Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN4T7JI)

• DOT Name: Sec1 family domain-containing protein 1 (SCFD1)
• Synonyms: SLY1 homolog; Sly1p; Syntaxin-binding protein 1-like 2
• Gene Name: SCFD1
• Related Disease:
  Advanced cancer
  Amyotrophic lateral sclerosis-parkinsonism-dementia complex
  Amyotrophic lateral sclerosis
  Alzheimer disease
• UniProt ID: SCFD1_HUMAN
• Pfam ID: PF00995
• Sequence:
  MAAAAAATAAAAASIRERQTVALKRMLNFNVPHIKNSTGEPVWKVLIYDRFGQDIISPLL
  SVKELRDMGITLHLLLHSDRDPIPDVPAVYFVMPTEENIDRMCQDLRNQLYESYYLNFIS
  AISRSKLEDIANAALAASAVTQVAKVFDQYLNFITLEDDMFVLCNQNKELVSYRAINRPD
  ITDTEMETVMDTIVDSLFCFFVTLGAVPIIRCSRGTAAEMVAVKLDKKLRENLRDARNSL
  FTGDTLGAGQFSFQRPLLVLVDRNIDLATPLHHTWTYQALVHDVLDFHLNRVNLEESSGV
  ENSPAGARPKRKNKKSYDLTPVDKFWQKHKGSPFPEVAESVQQELESYRAQEDEVKRLKS
  IMGLEGEDEGAISMLSDNTAKLTSAVSSLPELLEKKRLIDLHTNVATAVLEHIKARKLDV
  YFEYEEKIMSKTTLDKSLLDIISDPDAGTPEDKMRLFLIYYISTQQAPSEADLEQYKKAL
  TDAGCNLNPLQYIKQWKAFTKMASAPASYGSTTTKPMGLLSRVMNTGSQFVMEGVKNLVL
  KQQNLPVTRILDNLMEMKSNPETDDYRYFDPKMLRGNDSSVPRNKNPFQEAIVFVVGGGN
  YIEYQNLVDYIKGKQGKHILYGCSELFNATQFIKQLSQLGQK
• Function: Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with COG4. Involved in vesicular transport between the endoplasmic reticulum and the Golgi.
• Reactome Pathway:
  RHOA GTPase cycle (R-HSA-8980692)
  COPII-mediated vesicle transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Amyotrophic lateral sclerosis-parkinsonism-dementia complex	DISTHQI1	Strong	Biomarker	[2]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Genetic Variation	[3]
Alzheimer disease	DISF8S70	Limited	Genetic Variation	[3]

1 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 1 (SCFD1).	[4]

11 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 Sec1 family domain-containing protein 1 (SCFD1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sec1 family domain-containing protein 1 (SCFD1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Sec1 family domain-containing protein 1 (SCFD1).	[7]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Sec1 family domain-containing protein 1 (SCFD1).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Sec1 family domain-containing protein 1 (SCFD1).	[9]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Sec1 family domain-containing protein 1 (SCFD1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Sec1 family domain-containing protein 1 (SCFD1).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Sec1 family domain-containing protein 1 (SCFD1).	[6]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Sec1 family domain-containing protein 1 (SCFD1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Sec1 family domain-containing protein 1 (SCFD1).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Sec1 family domain-containing protein 1 (SCFD1).	[14]

References

• [1] Prognostic significance of downregulated expression of the candidate tumour suppressor gene SASH1 in colon cancer.Br J Cancer. 2006 Nov 20;95(10):1419-23. doi: 10.1038/sj.bjc.6603452. Epub 2006 Oct 31.
• [2] Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis. Nat Genet. 2016 Sep;48(9):1043-8. doi: 10.1038/ng.3622. Epub 2016 Jul 25.
• [3] Does SCFD1 rs10139154 Polymorphism Decrease Alzheimer's Disease Risk?.J Mol Neurosci. 2019 Oct;69(2):343-350. doi: 10.1007/s12031-019-01363-3. Epub 2019 Jul 2.
• [4] 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.
• [5] 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.
• [6] Gene expression changes associated with cytotoxicity identified using cDNA arrays. Funct Integr Genomics. 2000 Sep;1(2):114-26.
• [7] 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.
• [8] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [11] 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.
• [12] Proteomic signatures in thapsigargin-treated hepatoma cells. Chem Res Toxicol. 2011 Aug 15;24(8):1215-22. doi: 10.1021/tx200109y. Epub 2011 Jul 1.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [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.