Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQUX50Z)

• DOT Name: Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4)
• Gene Name: LDLRAD4
• Related Disease:
  Advanced cancer
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Mental disorder
  Acute myelogenous leukaemia
  Pancreatic cancer
• UniProt ID: LRAD4_HUMAN
• Pfam ID: PF00057
• Sequence:
  MPEAGFQATNAFTECKFTCTSGKCLYLGSLVCNQQNDCGDNSDEENCLLVTEHPPPGIFN
  SELEFAQIIIIVVVVTVMVVVIVCLLNHYKVSTRSFINRPNQSRRREDGLPQEGCLWPSD
  SAAPRLGASEIMHAPRSRDRFTAPSFIQRDRFSRFQPTYPYVQHEIDLPPTISLSDGEEP
  PPYQGPCTLQLRDPEQQMELNRESVRAPPNRTIFDSDLIDIAMYSGGPCPPSSNSGISAS
  TCSSNGRMEGPPPTYSEVMGHHPGASFLHHQRSNAHRGSRLQFQQNNAESTIVPIKGKDR
  KPGNLV
• Function: Functions as a negative regulator of TGF-beta signaling and thereby probably plays a role in cell proliferation, differentiation, apoptosis, motility, extracellular matrix production and immunosuppression. In the canonical TGF-beta pathway, ZFYVE9/SARA recruits the intracellular signal transducer and transcriptional modulators SMAD2 and SMAD3 to the TGF-beta receptor. Phosphorylated by the receptor, SMAD2 and SMAD3 then form a heteromeric complex with SMAD4 that translocates to the nucleus to regulate transcription. Through interaction with SMAD2 and SMAD3, LDLRAD4 may compete with ZFYVE9 and SMAD4 and prevent propagation of the intracellular signal.
• Tissue Specificity: Expressed in lymphocytes.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[2]
Liver cancer	DISDE4BI	Strong	Biomarker	[2]
Mental disorder	DIS3J5R8	Strong	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[3]
Pancreatic cancer	DISJC981	moderate	Genetic Variation	[4]

18 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 Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[11]
Selenium	DM25CGV	Approved	Selenium increases the expression of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[12]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[13]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[14]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[15]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[16]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[17]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[21]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[15]
biochanin A	DM0HPWY	Investigative	biochanin A decreases the expression of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[22]

1 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 increases the methylation of Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4).	[18]

References

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• [19] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
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