Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT69VAOX)

DOT Name	Spindlin-1 (SPIN1)
Synonyms	Ovarian cancer-related protein; Spindlin1
Gene Name	SPIN1
Related Disease	Advanced cancer ( ) Breast cancer ( ) Breast carcinoma ( ) Carcinoma of liver and intrahepatic biliary tract ( ) Esophageal squamous cell carcinoma ( ) Hepatitis B virus infection ( ) Hepatocellular carcinoma ( ) Herpes simplex infection ( ) Leiomyoma ( ) Liver cancer ( ) Neoplasm ( ) Non-small-cell lung cancer ( ) Scleroderma ( ) Seasonal affective disorder ( ) Seminoma ( ) Squamous cell carcinoma ( ) Systemic sclerosis ( ) Triple negative breast cancer ( ) Uterine fibroids ( ) Liposarcoma ( ) Melanoma ( ) Sickle-cell anaemia ( ) Stroke ( )
UniProt ID	SPIN1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2NS2; 4H75; 4MZF; 4MZG; 4MZH; 5JSG; 5JSJ; 5Y5W; 6I8B; 6I8L; 6I8Y; 6QPL; 7BQZ; 7BU9; 7CNA; 7E9M; 7EA1; 7OCB; 8GTX
Pfam ID	PF02513
Sequence	MKTPFGKTPGQRSRADAGHAGVSANMMKKRTSHKKHRSSVGPSKPVSQPRRNIVGCRIQH GWKEGNGPVTQWKGTVLDQVPVNPSLYLIKYDGFDCVYGLELNKDERVSALEVLPDRVAT SRISDAHLADTMIGKAVEHMFETEDGSKDEWRGMVLARAPVMNTWFYITYEKDPVLYMYQ LLDDYKEGDLRIMPDSNDSPPAEREPGEVVDSLVGKQVEYAKEDGSKRTGMVIHQVEAKP SVYFIKFDDDFHIYVYDLVKTS
Function	Chromatin reader that specifically recognizes and binds histone H3 both trimethylated at 'Lys-4' and asymmetrically dimethylated at 'Arg-8' (H3K4me3 and H3R8me2a) and acts as an activator of Wnt signaling pathway downstream of PRMT2. In case of cancer, promotes cell cancer proliferation via activation of the Wnt signaling pathway. Overexpression induces metaphase arrest and chromosomal instability. Localizes to active rDNA loci and promotes the expression of rRNA genes. May play a role in cell-cycle regulation during the transition from gamete to embryo. Involved in oocyte meiotic resumption, a process that takes place before ovulation to resume meiosis of oocytes blocked in prophase I: may act by regulating maternal transcripts to control meiotic resumption.
Tissue Specificity	Highly expressed in ovarian cancer tissues.

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[3]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[4]
Leiomyoma	DISLDDFN	Strong	Biomarker	[5]
Liver cancer	DISDE4BI	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[6]
Scleroderma	DISVQ342	Strong	Genetic Variation	[7]
Seasonal affective disorder	DIS908VO	Strong	Biomarker	[8]
Seminoma	DIS3J8LJ	Strong	Altered Expression	[9]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[10]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[7]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[11]
Uterine fibroids	DISBZRMJ	Strong	Biomarker	[5]
Liposarcoma	DIS8IZVM	Limited	Biomarker	[12]
Melanoma	DIS1RRCY	Limited	Biomarker	[13]
Sickle-cell anaemia	DIS5YNZB	Limited	Biomarker	[14]
Stroke	DISX6UHX	Limited	Biomarker	[14]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Spindlin-1 (SPIN1).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Spindlin-1 (SPIN1).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Spindlin-1 (SPIN1).	[17]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Spindlin-1 (SPIN1).	[18]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Spindlin-1 (SPIN1).	[19]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Spindlin-1 (SPIN1).	[20]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Spindlin-1 (SPIN1).	[23]
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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 decreases the methylation of Spindlin-1 (SPIN1).	[21]
TAK-243	DM4GKV2	Phase 1	TAK-243 affects the sumoylation of Spindlin-1 (SPIN1).	[22]
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References

