Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKO7AUM)

DOT Name Regulator of microtubule dynamics protein 3 (RMDN3)
Synonyms RMD-3; hRMD-3; Cerebral protein 10; Protein FAM82A2; Protein FAM82C; Protein tyrosine phosphatase-interacting protein 51; TCPTP-interacting protein 51
Gene Name RMDN3
Related Disease
Amyotrophic lateral sclerosis ( )
HER2/NEU overexpressing breast cancer ( )
Rheumatoid arthritis ( )
Advanced cancer ( )
Alzheimer disease ( )
Autism spectrum disorder ( )
Breast neoplasm ( )
Carcinoma ( )
Cardiac failure ( )
Chronic kidney disease ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal neoplasm ( )
Congestive heart failure ( )
Diabetic kidney disease ( )
Endometriosis ( )
Epilepsy ( )
Frontotemporal dementia ( )
Glioma ( )
Hepatocellular carcinoma ( )
Lung adenocarcinoma ( )
Multiple sclerosis ( )
Myocardial infarction ( )
Neoplasm ( )
Nervous system inflammation ( )
Non-small-cell lung cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
Squamous cell carcinoma ( )
Systemic lupus erythematosus ( )
Tauopathy ( )
Breast cancer ( )
Breast carcinoma ( )
Coronary atherosclerosis ( )
Epithelial ovarian cancer ( )
Melanoma ( )
Acute lymphocytic leukaemia ( )
Acute myelogenous leukaemia ( )
Adult glioblastoma ( )
B-cell neoplasm ( )
Glioblastoma multiforme ( )
Hepatitis C virus infection ( )
High blood pressure ( )
Nasopharyngeal carcinoma ( )
Osteoarthritis ( )
Pancreatic cancer ( )
Parkinson disease ( )
Thyroid gland papillary carcinoma ( )
Type-1 diabetes ( )
Type-1/2 diabetes ( )
UniProt ID
RMD3_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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PDB ID
7CC7
Pfam ID
PF21033
Sequence
MSRLGALGGARAGLGLLLGTAAGLGFLCLLYSQRWKRTQRHGRSQSLPNSLDYTQTSDPG
RHVMLLRAVPGGAGDASVLPSLPREGQEKVLDRLDFVLTSLVALRREVEELRSSLRGLAG
EIVGEVRCHMEENQRVARRRRFPFVRERSDSTGSSSVYFTASSGATFTDAESEGGYTTAN
AESDNERDSDKESEDGEDEVSCETVKMGRKDSLDLEEEAASGASSALEAGGSSGLEDVLP
LLQQADELHRGDEQGKREGFQLLLNNKLVYGSRQDFLWRLARAYSDMCELTEEVSEKKSY
ALDGKEEAEAALEKGDESADCHLWYAVLCGQLAEHESIQRRIQSGFSFKEHVDKAIALQP
ENPMAHFLLGRWCYQVSHLSWLEKKTATALLESPLSATVEDALQSFLKAEELQPGFSKAG
RVYISKCYRELGKNSEARWWMKLALELPDVTKEDLAIQKDLEELEVILRD
Function Involved in cellular calcium homeostasis regulation. May participate in differentiation and apoptosis of keratinocytes. Overexpression induces apoptosis.
Tissue Specificity
Present at high level in epidermis and seminiferous epithelium: while basal cells in the epidermis and spermatogonia show no perceptible amount, keratinocytes of suprabasal layers and differentiating first-order spermatocytes up to spermatids exhibit high expression. In skeletal muscle, its presence is restricted to fibers of the fast twitch type. In surface epithelia containing ciliated cells, it is associated with the microtubular structures responsible for ciliary movement. Also present in specific structures of the central nervous system such as neurons of the hippocampal region, ganglion cells of the autonomic nervous system, and axons of the peripheral nervous system (at protein level). Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Amyotrophic lateral sclerosis DISF7HVM Definitive Biomarker [1]
HER2/NEU overexpressing breast cancer DISYKID5 Definitive Altered Expression [2]
Rheumatoid arthritis DISTSB4J Definitive Biomarker [3]
Advanced cancer DISAT1Z9 Strong Altered Expression [4]
Alzheimer disease DISF8S70 Strong Biomarker [5]
Autism spectrum disorder DISXK8NV Strong Biomarker [6]
Breast neoplasm DISNGJLM Strong Altered Expression [7]
Carcinoma DISH9F1N Strong Altered Expression [8]
Cardiac failure DISDC067 Strong Biomarker [9]
Chronic kidney disease DISW82R7 Strong Altered Expression [10]
Colon cancer DISVC52G Strong Altered Expression [11]
Colon carcinoma DISJYKUO Strong Altered Expression [11]
Colorectal neoplasm DISR1UCN Strong Altered Expression [12]
Congestive heart failure DIS32MEA Strong Biomarker [9]
Diabetic kidney disease DISJMWEY Strong Genetic Variation [13]
Endometriosis DISX1AG8 Strong Biomarker [14]
Epilepsy DISBB28L Strong Biomarker [15]
Frontotemporal dementia DISKYHXL Strong Biomarker [16]
