Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWN6N7T)

• DOT Name: Protein phosphatase 1 regulatory subunit 21 (PPP1R21)
• Synonyms: Coiled-coil domain-containing protein 128; KLRAQ motif-containing protein 1
• Gene Name: PPP1R21
• Related Disease:
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities
• UniProt ID: PPR21_HUMAN
• PDB ID: 7ND2
• Pfam ID: PF10205 ; PF21636 ; PF10212
• Sequence:
  MASAELQGKYQKLAQEYSKLRAQNQVLKKGVVDEQANSAALKEQLKMKDQSLRKLQQEMD
  SLTFRNLQLAKRVELLQDELALSEPRGKKNKKSGESSSQLSQEQKSVFDEDLQKKIEENE
  RLHIQFFEADEQHKHVEAELRSRLATLETEAAQHQAVVDGLTRKYMETIEKLQNDKAKLE
  VKSQTLEKEAKECRLRTEECQLQLKTLHEDLSGRLEESLSIINEKVPFNDTKYSQYNALN
  VPLHNRRHQLKMRDIAGQALAFVQDLVTALLNFHTYTEQRIQIFPVDSAIDTISPLNQKF
  SQYLHENASYVRPLEEGMLHLFESITEDTVTVLETTVKLKTFSEHLTSYICFLRKILPYQ
  LKSLEEECESSLCTSALRARNLELSQDMKKMTAVFEKLQTYIALLALPSTEPDGLLRTNY
  SSVLTNVGAALHGFHDVMKDISKHYSQKAAIEHELPTATQKLITTNDCILSSVVALTNGA
  GKIASFFSNNLDYFIASLSYGPKAASGFISPLSAECMLQYKKKAAAYMKSLRKPLLESVP
  YEEALANRRILLSSTESREGLAQQVQQSLEKISKLEQEKEHWMLEAQLAKIKLEKENQRI
  ADKLKNTGSAQLVGLAQENAAVSNTAGQDEATAKAVLEPIQSTSLIGTLTRTSDSEVPDV
  ESREDLIKNHYMARIVELTSQLQLADSKSVHFYAECRALSKRLALAEKSKEALTEEMKLA
  SQNISRLQDELTTTKRSYEDQLSMMSDHLCSMNETLSKQREEIDTLKMSSKGNSKKNKSR
• Function: Putative regulator of protein phosphatase 1 (PP1) activity. May play a role in the endosomal sorting process or in endosome maturation pathway.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Genetic Variation	[1]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[1]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[1]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[1]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[1]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[1]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[1]
Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities	DISZFOAR	Strong	Autosomal recessive	[2]

3 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 phosphatase 1 regulatory subunit 21 (PPP1R21).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein phosphatase 1 regulatory subunit 21 (PPP1R21).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein phosphatase 1 regulatory subunit 21 (PPP1R21).	[9]

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 Protein phosphatase 1 regulatory subunit 21 (PPP1R21).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein phosphatase 1 regulatory subunit 21 (PPP1R21).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein phosphatase 1 regulatory subunit 21 (PPP1R21).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein phosphatase 1 regulatory subunit 21 (PPP1R21).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein phosphatase 1 regulatory subunit 21 (PPP1R21).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Protein phosphatase 1 regulatory subunit 21 (PPP1R21).	[11]

References

• [1] Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.Gastroenterology. 2019 Apr;156(5):1455-1466. doi: 10.1053/j.gastro.2018.11.066. Epub 2018 Dec 6.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] 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.
• [10] Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S. Toxicol In Vitro. 2015 Aug;29(5):1060-9.
• [11] 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.