Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYM55ET)

• DOT Name: Sec1 family domain-containing protein 2 (SCFD2)
• Synonyms: Syntaxin-binding protein 1-like 1
• Gene Name: SCFD2
• Related Disease:
  Breast carcinoma
  Chronic obstructive pulmonary disease
  Uterine fibroids
  Sleep disorder, initiating and maintaining sleep
• UniProt ID: SCFD2_HUMAN
• Pfam ID: PF00995
• Sequence:
  MSASGVLSFTQQGWEQVLAKVKRAVVYLDAACAESLHWGCGSTRLLEAVGGPDCHLREFE
  PDAIGGGAKQPKAVFVLSCLLKGRTVEILRDIICRSHFQYCVVVTTVSHAVHLTANHVPA
  AAAAEMEGQQPVFEQLEEKLCEWMGNMNYTAEVFHVPLLLAPVAPHFALTPAFASLFPLL
  PQDVHLLNSARPDKRKLGSLGDVDSTTLTPELLLQIRCLVSGLSSLCEHLGVREECFAVG
  SLSQVIAADLANYAPAKNRKKTAAGRASVVFVDRTLDLTGAVGHHGDNLVEKIISALPQL
  PGHTNDVMVNMIALTALHTEEENYNVVAPGCLSQSSDTTAKALWEALLNTKHKEAVMEVR
  RHLVEAASRENLPIKMSMGRVTPGQLMSYIQLFKNNLKALMNHCGLLQLGLATAQTLKHP
  QTAKWDNFLAFERLLLQSIGESAMSVVLNQLLPMIKPVTQRTNEDYSPEELLILLIYIYS
  VTGELTVDKDLCEAEEKVKKALAQVFCEESGLSPLLQKITDWDSSINLTFHKSKIAVDEL
  FTSLRDIAGARSLLKQFKSVYVPGNHTHQASYKPLLKQVVEEIFHPERPDSVDIEHMSSG
  LTDLLKTGFSMFMKVSRPHPSDYPLLILFVVGGVTVSEVKMVKDLVASLKPGTQVIVLST
  RLLKPLNIPELLFATDRLHPDLGF
• Function: May be involved in protein transport.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[2]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[3]
Sleep disorder, initiating and maintaining sleep	DISVOIRA	Disputed	Genetic Variation	[4]

3 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 Sec1 family domain-containing protein 2 (SCFD2).	[5]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Sec1 family domain-containing protein 2 (SCFD2).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Sec1 family domain-containing protein 2 (SCFD2).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sec1 family domain-containing protein 2 (SCFD2).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sec1 family domain-containing protein 2 (SCFD2).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sec1 family domain-containing protein 2 (SCFD2).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Sec1 family domain-containing protein 2 (SCFD2).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Sec1 family domain-containing protein 2 (SCFD2).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Sec1 family domain-containing protein 2 (SCFD2).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Sec1 family domain-containing protein 2 (SCFD2).	[12]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Sec1 family domain-containing protein 2 (SCFD2).	[13]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Sec1 family domain-containing protein 2 (SCFD2).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Sec1 family domain-containing protein 2 (SCFD2).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Sec1 family domain-containing protein 2 (SCFD2).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Sec1 family domain-containing protein 2 (SCFD2).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Sec1 family domain-containing protein 2 (SCFD2).	[20]

References

• [1] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [2] Genome-wide association study of smoking behaviours in patients with COPD.Thorax. 2011 Oct;66(10):894-902. doi: 10.1136/thoraxjnl-2011-200154. Epub 2011 Jun 16.
• [3] 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.
• [4] Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits.Nat Genet. 2017 Nov;49(11):1584-1592. doi: 10.1038/ng.3888. Epub 2017 Jun 12.
• [5] 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.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [10] 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.
• [11] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [12] 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.
• [13] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [14] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [15] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [16] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [17] 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.
• [18] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [19] 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.
• [20] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.