Glioma DIS5RPEH Strong Altered Expression [17]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [18]
Lung adenocarcinoma DISD51WR Strong Genetic Variation [19]
Multiple sclerosis DISB2WZI Strong Biomarker [20]
Myocardial infarction DIS655KI Strong Biomarker [21]
Neoplasm DISZKGEW Strong Biomarker [22]
Nervous system inflammation DISB3X5A Strong Biomarker [23]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [24]
Prostate cancer DISF190Y Strong Biomarker [25]
Prostate carcinoma DISMJPLE Strong Altered Expression [26]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [27]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [23]
Tauopathy DISY2IPA Strong Biomarker [28]
Breast cancer DIS7DPX1 moderate Biomarker [2]
Breast carcinoma DIS2UE88 moderate Biomarker [2]
Coronary atherosclerosis DISKNDYU moderate Biomarker [29]
Epithelial ovarian cancer DIS56MH2 moderate Biomarker [30]
Melanoma DIS1RRCY moderate Biomarker [31]
Acute lymphocytic leukaemia DISPX75S Disputed Altered Expression [32]
Acute myelogenous leukaemia DISCSPTN Disputed Altered Expression [32]
Adult glioblastoma DISVP4LU Limited Altered Expression [33]
B-cell neoplasm DISVY326 Limited Altered Expression [34]
Glioblastoma multiforme DISK8246 Limited Altered Expression [33]
Hepatitis C virus infection DISQ0M8R Limited Biomarker [35]
High blood pressure DISY2OHH Limited Biomarker [36]
Nasopharyngeal carcinoma DISAOTQ0 Limited Biomarker [37]
Osteoarthritis DIS05URM Limited Biomarker [38]
Pancreatic cancer DISJC981 Limited Altered Expression [39]
Parkinson disease DISQVHKL Limited Biomarker [23]
Thyroid gland papillary carcinoma DIS48YMM Limited Biomarker [40]
Type-1 diabetes DIS7HLUB Limited Biomarker [41]
Type-1/2 diabetes DISIUHAP Limited Altered Expression [42]
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⏷ Show the Full List of 50 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 Regulator of microtubule dynamics protein 3 (RMDN3). [43]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Regulator of microtubule dynamics protein 3 (RMDN3). [48]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Regulator of microtubule dynamics protein 3 (RMDN3). [44]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Regulator of microtubule dynamics protein 3 (RMDN3). [45]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Regulator of microtubule dynamics protein 3 (RMDN3). [46]
Efavirenz DMC0GSJ Approved Efavirenz increases the expression of Regulator of microtubule dynamics protein 3 (RMDN3). [47]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Regulator of microtubule dynamics protein 3 (RMDN3). [49]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Regulator of microtubule dynamics protein 3 (RMDN3). [50]
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⏷ Show the Full List of 6 Drug(s)

References

1 The VAPB-PTPIP51 endoplasmic reticulum-mitochondria tethering proteins are present in neuronal synapses and regulate synaptic activity.Acta Neuropathol Commun. 2019 Mar 6;7(1):35. doi: 10.1186/s40478-019-0688-4.
2 Crosstalks of the PTPIP51 interactome revealed in Her2 amplified breast cancer cells by the novel small molecule LDC3/Dynarrestin.PLoS One. 2019 May 10;14(5):e0216642. doi: 10.1371/journal.pone.0216642. eCollection 2019.
3 Arsenic Trioxide in Synergy with Vitamin D Rescues the Defective VDR-PPAR- Functional Module of Autophagy in Rheumatoid Arthritis.PPAR Res. 2019 May 7;2019:6403504. doi: 10.1155/2019/6403504. eCollection 2019.
4 The prognostic value of theTau protein serum level in metastatic breast cancer patients and its correlation with brain metastases.BMC Cancer. 2019 Jan 30;19(1):110. doi: 10.1186/s12885-019-5287-z.
5 Effect of site-specific amino acid D-isomerization on -sheet transition and fibril formation profiles of Tau microtubule-binding repeat peptides.Biochem Biophys Res Commun. 2019 Jan 1;508(1):184-190. doi: 10.1016/j.bbrc.2018.11.043. Epub 2018 Nov 22.
6 Role of Microtubule-Associated Protein in Autism Spectrum Disorder.Neurosci Bull. 2018 Dec;34(6):1119-1126. doi: 10.1007/s12264-018-0246-2. Epub 2018 Jun 23.
