Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUQ4CQY)

• DOT Name: AT-rich interactive domain-containing protein 5B (ARID5B)
• Synonyms: ARID domain-containing protein 5B; MRF1-like protein; Modulator recognition factor 2; MRF-2
• Gene Name: ARID5B
• Related Disease:
  Acute myelogenous leukaemia
  Metabolic disorder
  Acute leukaemia
  Acute lymphocytic leukaemia
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Autoimmune disease
  Autoimmune disease, susceptibility to, 6
  Cardiovascular disease
  Coronary heart disease
  Hypothyroidism
  leukaemia
  Nasopharyngeal carcinoma
  Nijmegen breakage syndrome
  Prostate cancer
  Prostate carcinoma
  Rheumatoid arthritis
  STAT3-related early-onset multisystem autoimmune disease
  Systemic lupus erythematosus
  T-cell acute lymphoblastic leukaemia
  Vitiligo
  Graves disease
  Childhood acute lymphoblastic leukemia
  Coronary atherosclerosis
  Leukemia
  Neoplasm
  Non-insulin dependent diabetes
  Isolated cleft palate
• UniProt ID: ARI5B_HUMAN
• PDB ID: 1IG6; 2OEH
• Pfam ID: PF01388
• Sequence:
  MEPNSLQWVGSPCGLHGPYIFYKAFQFHLEGKPRILSLGDFFFVRCTPKDPICIAELQLL
  WEERTSRQLLSSSKLYFLPEDTPQGRNSDHGEDEVIAVSEKVIVKLEDLVKWVHSDFSKW
  RCGFHAGPVKTEALGRNGQKEALLKYRQSTLNSGLNFKDVLKEKADLGEDEEETNVIVLS
  YPQYCRYRSMLKRIQDKPSSILTDQFALALGGIAVVSRNPQILYCRDTFDHPTLIENESI
  CDEFAPNLKGRPRKKKPCPQRRDSFSGVKDSNNNSDGKAVAKVKCEARSALTKPKNNHNC
  KKVSNEEKPKVAIGEECRADEQAFLVALYKYMKERKTPIERIPYLGFKQINLWTMFQAAQ
  KLGGYETITARRQWKHIYDELGGNPGSTSAATCTRRHYERLILPYERFIKGEEDKPLPPI
  KPRKQENSSQENENKTKVSGTKRIKHEIPKSKKEKENAPKPQDAAEVSSEQEKEQETLIS
  QKSIPEPLPAADMKKKIEGYQEFSAKPLASRVDPEKDNETDQGSNSEKVAEEAGEKGPTP
  PLPSAPLAPEKDSALVPGASKQPLTSPSALVDSKQESKLCCFTESPESEPQEASFPSFPT
  TQPPLANQNETEDDKLPAMADYIANCTVKVDQLGSDDIHNALKQTPKVLVVQSFDMFKDK
  DLTGPMNENHGLNYTPLLYSRGNPGIMSPLAKKKLLSQVSGASLSSSYPYGSPPPLISKK
  KLIARDDLCSSLSQTHHGQSTDHMAVSRPSVIQHVQSFRSKPSEERKTINDIFKHEKLSR
  SDPHRCSFSKHHLNPLADSYVLKQEIQEGKDKLLEKRALPHSHMPSFLADFYSSPHLHSL
  YRHTEHHLHNEQTSKYPSRDMYRESENSSFPSHRHQEKLHVNYLTSLHLQDKKSAAAEAP
  TDDQPTDLSLPKNPHKPTGKVLGLAHSTTGPQESKGISQFQVLGSQSRDCHPKACRVSPM
  TMSGPKKYPESLSRSGKPHHVRLENFRKMEGMVHPILHRKMSPQNIGAARPIKRSLEDLD
  LVIAGKKARAVSPLDPSKEVSGKEKASEQESEGSKAAHGGHSGGGSEGHKLPLSSPIFPG
  LYSGSLCNSGLNSRLPAGYSHSLQYLKNQTVLSPLMQPLAFHSLVMQRGIFTSPTNSQQL
  YRHLAAATPVGSSYGDLLHNSIYPLAAINPQAAFPSSQLSSVHPSTKL
• Function: Transcription coactivator that binds to the 5'-AATA[CT]-3' core sequence and plays a key role in adipogenesis and liver development. Acts by forming a complex with phosphorylated PHF2, which mediates demethylation at Lys-336, leading to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2), followed by transcription activation of target genes. The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver. Required for adipogenesis: regulates triglyceride metabolism in adipocytes by regulating expression of adipogenic genes. Overexpression leads to induction of smooth muscle marker genes, suggesting that it may also act as a regulator of smooth muscle cell differentiation and proliferation. Represses the cytomegalovirus enhancer.
• Tissue Specificity: Widely expressed, including in liver (at protein level).
• Reactome Pathway: HDMs demethylate histones (R-HSA-3214842)

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Genetic Variation	[1]
Metabolic disorder	DIS71G5H	Definitive	Biomarker	[2]
Acute leukaemia	DISDQFDI	Strong	Genetic Variation	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Genetic Variation	[3]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[4]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[5]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[5]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[6]
Autoimmune disease, susceptibility to, 6	DISHNUXI	Strong	Genetic Variation	[6]
Cardiovascular disease	DIS2IQDX	Strong	Altered Expression	[5]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[7]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[6]
leukaemia	DISS7D1V	Strong	Genetic Variation	[8]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Genetic Variation	[9]
Nijmegen breakage syndrome	DIS98HVL	Strong	Genetic Variation	[10]
Prostate cancer	DISF190Y	Strong	Altered Expression	[11]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[11]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[12]
STAT3-related early-onset multisystem autoimmune disease	DISAXTN7	Strong	Genetic Variation	[6]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[13]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Genetic Variation	[14]
Vitiligo	DISR05SL	Strong	Genetic Variation	[15]
Graves disease	DISU4KOQ	moderate	Genetic Variation	[16]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Limited	Altered Expression	[17]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[7]
Leukemia	DISNAKFL	Limited	Genetic Variation	[8]
Neoplasm	DISZKGEW	Limited	Biomarker	[18]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[7]
Isolated cleft palate	DISV80CD	No Known	Unknown	[19]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	AT-rich interactive domain-containing protein 5B (ARID5B) affects the abundance of Methotrexate.	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	AT-rich interactive domain-containing protein 5B (ARID5B) affects the response to substance of Fluorouracil.	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[21]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[22]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[24]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[25]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[27]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[28]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[29]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[28]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[30]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[32]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[33]
Celastrol	DMWQIJX	Preclinical	Celastrol decreases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[36]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[37]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[38]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[39]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[40]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[41]
biochanin A	DM0HPWY	Investigative	biochanin A increases the expression of AT-rich interactive domain-containing protein 5B (ARID5B).	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of AT-rich interactive domain-containing protein 5B (ARID5B).	[26]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of AT-rich interactive domain-containing protein 5B (ARID5B).	[34]

References

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