Details of Drug Off-Target (DOT)

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

• DOT Name: Histone-lysine N-methyltransferase SETD1A (SETD1A)
• Synonyms: EC 2.1.1.364; Lysine N-methyltransferase 2F; SET domain-containing protein 1A; hSET1A; Set1/Ash2 histone methyltransferase complex subunit SET1
• Gene Name: SETD1A
• Related Disease:
  Bacteremia
  Breast cancer
  Breast carcinoma
  Invasive breast carcinoma
  Neoplasm
  Acute myelogenous leukaemia
  Adenocarcinoma
  Advanced cancer
  Autism spectrum disorder
  Bacillary dysentery
  Breast neoplasm
  Candidiasis
  Candidiasis, invasive
  Cholangiocarcinoma
  Cognitive impairment
  Congenital contractural arachnodactyly
  Epilepsy
  Epithelial ovarian cancer
  Estrogen-receptor positive breast cancer
  Graves disease
  Hepatitis B virus infection
  Intellectual disability, autosomal dominant 40
  Invasive candidiasis
  leukaemia
  Leukemia
  Neurodevelopmental disorder
  Neurodevelopmental disorder with speech impairment and dysmorphic facies
  Obsessive compulsive disorder
  Squamous cell carcinoma
  Systemic lupus erythematosus
  Triple negative breast cancer
  Intellectual disability
  Pancreatic cancer
  Schizophrenia
  Parkinson disease
  Ankylosing spondylitis
  Crohn disease
  Epilepsy, early-onset, with or without developmental delay
  Lung cancer
  Lung carcinoma
  Psoriasis
  Sclerosing cholangitis
  Ulcerative colitis
• UniProt ID: SET1A_HUMAN
• PDB ID: 3S8S; 3UVN; 4EWR; 8ILY
• EC Number: 2.1.1.364
• Pfam ID: PF11764 ; PF00076 ; PF00856
• Sequence:
  MDQEGGGDGQKAPSFQWRNYKLIVDPALDPALRRPSQKVYRYDGVHFSVNDSKYIPVEDL
  QDPRCHVRSKNRDFSLPVPKFKLDEFYIGQIPLKEVTFARLNDNVRETFLKDMCRKYGEV
  EEVEILLHPRTRKHLGLARVLFTSTRGAKETVKNLHLTSVMGNIIHAQLDIKGQQRMKYY
  ELIVNGSYTPQTVPTGGKALSEKFQGSGAATETAESRRRSSSDTAAYPAGTTAVGTPGNG
  TPCSQDTSFSSSRQDTPSSFGQFTPQSSQGTPYTSRGSTPYSQDSAYSSSTTSTSFKPRR
  SENSYQDAFSRRHFSASSASTTASTAIAATTAATASSSASSSSLSSSSSSSSSSSSSQFR
  SSDANYPAYYESWNRYQRHTSYPPRRATREEPPGAPFAENTAERFPPSYTSYLPPEPSRP
  TDQDYRPPASEAPPPEPPEPGGGGGGGGPSPEREEVRTSPRPASPARSGSPAPETTNESV
  PFAQHSSLDSRIEMLLKEQRSKFSFLASDTEEEEENSSMVLGARDTGSEVPSGSGHGPCT
  PPPAPANFEDVAPTGSGEPGATRESPKANGQNQASPCSSGDDMEISDDDRGGSPPPAPTP
  PQQPPPPPPPPPPPPPYLASLPLGYPPHQPAYLLPPRPDGPPPPEYPPPPPPPPHIYDFV
  NSLELMDRLGAQWGGMPMSFQMQTQMLTRLHQLRQGKGLIAASAGPPGGAFGEAFLPFPP
  PQEAAYGLPYALYAQGQEGRGAYSREAYHLPMPMAAEPLPSSSVSGEEARLPPREEAELA
  EGKTLPTAGTVGRVLAMLVQEMKSIMQRDLNRKMVENVAFGAFDQWWESKEEKAKPFQNA
  AKQQAKEEDKEKTKLKEPGLLSLVDWAKSGGTTGIEAFAFGSGLRGALRLPSFKVKRKEP
  SEISEASEEKRPRPSTPAEEDEDDPEQEKEAGEPGRPGTKPPKRDEERGKTQGKHRKSFA
  LDSEGEEASQESSSEKDEEDDEEDEEDEDREEAVDTTKKETEVSDGEDEESDSSSKCSLY
  ADSDGENDSTSDSESSSSSSSSSSSSSSSSSSSSSSSSESSSEDEEEEERPAALPSASPP
  PREVPVPTPAPVEVPVPERVAGSPVTPLPEQEASPARPAGPTEESPPSAPLRPPEPPAGP
  PAPAPRPDERPSSPIPLLPPPKKRRKTVSFSAIEVVPAPEPPPATPPQAKFPGPASRKAP
  RGVERTIRNLPLDHASLVKSWPEEVSRGGRSRAGGRGRLTEEEEAEPGTEVDLAVLADLA
  LTPARRGLPALPAVEDSEATETSDEAERPRPLLSHILLEHNYALAVKPTPPAPALRPPEP
  VPAPAALFSSPADEVLEAPEVVVAEAEEPKPQQLQQQREEGEEEGEEEGEEEEEESSDSS
  SSSDGEGALRRRSLRSHARRRRPPPPPPPPPPRAYEPRSEFEQMTILYDIWNSGLDSEDM
  SYLRLTYERLLQQTSGADWLNDTHWVHHTITNLTTPKRKRRPQDGPREHQTGSARSEGYY
  PISKKEKDKYLDVCPVSARQLEGVDTQGTNRVLSERRSEQRRLLSAIGTSAIMDSDLLKL
  NQLKFRKKKLRFGRSRIHEWGLFAMEPIAADEMVIEYVGQNIRQMVADMREKRYVQEGIG
  SSYLFRVDHDTIIDATKCGNLARFINHCCTPNCYAKVITIESQKKIVIYSKQPIGVDEEI
  TYDYKFPLEDNKIPCLCGTESCRGSLN
• Function: Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery, forms H3K4me1, H3K4me2 and H3K4me3 methylation marks at active chromatin sites where transcription and DNA repair take place. Responsible for H3K4me3 enriched promoters and transcriptional programming of inner mass stem cells and neuron progenitors during embryogenesis. Required for H3K4me1 mark at stalled replication forks. Mediates FANCD2-dependent nucleosome remodeling and RAD51 nucleofilaments stabilization at reversed forks, protecting them from nucleolytic degradation. Does not methylate 'Lys-4' of histone H3 if the neighboring 'Lys-9' residue is already methylated. Binds RNAs involved in RNA processing and the DNA damage response.
• KEGG Pathway:
  Lysine degradation (hsa00310)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (R-HSA-8936459)
  Formation of WDR5-containing histone-modifying complexes (R-HSA-9772755)
