Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5FV5NS)

• DOT Name: Myosin phosphatase Rho-interacting protein (MPRIP)
• Synonyms: M-RIP; Rho-interacting protein 3; RIP3; p116Rip
• Gene Name: MPRIP
• Related Disease:
  Acute myelogenous leukaemia
  Advanced cancer
  Crohn disease
  Neoplasm
  Acute lymphocytic leukaemia
  Adult glioblastoma
  Alcoholic liver diseases
  Arteriosclerosis
  Atherosclerosis
  Carcinoma of esophagus
  Cardiac failure
  Childhood acute lymphoblastic leukemia
  Colitis
  Colorectal carcinoma
  Congestive heart failure
  Coronary heart disease
  Diabetic kidney disease
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Fatty liver disease
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Inflammatory bowel disease
  Lung cancer
  Lung carcinoma
  Myocardial infarction
  Neoplasm of esophagus
  Non-alcoholic fatty liver disease
  Non-small-cell lung cancer
  Pancreatic cancer
  Parkinson disease
  Subarachnoid hemorrhage
  Toxic epidermal necrolysis
  Ulcerative colitis
  Birt-Hogg-Dube syndrome
  Breast cancer
  Breast carcinoma
  Coronary atherosclerosis
  Familial spontaneous pneumothorax
  Small lymphocytic lymphoma
  Small-cell lung cancer
  Systemic lupus erythematosus
  Hereditary neoplastic syndrome
  Abdominal aortic aneurysm
  Pneumonia
• UniProt ID: MPRIP_HUMAN
• Pfam ID: PF00169
• Sequence:
  MSAAKENPCRKFQANIFNKSKCQNCFKPRESHLLNDEDLTQAKPIYGGWLLLAPDGTDFD
  NPVHRSRKWQRRFFILYEHGLLRYALDEMPTTLPQGTINMNQCTDVVDGEGRTGQKFSLC
  ILTPEKEHFIRAETKEIVSGWLEMLMVYPRTNKQNQKKKRKVEPPTPQEPGPAKVAVTSS
  SSSSSSSSSIPSAEKVPTTKSTLWQEEMRTKDQPDGSSLSPAQSPSQSQPPAASSLREPG
  LESKEEESAMSSDRMDCGRKVRVESGYFSLEKTKQDLKAEEQQLPPPLSPPSPSTPNHRR
  SQVIEKFEALDIEKAEHMETNAVGPSPSSDTRQGRSEKRAFPRKRDFTNEAPPAPLPDAS
  ASPLSPHRRAKSLDRRSTEPSVTPDLLNFKKGWLTKQYEDGQWKKHWFVLADQSLRYYRD
  SVAEEAADLDGEIDLSACYDVTEYPVQRNYGFQIHTKEGEFTLSAMTSGIRRNWIQTIMK
  HVHPTTAPDVTSSLPEEKNKSSCSFETCPRPTEKQEAELGEPDPEQKRSRARERRREGRS
  KTFDWAEFRPIQQALAQERVGGVGPADTHEPLRPEAEPGELERERARRREERRKRFGMLD
  ATDGPGTEDAALRMEVDRSPGLPMSDLKTHNVHVEIEQRWHQVETTPLREEKQVPIAPVH
  LSSEDGGDRLSTHELTSLLEKELEQSQKEASDLLEQNRLLQDQLRVALGREQSAREGYVL
  QATCERGFAAMEETHQKKIEDLQRQHQRELEKLREEKDRLLAEETAATISAIEAMKNAHR
  EEMERELEKSQRSQISSVNSDVEALRRQYLEELQSVQRELEVLSEQYSQKCLENAHLAQA
  LEAERQALRQCQRENQELNAHNQELNNRLAAEITRLRTLLTGDGGGEATGSPLAQGKDAY
  ELEVLLRVKESEIQYLKQEISSLKDELQTALRDKKYASDKYKDIYTELSIAKAKADCDIS
  RLKEQLKAATEALGEKSPDSATVSGYDIMKSKSNPDFLKKDRSCVTRQLRNIRSKSVIEQ
  VSWDT
• Function: Targets myosin phosphatase to the actin cytoskeleton. Required for the regulation of the actin cytoskeleton by RhoA and ROCK1. Depletion leads to an increased number of stress fibers in smooth muscle cells through stabilization of actin fibers by phosphorylated myosin. Overexpression of MRIP as well as its F-actin-binding region leads to disassembly of stress fibers in neuronal cells.
• Reactome Pathway: Signaling by BRAF and RAF1 fusions (R-HSA-6802952)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[2]
Crohn disease	DIS2C5Q8	Definitive	Altered Expression	[3]
Neoplasm	DISZKGEW	Definitive	Biomarker	[2]
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[4]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[5]
Alcoholic liver diseases	DISXEPHQ	Strong	Biomarker	[6]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[7]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[7]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[8]
Cardiac failure	DISDC067	Strong	Genetic Variation	[9]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[4]
Colitis	DISAF7DD	Strong	Biomarker	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[9]
Coronary heart disease	DIS5OIP1	Strong	Altered Expression	[11]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[12]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[8]
Fatty liver disease	DIS485QZ	Strong	Genetic Variation	[13]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[5]
Glioma	DIS5RPEH	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[16]
Lung cancer	DISCM4YA	Strong	Biomarker	[17]
Lung carcinoma	DISTR26C	Strong	Biomarker	[17]
Myocardial infarction	DIS655KI	Strong	Biomarker	[18]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[8]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Genetic Variation	[13]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[19]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[20]
Parkinson disease	DISQVHKL	Strong	Biomarker	[21]
Subarachnoid hemorrhage	DISI7I8Y	Strong	Biomarker	[22]
Toxic epidermal necrolysis	DISIWPFR	Strong	Altered Expression	[23]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[24]
Birt-Hogg-Dube syndrome	DISIN5TD	moderate	CausalMutation	[25]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[26]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[26]
Coronary atherosclerosis	DISKNDYU	moderate	Biomarker	[27]
Familial spontaneous pneumothorax	DISNM7SU	moderate	CausalMutation	[28]
Small lymphocytic lymphoma	DIS30POX	moderate	Altered Expression	[29]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[30]
Systemic lupus erythematosus	DISI1SZ7	moderate	Biomarker	[31]
Hereditary neoplastic syndrome	DISGXLG5	Disputed	CausalMutation	[32]
Abdominal aortic aneurysm	DISD06OF	Limited	Genetic Variation	[33]
Pneumonia	DIS8EF3M	Limited	Biomarker	[34]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Myosin phosphatase Rho-interacting protein (MPRIP) affects the response to substance of Fluorouracil.	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Myosin phosphatase Rho-interacting protein (MPRIP).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Myosin phosphatase Rho-interacting protein (MPRIP).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Myosin phosphatase Rho-interacting protein (MPRIP).	[37]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Myosin phosphatase Rho-interacting protein (MPRIP).	[38]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Myosin phosphatase Rho-interacting protein (MPRIP).	[40]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Myosin phosphatase Rho-interacting protein (MPRIP).	[40]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Myosin phosphatase Rho-interacting protein (MPRIP).	[41]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Myosin phosphatase Rho-interacting protein (MPRIP).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Myosin phosphatase Rho-interacting protein (MPRIP).	[43]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Myosin phosphatase Rho-interacting protein (MPRIP).	[44]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Myosin phosphatase Rho-interacting protein (MPRIP).	[46]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Myosin phosphatase Rho-interacting protein (MPRIP).	[47]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Myosin phosphatase Rho-interacting protein (MPRIP).	[48]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Myosin phosphatase Rho-interacting protein (MPRIP).	[49]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Myosin phosphatase Rho-interacting protein (MPRIP).	[39]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Myosin phosphatase Rho-interacting protein (MPRIP).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Myosin phosphatase Rho-interacting protein (MPRIP).	[45]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Myosin phosphatase Rho-interacting protein (MPRIP).	[39]

