Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSM5QIO)

• DOT Name: SLAIN motif-containing protein 2 (SLAIN2)
• Gene Name: SLAIN2
• Related Disease:
  Uterine fibroids
  Colorectal carcinoma
  Crohn disease
  Inflammatory bowel disease
• UniProt ID: SLAI2_HUMAN
• PDB ID: 3RDV
• Pfam ID: PF15301
• Sequence:
  MEDVNSNVNADQEVRKLQELVKKLEKQNEQLRSRSGAVQGAGSLGPGSPVRAGASIPSSG
  AASPRGFPLGLSAKSGGGPGSGPRRTSSEELRDATSLLAAGEGGLLDEVEPLRPDELERL
  SGWEEEEESWLYSSPKKKLTPMQKSVSPLVWCRQVLDYPSPDVECAKKSLIHKLDQTMSA
  LKRQNLYNNPFNSMSYTSPYSPNASSPYSSGFNSPSSTPVRPPIVKQLILPGNSGNLKSS
  DRNPPLSPQSSIDSELSASELDEDSIGSNYKLNDVTDVQILARMQEESLRQEYAATTSRR
  SSGSSCNSTRRGTFSDQELDAQSLDDEDDNMHHAVYPAVNRFSPSPRNSPRPSPKQSPRN
  SPRSRSPARGIEYSRVSPQPMISRLQQPRLSLQGHPTDLQTSNVKNEEKLRRSLPNLSRT
  SNTQVDSVKSSRSDSNFQVPNGGIPRMQPQASAIPSPGKFRSPAAPSPLALRQPVKAFSN
  HGSGSPGSQEITQLTQTTSSPGPPMVQSTVSANPPSNINSATLTRPAGTTAMRSGLPRPS
  APSAGGIPVPRSKLAQPVRRSLPAPKTYGSMKDDSWKDGCY
• Function: Binds to the plus end of microtubules and regulates microtubule dynamics and microtubule organization. Promotes cytoplasmic microtubule nucleation and elongation. Required for normal structure of the microtubule cytoskeleton during interphase.
• Tissue Specificity: Widely expressed with highest levels in adult liver, testis and ovary, and lowest levels in adult pancreas and spleen and in fetal brain.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[2]
Crohn disease	DIS2C5Q8	moderate	Genetic Variation	[3]
Inflammatory bowel disease	DISGN23E	moderate	Genetic Variation	[3]

11 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 SLAIN motif-containing protein 2 (SLAIN2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of SLAIN motif-containing protein 2 (SLAIN2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of SLAIN motif-containing protein 2 (SLAIN2).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of SLAIN motif-containing protein 2 (SLAIN2).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of SLAIN motif-containing protein 2 (SLAIN2).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of SLAIN motif-containing protein 2 (SLAIN2).	[9]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of SLAIN motif-containing protein 2 (SLAIN2).	[10]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of SLAIN motif-containing protein 2 (SLAIN2).	[12]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of SLAIN motif-containing protein 2 (SLAIN2).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of SLAIN motif-containing protein 2 (SLAIN2).	[14]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of SLAIN motif-containing protein 2 (SLAIN2).	[15]

2 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 affects the phosphorylation of SLAIN motif-containing protein 2 (SLAIN2).	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of SLAIN motif-containing protein 2 (SLAIN2).	[11]

References

• [1] Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits.Nat Commun. 2018 Sep 7;9(1):3636. doi: 10.1038/s41467-018-05428-6.
• [2] MALAT1 sponges miR-106b-5p to promote the invasion and metastasis of colorectal cancer via SLAIN2 enhanced microtubules mobility.EBioMedicine. 2019 Mar;41:286-298. doi: 10.1016/j.ebiom.2018.12.049. Epub 2019 Feb 21.
• [3] Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.Nat Genet. 2015 Sep;47(9):979-986. doi: 10.1038/ng.3359. Epub 2015 Jul 20.
• [4] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [5] 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.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] 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.
• [8] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] 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.
• [12] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [13] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [14] 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.
• [15] Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.