Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQJSL7M)

• DOT Name: Translocon-associated protein subunit beta (SSR2)
• Synonyms: TRAP-beta; Signal sequence receptor subunit beta; SSR-beta
• Gene Name: SSR2
• Related Disease:
  Malaria
  Neoplasm
  Pancreatic cancer
  Prostate cancer
  Prostate neoplasm
  Medulloblastoma
  Neuroblastoma
  Neuroendocrine neoplasm
  Primitive neuroectodermal tumor
  Melanoma
• UniProt ID: SSRB_HUMAN
• PDB ID: 8B6L
• Pfam ID: PF05753
• Sequence:
  MRLLSFVVLALFAVTQAEEGARLLASKSLLNRYAVEGRDLTLQYNIYNVGSSAALDVELS
  DDSFPPEDFGIVSGMLNVKWDRIAPASNVSHTVVLRPLKAGYFNFTSATITYLAQEDGPV
  VIGSTSAPGQGGILAQREFDRRFSPHFLDWAAFGVMTLPSIGIPLLLWYSSKRKYDTPKT
  KKN
• Function: TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway: SRP-dependent cotranslational protein targeting to membrane (R-HSA-1799339)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malaria	DISQ9Y50	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Pancreatic cancer	DISJC981	Strong	Biomarker	[3]
Prostate cancer	DISF190Y	Strong	Biomarker	[4]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[4]
Medulloblastoma	DISZD2ZL	moderate	Biomarker	[5]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[6]
Neuroendocrine neoplasm	DISNPLOO	moderate	Altered Expression	[6]
Primitive neuroectodermal tumor	DISFHXHA	moderate	Biomarker	[5]
Melanoma	DIS1RRCY	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Translocon-associated protein subunit beta (SSR2).	[8]
Sertraline	DM0FB1J	Approved	Sertraline increases the expression of Translocon-associated protein subunit beta (SSR2).	[9]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Translocon-associated protein subunit beta (SSR2).	[10]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Translocon-associated protein subunit beta (SSR2).	[13]

2 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 Translocon-associated protein subunit beta (SSR2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Translocon-associated protein subunit beta (SSR2).	[12]

References

• [1] Retrospective analysis of risk factors of slide positivity among febrile patients in the Salween river valley of Shan Special Region II, northern Myanmar.BMC Public Health. 2018 Apr 27;18(1):560. doi: 10.1186/s12889-018-5469-7.
• [2] Differentially expressed genes in multidrug resistant variants of U-2 OS human osteosarcoma cells.Oncol Rep. 2004 Jun;11(6):1257-63.
• [3] Somatostatin receptor subtype 2 gene therapy inhibits pancreatic cancer in vitro.J Surg Res. 2002 Jun 1;105(1):58-64. doi: 10.1006/jsre.2002.6450.
• [4] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [5] Differential expression of somatostatin receptors, P44/42 MAPK, and mTOR activation in medulloblastomas and primitive neuroectodermal tumors.Appl Immunohistochem Mol Morphol. 2013 Dec;21(6):532-8. doi: 10.1097/PAI.0b013e3182813724.
• [6] SSR2(a) receptor expression and adrenergic/cholinergic characteristics in differentiated SH-SY5Y cells.Neurochem Res. 2003 Apr;28(3-4):449-60. doi: 10.1023/a:1022848718109.
• [7] Signal Sequence Receptor 2 is required for survival of human melanoma cells as part of an unfolded protein response to endoplasmic reticulum stress.Mutagenesis. 2016 Sep;31(5):573-82. doi: 10.1093/mutage/gew023. Epub 2016 May 14.
• [8] 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.
• [9] Sertraline induces endoplasmic reticulum stress in hepatic cells. Toxicology. 2014 Aug 1;322:78-88. doi: 10.1016/j.tox.2014.05.007. Epub 2014 May 24.
• [10] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [11] 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.
• [12] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [13] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.