7 Improving breast cancer sensitivity to paclitaxel by increasing aneuploidy.Proc Natl Acad Sci U S A. 2019 Nov 19;116(47):23691-23697. doi: 10.1073/pnas.1910824116. Epub 2019 Nov 4.
8 The novel protein PTPIP51 is expressed in human keratinocyte carcinomas and their surrounding stroma.J Cell Mol Med. 2008 Oct;12(5B):2083-95. doi: 10.1111/j.1582-4934.2008.00198.x.
9 Ultrastructure and regulation of lateralized connexin43 in the failing heart.Circ Res. 2010 Apr 2;106(6):1153-63. doi: 10.1161/CIRCRESAHA.108.182147. Epub 2010 Feb 18.
10 Hyperphosphatemia induces protective autophagy in endothelial cells through the inhibition of Akt/mTOR signaling.J Vasc Surg. 2015 Jul;62(1):210-221.e2. doi: 10.1016/j.jvs.2014.02.040. Epub 2014 May 3.
11 TPX2 is a novel prognostic marker for the growth and metastasis of colon cancer.J Transl Med. 2013 Dec 17;11:313. doi: 10.1186/1479-5876-11-313.
12 Expression of the microtubule-associated protein MAP9/ASAP and its partners AURKA and PLK1 in colorectal and breast cancers.Dis Markers. 2014;2014:798170. doi: 10.1155/2014/798170. Epub 2014 Apr 30.
13 Evaluation of urinary autophagy transcripts expression in diabetic kidney disease.J Diabetes Complications. 2017 Oct;31(10):1491-1498. doi: 10.1016/j.jdiacomp.2017.06.009. Epub 2017 Jun 27.
14 Expression and significance of autophagy genes LC3, Beclin1 and MMP-2 in endometriosis.Exp Ther Med. 2018 Sep;16(3):1958-1962. doi: 10.3892/etm.2018.6362. Epub 2018 Jun 27.
15 Tau Related Pathways as a Connecting Link between Epilepsy and Alzheimer's Disease.ACS Chem Neurosci. 2019 Oct 16;10(10):4199-4212. doi: 10.1021/acschemneuro.9b00460. Epub 2019 Sep 30.
16 Tau in neurodegenerative disease.Ann Transl Med. 2018 May;6(10):175. doi: 10.21037/atm.2018.04.23.
17 AMPK-dependent autophagy upregulation serves as a survival mechanism in response to Tumor Treating Fields (TTFields).Cell Death Dis. 2018 Oct 19;9(11):1074. doi: 10.1038/s41419-018-1085-9.
18 Suppressor of hepatocellular carcinoma RASSF1A activates autophagy initiation and maturation.Cell Death Differ. 2019 Aug;26(8):1379-1395. doi: 10.1038/s41418-018-0211-7. Epub 2018 Oct 12.
19 The human Bcl-2 family member Bcl-rambo and voltage-dependent anion channels manifest a genetic interaction in Drosophila and cooperatively promote the activation of effector caspases in human cultured cells.Exp Cell Res. 2019 Aug 15;381(2):223-234. doi: 10.1016/j.yexcr.2019.05.015. Epub 2019 May 15.
20 Sex-specific Tau methylation patterns and synaptic transcriptional alterations are associated with neural vulnerability during chronic neuroinflammation.J Autoimmun. 2019 Jul;101:56-69. doi: 10.1016/j.jaut.2019.04.003. Epub 2019 Apr 19.
21 Alterations of autophagic-lysosomal system in the peripheral leukocytes of patients with myocardial infarction.Clin Chim Acta. 2011 Aug 17;412(17-18):1567-71. doi: 10.1016/j.cca.2011.05.002. Epub 2011 May 7.
22 Dual-functionality of RASSF1A overexpression in A375 cells is mediated by activation of IL-6/STAT3 regulatory loop.Mol Biol Rep. 2018 Oct;45(5):1277-1287. doi: 10.1007/s11033-018-4288-3. Epub 2018 Aug 3.
23 Autophagy: a potential key contributor to the therapeutic action of mesenchymal stem cells.Autophagy. 2020 Jan;16(1):28-37. doi: 10.1080/15548627.2019.1630223. Epub 2019 Jun 18.
24 AZD9291 promotes autophagy and inhibits PI3K/Akt pathway in NSCLC cancer cells. J Cell Biochem. 2019 Jan;120(1):756-767. doi: 10.1002/jcb.27434. Epub 2018 Aug 26.
25 A novel role for MAP1 LC3 in nonautophagic cytoplasmic vacuolation death of cancer cells.Oncogene. 2009 Jul 16;28(28):2556-68. doi: 10.1038/onc.2009.118. Epub 2009 May 18.
