Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT16MVL9)

• DOT Name: Dipeptidyl peptidase 4 (DPP4)
• Synonyms: EC 3.4.14.5; ADABP; Adenosine deaminase complexing protein 2; ADCP-2; Dipeptidyl peptidase IV; DPP IV; T-cell activation antigen CD26; TP103; CD antigen CD26
• Gene Name: DPP4
• UniProt ID: DPP4_HUMAN
• PDB ID: 1J2E ; 1N1M ; 1NU6 ; 1NU8 ; 1PFQ ; 1R9M ; 1R9N ; 1RWQ ; 1TK3 ; 1TKR ; 1U8E ; 1W1I ; 1WCY ; 1X70 ; 2AJL ; 2BGN ; 2BGR ; 2BUB ; 2FJP ; 2G5P ; 2G5T ; 2G63 ; 2HHA ; 2I03 ; 2I78 ; 2IIT ; 2IIV ; 2JID ; 2OAG ; 2OGZ ; 2OLE ; 2ONC ; 2OPH ; 2OQI ; 2OQV ; 2P8S ; 2QJR ; 2QKY ; 2QOE ; 2QT9 ; 2QTB ; 2RGU ; 2RIP ; 3BJM ; 3C43 ; 3C45 ; 3CCB ; 3CCC ; 3D4L ; 3EIO ; 3F8S ; 3G0B ; 3G0C ; 3G0D ; 3G0G ; 3H0C ; 3HAB ; 3HAC ; 3KWF ; 3KWJ ; 3NOX ; 3O95 ; 3O9V ; 3OC0 ; 3OPM ; 3Q0T ; 3Q8W ; 3QBJ ; 3SWW ; 3SX4 ; 3VJK ; 3VJL ; 3VJM ; 3W2T ; 3WQH ; 4A5S ; 4DSA ; 4DSZ ; 4DTC ; 4G1F ; 4J3J ; 4JH0 ; 4KR0 ; 4L72 ; 4LKO ; 4N8D ; 4N8E ; 4PNZ ; 4PV7 ; 4QZV ; 5I7U ; 5ISM ; 5J3J ; 5KBY ; 5T4B ; 5T4E ; 5T4F ; 5T4H ; 5Y7H ; 5Y7J ; 5Y7K ; 5ZID ; 6B1E ; 6B1O
• EC Number: 3.4.14.5
• Pfam ID: PF00930 ; PF00326
• Sequence:
  MKTPWKVLLGLLGAAALVTIITVPVVLLNKGTDDATADSRKTYTLTDYLKNTYRLKLYSL
  RWISDHEYLYKQENNILVFNAEYGNSSVFLENSTFDEFGHSINDYSISPDGQFILLEYNY
  VKQWRHSYTASYDIYDLNKRQLITEERIPNNTQWVTWSPVGHKLAYVWNNDIYVKIEPNL
  PSYRITWTGKEDIIYNGITDWVYEEEVFSAYSALWWSPNGTFLAYAQFNDTEVPLIEYSF
  YSDESLQYPKTVRVPYPKAGAVNPTVKFFVVNTDSLSSVTNATSIQITAPASMLIGDHYL
  CDVTWATQERISLQWLRRIQNYSVMDICDYDESSGRWNCLVARQHIEMSTTGWVGRFRPS
  EPHFTLDGNSFYKIISNEEGYRHICYFQIDKKDCTFITKGTWEVIGIEALTSDYLYYISN
  EYKGMPGGRNLYKIQLSDYTKVTCLSCELNPERCQYYSVSFSKEAKYYQLRCSGPGLPLY
  TLHSSVNDKGLRVLEDNSALDKMLQNVQMPSKKLDFIILNETKFWYQMILPPHFDKSKKY
  PLLLDVYAGPCSQKADTVFRLNWATYLASTENIIVASFDGRGSGYQGDKIMHAINRRLGT
  FEVEDQIEAARQFSKMGFVDNKRIAIWGWSYGGYVTSMVLGSGSGVFKCGIAVAPVSRWE
  YYDSVYTERYMGLPTPEDNLDHYRNSTVMSRAENFKQVEYLLIHGTADDNVHFQQSAQIS
  KALVDVGVDFQAMWYTDEDHGIASSTAHQHIYTHMSHFIKQCFSLP
• Function: Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones such as brain natriuretic peptide 32. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline ; (Microbial infection) Acts as a receptor for human coronavirus MERS-CoV-2.
• Tissue Specificity: Expressed specifically in lymphatic vessels but not in blood vessels in the skin, small intestine, esophagus, ovary, breast and prostate glands. Not detected in lymphatic vessels in the lung, kidney, uterus, liver and stomach (at protein level). Expressed in the poorly differentiated crypt cells of the small intestine as well as in the mature villous cells. Expressed at very low levels in the colon.
• KEGG Pathway: Protein digestion and absorption (hsa04974)
• Reactome Pathway:
  Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) (R-HSA-400511)
  Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) (R-HSA-381771)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Dipeptidyl peptidase 4 (DPP4).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Dipeptidyl peptidase 4 (DPP4).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Dipeptidyl peptidase 4 (DPP4).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Dipeptidyl peptidase 4 (DPP4).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Dipeptidyl peptidase 4 (DPP4).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Dipeptidyl peptidase 4 (DPP4).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Dipeptidyl peptidase 4 (DPP4).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Dipeptidyl peptidase 4 (DPP4).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Dipeptidyl peptidase 4 (DPP4).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Dipeptidyl peptidase 4 (DPP4).	[10]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Dipeptidyl peptidase 4 (DPP4).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Dipeptidyl peptidase 4 (DPP4).	[12]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Dipeptidyl peptidase 4 (DPP4).	[13]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Dipeptidyl peptidase 4 (DPP4).	[14]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Dipeptidyl peptidase 4 (DPP4).	[15]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of Dipeptidyl peptidase 4 (DPP4).	[16]
Enzalutamide	DMGL19D	Approved	Enzalutamide decreases the expression of Dipeptidyl peptidase 4 (DPP4).	[17]
Adenosine	DMM2NSK	Approved	Adenosine decreases the expression of Dipeptidyl peptidase 4 (DPP4).	[18]
Vildagliptin	DMYN59P	Approved	Vildagliptin decreases the activity of Dipeptidyl peptidase 4 (DPP4).	[20]
Saxagliptin	DMGXENV	Approved	Saxagliptin decreases the activity of Dipeptidyl peptidase 4 (DPP4).	[21]
Anagliptin	DMJXIC9	Approved	Anagliptin decreases the activity of Dipeptidyl peptidase 4 (DPP4).	[22]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Dipeptidyl peptidase 4 (DPP4).	[17]
Isoflavone	DM7U58J	Phase 4	Isoflavone affects the expression of Dipeptidyl peptidase 4 (DPP4).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Dipeptidyl peptidase 4 (DPP4).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Dipeptidyl peptidase 4 (DPP4).	[25]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Dipeptidyl peptidase 4 (DPP4).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Dipeptidyl peptidase 4 (DPP4).	[27]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Dipeptidyl peptidase 4 (DPP4).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Dipeptidyl peptidase 4 (DPP4).	[28]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Dipeptidyl peptidase 4 (DPP4).	[29]
Manganese	DMKT129	Investigative	Manganese increases the expression of Dipeptidyl peptidase 4 (DPP4).	[30]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Alogliptin	DM8WI3R	Approved	Alogliptin affects the binding of Dipeptidyl peptidase 4 (DPP4).	[19]

References

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