Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA2ENZQ)

• DOT Name: 55 kDa erythrocyte membrane protein (MPP1)
• Synonyms: p55; Membrane protein, palmitoylated 1
• Gene Name: MPP1
• Related Disease:
  Acute myelogenous leukaemia
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Acute lymphocytic leukaemia
  Adenocarcinoma
  Adult glioblastoma
  Adult respiratory distress syndrome
  Ankylosing spondylitis
  Beta-thalassemia intermedia
  Bone osteosarcoma
  Classic Hodgkin lymphoma
  Glioblastoma multiforme
  Hereditary spherocytosis
  Lung cancer
  Lung neoplasm
  Mixed connective tissue disease
  Monocytic leukemia
  Multiple sclerosis
  Osteoarthritis
  Osteosarcoma
  Rheumatoid arthritis
  Sarcoidosis
  Subacute cutaneous lupus erythematosus
  Systemic lupus erythematosus
  T-cell leukaemia
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Type-1 diabetes
  Pneumonia
  Arthritis
  Neoplasm
  Pneumocystis pneumonia
• UniProt ID: EM55_HUMAN
• PDB ID: 2EJY; 2EV8; 3NEY
• Pfam ID: PF00625 ; PF00595 ; PF00018
• Sequence:
  MTLKASEGESGGSMHTALSDLYLEHLLQKRSRPEAVSHPLNTVTEDMYTNGSPAPGSPAQ
  VKGQEVRKVRLIQFEKVTEEPMGITLKLNEKQSCTVARILHGGMIHRQGSLHVGDEILEI
  NGTNVTNHSVDQLQKAMKETKGMISLKVIPNQQSRLPALQMFMRAQFDYDPKKDNLIPCK
  EAGLKFATGDIIQIINKDDSNWWQGRVEGSSKESAGLIPSPELQEWRVASMAQSAPSEAP
  SCSPFGKKKKYKDKYLAKHSSIFDQLDVVSYEEVVRLPAFKRKTLVLIGASGVGRSHIKN
  ALLSQNPEKFVYPVPYTTRPPRKSEEDGKEYHFISTEEMTRNISANEFLEFGSYQGNMFG
  TKFETVHQIHKQNKIAILDIEPQTLKIVRTAELSPFIVFIAPTDQGTQTEALQQLQKDSE
  AIRSQYAHYFDLSLVNNGVDETLKKLQEAFDQACSSPQWVPVSWVY
• Function: Essential regulator of neutrophil polarity. Regulates neutrophil polarization by regulating AKT1 phosphorylation through a mechanism that is independent of PIK3CG activity.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway: Sensory processing of sound by outer hair cells of the cochlea (R-HSA-9662361)

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Genetic Variation	[1]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Definitive	Biomarker	[2]
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[3]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[4]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[5]
Adult respiratory distress syndrome	DISIJV47	Strong	Biomarker	[6]
Ankylosing spondylitis	DISRC6IR	Strong	Genetic Variation	[7]
Beta-thalassemia intermedia	DISYQ0NL	Strong	Biomarker	[8]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[9]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[10]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[5]
Hereditary spherocytosis	DISQYJP5	Strong	Biomarker	[8]
Lung cancer	DISCM4YA	Strong	Biomarker	[4]
Lung neoplasm	DISVARNB	Strong	Biomarker	[4]
Mixed connective tissue disease	DISXX0H8	Strong	Biomarker	[11]
Monocytic leukemia	DIS8M755	Strong	Biomarker	[12]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[7]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[13]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[9]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[14]
Sarcoidosis	DISE5B8Z	Strong	Biomarker	[15]
Subacute cutaneous lupus erythematosus	DIS6XDK0	Strong	Biomarker	[11]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[11]
T-cell leukaemia	DISJ6YIF	Strong	Altered Expression	[16]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Altered Expression	[17]
Liver cancer	DISDE4BI	moderate	Altered Expression	[17]
Type-1 diabetes	DIS7HLUB	moderate	Altered Expression	[18]
Pneumonia	DIS8EF3M	Disputed	Biomarker	[19]
Arthritis	DIST1YEL	Limited	Genetic Variation	[20]
Neoplasm	DISZKGEW	Limited	Biomarker	[21]
Pneumocystis pneumonia	DISFSOM3	Limited	Biomarker	[22]

10 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 55 kDa erythrocyte membrane protein (MPP1).	[23]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of 55 kDa erythrocyte membrane protein (MPP1).	[24]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of 55 kDa erythrocyte membrane protein (MPP1).	[25]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of 55 kDa erythrocyte membrane protein (MPP1).	[26]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 55 kDa erythrocyte membrane protein (MPP1).	[27]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of 55 kDa erythrocyte membrane protein (MPP1).	[28]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of 55 kDa erythrocyte membrane protein (MPP1).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of 55 kDa erythrocyte membrane protein (MPP1).	[31]
CHIR-99021	DMB8MNU	Patented	CHIR-99021 increases the expression of 55 kDa erythrocyte membrane protein (MPP1).	[32]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of 55 kDa erythrocyte membrane protein (MPP1).	[34]

