Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUP99ZD)

• DOT Name: Protein Shroom1 (SHROOM1)
• Synonyms: Apical protein 2
• Gene Name: SHROOM1
• Related Disease:
  Neural tube defect
  Osteoarthritis
• UniProt ID: SHRM1_HUMAN
• Pfam ID: PF08688 ; PF08687
• Sequence:
  MEALGPGGDRASPASSTSSLDLWHLSMRADSAYSSFSAASGGPEPRTQSPGTDLLPYLDW
  DYVRVVWGGPGPAPPDAALCTSPRPRPAVAARSGPQPTEVPGTPGPLNRQATPLLYALAA
  EAEAAAQAAEPPSPPASRAAYRQRLQGAQRRVLRETSFQRKELRMSLPARLRPTVPARPP
  ATHPRSASLSHPGGEGEPARSRAPAPGTAGRGPLANQQRKWCFSEPGKLDRVGRGGGPAR
  ECLGEACSSSGLPGPEPLEFQHPALAKFEDHEVGWLPETQPQGSMNLDSGSLKLGDAFRP
  ASRSRSASGEVLGSWGGSGGTIPIVQAVPQGAETPRPLFQTKLSRFLPQKEAAVMYPAEL
  PQSSPADSEQRVSETCIVPAWLPSLPDEVFLEEAPLVRMRSPPDPHASQGPPASVHASDQ
  PYGTGLGQRTGQVTVPTEYPLHECPGTAGADDCWQGVNGSVGISRPTSHTPTGTANDNIP
  TIDPTGLTTNPPTAAESDLLKPVPADALGLSGNDTPGPSHNTALARGTGQPGSRPTWPSQ
  CLEELVQELARLDPSLCDPLASQPSPEPPLGLLDGLIPLAEVRAAMRPACGEAGEEAAST
  FEPGSYQFSFTQLLPAPREETRLENPATHPVLDQPCGQGLPAPNNSIQGKKVELAARLQK
  MLQDLHTEQERLQGEAQAWARRQAALEAAVRQACAPQELERFSRFMADLERVLGLLLLLG
  SRLARVRRALARAASDSDPDEQASLLQRLRLLQRQEEDAKELKEHVARRERAVREVLVRA
  LPVEELRVYCALLAGKAAVLAQQRNLDERIRLLQDQLDAIRDDLGHHAPSPSPARPPGTC
  PPVQPPFPLLLT
• Function: May be involved in the assembly of microtubule arrays during cell elongation.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neural tube defect	DIS5J95E	Definitive	Genetic Variation	[1]
Osteoarthritis	DIS05URM	Strong	Biomarker	[2]

5 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 Protein Shroom1 (SHROOM1).	[3]
Quercetin	DM3NC4M	Approved	Quercetin affects the phosphorylation of Protein Shroom1 (SHROOM1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Protein Shroom1 (SHROOM1).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein Shroom1 (SHROOM1).	[4]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Protein Shroom1 (SHROOM1).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Protein Shroom1 (SHROOM1).	[5]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Protein Shroom1 (SHROOM1).	[6]

References

• [1] Genetic and functional analysis of SHROOM1-4 in a Chinese neural tube defect cohort.Hum Genet. 2018 Mar;137(3):195-202. doi: 10.1007/s00439-017-1864-x. Epub 2018 Feb 8.
• [2] Identification of differentially methylated regions in new genes associated with knee osteoarthritis.Gene. 2016 Jan 15;576(1 Pt 2):312-8. doi: 10.1016/j.gene.2015.10.037. Epub 2015 Oct 17.
• [3] 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.
• [4] 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.
• [5] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [6] 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.
• [7] 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.