1	SPIN1 triggers abnormal lipid metabolism and enhances tumor growth in liver cancer.Cancer Lett. 2020 Feb 1;470:54-63. doi: 10.1016/j.canlet.2019.11.032. Epub 2019 Nov 29.
2	SPIN1, negatively regulated by miR-148/152, enhances Adriamycin resistance via upregulating drug metabolizing enzymes and transporter in breast cancer.J Exp Clin Cancer Res. 2018 May 9;37(1):100. doi: 10.1186/s13046-018-0748-9.
3	LINC00473/miR-374a-5p regulates esophageal squamous cell carcinoma via targeting SPIN1 to weaken the effect of radiotherapy.J Cell Biochem. 2019 Sep;120(9):14562-14572. doi: 10.1002/jcb.28717. Epub 2019 Apr 24.
4	The Tudor domain protein Spindlin1 is involved in intrinsic antiviral defense against incoming hepatitis B Virus and herpes simplex virus type 1.PLoS Pathog. 2014 Sep 11;10(9):e1004343. doi: 10.1371/journal.ppat.1004343. eCollection 2014 Sep.
5	Romina: A powerful strawberry with in vitro efficacy against uterine leiomyoma cells.J Cell Physiol. 2019 May;234(5):7622-7633. doi: 10.1002/jcp.27524. Epub 2018 Oct 14.
6	miR-409 Inhibits Human Non-Small-Cell Lung Cancer Progression by Directly Targeting SPIN1.Mol Ther Nucleic Acids. 2018 Dec 7;13:154-163. doi: 10.1016/j.omtn.2018.08.020. Epub 2018 Sep 1.
7	Scleroderma Patient-centered Intervention Network-Scleroderma Support group Leader EDucation (SPIN-SSLED) program: non-randomised feasibility trial.BMJ Open. 2019 Nov 11;9(11):e029935. doi: 10.1136/bmjopen-2019-029935.
8	Genetics and personality traits in patients with social anxiety disorder: a case-control study in South Africa.Eur Neuropsychopharmacol. 2007 Apr;17(5):321-7. doi: 10.1016/j.euroneuro.2006.06.010. Epub 2006 Aug 8.
9	SPIN1 is a proto-oncogene and SPIN3 is a tumor suppressor in human seminoma.Oncotarget. 2018 Aug 21;9(65):32466-32477. doi: 10.18632/oncotarget.25977. eCollection 2018 Aug 21.
10	A Chemical Probe for Tudor Domain Protein Spindlin1 to Investigate Chromatin Function.J Med Chem. 2019 Oct 24;62(20):9008-9025. doi: 10.1021/acs.jmedchem.9b00562. Epub 2019 Oct 15.
11	Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer through SPIN1 regulation.Oncotarget. 2017 Apr 25;8(17):28939-28958. doi: 10.18632/oncotarget.15960.
12	The histone code reader SPIN1 controls RET signaling in liposarcoma.Oncotarget. 2015 Mar 10;6(7):4773-89. doi: 10.18632/oncotarget.3000.
13	Bioenergetic modulation with the mitochondria uncouplers SR4 and niclosamide prevents proliferation and growth of treatment-nave and vemurafenib-resistant melanomas.Oncotarget. 2018 Dec 11;9(97):36945-36965. doi: 10.18632/oncotarget.26421. eCollection 2018 Dec 11.
14	Feasibility trial for primary stroke prevention in children with sickle cell anemia in Nigeria (SPIN trial).Am J Hematol. 2017 Aug;92(8):780-788. doi: 10.1002/ajh.24770. Epub 2017 Jun 15.
15	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.
16	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.
17	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
18	Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
19	Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
20	Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
21	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.
22	Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
23	Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.