Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIGHER7)

DOT Name Rab11 family-interacting protein 4 (RAB11FIP4)
Synonyms FIP4-Rab11; Rab11-FIP4; Arfophilin-2
Gene Name RAB11FIP4
Related Disease
Colorectal carcinoma ( )
Hepatocellular carcinoma ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Pancreatic cancer ( )
Acute myelogenous leukaemia ( )
UniProt ID
RFIP4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF09457
Sequence
MAGGAGWSGAPAALLRSVRRLREVFEVCGRDPDGFLRVERVAALGLRFGQGEEVEKLVKY
LDPNDLGRINFKDFCRGVFAMKGCEELLKDVLSVESAGTLPCAPEIPDCVEQGSEVTGPT
FADGELIPREPGFFPEDEEEAMTLAPPEGPQELYTDSPMESTQSLEGSVGSPAEKDGGLG
GLFLPEDKSLVHTPSMTTSDLSTHSTTSLISNEEQFEDYGEGDDVDCAPSSPCPDDETRT
NVYSDLGSSVSSSAGQTPRKMRHVYNSELLDVYCSQCCKKINLLNDLEARLKNLKANSPN
RKISSTAFGRQLMHSSNFSSSNGSTEDLFRDSIDSCDNDITEKVSFLEKKVTELENDSLT
NGDLKSKLKQENTQLVHRVHELEEMVKDQETTAEQALEEEARRHREAYGKLEREKATEVE
LLNARVQQLEEENTELRTTVTRLKSQTEKLDEERQRMSDRLEDTSLRLKDEMDLYKRMMD
KLRQNRLEFQKEREATQELIEDLRKELEHLQMYKLDCERPGRGRSASSGLGEFNARAREV
ELEHEVKRLKQENYKLRDQNDDLNGQILSLSLYEAKNLFAAQTKAQSLAAEIDTASRDEL
MEALKEQEEINFRLRQYMDKIILAILDHNPSILEIKH
Function
Acts as a regulator of endocytic traffic by participating in membrane delivery. Required for the abcission step in cytokinesis, possibly by acting as an 'address tag' delivering recycling endosome membranes to the cleavage furrow during late cytokinesis. In case of infection by HCMV (human cytomegalovirus), may participate in egress of the virus out of nucleus; this function is independent of ARF6.
Tissue Specificity Present at high level in testis (at protein level). Weakly expressed in other tissues.
KEGG Pathway
Endocytosis (hsa04144 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Colorectal carcinoma DIS5PYL0 Strong Biomarker [1]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [2]
Metastatic malignant neoplasm DIS86UK6 Strong Altered Expression [1]
Neoplasm DISZKGEW Strong Altered Expression [3]
Pancreatic cancer DISJC981 Strong Altered Expression [3]
Acute myelogenous leukaemia DISCSPTN Limited Genetic Variation [4]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Rab11 family-interacting protein 4 (RAB11FIP4). [5]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Rab11 family-interacting protein 4 (RAB11FIP4). [15]
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14 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Rab11 family-interacting protein 4 (RAB11FIP4). [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Rab11 family-interacting protein 4 (RAB11FIP4). [7]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Rab11 family-interacting protein 4 (RAB11FIP4). [8]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Rab11 family-interacting protein 4 (RAB11FIP4). [9]
Triclosan DMZUR4N Approved Triclosan increases the expression of Rab11 family-interacting protein 4 (RAB11FIP4). [10]
Menadione DMSJDTY Approved Menadione affects the expression of Rab11 family-interacting protein 4 (RAB11FIP4). [9]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Rab11 family-interacting protein 4 (RAB11FIP4). [11]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of Rab11 family-interacting protein 4 (RAB11FIP4). [12]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Rab11 family-interacting protein 4 (RAB11FIP4). [13]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Rab11 family-interacting protein 4 (RAB11FIP4). [11]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Rab11 family-interacting protein 4 (RAB11FIP4). [6]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Rab11 family-interacting protein 4 (RAB11FIP4). [14]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Rab11 family-interacting protein 4 (RAB11FIP4). [16]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Rab11 family-interacting protein 4 (RAB11FIP4). [17]
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⏷ Show the Full List of 14 Drug(s)

References

1 Hypoxia-induced Rab11-family interacting protein4expression promotes migration and invasion of colon cancer and correlates with poor prognosis.Mol Med Rep. 2018 Mar;17(3):3797-3806. doi: 10.3892/mmr.2017.8283. Epub 2017 Dec 15.
2 Hypoxia upregulates Rab11-family interacting protein 4 through HIF-1 to promote the metastasis of hepatocellular carcinoma.Oncogene. 2015 Dec 3;34(49):6007-17. doi: 10.1038/onc.2015.49. Epub 2015 Mar 9.
3 High Rab11-FIP4 expression predicts poor prognosis and exhibits tumor promotion in pancreatic cancer.Int J Oncol. 2017 Feb;50(2):396-404. doi: 10.3892/ijo.2016.3828. Epub 2016 Dec 30.
4 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
5 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.
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 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
9 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
10 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
11 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
12 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
13 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
14 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.
15 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
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 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.