Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT46SDNQ)

• DOT Name: Sciellin (SCEL)
• Gene Name: SCEL
• Related Disease:
  Carcinoma of esophagus
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Kallmann syndrome
  Neoplasm of esophagus
  Chronic renal failure
  End-stage renal disease
  Thyroid gland papillary carcinoma
• UniProt ID: SCEL_HUMAN
• Sequence:
  MSNVTLRKMSPTGNEMKSTTQGTTRKQQDFHEVNKRRTFLQDNSWIKKRPEEEKDENYGR
  VVLNRHNSHDALDRKVNERDVPKATISRYSSDDTLDRISDRNDAAKTYKANTLDNQLTNR
  SMSMFRSLEVTKLQPGGSLNANTSNTIASTSATTPVKKKRQSWFPPPPPGYNASSSTGTR
  RREPGVHPPIPPKPSSPVSSPNQLRQDNRQIHPPKPGVYTETNRSAERNIRSQDLDNIVK
  VATSLQRSDKGEELDNLIKMNKSLNRNQGLDSLFRANPKVEEREKRAKSLESLIYMSTRT
  DKDGKGIQSLGSPIKVNQRTDKNEKGRQNLESVAKVNARMNKTSRRSEDLDNATEVNPKG
  HENTTGKKDLDGLIKVDPETNKNITRGQSLDNLIKVTPEVKRSNQGSKDLNNFIKVYPGT
  EKSTEGGQSLDSLIKVTPERNRTNQGNQDLENLIKVIPSANKSSEQGLDEHINVSPKAVK
  NTDGKQDLDKLIKVNPEIFTNNQRNQDLANLIKVNPAVIRNNQSQDLDNLIKVKPSALRN
  TNRDQNLENLIEVNSHVSENKNGSSNTGAKQAGPQDTVVYTRTYVENSKSPKDGYQENIS
  GKYIQTVYSTSDRSVIERDMCTYCRKPLGVETKMILDELQICCHSTCFKCEICKQPLENL
  QAGDSIWIYRQTIHCEPCYSKIMAKWIP
• Function: May function in the assembly or regulation of proteins in the cornified envelope. The LIM domain may be involved in homotypic or heterotypic associations and may function to localize sciellin to the cornified envelope.
• Tissue Specificity: Highly expressed in esophagus. It is also expressed in keratinocytes, amniotic tissue, foreskin stratum spinosum and stratum granulosum, hair follicle and nail.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of esophagus	DISS6G4D	Strong	Genetic Variation	[1]
Esophageal cancer	DISGB2VN	Strong	Genetic Variation	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[1]
Kallmann syndrome	DISO3HDG	Strong	Biomarker	[2]
Neoplasm of esophagus	DISOLKAQ	Strong	Genetic Variation	[1]
Chronic renal failure	DISGG7K6	moderate	Altered Expression	[3]
End-stage renal disease	DISXA7GG	moderate	Altered Expression	[3]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Sciellin (SCEL).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sciellin (SCEL).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Sciellin (SCEL).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Sciellin (SCEL).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Sciellin (SCEL).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Sciellin (SCEL).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Sciellin (SCEL).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Sciellin (SCEL).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Sciellin (SCEL).	[13]

1 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 Sciellin (SCEL).	[12]

References

• [1] Analysis of Sciellin (SCEL) as a candidate gene in esophageal squamous cell carcinoma.Anticancer Res. 2004 May-Jun;24(3a):1417-9.
• [2] Identification of ROBO1/2 and SCEL as candidate genes in Kallmann syndrome with emerging bioinformatic analysis.Endocrine. 2020 Jan;67(1):224-232. doi: 10.1007/s12020-019-02010-y. Epub 2019 Jul 19.
• [3] High risk of development of renal cell tumor in end-stage kidney disease: the role of microenvironment.Tumour Biol. 2016 Jul;37(7):9511-9. doi: 10.1007/s13277-016-4855-y. Epub 2016 Jan 20.
• [4] Gene expression in papillary thyroid carcinoma reveals highly consistent profiles.Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15044-9. doi: 10.1073/pnas.251547398.
• [5] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [6] Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [9] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [11] Glucocorticoids inhibit cell death in ovarian cancer and up-regulate caspase inhibitor cIAP2. Clin Cancer Res. 2005 Sep 1;11(17):6325-32. doi: 10.1158/1078-0432.CCR-05-0182.
• [12] 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.
• [13] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.