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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/21 07:37:56」(JST)

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

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 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]

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

Animal studies

Animal studies suggest its pathogenetic role in development of fibrosis of various organs, such as liver and kidney.^[7]^[8]

Clinical significance

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.^[9]

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.^[10]

A new coronavirus related to SARS, named Middle East respiratory syndrome coronavirus, has been found to bind to DPP4. DPP4 is found on the surface of cells in the airways (such as the lungs) and kidneys. Scientists may be able to use this to their advantage by blocking the virus's entry into the cell.^[11]

References

^ Kameoka J, Tanaka T, Nojima Y, Schlossman SF, Morimoto C (Jul 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.
^ Chen X (2006). "Biochemical properties of recombinant prolyl dipeptidases DPP-IV and DPP8". Advances in Experimental Medicine and Biology. 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.
^ Barnett A (Nov 2006). "DPP-4 inhibitors and their potential role in the management of type 2 diabetes". International Journal of Clinical Practice 60 (11): 1454–70. doi:10.1111/j.1742-1241.2006.01178.x. PMID 17073841.
^ Pro B, Dang NH (Oct 2004). "CD26/dipeptidyl peptidase IV and its role in cancer". Histology and Histopathology 19 (4): 1345–51. PMID 15375776.
^ Masur K, Schwartz F, Entschladen F, Niggemann B, Zaenker KS (Dec 2006). "DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells". Regulatory Peptides 137 (3): 147–55. doi:10.1016/j.regpep.2006.07.003. PMID 16908079.
^ Wesley UV, McGroarty M, Homoyouni A (Feb 2005). "Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway". Cancer Research 65 (4): 1325–34. doi:10.1158/0008-5472.CAN-04-1852. PMID 15735018.
^ Kaji K, Yoshiji H, Ikenaka Y, Noguchi R, Aihara Y, Douhara A, Moriya K, Kawaratani H, Shirai Y, Yoshii J, Yanase K, Kitade M, Namisaki T, Fukui H (Mar 2014). "Dipeptidyl peptidase-4 inhibitor attenuates hepatic fibrosis via suppression of activated hepatic stellate cell in rats". Journal of Gastroenterology 49 (3): 481–91. doi:10.1007/s00535-013-0783-4. PMID 23475323.
^ Min HS, Kim JE, Lee MH, Song HK, Kang YS, Lee MJ, Lee JE, Kim HW, Cha JJ, Chung YY, Hyun YY, Han JY, Cha DR (Jun 2014). "Dipeptidyl peptidase IV inhibitor protects against renal interstitial fibrosis in a mouse model of ureteral obstruction". Laboratory Investigation; A Journal of Technical Methods and Pathology 94 (6): 598–607. doi:10.1038/labinvest.2014.50. PMID 24687121.
^ Havre PA, Abe M, Urasaki Y, Ohnuma K, Morimoto C, Dang NH (2008). "The role of CD26/dipeptidyl peptidase IV in cancer". Frontiers in Bioscience 13 (13): 1634–45. doi:10.2741/2787. PMID 17981655.
^ Rosenstock J, Zinman B (Apr 2007). "Dipeptidyl peptidase-4 inhibitors and the management of type 2 diabetes mellitus". Current Opinion in Endocrinology, Diabetes, and Obesity 14 (2): 98–107. doi:10.1097/MED.0b013e3280a02f65. PMID 17940427.
^ Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL (Mar 2013). "Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC". Nature (ScienceNews) 495 (7440): 251–4. doi:10.1038/nature12005. PMID 23486063. Lay summary – ScienceNews.

