Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI86ECP)

• DOT Name: Ankyrin repeat domain-containing protein SOWAHC (SOWAHC)
• Synonyms: Ankyrin repeat domain-containing protein 57; Protein sosondowah homolog C
• Gene Name: SOWAHC
• UniProt ID: SWAHC_HUMAN
• Pfam ID: PF12796
• Sequence:
  MEGPAEWGPEAALGPEAVLRFLAERGGRALHAELVQHFRGALGGEPEQRARARAHFKELV
  NAVATVRVDPADGAKYVHLKKRFCEGPSEPSGDPPRIQVTAEPEAPDGPAGPEARDRLPD
  AAAPESLPGQGRELGEGEPPAPAHWPPLSAGARRKNSRRDVQPLPRTPAPGPSEDLELPP
  HGCEEADRGSSLVGATAQRPARQNLRDLVMGSSPQLKRSVCPGGSSPGSSSGGGRGRGGG
  DSDSASVASSSAEEESSGGGSVTLDPLEHAWMLSASDGKWDSLEGLLTCEPGLLVKRDFI
  TGFTCLHWAAKHGRQELLAMLVNFANKHQLPVNIDARTSGGYTALHLAAMHGHVEVVKLL
  VGAYDADVDIRDYSGKKASQYLSRSIAEEIKNLVGALDEGDGESAAGSGGGRWRLSKVLP
  SHLITYKLSHALEDGGDHHHHHHSAEGWVGGKAKDPGRKASGSSSGRIKPRLNKIRFRTQ
  IVHTTPSFRDPEQPLEGRGEEGVGEERPVKGHSPFTLRPKSNVFG
• Reactome Pathway:
  RHOB GTPase cycle (R-HSA-9013026)
  RHOF GTPase cycle (R-HSA-9035034)
  RHOA GTPase cycle (R-HSA-8980692)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[1]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[18]

16 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 Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[11]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ankyrin repeat domain-containing protein SOWAHC (SOWAHC).	[17]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [11] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [12] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] 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.
• [17] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [18] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.