Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC4FW0J)

DOT Name	Ras-related protein Rab-11A (RAB11A)
Synonyms	Rab-11; EC 3.6.5.2; YL8
Gene Name	RAB11A
Related Disease	Non-insulin dependent diabetes ( ) Advanced cancer ( ) Alzheimer disease ( ) Amyloidosis ( ) Bladder cancer ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Burkitt lymphoma ( ) Cervical cancer ( ) Cervical carcinoma ( ) Charcot-Marie-Tooth disease type 4C ( ) Cholestasis ( ) Colon cancer ( ) Colon carcinoma ( ) Hereditary hemochromatosis ( ) Huntington disease ( ) Influenza ( ) Intestinal disorder ( ) Lysosomal lipid storage disorder ( ) Malabsorption syndrome ( ) Microvillus inclusion disease ( ) Neoplasm ( ) Nephrotic syndrome ( ) Neurodevelopmental disorder ( ) Non-small-cell lung cancer ( ) Pancreatic cancer ( ) Skin cancer ( ) Squamous cell carcinoma ( ) Steroid-resistant nephrotic syndrome ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( ) Amyotrophic lateral sclerosis ( ) Colorectal carcinoma ( ) Intellectual disability ( ) Autosomal dominant non-syndromic intellectual disability ( ) Acute respiratory failure ( ) Cystinosis ( ) Ebola virus infection ( ) Enterovirus infection ( ) Hepatocellular carcinoma ( ) Inflammation ( ) Nasopharyngeal carcinoma ( ) Rheumatic fever ( ) Thyroid cancer ( ) Thyroid gland carcinoma ( ) Thyroid tumor ( )
UniProt ID	RB11A_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1OIV; 1OIW; 1OIX; 1YZK; 2D7C; 2GZD; 2GZH; 2HV8; 4C4P; 4D0L; 4D0M; 4LWZ; 4LX0; 4UJ3; 4UJ4; 4UJ5; 5C46; 5C4G; 5EUQ; 5EZ5; 5FBL; 5FBQ; 5FBR; 5FBV; 5FBW; 5JCZ; 6DJL; 6IXV
EC Number	3.6.5.2
Pfam ID	PF00071
Sequence	MGTRDDEYDYLFKVVLIGDSGVGKSNLLSRFTRNEFNLESKSTIGVEFATRSIQVDGKTI KAQIWDTAGQERYRAITSAYYRGAVGALLVYDIAKHLTYENVERWLKELRDHADSNIVIM LVGNKSDLRHLRAVPTDEARAFAEKNGLSFIETSALDSTNVEAAFQTILTEIYRIVSQKQ MSDRRENDMSPSNNVVPIHVPPTTENKPKVQCCQNI
Function	The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. The small Rab GTPase RAB11A regulates endocytic recycling. Forms a functional Rab11/FIP3/dynein complex that regulates the movement of peripheral sorting endosomes (SE) along microtubule tracks toward the microtubule organizing center/centrosome, generating the endosomal recycling compartment (ERC). Acts as a major regulator of membrane delivery during cytokinesis. Together with MYO5B and RAB8A participates in epithelial cell polarization. Together with RAB3IP, RAB8A, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis. Together with MYO5B participates in CFTR trafficking to the plasma membrane and TF (Transferrin) recycling in nonpolarized cells. Required in a complex with MYO5B and RAB11FIP2 for the transport of NPC1L1 to the plasma membrane. Participates in the sorting and basolateral transport of CDH1 from the Golgi apparatus to the plasma membrane. Regulates the recycling of FCGRT (receptor of Fc region of monomeric Ig G) to basolateral membranes. May also play a role in melanosome transport and release from melanocytes. Promotes Rabin8/RAB3IP preciliary vesicular trafficking to mother centriole by forming a ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, thereby regulating ciliogenesis initiation. On the contrary, upon LPAR1 receptor signaling pathway activation, interaction with phosphorylated WDR44 prevents Rab11-RAB3IP-RAB11FIP3 complex formation and cilia growth. Participates in the export of a subset of neosynthesized proteins through a Rab8-Rab10-Rab11-endososomal dependent export route via interaction with WDR44.
