Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEIZ7N1)

• DOT Name: Afadin- and alpha-actinin-binding protein (SSX2IP)
• Synonyms: ADIP; Afadin DIL domain-interacting protein; SSX2-interacting protein
• Gene Name: SSX2IP
• UniProt ID: ADIP_HUMAN
• Pfam ID: PF11559
• Sequence:
  MGDWMTVTDPGLSSESKTISQYTSETKMSPSSLYSQQVLCSSIPLSKNVHSFFSAFCTED
  NIEQSISYLDQELTTFGFPSLYEESKGKETKRELNIVAVLNCMNELLVLQRKNLLAQENV
  ETQNLKLGSDMDHLQSCYSKLKEQLETSRREMIGLQERDRQLQCKNRNLHQLLKNEKDEV
  QKLQNIIASRATQYNHDMKRKEREYNKLKERLHQLVMNKKDKKIAMDILNYVGRADGKRG
  SWRTGKTEARNEDEMYKILLNDYEYRQKQILMENAELKKVLQQMKKEMISLLSPQKKKPR
  ERVDDSTGTVISDVEEDAGELSRESMWDLSCETVREQLTNSIRKQWRILKSHVEKLDNQV
  SKVHLEGFNDEDVISRQDHEQETEKLELEIQQCKEMIKTQQQLLQQQLATAYDDDTTSLL
  RDCYLLEEKERLKEEWSLFKEQKKNFERERRSFTEAAIRLGLERKAFEEERASWLKQQFL
  NMTTFDHQNSENVKLFSAFSGSSDWDNLIVHSRQPQKKPHSVSNGSPVCMSKLTKSLPAS
  PSTSDFCQTRSCISEHSSINVLNITAEEIKPNQVGGECTNQKWSVASRPGSQEGCYSGCS
  LSYTNSHVEKDDLP
• Function: Belongs to an adhesion system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs). May connect the nectin-afadin and E-cadherin-catenin system through alpha-actinin and may be involved in organization of the actin cytoskeleton at AJs through afadin and alpha-actinin. Involved in cell movement: localizes at the leading edge of moving cells in response to PDGF and is required for the formation of the leading edge and the promotion of cell movement, possibly via activation of Rac signaling. Acts as a centrosome maturation factor, probably by maintaining the integrity of the pericentriolar material and proper microtubule nucleation at mitotic spindle poles. The function seems to implicate at least in part WRAP73; the SSX2IP:WRAP73 complex is proposed to act as regulator of spindle anchoring at the mitotic centrosome. Involved in ciliogenesis. It is required for targeted recruitment of the BBSome, CEP290, RAB8, and SSTR3 to the cilia.
• Tissue Specificity: Widely expressed, with the highest expression in brain, intermediate expression in kidney, testis, spinal cord, liver, heart, lung, skeletal muscle, ovary, fetal liver and fetal brain, and little to no expression in pancreas and spleen. All specific brain regions showed intermediate to high expression, with highest expression in amygdala. Also expressed in fetal tissues, mainly in liver and brain.
• KEGG Pathway: Adherens junction (hsa04520)

Molecular Interaction Atlas (MIA) of This DOT

17 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 Afadin- and alpha-actinin-binding protein (SSX2IP).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Afadin- and alpha-actinin-binding protein (SSX2IP).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Afadin- and alpha-actinin-binding protein (SSX2IP).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Afadin- and alpha-actinin-binding protein (SSX2IP).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Afadin- and alpha-actinin-binding protein (SSX2IP).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Afadin- and alpha-actinin-binding protein (SSX2IP).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Afadin- and alpha-actinin-binding protein (SSX2IP).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Afadin- and alpha-actinin-binding protein (SSX2IP).	[8]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Afadin- and alpha-actinin-binding protein (SSX2IP).	[9]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Afadin- and alpha-actinin-binding protein (SSX2IP).	[10]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Afadin- and alpha-actinin-binding protein (SSX2IP).	[11]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Afadin- and alpha-actinin-binding protein (SSX2IP).	[12]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Afadin- and alpha-actinin-binding protein (SSX2IP).	[13]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Afadin- and alpha-actinin-binding protein (SSX2IP).	[9]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Afadin- and alpha-actinin-binding protein (SSX2IP).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Afadin- and alpha-actinin-binding protein (SSX2IP).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Afadin- and alpha-actinin-binding protein (SSX2IP).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Afadin- and alpha-actinin-binding protein (SSX2IP).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Afadin- and alpha-actinin-binding protein (SSX2IP).	[16]

References

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• [3] 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.
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• [7] 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.
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• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [11] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [12] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [13] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [14] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [15] 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.
• [16] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [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] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.