Dipeptidyl peptidase-4

Dipeptidyl peptidase-4
Dipeptidyl-peptidase 4

Ribbon diagram of human DPP-4.
From PDB 1PFQ.
Symbols DPP4; ADABP; ADCP2; CD26; DPPIV; TP103
External IDs OMIM102720 MGI94919 HomoloGene3279 GeneCards: DPP4 Gene
EC number
RNA expression pattern
PBB GE DPP4 203717 at tn.png
PBB GE DPP4 203716 s at tn.png
PBB GE DPP4 211478 s at tn.png
More reference expression data
Species Human Mouse
Entrez 1803 13482
Ensembl ENSG00000197635 ENSMUSG00000035000
UniProt P27487 Q3TR43
RefSeq (mRNA) NM_001935.3 NM_010074
RefSeq (protein) NP_001926.2 NP_034204
Location (UCSC) Chr 2:
162.85 – 162.93 Mb
Chr 2:
62.17 – 62.25 Mb
PubMed search [1] [2]

Dipeptidyl peptidase-4 (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.[1]



The protein encoded by the DPP4 gene is an antigenic enzyme expressed on the surface of most cell types and is associated with immune regulation, signal transduction and apoptosis. It is an intrinsic membrane glycoprotein and a serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides.

It is a rather indiscriminate enzyme for which a diverse range of substrates are known.[2] The substrates of CD26/DPPIV are proline(or alanine)-containing peptides and include growth factors, chemokines, neuropeptides, and vasoactive peptides.

DPP4 is related to attractin, FAP, DPP8 and DPP9.

DPP4 plays a major role in glucose metabolism. It is responsible for the degradation of incretins such as GLP-1.[3]

Furthermore, it appears to work as a suppressor in the development of cancer and tumours.[4][5][6]

CD26/DPPIV plays an important role in tumor biology, and is useful as a marker for various cancers, with its levels either on the cell surface or in the serum increased in some neoplasms and decreased in others.[7]

DPP-4 also binds the enzyme adenosine deaminase specifically and with high affinity. The significance of this interaction has yet to be established.

Clinical significance

A new class of oral hypoglycemics called dipeptidyl peptidase-4 inhibitors work by inhibiting the action of this enzyme, thereby prolonging incretin effect in vivo.[8]

See also


  1. ^ Kameoka J, Tanaka T, Nojima Y, Schlossman SF, Morimoto C (July 1993). "Direct association of adenosine deaminase with a T cell activation antigen, CD26". Science 261 (5120): 466–9. doi:10.1126/science.8101391. PMID 8101391. http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=8101391. 
  2. ^ Chen X (2006). "Biochemical properties of recombinant prolyl dipeptidases DPP-IV and DPP8". Adv. Exp. Med. Biol.. Advances in Experimental Medicine and Biology 575: 27–32. doi:10.1007/0-387-32824-6_3. ISBN 978-0-387-29058-4. PMID 16700505. 
  3. ^ Barnett A (November 2006). "DPP-4 inhibitors and their potential role in the management of type 2 diabetes". Int. J. Clin. Pract. 60 (11): 1454–70. doi:10.1111/j.1742-1241.2006.01178.x. PMID 17073841. 
  4. ^ Pro B, Dang N (2004). "CD26/dipeptidyl peptidase IV and its role in cancer". Histol Histopathol 19 (4): 1345–51. PMID 15375776. 
  5. ^ Masur K et al. (2006). "DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells". Regul Pept. 137 (3): 147–55. doi:10.1016/j.regpep.2006.07.003. PMID 16908079. 
  6. ^ Wesley UV et al. (2005). "Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway". Cancer Res. 65 (4): 1325–34. doi:10.1158/0008-5472.CAN-04-1852. PMID 15735018. 
  7. ^ Havre PA, Abe M, Urasaki Y, Ohnuma K, Morimoto C, Dang NH (2008). "The role of CD26/dipeptidyl peptidase IV in cancer". Front. Biosci. 13 (13): 1634–45. doi:10.2741/2787. PMID 17981655. http://www.bioscience.org/2008/v13/af/2787/fulltext.htm. 
  8. ^ Rosenstock J, Zinman B (April 2007). "Dipeptidyl peptidase-4 inhibitors and the management of type 2 diabetes mellitus". Curr Opin Endocrinol Diabetes Obes 14 (2): 98–107. doi:10.1097/MED.0b013e3280a02f65. PMID 17940427. 

External links

Further reading

  • Ansorge S, Bühling F, Kähne T, et al. (1997). "CD26/dipeptidyl peptidase IV in lymphocyte growth regulation". Adv. Exp. Med. Biol. 421: 127–40. PMID 9330689. 
  • Reinhold D, Kähne T, Steinbrecher A, et al. (2003). "The role of dipeptidyl peptidase IV (DP IV) enzymatic activity in T cell activation and autoimmunity". Biol. Chem. 383 (7–8): 1133–8. doi:10.1515/BC.2002.123. PMID 12437097. 
  • Sato K, Dang NH (2003). "CD26: a novel treatment target for T-cell lymphoid malignancies? (Review)". Int. J. Oncol. 22 (3): 481–97. PMID 12579300. 
  • de Meester I, Lambeir AM, Proost P, Scharpé S (2003). "Dipeptidyl peptidase IV substrates. An update on in vitro peptide hydrolysis by human DPPIV". Adv. Exp. Med. Biol.. Advances in Experimental Medicine and Biology 524: 3–17. doi:10.1007/0-306-47920-6_1. ISBN 0-306-47717-3. PMID 12675218. 
  • Koch S, Anthonsen D, Skovbjerg H, Sjöström H (2003). "On the role of dipeptidyl peptidase IV in the digestion of an immunodominant epitope in celiac disease". Adv. Exp. Med. Biol.. Advances in Experimental Medicine and Biology 524: 181–7. doi:10.1007/0-306-47920-6_22. ISBN 0-306-47717-3. PMID 12675238. 
  • Pro B, Dang NH (2005). "CD26/dipeptidyl peptidase IV and its role in cancer". Histol. Histopathol. 19 (4): 1345–51. PMID 15375776.