Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3QW6PH)

• DOT Name: TSSK6-activating co-chaperone protein (TSACC)
• Synonyms: SSTK-interacting protein; SIP; SSTK-IP
• Gene Name: TSACC
• Related Disease:
  Anxiety
  Anxiety disorder
  Breast cancer
  Breast carcinoma
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Depression
  Gastric cancer
  Glioma
  Neoplasm
  Renal cell carcinoma
  Stomach cancer
  Type-1/2 diabetes
  Varicose veins
  Major depressive disorder
  Melanoma
  Dermatomyositis
  Generalized anxiety disorder
  Metastatic malignant neoplasm
  Neuroblastoma
  Pancreatic cancer
  Small lymphocytic lymphoma
  Stroke
• UniProt ID: TSACC_HUMAN
• Pfam ID: PF15836
• Sequence:
  MERHTSHPNRKVPAKEEANAVPLCRAKPSPSYINLQASSPPATFLNIQTTKLPSVDHKPK
  ECLGLLECMYANLQLQTQLAQQQMAVLEHLQASVTQLAPGRGSNNSSLPALSPNPLLNHL
  PQFSK
• Function: Co-chaperone that facilitates HSP-mediated activation of TSSK6.
• Tissue Specificity: Expressed in testis but is absent from mature sperm.

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety	DISIJDBA	Strong	Biomarker	[1]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[3]
Colon cancer	DISVC52G	Strong	Genetic Variation	[4]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[4]
Depression	DIS3XJ69	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	Strong	Biomarker	[5]
Glioma	DIS5RPEH	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[3]
Stomach cancer	DISKIJSX	Strong	Biomarker	[5]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[8]
Varicose veins	DISIMBN2	Strong	Biomarker	[9]
Major depressive disorder	DIS4CL3X	moderate	Genetic Variation	[10]
Melanoma	DIS1RRCY	moderate	Biomarker	[11]
Dermatomyositis	DIS50C5O	Limited	Biomarker	[12]
Generalized anxiety disorder	DISPSQCW	Limited	Genetic Variation	[10]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[7]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[13]
Pancreatic cancer	DISJC981	Limited	Biomarker	[14]
Small lymphocytic lymphoma	DIS30POX	Limited	Altered Expression	[15]
Stroke	DISX6UHX	Limited	Biomarker	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of TSSK6-activating co-chaperone protein (TSACC).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of TSSK6-activating co-chaperone protein (TSACC).	[18]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of TSSK6-activating co-chaperone protein (TSACC).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the expression of TSSK6-activating co-chaperone protein (TSACC).	[20]

References

• [1] Anxiety, Depression, and Pain Symptoms: Associations With the Course of Marijuana Use and Drug Use Consequences Among Urban Primary Care Patients.J Addict Med. 2018 Jan/Feb;12(1):45-52. doi: 10.1097/ADM.0000000000000362.
• [2] TGF- drives epithelial-mesenchymal transition through EF1-mediated downregulation of ESRP.Oncogene. 2012 Jun 28;31(26):3190-201. doi: 10.1038/onc.2011.493. Epub 2011 Oct 31.
• [3] Overexpressed CacyBP/SIP leads to the suppression of growth in renal cell carcinoma.Biochem Biophys Res Commun. 2007 May 18;356(4):864-71. doi: 10.1016/j.bbrc.2007.03.080. Epub 2007 Mar 26.
• [4] The effect of S100A6 on nuclear translocation of CacyBP/SIP in colon cancer cells.PLoS One. 2018 Mar 13;13(3):e0192208. doi: 10.1371/journal.pone.0192208. eCollection 2018.
• [5] Calcyclin-binding protein inhibits proliferation, tumorigenicity, and invasion of gastric cancer.Mol Cancer Res. 2007 Dec;5(12):1254-62. doi: 10.1158/1541-7786.MCR-06-0426.
• [6] CacyBP/SIP protein is important for the proliferation of human glioma cells.IUBMB Life. 2014 Apr;66(4):286-91. doi: 10.1002/iub.1263. Epub 2014 Apr 17.
• [7] Sulfated polysaccharide of Sepiella Maindroni ink inhibits the migration, invasion and matrix metalloproteinase-2 expression through suppressing EGFR-mediated p38/MAPK and PI3K/Akt/mTOR signaling pathways in SKOV-3 cells.Int J Biol Macromol. 2018 Feb;107(Pt A):349-362. doi: 10.1016/j.ijbiomac.2017.08.178. Epub 2017 Sep 9.
• [8] Nitric oxide and its role as a non-adrenergic, non-cholinergic inhibitory neurotransmitter in the gastrointestinal tract.Br J Pharmacol. 2019 Jan;176(2):212-227. doi: 10.1111/bph.14459. Epub 2018 Sep 3.
• [9] Inhibitory Neural Regulation of the Ca (2+) Transients in Intramuscular Interstitial Cells of Cajal in the Small Intestine.Front Physiol. 2018 Apr 9;9:328. doi: 10.3389/fphys.2018.00328. eCollection 2018.
• [10] Is the effect of work-related psychosocial exposure on depressive and anxiety disorders short-term, lagged or cumulative?.Int Arch Occup Environ Health. 2020 Jan;93(1):87-104. doi: 10.1007/s00420-019-01466-9. Epub 2019 Aug 3.
• [11] Anti-metastatic and anti-angiogenic activities of sulfated polysaccharide of Sepiella maindroni ink.Carbohydr Polym. 2013 Jan 2;91(1):403-9. doi: 10.1016/j.carbpol.2012.08.050. Epub 2012 Aug 22.
• [12] Efficacy and safety of oral high-trough level tacrolimus in acute/subacute interstitial pneumonia with dermatomyositis.Int J Rheum Dis. 2019 Feb;22(2):303-313. doi: 10.1111/1756-185X.13414. Epub 2018 Nov 5.
• [13] CacyBP/SIP phosphatase activity in neuroblastoma NB2a and colon cancer HCT116 cells.Biochem Cell Biol. 2012 Aug;90(4):558-64. doi: 10.1139/o2012-011. Epub 2012 Apr 5.
• [14] CacyBP/SIP enhances multidrug resistance of pancreatic cancer cells by regulation of P-gp and Bcl-2.Apoptosis. 2013 Jul;18(7):861-9. doi: 10.1007/s10495-013-0831-9.
• [15] Expression and regulation of CacyBP/SIP in chronic lymphocytic leukemia cell balances of cell proliferation with apoptosis.J Cancer Res Clin Oncol. 2016 Apr;142(4):741-8. doi: 10.1007/s00432-015-2077-0. Epub 2015 Nov 25.
• [16] Effects of virtual reality-based training with BTs-Nirvana on functional recovery in stroke patients: preliminary considerations.Int J Neurosci. 2018 Sep;128(9):791-796. doi: 10.1080/00207454.2017.1403915. Epub 2018 Feb 2.
• [17] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [18] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [19] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [20] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.