Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6F9T6F)

DOT Name Dihydropyrimidinase-related protein 5 (DPYSL5)
Synonyms DRP-5; CRMP3-associated molecule; CRAM; Collapsin response mediator protein 5; CRMP-5; UNC33-like phosphoprotein 6; ULIP-6
Gene Name DPYSL5
Related Disease
Adult glioblastoma ( )
Alzheimer disease ( )
Autoimmune disease ( )
Blindness ( )
Colorectal carcinoma ( )
Glioblastoma multiforme ( )
Lung neoplasm ( )
Myelitis ( )
Myelopathy ( )
Optic neuritis ( )
Polyneuropathy ( )
Polyradiculoneuropathy ( )
Prostate cancer ( )
Prostate carcinoma ( )
Retinitis ( )
Ritscher-Schinzel syndrome 4 ( )
Uveitis ( )
Choreatic disease ( )
Syndromic intellectual disability ( )
Small-cell lung cancer ( )
Encephalitis ( )
Glaucoma/ocular hypertension ( )
Myasthenia gravis ( )
Neurodevelopmental disorder ( )
Paraneoplastic syndrome ( )
UniProt ID
DPYL5_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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PDB ID
4B90; 4B91; 4B92
Pfam ID
PF01979
Sequence
MLANSASVRILIKGGKVVNDDCTHEADVYIENGIIQQVGRELMIPGGAKVIDATGKLVIP
GGIDTSTHFHQTFMNATCVDDFYHGTKAALVGGTTMIIGHVLPDKETSLVDAYEKCRGLA
DPKVCCDYALHVGITWWAPKVKAEMETLVREKGVNSFQMFMTYKDLYMLRDSELYQVLHA
CKDIGAIARVHAENGELVAEGAKEALDLGITGPEGIEISRPEELEAEATHRVITIANRTH
CPIYLVNVSSISAGDVIAAAKMQGKVVLAETTTAHATLTGLHYYHQDWSHAAAYVTVPPL
RLDTNTSTYLMSLLANDTLNIVASDHRPFTTKQKAMGKEDFTKIPHGVSGVQDRMSVIWE
RGVVGGKMDENRFVAVTSSNAAKLLNLYPRKGRIIPGADADVVVWDPEATKTISASTQVQ
GGDFNLYENMRCHGVPLVTISRGRVVYENGVFMCAEGTGKFCPLRSFPDTVYKKLVQREK
TLKVRGVDRTPYLGDVAVVVHPGKKEMGTPLADTPTRPVTRHGGMRDLHESSFSLSGSQI
DDHVPKRASARILAPPGGRSSGIW
Function Involved in the negative regulation of dendrite outgrowth.
KEGG Pathway
Axon guidance (hsa04360 )
Reactome Pathway
CRMPs in Sema3A signaling (R-HSA-399956 )

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult glioblastoma DISVP4LU Strong Biomarker [1]
Alzheimer disease DISF8S70 Strong Biomarker [2]
Autoimmune disease DISORMTM Strong Biomarker [3]
Blindness DISTIM10 Strong Genetic Variation [4]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [5]
Glioblastoma multiforme DISK8246 Strong Biomarker [1]
Lung neoplasm DISVARNB Strong Biomarker [6]
Myelitis DIS1KV65 Strong Biomarker [7]
Myelopathy DISXV8FG Strong Biomarker [8]
Optic neuritis DISDYCHC Strong Biomarker [9]
Polyneuropathy DISB9G3W Strong Biomarker [10]
Polyradiculoneuropathy DIS1KDVQ Strong Biomarker [11]
Prostate cancer DISF190Y Strong Altered Expression [12]
Prostate carcinoma DISMJPLE Strong Altered Expression [12]
Retinitis DISRWZEG Strong Biomarker [9]
Ritscher-Schinzel syndrome 4 DIS2TPN4 Strong Autosomal dominant [13]
Uveitis DISV0RYS Strong Genetic Variation [3]
Choreatic disease DISH8K3M moderate Genetic Variation [14]
Syndromic intellectual disability DISH7SDF Supportive Autosomal dominant [15]
Small-cell lung cancer DISK3LZD Disputed Genetic Variation [7]
Encephalitis DISLD1RL Limited Genetic Variation [7]
Glaucoma/ocular hypertension DISLBXBY Limited Biomarker [16]
Myasthenia gravis DISELRCI Limited Biomarker [17]
Neurodevelopmental disorder DIS372XH Limited Altered Expression [18]
Paraneoplastic syndrome DISJUN66 Limited Biomarker [17]
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⏷ Show the Full List of 25 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 decreases the methylation of Dihydropyrimidinase-related protein 5 (DPYSL5). [19]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Dihydropyrimidinase-related protein 5 (DPYSL5). [23]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Dihydropyrimidinase-related protein 5 (DPYSL5). [20]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Dihydropyrimidinase-related protein 5 (DPYSL5). [21]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Dihydropyrimidinase-related protein 5 (DPYSL5). [22]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Dihydropyrimidinase-related protein 5 (DPYSL5). [24]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Dihydropyrimidinase-related protein 5 (DPYSL5). [25]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of Dihydropyrimidinase-related protein 5 (DPYSL5). [26]
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⏷ Show the Full List of 6 Drug(s)

