Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRMK3PU)

• DOT Name: Sickle tail protein homolog (KIAA1217)
• Gene Name: KIAA1217
• Related Disease:
  Alzheimer disease
  Intervertebral disc degeneration
  Knee osteoarthritis
  Lung adenocarcinoma
  Non-small-cell lung cancer
  Coronary heart disease
• UniProt ID: SKT_HUMAN
• Pfam ID: PF03915
• Sequence:
  MEENESQKCEPCLPYSADRRQMQEQGKGNLHVTSPEDAECRRTKERLSNGNSRGSVSKSS
  RNIPRRHTLGGPRSSKEILGMQTSEMDRKREAFLEHLKQKYPHHASAIMGHQERLRDQTR
  SPKLSHSPQPPSLGDPVEHLSETSADSLEAMSEGDAPTPFSRGSRTRASLPVVRSTNQTK
  ERSLGVLYLQYGDETKQLRMPNEITSADTIRALFVSAFPQQLTMKMLESPSVAIYIKDES
  RNVYYELNDVRNIQDRSLLKVYNKDPAHAFNHTPKTMNGDMRMQRELVYARGDGPGAPRP
  GSTAHPPHAIPNSPPSTPVPHSMPPSPSRIPYGGTRSMVVPGNATIPRDRISSLPVSRPI
  SPSPSAILERRDVKPDEDMSGKNIAMYRNEGFYADPYLYHEGRMSIASSHGGHPLDVPDH
  IIAYHRTAIRSASAYCNPSMQAEMHMEQSLYRQKSRKYPDSHLPTLGSKTPPASPHRVSD
  LRMIDMHAHYNAHGPPHTMQPDRASPSRQAFKKEPGTLVYIEKPRSAAGLSSLVDLGPPL
  MEKQVFAYSTATIPKDRETRERMQAMEKQIASLTGLVQSALFKGPITSYSKDASSEKMMK
  TTANRNHTDSAGTPHVSGGKMLSALESTVPPSQPPPVGTSAIHMSLLEMRRSVAELRLQL
  QQMRQLQLQNQELLRAMMKKAELEISGKVMETMKRLEDPVQRQRVLVEQERQKYLHEEEK
  IVKKLCELEDFVEDLKKDSTAASRLVTLKDVEDGAFLLRQVGEAVATLKGEFPTLQNKMR
  AILRIEVEAVRFLKEEPHKLDSLLKRVRSMTDVLTMLRRHVTDGLLKGTDAAQAAQYMAM
  EKATAAEVLKSQEEAAHTSGQPFHSTGAPGDAKSEVVPLSGMMVRHAQSSPVVIQPSQHS
  VALLNPAQNLPHVASSPAVPQEATSTLQMSQAPQSPQIPMNGSAMQSLFIEEIHSVSAKN
  RAVSIEKAEKKWEEKRQNLDHYNGKEFEKLLEEAQANIMKSIPNLEMPPATGPLPRGDAP
  VDKVELSEDSPNSEQDLEKLGGKSPPPPPPPPRRSYLPGSGLTTTRSGDVVYTGRKENIT
  AKASSEDAGPSPQTRATKYPAEEPASAWTPSPPPVTTSSSKDEEEEEEEGDKIMAELQAF
  QKCSFMDVNSNSHAEPSRADSHVKDTRSGATVPPKEKKNLEFFHEDVRKSDVEYENGPQM
  EFQKVTTGAVRPSDPPKWERGMENSISDASRTSEYKTEIIMKENSISNMSLLRDSRNYSQ
  ETVPKASFGFSGISPLEDEINKGSKISGLQYSIPDTENQTLNYGKTKEMEKQNTDKCHVS
  SHTRLTESSVHDFKTEDQEVITTDFGQVVLRPKEARHANVNPNEDGESSSSSPTEENAAT
  DNIAFMITETTVQVLSSGEVHDIVSQKGEDIQTVNIDARKEMTPRQEGTDNEDPVVCLDK
  KPVIIIFDEPMDIRSAYKRLSTIFEECDEELERMMMEEKIEEEEEEENGDSVVQNNNTSQ
  MSHKKVAPGNLRTGQQVETKSQPHSLATETRNPGGQEMNRTELNKFSHVDSPNSECKGED
  ATDDQFESPKKKFKFKFPKKQLAALTQAIRTGTKTGKKTLQVVVYEEEEEDGTLKQHKEA
  KRFEIARSQPEDTPENTVRRQEQPSIESTSPISRTDEIRKNTYRTLDSLEQTIKQLENTI
  SEMSPKALVDTSCSSNRDSVASSSHIAQEASPRPLLVPDEGPTALEPPTSIPSASRKGSS
  GAPQTSRMPVPMSAKNRPGTLDKPGKQSKLQDPRQYRQANGSAKKSGGDFKPTSPSLPAS
  KIPALSPSSGKSSSLPSSSGDSSNLPNPPATKPSIASNPLSPQTGPPAHSASLIPSVSNG
  SLKFQSLTHTGKGHHLSFSPQSQNGRAPPPLSFSSSPPSPASSVSLNQGAKGTRTIHTPS
  LTSYKAQNGSSSKATPSTAKETS
• Function: Required for normal development of intervertebral disks.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Intervertebral disc degeneration	DISG3AIM	Strong	Biomarker	[2]
Knee osteoarthritis	DISLSNBJ	Strong	Genetic Variation	[3]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[4]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[5]

4 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 Sickle tail protein homolog (KIAA1217).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Sickle tail protein homolog (KIAA1217).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Sickle tail protein homolog (KIAA1217).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Sickle tail protein homolog (KIAA1217).	[9]

12 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 Sickle tail protein homolog (KIAA1217).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sickle tail protein homolog (KIAA1217).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Sickle tail protein homolog (KIAA1217).	[10]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Sickle tail protein homolog (KIAA1217).	[11]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Sickle tail protein homolog (KIAA1217).	[12]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Sickle tail protein homolog (KIAA1217).	[13]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone decreases the expression of Sickle tail protein homolog (KIAA1217).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Sickle tail protein homolog (KIAA1217).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sickle tail protein homolog (KIAA1217).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Sickle tail protein homolog (KIAA1217).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Sickle tail protein homolog (KIAA1217).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Sickle tail protein homolog (KIAA1217).	[19]

References

• [1] Primate-specific miR-603 is implicated in the risk and pathogenesis of Alzheimer's disease.Aging (Albany NY). 2016 Feb;8(2):272-90. doi: 10.18632/aging.100887.
• [2] Genetic susceptibility of intervertebral disc degeneration among young Finnish adults.BMC Med Genet. 2011 Nov 22;12:153. doi: 10.1186/1471-2350-12-153.
• [3] Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis.Nat Genet. 2018 Apr;50(4):549-558. doi: 10.1038/s41588-018-0079-y. Epub 2018 Mar 20.
• [4] Identification of a novel partner gene, KIAA1217, fused to RET: Functional characterization and inhibitor sensitivity of two isoforms in lung adenocarcinoma.Oncotarget. 2016 Jun 14;7(24):36101-36114. doi: 10.18632/oncotarget.9137.
• [5] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [6] 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.
• [7] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [8] 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.
• [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] 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.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [13] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [14] Androgen receptor-mediated repression of novel target genes. Prostate. 2007 Sep 15;67(13):1371-83. doi: 10.1002/pros.20623.
• [15] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [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] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [18] 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.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.