Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTX9RWE)

• DOT Name: Rab11 family-interacting protein 2 (RAB11FIP2)
• Synonyms: Rab11-FIP2; NRip11
• Gene Name: RAB11FIP2
• Related Disease:
  Colorectal carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Gastric cancer
  Stomach cancer
  Inflammation
  Nasopharyngeal carcinoma
• UniProt ID: RFIP2_HUMAN
• PDB ID: 2GZD; 2GZH; 2K6S; 3TSO; 4C4P; 6S8X
• Pfam ID: PF00168 ; PF09457
• Sequence:
  MMLSEQAQKWFPTHVQVTVLQAKDLKPKGKSGTNDTYTIIQLGKEKYSTSVAEKTLEPVW
  KEEASFELPGLLIQGSPEKYILFLIVMHRSLVGLDKFLGQVAINLNDIFEDKQRRKTEWF
  RLESKQGKRIKNRGEIKVNIQFMRNNMTASMFDLSMKDKTRSPFAKLKDKMKGRKNDGTF
  SDTSSAIIPSTHMPDANSEFSSGEIQMKSKPKKPFLLGPQRLSSAHSMSDLSGSHMSSEK
  LKAGTIGQTHLLGHQLDSFGTVPESGSLKSPHRRTLSFDTSKMNQPDSIVDEGELCFGRQ
  NDPFTNVTASLPQKFATLPRKKNPFEESSETWDSSMNLFSKPIEIRKENKREKREKVSLF
  ERVTGKKDSRRSDKLNNGGSDSPCDLKSPNAFSENRQDYFDYESTNPFTAKFRASNIMPS
  SSFHMSPTSNEDLRKIPDSNPFDATAGYRSLTYEEVLQELVKHKELLRRKDTHIRELEDY
  IDNLLVRVMEETPSILRVPYEPSRKAGKFSNS
• Function: A Rab11 effector binding preferentially phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and phosphatidic acid (PA) and acting in the regulation of the transport of vesicles from the endosomal recycling compartment (ERC) to the plasma membrane. Involved in insulin granule exocytosis. Also involved in receptor-mediated endocytosis and membrane trafficking of recycling endosomes, probably originating from clathrin-coated vesicles. Required in a complex with MYO5B and RAB11 for the transport of NPC1L1 to the plasma membrane. Also acts as a regulator of cell polarity. Plays an essential role in phagocytosis through a mechanism involving TICAM2, RAC1 and CDC42 Rho GTPases for controlling actin-dynamics.
• KEGG Pathway: Endocytosis (hsa04144)
• Reactome Pathway: Vasopressin regulates renal water homeostasis via Aquaporins (R-HSA-432040)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Posttranslational Modification	[2]
Gastric cancer	DISXGOUK	moderate	Biomarker	[3]
Stomach cancer	DISKIJSX	moderate	Biomarker	[3]
Inflammation	DISJUQ5T	Limited	Biomarker	[4]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Rab11 family-interacting protein 2 (RAB11FIP2) affects the response to substance of Methotrexate.	[18]

11 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 Rab11 family-interacting protein 2 (RAB11FIP2).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Rab11 family-interacting protein 2 (RAB11FIP2).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Rab11 family-interacting protein 2 (RAB11FIP2).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Rab11 family-interacting protein 2 (RAB11FIP2).	[9]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Rab11 family-interacting protein 2 (RAB11FIP2).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Rab11 family-interacting protein 2 (RAB11FIP2).	[12]
Marinol	DM70IK5	Approved	Marinol increases the expression of Rab11 family-interacting protein 2 (RAB11FIP2).	[13]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Rab11 family-interacting protein 2 (RAB11FIP2).	[14]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Rab11 family-interacting protein 2 (RAB11FIP2).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Rab11 family-interacting protein 2 (RAB11FIP2).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Rab11 family-interacting protein 2 (RAB11FIP2).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Rab11 family-interacting protein 2 (RAB11FIP2).	[11]

References

• [1] Overexpression of Rab11-FIP2 in colorectal cancer cells promotes tumor migration and angiogenesis through increasing secretion of PAI-1.Cancer Cell Int. 2018 Mar 9;18:35. doi: 10.1186/s12935-018-0532-0. eCollection 2018.
• [2] Rab11-FIP2 suppressed tumor growth via regulation of PGK1 ubiquitination in non-small cell lung cancer.Biochem Biophys Res Commun. 2019 Jan 1;508(1):60-65. doi: 10.1016/j.bbrc.2018.11.108. Epub 2018 Nov 22.
• [3] Inhibition of the miR-192/215-Rab11-FIP2 axis suppresses human gastric cancer progression.Cell Death Dis. 2018 Jul 13;9(7):778. doi: 10.1038/s41419-018-0785-5.
• [4] Rab11a Mediates Vascular Endothelial-Cadherin Recycling and Controls Endothelial Barrier Function.Arterioscler Thromb Vasc Biol. 2016 Feb;36(2):339-49. doi: 10.1161/ATVBAHA.115.306549. Epub 2015 Dec 10.
• [5] Knockdown Rab11-FIP2 inhibits migration and invasion of nasopharyngeal carcinoma via suppressing Rho GTPase signaling.J Cell Biochem. 2020 Feb;121(2):1072-1086. doi: 10.1002/jcb.29344. Epub 2019 Aug 26.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] 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.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] 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.
• [10] Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Mol Biol Cell. 2004 Mar;15(3):1262-72. doi: 10.1091/mbc.e03-06-0360. Epub 2003 Dec 29.
• [11] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [12] 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.
• [13] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [14] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [15] 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.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [18] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.