References

1 CRMP5 Controls Glioblastoma Cell Proliferation and Survival through Notch-Dependent Signaling.Cancer Res. 2015 Sep 1;75(17):3519-28. doi: 10.1158/0008-5472.CAN-14-0631. Epub 2015 Jun 29.
2 Collapsin response mediator protein 5 (CRMP5) causes social deficits and accelerates memory loss in an animal model of Alzheimer's disease.Neuropharmacology. 2019 Oct;157:107673. doi: 10.1016/j.neuropharm.2019.107673. Epub 2019 Jun 21.
3 Collapsin Response-Mediator Protein 5-Associated Retinitis, Vitritis, and Optic Disc Edema.Ophthalmology. 2020 Feb;127(2):221-229. doi: 10.1016/j.ophtha.2019.09.012. Epub 2019 Sep 20.
4 Paraneoplastic Optic Neuropathy Associated With Purkinje Cell Antibody-2 in a Patient With Small Cell Lung Cancer.J Neuroophthalmol. 2017 Mar;37(1):53-55. doi: 10.1097/WNO.0000000000000458.
5 CRMP5-associated GTPase (CRAG) Is a Candidate Driver Gene for Colorectal Cancer Carcinogenesis.Anticancer Res. 2019 Jan;39(1):99-106. doi: 10.21873/anticanres.13084.
6 High-titer collapsin response-mediating protein-associated (CRMP-5) paraneoplastic optic neuropathy and Vitritis as the only clinical manifestations in a patient with small cell lung carcinoma.J Neuroophthalmol. 2008 Mar;28(1):17-22. doi: 10.1097/WNO.0b013e3181675479.
7 Inflammatory flaccid myelitis in a patient with both anti-CRMP-5 IgG and CNS HIV escape.BMJ Case Rep. 2019 May 21;12(5):e228378. doi: 10.1136/bcr-2018-228378.
8 Autoimmune myelopathy associated with collapsin response-mediator protein-5 immunoglobulin G.Ann Neurol. 2008 Apr;63(4):531-4. doi: 10.1002/ana.21324.
9 Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG.Ann Neurol. 2003 Jul;54(1):38-50. doi: 10.1002/ana.10587.
10 Amphiphysin-IgG autoimmune neuropathy: A recognizable clinicopathologic syndrome.Neurology. 2019 Nov 12;93(20):e1873-e1880. doi: 10.1212/WNL.0000000000008472. Epub 2019 Oct 17.
11 Autoimmune CRMP5 neuropathy phenotype and outcome defined from 105 cases.Neurology. 2018 Jan 9;90(2):e103-e110. doi: 10.1212/WNL.0000000000004803. Epub 2017 Dec 8.
12 miR-214-5p inhibits human prostate cancer proliferation and migration through regulating CRMP5.Cancer Biomark. 2019;26(2):193-202. doi: 10.3233/CBM-190128.
13 Prevalence and architecture of de novo mutations in developmental disorders. Nature. 2017 Feb 23;542(7642):433-438. doi: 10.1038/nature21062. Epub 2017 Jan 25.
14 Paraneoplastic autoimmune movement disorders.Parkinsonism Relat Disord. 2017 Nov;44:106-109. doi: 10.1016/j.parkreldis.2017.08.017. Epub 2017 Oct 13.
15 Missense variants in DPYSL5 cause a neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities. Am J Hum Genet. 2021 May 6;108(5):951-961. doi: 10.1016/j.ajhg.2021.04.004. Epub 2021 Apr 23.
16 Neuroprotective and neuroregenerative effects of CRMP-5 on retinal ganglion cells in an experimental in vivo and in vitro model of glaucoma.PLoS One. 2019 Jan 23;14(1):e0207190. doi: 10.1371/journal.pone.0207190. eCollection 2019.
17 CRMP5 antibodies found in a patient with limbic encephalitis and myasthenia gravis.J Neurol Neurosurg Psychiatry. 2009 Feb;80(2):241-2. doi: 10.1136/jnnp.2008.149336.
18 Pharmacological and proteomic analyses of neonatal polyI:C-treated adult mice.Neurosci Res. 2019 Oct;147:39-47. doi: 10.1016/j.neures.2018.10.007. Epub 2018 Oct 26.
19 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.
20 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
21 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.
22 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
23 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
24 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.
25 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.
26 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.