26 PTPIP51 mRNA and protein expression in tissue microarrays and promoter methylation of benign prostate hyperplasia and prostate carcinoma.Prostate. 2009 Dec 1;69(16):1751-62. doi: 10.1002/pros.21025.
27 Overexpression of the receptor for hyaluronan-mediated motility, correlates with expression of microtubule-associated protein in human oral squamous cell carcinomas.Int J Oncol. 2009 Jun;34(6):1565-71. doi: 10.3892/ijo_00000286.
28 Why Microtubules Should Be Considered as One of the Supplementary Targets for Designing Neurotherapeutics.ACS Chem Neurosci. 2019 Mar 20;10(3):1118-1120. doi: 10.1021/acschemneuro.9b00002. Epub 2019 Jan 18.
29 PTPIP51 regulates mouse cardiac ischemia/reperfusion through mediating the mitochondria-SR junction.Sci Rep. 2017 Mar 27;7:45379. doi: 10.1038/srep45379.
30 Decreased expression of autophagy-related proteins in malignant epithelial ovarian cancer.Autophagy. 2008 Nov;4(8):1067-8. doi: 10.4161/auto.6827. Epub 2008 Nov 20.
31 JWA inhibits melanoma angiogenesis by suppressing ILK signaling and is an independent prognostic biomarker for melanoma.Carcinogenesis. 2013 Dec;34(12):2778-88. doi: 10.1093/carcin/bgt318. Epub 2013 Sep 24.
32 Beclin-1 and hypoxia-inducible factor-1 genes expression: Potential biomarkers in acute leukemia patients.Cancer Biomark. 2016 Mar 18;16(4):619-26. doi: 10.3233/CBM-160603.
33 Sinomenine Hydrochloride Inhibits the Metastasis of Human Glioblastoma Cells by Suppressing the Expression of Matrix Metalloproteinase-2/-9 and Reversing the Endogenous and Exogenous Epithelial-Mesenchymal Transition.Int J Mol Sci. 2018 Mar 14;19(3):844. doi: 10.3390/ijms19030844.
34 Streptozotocin-Induced Autophagy Reduces Intracellular Insulin in Insulinoma INS-1E Cells.DNA Cell Biol. 2018 Mar;37(3):160-167. doi: 10.1089/dna.2017.3874. Epub 2018 Feb 27.
35 Autophagy protects cells from HCV-induced defects in lipid metabolism.Gastroenterology. 2012 Mar;142(3):644-653.e3. doi: 10.1053/j.gastro.2011.11.033. Epub 2011 Dec 7.
36 Pharmacological restoration of autophagy reduces hypertension-related stroke occurrence.Autophagy. 2020 Aug;16(8):1468-1481. doi: 10.1080/15548627.2019.1687215. Epub 2019 Nov 12.
37 Prognostic value of TIGAR and LC3B protein expression in nasopharyngeal carcinoma.Cancer Manag Res. 2018 Nov 12;10:5605-5616. doi: 10.2147/CMAR.S175501. eCollection 2018.
38 Autophagy promotes citrullination of VIM (vimentin) and its interaction with major histocompatibility complex class II in synovial fibroblasts.Autophagy. 2020 May;16(5):946-955. doi: 10.1080/15548627.2019.1664144. Epub 2019 Sep 8.
39 Autophagy Is Required for Activation of Pancreatic Stellate Cells, Associated With Pancreatic Cancer Progression and Promotes Growth of Pancreatic Tumors in Mice.Gastroenterology. 2017 May;152(6):1492-1506.e24. doi: 10.1053/j.gastro.2017.01.010. Epub 2017 Jan 23.
40 Expression of autophagy-associated proteins in papillary thyroid carcinoma.Oncol Lett. 2017 Jul;14(1):411-415. doi: 10.3892/ol.2017.6101. Epub 2017 Apr 28.
41 Recurrent nonsevere hypoglycemia exacerbates imbalance of mitochondrial homeostasis leading to synapse injury and cognitive deficit in diabetes.Am J Physiol Endocrinol Metab. 2018 Nov 1;315(5):E973-E986. doi: 10.1152/ajpendo.00133.2018. Epub 2018 Jul 3.
42 Lycium barbarum polysaccharide protects diabetic peripheral neuropathy by enhancing autophagy via mTOR/p70S6K inhibition in Streptozotocin-induced diabetic rats.J Chem Neuroanat. 2018 Apr;89:37-42. doi: 10.1016/j.jchemneu.2017.12.011. Epub 2017 Dec 30.
43 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.
44 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
45 Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
46 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.
47 Lon protease: a novel mitochondrial matrix protein in the interconnection between drug-induced mitochondrial dysfunction and endoplasmic reticulum stress. Br J Pharmacol. 2017 Dec;174(23):4409-4429. doi: 10.1111/bph.14045. Epub 2017 Nov 7.
48 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.
49 Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
50 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.