Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPQ0BFY)

• DOT Name: StAR-related lipid transfer protein 4 (STARD4)
• Synonyms: START domain-containing protein 4; StARD4
• Gene Name: STARD4
• UniProt ID: STAR4_HUMAN
• PDB ID: 6L1D; 6L1M
• Pfam ID: PF01852
• Sequence:
  MEGLSDVASFATKLKNTLIQYHSIEEDKWRVAKKTKDVTVWRKPSEEFNGYLYKAQGVID
  DLVYSIIDHIRPGPCRLDWDSLMTSLDILENFEENCCVMRYTTAGQLWNIISPREFVDFS
  YTVGYKEGLLSCGISLDWDEKRPEFVRGYNHPCGWFCVPLKDNPNQSLLTGYIQTDLRGM
  IPQSAVDTAMASTLTNFYGDLRKAL
• Function: Involved in the intracellular transport of cholesterol. Binds cholesterol or other sterols.
• Reactome Pathway: Pregnenolone biosynthesis (R-HSA-196108)

Molecular Interaction Atlas (MIA) of This DOT

3 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 StAR-related lipid transfer protein 4 (STARD4).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of StAR-related lipid transfer protein 4 (STARD4).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of StAR-related lipid transfer protein 4 (STARD4).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of StAR-related lipid transfer protein 4 (STARD4).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of StAR-related lipid transfer protein 4 (STARD4).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of StAR-related lipid transfer protein 4 (STARD4).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of StAR-related lipid transfer protein 4 (STARD4).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of StAR-related lipid transfer protein 4 (STARD4).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of StAR-related lipid transfer protein 4 (STARD4).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of StAR-related lipid transfer protein 4 (STARD4).	[8]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of StAR-related lipid transfer protein 4 (STARD4).	[9]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of StAR-related lipid transfer protein 4 (STARD4).	[10]
UNC0379	DMD1E4J	Preclinical	UNC0379 increases the expression of StAR-related lipid transfer protein 4 (STARD4).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of StAR-related lipid transfer protein 4 (STARD4).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of StAR-related lipid transfer protein 4 (STARD4).	[14]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of StAR-related lipid transfer protein 4 (STARD4).	[15]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of StAR-related lipid transfer protein 4 (STARD4).	[16]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics. Sci Rep. 2023 Jun 29;13(1):10519. doi: 10.1038/s41598-023-37488-0.
• [10] A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol Appl Pharmacol. 2015 Jun 1;285(2):79-88.
• [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] Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63.
• [13] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Whole genome mRNA transcriptomics analysis reveals different modes of action of the diarrheic shellfish poisons okadaic acid and dinophysis toxin-1 versus azaspiracid-1 in Caco-2 cells. Toxicol In Vitro. 2018 Feb;46:102-112.
• [16] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.