Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTF928K)

• DTT Name: HUMAN dipeptidyl peptidase 4 (DPP-4)
• Synonyms: Tcell activation antigen CD26; TP103; T-cell activation antigen CD26; Dipeptidyl peptidase IV; Dipeptidyl peptidase 4 soluble form; DPP-IV; DPP IV; DPP 4; CD26; Adenosine deaminase complexing protein-2; Adenosine deaminase complexing protein 2; ADCP2; ADCP-2; ADABP
• Gene Name: DPP4
• BioChemical Class: Peptidase
• UniProt ID: DPP4_HUMAN
• TTD ID: T99041
• EC Number: EC 3.4.14.5
• Sequence:
  MKTPWKVLLGLLGAAALVTIITVPVVLLNKGTDDATADSRKTYTLTDYLKNTYRLKLYSL
  RWISDHEYLYKQENNILVFNAEYGNSSVFLENSTFDEFGHSINDYSISPDGQFILLEYNY
  VKQWRHSYTASYDIYDLNKRQLITEERIPNNTQWVTWSPVGHKLAYVWNNDIYVKIEPNL
  PSYRITWTGKEDIIYNGITDWVYEEEVFSAYSALWWSPNGTFLAYAQFNDTEVPLIEYSF
  YSDESLQYPKTVRVPYPKAGAVNPTVKFFVVNTDSLSSVTNATSIQITAPASMLIGDHYL
  CDVTWATQERISLQWLRRIQNYSVMDICDYDESSGRWNCLVARQHIEMSTTGWVGRFRPS
  EPHFTLDGNSFYKIISNEEGYRHICYFQIDKKDCTFITKGTWEVIGIEALTSDYLYYISN
  EYKGMPGGRNLYKIQLSDYTKVTCLSCELNPERCQYYSVSFSKEAKYYQLRCSGPGLPLY
  TLHSSVNDKGLRVLEDNSALDKMLQNVQMPSKKLDFIILNETKFWYQMILPPHFDKSKKY
  PLLLDVYAGPCSQKADTVFRLNWATYLASTENIIVASFDGRGSGYQGDKIMHAINRRLGT
  FEVEDQIEAARQFSKMGFVDNKRIAIWGWSYGGYVTSMVLGSGSGVFKCGIAVAPVSRWE
  YYDSVYTERYMGLPTPEDNLDHYRNSTVMSRAENFKQVEYLLIHGTADDNVHFQQSAQIS
  KALVDVGVDFQAMWYTDEDHGIASSTAHQHIYTHMSHFIKQCFSLP
• Function: 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. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline. Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation.
• 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 DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Linagliptin	DMWFJTR	Non-insulin dependent diabetes	5A11	Approved	[2]

1 Investigative Agents Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
YS110 mAb clone	DMTURZ6	Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[3]

References

• [1] In-vitro renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during Middle East Respira... Virol J. 2013 Dec 23;10:359.
• [2] DPP4 inhibition: preventing SARS-CoV-2 infection and/or progression of COVID-19 Diabetes Metab Res Rev. 2020 Apr 26.
• [3] Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.