Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAX4ITH)

• DOT Name: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1)
• Synonyms: BRG1-associated factor 57; BAF57
• Gene Name: SMARCE1
• Related Disease:
  Anaplastic astrocytoma
  Familial meningioma
  Autoimmune disease
  Breast cancer
  Breast neoplasm
  Castration-resistant prostate carcinoma
  Coffin-Siris syndrome 1
  Coffin-Siris syndrome 5
  Ductal carcinoma
  Endometrial carcinoma
  Gastric cancer
  Intellectual disability
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Metastatic prostate carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Schwannomatosis
  Stomach cancer
  Trichohepatoenteric syndrome
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Coffin-Siris syndrome
  Familial multiple meningioma
  Ductal breast carcinoma in situ
  Meningioma
  Neurofibromatosis type 2
• UniProt ID: SMCE1_HUMAN
• PDB ID: 6LTH; 6LTJ; 7CYU; 7VDV; 7Y8R
• Pfam ID: PF00505
• Sequence:
  MSKRPSYAPPPTPAPATQMPSTPGFVGYNPYSHLAYNNYRLGGNPGTNSRVTASSGITIP
  KPPKPPDKPLMPYMRYSRKVWDQVKASNPDLKLWEIGKIIGGMWRDLTDEEKQEYLNEYE
  AEKIEYNESMKAYHNSPAYLAYINAKSRAEAALEEESRQRQSRMEKGEPYMSIQPAEDPD
  DYDDGFSMKHTATARFQRNHRLISEILSESVVPDVRSVVTTARMQVLKRQVQSLMVHQRK
  LEAELLQIEERHQEKKRKFLESTDSFNNELKRLCGLKVEVDMEKIAAEIAQAEEQARKRQ
  EEREKEAAEQAERSQSSIVPEEEQAANKGEEKKDDENIPMETEETHLEETTESQQNGEEG
  TSTPEDKESGQEGVDSMAEEGTSDSNTGSESNSATVEEPPTDPIPEDEKKE
• Function: Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth. Required for the coactivation of estrogen responsive promoters by SWI/SNF complexes and the SRC/p160 family of histone acetyltransferases (HATs). Also specifically interacts with the CoREST corepressor resulting in repression of neuronal specific gene promoters in non-neuronal cells.
• KEGG Pathway:
  ATP-dependent chromatin remodeling (hsa03082)
  Thermogenesis (hsa04714)
  Hepatocellular carcinoma (hsa05225)
• Reactome Pathway:
  RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known (R-HSA-8939243)
  RMTs methylate histone arginines (R-HSA-3214858)

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anaplastic astrocytoma	DISSBE0K	Definitive	Genetic Variation	[1]
Familial meningioma	DIS30G91	Definitive	Autosomal dominant	[2]
Autoimmune disease	DISORMTM	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Altered Expression	[5]
Coffin-Siris syndrome 1	DIS95FRP	Strong	Autosomal dominant	[6]
Coffin-Siris syndrome 5	DISLK30A	Strong	Autosomal dominant	[6]
Ductal carcinoma	DIS15EA5	Strong	Biomarker	[7]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[8]
Gastric cancer	DISXGOUK	Strong	Biomarker	[9]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[10]
Lung cancer	DISCM4YA	Strong	Altered Expression	[11]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[11]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[5]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Altered Expression	[5]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[11]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[12]
Prostate cancer	DISF190Y	Strong	Altered Expression	[5]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[5]
Schwannomatosis	DISDWAM1	Strong	Biomarker	[13]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Biomarker	[14]
Hepatitis B virus infection	DISLQ2XY	moderate	Altered Expression	[15]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[15]
Coffin-Siris syndrome	DIS8L03H	Supportive	Autosomal dominant	[16]
Familial multiple meningioma	DIS7ZS52	Supportive	Autosomal dominant	[17]
Ductal breast carcinoma in situ	DISLCJY7	Limited	Biomarker	[18]
Meningioma	DISPT4TG	Limited	Genetic Variation	[19]
Neurofibromatosis type 2	DISI8ECS	Limited	Biomarker	[20]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
PEITC	DMOMN31	Phase 2	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1) affects the binding of PEITC.	[37]

13 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 SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1).	[21]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1).	[22]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1).	[24]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1).	[25]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1).	[27]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1).	[28]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1).	[29]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1).	[30]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1).	[34]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1).	[35]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1).	[36]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1).	[31]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1).	[32]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1).	[33]

References

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