2 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 increases the methylation of 55 kDa erythrocyte membrane protein (MPP1).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of 55 kDa erythrocyte membrane protein (MPP1).	[33]

References

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• [4] Varied pathways of stage IA lung adenocarcinomas discovered by integrated gene expression analysis.Int J Biol Sci. 2011 Apr 28;7(5):551-66. doi: 10.7150/ijbs.7.551.
• [5] p55 and p75 tumor necrosis factor receptor expression on human glioblastoma cells.Neurol Med Chir (Tokyo). 1995 Aug;35(8):567-74. doi: 10.2176/nmc.35.567.
• [6] Inhibition of TNF Receptor p55 By a Domain Antibody Attenuates the Initial Phase of Acid-Induced Lung Injury in Mice.Front Immunol. 2017 Feb 13;8:128. doi: 10.3389/fimmu.2017.00128. eCollection 2017.
• [7] The severity of ankylosing spondylitis and responses to anti-tumour necrosis factor biologics are not influenced by the tumour necrosis factor receptor polymorphism incriminated in multiple sclerosis.Genes Immun. 2019 Feb;20(2):167-171. doi: 10.1038/s41435-018-0017-0. Epub 2018 Mar 10.
• [8] Optimal Reference Gene Selection for Expression Studies in Human Reticulocytes.J Mol Diagn. 2018 May;20(3):326-333. doi: 10.1016/j.jmoldx.2018.01.009. Epub 2018 Feb 21.
• [9] Epstein-Barr virus infection induces expression in B lymphocytes of a novel gene encoding an evolutionarily conserved 55-kilodalton actin-bundling protein.J Virol. 1994 Nov;68(11):7320-8. doi: 10.1128/JVI.68.11.7320-7328.1994.
• [10] Expression of p55 (Tac) interleukin-2 receptor (IL-2R), but not p75 IL-2R, in cultured H-RS cells and H-RS cells in tissues.Am J Pathol. 1990 Apr;136(4):735-44.
• [11] Antibodies to retroviral proteins in autoimmune connective tissue disease. Relation to clinical manifestations and ribonucleoprotein autoantibodies.Arthritis Rheum. 1992 Dec;35(12):1483-91. doi: 10.1002/art.1780351212.
• [12] Chromosome 22 complements apoptosis in Fas-and TNF-resistant mutant UK110 cells.Oncogene. 1996 Jul 4;13(1):39-46.
• [13] Enhanced expression of tumor necrosis factor receptor mRNA and protein in mononuclear cells isolated from rheumatoid arthritis synovial joints.Eur J Immunol. 1992 Jul;22(7):1907-12. doi: 10.1002/eji.1830220734.
• [14] Local production of complement proteins in rheumatoid arthritis synovium.Arthritis Rheum. 2002 Apr;46(4):934-45. doi: 10.1002/art.10183.
• [15] Spontaneous expression of the interleukin 2 receptor gene and presence of functional interleukin 2 receptors on T lymphocytes in the blood of individuals with active pulmonary sarcoidosis.J Clin Invest. 1988 Sep;82(3):775-81. doi: 10.1172/JCI113678.
• [16] Immunomodulatory effects of RXR rexinoids: modulation of high-affinity IL-2R expression enhances susceptibility to denileukin diftitox.Blood. 2002 Aug 15;100(4):1399-403. doi: 10.1182/blood-2002-01-0300.
• [17] Phenotypic and functional differences between human liver cancer endothelial cells and liver sinusoidal endothelial cells.J Vasc Res. 2008;45(1):78-86. doi: 10.1159/000109079. Epub 2007 Sep 27.
• [18] Monokine antagonism is reduced in patients with IDDM.Diabetes. 1994 Oct;43(10):1242-7. doi: 10.2337/diab.43.10.1242.
• [19] DNA-based testing in lung transplant recipients with suspected non-viral lower respiratory tract infection: A prospective observational study.Transpl Infect Dis. 2018 Feb;20(1). doi: 10.1111/tid.12811. Epub 2017 Dec 21.
• [20] Soluble human p55 and p75 tumor necrosis factor receptors reverse spontaneous arthritis in transgenic mice expressing transmembrane tumor necrosis factor alpha.Arthritis Rheum. 2006 Sep;54(9):2872-85. doi: 10.1002/art.22077.
• [21] Tumor necrosis factor and its receptors in human ovarian cancer. Potential role in disease progression.J Clin Invest. 1993 May;91(5):2194-206. doi: 10.1172/JCI116446.
• [22] Synthetic p55 tandem DNA vaccine against Pneumocystis carinii in rats.Microbiol Immunol. 2016 Jun;60(6):397-406. doi: 10.1111/1348-0421.12386.
• [23] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [24] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [25] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [26] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [27] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [28] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [29] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [30] 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.
• [31] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [32] Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
• [33] 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.
• [34] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.