Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDKHN1E)

• DOT Name: Protein SSXT (SS18)
• Synonyms: Protein SYT; Synovial sarcoma translocated to X chromosome protein
• Gene Name: SS18
• Related Disease:
  Adenocarcinoma
  Carcinoma
  Chromosomal disorder
  Desmoplastic small round cell tumor
  Metastatic malignant neoplasm
  Mycosis fungoides
  Soft tissue neoplasm
  Soft tissue sarcoma
  Rhabdomyosarcoma
  Ventricular fibrillation
  Benign neoplasm
  Recessive X-linked ichthyosis
• UniProt ID: SSXT_HUMAN
• PDB ID: 7VRB
• Pfam ID: PF05030
• Sequence:
  MSVAFAAPRQRGKGEITPAAIQKMLDDNNHLIQCIMDSQNKGKTSECSQYQQMLHTNLVY
  LATIADSNQNMQSLLPAPPTQNMPMGPGGMNQSGPPPPPRSHNMPSDGMVGGGPPAPHMQ
  NQMNGQMPGPNHMPMQGPGPNQLNMTNSSMNMPSSSHGSMGGYNHSVPSSQSMPVQNQMT
  MSQGQPMGNYGPRPNMSMQPNQGPMMHQQPPSQQYNMPQGGGQHYQGQQPPMGMMGQVNQ
  GNHMMGQRQIPPYRPPQQGPPQQYSGQEDYYGDQYSHGGQGPPEGMNQQYYPDGHNDYGY
  QQPSYPEQGYDRPYEDSSQHYYEGGNSQYGQQQDAYQGPPPQQGYPPQQQQYPGQQGYPG
  QQQGYGPSQGGPGPQYPNYPQGQGQQYGGYRPTQPGPPQPPQQRPYGYDQGQYGNYQQ
• Function: Appears to function synergistically with RBM14 as a transcriptional coactivator. Isoform 1 and isoform 2 function in nuclear receptor coactivation. Isoform 1 and isoform 2 function in general transcriptional coactivation. Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner.
• Tissue Specificity: Fairly ubiquitously expressed. Expressed in synovial sarcomas and in other human cell lines. The fusion genes SSXT-SSX1 and SSXT-SSX2 are expressed only in synovial sarcomas.
• KEGG Pathway:
  ATP-dependent chromatin remodeling (hsa03082)
  Transcriptio.l misregulation in cancer (hsa05202)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[1]
Carcinoma	DISH9F1N	Strong	Biomarker	[2]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[3]
Desmoplastic small round cell tumor	DISLI2ME	Strong	Genetic Variation	[4]
Metastatic malignant neoplasm	DIS86UK6	Strong	Genetic Variation	[5]
Mycosis fungoides	DIS62RB8	Strong	Biomarker	[6]
Soft tissue neoplasm	DISP2OHE	Strong	Genetic Variation	[7]
Soft tissue sarcoma	DISSN8XB	Strong	Biomarker	[8]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[9]
Ventricular fibrillation	DIS7IN76	moderate	Biomarker	[10]
Benign neoplasm	DISDUXAD	Limited	Genetic Variation	[11]
Recessive X-linked ichthyosis	DISZY56W	Limited	Altered Expression	[11]

6 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 Protein SSXT (SS18).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein SSXT (SS18).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Protein SSXT (SS18).	[14]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Protein SSXT (SS18).	[13]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protein SSXT (SS18).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein SSXT (SS18).	[16]

References

• [1] Microsecretory Adenocarcinoma: A Novel Salivary Gland Tumor Characterized by a Recurrent MEF2C-SS18 Fusion.Am J Surg Pathol. 2019 Aug;43(8):1023-1032. doi: 10.1097/PAS.0000000000001273.
• [2] Expression of TLE-1 and CD99 in Carcinoma: Pitfalls in Diagnosis of Synovial Sarcoma.Appl Immunohistochem Mol Morphol. 2018 Jul;26(6):368-373. doi: 10.1097/PAI.0000000000000436.
• [3] Diagnosis of synovial sarcoma with the reverse transcriptase-polymerase chain reaction: analyses of 84 soft tissue and bone tumors.Diagn Mol Pathol. 1998 Apr;7(2):102-10. doi: 10.1097/00019606-199804000-00007.
• [4] Defining Ewing and Ewing-like small round cell tumors (SRCT): The need for molecular techniques in their categorization and differential diagnosis. A study of 200 cases.Ann Diagn Pathol. 2016 Jun;22:25-32. doi: 10.1016/j.anndiagpath.2016.03.002. Epub 2016 Mar 14.
• [5] Clinical impact of molecular and cytogenetic findings in synovial sarcoma.Genes Chromosomes Cancer. 2001 Aug;31(4):362-72. doi: 10.1002/gcc.1155.
• [6] Primary cutaneous T-cell lymphomas do not show specific NAV3 gene deletion or translocation.J Invest Dermatol. 2008 Oct;128(10):2458-66. doi: 10.1038/jid.2008.113. Epub 2008 May 29.
• [7] The synovial sarcoma translocation protein SYT-SSX2 recruits beta-catenin to the nucleus and associates with it in an active complex.Oncogene. 2006 Jun 22;25(26):3661-9. doi: 10.1038/sj.onc.1209413. Epub 2006 Feb 6.
• [8] The prognostic impact of SYT-SSX fusion type and histological grade in pediatric patients with synovial sarcoma treated according to the CWS (Cooperative Weichteilsarkom Studie) trials.Pediatr Blood Cancer. 2017 Jan;64(1):89-95. doi: 10.1002/pbc.26206. Epub 2016 Sep 13.
• [9] Differentiating Ewing's sarcoma from other round blue cell tumors using a RT-PCR translocation panel on formalin-fixed paraffin-embedded tissues.Mod Pathol. 2007 Mar;20(3):397-404. doi: 10.1038/modpathol.3800755.
• [10] Clinical and Angiographic Predictors of Mortality in Sudden Cardiac Arrest Patients Having Cardiac Catheterisation: A Single Centre Registry.Heart Lung Circ. 2019 Mar;28(3):370-378. doi: 10.1016/j.hlc.2018.01.005. Epub 2018 Feb 8.
• [11] Molecular analyses in the diagnosis and prediction of prognosis in non-GIST soft tissue sarcomas: A systematic review and meta-analysis.Cancer Treat Rev. 2018 May;66:74-81. doi: 10.1016/j.ctrv.2018.04.005. Epub 2018 Apr 22.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [14] 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.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.