Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH2TFYH)

• DOT Name: Rab effector MyRIP (MYRIP)
• Synonyms: Exophilin-8; Myosin-VIIa- and Rab-interacting protein; Synaptotagmin-like protein lacking C2 domains C; SlaC2-c; Slp homolog lacking C2 domains c
• Gene Name: MYRIP
• Related Disease:
  Age-related macular degeneration
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Pancreatic cancer
• UniProt ID: MYRIP_HUMAN
• Pfam ID: PF02318 ; PF04698
• Sequence:
  MGRKLDLSGLTDDETEHVLQVVQRDFNLRKKEEERLSELKQKLDEEGSKCSILSKHQQFV
  EHCCMRCCSPFTFLVNTKRQCGDCKFNVCKSCCSYQKHEKAWVCCVCQQARLLRAQSLEW
  FYNNVKSRFKRFGSAKVLKNLYRKHRLESGACFDILGGSLFESNLENEGSISGSDSTFYR
  QSEGHSVMDTLAVALRVAEEAIEEAISKAEAYGDSLDKQNEASYLRDHKEELTEELATTI
  LQKIIRKQKSKSEQQVEEEPGWPHPQSCSTKVADEGTSASPGGYRAPAALWRSQSAFSIT
  GEEALKTPPVEAPSRQPRDQGQHPRAESALPSWKSVDRLDETNLAPVLQSPDGNWVALKD
  GAPPPTRLLAKPKSGTFQALEVASSVASAYDEMGSDSEEDFDWSEALSKLCPRSRALPRN
  PQPQPTQAQSSDQGPIAASPSSALSPNPEAMCSDSETSSAGSSREVGHQARLSWLQRKAP
  RNPAAEKMRLHGELDVNFNPQLASRETSDSSEPEEAPHTTDRRARRWRRARLGSEEPSKE
  PSSPSAQLRDLDTHQVSDDLSETDISNEARDPQTLTDTTEEKRRNRLYELAMKMSEKETS
  SGEDQESEPKTESENQKESLSSEDNSQSVQEELKKKFSAVSLCNISTEVLKVINATEELI
  AGSTGPWESPQVPPDRQKGMFPRGTDQVRLDEQLTSLEENVYLAAGTVYGLETQLTELED
  AARCIHSGTDETHLADLEDQVATAAAQVHHAELQISDIESRISALTIAGLNIAPCVRFTR
  RRDQKQRTQVQTIDTSRQQRRKLPAPPVKAEKIETSSVTTIKTFNHNFILQGSSTNRTKE
  RKGTTKDLMEPALESAVMY
• Function: Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor proteins MYO5A and MYO7A. May link RAB27A-containing vesicles to actin filaments. Functions as a protein kinase A-anchoring protein (AKAP). May act as a scaffolding protein that links PKA to components of the exocytosis machinery, thus facilitating exocytosis, including insulin release.
• Tissue Specificity: Detected in brain, skin, heart, adrenal medulla, pancreas, intestine, liver, kidney, muscle and testis.
• Reactome Pathway: Insulin processing (R-HSA-264876)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Pancreatic cancer	DISJC981	moderate	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Rab effector MyRIP (MYRIP).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Rab effector MyRIP (MYRIP).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Rab effector MyRIP (MYRIP).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Rab effector MyRIP (MYRIP).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Rab effector MyRIP (MYRIP).	[12]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Rab effector MyRIP (MYRIP).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Rab effector MyRIP (MYRIP).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Rab effector MyRIP (MYRIP).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Rab effector MyRIP (MYRIP).	[11]

References

• [1] Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration.Genes Immun. 2010 Dec;11(8):609-21. doi: 10.1038/gene.2010.39. Epub 2010 Sep 23.
• [2] Circadian pathway genes in relation to glioma risk and outcome.Cancer Causes Control. 2014 Jan;25(1):25-32. doi: 10.1007/s10552-013-0305-y. Epub 2013 Oct 18.
• [3] Genes associated with recurrence of hepatocellular carcinoma: integrated analysis by gene expression and methylation profiling.J Korean Med Sci. 2011 Nov;26(11):1428-38. doi: 10.3346/jkms.2011.26.11.1428. Epub 2011 Oct 27.
• [4] Integrated microRNA-mRNA analysis of pancreatic ductal adenocarcinoma.Genet Mol Res. 2015 Aug 28;14(3):10288-97. doi: 10.4238/2015.August.28.14.
• [5] 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.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] 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.
• [9] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [10] 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.
• [11] 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.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [13] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.