Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7DAO0F)

• DOT Name: Macrophage-expressed gene 1 protein (MPEG1)
• Synonyms: Macrophage gene 1 protein; Mpg-1; Perforin-2; P-2
• Gene Name: MPEG1
• Related Disease:
  Inborn error of metabolism
  Matthew-Wood syndrome
  Arteriosclerosis
  Atherosclerosis
  Blindness
  Brain disease
  Breast cancer
  Colon cancer
  Colon carcinoma
  Familial Alzheimer disease
  Gastric cancer
  Gaucher disease
  Hartnup disease
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Hurler syndrome
  Hurler-Scheie syndrome
  Lymphoblastic lymphoma
  Lysosomal storage disease
  Malignant mesothelioma
  Medulloblastoma
  Mucopolysaccharidosis
  Mucopolysaccharidosis I
  Mucopolysaccharidosis II
  Mucopolysaccharidosis type 3A
  Mucopolysaccharidosis type 4A
  Mycobacterium infection
  Neoplasm
  Plasma cell myeloma
  Stomach cancer
  Thyroid gland carcinoma
  Bacterial infection
  Breast carcinoma
  Pancreatic ductal carcinoma
  Adult glioblastoma
  Carcinoma of liver and intrahepatic biliary tract
  Cardiomyopathy
  Childhood acute lymphoblastic leukemia
  Colorectal carcinoma
  Fabry disease
  Glioblastoma multiforme
  Immunodeficiency 77
  Liver cancer
  Melanoma
  Metastatic malignant neoplasm
  Nervous system disease
  Panic disorder
  Small lymphocytic lymphoma
  Triple negative breast cancer
• UniProt ID: MPEG1_HUMAN
• PDB ID: 6U23; 6U2J; 6U2K; 6U2L; 6U2W
• Pfam ID: PF01823
• Sequence:
  MNNFRATILFWAAAAWAKSGKPSGEMDEVGVQKCKNALKLPVLEVLPGGGWDNLRNVDMG
  RVMELTYSNCRTTEDGQYIIPDEIFTIPQKQSNLEMNSEILESWANYQSSTSYSINTELS
  LFSKVNGKFSTEFQRMKTLQVKDQAITTRVQVRNLVYTVKINPTLELSSGFRKELLDISD
  RLENNQTRMATYLAELLVLNYGTHVTTSVDAGAALIQEDHLRASFLQDSQSSRSAVTASA
  GLAFQNTVNFKFEENYTSQNVLTKSYLSNRTNSRVQSIGGVPFYPGITLQAWQQGITNHL
  VAIDRSGLPLHFFINPNMLPDLPGPLVKKVSKTVETAVKRYYTFNTYPGCTDLNSPNFNF
  QANTDDGSCEGKMTNFSFGGVYQECTQLSGNRDVLLCQKLEQKNPLTGDFSCPSGYSPVH
  LLSQIHEEGYNHLECHRKCTLLVFCKTVCEDVFQVAKAEFRAFWCVASSQVPENSGLLFG
  GLFSSKSINPMTNAQSCPAGYFPLRLFENLKVCVSQDYELGSRFAVPFGGFFSCTVGNPL
  VDPAISRDLGAPSLKKCPGGFSQHPALISDGCQVSYCVKSGLFTGGSLPPARLPPFTRPP
  LMSQAATNTVIVTNSENARSWIKDSQTHQWRLGEPIELRRAMNVIHGDGGGLSGGAAAGV
  TVGVTTILAVVITLAIYGTRKFKKKAYQAIEERQSLVPGTAATGDTTYQEQGQSPA
• Function: Pore-forming protein involved in both innate and adaptive immunity. Plays a central role in antigen cross-presentation in dendritic cells by forming a pore in antigen-containing compartments, thereby promoting delivery of antigens for cross-presentation. Also involved in innate immune response following bacterial infection; shows antibacterial activity against a wide spectrum of Gram-positive, Gram-negative and acid-fast bacteria. Reduces the viability of the intracytosolic pathogen L.monocytogenes by inhibiting acidification of the phagocytic vacuole of host cells which restricts bacterial translocation from the vacuole to the cytosol. Required for the antibacterial activity of reactive oxygen species and nitric oxide; [Macrophage-expressed gene 1 protein, processed form]: Pore-forming protein that plays a central role in antigen cross-presentation in dendritic cells by mediating delivery of antigens for cross-presentation. Dendritic cells bridge innate and adaptive immunity by capturing exogenous antigens on MHC class-I molecules and presenting them to naive CD8(+) T-cells. Acts by forming a pore in antigen-containing compartments, promoting the release of antigens into the cytosol, enabling generation of MHCI:peptide complexes and T-cell priming.
• Tissue Specificity: Expressed constitutively in a variety of cell types including macrophages, natural killer cells, neutrophils, keratinocytes and monocytes . In skin, expressed in both hematopoietic and non-hematopoietic cells with expression detected in a variety of cell types including keratinocytes, fibroblasts and endothelial cells .

