Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2LK4JW)

• DOT Name: Sterile alpha motif domain-containing protein 1 (SAMD1)
• Synonyms: SAM domain-containing protein 1; Atherin
• Gene Name: SAMD1
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Neuroblastic tumor
• UniProt ID: SAMD1_HUMAN
• PDB ID: 6LUI; 6LUJ; 6LUK
• Pfam ID: PF00536 ; PF21524
• Sequence:
  MAGPPALPPPETAAAATTAAAASSSAASPHYQEWILDTIDSLRSRKARPDLERICRMVRR
  RHGPEPERTRAELEKLIQQRAVLRVSYKGSISYRNAARVQPPRRGATPPAPPRAPRGAPA
  AAAAAAPPPTPAPPPPPAPVAAAAPARAPRAAAAAATAPPSPGPAQPGPRAQRAAPLAAP
  PPAPAAPPAVAPPAGPRRAPPPAVAAREPPLPPPPQPPAPPQQQQPPPPQPQPPPEGGAV
  RAGGAARPVSLREVVRYLGGSGGAGGRLTRGRVQGLLEEEAAARGRLERTRLGALALPRG
  DRPGRAPPAASARPSRSKRGGEERVLEKEEEEDDDEDEDEEDDVSEGSEVPESDRPAGAQ
  HHQLNGERGPQSAKERVKEWTPCGPHQGQDEGRGPAPGSGTRQVFSMAAMNKEGGTASVA
  TGPDSPSPVPLPPGKPALPGADGTPFGCPPGRKEKPSDPVEWTVMDVVEYFTEAGFPEQA
  TAFQEQEIDGKSLLLMQRTDVLTGLSIRLGPALKIYEHHIKVLQQGHFEDDDPDGFLG
• Function: Unmethylated CpG islands (CGIs)-binding protein which localizes to H3K4me3-decorated CGIs, where it acts as a transcriptional repressor. Tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs. Plays a role in atherogenesis by binding with LDL on cell surface and promoting LDL oxidation which leads to the formation of foam cell.
• Tissue Specificity: Expressed in atherosclerotic lesions, not in normal intima. Expressed in foam cells.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[1]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[1]
Neuroblastic tumor	DISKWPS1	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sterile alpha motif domain-containing protein 1 (SAMD1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Sterile alpha motif domain-containing protein 1 (SAMD1).	[4]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Sterile alpha motif domain-containing protein 1 (SAMD1).	[5]
Ampicillin	DMHWE7P	Approved	Ampicillin increases the expression of Sterile alpha motif domain-containing protein 1 (SAMD1).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Sterile alpha motif domain-containing protein 1 (SAMD1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Sterile alpha motif domain-containing protein 1 (SAMD1).	[8]

1 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 decreases the phosphorylation of Sterile alpha motif domain-containing protein 1 (SAMD1).	[9]

References

• [1] Atherin: a newly identified, lesion-specific, LDL-binding protein in human atherosclerosis.Atherosclerosis. 2005 Oct;182(2):219-30. doi: 10.1016/j.atherosclerosis.2005.01.041.
• [2] Exome sequencing identifies predisposing and fusion gene in ganglioneuroma, ganglioneuroblastoma and neuroblastoma.Math Biosci Eng. 2019 Aug 8;16(6):7217-7229. doi: 10.3934/mbe.2019362.
• [3] 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.
• [4] 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.
• [5] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [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.