Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCWEL5F)

• DOT Name: Translocation protein SEC62 (SEC62)
• Synonyms: Translocation protein 1; TP-1; hTP-1
• Gene Name: SEC62
• Related Disease:
  Gastric cancer
  Stomach cancer
  Advanced cancer
  Carcinoma
  Cervical cancer
  Cervical carcinoma
  Cervical Intraepithelial neoplasia
  Dysplasia of cervix
  Head-neck squamous cell carcinoma
  Leiomyoma
  Neoplasm
  Non-small-cell lung cancer
  Prostate neoplasm
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Uterine fibroids
  Vulvar intraepithelial neoplasia
  Hepatocellular carcinoma
  Squamous cell carcinoma
  Breast cancer
  Breast carcinoma
  Invasive ductal breast carcinoma
  Prostate cancer
  Prostate carcinoma
• UniProt ID: SEC62_HUMAN
• PDB ID: 7BRT
• Pfam ID: PF03839
• Sequence:
  MAERRRHKKRIQEVGEPSKEEKAVAKYLRFNCPTKSTNMMGHRVDYFIASKAVDCLLDSK
  WAKAKKGEEALFTTRESVVDYCNRLLKKQFFHRALKVMKMKYDKDIKKEKDKGKAESGKE
  EDKKSKKENIKDEKTKKEKEKKKDGEKEESKKEETPGTPKKKETKKKFKLEPHDDQVFLD
  GNEVYVWIYDPVHFKTFVMGLILVIAVIAATLFPLWPAEMRVGVYYLSVGAGCFVASILL
  LAVARCILFLIIWLITGGRHHFWFLPNLTADVGFIDSFRPLYTHEYKGPKADLKKDEKSE
  TKKQQKSDSEEKSDSEKKEDEEGKVGPGNHGTEGSGGERHSDTDSDRREDDRSQHSSGNG
  NDFEMITKEELEQQTDGDCEEDEEEENDGETPKSSHEKS
• Function: Mediates post-translational transport of precursor polypeptides across endoplasmic reticulum (ER). Proposed to act as a targeting receptor for small presecretory proteins containing short and apolar signal peptides. Targets and properly positions newly synthesized presecretory proteins into the SEC61 channel-forming translocon complex, triggering channel opening for polypeptide translocation to the ER lumen.
• KEGG Pathway:
  Protein export (hsa03060)
  Protein processing in endoplasmic reticulum (hsa04141)

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Definitive	Biomarker	[1]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Carcinoma	DISH9F1N	Strong	Biomarker	[3]
Cervical cancer	DISFSHPF	Strong	Biomarker	[2]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[2]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Altered Expression	[2]
Dysplasia of cervix	DISOAROS	Strong	Altered Expression	[2]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[4]
Leiomyoma	DISLDDFN	Strong	Altered Expression	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[4]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[6]
Thyroid cancer	DIS3VLDH	Strong	Altered Expression	[7]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[7]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[7]
Uterine fibroids	DISBZRMJ	Strong	Altered Expression	[5]
Vulvar intraepithelial neoplasia	DISA474V	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[8]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[9]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[10]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[10]
Invasive ductal breast carcinoma	DIS43J58	Limited	Biomarker	[10]
Prostate cancer	DISF190Y	Limited	Biomarker	[11]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Translocation protein SEC62 (SEC62).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Translocation protein SEC62 (SEC62).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Translocation protein SEC62 (SEC62).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Translocation protein SEC62 (SEC62).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Translocation protein SEC62 (SEC62).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Translocation protein SEC62 (SEC62).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Translocation protein SEC62 (SEC62).	[18]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Translocation protein SEC62 (SEC62).	[19]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Translocation protein SEC62 (SEC62).	[21]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Translocation protein SEC62 (SEC62).	[22]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Translocation protein SEC62 (SEC62).	[23]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Translocation protein SEC62 (SEC62).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Translocation protein SEC62 (SEC62).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Translocation protein SEC62 (SEC62).	[25]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Translocation protein SEC62 (SEC62).	[22]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Translocation protein SEC62 (SEC62).	[26]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Translocation protein SEC62 (SEC62).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the ubiquitination of Translocation protein SEC62 (SEC62).	[20]

References

• [1] MiR-4429 prevented gastric cancer progression through targeting METTL3 to inhibit m(6)A-caused stabilization of SEC62.Biochem Biophys Res Commun. 2019 Oct 1;517(4):581-587. doi: 10.1016/j.bbrc.2019.07.058. Epub 2019 Aug 5.
• [2] Sec62/Ki67 dual staining in cervical cytology specimens: a new marker for high-grade dysplasia.Arch Gynecol Obstet. 2019 Feb;299(2):481-488. doi: 10.1007/s00404-018-4981-4. Epub 2018 Nov 29.
• [3] Sec62/Ki67 and p16/Ki67 dual-staining immunocytochemistry in vulvar cytology for the identification of vulvar intraepithelial neoplasia and vulvar cancer: a pilot study.Arch Gynecol Obstet. 2019 Mar;299(3):825-833. doi: 10.1007/s00404-018-5021-0. Epub 2019 Jan 4.
• [4] Expression of 3q oncogene SEC62 in atypical fibroxanthoma-immunohistochemical analysis of 41 cases and correlation with clinical, viral and histopathologic features.Oncol Lett. 2019 Feb;17(2):1768-1776. doi: 10.3892/ol.2018.9767. Epub 2018 Nov 27.
• [5] The Mechanism and Function of Epigenetics in Uterine Leiomyoma Development.Reprod Sci. 2016 Feb;23(2):163-75. doi: 10.1177/1933719115584449. Epub 2015 Apr 28.
• [6] Genomic and expression analysis of the 3q25-q26 amplification unit reveals TLOC1/SEC62 as a probable target gene in prostate cancer.Mol Cancer Res. 2006 Mar;4(3):169-76. doi: 10.1158/1541-7786.MCR-05-0165.
• [7] Targeting cell migration and the endoplasmic reticulum stress response with calmodulin antagonists: a clinically tested small molecule phenocopy of SEC62 gene silencing in human tumor cells.BMC Cancer. 2013 Dec 5;13:574. doi: 10.1186/1471-2407-13-574.
• [8] Sec62 promotes early recurrence of hepatocellular carcinoma through activating integrin/CAV1 signalling.Oncogenesis. 2019 Dec 10;8(12):74. doi: 10.1038/s41389-019-0183-6.
• [9] Identification of SEC62 as a potential marker for 3q amplification and cellular migration in dysplastic cervical lesions.BMC Cancer. 2016 Aug 23;16(1):676. doi: 10.1186/s12885-016-2739-6.
• [10] Identification of 3q oncogene SEC62 as a marker for distant metastasis and poor clinical outcome in invasive ductal breast cancer.Arch Gynecol Obstet. 2019 May;299(5):1405-1413. doi: 10.1007/s00404-019-05081-4. Epub 2019 Feb 12.
• [11] Silencing of the SEC62 gene inhibits migratory and invasive potential of various tumor cells.Int J Cancer. 2011 May 15;128(10):2284-95. doi: 10.1002/ijc.25580.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [14] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [15] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [16] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [19] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [20] Quantitative Assessment of Arsenite-Induced Perturbation of Ubiquitinated Proteome. Chem Res Toxicol. 2022 Sep 19;35(9):1589-1597. doi: 10.1021/acs.chemrestox.2c00197. Epub 2022 Aug 22.
• [21] 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.
• [22] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [23] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [24] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [25] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [26] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [27] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.