External links

The MEROPS online database for peptidases and their inhibitors: S09.003
Dipeptidyl-Peptidase IV at the US National Library of Medicine Medical Subject Headings (MeSH)
Banting and Best Diabetes Centre at UT dpp4

UpToDate Contents

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1. 2型糖尿病の治療に用いるジペプチジルペプチダーゼ4（DPP-4）阻害薬 dipeptidyl peptidase 4 dpp 4 inhibitors for the treatment of type 2 diabetes mellitus
2. 2型糖尿病治療に用いるナトリウム-グルコース共輸送体2（SGLT2）阻害薬 sodium glucose co transporter 2 inhibitors for the treatment of type 2 diabetes mellitus
3. 2型糖尿病治療のためのGlucagon-like peptide-1受容体拮抗剤 glucagon like peptide 1 receptor agonists for the treatment of type 2 diabetes mellitus
4. ACE 阻害薬誘発性血管浮腫 ace inhibitor induced angioedema
5. 2型糖尿病における持続性高血糖のマネージメント management of persistent hyperglycemia in type 2 diabetes mellitus

English Journal

Japanese Journal

Recent Perspectives for Combined Status of Type 2 Diabetes Mellitus (T2DM) and Non-Alcoholic Fatty Liver Disease (NAFLD)

Bando Hiroshi
Edelweiss Journal of Biomedical Research and Review 3(1), 9-11, 2021-04-28
… Treatments for T2DM and NAFLD include Glucagon-Like Peptide 1 Receptor Agonist (GLP-1 RA), Dipeptidyl-Peptidase 4 Inhibitors (DPP-4i) and Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i). …
NAID 120007034530

The impact of vildagliptin on the daily glucose profile and coronary plaque stability in impaired glucose tolerance patients with coronary artery disease: VOGUE-A multicenter randomized controlled trial

Yamamoto Hiroyuki,Konishi Akihide,Shinke Toshiro,Otake Hiromasa,Kuroda Masaru,Osue Tsuyoshi,Sawada Takahiro,Takaya Tomofumi,Kawai Hiroya,Hashimoto Naoko,Ohara Takeshi,Hirota Yushi,Sakaguchi Kazuhiko,Omori Takashi,Ogawa Wataru,Hirata Ken-ichi
BMC Cardiovascular Disorders 21(1), 92, 2021-02-15
… This study aimed to elucidate whether a dipeptidyl peptidase 4 inhibitor could reduce the glycemic excursion and stabilize the coronary plaques compared with conventional management in coronary artery disease (CAD) patients with impaired glucose tolerance (IGT). …
NAID 120006993640

Dipeptidyl Peptidase-4阻害薬長期内服後に発症した抗ラミニンγ1類天疱瘡の1例

野村史絵,西部明子,牛上敢,二ッ谷剛俊,池村渓伺,八田順子,望月隆,南部昌之,石井文人,橋本隆
皮膚科の臨床 63(2), 219-223, 2021-02
NAID 40022499111

「peptidase」

Dipeptidyl-peptidase 4
	Ribbon diagram of human DPP-4.; From PDB: 1PFQ.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	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, 3O95, 3O9V, 3OC0, 3OPM, 3Q0T, 3Q8W, 3QBJ, 3SWW, 3SX4, 3VJK, 3VJL, 3VJM, 3W2T, 4A5S, 4DSA, 4DSZ, 4DTC, 4G1F, 4J3J, 4JH0, 4KR0, 4L72, 4LKO, 4N8D, 4N8E, 4PNZ, 4PV7, 4QZV
Identifiers
Symbols	DPP4 ; ADABP; ADCP2; CD26; DPPIV; TP103
External IDs	OMIM: 102720 MGI: 94919 HomoloGene: 3279 ChEMBL: 284 GeneCards: DPP4 Gene
EC number	3.4.14.5
Gene ontology
Molecular function	• virus receptor activity; • protease binding; • serine-type endopeptidase activity; • receptor binding; • protein binding; • serine-type peptidase activity; • dipeptidyl-peptidase activity; • identical protein binding; • protein homodimerization activity;
Cellular component	• lysosomal membrane; • plasma membrane; • focal adhesion; • cell surface; • membrane; • integral component of membrane; • apical plasma membrane; • lamellipodium; • endocytic vesicle; • lamellipodium membrane; • membrane raft; • intercellular canaliculus; • extracellular exosome; • invadopodium membrane;
Biological process	• behavioral fear response; • response to hypoxia; • proteolysis; • positive regulation of cell proliferation; • negative regulation of extracellular matrix disassembly; • T cell costimulation; • regulation of cell-cell adhesion mediated by integrin; • locomotory exploration behavior; • psychomotor behavior; • T cell activation; • endothelial cell migration; • viral entry into host cell;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;