  PKMTs methylate histone lysines (R-HSA-3214841)
• BioCyc Pathway: MetaCyc:HS01894-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bacteremia	DIS6N9RZ	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Definitive	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Definitive	Altered Expression	[2]
Invasive breast carcinoma	DISANYTW	Definitive	Altered Expression	[3]
Neoplasm	DISZKGEW	Definitive	Biomarker	[4]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[5]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[6]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[7]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[8]
Bacillary dysentery	DISFZHKN	Strong	Biomarker	[9]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[10]
Candidiasis	DISIRYMU	Strong	Biomarker	[11]
Candidiasis, invasive	DIS5VDG3	Strong	Biomarker	[11]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[12]
Cognitive impairment	DISH2ERD	Strong	Altered Expression	[13]
Congenital contractural arachnodactyly	DISOM1K7	Strong	Biomarker	[12]
Epilepsy	DISBB28L	Strong	Biomarker	[14]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[15]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Biomarker	[10]
Graves disease	DISU4KOQ	Strong	Altered Expression	[16]
Hepatitis B virus infection	DISLQ2XY	Strong	Posttranslational Modification	[17]
Intellectual disability, autosomal dominant 40	DISAI0IH	Strong	Autosomal dominant	[18]
Invasive candidiasis	DIS5EI0L	Strong	Biomarker	[11]
leukaemia	DISS7D1V	Strong	Biomarker	[19]
Leukemia	DISNAKFL	Strong	Biomarker	[20]
Neurodevelopmental disorder	DIS372XH	Strong	Genetic Variation	[14]
Neurodevelopmental disorder with speech impairment and dysmorphic facies	DISDI5NR	Strong	Autosomal dominant	[21]
Obsessive compulsive disorder	DIS1ZMM2	Strong	Biomarker	[8]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[6]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[22]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[23]
Intellectual disability	DISMBNXP	moderate	Biomarker	[21]
Pancreatic cancer	DISJC981	moderate	Genetic Variation	[24]
Schizophrenia	DISSRV2N	moderate	Genetic Variation	[13]
Parkinson disease	DISQVHKL	Disputed	Biomarker	[25]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[26]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[26]
Epilepsy, early-onset, with or without developmental delay	DISY1Y6T	Limited	Autosomal dominant	[27]
Lung cancer	DISCM4YA	Limited	Posttranslational Modification	[28]
Lung carcinoma	DISTR26C	Limited	Posttranslational Modification	[28]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[26]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[26]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Histone-lysine N-methyltransferase SETD1A (SETD1A).	[29]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Histone-lysine N-methyltransferase SETD1A (SETD1A).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Histone-lysine N-methyltransferase SETD1A (SETD1A).	[38]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Histone-lysine N-methyltransferase SETD1A (SETD1A).	[40]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Histone-lysine N-methyltransferase SETD1A (SETD1A).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histone-lysine N-methyltransferase SETD1A (SETD1A).	[31]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Histone-lysine N-methyltransferase SETD1A (SETD1A).	[32]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Histone-lysine N-methyltransferase SETD1A (SETD1A).	[33]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Histone-lysine N-methyltransferase SETD1A (SETD1A).	[34]
Marinol	DM70IK5	Approved	Marinol increases the expression of Histone-lysine N-methyltransferase SETD1A (SETD1A).	[35]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Histone-lysine N-methyltransferase SETD1A (SETD1A).	[36]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Histone-lysine N-methyltransferase SETD1A (SETD1A).	[37]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Histone-lysine N-methyltransferase SETD1A (SETD1A).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Histone-lysine N-methyltransferase SETD1A (SETD1A).	[41]

References

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