Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEW72FR)

• DOT Name: Guanine nucleotide exchange factor MSS4 (RABIF)
• Synonyms: Rab-interacting factor
• Gene Name: RABIF
• Related Disease:
  Advanced cancer
  Pancreatic cancer
• UniProt ID: MSS4_HUMAN
• PDB ID: 1FWQ; 2FU5
• Pfam ID: PF04421
• Sequence:
  MEPAEQPSELVSAEGRNRKAVLCQRCGSRVLQPGTALFSRRQLFLPSMRKKPALSDGSNP
  DGDLLQEHWLVEDMFIFENVGFTKDVGNIKFLVCADCEIGPIGWHCLDDKNSFYVALERV
  SHE
• Function: Guanine-nucleotide-releasing protein that acts on members of the SEC4/YPT1/RAB subfamily. Stimulates GDP release from both YPT1, RAB3A and RAB10, but is less active on these proteins than on the SEC4 protein. Might play a general role in vesicular transport.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Genetic Variation	[1]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[2]

10 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 Guanine nucleotide exchange factor MSS4 (RABIF).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Guanine nucleotide exchange factor MSS4 (RABIF).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Guanine nucleotide exchange factor MSS4 (RABIF).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Guanine nucleotide exchange factor MSS4 (RABIF).	[6]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Guanine nucleotide exchange factor MSS4 (RABIF).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Guanine nucleotide exchange factor MSS4 (RABIF).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Guanine nucleotide exchange factor MSS4 (RABIF).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Guanine nucleotide exchange factor MSS4 (RABIF).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Guanine nucleotide exchange factor MSS4 (RABIF).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Guanine nucleotide exchange factor MSS4 (RABIF).	[12]

References

• [1] Risk Stratification by Urinary Prostate Cancer Gene 3 Testing Before Magnetic Resonance Imaging-Ultrasound Fusion-targeted Prostate Biopsy Among Men With No History of Biopsy.Urology. 2017 Jan;99:174-179. doi: 10.1016/j.urology.2016.08.022. Epub 2016 Aug 22.
• [2] Cloning of novel transcripts of the human guanine-nucleotide-exchange factor Mss4: in situ chromosomal mapping and expression in pancreatic cancer.Genomics. 1997 Dec 15;46(3):389-96. doi: 10.1006/geno.1997.5049.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [10] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.