Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTT4DY3)

• DOT Name: Ras-related protein Rab-4B (RAB4B)
• Synonyms: EC 3.6.5.2
• Gene Name: RAB4B
• Related Disease:
  Chronic obstructive pulmonary disease
  Obesity
  Prostate cancer
  Prostate neoplasm
• UniProt ID: RAB4B_HUMAN
• PDB ID: 2O52
• EC Number: 3.6.5.2
• Pfam ID: PF00071
• Sequence:
  MAETYDFLFKFLVIGSAGTGKSCLLHQFIENKFKQDSNHTIGVEFGSRVVNVGGKTVKLQ
  IWDTAGQERFRSVTRSYYRGAAGALLVYDITSRETYNSLAAWLTDARTLASPNIVVILCG
  NKKDLDPEREVTFLEASRFAQENELMFLETSALTGENVEEAFLKCARTILNKIDSGELDP
  ERMGSGIQYGDASLRQLRQPRSAQAVAPQPCGC
• Function: Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. Protein transport. Probably involved in vesicular traffic. Acts as a regulator of platelet alpha-granule release during activation and aggregation of platelets.
• Reactome Pathway:
  RAB geranylgeranylation (R-HSA-8873719)
  MET receptor recycling (R-HSA-8875656)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[1]
Obesity	DIS47Y1K	Strong	Altered Expression	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[3]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ras-related protein Rab-4B (RAB4B).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ras-related protein Rab-4B (RAB4B).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ras-related protein Rab-4B (RAB4B).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Ras-related protein Rab-4B (RAB4B).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Ras-related protein Rab-4B (RAB4B).	[7]

References

• [1] Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.Nat Genet. 2017 Mar;49(3):426-432. doi: 10.1038/ng.3752. Epub 2017 Feb 6.
• [2] Rab4b Deficiency in T Cells Promotes Adipose Treg/Th17 Imbalance, Adipose Tissue Dysfunction, and Insulin Resistance.Cell Rep. 2018 Dec 18;25(12):3329-3341.e5. doi: 10.1016/j.celrep.2018.11.083.
• [3] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.