Dipeptidyl peptidase-4

Dipeptidyl-peptidase 4
Ribbon diagram of human DPP-4. From PDB 1PFQ.
Available structures PDB 1J2E, 1N1M, 1NU6, 1NU8, 1PFQ, 1R9M, 1R9N, 1RWQ, 1TK3, 1TKR, 1U8E, 1W1I, 1WCY, 1X70, 2AJL, 2BGN, 2BGR, 2BUB, 2FJP, 2G5P, 2G5T, 2G63, 2HHA, 2I03, 2I78, 2IIT, 2IIV, 2JID, 2OAG, 2OGZ, 2OLE, 2ONC, 2OPH, 2OQI, 2OQV, 2P8S, 2QJR, 2QKY, 2QOE, 2QT9, 2QTB, 2RGU, 2RIP, 3BJM, 3C43, 3C45, 3CCB, 3CCC, 3D4L, 3EIO, 3F8S, 3G0B, 3G0C, 3G0D, 3G0G, 3H0C, 3HAB, 3HAC, 3KWF, 3KWJ, 3NOX, 3OC0
Identifiers
Symbols	DPP4; ADABP; ADCP2; CD26; DPPIV; TP103
External IDs	OMIM: 102720 MGI: 94919 HomoloGene: 3279 GeneCards: DPP4 Gene
EC number	3.4.14.5
Gene Ontology Molecular function • protease binding • aminopeptidase activity • serine-type endopeptidase activity • receptor activity • receptor binding • protein binding • collagen binding • peptidase activity • serine-type peptidase activity • dipeptidyl-peptidase activity • peptide binding • protein homodimerization activity Cellular component • extracellular region • membrane fraction • soluble fraction • endoplasmic reticulum • Golgi apparatus • plasma membrane • cell surface • integral to membrane • apical plasma membrane • lamellipodium • cell junction • endocytic vesicle • lamellipodium membrane • membrane raft • intercellular canaliculus • invadopodium membrane Biological process • response to hypoxia • regulation of T cell mediated immunity • proteolysis • cell adhesion • positive regulation of cell proliferation • negative regulation of extracellular matrix disassembly • T cell costimulation • regulation of cell-cell adhesion mediated by integrin • T cell activation • endothelial cell migration • establishment of localization Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
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]

Function

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

• Development of dipeptidyl peptidase-4 inhibitors
• Berberine

References

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

• The MEROPS online database for peptidases and their inhibitors: S09.003
• MeSH Dipeptidyl-Peptidase+IV
• Banting and Best Diabetes Centre at UT dpp4

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. 

This hydrolase article is a stub. You can help Wikipedia by expanding it.v · Categories: Human proteins EC 3.4.14 Peptidase Hydrolase stubs Wikimedia Foundation. 2010. Игры ⚽ Нужна курсовая? Bukit Antarabangsa Acts of the Kings of Israel Look at other dictionaries: Dipeptidyl peptidase — is a type of enzyme classified under EC 3.4.14. Types include: Cathepsin C, dipeptidyl peptidase 1[1] DPP3, dipeptidyl peptidase 3 Dipeptidyl peptidase 4 DPP6, dipeptidyl peptidase 6 DPP7, dipeptidyl peptidase 7 DPP8, dipeptidyl peptidase 8 DPP9 …   Wikipedia Dipeptidyl-peptidase IV family — Dipeptidyl peptidase IV (DPP IV) N terminal region porcine dipeptidyl peptidase iv (cd26) in complex with 4 (2 aminoethyl) benzene sulphonyl fluoride (aebsf) Identifiers Symbol DPPIV N …   Wikipedia Dipeptidyl peptidase-4 inhibitor — DPP 4 inhibitors and GLP 1 Inhibitors of dipeptidyl peptidase 4, also DPP 4 inhibitors or gliptins, are a class of oral hypoglycemics that block DPP 4. They can be used to treat diabetes mellitus type 2. The first agent of the class sitagliptin… …   Wikipedia Dipeptidyl peptidase-4 inhibitors — Inhibitors of Dipeptidyl peptidase 4 , also DPP 4 inhibitors, are a new class of oral hypoglycemics which block DPP 4.Their mechanism of action is thought to result from increased Incretin levels (GLP 1 and GIP), [ McIntosh CH, Demuth HU,… …   Wikipedia Dipeptidyl-Peptidase-4-Inhibitor — Sitagliptin, Leitsubstanz der neuen Antidiabetika Klasse der Dipeptidyl Peptidase 4 Inhibitoren Inhibitoren der Dipeptidylpeptidase 4, auch kurz als DPP4 Inhibitoren oder als Inkretinverstärker bezeichnet, sind Substanzen, welche den Abbau des… …   Deutsch Wikipedia Dipeptidyl-Peptidase-IV-Inhibitor — Sitagliptin, Leitsubstanz der neuen Antidiabetika Klasse der Dipeptidyl Peptidase 4 Inhibitoren Inhibitoren der Dipeptidylpeptidase 4, auch kurz als DPP4 Inhibitoren oder als Inkretinverstärker bezeichnet, sind Substanzen, welche den Abbau des… …   Deutsch Wikipedia Dipeptidyl Peptidase 4 Inhibitor — Sitagliptin, Leitsubstanz der neuen Antidiabetika Klasse der Dipeptidyl Peptidase 4 Inhibitoren Inhibitoren der Dipeptidylpeptidase 4, auch kurz als DPP4 Inhibitoren oder als Inkretinverstärker bezeichnet, sind Substanzen, welche den Abbau des… …   Deutsch Wikipedia Dipeptidyl Peptidase IV Inhibitor — Sitagliptin, Leitsubstanz der neuen Antidiabetika Klasse der Dipeptidyl Peptidase 4 Inhibitoren Inhibitoren der Dipeptidylpeptidase 4, auch kurz als DPP4 Inhibitoren oder als Inkretinverstärker bezeichnet, sind Substanzen, welche den Abbau des… …   Deutsch Wikipedia dipeptidyl peptidase — A hydrolase occurring in a number of forms: d. I, dipeptidyl transferase, cleaving dipeptides from the amino end of polypeptides; d. II, with properties similar to those of I, has a different specificity and acts preferably on tripeptides; d. III …   Medical dictionary Development of dipeptidyl peptidase-4 inhibitors — Dipeptidyl peptidase 4 inhibitors (DPP 4 inhibitors) are enzyme inhibitors that inhibit the enzyme dipeptidyl peptidase 4 (DPP 4) and are a potent treatment for type 2 diabetes. Inhibition of the DPP 4 enzyme prolongs and enhances the activity of …   Wikipedia 18+ © Academic, 2000-2024 Contact us: Technical Support, Advertising Dictionaries export, created on PHP, Joomla, Drupal, WordPress, MODx. Mark and share Search through all dictionaries Translate… Search Internet Share the article and excerpts Direct link … Do a right-click on the link above and select “Copy Link”