Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCIF6KC)

• DOT Name: Transcription factor SOX-13 (SOX13)
• Synonyms: Islet cell antigen 12; SRY (Sex determining region Y)-box 13; Type 1 diabetes autoantigen ICA12
• Gene Name: SOX13
• Related Disease:
  Type-1 diabetes
  Anxiety disorder
  Glioma
  Neoplasm
  Non-small-cell lung cancer
  Colorectal carcinoma
  Non-insulin dependent diabetes
  Plasma cell myeloma
  Type-1/2 diabetes
• UniProt ID: SOX13_HUMAN
• Pfam ID: PF00505
• Sequence:
  MSMRSPISAQLALDGVGTMVNCTIKSEEKKEPCHEAPQGSATAAEPQPGDPARASQDSAD
  PQAPAQGNFRGSWDCSSPEGNGSPEPKRPGVSEAASGSQEKLDFNRNLKEVVPAIEKLLS
  SDWKERFLGRNSMEAKDVKGTQESLAEKELQLLVMIHQLSTLRDQLLTAHSEQKNMAAML
  FEKQQQQMELARQQQEQIAKQQQQLIQQQHKINLLQQQIQQVNMPYVMIPAFPPSHQPLP
  VTPDSQLALPIQPIPCKPVEYPLQLLHSPPAPVVKRPGAMATHHPLQEPSQPLNLTAKPK
  APELPNTSSSPSLKMSSCVPRPPSHGGPTRDLQSSPPSLPLGFLGEGDAVTKAIQDARQL
  LHSHSGALDGSPNTPFRKDLISLDSSPAKERLEDGCVHPLEEAMLSCDMDGSRHFPESRN
  SSHIKRPMNAFMVWAKDERRKILQAFPDMHNSSISKILGSRWKSMTNQEKQPYYEEQARL
  SRQHLEKYPDYKYKPRPKRTCIVEGKRLRVGEYKALMRTRRQDARQSYVIPPQAGQVQMS
  SSDVLYPRAAGMPLAQPLVEHYVPRSLDPNMPVIVNTCSLREEGEGTDDRHSVADGEMYR
  YSEDEDSEGEEKSDGELVVLTD
• Function: Transcription factor that binds to DNA at the consensus sequence 5'-AACAAT-3'. Binds to the proximal promoter region of the myelin protein MPZ gene, and may thereby be involved in the differentiation of oligodendroglia in the developing spinal tube. Binds to the gene promoter of MBP and acts as a transcriptional repressor. Binds to and modifies the activity of TCF7/TCF1, thereby inhibiting transcription and modulates normal gamma-delta T-cell development and differentiation of IL17A expressing gamma-delta T-cells. Regulates expression of BLK in the differentiation of IL17A expressing gamma-delta T-cells. Promotes brown adipocyte differentiation. Inhibitor of WNT signaling.
• Tissue Specificity: Expressed in exocrine cells and islets of Langerhans in the pancreas (at protein level) . Expressed in the pancreas, placenta, kidney, brain, heart, lung, and liver . Expressed in adipose tissue, cervix, colon, esophagus, ovary, prostate, small intestine, spleen, testicle, thymus and thyroid .
• Reactome Pathway: Deactivation of the beta-catenin transactivating complex (R-HSA-3769402)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Type-1 diabetes	DIS7HLUB	Definitive	Biomarker	[1]
Anxiety disorder	DISBI2BT	Strong	Genetic Variation	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[5]
Non-insulin dependent diabetes	DISK1O5Z	moderate	Biomarker	[6]
Plasma cell myeloma	DIS0DFZ0	moderate	Altered Expression	[7]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription factor SOX-13 (SOX13).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor SOX-13 (SOX13).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transcription factor SOX-13 (SOX13).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transcription factor SOX-13 (SOX13).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transcription factor SOX-13 (SOX13).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transcription factor SOX-13 (SOX13).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Transcription factor SOX-13 (SOX13).	[15]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Transcription factor SOX-13 (SOX13).	[16]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Transcription factor SOX-13 (SOX13).	[17]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transcription factor SOX-13 (SOX13).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transcription factor SOX-13 (SOX13).	[19]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Transcription factor SOX-13 (SOX13).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transcription factor SOX-13 (SOX13).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Transcription factor SOX-13 (SOX13).	[21]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Transcription factor SOX-13 (SOX13).	[23]

References

• [1] ICA12 autoantibodies are associated with non-DR3/non-DR4 in patients with latent autoimmune diabetes in adults from northern India.Ann N Y Acad Sci. 2002 Apr;958:329-32. doi: 10.1111/j.1749-6632.2002.tb02998.x.
• [2] A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders.Transl Psychiatry. 2019 May 23;9(1):150. doi: 10.1038/s41398-019-0481-y.
• [3] FUS/circ_002136/miR-138-5p/SOX13 feedback loop regulates angiogenesis in Glioma.J Exp Clin Cancer Res. 2019 Feb 8;38(1):65. doi: 10.1186/s13046-019-1065-7.
• [4] MiR-185 inhibits tumor growth and enhances chemo-resistance via targeting SRY-related high mobility group box transcription factor 13 in non-small-cell carcinoma.Am J Transl Res. 2018 Aug 15;10(8):2600-2609. eCollection 2018.
• [5] p38-regulated FOXC1 stability is required for colorectal cancer metastasis.J Pathol. 2020 Feb;250(2):217-230. doi: 10.1002/path.5362. Epub 2019 Nov 28.
• [6] Sex-determining region Y-related protein SOX13 is a diabetes autoantigen expressed in pancreatic islets.Diabetes. 2000 Apr;49(4):555-61. doi: 10.2337/diabetes.49.4.555.
• [7] NEAT1 promotes cell proliferation in multiple myeloma by activating PI3K/AKT pathway.Eur Rev Med Pharmacol Sci. 2018 Oct;22(19):6403-6411. doi: 10.26355/eurrev_201810_16053.
• [8] Antibodies to new beta cell antigen ICA12 in Latvian diabetes patients.Ann N Y Acad Sci. 2002 Apr;958:297-304. doi: 10.1111/j.1749-6632.2002.tb02991.x.
• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [17] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [18] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [19] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [20] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [21] 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.
• [22] 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.
• [23] 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.