Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE2MIMZ)

• DOT Name: Histone-lysine N-methyltransferase SETMAR (SETMAR)
• Synonyms: SET domain and mariner transposase fusion protein; Metnase
• Gene Name: SETMAR
• Related Disease:
  Arthritis
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Pneumonia
  Rheumatoid arthritis
  Acute erythroid leukemia
  Acute myelogenous leukaemia
  Alzheimer disease
  Cognitive impairment
  Colitis
  Fatty liver disease
  Inflammation
  Latent tuberculosis infection
  Mantle cell lymphoma
  Neuralgia
  Non-alcoholic fatty liver disease
  Obesity
  Periodontitis
  Psoriasis
  Tuberculosis
  Ulcerative colitis
  Adult glioblastoma
  Glioblastoma multiforme
  Leiomyosarcoma
  Metastatic melanoma
  Neoplasm
  Non-alcoholic steatohepatitis
  Periodontal disease
  Stroke
• UniProt ID: SETMR_HUMAN
• PDB ID: 3BO5; 3F2K; 3K9J; 3K9K; 7S03
• EC Number: 2.1.1.357; 3.1.-.-
• Pfam ID: PF17906 ; PF05033 ; PF00856 ; PF01359
• Sequence:
  MFAEAAKTTRPCGMAEFKEKPEAPTEQLDVACGQENLPVGAWPPGAAPAPFQYTPDHVVG
  PGADIDPTQITFPGCICVKTPCLPGTCSCLRHGENYDDNSCLRDIGSGGKYAEPVFECNV
  LCRCSDHCRNRVVQKGLQFHFQVFKTHKKGWGLRTLEFIPKGRFVCEYAGEVLGFSEVQR
  RIHLQTKSDSNYIIAIREHVYNGQVMETFVDPTYIGNIGRFLNHSCEPNLLMIPVRIDSM
  VPKLALFAAKDIVPEEELSYDYSGRYLNLTVSEDKERLDHGKLRKPCYCGAKSCTAFLPF
  DSSLYCPVEKSNISCGNEKEPSMCGSAPSVFPSCKRLTLETMKMMLDKKQIRAIFLFEFK
  MGRKAAETTRNINNAFGPGTANERTVQWWFKKFCKGDESLEDEERSGRPSEVDNDQLRAI
  IEADPLTTTREVAEELNVNHSTVVRHLKQIGKVKKLDKWVPHELTENQKNRRFEVSSSLI
  LRNHNEPFLDRIVTCDEKWILYDNRRRSAQWLDQEEAPKHFPKPILHPKKVMVTIWWSAA
  GLIHYSFLNPGETITSEKYAQEIDEMNQKLQRLQLALVNRKGPILLHDNARPHVAQPTLQ
  KLNELGYEVLPHPPYSPDLLPTNYHVFKHLNNFLQGKRFHNQQDAENAFQEFVESQSTDF
  YATGINQLISRWQKCVDCNGSYFD
• Function: Protein derived from the fusion of a methylase with the transposase of an Hsmar1 transposon that plays a role in DNA double-strand break repair, stalled replication fork restart and DNA integration. DNA-binding protein, it is indirectly recruited to sites of DNA damage through protein-protein interactions. Has also kept a sequence-specific DNA-binding activity recognizing the 19-mer core of the 5'-terminal inverted repeats (TIRs) of the Hsmar1 element and displays a DNA nicking and end joining activity. In parallel, has a histone methyltransferase activity and methylates 'Lys-4' and 'Lys-36' of histone H3. Specifically mediates dimethylation of H3 'Lys-36' at sites of DNA double-strand break and may recruit proteins required for efficient DSB repair through non-homologous end-joining. Also regulates replication fork processing, promoting replication fork restart and regulating DNA decatenation through stimulation of the topoisomerase activity of TOP2A.
• Tissue Specificity: Widely expressed, with highest expression in placenta and ovary and lowest expression in skeletal muscle.
• KEGG Pathway:
  Lysine degradation (hsa00310)
  Metabolic pathways (hsa01100)
• BioCyc Pathway: MetaCyc:HS10111-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthritis	DIST1YEL	Definitive	Biomarker	[1]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Definitive	Biomarker	[2]
Pneumonia	DIS8EF3M	Definitive	Biomarker	[3]
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[1]
Acute erythroid leukemia	DISZFC1O	Strong	Genetic Variation	[4]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Cognitive impairment	DISH2ERD	Strong	Biomarker	[6]
Colitis	DISAF7DD	Strong	Biomarker	[3]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[7]
Inflammation	DISJUQ5T	Strong	Biomarker	[8]
Latent tuberculosis infection	DIS6R1EH	Strong	Biomarker	[9]
Mantle cell lymphoma	DISFREOV	Strong	Biomarker	[10]
Neuralgia	DISWO58J	Strong	Biomarker	[11]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[7]
Obesity	DIS47Y1K	Strong	Biomarker	[12]
Periodontitis	DISI9JOI	Strong	Altered Expression	[13]
Psoriasis	DIS59VMN	Strong	Biomarker	[8]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[9]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[14]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[15]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[15]
Leiomyosarcoma	DIS6COXM	Limited	Genetic Variation	[16]
Metastatic melanoma	DISSL43L	Limited	Biomarker	[17]
Neoplasm	DISZKGEW	Limited	Biomarker	[15]
Non-alcoholic steatohepatitis	DIST4788	Limited	Biomarker	[18]
Periodontal disease	DISJQHVN	Limited	Altered Expression	[13]
Stroke	DISX6UHX	Limited	Biomarker	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Histone-lysine N-methyltransferase SETMAR (SETMAR) increases the response to substance of Arsenic trioxide.	[35]

2 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 Histone-lysine N-methyltransferase SETMAR (SETMAR).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Histone-lysine N-methyltransferase SETMAR (SETMAR).	[32]

14 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 Histone-lysine N-methyltransferase SETMAR (SETMAR).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histone-lysine N-methyltransferase SETMAR (SETMAR).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Histone-lysine N-methyltransferase SETMAR (SETMAR).	[23]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Histone-lysine N-methyltransferase SETMAR (SETMAR).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Histone-lysine N-methyltransferase SETMAR (SETMAR).	[25]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Histone-lysine N-methyltransferase SETMAR (SETMAR).	[26]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Histone-lysine N-methyltransferase SETMAR (SETMAR).	[27]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Histone-lysine N-methyltransferase SETMAR (SETMAR).	[28]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Histone-lysine N-methyltransferase SETMAR (SETMAR).	[29]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Histone-lysine N-methyltransferase SETMAR (SETMAR).	[30]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Histone-lysine N-methyltransferase SETMAR (SETMAR).	[31]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Histone-lysine N-methyltransferase SETMAR (SETMAR).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Histone-lysine N-methyltransferase SETMAR (SETMAR).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Histone-lysine N-methyltransferase SETMAR (SETMAR).	[34]

References

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