Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNA33DE)

• DOT Name: Rab11 family-interacting protein 5 (RAB11FIP5)
• Synonyms: Rab11-FIP5; Gamma-SNAP-associated factor 1; Gaf-1; Phosphoprotein pp75; Rab11-interacting protein Rip11
• Gene Name: RAB11FIP5
• Related Disease:
  Autism
  Autism spectrum disorder
  Colorectal carcinoma
  Pervasive developmental disorder
  Prostate cancer
  Prostate carcinoma
  Schizophrenia
• UniProt ID: RFIP5_HUMAN
• Pfam ID: PF00168 ; PF09457
• Sequence:
  MALVRGAEPAAGPSRWLPTHVQVTVLRARGLRGKSSGAGSTSDAYTVIQVGREKYSTSVV
  EKTHGCPEWREECSFELPPGALDGLLRAQEADAGPAPWAASSAAACELVLTTMHRSLIGV
  DKFLGQATVALDEVFGAGRAQHTQWYKLHSKPGKKEKERGEIEVTIQFTRNNLSASMFDL
  SMKDKPRSPFSKIRDKMKGKKKYDLESASAILPSSAIEDPDLGSLGKMGKAKGFFLRNKL
  RKSSLTQSNTSLGSDSTLSSASGSLAYQGPGAELLTRSPSRSSWLSTEGGRDSAQSPKLF
  THKRTYSDEANQMRVAPPRALLDLQGHLDAASRSSLCVNGSHIYNEEPQGPVRHRSSISG
  SLPSSGSLQAVSSRFSEEGPRSTDDTWPRGSRSNSSSEAVLGQEELSAQAKVLAPGASHP
  GEEEGARLPEGKPVQVATPIVASSEAVAEKEGARKEERKPRMGLFHHHHQGLSRSELGRR
  SSLGEKGGPILGASPHHSSSGEEKAKSSWFGLREAKDPTQKPSPHPVKPLSAAPVEGSPD
  RKQSRSSLSIALSSGLEKLKTVTSGSIQPVTQAPQAGQMVDTKRLKDSAVLDQSAKYYHL
  THDELISLLLQRERELSQRDEHVQELESYIDRLLVRIMETSPTLLQIPPGPPK
• Function: Rab effector involved in protein trafficking from apical recycling endosomes to the apical plasma membrane. Involved in insulin granule exocytosis. May regulate V-ATPase intracellular transport in response to extracellular acidosis.
• Tissue Specificity: Detected at low levels in heart, brain, placenta, lung, liver, adipocytes, kidney, spleen, skeletal muscle and pancreas.
• KEGG Pathway: Endocytosis (hsa04144)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Biomarker	[1]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[2]
Pervasive developmental disorder	DIS51975	Strong	Genetic Variation	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[3]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[4]

9 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 Rab11 family-interacting protein 5 (RAB11FIP5).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Rab11 family-interacting protein 5 (RAB11FIP5).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Rab11 family-interacting protein 5 (RAB11FIP5).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Rab11 family-interacting protein 5 (RAB11FIP5).	[8]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Rab11 family-interacting protein 5 (RAB11FIP5).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Rab11 family-interacting protein 5 (RAB11FIP5).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Rab11 family-interacting protein 5 (RAB11FIP5).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Rab11 family-interacting protein 5 (RAB11FIP5).	[12]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Rab11 family-interacting protein 5 (RAB11FIP5).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Rab11 family-interacting protein 5 (RAB11FIP5).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Rab11 family-interacting protein 5 (RAB11FIP5).	[13]

References

• [1] A de novo apparently balanced translocation [46,XY,t(2;9)(p13;p24)] interrupting RAB11FIP5 identifies a potential candidate gene for autism spectrum disorder.Am J Med Genet B Neuropsychiatr Genet. 2008 Jun 5;147B(4):411-7. doi: 10.1002/ajmg.b.30755.
• [2] Recurrent, low-frequency coding variants contributing to colorectal cancer in the Swedish population.PLoS One. 2018 Mar 16;13(3):e0193547. doi: 10.1371/journal.pone.0193547. eCollection 2018.
• [3] Novel Regulation of Integrin Trafficking by Rab11-FIP5 in Aggressive Prostate Cancer.Mol Cancer Res. 2018 Aug;16(8):1319-1331. doi: 10.1158/1541-7786.MCR-17-0589. Epub 2018 May 14.
• [4] Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.Am J Hum Genet. 2019 Aug 1;105(2):334-350. doi: 10.1016/j.ajhg.2019.06.012.
• [5] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] 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.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.