Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHH06X8)

• DOT Name: SEC14 domain and spectrin repeat-containing protein 1 (SESTD1)
• Synonyms: Huntingtin-interacting protein-like protein; Protein Solo
• Gene Name: SESTD1
• Related Disease:
  Advanced cancer
  Bipolar disorder
  High blood pressure
  Thrombocytopenia
  Endocarditis
  Atopic dermatitis
• UniProt ID: SESD1_HUMAN
• Pfam ID: PF13716
• Sequence:
  MEASVILPILKKKLAFLSGGKDRRSGLILTIPLCLEQTNMDELSVTLDYLLSIPSEKCKA
  RGFTVIVDGRKSQWNVVKTVVVMLQNVVPAEVSLVCVVKPDEFWDKKVTHFCFWKEKDRL
  GFEVILVSANKLTRYIEPCQLTEDFGGSLTYDHMDWLNKRLVFEKFTKESTSLLDELALI
  NNGSDKGNQQEKERSVDLNFLPSVDPETVLQTGHELLSELQQRRFNGSDGGVSWSPMDDE
  LLAQPQVMKLLDSLREQYTRYQEVCRQRSKRTQLEEIQQKVMQVVNWLEGPGSEQLRAQW
  GIGDSIRASQALQQKHEEIESQHSEWFAVYVELNQQIAALLNAGDEEDLVELKSLQQQLS
  DVCYRQASQLEFRQNLLQAALEFHGVAQDLSQQLDGLLGMLCVDVAPADGASIQQTLKLL
  EEKLKSVDVGLQGLREKGQGLLDQISNQASWAYGKDVTIENKENVDHIQGVMEDMQLRKQ
  RCEDMVDVRRLKMLQMVQLFKCEEDAAQAVEWLSELLDALLKTHIRLGDDAQETKVLLEK
  HRKFVDVAQSTYDYGRQLLQATVVLCQSLRCTSRSSGDTLPRLNRVWKQFTIASEERVHR
  LEMAIAFHSNAEKILQDCPEEPEAINDEEQFDEIEAVGKSLLDRLTVPVVYPDGTEQYFG
  SPSDMASTAENIRDRMKLVNLKRQQLRHPEMVTTES
• Function: May act as the primary docking protein directing membrane turnover and assembly of the transient receptor potential channels TRPC4 and TRPC5. Binds phospholipids such as phosphatidylinositol monophosphates, phosphatidylinositol diphosphates (PIP2s) and phosphatidic acid, but not less polar lipids including phosphatidylcholine, phosphatidylserine, and phosphatidylinositol. The binding to PIP2s is calcium dependent. Might be involved in the plasma membrane localization of CTNNB1.
• Tissue Specificity: Broad expression. High expression in thalamus and brain. Significantly expressed in vasculature.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[2]
High blood pressure	DISY2OHH	Strong	Biomarker	[3]
Thrombocytopenia	DISU61YW	Strong	Biomarker	[4]
Endocarditis	DISBU610	Disputed	Genetic Variation	[5]
Atopic dermatitis	DISTCP41	Limited	Biomarker	[6]

9 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 SEC14 domain and spectrin repeat-containing protein 1 (SESTD1).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of SEC14 domain and spectrin repeat-containing protein 1 (SESTD1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of SEC14 domain and spectrin repeat-containing protein 1 (SESTD1).	[9]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of SEC14 domain and spectrin repeat-containing protein 1 (SESTD1).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of SEC14 domain and spectrin repeat-containing protein 1 (SESTD1).	[11]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of SEC14 domain and spectrin repeat-containing protein 1 (SESTD1).	[12]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of SEC14 domain and spectrin repeat-containing protein 1 (SESTD1).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of SEC14 domain and spectrin repeat-containing protein 1 (SESTD1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of SEC14 domain and spectrin repeat-containing protein 1 (SESTD1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of SEC14 domain and spectrin repeat-containing protein 1 (SESTD1).	[14]

References

• [1] Paradoxical expression of anti-apoptotic and MRP genes on cancer stem-like cell isolated from TJ905 glioblastoma multiforme cell line.Cancer Invest. 2008 May;26(4):338-43. doi: 10.1080/07357900701788064.
• [2] Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder.Mol Psychiatry. 2016 Sep;21(9):1290-7. doi: 10.1038/mp.2015.165. Epub 2015 Oct 27.
• [3] Six-Month Results of Treatment-Blinded Medication Titration for Hypertension Control After Randomization to Endovascular Ultrasound Renal Denervation or a Sham Procedure in the RADIANCE-HTN SOLO Trial.Circulation. 2019 May 28;139(22):2542-2553. doi: 10.1161/CIRCULATIONAHA.119.040451. Epub 2019 Mar 17.
• [4] Freedom SOLO-Associated Thrombocytopaenia is Valve-Dependent and Not Due to In Vitro Pseudothrombocytopaenia.Heart Lung Circ. 2017 Mar;26(3):268-275. doi: 10.1016/j.hlc.2016.07.002. Epub 2016 Aug 16.
• [5] Is the Freedom SOLO Stentless Bioprosthesis a Useful Tool for Patients with Aortic Endocarditis and Aortic Annular Destruction?.Thorac Cardiovasc Surg. 2019 Dec;67(8):644-651. doi: 10.1055/s-0038-1668134. Epub 2018 Aug 16.
• [6] Dupilumab improves patient-reported symptoms of atopic dermatitis, symptoms of anxiety and depression, and health-related quality of life in moderate-to-severe atopic dermatitis: analysis of pooled data from the randomized trials SOLO 1 and SOLO 2.J Dermatolog Treat. 2020 Sep;31(6):606-614. doi: 10.1080/09546634.2019.1612836. Epub 2019 Jun 9.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [11] 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.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [14] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [15] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.