Protein / target
Dipeptidyl peptidase 4
Protein at a glance
Biological role
Serine-type endopeptidase activity
Primary system
Immune system
Strongest disease association
intelligence
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
15 approved · 6 in clinical development
Research activity
Emerging research
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation (PubMed:10900005, PubMed:10951221, PubMed:11772392, PubMed:17287217). Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC (PubMed:10900005, PubMed:10951221, PubMed:11772392, PubMed:14691230). Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner (PubMed:17287217). Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion (PubMed:11772392). 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 (PubMed:10593948, PubMed:16651416). May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation (PubMed:18708048). When overexpressed, enhanced cell proliferation, a process inhibited by GPC3 (PubMed:17549790). Also acts 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 (PubMed:10570924, PubMed:16254193). Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline (PubMed:10593948)
Subcellular location
Domains and Gene Ontology detail (39)Hide
Gene Ontology
- Capical plasma membrane
- Ccell surface
- Cendocytic vesicle
- Cextracellular exosome
- Cextracellular region
- Cfocal adhesion
- Cintercellular canaliculus
- Clamellipodium
- Clamellipodium membrane
- Clysosomal membrane
- Cmembrane
- Cmembrane raft
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Cell adhesion
- ·Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-…
- ·Cell junction
- ·cell adhesion
- ·negative regulation of extracellular matrix disassembly
Proteolysis
- ·Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-…
- ·aminopeptidase activity
- ·dipeptidyl-peptidase activity
- ·protease binding
Immune signalling
- ·receptor-mediated endocytosis of virus by host cell
- ·receptor-mediated virion attachment to host cell
- ·symbiont entry into host cell
- ·T cell activation
View underlying pathways (2)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Dipeptidyl peptidase IV inhibitor
Appears in clinical studies involving type 2 diabetes mellitus, hyperlipidemia, myocardial infarction, stroke disorder
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 1,465 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 21 total
type 2 diabetes mellitus · type 2 diabetes mellitus · chronic kidney disease
type 2 diabetes mellitus · diabetes mellitus · type 2 diabetes mellitus
type 2 diabetes mellitus · metabolic disease · type 2 diabetes mellitus
diabetes mellitus · type 2 diabetes mellitus · type 2 diabetes mellitus
type 2 diabetes mellitus
diabetes mellitus · type 2 diabetes mellitus · type 2 diabetes mellitus
type 2 diabetes mellitus · type 2 diabetes mellitus · type 2 diabetes mellitus
type 2 diabetes mellitus · type 2 diabetes mellitus
type 2 diabetes mellitus
metabolic disease · type 2 diabetes mellitus · type 2 diabetes mellitus
Tractability
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Research activity
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- New publicationDPP-4 inhibitors sitagliptin and PF-00734,200 mitigate dopaminergic neurodegeneration, neuroinflammation and behavioral impairment in the rat 6-OHDA model of Parkinson's disease.
- New publicationSitagliptin Treatment at the Time of Hospitalization Was Associated With Reduced Mortality in Patients With Type 2 Diabetes and COVID-19: A Multicenter, Case-Control, Retrospective, Observational Study.
- New publicationEfficacy and tolerability of sitagliptin monotherapy in elderly patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial.
- New publicationEfficacy and safety of sitagliptin monotherapy compared with voglibose in Japanese patients with type 2 diabetes: a randomized, double-blind trial.
- New publicationDose-ranging efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes mellitus.
- New publicationEfficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes.
- New publicationEfficacy and safety of monotherapy of sitagliptin compared with metformin in patients with type 2 diabetes.
- New publicationEfficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.