Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7N88T1)

• DOT Name: SAM domain-containing protein SAMSN-1 (SAMSN1)
• Synonyms: Hematopoietic adaptor containing SH3 and SAM domains 1; Nash1; SAM domain, SH3 domain and nuclear localization signals protein 1; SH3-SAM adaptor protein
• Gene Name: SAMSN1
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Glioblastoma multiforme
  Glioma
  Haematological malignancy
  Hepatitis
  Hepatocellular carcinoma
  Knee osteoarthritis
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Malignant glioma
  Neoplasm
  Angioimmunoblastic T-cell Lymphoma
  Plasma cell myeloma
• UniProt ID: SAMN1_HUMAN
• PDB ID: 6UZJ
• Pfam ID: PF07647 ; PF07653 ; PF12485
• Sequence:
  MLKRKPSNVSEKEKHQKPKRSSSFGNFDRFRNNSLSKPDDSTEAHEGDPTNGSGEQSKTS
  NNGGGLGKKMRAISWTMKKKVGKKYIKALSEEKDEEDGENAHPYRNSDPVIGTHTEKVSL
  KASDSMDSLYSGQSSSSGITSCSDGTSNRDSFRLDDDGPYSGPFCGRARVHTDFTPSPYD
  TDSLKIKKGDIIDIICKTPMGMWTGMLNNKVGNFKFIYVDVISEEEAAPKKIKANRRSNS
  KKSKTLQEFLERIHLQEYTSTLLLNGYETLEDLKDIKESHLIELNIENPDDRRRLLSAAE
  NFLEEEIIQEQENEPEPLSLSSDISLNKSQLDDCPRDSGCYISSGNSDNGKEDLESENLS
  DMVHKIIITEPSD
• Function: Negative regulator of B-cell activation. Down-regulates cell proliferation (in vitro). Promotes RAC1-dependent membrane ruffle formation and reorganization of the actin cytoskeleton. Regulates cell spreading and cell polarization. Stimulates HDAC1 activity. Regulates LYN activity by modulating its tyrosine phosphorylation.
• Tissue Specificity: Detected in peripheral blood B-cells (at protein level). Detected in spleen, liver and peripheral blood.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[1]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[1]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[2]
Haematological malignancy	DISCDP7W	Strong	Biomarker	[3]
Hepatitis	DISXXX35	Strong	Altered Expression	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Knee osteoarthritis	DISLSNBJ	Strong	Biomarker	[5]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[6]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[6]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[6]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Angioimmunoblastic T-cell Lymphoma	DISZPFTL	Limited	Biomarker	[7]
Plasma cell myeloma	DIS0DFZ0	Limited	Genetic Variation	[8]

12 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 SAM domain-containing protein SAMSN-1 (SAMSN1).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of SAM domain-containing protein SAMSN-1 (SAMSN1).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of SAM domain-containing protein SAMSN-1 (SAMSN1).	[11]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of SAM domain-containing protein SAMSN-1 (SAMSN1).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of SAM domain-containing protein SAMSN-1 (SAMSN1).	[13]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of SAM domain-containing protein SAMSN-1 (SAMSN1).	[14]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of SAM domain-containing protein SAMSN-1 (SAMSN1).	[9]
Marinol	DM70IK5	Approved	Marinol increases the expression of SAM domain-containing protein SAMSN-1 (SAMSN1).	[15]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of SAM domain-containing protein SAMSN-1 (SAMSN1).	[16]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of SAM domain-containing protein SAMSN-1 (SAMSN1).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of SAM domain-containing protein SAMSN-1 (SAMSN1).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of SAM domain-containing protein SAMSN-1 (SAMSN1).	[16]

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 increases the phosphorylation of SAM domain-containing protein SAMSN-1 (SAMSN1).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of SAM domain-containing protein SAMSN-1 (SAMSN1).	[20]

References

• [1] A genome-wide trans-ethnic interaction study links the PIGR-FCAMR locus to coronary atherosclerosis via interactions between genetic variants and residential exposure to traffic.PLoS One. 2017 Mar 29;12(3):e0173880. doi: 10.1371/journal.pone.0173880. eCollection 2017.
• [2] SAMSN1 is highly expressed and associated with a poor survival in glioblastoma multiforme.PLoS One. 2013 Nov 22;8(11):e81905. doi: 10.1371/journal.pone.0081905. eCollection 2013.
• [3] HACS1 encodes a novel SH3-SAM adaptor protein differentially expressed in normal and malignant hematopoietic cells.Oncogene. 2001 Aug 30;20(38):5373-7. doi: 10.1038/sj.onc.1204698.
• [4] Suppression of SAMSN1 Expression is Associated with the Malignant Phenotype of Hepatocellular Carcinoma.Ann Surg Oncol. 2015 Dec;22 Suppl 3:S1453-60. doi: 10.1245/s10434-015-4524-1. Epub 2015 Mar 25.
• [5] Intra-articular injection of hydrogen sulfide decreased the progression of gonarthrosis.Can J Physiol Pharmacol. 2019 Jan;97(1):47-54. doi: 10.1139/cjpp-2018-0574. Epub 2018 Dec 6.
• [6] Detailed characterization of a homozygously deleted region corresponding to a candidate tumor suppressor locus at 21q11-21 in human lung cancer.Genes Chromosomes Cancer. 2008 Sep;47(9):810-8. doi: 10.1002/gcc.20582.
• [7] Angioimmunoblastic T cell lymphoma: novel molecular insights by mutation profiling.Oncotarget. 2017 Mar 14;8(11):17763-17770. doi: 10.18632/oncotarget.14846.
• [8] Whole Genome Sequence of Multiple Myeloma-Prone C57BL/KaLwRij Mouse Strain Suggests the Origin of Disease Involves Multiple Cell Types.PLoS One. 2015 May 28;10(5):e0127828. doi: 10.1371/journal.pone.0127828. eCollection 2015.
• [9] 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.
• [10] 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.
• [11] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [12] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [13] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [14] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [15] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [17] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [18] Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[alpha]pyrene. Int J Mol Sci. 2018 Nov 17;19(11).
• [19] 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.
• [20] 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.