Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB2DNQU)

• DOT Name: DNA/RNA-binding protein KIN17 (KIN)
• Synonyms: Binding to curved DNA; KIN, antigenic determinant of recA protein homolog
• Gene Name: KIN
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cervical cancer
  Cervical carcinoma
  Karyomegalic interstitial nephritis
  Neoplasm
  Non-small-cell lung cancer
  Triple negative breast cancer
• UniProt ID: KIN17_HUMAN
• PDB ID: 2CKK; 2V1N; 7ABH; 7ABI
• Pfam ID: PF10357 ; PF18131
• Sequence:
  MGKSDFLTPKAIANRIKSKGLQKLRWYCQMCQKQCRDENGFKCHCMSESHQRQLLLASEN
  PQQFMDYFSEEFRNDFLELLRRRFGTKRVHNNIVYNEYISHREHIHMNATQWETLTDFTK
  WLGREGLCKVDETPKGWYIQYIDRDPETIRRQLELEKKKKQDLDDEEKTAKFIEEQVRRG
  LEGKEQEVPTFTELSRENDEEKVTFNLSKGACSSSGATSSKSSTLGPSALKTIGSSASVK
  RKESSQSSTQSKEKKKKKSALDEIMEIEEEKKRTARTDYWLQPEIIVKIITKKLGEKYHK
  KKAIVKEVIDKYTAVVKMIDSGDKLKLDQTHLETVIPAPGKRILVLNGGYRGNEGTLESI
  NEKTFSATIVIETGPLKGRRVEGIQYEDISKLA
• Function: Involved in DNA replication and the cellular response to DNA damage. May participate in DNA replication factories and create a bridge between DNA replication and repair mediated by high molecular weight complexes. May play a role in illegitimate recombination and regulation of gene expression. May participate in mRNA processing. Binds, in vitro, to double-stranded DNA. Also shown to bind preferentially to curved DNA in vitro and in vivo. Binds via its C-terminal domain to RNA in vitro.
• Tissue Specificity: Ubiquitously expressed in all tissues examined, with highest levels in skeletal muscle, heart and testis. Differentially expressed in non-tumorigenic and tumorigenic cell lines. Highly expressed in proliferating epithelial keratinocyte cells in vitro (at protein level).
• Reactome Pathway: Protein methylation (R-HSA-8876725)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[3]
Cervical cancer	DISFSHPF	Strong	Biomarker	[4]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[4]
Karyomegalic interstitial nephritis	DISY3YH1	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[6]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[2]

5 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 DNA/RNA-binding protein KIN17 (KIN).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of DNA/RNA-binding protein KIN17 (KIN).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of DNA/RNA-binding protein KIN17 (KIN).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of DNA/RNA-binding protein KIN17 (KIN).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of DNA/RNA-binding protein KIN17 (KIN).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of DNA/RNA-binding protein KIN17 (KIN).	[9]

References

• [1] Molecular Profiling Establishes Genetic Features Predictive of the Efficacy of the p110 Inhibitor KIN-193.Cancer Res. 2019 Sep 1;79(17):4524-4531. doi: 10.1158/0008-5472.CAN-19-0588. Epub 2019 Jul 10.
• [2] Knockdown of DNA/RNA-binding protein KIN17 promotes apoptosis of triple-negative breast cancer cells.Oncol Lett. 2019 Jan;17(1):288-293. doi: 10.3892/ol.2018.9597. Epub 2018 Oct 18.
• [3] Up-regulation of kin17 is essential for proliferation of breast cancer.PLoS One. 2011;6(9):e25343. doi: 10.1371/journal.pone.0025343. Epub 2011 Sep 29.
• [4] Elevated Expression of Kin17 in Cervical Cancer and Its Association With Cancer Cell Proliferation and Invasion.Int J Gynecol Cancer. 2017 May;27(4):628-633. doi: 10.1097/IGC.0000000000000928.
• [5] Critical review of renal tubule karyomegaly in non-clinical safety evaluation studies and its significance for human risk assessment.Crit Rev Toxicol. 2018 Aug;48(7):575-595. doi: 10.1080/10408444.2018.1503641. Epub 2018 Oct 2.
• [6] Upregulation of KIN17 is associated with non-small cell lung cancer invasiveness.Oncol Lett. 2017 Apr;13(4):2274-2280. doi: 10.3892/ol.2017.5707. Epub 2017 Feb 9.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] 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.
• [11] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.