Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBLO7RW)

• DOT Name: Transmembrane emp24 domain-containing protein 2 (TMED2)
• Synonyms: Membrane protein p24A; p24; p24 family protein beta-1; p24beta1
• Gene Name: TMED2
• Related Disease:
  Neoplasm
  Adenocarcinoma
  Adult T-cell leukemia/lymphoma
  Breast cancer
  Breast carcinoma
  Chorioamnionitis
  Chronic fatigue syndrome
  Colon carcinoma
  Cytomegalovirus infection
  Epithelial ovarian cancer
  Hepatitis D virus infection
  Immunodeficiency
  Influenza
  Large cell lymphoma
  Leukemia
  Lymphoma
  Mental disorder
  Myelopathy
  Myocardial ischemia
  Non-alcoholic fatty liver disease
  Ovarian cancer
  Ovarian neoplasm
  Progressive multifocal leukoencephalopathy
  Pulmonary disease
  Schizophrenia
  Sjogren syndrome
  Spastic paralysis
  T-cell leukaemia
  Urticaria
  Vibrio cholerae infection
  Choriocarcinoma
  Neuroblastoma
  Tuberculosis
  Malaria
  Mood disorder
  Psychotic disorder
  Rheumatoid arthritis
• UniProt ID: TMED2_HUMAN
• PDB ID: 5AZW
• Pfam ID: PF01105
• Sequence:
  MVTLAELLVLLAALLATVSGYFVSIDAHAEECFFERVTSGTKMGLIFEVAEGGFLDIDVE
  ITGPDNKGIYKGDRESSGKYTFAAHMDGTYKFCFSNRMSTMTPKIVMFTIDIGEAPKGQD
  METEAHQNKLEEMINELAVAMTAVKHEQEYMEVRERIHRAINDNTNSRVVLWSFFEALVL
  VAMTLGQIYYLKRFFEVRRVV
• Function: Involved in vesicular protein trafficking. Mainly functions in the early secretory pathway but also in post-Golgi membranes. Thought to act as cargo receptor at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and to be involved in vesicle coat formation at the cytoplasmic side. In COPII vesicle-mediated anterograde transport involved in the transport of GPI-anchored proteins and proposed to act together with TMED10 as their cargo receptor; the function specifically implies SEC24C and SEC24D of the COPII vesicle coat and lipid raft-like microdomains of the ER. Recognizes GPI anchors structural remodeled in the ER by PGAP1 and MPPE1. In COPI vesicle-mediated retrograde transport inhibits the GTPase-activating activity of ARFGAP1 towards ARF1 thus preventing immature uncoating and allowing cargo selection to take place. Involved in trafficking of G protein-coupled receptors (GPCRs). Regulates F2RL1, OPRM1 and P2RY4 exocytic trafficking from the Golgi to the plasma membrane thus contributing to receptor resensitization. Facilitates CASR maturation and stabilization in the early secretory pathway and increases CASR plasma membrane targeting. Proposed to be involved in organization of intracellular membranes such as the maintenance of the Golgi apparatus. May also play a role in the biosynthesis of secreted cargo such as eventual processing.
• Reactome Pathway:
  COPII-mediated vesicle transport (R-HSA-204005)
  Cargo concentration in the ER (R-HSA-5694530)
  COPI-mediated anterograde transport (R-HSA-6807878)
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  Pre-NOTCH Processing in Golgi (R-HSA-1912420)

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[2]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Posttranslational Modification	[4]
Breast carcinoma	DIS2UE88	Strong	Posttranslational Modification	[4]
Chorioamnionitis	DISL1D9U	Strong	Altered Expression	[5]
Chronic fatigue syndrome	DIS34WJ5	Strong	Biomarker	[6]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[7]
Cytomegalovirus infection	DISCEMGC	Strong	Altered Expression	[8]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[9]
Hepatitis D virus infection	DISESSLZ	Strong	Biomarker	[10]
Immunodeficiency	DIS093I0	Strong	Biomarker	[11]
Influenza	DIS3PNU3	Strong	Biomarker	[12]
Large cell lymphoma	DISYZHCP	Strong	Altered Expression	[1]
Leukemia	DISNAKFL	Strong	Biomarker	[13]
Lymphoma	DISN6V4S	Strong	Biomarker	[14]
Mental disorder	DIS3J5R8	Strong	Biomarker	[15]
Myelopathy	DISXV8FG	Strong	Biomarker	[16]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[17]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[18]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[9]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[9]
Progressive multifocal leukoencephalopathy	DISX02WS	Strong	Biomarker	[19]
Pulmonary disease	DIS6060I	Strong	Altered Expression	[20]
Schizophrenia	DISSRV2N	Strong	Biomarker	[15]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[21]
Spastic paralysis	DISVQ6I2	Strong	Biomarker	[16]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[3]
Urticaria	DIS9WQAI	Strong	Altered Expression	[22]
Vibrio cholerae infection	DISW7E3U	Strong	Biomarker	[23]
Choriocarcinoma	DISDBVNL	moderate	Altered Expression	[24]
Neuroblastoma	DISVZBI4	moderate	Genetic Variation	[25]
Tuberculosis	DIS2YIMD	moderate	Biomarker	[14]
Malaria	DISQ9Y50	Limited	Biomarker	[26]
Mood disorder	DISLVMWO	Limited	Altered Expression	[27]
Psychotic disorder	DIS4UQOT	Limited	Biomarker	[27]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[28]

11 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 2 (TMED2).	[29]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane emp24 domain-containing protein 2 (TMED2).	[30]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transmembrane emp24 domain-containing protein 2 (TMED2).	[31]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transmembrane emp24 domain-containing protein 2 (TMED2).	[32]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Transmembrane emp24 domain-containing protein 2 (TMED2).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane emp24 domain-containing protein 2 (TMED2).	[35]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Transmembrane emp24 domain-containing protein 2 (TMED2).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transmembrane emp24 domain-containing protein 2 (TMED2).	[37]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transmembrane emp24 domain-containing protein 2 (TMED2).	[38]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Transmembrane emp24 domain-containing protein 2 (TMED2).	[39]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Transmembrane emp24 domain-containing protein 2 (TMED2).	[40]

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 decreases the methylation of Transmembrane emp24 domain-containing protein 2 (TMED2).	[34]

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