674(01)00622-5.
• [7] Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A. 2011 May;155A(5):943-68. doi: 10.1002/ajmg.a.33909. Epub 2011 Mar 15.
• [8] Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer.Dev Cell. 2017 Jun 5;41(5):467-480.e3. doi: 10.1016/j.devcel.2017.05.005.
• [9] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [10] Small ubiquitin-related modifier-1 modification regulates all-trans-retinoic acid-induced differentiation via stabilization of retinoic acid receptor . FEBS J. 2014 Jul;281(13):3032-47. doi: 10.1111/febs.12840. Epub 2014 Jun 2.
• [11] Resveratrol enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via ER-dependent ERK1/2 activation. Phytomedicine. 2007 Dec;14(12):806-14. doi: 10.1016/j.phymed.2007.04.003. Epub 2007 Aug 8.
• [12] Naringin protects human adipose-derived mesenchymal stem cells against hydrogen peroxide-induced inhibition of osteogenic differentiation. Chem Biol Interact. 2015 Dec 5;242:255-61. doi: 10.1016/j.cbi.2015.10.010. Epub 2015 Oct 19.
• [13] Cannabidiol induces osteoblast differentiation via angiopoietin1 and p38 MAPK. Environ Toxicol. 2020 Dec;35(12):1318-1325. doi: 10.1002/tox.22996. Epub 2020 Jul 13.
• [14] Berberine promotes bone marrow-derived mesenchymal stem cells osteogenic differentiation via canonical Wnt/-catenin signaling pathway. Toxicol Lett. 2016 Jan 5;240(1):68-80. doi: 10.1016/j.toxlet.2015.10.007. Epub 2015 Oct 22.
• [15] 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.
• [16] Repercussions of Bisphenol A on the Physiology of Human Osteoblasts. Int J Mol Sci. 2022 May 11;23(10):5349. doi: 10.3390/ijms23105349.
• [17] Alpha ketoglutarate exerts a pro-osteogenic effect in osteoblast cell lines through activation of JNK and mTOR/S6K1/S6 signaling pathways. Toxicol Appl Pharmacol. 2019 Jul 1;374:53-64.