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Inborn error of metabolism	DISO5FAY	Definitive	Biomarker	[1]
Matthew-Wood syndrome	DISA7HR7	Definitive	Altered Expression	[2]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[3]
Blindness	DISTIM10	Strong	Biomarker	[4]
Brain disease	DIS6ZC3X	Strong	Genetic Variation	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Colon cancer	DISVC52G	Strong	Biomarker	[7]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[7]
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[8]
Gastric cancer	DISXGOUK	Strong	Biomarker	[9]
Gaucher disease	DISTW5JG	Strong	Biomarker	[10]
Hartnup disease	DISYK0UH	Strong	Biomarker	[11]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[7]
Hurler syndrome	DIS1DPSN	Strong	Biomarker	[1]
Hurler-Scheie syndrome	DIS1YJC5	Strong	Genetic Variation	[13]
Lymphoblastic lymphoma	DISB9ZYC	Strong	Biomarker	[14]
Lysosomal storage disease	DIS6QM6U	Strong	Genetic Variation	[15]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[16]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[17]
Mucopolysaccharidosis	DISB083T	Strong	Genetic Variation	[18]
Mucopolysaccharidosis I	DISTS29G	Strong	Genetic Variation	[19]
Mucopolysaccharidosis II	DIS87GLG	Strong	Genetic Variation	[20]
Mucopolysaccharidosis type 3A	DIS2TLNF	Strong	Biomarker	[21]
Mucopolysaccharidosis type 4A	DISTYFQS	Strong	Biomarker	[22]
Mycobacterium infection	DISNSMUD	Strong	Genetic Variation	[23]
Neoplasm	DISZKGEW	Strong	Biomarker	[24]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[25]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[26]
Bacterial infection	DIS5QJ9S	moderate	Altered Expression	[27]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[6]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Biomarker	[28]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[6]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[29]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[30]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Limited	Genetic Variation	[31]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[32]
Fabry disease	DISUUQJF	Limited	Biomarker	[33]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[6]
Immunodeficiency 77	DIS3R5N8	Limited	Unknown	[34]
Liver cancer	DISDE4BI	Limited	Biomarker	[29]
Melanoma	DIS1RRCY	Limited	Biomarker	[32]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[31]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[30]
Panic disorder	DISD3VNY	Limited	Genetic Variation	[35]
Small lymphocytic lymphoma	DIS30POX	Limited	Biomarker	[36]
Triple negative breast cancer	DISAMG6N	Limited	Biomarker	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Macrophage-expressed gene 1 protein (MPEG1).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Macrophage-expressed gene 1 protein (MPEG1).	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Macrophage-expressed gene 1 protein (MPEG1).	[39]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Macrophage-expressed gene 1 protein (MPEG1).	[40]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Macrophage-expressed gene 1 protein (MPEG1).	[42]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Macrophage-expressed gene 1 protein (MPEG1).	[43]

References

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