KEGG Pathway	Endocytosis (hsa04144 ) Endocrine and other factor-regulated calcium reabsorption (hsa04961 ) Vasopressin-regulated water reabsorption (hsa04962 ) Pancreatic secretion (hsa04972 ) Influenza A (hsa05164 )
Reactome Pathway	Vasopressin regulates renal water homeostasis via Aquaporins (R-HSA-432040 ) Anchoring of the basal body to the plasma membrane (R-HSA-5620912 ) VxPx cargo-targeting to cilium (R-HSA-5620916 ) TBC/RABGAPs (R-HSA-8854214 ) RAB geranylgeranylation (R-HSA-8873719 ) Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Amyloidosis	DISHTAI2	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[5]
Burkitt lymphoma	DIS9D5XU	Strong	Biomarker	[6]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[7]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[7]
Charcot-Marie-Tooth disease type 4C	DIS0SF7F	Strong	Altered Expression	[8]
Cholestasis	DISDJJWE	Strong	Biomarker	[9]
Colon cancer	DISVC52G	Strong	Biomarker	[10]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[10]
Hereditary hemochromatosis	DISVG5MT	Strong	Genetic Variation	[11]
Huntington disease	DISQPLA4	Strong	Biomarker	[12]
Influenza	DIS3PNU3	Strong	Biomarker	[13]
Intestinal disorder	DISGPMUQ	Strong	Biomarker	[14]
Lysosomal lipid storage disorder	DISXQRTX	Strong	Biomarker	[15]
Malabsorption syndrome	DISGMUVS	Strong	Biomarker	[16]
Microvillus inclusion disease	DIS6L4RW	Strong	Biomarker	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Nephrotic syndrome	DISSPSC2	Strong	Biomarker	[19]
Neurodevelopmental disorder	DIS372XH	Strong	Genetic Variation	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[2]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[21]
Skin cancer	DISTM18U	Strong	Biomarker	[22]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[23]
Steroid-resistant nephrotic syndrome	DISVEBC9	Strong	Biomarker	[19]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[4]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Biomarker	[24]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[25]
Intellectual disability	DISMBNXP	moderate	Biomarker	[26]
Autosomal dominant non-syndromic intellectual disability	DISD6L06	Supportive	Autosomal dominant	[26]
Acute respiratory failure	DIS5KQ5Y	Limited	Biomarker	[27]
Cystinosis	DISXY3VI	Limited	Biomarker	[28]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[29]
Enterovirus infection	DISH2UDP	Limited	Biomarker	[30]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[31]
Inflammation	DISJUQ5T	Limited	Biomarker	[32]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[33]
Rheumatic fever	DISLUF66	Limited	Biomarker	[27]
Thyroid cancer	DIS3VLDH	Limited	Altered Expression	[34]
Thyroid gland carcinoma	DISMNGZ0	Limited	Altered Expression	[34]
Thyroid tumor	DISLVKMD	Limited	Altered Expression	[34]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ras-related protein Rab-11A (RAB11A).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Ras-related protein Rab-11A (RAB11A).	[36]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Ras-related protein Rab-11A (RAB11A).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ras-related protein Rab-11A (RAB11A).	[39]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ras-related protein Rab-11A (RAB11A).	[40]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Ras-related protein Rab-11A (RAB11A).	[41]
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⏷ Show the Full List of 6 Drug(s)

1 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 Ras-related protein Rab-11A (RAB11A).	[38]
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References

1	Allosteric binding sites in Rab11 for potential drug candidates.PLoS One. 2018 Jun 6;13(6):e0198632. doi: 10.1371/journal.pone.0198632. eCollection 2018.
2	Rab11a promotes proliferation and invasion through regulation of YAP in non-small cell lung cancer.Oncotarget. 2017 Apr 25;8(17):27800-27811. doi: 10.18632/oncotarget.15359.
3	A paired RNAi and RabGAP overexpression screen identifies Rab11 as a regulator of -amyloid production.Cell Rep. 2013 Dec 26;5(6):1536-51. doi: 10.1016/j.celrep.2013.12.005.
4	Rab11 Functions as an Oncoprotein via Nuclear Factor kappa B (NF-B) Signaling Pathway in Human Bladder Carcinoma.Med Sci Monit. 2018 Jul 22;24:5093-5101. doi: 10.12659/MSM.911454.
5	The breast cancer antigen 5T4 interacts with Rab11, and is a target and regulator of Rab11 mediated trafficking.Int J Biochem Cell Biol. 2018 Jun;99:28-37. doi: 10.1016/j.biocel.2018.03.002. Epub 2018 Mar 13.
6	Epstein-Barr virus exploits host endocytic machinery for cell-to-cell viral transmission rather than a virological synapse.J Gen Virol. 2016 Nov;97(11):2989-3006. doi: 10.1099/jgv.0.000605. Epub 2016 Sep 19.
7	Hypoxia stimulates invasion and migration of human cervical cancer cell lines HeLa/SiHa through the Rab11 trafficking of integrin v3/FAK/PI3K pathway-mediated Rac1 activation.J Biosci. 2017 Sep;42(3):491-499. doi: 10.1007/s12038-017-9699-0.
8	Exclusive expression of the Rab11 effector SH3TC2 in Schwann cells links integrin-6 and myelin maintenance to Charcot-Marie-Tooth disease type 4C.Biochim Biophys Acta. 2016 Jul;1862(7):1279-90. doi: 10.1016/j.bbadis.2016.04.003. Epub 2016 Apr 9.
9	MYO5B and bile salt export pump contribute to cholestatic liver disorder in microvillous inclusion disease.Hepatology. 2014 Jul;60(1):301-10. doi: 10.1002/hep.26974. Epub 2014 May 27.
10	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.
11	Small GTPases in hedgehog signalling: emerging insights into the disease mechanisms of Rab23-mediated and Arl13b-mediated ciliopathies.Curr Opin Genet Dev. 2019 Jun;56:61-68. doi: 10.1016/j.gde.2019.07.009. Epub 2019 Aug 27.
