Details of Drug Off-Target (DOT)

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

• DOT Name: AT-rich interactive domain-containing protein 4B (ARID4B)
• Synonyms: ARID domain-containing protein 4B; 180 kDa Sin3-associated polypeptide; Sin3-associated polypeptide p180; Breast cancer-associated antigen BRCAA1; Histone deacetylase complex subunit SAP180; Retinoblastoma-binding protein 1-like 1
• Gene Name: ARID4B
• Related Disease:
  Metabolic disorder
  Advanced cancer
  Alzheimer disease
  Breast neoplasm
  Carcinoma
  Cardiovascular disease
  Chordoma
  Chronic kidney disease
  Chronic renal failure
  Colorectal carcinoma
  End-stage renal disease
  Exanthem
  Fatty liver disease
  Hyperinsulinemia
  Leukemia
  Liver cirrhosis
  Maple syrup urine disease
  Meningioma
  Metastatic malignant neoplasm
  Neoplasm
  Non-alcoholic fatty liver disease
  Non-insulin dependent diabetes
  Ovarian cancer
  Polycystic ovarian syndrome
  Postpartum depression
  Propionic acidemia
  Prostate cancer
  Prostate carcinoma
  Retinoblastoma
  Spinal muscular atrophy
  Type-1 diabetes
  Urea cycle disorder
  Breast cancer
  Breast carcinoma
  Atrial septal defect
  Autism spectrum disorder
  Hepatocellular carcinoma
  Inborn disorder of amino acid metabolism
  Type-1/2 diabetes
• UniProt ID: ARI4B_HUMAN
• PDB ID: 7DM4
• Pfam ID: PF01388 ; PF08169 ; PF11717
• Sequence:
  MKALDEPPYLTVGTDVSAKYRGAFCEAKIKTAKRLVKVKVTFRHDSSTVEVQDDHIKGPL
  KVGAIVEVKNLDGAYQEAVINKLTDASWYTVVFDDGDEKTLRRSSLCLKGERHFAESETL
  DQLPLTNPEHFGTPVIGKKTNRGRRSNHIPEEESSSSSSDEDEDDRKQIDELLGKVVCVD
  YISLDKKKALWFPALVVCPDCSDEIAVKKDNILVRSFKDGKFTSVPRKDVHEITSDTAPK
  PDAVLKQAFEQALEFHKSRTIPANWKTELKEDSSSSEAEEEEEEEDDEKEKEDNSSEEEE
  EIEPFPEERENFLQQLYKFMEDRGTPINKRPVLGYRNLNLFKLFRLVHKLGGFDNIESGA
  VWKQVYQDLGIPVLNSAAGYNVKCAYKKYLYGFEEYCRSANIEFQMALPEKVVNKQCKEC
  ENVKEIKVKEENETEIKEIKMEEERNIIPREEKPIEDEIERKENIKPSLGSKKNLLESIP
  THSDQEKEVNIKKPEDNENLDDKDDDTTRVDESLNIKVEAEEEKAKSGDETNKEEDEDDE
  EAEEEEEEEEEEEDEDDDDNNEEEEFECYPPGMKVQVRYGRGKNQKMYEASIKDSDVEGG
  EVLYLVHYCGWNVRYDEWIKADKIVRPADKNVPKIKHRKKIKNKLDKEKDKDEKYSPKNC
  KLRRLSKPPFQTNPSPEMVSKLDLTDAKNSDTAHIKSIEITSILNGLQASESSAEDSEQE
  DERGAQDMDNNGKEESKIDHLTNNRNDLISKEEQNSSSLLEENKVHADLVISKPVSKSPE
  RLRKDIEVLSEDTDYEEDEVTKKRKDVKKDTTDKSSKPQIKRGKRRYCNTEECLKTGSPG
  KKEEKAKNKESLCMENSSNSSSDEDEEETKAKMTPTKKYNGLEEKRKSLRTTGFYSGFSE
  VAEKRIKLLNNSDERLQNSRAKDRKDVWSSIQGQWPKKTLKELFSDSDTEAAASPPHPAP
  EEGVAEESLQTVAEEESCSPSVELEKPPPVNVDSKPIEEKTVEVNDRKAEFPSSGSNSVL
  NTPPTTPESPSSVTVTEGSRQQSSVTVSEPLAPNQEEVRSIKSETDSTIEVDSVAGELQD
  LQSEGNSSPAGFDASVSSSSSNQPEPEHPEKACTGQKRVKDAQGGGSSSKKQKRSHKATV
  VNNKKKGKGTNSSDSEELSAGESITKSQPVKSVSTGMKSHSTKSPARTQSPGKCGKNGDK
  DPDLKEPSNRLPKVYKWSFQMSDLENMTSAERITILQEKLQEIRKHYLSLKSEVASIDRR
  RKRLKKKERESAATSSSSSSPSSSSITAAVMLTLAEPSMSSASQNGMSVECR
• Function: Acts as a transcriptional repressor. May function in the assembly and/or enzymatic activity of the Sin3A corepressor complex or in mediating interactions between the complex and other regulatory complexes. Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4A. Involved in spermatogenesis, together with ARID4A, where it functions as a transcriptional coactivator for AR (androgen receptor) and enhances expression of genes required for sperm maturation. Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier. Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis. May function as a leukemia suppressor.
• Tissue Specificity: Highly expressed in the testis and in breast, lung, colon, pancreatic and ovarian cancers. Expressed at low levels in the thymus, prostate and ovary.
• Reactome Pathway:
  NoRC negatively regulates rRNA expression (R-HSA-427413)
  Potential therapeutics for SARS (R-HSA-9679191)
  HDACs deacetylate histones (R-HSA-3214815)

