Dipeptidyl peptidase 4
Also known as: ADCP2, CD26, DPP4
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. 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. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.
Classification
- Family (Pfam)
- PF00930 DPPIV_N, PF00326 Peptidase_S9
- InterPro
- AB_hydrolase_fold, Pept_S9_AS, Peptidase_S9_cat, Peptidase_S9B_N, Serine_Prot_S9B/DPPIV
- Functional cluster
- Secreted Hydrolases & Toxins
Experimental structures · PDB · 117
- 1J2E X-ray 2.60A
- 1N1M X-ray 2.50A
- 1NU6 X-ray 2.10A
- 1NU8 X-ray 2.50A
- 1PFQ X-ray 1.90A
- 1R9M X-ray 2.10A
- 1R9N X-ray 2.30A
- 1RWQ X-ray 2.20A
- 1TK3 X-ray 2.00A
- 1TKR X-ray 2.70A
- 1U8E X-ray 2.20A
- 1W1I X-ray 3.03A
- … and 105 more
A predicted model is available from AlphaFold.
Gene Ontology · 39
- GO:0016324 apical plasma membrane
- GO:0009986 cell surface
- GO:0030139 endocytic vesicle
- GO:0070062 extracellular exosome
- GO:0005576 extracellular region
- GO:0005925 focal adhesion
- GO:0046581 intercellular canaliculus
- GO:0030027 lamellipodium
- GO:0031258 lamellipodium membrane
- GO:0005765 lysosomal membrane
- GO:0016020 membrane
- GO:0045121 membrane raft
- GO:0005886 plasma membrane
- GO:0004177 aminopeptidase activity
- GO:0045499 chemorepellent activity
- GO:0008239 dipeptidyl-peptidase activity
- GO:0042802 identical protein binding
- GO:0002020 protease binding
- GO:0042803 protein homodimerization activity
- GO:0004252 serine-type endopeptidase activity
- GO:0008236 serine-type peptidase activity
- GO:0005102 signaling receptor binding
- GO:0001618 virus receptor activity
- GO:0007155 cell adhesion
- GO:0043542 endothelial cell migration
- GO:0120116 glucagon processing
- GO:0061025 membrane fusion
- GO:0010716 negative regulation of extracellular matrix disassembly
- GO:0090024 negative regulation of neutrophil chemotaxis
- GO:0016486 peptide hormone processing
- GO:0008284 positive regulation of cell population proliferation
- GO:0006508 proteolysis
- GO:0019065 receptor-mediated endocytosis of virus by host cell
- GO:0046813 receptor-mediated virion attachment to host cell
- GO:0033632 regulation of cell-cell adhesion mediated by integrin
- GO:0001666 response to hypoxia
- GO:0046718 symbiont entry into host cell
- GO:0042110 T cell activation
- GO:0031295 T cell costimulation
Drugs targeting this protein · 18
- DBPR-108 inhibitor
- SITAGLIPTIN PHOSPHATE inhibitor
- SAXAGLIPTIN HYDROCHLORIDE inhibitor
- VILDAGLIPTIN inhibitor
- EVOGLIPTIN inhibitor
- ANAGLIPTIN inhibitor
- TRELAGLIPTIN SUCCINATE inhibitor
- OMARIGLIPTIN inhibitor
- TENELIGLIPTIN inhibitor
- ALOGLIPTIN BENZOATE inhibitor
- LINAGLIPTIN inhibitor
- GEMIGLIPTIN inhibitor
- DUTOGLIPTIN inhibitor
- BISEGLIPTIN inhibitor
- GOSOGLIPTIN inhibitor
- SITAGLIPTIN FUMARATE inhibitor
- CARMEGLIPTIN inhibitor
- SITAGLIPTIN HYDROCHLORIDE MONOHYDRATE inhibitor
Related proteins · sequence + function similarity
- Dipeptidyl peptidase 4 0.99
- Dipeptidyl peptidase 4 0.99
- Dipeptidyl peptidase 4 0.98
- Dipeptidyl peptidase 4 0.98
- Dipeptidyl peptidase 4 0.98
- Prolyl endopeptidase FAP 0.95
- Prolyl endopeptidase FAP 0.95
- Prolyl endopeptidase FAP 0.94
- Venom dipeptidyl peptidase 4 0.91
- Venom dipeptidyl peptidase 4 0.90
- Venom dipeptidyl peptidase 4 0.90
- Dipeptidyl peptidase family member 2 0.86
Co-cited proteins · studied together in the literature
- Adenosine deaminase 7 shared papers
- Sucrase-isomaltase, intestinal 1 shared papers
- Spike glycoprotein 1 shared papers
- Prolyl endopeptidase FAP 2 shared papers
- Cation-independent mannose-6-phosphate receptor 1 shared papers
- Glypican-3 1 shared papers
- Receptor-type tyrosine-protein phosphatase C 1 shared papers
- Neprilysin 1 shared papers
- Plasminogen 1 shared papers
- Natriuretic peptides A 1 shared papers
- Natriuretic peptides B 1 shared papers
- Furin 1 shared papers
Literature · 47 cited papers
- COVID-19 and Genetic Variants of Protein Involved in the SARS-CoV-2 Entry into the Host Cells. Genes (Basel) · 2020
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4. Cell Res. · 2013
- Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature · 2013
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- Discovery of 6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxamides as potent, selective dipeptidyl peptidase-4 (DPP4) inhibitors. J. Med. Chem. · 2010
- On the origin of serum CD26 and its altered concentration in cancer patients. Cancer Immunol. Immunother. · 2009
- Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J. Proteome Res. · 2009
- Human protein factory for converting the transcriptome into an in vitro-expressed proteome. Nat. Methods · 2008
- Lymphatic-specific expression of dipeptidyl peptidase IV and its dual role in lymphatic endothelial function. Exp. Cell Res. · 2008
- The Simpson-Golabi-Behmel syndrome causative glypican-3, binds to and inhibits the dipeptidyl peptidase activity of CD26. Proteomics · 2007
- Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1. J. Biol. Chem. · 2007
- … and 35 more in the literature graph