Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAY2IP6)

• DOT Name: Serine/arginine repetitive matrix protein 1 (SRRM1)
• Synonyms: SR-related nuclear matrix protein of 160 kDa; SRm160; Ser/Arg-related nuclear matrix protein
• Gene Name: SRRM1
• Related Disease: Alopecia
• UniProt ID: SRRM1_HUMAN
• PDB ID: 1MP1; 6FF4; 6FF7; 7ABG; 7ABH; 7ABI; 7DVQ
• Pfam ID: PF01480
• Sequence:
  MDAGFFRGTSAEQDNRFSNKQKKLLKQLKFAECLEKKVDMSKVNLEVIKPWITKRVTEIL
  GFEDDVVIEFIFNQLEVKNPDSKMMQINLTGFLNGKNAREFMGELWPLLLSAQENIAGIP
  SAFLELKKEEIKQRQIEQEKLASMKKQDEDKDKRDKEEKESSREKRERSRSPRRRKSRSP
  SPRRRSSPVRRERKRSHSRSPRHRTKSRSPSPAPEKKEKTPELPEPSVKVKEPSVQEATS
  TSDILKVPKPEPIPEPKEPSPEKNSKKEKEKEKTRPRSRSRSKSRSRTRSRSPSHTRPRR
  RHRSRSRSYSPRRRPSPRRRPSPRRRTPPRRMPPPPRHRRSRSPVRRRRRSSASLSGSSS
  SSSSSRSRSPPKKPPKRTSSPPRKTRRLSPSASPPRRRHRPSPPATPPPKTRHSPTPQQS
  NRTRKSRVSVSPGRTSGKVTKHKGTEKRESPSPAPKPRKVELSESEEDKGGKMAAADSVQ
  QRRQYRRQNQQSSSDSGSSSSSEDERPKRSHVKNGEVGRRRRHSPSRSASPSPRKRQKET
  SPRGRRRRSPSPPPTRRRRSPSPAPPPRRRRTPTPPPRRRTPSPPPRRRSPSPRRYSPPI
  QRRYSPSPPPKRRTASPPPPPKRRASPSPPPKRRVSHSPPPKQRSSPVTKRRSPSLSSKH
  RKGSSPSRSTREARSPQPNKRHSPSPRPRAPQTSSSPPPVRRGASSSPQRRQSPSPSTRP
  IRRVSRTPEPKKIKKAASPSPQSVRRVSSSRSVSGSPEPAAKKPPAPPSPVQSQSPSTNW
  SPAVPVKKAKSPTPSPSPPRNSDQEGGGKKKKKKKDKKHKKDKKHKKHKKHKKEKAVAAA
  AAAAVTPAAIAAATTTLAQEEPVAAPEPKKETESEAEDNLDDLEKHLREKALRSMRKAQV
  SPQS
• Function: Part of pre- and post-splicing multiprotein mRNP complexes. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Involved in numerous pre-mRNA processing events. Promotes constitutive and exonic splicing enhancer (ESE)-dependent splicing activation by bridging together sequence-specific (SR family proteins, SFRS4, SFRS5 and TRA2B/SFRS10) and basal snRNP (SNRP70 and SNRPA1) factors of the spliceosome. Stimulates mRNA 3'-end cleavage independently of the formation of an exon junction complex. Binds both pre-mRNA and spliced mRNA 20-25 nt upstream of exon-exon junctions. Binds RNA and DNA with low sequence specificity and has similar preference for either double- or single-stranded nucleic acid substrates.
• KEGG Pathway:
  Nucleocytoplasmic transport (hsa03013)
  mR. surveillance pathway (hsa03015)
• Reactome Pathway:
  mRNA Splicing - Major Pathway (R-HSA-72163)
  mRNA 3'-end processing (R-HSA-72187)
  RNA Polymerase II Transcription Termination (R-HSA-73856)
  RHOBTB2 GTPase cycle (R-HSA-9013418)
  RHOBTB1 GTPase cycle (R-HSA-9013422)
  Transport of Mature mRNA derived from an Intron-Containing Transcript (R-HSA-159236)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alopecia	DIS37HU4	Limited	Genetic Variation	[1]

7 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 Serine/arginine repetitive matrix protein 1 (SRRM1).	[2]
Quercetin	DM3NC4M	Approved	Quercetin affects the phosphorylation of Serine/arginine repetitive matrix protein 1 (SRRM1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Serine/arginine repetitive matrix protein 1 (SRRM1).	[12]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Serine/arginine repetitive matrix protein 1 (SRRM1).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Serine/arginine repetitive matrix protein 1 (SRRM1).	[7]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Serine/arginine repetitive matrix protein 1 (SRRM1).	[7]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Serine/arginine repetitive matrix protein 1 (SRRM1).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Serine/arginine repetitive matrix protein 1 (SRRM1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Serine/arginine repetitive matrix protein 1 (SRRM1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Serine/arginine repetitive matrix protein 1 (SRRM1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine/arginine repetitive matrix protein 1 (SRRM1).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Serine/arginine repetitive matrix protein 1 (SRRM1).	[8]
Marinol	DM70IK5	Approved	Marinol increases the expression of Serine/arginine repetitive matrix protein 1 (SRRM1).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Serine/arginine repetitive matrix protein 1 (SRRM1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Serine/arginine repetitive matrix protein 1 (SRRM1).	[14]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Serine/arginine repetitive matrix protein 1 (SRRM1).	[15]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Serine/arginine repetitive matrix protein 1 (SRRM1).	[11]

References

• [1] Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [10] Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery. Mol Cancer. 2006 May 18;5:20. doi: 10.1186/1476-4598-5-20.
• [11] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [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] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [14] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [15] 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.
• [16] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.