The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

DPP8  -  dipeptidyl-peptidase 8

Homo sapiens

Synonyms: DP8, DPP VIII, DPRP-1, DPRP1, Dipeptidyl peptidase 8, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of DPP8

  • In dogs, the DPP8/9 inhibitor produced gastrointestinal toxicity [1].
  • In rats, the DPP8/9 inhibitor produced alopecia, thrombocytopenia, reticulocytopenia, enlarged spleen, multiorgan histopathological changes, and mortality [1].
  • To study its structure and biochemical properties, we have overexpressed the human DPP8 protein in baculovirus infected Sf9 cells [2].
  • The low-MW form of DPP-IV-like enzyme activity, corresponding most probably to DPP-8, observed only in glioma cells but not in human plasma, was inhibited preferentially by SA, CHE and EX, and only slightly by FA [3].

High impact information on DPP8

  • Unlike DPP-IV, a drug target for type II diabetes, no information is available on the crystal structure of DPP8, the regulation of its enzymatic activity, or its substrate specificity [4].
  • Our study has identified the residues absolutely required for the optimal activity of DPP8 and its unique substrate specificity [4].
  • DPP8 belongs to the family of prolyl dipeptidases, which are capable of cleaving the peptide bond after a penultimate proline residue [4].
  • Surprisingly, unlike DPP-IV, these single-site mutations abolished the enzymatic activity of DPP8 without disrupting its quaternary structure, indicating that dimerization itself is not sufficient for the optimal enzymatic activity of DPP8 [4].
  • Investigation of the Dimer Interface and Substrate Specificity of Prolyl Dipeptidase DPP8 [4].

Biological context of DPP8


Anatomical context of DPP8


Associations of DPP8 with chemical compounds

  • Isoindoline derivatives were found to be more potent DPP8 inhibitors than isoquinoline derivatives [9].
  • DPP8 catalyzes the cleavage at the carboxyl side of the proline residue at the penultimate position [2].
  • anti-Substituted beta-methylphenylalanine derived amides have been shown to be potent DPP-IV inhibitors exhibiting excellent selectivity over both DPP8 and DPP9 [10].
  • Analogues that incorporated a bulky substituent at the first carbon position of benzylamine or isoquinoline showed over 30-fold selectivity for DPP-IV over both DPP8 and DPP-II [11].
  • Structure-activity studies of substitutions at the C5 position of the 2-cyanopyrrolidide warhead led to the discovery of potent inhibitors of DPP-IV that lack activity against DPP8 and DPP9 [12].

Regulatory relationships of DPP8


Other interactions of DPP8

  • Elucidation of the physiological or pathophysiological role of DPP8, DPP9 and DPP10 and characterization of their structure-function relationships will add impetus to the development of inhibitor molecules for pharmacological or therapeutic use [14].
  • The effects of dipeptidyl peptidase 8 and dipeptidyl peptidase 9 on cell adhesion, cell migration, wound healing and apoptosis were measured by using green fluorescent protein fusion proteins to identify transfected cells [6].
  • Here we describe DPP8, a novel human postproline dipeptidyl aminopeptidase that is homologous to DPPIV and FAP [5].
  • Replacing the C-terminal portion of the predicted alpha/beta hydrolase domain of CD26 (residues 501-766) with the homologous portion of DP8 or DP9 produced intact proteins [15].
  • The catalytic triad of DP8 was shown to be Ser(739)-Asp (817)-His(849) [15].

Analytical, diagnostic and therapeutic context of DPP8

  • Northern-blot hybridization showed that the tissue expression of DPP8 mRNA is ubiquitous, similar to that of DPPIV [5].
  • In this study, using analytical ultracentrifugation and native gel electrophoresis, we show that the DPP8 protein is predominantly dimeric when purified or in the cell extracts [4].


