Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWSYFI7)

• DOT Name: Antigen peptide transporter 2 (TAP2)
• Synonyms: APT2; EC 7.4.2.14; ATP-binding cassette sub-family B member 3; Peptide supply factor 2; Peptide transporter PSF2; PSF-2; Peptide transporter TAP2; Peptide transporter involved in antigen processing 2; Really interesting new gene 11 protein; RING11
• Gene Name: TAP2
• Related Disease:
  Behcet disease
  Acute myelogenous leukaemia
  Alzheimer disease
  Ankylosing spondylitis
  Autoimmune disease
  Autoimmune thyroid disease
  B-cell lymphoma
  Breast neoplasm
  Bronchiectasis
  Carcinoma of esophagus
  Cervical cancer
  Cervical carcinoma
  Clear cell renal carcinoma
  Colorectal carcinoma
  Crohn disease
  Dengue
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Immunodeficiency
  Liver cirrhosis
  Lung cancer
  Lung carcinoma
  MHC class I deficiency
  Narcolepsy
  Plasma cell myeloma
  Pulmonary tuberculosis
  Renal cell carcinoma
  Rheumatoid arthritis
  Sjogren syndrome
  Small-cell lung cancer
  Systemic lupus erythematosus
  Tuberculosis
  Ulcerative colitis
  Asthma
  Type-1/2 diabetes
  Melanoma
  Advanced cancer
  Arthritis
  Breast cancer
  Breast carcinoma
  Coeliac disease
  Graves disease
  Hepatitis B virus infection
  Neoplasm
  Pemphigus vulgaris
  Sarcoidosis
  Small lymphocytic lymphoma
  Systemic sclerosis
• UniProt ID: TAP2_HUMAN
• PDB ID: 5U1D
• EC Number: 7.4.2.14
• Pfam ID: PF00664 ; PF00005
• Sequence:
  MRLPDLRPWTSLLLVDAALLWLLQGPLGTLLPQGLPGLWLEGTLRLGGLWGLLKLRGLLG
  FVGTLLLPLCLATPLTVSLRALVAGASRAPPARVASAPWSWLLVGYGAAGLSWSLWAVLS
  PPGAQEKEQDQVNNKVLMWRLLKLSRPDLPLLVAAFFFLVLAVLGETLIPHYSGRVIDIL
  GGDFDPHAFASAIFFMCLFSFGSSLSAGCRGGCFTYTMSRINLRIREQLFSSLLRQDLGF
  FQETKTGELNSRLSSDTTLMSNWLPLNANVLLRSLVKVVGLYGFMLSISPRLTLLSLLHM
  PFTIAAEKVYNTRHQEVLREIQDAVARAGQVVREAVGGLQTVRSFGAEEHEVCRYKEALE
  QCRQLYWRRDLERALYLLVRRVLHLGVQMLMLSCGLQQMQDGELTQGSLLSFMIYQESVG
  SYVQTLVYIYGDMLSNVGAAEKVFSYMDRQPNLPSPGTLAPTTLQGVVKFQDVSFAYPNR
  PDRPVLKGLTFTLRPGEVTALVGPNGSGKSTVAALLQNLYQPTGGQVLLDEKPISQYEHC
  YLHSQVVSVGQEPVLFSGSVRNNIAYGLQSCEDDKVMAAAQAAHADDFIQEMEHGIYTDV
  GEKGSQLAAGQKQRLAIARALVRDPRVLILDEATSALDVQCEQALQDWNSRGDRTVLVIA
  HRLQTVQRAHQILVLQEGKLQKLAQL
• Function: ABC transporter associated with antigen processing. In complex with TAP1 mediates unidirectional translocation of peptide antigens from cytosol to endoplasmic reticulum (ER) for loading onto MHC class I (MHCI) molecules. Uses the chemical energy of ATP to export peptides against the concentration gradient. During the transport cycle alternates between 'inward-facing' state with peptide binding site facing the cytosol to 'outward-facing' state with peptide binding site facing the ER lumen. Peptide antigen binding to ATP-loaded TAP1-TAP2 induces a switch to hydrolysis-competent 'outward-facing' conformation ready for peptide loading onto nascent MHCI molecules. Subsequently ATP hydrolysis resets the transporter to the 'inward facing' state for a new cycle. Typically transports intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via IFNG-induced immunoproteasome. Binds peptides with free N- and C-termini, the first three and the C-terminal residues being critical. Preferentially selects peptides having a highly hydrophobic residue at position 3 and hydrophobic or charged residues at the C-terminal anchor. Proline at position 2 has the most destabilizing effect. As a component of the peptide loading complex (PLC), acts as a molecular scaffold essential for peptide-MHCI assembly and antigen presentation.
• KEGG Pathway:
  ABC transporters (hsa02010)
  Phagosome (hsa04145)
  Antigen processing and presentation (hsa04612)
  Human cytomegalovirus infection (hsa05163)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Human immunodeficiency virus 1 infection (hsa05170)
  Primary immunodeficiency (hsa05340)
• Reactome Pathway:
  Antigen Presentation (R-HSA-983170)
  ER-Phagosome pathway (R-HSA-1236974)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Behcet disease	DISSYMBS	Definitive	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[3]
Ankylosing spondylitis	DISRC6IR	Strong	Genetic Variation	[4]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[5]
