Details of Drug Off-Target (DOT)

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

DOT Name Serine/arginine repetitive matrix protein 4 (SRRM4)
Synonyms Medulloblastoma antigen MU-MB-2.76; Neural-specific serine/arginine repetitive splicing factor of 100 kDa; Neural-specific SR-related protein of 100 kDa; nSR100
Gene Name SRRM4
Related Disease
Adenocarcinoma ( )
Autism ( )
Autism spectrum disorder ( )
Castration-resistant prostate carcinoma ( )
Hearing disorder ( )
Lung cancer ( )
Lung carcinoma ( )
Major depressive disorder ( )
Pervasive developmental disorder ( )
Prostate adenocarcinoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
Small-cell lung cancer ( )
Neoplasm ( )
UniProt ID
SRRM4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF15230
Sequence
MASVQQGEKQLFEKFWRGTFKAVATPRPESIIVASITARKPLPRTEPQNNPVVPAQDGPS
EKLGQHLATEPLGTNSWERDKTCRELGATRGHSASHDKDLTPPPSSRGKKKKKKSTRKKR
RRSSSYSPSPVKKKKKKSSKKHKRRRSFSKKRRHSSSSPKSKRRDEKRHKKQSRSRPRKS
HRHRHHRCPSRSQSSESRPSSCESRHRGRSPEEGQKSRRRHSRRCSKTLCKDSPEAQSSR
PPSQPLQMLGYLSARGVITGSGSAADLFTKTASPLTTSRGRSQEYDSGNDTSSPPSTQTS
SARSRGQEKGSPSGGLSKSRELNSGNTSDSGNSFTTSSPQNKGAMLENLSPTSRGRESRG
FQSPCLECAEVKKSSLVPSTARSSPMKGCSRSSSYASTRSSSHSSRSPNPRASPRYTQSR
STSSEKRSYSRSPSYSSKSGKRSPPSRSSRSRRSPSYSRYSPSRERDPKYSEKDSQQRER
ERARRRRRSYSPMRKRRRDSPSHLEARRITSARKRPIPYYRPSPSSSGSLSSTSSWYSSS
SSRSASRSYSRSRSRSRSRRRSRTRTSSSSSSRSPSPGSRSRSRSRSRSRSRSRSQSRSY
SSADSYSSTRR
Function
Splicing factor specifically required for neural cell differentiation. Acts in conjunction with nPTB/PTBP2 by binding directly to its regulated target transcripts and promotes neural-specific exon inclusion in many genes that function in neural cell differentiation. Required to promote the inclusion of neural-specific exon 10 in nPTB/PTBP2, leading to increased expression of neural-specific nPTB/PTBP2. Also promotes the inclusion of exon 16 in DAAM1 in neuron extracts. Promotes alternative splicing of REST transcripts to produce REST isoform 3 (REST4) with greatly reduced repressive activity, thereby activating expression of REST targets in neural cells. Plays an important role during embryonic development as well as in the proper functioning of the adult nervous system. Regulates alternative splicing events in genes with important neuronal functions.
Tissue Specificity Specifically expressed in neuronal cells (at protein level). Expressed in the cerebellum.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adenocarcinoma DIS3IHTY Strong Biomarker [1]
Autism DISV4V1Z Strong Altered Expression [2]
Autism spectrum disorder DISXK8NV Strong Altered Expression [3]
Castration-resistant prostate carcinoma DISVGAE6 Strong Biomarker [4]
Hearing disorder DIS4UTK4 Strong Biomarker [5]
Lung cancer DISCM4YA Strong Biomarker [6]
Lung carcinoma DISTR26C Strong Biomarker [6]
Major depressive disorder DIS4CL3X Strong Altered Expression [7]
Pervasive developmental disorder DIS51975 Strong Altered Expression [3]
Prostate adenocarcinoma DISBZYU8 Strong Biomarker [1]
Prostate cancer DISF190Y Strong Altered Expression [8]
Prostate carcinoma DISMJPLE Strong Altered Expression [8]
Prostate neoplasm DISHDKGQ Strong Altered Expression [8]
Small-cell lung cancer DISK3LZD Strong Biomarker [6]
Neoplasm DISZKGEW Limited Altered Expression [8]
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⏷ Show the Full List of 15 Disease(s)
Molecular Interaction Atlas (MIA) 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
Valproate DMCFE9I Approved Valproate increases the expression of Serine/arginine repetitive matrix protein 4 (SRRM4). [9]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Serine/arginine repetitive matrix protein 4 (SRRM4). [10]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Serine/arginine repetitive matrix protein 4 (SRRM4). [11]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Serine/arginine repetitive matrix protein 4 (SRRM4). [11]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Serine/arginine repetitive matrix protein 4 (SRRM4). [13]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Serine/arginine repetitive matrix protein 4 (SRRM4). [9]
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⏷ Show the Full List of 6 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Serine/arginine repetitive matrix protein 4 (SRRM4). [12]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Serine/arginine repetitive matrix protein 4 (SRRM4). [14]
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References

1 SRRM4 Drives Neuroendocrine Transdifferentiation of Prostate Adenocarcinoma Under Androgen Receptor Pathway Inhibition.Eur Urol. 2017 Jan;71(1):68-78. doi: 10.1016/j.eururo.2016.04.028. Epub 2016 May 11.
2 Misregulation of an Activity-Dependent Splicing Network as a Common Mechanism Underlying Autism Spectrum Disorders.Mol Cell. 2016 Dec 15;64(6):1023-1034. doi: 10.1016/j.molcel.2016.11.033.
3 A highly conserved program of neuronal microexons is misregulated in autistic brains.Cell. 2014 Dec 18;159(7):1511-23. doi: 10.1016/j.cell.2014.11.035.
4 Alternative RNA splicing of the GIT1 gene is associated with neuroendocrine prostate cancer.Cancer Sci. 2019 Jan;110(1):245-255. doi: 10.1111/cas.13869. Epub 2018 Dec 12.
5 Stereotypic circling behavior in mice with vestibular dysfunction: asymmetrical effects of intrastriatal microinjection of a dopamine agonist.Int J Neurosci. 2007 Jul;117(7):1049-64. doi: 10.1080/00207450600936874.
6 A gapmer antisense oligonucleotide targeting SRRM4 is a novel therapeutic medicine for lung cancer.Sci Rep. 2019 May 20;9(1):7618. doi: 10.1038/s41598-019-43100-1.
7 A Novel Alternative Splicing Mechanism That Enhances Human 5-HT1A Receptor RNA Stability Is Altered in Major Depression.J Neurosci. 2018 Sep 19;38(38):8200-8210. doi: 10.1523/JNEUROSCI.0902-18.2018. Epub 2018 Aug 7.
8 SRRM4 gene expression correlates with neuroendocrine prostate cancer.Prostate. 2019 Jan;79(1):96-104. doi: 10.1002/pros.23715. Epub 2018 Aug 28.
9 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.
10 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
11 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
12 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.
13 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.
14 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.