  1. Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9. Lankas, G.R., Leiting, B., Roy, R.S., Eiermann, G.J., Beconi, M.G., Biftu, T., Chan, C.C., Edmondson, S., Feeney, W.P., He, H., Ippolito, D.E., Kim, D., Lyons, K.A., Ok, H.O., Patel, R.A., Petrov, A.N., Pryor, K.A., Qian, X., Reigle, L., Woods, A., Wu, J.K., Zaller, D., Zhang, X., Zhu, L., Weber, A.E., Thornberry, N.A. Diabetes (2005) [Pubmed]
  2. Purification and characterization of human prolyl dipeptidase DPP8 in Sf9 insect cells. Chen, Y.S., Chien, C.H., Goparaju, C.M., Hsu, J.T., Liang, P.H., Chen, X. Protein Expr. Purif. (2004) [Pubmed]
  3. Quaternary benzo[c]phenanthridine alkaloids as inhibitors of dipeptidyl peptidase IV-like activity baring enzymes in human blood plasma and glioma cell lines. Sedo, A., Malík, R., Vicar, J., Simánek, V., Ulrichová, J. Physiological research / Academia Scientiarum Bohemoslovaca. (2003) [Pubmed]
  4. Investigation of the Dimer Interface and Substrate Specificity of Prolyl Dipeptidase DPP8. Lee, H.J., Chen, Y.S., Chou, C.Y., Chien, C.H., Lin, C.H., Chang, G.G., Chen, X. J. Biol. Chem. (2006) [Pubmed]
  5. Cloning, expression and chromosomal localization of a novel human dipeptidyl peptidase (DPP) IV homolog, DPP8. Abbott, C.A., Yu, D.M., Woollatt, E., Sutherland, G.R., McCaughan, G.W., Gorrell, M.D. Eur. J. Biochem. (2000) [Pubmed]
  6. Extraenzymatic functions of the dipeptidyl peptidase IV-related proteins DP8 and DP9 in cell adhesion, migration and apoptosis. Yu, D.M., Wang, X.M., McCaughan, G.W., Gorrell, M.D. FEBS J. (2006) [Pubmed]
  7. Expression of a novel dipeptidyl peptidase 8 (DPP8) transcript variant, DPP8-v3, in human testis. Zhu, H., Zhou, Z.M., Lu, L., Xu, M., Wang, H., Li, J.M., Sha, J.H. Asian J. Androl. (2005) [Pubmed]
  8. Dipeptidyl peptidase IV and related enzymes in cell biology and liver disorders. Gorrell, M.D. Clin. Sci. (2005) [Pubmed]
  9. Novel isoindoline compounds for potent and selective inhibition of prolyl dipeptidase DPP8. Jiaang, W.T., Chen, Y.S., Hsu, T., Wu, S.H., Chien, C.H., Chang, C.N., Chang, S.P., Lee, S.J., Chen, X. Bioorg. Med. Chem. Lett. (2005) [Pubmed]
  10. Discovery of potent, selective, and orally bioavailable pyridone-based dipeptidyl peptidase-4 inhibitors. Xu, J., Wei, L., Mathvink, R., Edmondson, S.D., Mastracchio, A., Eiermann, G.J., He, H., Leone, J.F., Leiting, B., Lyons, K.A., Marsilio, F., Patel, R.A., Petrov, A., Wu, J.K., Thornberry, N.A., Weber, A.E. Bioorg. Med. Chem. Lett. (2006) [Pubmed]
  11. Glutamic acid analogues as potent dipeptidyl peptidase IV and 8 inhibitors. Lu, I.L., Lee, S.J., Tsu, H., Wu, S.Y., Kao, K.H., Chien, C.H., Chang, Y.Y., Chen, Y.S., Cheng, J.H., Chang, C.N., Chen, T.W., Chang, S.P., Chen, X., Jiaang, W.T. Bioorg. Med. Chem. Lett. (2005) [Pubmed]
  12. Discovery of 2-[4-{{2-(2S,5R)-2-Cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]- 4-methyl-1-piperidinyl]-4-pyridinecarboxylic Acid (ABT-279): A Very Potent, Selective, Effective, and Well-Tolerated Inhibitor of Dipeptidyl Peptidase-IV, Useful for the Treatment of Diabetes. Madar, D.J., Kopecka, H., Pireh, D., Yong, H., Pei, Z., Li, X., Wiedeman, P.E., Djuric, S.W., Von Geldern, T.W., Fickes, M.G., Bhagavatula, L., McDermott, T., Wittenberger, S., Richards, S.J., Longenecker, K.L., Stewart, K.D., Lubben, T.H., Ballaron, S.J., Stashko, M.A., Long, M.A., Wells, H., Zinker, B.A., Mika, A.K., Beno, D.W., Kempf-Grote, A.J., Polakowski, J., Segreti, J., Reinhart, G.A., Fryer, R.M., Sham, H.L., Trevillyan, J.M. J. Med. Chem. (2006) [Pubmed]
  13. Inhibition of dipeptidyl-peptidase IV catalyzed peptide truncation by Vildagliptin ((2S)-{[(3-hydroxyadamantan-1-yl)amino]acetyl}-pyrrolidine-2-carbonitrile). Brandt, I., Joossens, J., Chen, X., Maes, M.B., Scharpé, S., De Meester, I., Lambeir, A.M. Biochem. Pharmacol. (2005) [Pubmed]
  14. Cloning and characterization of dipeptidyl peptidase 10, a new member of an emerging subgroup of serine proteases. Qi, S.Y., Riviere, P.J., Trojnar, J., Junien, J.L., Akinsanya, K.O. Biochem. J. (2003) [Pubmed]
  15. Structural requirements for catalysis, expression, and dimerization in the CD26/DPIV gene family. Ajami, K., Abbott, C.A., Obradovic, M., Gysbers, V., Kähne, T., McCaughan, G.W., Gorrell, M.D. Biochemistry (2003) [Pubmed]
WikiGenes - Universities