12	Glucose transporter 3 is a rab11-dependent trafficking cargo and its transport to the cell surface is reduced in neurons of CAG140 Huntington's disease mice.Acta Neuropathol Commun. 2014 Dec 20;2:179. doi: 10.1186/s40478-014-0178-7.
13	Influenza virus genome reaches the plasma membrane via a modified endoplasmic reticulum and Rab11-dependent vesicles.Nat Commun. 2017 Nov 9;8(1):1396. doi: 10.1038/s41467-017-01557-6.
14	Disruption of Rab8a and Rab11a causes formation of basolateral microvilli in neonatal enteropathy.J Cell Sci. 2017 Aug 1;130(15):2491-2505. doi: 10.1242/jcs.201897. Epub 2017 Jun 8.
15	Rab proteins mediate Golgi transport of caveola-internalized glycosphingolipids and correct lipid trafficking in Niemann-Pick C cells.J Clin Invest. 2002 Jun;109(12):1541-50. doi: 10.1172/JCI15420.
16	Myosin Vb and Rab11a regulate phosphorylation of ezrin in enterocytes.J Cell Sci. 2014 Mar 1;127(Pt 5):1007-17. doi: 10.1242/jcs.137273. Epub 2014 Jan 10.
17	Abnormal Rab11-Rab8-vesicles cluster in enterocytes of patients with microvillus inclusion disease.Traffic. 2017 Jul;18(7):453-464. doi: 10.1111/tra.12486. Epub 2017 May 17.
18	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.
19	TBC1D8B Mutations Implicate RAB11-Dependent Vesicular Trafficking in the Pathogenesis of Nephrotic Syndrome.J Am Soc Nephrol. 2019 Dec;30(12):2338-2353. doi: 10.1681/ASN.2019040414. Epub 2019 Nov 15.
20	Bi-allelic mutations in TRAPPC2L result in a neurodevelopmental disorder and have an impact on RAB11 in fibroblasts. J Med Genet. 2018 Nov;55(11):753-764. doi: 10.1136/jmedgenet-2018-105441. Epub 2018 Aug 17.
21	Rab11a sustains GSK3/Wnt/-catenin signaling to enhance cancer progression in pancreatic cancer.Tumour Biol. 2016 Oct;37(10):13821-13829. doi: 10.1007/s13277-016-5172-1. Epub 2016 Aug 1.
22	c-Fos-dependent induction of the small ras-related GTPase Rab11a in skin carcinogenesis.Am J Pathol. 2005 Jul;167(1):243-53. doi: 10.1016/S0002-9440(10)62969-0.
23	Differential gene expression between squamous cell carcinoma of esophageus and its normal epithelium; altered pattern of mal, akr1c2, and rab11a expression.World J Gastroenterol. 2004 Jun 15;10(12):1716-21. doi: 10.3748/wjg.v10.i12.1716.
24	Loss of endosomal recycling factor RAB11 coupled with complex regulation of MAPK/ERK/AKT signaling in postmortem spinal cord specimens of sporadic amyotrophic lateral sclerosis patients.Mol Brain. 2019 Jun 13;12(1):55. doi: 10.1186/s13041-019-0475-y.
25	Recycling Endosomes in Mature Epithelia Restrain Tumorigenic Signaling.Cancer Res. 2019 Aug 15;79(16):4099-4112. doi: 10.1158/0008-5472.CAN-18-4075. Epub 2019 Jun 25.
26	High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies. Am J Hum Genet. 2017 Nov 2;101(5):664-685. doi: 10.1016/j.ajhg.2017.09.008.
27	FIP4/Arfophilin-2 plays overlapping but distinct roles from FIP3/Arfophilin-1 in neuronal migration during cortical layer formation.Eur J Neurosci. 2018 Nov;48(9):3082-3096. doi: 10.1111/ejn.14199. Epub 2018 Nov 2.
28	Cystinosin, the small GTPase Rab11, and the Rab7 effector RILP regulate intracellular trafficking of the chaperone-mediated autophagy receptor LAMP2A.J Biol Chem. 2017 Jun 23;292(25):10328-10346. doi: 10.1074/jbc.M116.764076. Epub 2017 May 2.
29	Budding of Ebola Virus Particles Requires the Rab11-Dependent Endocytic Recycling Pathway.J Infect Dis. 2018 Nov 22;218(suppl_5):S388-S396. doi: 10.1093/infdis/jiy460.
30	Essential domains of phosphatidylinositol-4 kinase III required for enterovirus replication.Microbiol Immunol. 2019 Jul;63(7):285-288. doi: 10.1111/1348-0421.12718. Epub 2019 Jun 27.
31	Role of exosomal competing endogenous RNA in patients with hepatocellular carcinoma.J Cell Biochem. 2018 Nov;119(10):8600-8610. doi: 10.1002/jcb.27109. Epub 2018 Jul 17.
32	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.
33	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.
34	MiR-150 Inhibits Cell Growth In Vitro and In Vivo by Restraining the RAB11A/WNT/-Catenin Pathway in Thyroid Cancer.Med Sci Monit. 2017 Oct 12;23:4885-4894. doi: 10.12659/msm.906997.
35	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.
36	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.
37	Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
38	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.
39	Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
40	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
41	Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.