Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS2FZ8O)

• DOT Name: TIP41-like protein (TIPRL)
• Synonyms: Putative MAPK-activating protein PM10; Type 2A-interacting protein; TIP
• Gene Name: TIPRL
• Related Disease:
  Acute otitis media
  Adult teratoma
  Breast neoplasm
  Carcinoma of liver and intrahepatic biliary tract
  Cystic fibrosis
  Endometrial carcinoma
  Joubert syndrome
  Liver cancer
  Neoplasm
  Otitis media
  Teratoma
  Advanced cancer
  Hepatocellular carcinoma
  Acute graft versus host disease
  Graft-versus-host disease
• UniProt ID: TIPRL_HUMAN
• PDB ID: 5D9G
• Pfam ID: PF04176
• Sequence:
  MMIHGFQSSHRDFCFGPWKLTASKTHIMKSADVEKLADELHMPSLPEMMFGDNVLRIQHG
  SGFGIEFNATDALRCVNNYQGMLKVACAEEWQESRTEGEHSKEVIKPYDWTYTTDYKGTL
  LGESLKLKVVPTTDHIDTEKLKAREQIKFFEEVLLFEDELHDHGVSSLSVKIRVMPSSFF
  LLLRFFLRIDGVLIRMNDTRLYHEADKTYMLREYTSRESKISSLMHVPPSLFTEPNEISQ
  YLPIKEAVCEKLIFPERIDPNPADSQKSTQVE
• Function: May be a allosteric regulator of serine/threonine-protein phosphatase 2A (PP2A). Isoform 1 inhibits catalytic activity of the PP2A(D) core complex in vitro. The PP2A(C):TIPRL complex does not show phosphatase activity. Acts as a negative regulator of serine/threonine-protein phosphatase 4 probably by inhibiting the formation of the active PPP4C:PPP4R2 complex; the function is proposed to implicate it in DNA damage response by promoting H2AX phosphorylated on Ser-140 (gamma-H2AX). May play a role in the regulation of ATM/ATR signaling pathway controlling DNA replication and repair.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute otitis media	DISL8D8G	Strong	Biomarker	[1]
Adult teratoma	DISBY81U	Strong	Genetic Variation	[2]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[3]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[4]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[5]
Endometrial carcinoma	DISXR5CY	Strong	Posttranslational Modification	[6]
Joubert syndrome	DIS7P5CO	Strong	Biomarker	[7]
Liver cancer	DISDE4BI	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Otitis media	DISGZDUO	Strong	Biomarker	[1]
Teratoma	DIS6ICY4	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[4]
Acute graft versus host disease	DIS8KLVM	Limited	Biomarker	[9]
Graft-versus-host disease	DIS0QADF	Limited	Biomarker	[9]

8 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 TIP41-like protein (TIPRL).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of TIP41-like protein (TIPRL).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of TIP41-like protein (TIPRL).	[12]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of TIP41-like protein (TIPRL).	[13]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of TIP41-like protein (TIPRL).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of TIP41-like protein (TIPRL).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of TIP41-like protein (TIPRL).	[17]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of TIP41-like protein (TIPRL).	[18]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of TIP41-like protein (TIPRL).	[16]

References

• [1] The "TIP algorithm" for the accurate diagnosis of pediatric otitis media.Int J Pediatr Otorhinolaryngol. 2019 Sep;124:185-189. doi: 10.1016/j.ijporl.2019.05.028. Epub 2019 May 27.
• [2] Surgical Management of Patients with Advanced Germ Cell Tumors Following Salvage Chemotherapy: Memorial Sloan Kettering Cancer Center (MSKCC) Experience.Urology. 2019 Feb;124:174-178. doi: 10.1016/j.urology.2018.09.024. Epub 2018 Oct 6.
• [3] #NAME?
• [4] The positive correlation of TIPRL with LC3 and CD133 contributes to cancer aggressiveness: potential biomarkers for early liver cancer.Sci Rep. 2019 Nov 14;9(1):16802. doi: 10.1038/s41598-019-53191-5.
• [5] Economic Evaluation of Tobramycin Inhalation Powder for the Treatment of Chronic Pulmonary Pseudomonas aeruginosa Infection in Patients with Cystic Fibrosis.Clin Drug Investig. 2017 Aug;37(8):795-805. doi: 10.1007/s40261-017-0537-9.
• [6] Recurrent PPP2R1A Mutations in Uterine Cancer Act through a Dominant-Negative Mechanism to Promote Malignant Cell Growth.Cancer Res. 2016 Oct 1;76(19):5719-5731. doi: 10.1158/0008-5472.CAN-15-3342. Epub 2016 Aug 2.
• [7] A CEP104-CSPP1 Complex Is Required for Formation of Primary Cilia Competent in Hedgehog Signaling.Cell Rep. 2019 Aug 13;28(7):1907-1922.e6. doi: 10.1016/j.celrep.2019.07.025.
• [8] TIP: A Web Server for Resolving Tumor Immunophenotype Profiling.Cancer Res. 2018 Dec 1;78(23):6575-6580. doi: 10.1158/0008-5472.CAN-18-0689. Epub 2018 Aug 28.
• [9] TIP, a T-cell factor identified using high-throughput screening increases survival in a graft-versus-host disease model.Nat Biotechnol. 2003 Mar;21(3):302-7. doi: 10.1038/nbt797. Epub 2003 Feb 24.
• [10] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [11] 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.
• [12] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [13] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [14] Gene expression in human hippocampus from cocaine abusers identifies genes which regulate extracellular matrix remodeling. PLoS One. 2007 Nov 14;2(11):e1187. doi: 10.1371/journal.pone.0001187.
• [15] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [16] 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.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [18] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.