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Metabolic disorder	DIS71G5H	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Carcinoma	DISH9F1N	Strong	Altered Expression	[5]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[6]
Chordoma	DISCHJE7	Strong	Biomarker	[7]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[8]
Chronic renal failure	DISGG7K6	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
End-stage renal disease	DISXA7GG	Strong	Biomarker	[8]
Exanthem	DISAFOQN	Strong	Biomarker	[10]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[11]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[12]
Leukemia	DISNAKFL	Strong	Biomarker	[7]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[13]
Maple syrup urine disease	DIS61XRH	Strong	Biomarker	[14]
Meningioma	DISPT4TG	Strong	Biomarker	[7]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Altered Expression	[15]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[16]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[5]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[17]
Postpartum depression	DIS08UKE	Strong	Biomarker	[18]
Propionic acidemia	DIS56N48	Strong	Altered Expression	[19]
Prostate cancer	DISF190Y	Strong	Biomarker	[20]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[20]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[5]
Spinal muscular atrophy	DISTLKOB	Strong	Biomarker	[21]
Type-1 diabetes	DIS7HLUB	Strong	Biomarker	[8]
Urea cycle disorder	DIS5O5V0	Strong	Altered Expression	[19]
Breast cancer	DIS7DPX1	moderate	Biomarker	[7]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[7]
Atrial septal defect	DISJT76B	Limited	Biomarker	[22]
Autism spectrum disorder	DISXK8NV	Limited	Altered Expression	[22]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[2]
Inborn disorder of amino acid metabolism	DISFWXCM	Limited	Genetic Variation	[10]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	AT-rich interactive domain-containing protein 4B (ARID4B) increases the response to substance of Arsenic trioxide.	[40]

5 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 AT-rich interactive domain-containing protein 4B (ARID4B).	[24]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of AT-rich interactive domain-containing protein 4B (ARID4B).	[33]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of AT-rich interactive domain-containing protein 4B (ARID4B).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of AT-rich interactive domain-containing protein 4B (ARID4B).	[36]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of AT-rich interactive domain-containing protein 4B (ARID4B).	[34]

12 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 AT-rich interactive domain-containing protein 4B (ARID4B).	[25]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of AT-rich interactive domain-containing protein 4B (ARID4B).	[26]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of AT-rich interactive domain-containing protein 4B (ARID4B).	[27]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of AT-rich interactive domain-containing protein 4B (ARID4B).	[28]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of AT-rich interactive domain-containing protein 4B (ARID4B).	[29]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of AT-rich interactive domain-containing protein 4B (ARID4B).	[30]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of AT-rich interactive domain-containing protein 4B (ARID4B).	[31]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of AT-rich interactive domain-containing protein 4B (ARID4B).	[32]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of AT-rich interactive domain-containing protein 4B (ARID4B).	[35]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of AT-rich interactive domain-containing protein 4B (ARID4B).	[37]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of AT-rich interactive domain-containing protein 4B (ARID4B).	[38]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of AT-rich interactive domain-containing protein 4B (ARID4B).	[39]

References

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