Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT83V0ZK)

• DOT Name: Protein phosphatase Slingshot homolog 3 (SSH3)
• Synonyms: EC 3.1.3.16; EC 3.1.3.48; SSH-like protein 3; SSH-3L; hSSH-3L
• Gene Name: SSH3
• Related Disease:
  Colorectal carcinoma
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
• UniProt ID: SSH3_HUMAN
• EC Number: 3.1.3.16; 3.1.3.48
• Pfam ID: PF08766 ; PF00782
• Sequence:
  MALVTVSRSPPGSGASTPVGPWDQAVQRRSRLQRRQSFAVLRGAVLGLQDGGDNDDAAEA
  SSEPTEKAPSEEELHGDQTDFGQGSQSPQKQEEQRQHLHLMVQLLRPQDDIRLAAQLEAP
  RPPRLRYLLVVSTREGEGLSQDETVLLGVDFPDSSSPSCTLGLVLPLWSDTQVYLDGDGG
  FSVTSGGQSRIFKPISIQTMWATLQVLHQACEAALGSGLVPGGSALTWASHYQERLNSEQ
  SCLNEWTAMADLESLRPPSAEPGGSSEQEQMEQAIRAELWKVLDVSDLESVTSKEIRQAL
  ELRLGLPLQQYRDFIDNQMLLLVAQRDRASRIFPHLYLGSEWNAANLEELQRNRVTHILN
  MAREIDNFYPERFTYHNVRLWDEESAQLLPHWKETHRFIEAARAQGTHVLVHCKMGVSRS
  AATVLAYAMKQYECSLEQALRHVQELRPIARPNPGFLRQLQIYQGILTASRQSHVWEQKV
  GGVSPEEHPAPEVSTPFPPLPPEPEGGGEEKVVGMEESQAAPKEEPGPRPRINLRGVMRS
  ISLLEPSLELESTSETSDMPEVFSSHESSHEEPLQPFPQLARTKGGQQVDRGPQPALKSR
  QSVVTLQGSAVVANRTQAFQEQEQGQGQGQGEPCISSTPRFRKVVRQASVHDSGEEGEA
• Function: Protein phosphatase which may play a role in the regulation of actin filament dynamics. Can dephosphorylate and activate the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly.
• KEGG Pathway:
  Axon guidance (hsa04360)
  Regulation of actin cytoskeleton (hsa04810)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[2]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[2]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[2]

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 Protein phosphatase Slingshot homolog 3 (SSH3).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein phosphatase Slingshot homolog 3 (SSH3).	[11]

11 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 Protein phosphatase Slingshot homolog 3 (SSH3).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein phosphatase Slingshot homolog 3 (SSH3).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein phosphatase Slingshot homolog 3 (SSH3).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Protein phosphatase Slingshot homolog 3 (SSH3).	[7]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Protein phosphatase Slingshot homolog 3 (SSH3).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein phosphatase Slingshot homolog 3 (SSH3).	[9]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Protein phosphatase Slingshot homolog 3 (SSH3).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Protein phosphatase Slingshot homolog 3 (SSH3).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein phosphatase Slingshot homolog 3 (SSH3).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein phosphatase Slingshot homolog 3 (SSH3).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein phosphatase Slingshot homolog 3 (SSH3).	[14]

References

• [1] SSH3 facilitates colorectal cancer cell invasion and metastasis by affecting signaling cascades involving LIMK1/Rac1.Am J Cancer Res. 2019 May 1;9(5):1061-1073. eCollection 2019.
• [2] Transmembrane protein 88 (TMEM88) promoter hypomethylation is associated with platinum resistance in ovarian cancer.Gynecol Oncol. 2016 Sep;142(3):539-47. doi: 10.1016/j.ygyno.2016.06.017. Epub 2016 Jun 30.
• [3] 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.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Gamma-irradiation and doxorubicin treatment of normal human cells cause cell cycle arrest via different pathways. Mol Cells. 2005 Dec 31;20(3):331-8.
• [7] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [8] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [9] 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.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [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] BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res. 2014 Feb 15;20(4):912-25.
• [13] 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.
• [14] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.