Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT70W1J8)

• DOT Name: Transmembrane emp24 domain-containing protein 5 (TMED5)
• Synonyms: p24 family protein gamma-2; p24gamma2; p28
• Gene Name: TMED5
• Related Disease:
  B-cell neoplasm
  Neoplasm
  Adult T-cell leukemia/lymphoma
  Advanced cancer
  Autoimmune disease
  Brain neoplasm
  Carcinoma of esophagus
  Encephalitis
  Glioma
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Multiple sclerosis
  Myocardial infarction
  Myopia
  Schizophrenia
  Breast cancer
  Breast carcinoma
  Influenza
  Melanoma
  Acute myelogenous leukaemia
  Nervous system inflammation
• UniProt ID: TMED5_HUMAN
• Pfam ID: PF01105
• Sequence:
  MGDKIWLPFPVLLLAALPPVLLPGAAGFTPSLDSDFTFTLPAGQKECFYQPMPLKASLEI
  EYQVLDGAGLDIDFHLASPEGKTLVFEQRKSDGVHTVETEVGDYMFCFDNTFSTISEKVI
  FFELILDNMGEQAQEQEDWKKYITGTDILDMKLEDILESINSIKSRLSKSGHIQTLLRAF
  EARDRNIQESNFDRVNFWSMVNLVVMVVVSAIQVYMLKSLFEDKRKSRT
• Function: Potential role in vesicular protein trafficking, mainly in the early secretory pathway. Required for the maintenance of the Golgi apparatus; involved in protein exchange between Golgi stacks during assembly. Probably not required for COPI-vesicle-mediated retrograde transport.
• Reactome Pathway: WNT ligand biogenesis and trafficking (R-HSA-3238698)

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Altered Expression	[1]
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[4]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[5]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[6]
Encephalitis	DISLD1RL	Strong	Biomarker	[7]
Glioma	DIS5RPEH	Strong	Biomarker	[5]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[8]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[10]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[4]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[11]
Myopia	DISK5S60	Strong	Biomarker	[12]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[13]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[14]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[14]
Influenza	DIS3PNU3	moderate	Altered Expression	[15]
Melanoma	DIS1RRCY	moderate	Altered Expression	[14]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[16]
Nervous system inflammation	DISB3X5A	Limited	Altered Expression	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Transmembrane emp24 domain-containing protein 5 (TMED5).	[18]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Transmembrane emp24 domain-containing protein 5 (TMED5).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transmembrane emp24 domain-containing protein 5 (TMED5).	[19]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane emp24 domain-containing protein 5 (TMED5).	[20]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane emp24 domain-containing protein 5 (TMED5).	[21]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transmembrane emp24 domain-containing protein 5 (TMED5).	[22]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transmembrane emp24 domain-containing protein 5 (TMED5).	[23]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Transmembrane emp24 domain-containing protein 5 (TMED5).	[24]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Transmembrane emp24 domain-containing protein 5 (TMED5).	[25]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Transmembrane emp24 domain-containing protein 5 (TMED5).	[26]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Transmembrane emp24 domain-containing protein 5 (TMED5).	[27]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate decreases the expression of Transmembrane emp24 domain-containing protein 5 (TMED5).	[28]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Transmembrane emp24 domain-containing protein 5 (TMED5).	[29]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Transmembrane emp24 domain-containing protein 5 (TMED5).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Transmembrane emp24 domain-containing protein 5 (TMED5).	[31]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transmembrane emp24 domain-containing protein 5 (TMED5).	[32]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Transmembrane emp24 domain-containing protein 5 (TMED5).	[33]

References

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• [16] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [17] IL-27 blocks RORc expression to inhibit lineage commitment of Th17 cells.J Immunol. 2009 May 1;182(9):5748-56. doi: 10.4049/jimmunol.0801162.
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• [19] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
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• [21] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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• [23] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
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