References

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• [2] RIP3 promotes colitis-associated colorectal cancer by controlling tumor cell proliferation and CXCL1-induced immune suppression.Theranostics. 2019 Jun 2;9(12):3659-3673. doi: 10.7150/thno.32126. eCollection 2019.
• [3] Caspase-8 regulates TNF--induced epithelial necroptosis and terminal ileitis.Nature. 2011 Sep 14;477(7364):335-9. doi: 10.1038/nature10400.
• [4] A Bak-dependent mitochondrial amplification step contributes to Smac mimetic/glucocorticoid-induced necroptosis.Cell Death Differ. 2017 Jan;24(1):83-97. doi: 10.1038/cdd.2016.102. Epub 2016 Nov 11.
• [5] RIP3 antagonizes a TSC2-mediated pro-survival pathway in glioblastoma cell death.Biochim Biophys Acta Mol Cell Res. 2017 Jan;1864(1):113-124. doi: 10.1016/j.bbamcr.2016.10.014. Epub 2016 Oct 27.
• [6] New advances in molecular mechanisms and emerging therapeutic targets in alcoholic liver diseases.World J Gastroenterol. 2014 Sep 28;20(36):12908-33. doi: 10.3748/wjg.v20.i36.12908.
• [7] Exogenous hydrogen sulfide protects human umbilical vein endothelial cells against high glucoseinduced injury by inhibiting the necroptosis pathway.Int J Mol Med. 2018 Mar;41(3):1477-1486. doi: 10.3892/ijmm.2017.3330. Epub 2017 Dec 19.
• [8] Down-regulation of RIP3 potentiates cisplatin chemoresistance by triggering HSP90-ERK pathway mediated DNA repair in esophageal squamous cell carcinoma.Cancer Lett. 2018 Apr 1;418:97-108. doi: 10.1016/j.canlet.2018.01.022. Epub 2018 Jan 10.
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• [10] RIP3 deficiency exacerbates inflammation in dextran sodium sulfate-induced ulcerative colitis mice model.Cell Biochem Funct. 2017 Apr;35(3):156-163. doi: 10.1002/cbf.3257. Epub 2017 Mar 2.
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