Autoimmune thyroid disease	DISIHC6A	Strong	Genetic Variation	[6]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[7]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[8]
Bronchiectasis	DIS5MYEE	Strong	Biomarker	[9]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[10]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[2]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Posttranslational Modification	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[12]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[13]
Dengue	DISKH221	Strong	Genetic Variation	[14]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[16]
Immunodeficiency	DIS093I0	Strong	Biomarker	[17]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[18]
Lung cancer	DISCM4YA	Strong	Altered Expression	[19]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[19]
MHC class I deficiency	DISSMWCT	Strong	Autosomal recessive	[20]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[21]
Plasma cell myeloma	DIS0DFZ0	Strong	Genetic Variation	[22]
Pulmonary tuberculosis	DIS6FLUM	Strong	Genetic Variation	[23]
Renal cell carcinoma	DISQZ2X8	Strong	Posttranslational Modification	[11]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[24]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[25]
Small-cell lung cancer	DISK3LZD	Strong	Altered Expression	[26]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[27]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[28]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[29]
Asthma	DISW9QNS	moderate	Genetic Variation	[30]
Type-1/2 diabetes	DISIUHAP	moderate	Genetic Variation	[31]
Melanoma	DIS1RRCY	Disputed	Biomarker	[32]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[33]
Arthritis	DIST1YEL	Limited	Genetic Variation	[34]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[8]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[8]
Coeliac disease	DISIY60C	Limited	Genetic Variation	[35]
Graves disease	DISU4KOQ	Limited	Genetic Variation	[36]
Hepatitis B virus infection	DISLQ2XY	Limited	Genetic Variation	[37]
Neoplasm	DISZKGEW	Limited	Altered Expression	[8]
Pemphigus vulgaris	DISENR62	Limited	Genetic Variation	[38]
Sarcoidosis	DISE5B8Z	Limited	Genetic Variation	[39]
Small lymphocytic lymphoma	DIS30POX	Limited	Genetic Variation	[22]
Systemic sclerosis	DISF44L6	Limited	Genetic Variation	[40]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Antigen peptide transporter 2 (TAP2) affects the response to substance of Aspirin.	[9]
Daunorubicin	DMQUSBT	Approved	Antigen peptide transporter 2 (TAP2) affects the response to substance of Daunorubicin.	[58]

15 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 Antigen peptide transporter 2 (TAP2).	[41]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Antigen peptide transporter 2 (TAP2).	[42]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Antigen peptide transporter 2 (TAP2).	[43]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Antigen peptide transporter 2 (TAP2).	[44]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Antigen peptide transporter 2 (TAP2).	[45]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Antigen peptide transporter 2 (TAP2).	[46]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Antigen peptide transporter 2 (TAP2).	[48]
Marinol	DM70IK5	Approved	Marinol increases the expression of Antigen peptide transporter 2 (TAP2).	[49]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Antigen peptide transporter 2 (TAP2).	[50]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Antigen peptide transporter 2 (TAP2).	[51]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Antigen peptide transporter 2 (TAP2).	[52]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Antigen peptide transporter 2 (TAP2).	[53]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Antigen peptide transporter 2 (TAP2).	[54]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Antigen peptide transporter 2 (TAP2).	[55]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Antigen peptide transporter 2 (TAP2).	[56]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Antigen peptide transporter 2 (TAP2).	[47]

References

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