DPPIV, Dipeptidyl peptidase IV membrane form, T-cell activation antigen CD26, Adenosine deaminase complexing protein 2, Dipeptidyl peptidase IV soluble form, ADCP2, Dipeptidyl peptidase 4, ADCP-2, DPP4, Dipeptidylpeptidase IV (CD26, Adenosine Deaminase Complexing Protein 2), DPP IV, TP103, CD26, Dipeptidyl-Peptidase 4, CD26 Antigen, ADABP, Dipeptidylpeptidase 4, Dipeptidyl peptidase IV, Gly-Pro Naphthylamidase, Xaa-Pro-Dipeptidylaminopeptidase, Post-Proline Dipeptidyl Aminopeptidase IV


Dipeptidyl peptidase IV (DPP4), also known as adenosine deaminase complexing protein 2 or CD26 (cluster of differentiation 26) is a protein that, in humans, is encoded by the DPP4 gene.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. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.

KO Status


Drug Information

Launched drugs: 28
Drugs in clinical trials: 22
Latest Research Phase: Approved

Drug Name





Clinical Trials

Gemigliptin L-tartrate Sesquihydrate/Metformin Hydrochloride


Lg Life Sciences Ltd

Diabetes Mellitus, Type 2

Alogliptin Benzoate/Metformin Hydrochloride


Takeda Pharmaceutical Co Ltd

Diabetes Mellitus, Type 2

Saxagliptin Hydrochloride/Metformin Hydrochloride


Astrazeneca Pharmaceutical Co Ltd

Diabetes Mellitus, Type 2

Alogliptin Benzoate

SYR-322, TAK-322



Diabetes Mellitus, Type 2, Acute Coronary Syndrome, Diabetes Mellitus




Dong-A Pharmaceutical Co Ltd

Diabetes Mellitus, Type 2, Kidney Diseases, Aortic valve diseases, Liver Diseases

Metformin Hydrochloride/Sitagliptin Hydrochloride


Sandoz Bv


LAF-237, DSP-7238, LAF-237A, NVP-LAF-237


Novartis Pharma Ag

Prediabetic State, Diabetes Mellitus, Type 2, Renal Insufficiency, Kidney Diseases, Diabetes Mellitus

Sitagliptin Phosphate/Metformin Hydrochloride


Merck & Co Inc

Diabetes Mellitus, Type 2

Dapagliflozin/Saxagliptin/Metformin hydrochloride


Astrazeneca Pharmaceutical Co Ltd

Diabetes Mellitus, Type 2


BI 10773/BI 1356, BI 1356/BI 10773, BI 10773/linagliptin, Linagliptin/BI 10773, BI 1356/empagliflozin, Empagliflozin/BI 1356


C.H. Boehringer Sohn Ag & Co. Kg

Diabetes Mellitus, Type 2, Cardiovascular Diseases





Interleukin-12 enhances CD26 expression and dipeptidyl peptidase IV function on human activated lymphocytes

Cordero O.J., Salgado F.J., Vinuela J.E., Nogueira M.,

Immunobiology 197:522-533(1997)

Two highly conserved glutamic acid residues in the predicted beta propeller domain of dipeptidyl peptidase IV are required for its enzyme activity

Abbott C.A., McCaughan G.W., Gorrell M.D.,

FEBS Lett. 458:278-284(1999)

Fibroblast activation protein, a dual specificity serine protease expressed in reactive human tumor stromal fibroblasts

Park J.E., Lenter M.C., Zimmermann R.N., Garin-Chesa P., Old L.J., Rettig W.J.,

J. Biol. Chem. 274:36505-36512(1999)

Preoperative serum CD26 levels: diagnostic efficiency and predictive value for colorectal cancer

Cordero O.J., Ayude D., Nogueira M., Rodriguez-Berrocal F.J., de la Cadena M.P.,

Br. J. Cancer 83:1139-1146(2000)

Mechanisms of CD26/dipeptidyl peptidase IV cytokine-dependent regulation on human activated lymphocytes

Salgado F.J., Vela E., Martin M., Franco R., Nogueira M., Cordero O.J.,

Cytokine 12:1136-1141(2000)

Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry

Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.,

J. Proteome Res. 8:651-661(2009)

Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor II receptor contributes to T cell activation

Ikushima H., Munakata Y., Ishii T., Iwata S., Terashima M., Tanaka H., Schlossman S.F., Morimoto C.,

Proc. Natl. Acad. Sci. U.S.A. 97:8439-8444(2000)

Regulation of epithelial and lymphocyte cell adhesion by adenosine deaminase-CD26 interaction

Gines S., Marino M., Mallol J., Canela E.I., Morimoto C., Callebaut C., Hovanessian A., Casado V., Lluis C., Franco R.,

Biochem. J. 361:203-209(2002)

Intestinal dipeptidyl peptidase IV is efficiently sorted to the apical membrane through the concerted action of N- and O-glycans as well as association with lipid microdomains

Alfalah M., Jacob R., Naim H.Y.,

J. Biol. Chem. 277:10683-10690(2002)

A role for interleukin-12 in the regulation of T cell plasma membrane compartmentation

Salgado F.J., Lojo J., Alonso-Lebrero J.L., Lluis C., Franco R., Cordero O.J., Nogueira M.,

J. Biol. Chem. 278:24849-24857(2003)