Details of Drug Off-Target (DOT)

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

• DOT Name: Tripartite motif-containing protein 72 (TRIM72)
• Synonyms: Mitsugumin-53; Mg53
• Gene Name: TRIM72
• Related Disease:
  Aortic valve disorder
  Heart valve disorder
  Atrial fibrillation
  Cardiac failure
  Chronic kidney disease
  Colorectal carcinoma
  Congestive heart failure
  Duchenne muscular dystrophy
  Hyperinsulinemia
  Metabolic disorder
  Muscular dystrophy
  Myopathy
  Neoplasm
  Non-insulin dependent diabetes
  Pulmonary disease
  Type-1/2 diabetes
  Autosomal recessive limb-girdle muscular dystrophy type 2B
  Limb-girdle muscular dystrophy
  Colon cancer
  Colon carcinoma
  Metastatic malignant neoplasm
• UniProt ID: TRI72_HUMAN
• PDB ID: 3KB5; 7XT2; 7Y4S
• Pfam ID: PF13765 ; PF00622 ; PF00643 ; PF15227
• Sequence:
  MSAAPGLLHQELSCPLCLQLFDAPVTAECGHSFCRACLGRVAGEPAADGTVLCPCCQAPT
  RPQALSTNLQLARLVEGLAQVPQGHCEEHLDPLSIYCEQDRALVCGVCASLGSHRGHRLL
  PAAEAHARLKTQLPQQKLQLQEACMRKEKSVAVLEHQLVEVEETVRQFRGAVGEQLGKMR
  VFLAALEGSLDREAERVRGEAGVALRRELGSLNSYLEQLRQMEKVLEEVADKPQTEFLMK
  YCLVTSRLQKILAESPPPARLDIQLPIISDDFKFQVWRKMFRALMPALEELTFDPSSAHP
  SLVVSSSGRRVECSEQKAPPAGEDPRQFDKAVAVVAHQQLSEGEHYWEVDVGDKPRWALG
  VIAAEAPRRGRLHAVPSQGLWLLGLREGKILEAHVEAKEPRALRSPERRPTRIGLYLSFG
  DGVLSFYDASDADALVPLFAFHERLPRPVYPFFDVCWHDKGKNAQPLLLVGPEGAEA
• Function: Muscle-specific protein that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at injury sites. Specifically binds phosphatidylserine. Acts as a sensor of oxidation: upon membrane damage, entry of extracellular oxidative environment results in disulfide bond formation and homooligomerization at the injury site. This oligomerization acts as a nucleation site for recruitment of TRIM72-containing vesicles to the injury site, leading to membrane patch formation. Probably acts upstream of the Ca(2+)-dependent membrane resealing process. Required for transport of DYSF to sites of cell injury during repair patch formation. Regulates membrane budding and exocytosis. May be involved in the regulation of the mobility of KCNB1-containing endocytic vesicles.
• Reactome Pathway: Smooth Muscle Contraction (R-HSA-445355)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Aortic valve disorder	DISKLYD7	Definitive	Biomarker	[1]
Heart valve disorder	DIS84O7T	Definitive	Biomarker	[1]
Atrial fibrillation	DIS15W6U	Strong	Altered Expression	[2]
Cardiac failure	DISDC067	Strong	Biomarker	[3]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[3]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[6]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[7]
Metabolic disorder	DIS71G5H	Strong	Altered Expression	[7]
Muscular dystrophy	DISJD6P7	Strong	Biomarker	[8]
Myopathy	DISOWG27	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[7]
Pulmonary disease	DIS6060I	Strong	Biomarker	[10]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[7]
Autosomal recessive limb-girdle muscular dystrophy type 2B	DISWWCL7	moderate	Biomarker	[11]
Limb-girdle muscular dystrophy	DISI9Y1Z	moderate	Biomarker	[11]
Colon cancer	DISVC52G	Limited	Altered Expression	[12]
Colon carcinoma	DISJYKUO	Limited	Altered Expression	[5]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Tripartite motif-containing protein 72 (TRIM72).	[13]

References

• [1] MG 53 Protein Protects Aortic Valve Interstitial Cells From Membrane Injury and Fibrocalcific Remodeling.J Am Heart Assoc. 2019 Feb 19;8(4):e009960. doi: 10.1161/JAHA.118.009960.
• [2] Potential role of MG53 in the regulation of transforming-growth-factor-1-induced atrial fibrosis and vulnerability to atrial fibrillation.Exp Cell Res. 2018 Jan 15;362(2):436-443. doi: 10.1016/j.yexcr.2017.12.007. Epub 2017 Dec 9.
• [3] Cardiomyocyte damage control in heart failure and the role of the sarcolemma.J Muscle Res Cell Motil. 2019 Dec;40(3-4):319-333. doi: 10.1007/s10974-019-09539-5. Epub 2019 Sep 13.
• [4] Mitsugumin 53 promotes mitochondrial autophagy through regulating Ambra1 expression in C2C12 myoblast cells.Cell Biol Int. 2019 Mar;43(3):290-298. doi: 10.1002/cbin.11097. Epub 2019 Feb 7.
• [5] TRIM72 Immunohistochemical Expression Can Predict Relapse in Colorectal Carcinoma.Pathol Oncol Res. 2020 Apr;26(2):861-865. doi: 10.1007/s12253-019-00629-w. Epub 2019 Mar 9.
• [6] Lack of MG53 in human heart precludes utility as a biomarker of myocardial injury or endogenous cardioprotective factor.Cardiovasc Res. 2016 May 15;110(2):178-87. doi: 10.1093/cvr/cvw017. Epub 2016 Jan 19.
• [7] Glucose-Sensitive Myokine/Cardiokine MG53 Regulates Systemic Insulin Response and Metabolic Homeostasis.Circulation. 2019 Feb 12;139(7):901-914. doi: 10.1161/CIRCULATIONAHA.118.037216.
• [8] TRIM proteins in therapeutic membrane repair of muscular dystrophy.JAMA Neurol. 2013 Jul;70(7):928-31. doi: 10.1001/jamaneurol.2013.469.
• [9] Dysferlin, annexin A1, and mitsugumin 53 are upregulated in muscular dystrophy and localize to longitudinal tubules of the T-system with stretch.J Neuropathol Exp Neurol. 2011 Apr;70(4):302-13. doi: 10.1097/NEN.0b013e31821350b0.
• [10] Treatment of acute lung injury by targeting MG53-mediated cell membrane repair.Nat Commun. 2014 Jul 18;5:4387. doi: 10.1038/ncomms5387.
• [11] Treatment with Recombinant Human MG53 Protein Increases Membrane Integrity in a Mouse Model of Limb Girdle Muscular Dystrophy 2B.Mol Ther. 2017 Oct 4;25(10):2360-2371. doi: 10.1016/j.ymthe.2017.06.025. Epub 2017 Jul 3.
• [12] Serum Levels of TRIM72 Are Lower among Patients with Colon Cancer: Identification of a Potential Diagnostic Marker.Tohoku J Exp Med. 2018 May;245(1):61-68. doi: 10.1620/tjem.245.61.
• [13] 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.